endo2

Question 1

What is the epidemiology of Paget’s disease?

Answer 1

• most common in UK and british ancestry
• men more than women
• prevalence doubles each decade after 40
• incidentally elevated ALP
• unknocn cause, often genetic component.

Question 2

What is the pathophysiology of Paget’s Disease?

Answer 2

High bone turnover and disorganised osteoid formation.

Unknown cause.

Question 3

What are the clinical findings in Paget’s disease?

Answer 3

• can be mild and asymptomatic
• one bone (monostotic) or multiple (polyostotic)
• skull, femur, tibia, pelvis and humerus
• bones involved immediately, additional bones don’t get involved during it’s course
• pain is first symptom, either in involved bone or adjacent joint featuring degenerative arthtitis
• bones can soften –> bowed tibias, kyphosis, chalkstick fractures with slight trauma
• skull involvement - headaches and increased hat size.
• deafness
• vascular steal syndromes due to increase vascularity over involved bones (which are also warm to touch)

Question 4

What are the lab findings of Paget’s disease?

Answer 4

Markedly elevated ALP.

Serum bone specific ALP if normal, or to distinguish source of elevated ALP.

Serum C-telopeptide (CTx) is high

Urinary hydroxyproline is high in active disease

Elevated serum Ca esp if bed rested

Screen for OHD deficiency which can also present with elevated ALP and bone pain - correct before prescribing a bisphosphonate.

Question 5

What is the evidence for calcium and vitamin D supplementation/

Answer 5

The strongest evidence for fracture benefits of supplements is observed when both calcium and vitamin D are used by institutionalised women with low vitamin D levels and low dietary intake of calcium

Question 6

What are the imaging findings in Paget’s disease?

Answer 6

• ostelytic with focal radiolucencies ‘osteoporosis circumscripta’ in the skull or advancing flame shaped lytic lesions in long bones

Bones subsequently become sclerotic or mixed scleoritc and lytic, then thickened and deformed

Technetium pyrophosphate bone scans can help show activity of bone lesions before radiologic changes are evident.

Question 7

What is multisystem proteinopathy?

Answer 7

• constellation of Paget disease, inclusion body myopathy, and FTD
• caused by a mutation in gene that encodes valosin-containing protein.

Question 8

What are the important differentials of Paget disease?

Answer 8

• osteogenic sarcoma
• multiple myeloma
• fibrous dysplasia
• secondary bone lesions: metastatic Ca and osteititis fibrosa cystica

Question 9

What are the complications of Paget’s disease?

Answer 9

Hypercalcaemia and renal calculi

Vertebral collapse and spinal cord or root compression - radiculopathy or paralysis

High output cardiac failure due to increased vascularity

Arthritis in adjacent joints

Cranial nerve palsies from impingement of the neural foramina

Petrous temporal bone involvement frequently causes mixed hearing loss

Vascular steal syndrome - in the skull this can cause somnolence, stroke or optic nerve involvement and loss of vision

Misaligned teeth if jaw involved

Osteosarcoma rarely in longstanding lesions - marked increase in bone pain, sudden rise in ALP and new lytic bone lesion

Question 10

What is the treatment of Paget’s disease?

Answer 10

Surveillance if asymptomatic unless extensive involvement of skull, long bones, or vertebrae

Bisphosphnates are treatment of choice - given until ALP normalised, then a break for about 3 months or until ALP rises again

May get paradoxical increase in pain - first dose effects and go away.

If given IV - Improvement lasts several months

May get asthma in aspirin sensitive patients.

IV zoledronic acid more effective than daily risedronate.

Nasal calcitonin-salmon is used but bisphosphonates better

Question 11

What is the prognosis of Paget’s disease?

Answer 11

Good unless sarcoma

Prognosis worse if it starts early in life

In severe forms: intractable pain, deformity and cardiac features. Rare with prompt bisphosphonate tx.

Question 12

What are the general symptoms of chronic adrenocortical insuffiency (Addison’s disease)?

Answer 12

• weakness & fatigueability
• sparse axillary hair, crease & nipple pigmentation
• hypotension and small heart

Question 13

What are the general biochemical features of Addison disease?

Answer 13

Hyponatraemia

Hyperkalaemia

Eosinophilia and relative lymphocytosis

Question 14

What happens to cortisol in chronic adrenocortical insufficiency? (Addison disease)

Answer 14

Low plasma cortisol levels that fail to rise after administration of corticotropin

Elevated ACTH

Question 15

What is the difference between primary and secondary adrenal insufficiency?

Answer 15

Primary - dysfunction or absence of adrenal cortices

Secondary - deficient secretion of ACTH

Question 16

What does 21-hydroxylase do? What happens if you break it?

Answer 16

Catalyses conversion of progesterone to deoxycorticosterone which later becomes aldosterone.

Catalyses conversion of 17-alpha-hydroxyprogesterone to deoxycortisol which becomes cortisol.

Breaking it means cortisol and aldosterone insufficiency and sex steroid excess which is congenital adrenal hyperplasia

Question 17

What is the most common cause of Addison disease?

Answer 17

Autoimmune destruction of the adrenals.

Question 18

What is the mechanism of polyglandular autoimmune syndrome Type 1? (Type 1 PGA)

Answer 18

Defect in T-cell mediated immunity inherited as an autosomal recessive trait.

Question 19

What are the non-autoimmune causes of Addison’s disease?

Answer 19

• Tuberculosis
• Bilateral adrenal haemorrhage during sepsis, HITs, anticoagulation or antiphospholipid syndrome - presents at 1 week post
• Adrenoleukodystrophy

Question 20

What is adrenoleukodystrophy?

Answer 20

X-linked peroxisomal disorder causing accumulation of very long chain fatty acids.

Accumulate in adrenals, testes, brain, and spinal cord.

Occurs at any age and accounts for 1/3 of Addison disease in boys.

Question 21

What do peroxisomes do?

Answer 21

Break down very long chain fatty acids.

Question 22

What does 17 hydroxylase do?

What does a deficiency cause?

Answer 22

Catalyses conversion of pregnenolone and progesterone to 17a-hydroxypregnenolone and 17a-hydroxyprogesterone respectively.

These get converted to DHEA (pregnenlonone) and androstenedione (progesterone) respectively.

Deficiency forces progesterone and pregnenlone down the mineralocorticoid pathway only.

This results in hypertension, hyperkalemia, and primary hypogonadism.

It’s a rare form of CAH.

Question 23

What will a mild deficiency of 21 hydroxylase result in?

Answer 23

Women with hirstutism in adolescene but adequate cortisol.

Known as ‘late onset’ congenital adrenal hyperplasia

Question 24

What nail changes are evident in Addison disease?

Answer 24

Longitudinal pigmented bands

Question 25

What skin condition may be associated with Addison disease?

Answer 25

Vitiligo

Question 26

What effect does Addison disease have on blood pressure?

Answer 26

• hypotensive and orthostatic
• most have systolic BP less than 110

Question 27

What do you screen for in young men with idiopathic Addison disease?

How?

Answer 27

Adrenoleukodystrophy

Very long chain fatty acid levels - they’ll be really high

Question 28

How is the diagnosis of primary adrenal insufficiency made? (Addison’s disease)

What is the role of doing a morning cortisol test?

Answer 28

A diagnosis of primary adrenal insufficiency is confirmed by the combination of:

1. a positive short Synacthen test (ie an absent or severely blunted plasma cortisol response to tetracosactrin 30 to 60 minutes after injection)
2. elevated adrenocorticotrophic hormone (ACTH)
3. elevated plasma renin (measured by direct concentration or plasma renin activity).

Measuring diurnal (morning and afternoon) plasma or serum cortisol concentrations is not useful for evaluating adrenal insufficiency.

Question 29

What does hypercalcaemia in Addison disease mean?

Answer 29

Heralds an Addisonian crises

Question 30

What happens to the blood glucose in Addison disease?

Answer 30

Fasting blood glucose is low because there is no cortisol to help glycogenolysis

Question 31

Which drug must you avoid giving before a short synacthen test?

Answer 31

Hydrocortisone must not be given for at least 8 hours prior.

Other corticosteroids do not interfere with the assay and can be given.

Question 32

What is the common precursor to male female sex hormones?

Answer 32

Androstenedione is the common precursor of male and female sex hormones

Question 33

What does aromatase do?

Answer 33

It transforms androstenedione to estrone and testosterone to estradiol.

Estradiol is the primary premenopausal oestrogen and is made in the ovary from testosterone.

Estrone is in postmenopausal women and is made in adipose tissue.

Question 34

What is the role of serum DHEA in Addison disease?

Answer 34

Suppressed in Addison disease

Normal or elevated excludes

Low level not diagnostic because some of the population have low levels.

Question 35

What feature of congenital adrenal hyperplasia makes it diagnosable at birth?

What is required for diagnosis?

Answer 35

Ambiguous genitalia

Elevated 17-OH progesterone

Question 36

Aside from aiding in the diagnosis of Addison disease, how else is an elevated plasma renin useful?

Answer 36

• indicated intravascular volume depletion and need for higher doses of fludricortisone

Question 37

What happens to the serum adrenaline in Addison disease?

Why?

Answer 37

Low

Not enough cortisol required to induce the PNMT enzyme in the adrenal medulla which synthesies adrenalin from noradrenalin

Question 38

What antibodies are found in autoimmune Addison disease?

Answer 38

• anti-adrenal antibodies in 50%
• antibodies to thyroid in 45%

Question 39

What imaging is done in Addison disease?

Answer 39

If not clearly autoimmune –> CXR to look for TB, fungal infection or cancer

CT abdo will show small noncalcified adrenals in autoimmune addisons (calcified if TB or other causes)

Enlarged if metastatic or granulomatous causes.

Question 40

What is the DDx for Addison disease?

Answer 40

• secondary (hypopituitarism) - but lack ACTH and have normal skin pigmentation
• ACTH deficiency –> normal mineralocorticoid production and do not develop hyperkalemia.
• Haemochromatosis can cause skin pigmentation. Can also cause Addison, hypoPTHism and diabetes
• AIDS can cause hypocortisolism and frank adrenal insufficiency
• CAH - but will have features of androgen excess

Question 41

Which oral contraceptive component causes hyperkalemia?

Answer 41

Drosperinone. Progestin component of Yaz/Yazmin.

Question 42

What are the causes of hyperreninaemic hypoaldosteronism?

Answer 42

Myotonic dystrophy

Aldosterone synthase deficiency

17 hydroxylase deficiency (salt wasting CAH)

Question 43

What are the causes of hyporeninaemic hypoaldosteronism?

Answer 43

due to decreased angiotensin 2 production as well as intra-adrenal dysfunction

ACEIs and NSAIDs
RTA Type IV
Diabetic nephropathy

Hypertensive nephrosclerosis

Tubulointerstitial disease

AIDS

Question 44

Describe the mineralocorticoid, glucocorticoid and sex steroid pathway.

Question 45

What is the general management of Addison disease?

Answer 45

Hydrocortisone is the drug of choice - 15-30mg daily in 2 divided doses.

Fludrocortisone retains sodium. Used in presence of hyponatraemia, postural hypotension or hyperkalemia (gets exchanged for sodium). Titrate to postural BP, serum K+ and plasma renin (increase if renin elevated)

DHEA - improved sexual function in women and sense of general wellbeing in both, may increase lean body mass and bone density but not confirmed and replacement is not routine.

Question 46

What is the role of fludrocortisone in Addison disease?

Answer 46

• better symptom control when they receive routine mineralocorticoid therapy as well as gluco corticoid
• allows good control at a lower glucocorticoid dose, minimising side effects
• no need to adjust dose in times of stress

Question 47

What are the goals of therapy in Addison disease?

How is this limited?

Answer 47

Normal Blood pressure, sodium and potassium

Plasma renin at upper end of normal range.

Limited by plasma renin as increasing fludrocort causes oedema and hypokalemia.

Question 48

What is the prognosis of treated Addison disease?

Answer 48

Reasonably normal

Increased all-cause mortality, mainly from cardiovascular disease, malignancy and infection

May have ongoing chronic low-grade fatigue.

Question 49

What are the general clinical findings of hypercortisolism (Cushing Syndrome)?

Answer 49

Central obesity

Muscle wasting

Thin skin

Hirstutism

Purple striae

Psych changes

Osteoporosis

Hypertension

Poor wound healing

Question 50

What are the biochemical and serum changes of hypercortisolism (Cushing’s Syndrome)?

Answer 50

Hyperglycaemia and glycosuria

Leukocytosis

Lymphocytopaenia

Hypokalaemia

Elevated serum cortisol and urinary free cortisol without suppression by dexamethasone

Question 51

What is the general cause of Cushing syndrome?

Answer 51

Exogenous

Only rarely due to excessive corticosteroids produced by adrenal cortex

Question 52

What is Cushing disease?

Answer 52

ACTH hypersecretion by the pituitary.

Usually a benign pituitary adenoma that is <5mm and located in the anterior pituitary.

3x more common in women

Question 53

What party drug can induce ACTH-dependent Cushing syndrome?

Answer 53

GHB

Question 54

Aside from drugs and benign pituitary adenoma, what else causes Cushing syndrome?

Answer 54

Autonomous adrenal secretion independent of ACTH which is low, usually due to a unilateral adrenal tumour.

Nonpituitary ACTH secreting neoplasms (i.e. SCLC) that produce excessive ectopic ACTH. Usually hypokalaemic and hyperpigmented. Masses are usually large.

15% of cases are of unknown origin.

Question 55

Other than osteoporosis, what else does cortisol do to bone?

Answer 55

Avascular necrosis.

Question 56

What effect does excess cortisol have on the gonads?

Answer 56

Erectile dysfunction in men

Amenorrhoea or oligomenorrhea in women.

Question 57

What is the cause of polyuria in hypercortisolism?

Answer 57

Due to increased free water clearance - diabetes with glycosuria may worsen it.

Question 58

When is pharmacological blockade of corticosteroid production required? How do you do it?

Answer 58

• the patient requires control of hypercortisolism preoperatively
• the source of ACTH excess is unclear
• surgical resection has been unsuccessful.

Ketoconazole is the treatment of choice

Question 59

What is the screening test for Cushing syndrome?

Answer 59

Dex suppression test - 1mg given at 11pm then morning cortisol performed.

Low morning cortisol excludes Cushing - HOWEVER if still clinically expected, need to test further as this is only a screening test.

Question 60

How is the diagnosis of hypercortisolism made?

Answer 60

24 hour urine collection for free cortisol and creatinine - abnormally high free cortisol or cortisol/creatinine ration confirms hypercortisolism.

Creatinine is secreted constantly while cortisol is under diurnal control. Having the creatinine there makes sure enough urine was collected.

Question 61

What is the role of the midnight cortisol test?

Answer 61

Cortisol lowest at midnight (normally)

Even in Cushing’s, morning serum cortisol may be normal, an elevated midnight cortisol can distinguish it form other conditions that cause a high urine free cortisol (pseudo-Cushings).

A later night salivary version can be done too which is sensitive and specific.

Question 62

Which drugs can result in a lack of cortisol suppression on the dexamethasone suppression test and why?

Answer 62

Phenytoin and rifampicin accelerate dexamethasone metabolism, meaning that cortisol doesn’t get suppressed.

Estrogens i.e. in pregnancy or OCP can also stop suppression by dexamethasone.

Question 63

What are the non-Cushing’s causes of hypercortisolism?

Answer 63

Depression

Anorexia nervosa

Alcoholism

Familial cortisol resistance

Question 64

What is ACTH-independent macronodular adrenal hyperplasia?

Answer 64

Hypercortisolism due to the adrenal cortex’ cells abnormal stimulation by hormones such as caetcholamines, vasopressin, serotonin, HCG or GIP

When stimulated by GIP (gastric inhibitory polypeptide) –> cortisolism will be intermittent and food dependentent, ACTH may not be completely suppressed.

Question 65

Once hypercortisolism has been confirmed, which test should come next?

Answer 65

Serum ACTH

• low = probable adrenal tumor
• high = pituitary or ACTH secreting tumor

Question 66

In ACTH independent Cushing syndrome, what will CT of the adrenals show?

Answer 66

Usually a benign adrenal adenoma

Question 67

When should an adrenal carcinoma in the setting of hypercortisolism be suspected?

Answer 67

• diameter >4cm
• nodule growth
• atypical imaging ie density on noncon CT
• >10 Hounsfield units or high CT contrast washout

Question 68

What is the basic use of Hounsfield units?

Answer 68

Tissue differentiation on CT.

Zero is water

Greater than 10 tends to be organ or tissue (i.e kidney, blood, muscle, brain)

Greater than 100 tends to be soft tissue

Greater than 700 is bone.

Less than zero is fat down to -500, then lung, then air (1000)

Question 69

What imaging modality is required to confirm ACTH-dependent Cushing syndrome?

Answer 69

MRI

• will demonstrate pituitary lesion in 50% of cases often with premature cerebral atrophy
• if less than 5mm, further investigation (inferior petrosal venous sinus sampling) is required

Question 70

When is inferior petrosal venous sinus sampling in hypercortisolism required?

Answer 70

When equivocal on MRI but evidence of ACTH secretion

If more than twice peripheral venous ACTH levels, this is indicative of pituitary Cushing’s disease.

Can be done during CRH administration which will cause inf. petrosal sinus levels to b 3x greater than peripheral ACTH when the pituitary is the source.

Question 71

What testing is employed when inferior petrosal sinus sampling does not reveal a source of ACTH dependent hypercortisolism?

Answer 71

Chest CT/Abdo looking for carcinoid or SCLC. Also look at the thymus, pancreas and adrenals.

• must biopsy a chest mass as more risk of infection and may be infection rather than ACTH secreting mass.

If CT scanning fails - in octreaotide scan may help.

FDG-PET is not useful.

If unable to be found, bilateral adrenalectomy with ongoing investigation with imaging as the ectopic source may become detectable later.

Question 72

How is the hypercortisolism of severe obesity differentiated from the Cushing’s syndrome?

Answer 72

Both will have abnormal dex suppression test but urine free cortisol and diurnal variation of cortisol usually normal in the obese.

Question 73

What is Nelson syndrome?

Answer 73

Rapid enlargement of a pituitary adenoma following bilateral adrenalectomy (this is done v rarely now).

Can cause visual field defect and hyperpigmentation

Question 74

What is the treatment of Cushing disease?

Answer 74

Transphenoidal resection of the pituitary adenoma

Pituitary corticotrophs remained suppressed for up to 3 years - may need hydrocort or pred replacement in the meantime

Recurrence managed with cabergoline.

Lap adrenalectomy if unresponsive

Question 75

What is the treatment of refractory Cushing disease?

Answer 75

Pasireotide - a somastatin analog that targets multiple receptors

Question 76

What are the features of Pasireotide?

Answer 76

a somastatin analog that targets multiple receptors

Question 77

What are the indications for octreotide?

Answer 77

• symptom control and reduction of GH and IGF-1 in acromegaly, inc where surg/rtx/dopamine agonist treatment has failed.
• Acromegaly when unable to undergo surgery or awaiting tx effect of RTx
• symptomatic relief of carcinoid and VIPomas (but NOT curative)
• reduction of pancreatic surgery complications

Question 78

What is cortisol withdrawal syndrome?

Answer 78

Happens in patients successfully treated for Cushings, even with replacement steroids

• hypotension, nausea, fatigue, arthalgia and flaking skin
• increase hydrocort can improve the sx.

Question 79

What are the prognostic features of Cushing syndrome?

Answer 79

Residual MCI, muscle weakness and OP

Good survival

May get relapse if growth of an adrenal remnant post bilateral adrenalectomy

Question 80

What are the pathophysiological features of PCOS?

Answer 80

• Autosomal dominant functional disorder of the ovaries
• adrenal and ovarian androgen hypersecretion
• elevated serum testosterone or free

Question 81

What is the diagnostic criteria of PCOS?

Answer 81

For a diagnosis of PCOS, two of the following criteria must apply—menstrual irregularity, hyperandrogenism and polycystic appearance of the ovaries (which are not necessarily always present in PCOS)

Question 82

Which two hormones are implicated in PCOS?

Answer 82

Excessive LH release by the anterior pituitary, causing the ovaries to produce excess testosterone

High insulin levels increase GnRh pulse frequency, which further forces LH over FSH dominance.

Question 83

What is the source of androgen hypersecretion in PCOS?

Answer 83

Both adrenal and ovarian androgen hypersecretion.

Testosterone is best measure.

Question 84

How is the menstrual irregularity of PCOS treated?

Answer 84

Goal is to restore predictable uterine bleeding and effective endometrial shedding.

Combined OCP is most effective way to regulate menses and does not cause insulin resistance

Metformin can be used when COCP and OCP (progestin) aren’t tolerated and can improve menstrual frequence, although not as well.

Question 85

What happens if you don’t treat a baby girl with classic 21-hydroxylase deficiency?

Answer 85

Without corticosteroid, they will become virilized due to their ambiguous genitalia.

Question 86

What are the general features of androgen excess?

Answer 86

• increased hair (chin, upper lip, abdomen and chest)
• acne
• Menstrual irregularity
• defeminization - loss of breast, hips
• virilization - frontal balding, muscularity, clitoromegaly, voice deepening

Question 87

How should hirstutism and suspected androgen excess be investigated?

Answer 87

Serum or free testosterone

If elevated –> pelvic exam and ultrasound

If negative –> adrenal CT scan

Elevated androstenedione –> ovarian or adrenal neoplasm

Elevated DHEAs - adrenal source as this only produced by the adrenal gland. Usually due to adrenal hyperplasia –> do a CT

Elevated 17-hydroprogesterone in CAH (because 21 is missing)

Question 88

Why would serum LH and FSH be elevated in an amenorrheic woman?

What LH:FSH ratio is common in patients with PCOS?

Answer 88

Ovarian failure

LH:FSH ratio >2

Question 89

What is the treatment of severe hyperandrogenism?

Answer 89

Lap bilateral oophorectomy if CT adrenals is normal since small hilar cell tumors of the ovary may not be visible.

Also for salt-wasting and infertility CAH, or treatment resistant hyperandrogenism.

Spironolactone

Finasteride (inhibits 5-alpha reductase) improves hirtsutism but spironolactone is better

Flutamide suppresses testosterone and lowers corticosteroid dose required for CAH.

Question 90

What is the role of simvastatin in PCOS?

Answer 90

When used with OCP, aside from improving lipid profile, greater decreases in hirsutism and serum free testosterone levels

Question 91

What is the treatment of choice for women with PCOS and infertility?

Answer 91

Clomiphene

Question 92

How does clomiphene work?

Answer 92

Clomifene inhibits estrogen receptors in the hypothalamus, inhibiting negative feedback of estrogen on gonadotropin release, leading to up-regulation of the hypothalamic–pituitary–gonadal axis.

It is a selective oestrogen receptor modulator (SERM)

Question 93

What are the general features of primary aldosteronism?

Answer 93

Resistant hypertension

Hypokalaemia

Elevated plasma and urine aldosterone levels and low plasma renin that does not correct with sodium loading.

Question 94

What happens in excessive aldosterone production?

Answer 94

Increased sodium retention

Suppressed plasma renin

Increased renal potassium excretion –> hypokalemia

Increased cardiovascular events (moreso than essential HTN)

Question 95

What are the causes of primary hyperaldosteronism?

Answer 95

• Aldosterone producing adrenal adenoma (Conn syndrome), 40% of which have a mutation potassium channel gene
• Unilateral or bilateral adrenal hyperplasia
• Bilateral form may be corticosteroid suppressible due to an autosomal dominant genetic defect allowing ACTH stimulation of aldosterone production

Question 96

What the clinical findings of primary hyperaldosteronism?

Answer 96

Moderate hypertension or isolated diastolic hypertension

Hypokalaemia –> muscle weakness

Parasthesia, tetany, headache

Polyuria and polydipsia

Question 97

What are the causes of secondary hyperaldosteronism? (Mineralocorticoid excess with high plasma renin)

Answer 97

Usually Hypertensive

Renovascular disease (atherosclerotic, fibromuscular hyperplasia)

Coarctation of the aorta

Renin-secreting tumors

Usually Normo- or Hypotensive

Reduced Circulating Blood Volume:

Gitelman’s Syndrome

Bartter’s Syndrome

Pseudohypoaldosteronism Type I

Diuretic Use (surreptitious or prescribed therapy)

Reduced ‘Effective’ Circulating Blood Volume:

Congestive Heart Failure

Hepatic cirrhosis

Nephrotic Syndrome

Question 98

How is suspected hyperaldosteronism investigated?

Answer 98

• Plasma renin, plasma aldosterone plus ratio. If elevated, test further
• Hypokalemia helpful but normal in 50%
• may have metabolic alkalosis with increased HCO3
• further ix with sodium loading and morning plasma renin, with aldosterone measured as well. Normal or elevated makes primary aldosteronism unlikely.
• dx confirmed with 24 hour urine collection of aldosterone, free cortiisol and creatine. Low plasma renin plus high urine aldosterone = primary aldosteronism.

Question 99

What must be done before properly testing for primary aldosteronism?

Answer 99

Stop diuretics for 3 weeks

Stop dihydropyridine CCBs as can normal aldosterone secretion

Stop b-blockers as they suppress renin in essential htn

Useable anti-HTs are ACEIs, alpha blockers, verapamil, and hydralazine

Question 100

Why can’t a low plasma renin alone confirm hyperaldosteronism?

Answer 100

Occurs in many with with essential hypertension

Question 101

Why can’t a renin:aldosterone ratio diagnose primary hyperaldosteronism?

Answer 101

Not diagnostic - need to confirm with 24 hour urine

The two tests use different units and measurements

Question 102

How do you distinguish between unilateral and bilateral aldosteronism?

When is this indicated?

Answer 102

Adrenal vein sampling - gold standard

Only to direct surgeon to correct adrenal and should only be performed if surgery is being considered

Good test if not hypokalemic, over 40 or have an adrenal adenoma <1cm. Right adrenal vein hard to catheterise.

Samples are assayed for both aldosterone and cortisol during a synacthen infusion to ensure that sampking has got both.

Question 103

What is the role of imaging in hypercotisolism?

Answer 103

All patients with biochemically confirmed primary aldosteronism gets a thin section CT scan of the adrenals to screen for a rare adrenal carcinoma.

In the absence of a large mass, cannot distinguish between unilateral and bilat excess.

Question 104

What is the management of primary hyperaldosteronism?

Answer 104

Trial of spironolactone or eplerenone if no carcinoma or obvious source on adrenal CT and not for surgery

Question 105

What is the difference between spironolactone and eplenerone?

Answer 105

Spironolactone –> antiandrogen activity resulting in breast tenderness, gynecomastia and reduced libido

Eplerenone –> better for men since does not have anti-androgenic effects

Question 106

What is the mechanism of action of spironolactone?

Answer 106

antagonist of aldosterone, acting primarily through competitive binding of receptors at the aldosterone dependent sodium potassium exchange site in the distal convoluted renal tubule

Question 107

Who should be screened for hyperaldosteronism?

Answer 107

BP >160/100

Drug resistant hypertension

Hypertension with spontaneous or diuretic induced hypokalemia?

Hypertension with adrenal incidentaloma

Hypertension with an FHx of early onset hypretension or stroke before age 40

Hypertension and a first degree relative with primary aldosteronism

Question 108

What is the ddx of primary hyperaldosteronism?

Answer 108

• chronic intravascular depletion or renal vascular disease (but will have high renin)
• excessive ingestion of licorice can cause hypertension and hypokalemia as it contains a metabolite tha inhibits adrenal 11b hydroxysteroid dehydrogenase type 2 that normally inactivates cortisol in the renal tubule
• high renal tubular cortisol activates aldosterone receptors –> absorption of sodium and excretion of potassium
• excessive corticosteroid secretion will also cause hypertension with hypokalemia (i.e. CAH 17-hydroxylase deficiency)

Question 109

What are the complications of primary hyperaldosteronism?

Answer 109

Higher rate of CVS complications than essential hypertension

Following unilateral adrenalectomy for Conn syndrome, suppression of the contralateral adrenal may result in temporary postop hypoaldosteronism –> hyperkalemia and hypotension

Question 110

What is the treatment of primary hyperaldosteronism?

Answer 110

Conns (unilateral adenoma) –> lap adrenalectomy or long term spiro/eplerenone

Bilateral adrenal hyerplasia –> long term spironolactone or eplerenone

Need to monitor BP daily as will get a significant BP drop when added to other anti-HTs

Reversible in about 2/3rds of cases

Question 111

What are the general features of phaeo and paraganglionoma?

Answer 111

• attacks of headache, perspiration, palpitation and anxiety
• paroxysmal hypertension esp during surgery or delivery
• elevated urinary catecholamines or their metabolites
• normal serum T4 and TSH

Question 112

What is a phaeochromocytoma?

What is a paraganglionoma?

Answer 112

Phaeo: Adrenaline and noradrenaline secreting tumour of the adrenal medulla

Para: sympathetic paraganglia tumor that often metastasises and secretes norad or is nonsecretory. May be in the adrenals or along the sympathetic chain

Question 113

In phaeo, how do adrenalin and norad differ in their symptomatology?

Answer 113

Adrenaline: Tachyarrythmia

Norad: Hypertension

Question 114

Which diseases are associated with phaeochromocytoma?

Answer 114

Type 2 VHL

MEN 2A and 2B

Recklinghausen Neurofibromatosis Type 1 (NF-1)

Familial paraganglioma

Question 115

What is the chance of harboring a germline mutation in a patient with a family history of phaeo/paraganglionoma?

Answer 115

100%

These account for about 25% of patients with phaeos.

Question 116

What are the lethal manifestations of a phaeochromocytoma?

Answer 116

Catastrophic hypertensive crisis

Fatal cardiac arrhythmia

Question 117

What are the features of a paroxysmal attack of a phaeo?

Answer 117

Hypertension, headache, sweating, palpitations and anxiety

Question 118

What can trigger hypertensive attacks with a phaeo?

Answer 118

IV contrast

Glucagon

Needle biopsy / surgery

Anaesthesia

Exercise, bending, lifting or emotional stress

Certain drugs

Question 119

Which drugs can trigger a hypertensive attack in phaeochromocytoma?

Answer 119

MAO-Is

Caffeine & nicotine

Decongestants

Amphetamines

Cocaine

IV contrast

Adrenalin

Question 120

What is the common main mechanism of phaeochromocytoma associated ACS, stroke, aortic aneurysm rupture, and ischaemic bowel?

Answer 120

Vasospasm due to excess adrenalin release.

Question 121

What is the single most sensitive test for phaeochromocytoma?

Is it diagnostic?

Answer 121

Plasma free metanephrines. Normal levels rule it out.

Not diagnostic as physical/emotional stress, sleep apnoea and MAO-Is (amongst others will elevated).

You need to do a 24 hour urine for fractionated metanephrines and creatinine which will confirm most phaeos. 97% sensitive.

Question 122

Aside from metanephrines, what are the other lab findings of phaeo?

Answer 122

• serum chromogranin A is elevated in 90% and correlate with tumor size, higher in metastatic disease - but elevated in azotemia, hypergastrinemia, exogenous steroids and PPIs.
• neuron specific enolase is positive and implicate a malignant phaeo, normal levels are unhelpful. Often a tumor marker for SCLC

Mild hyperglycemia and leukocytosis

Elevated plasma renin activity

Question 123

What genetic tests should be performed in a patient with phaeochromocytoma or paraganglionoma?

Answer 123

VHL, ret proto-oncogene and SDHB/SDHD mutations

Question 124

What disease does mutation of the ret-proto-oncogene cause?

Answer 124

MEN2a and 2b

Question 125

What is the role and considerations of CT in phaeochromocytoma?

Answer 125

• performed when biochemically or genetically suspected
• non-contrast thin section adrenal CT followed by a contrast using nonionic contrast which reduces the risk of catecholamine release –> hypertensive crisis
• no glucagon should be used for the same reasons
• IV contrast itself can precipitate crisis especially when hypertension is uncontrolled

Question 126

What is the role and considerations of MRI in phaeochromocytoma?

Answer 126

• doesn’t need IV contrast or use radiation
• used in pregnancy and childhood

For CT and MRI

• sensitive for adrenal tumors >0.5cm
• less sensitive for recurrent tumors, mets and extra-adrenal paraganglionomas
• if no tumor: C/A/P performed

Question 127

What is the role of nuclear imaging in phaeochromocytoma?

Answer 127

I-MIBG can localise tumors but less sensitive for MEN2A/B disease or mets.

Used when CT cannot locate a phaeo, making a paraganglionoma more likely.

In-labelled octreotide scanning is sensitive for extra-adrenal disease and locating tumours missed by I-MIBG

FDG-PET similarly may find missed tumours and when combined with non-con CT, is highly sensitive.

Question 128

What is the management of phaeochromocytoma?

Answer 128

• surgical removal of phaeo or paraganglionomas is the treatment of choice.
• alpha blockers are given prior to surgery - BP must be maintained 4-7 days prior to surgery or until ECG changes have normalised (may be months)
• must give alpha or calcium blockers first as starting b-blockers first results in unopposed alpha-adrenergic action –> hypertensive crisis. Labetalol has alpha blocking activity but can still cause paradoxical hypertension.

Question 129

What is the perioperative management of phaeo?

Answer 129

Tachyarrthymia intraop - atenolol

Hypertension intra-op - short acting CCB or nitroprusside

Post-op hypotension (caused by desentisisation of alpha receptors) –> preop auto-transfusion of 1-2 units of PRBCs 12 hours prior can help prevent

Post-op shock –> IV saline and IV norad.

Post-op hypoglycaemia prevention –> IV 5% dex

Question 130

How do you tell if a phaeo is malignant?

Answer 130

Histopath does not reliably determine if tumour is malignant

Recheck plasma metanephrines 2-4 weeks postop and when minimal pain

MIBG scan 3 months post-op - undetected mets may reveal themselves

BP and symptom monitoring for life

Plasma metanephrines 6 monthly for 5 years

EBRTx for osteolytic bone mets

Question 131

What is the treatment for metastatic phaeo or paraganglionoma?

Answer 131

If sufficient uptake on diagnostic I-MIBG, then can have therapy with high-activity I-MIBG

Question 132

What are the features of vitamin-D resistant rickets?

Answer 132

• impaired renal tubular phosphate reabsorption
• normal serum Ca+, low phos, elevated ALP
• high dose Vit-D and oral phos is tx
• presence as failure to thrive in infancy, X-linked dominant

Question 133

What are the features of Von-Hippel Laundau syndrome?

Answer 133

cerebellar haemangiomas

retinal haemangiomas: vitreous haemorrhage

renal cysts (premalignant)

phaeochromocytoma

extra-renal cysts: epididymal, pancreatic, hepatic

endolymphatic sac tumours

Question 134

What are the general features of hypothyroidism?

Answer 134

Elevated TSH in primary hypothyroidism

Low FT4

Delayed deep tendon reflexes, bradycardia, and dry skin

Fatigue, cold, constipated, fat, hoarse and depressed

Question 135

What tests should be used for screening for hypo/hyperthyroidism?

Answer 135

TSH - most sensitive for primary hypo and hyperthyroidism

Free Thyroxine (Free T4)

Question 136

What tests should be performed for hypothyroidism and what will they show?

Answer 136

Serum TSH - high in primary and low in secondary hypothyroidism

Anti-thyroglobulin and anti-thyroperoxidase antibodies - both elevated in Hashimoto thyroiditis

Question 137

What tests should be performed for hyperthyroidism and what will they show?

Answer 137

Serum TSH - suppressed unless pituitary TSHoma/hyperplasia (rare)

T3 or FT3 - elevated

Antithyroglobulin and antimicrosomal (TPO) antibodies - elevated

Anti-TSHr (TRab) antibodies - 65% positive in Graves disease

123-I uptake and scan - diffuse increased uptake (as opposed to ‘hot’ area)

Question 138

What tests should be performed for thyroid nodules and what will they show?

Answer 138

FNA - best method for thyroid cancer

123-I uptake and scan - cancer usually ‘cold

99m Tc scan - vascular vs avascular

U/S - assists FNA bx, assesses malignancy risk (multinodular goitre or pure cysts are less likely to be malignant. Monitors nodules and patients post-op for carcinoma.

Question 139

What is the mechanism of myxedma in hypothyroidism?

Answer 139

Interstitial accumulation of hydrophilic mucopolysaccharides –> lymphoedema

Question 140

What is the mechanism of hyponatraemia in hypothyroidism?

Answer 140

Impaired renal NA+-K+-ATPase activity –> reduced renal tubular reabsorption of sodium

Question 141

What is the most common cause of hypothyroidism?

Answer 141

Hashimoto thyroiditis

Question 142

Which TKI causes transient primary hypothyroidism?

Answer 142

Sunitinib - used to treat GIST

Question 143

When does amiodarone-induced hypothyroidism most occur?

What happens to the TSH and T4?

What is the role of thyroxine replacement?

Answer 143

Pre-existing auto-immune thyroiditis who are not iodine deficient.

Elevated TSH w/ low or normal T4

Given just enough thyroxine to relieve symptoms

Question 144

Which infectious disease is an associated with an increased risk of auto-immune thyroiditis and how does treatment of that disease affect it?

Answer 144

Hepatitis-C

Risk of dysfunction even high when treated with either IFN-a or IFN-b

Question 145

What happens to a hypothyroid woman’s period?

Answer 145

Menorrhagia

Question 146

What cardiopulmonary manifestations may less commonly occur with hypothyroidism?

Answer 146

Cardiac enlargement ‘myxedema heart’

Pericardial effusion

Question 147

What autoimmune conditions are associated with Hashimoto thyroiditis?

Answer 147

Coeliac disease
Also - Addison, hypoPTH, DM, pernicious anaemia, Sjogren, vitiligo, and PBC.

Question 148

What will deficiencies of the fat soluble vitamins cause?

Answer 148

Vitamin K - easy bruising

Vitamin A - hyperkeratosis & night blindness

Vitamin D - bone pain

Vitamin E - neuropathy/ataxia (also B12)

Question 149

What lab abnormalities may be seen in hypothyroidism other than thyroid-specific ones?

Answer 149

Increased LDL, TGL, lipoprotein-a

Increased liver enzymes and CK

Increased prolactin

Hyponatraemia

Hypoglycaemia

Anaemia

Elevated ANA (but not indicative of lupus)

Question 150

What is subclinical hypothyroidism?

What is the treatment?

Answer 150

Serum TSH in upper range of normal with normal T4 levels

Usually asymptomatic or subtle signs (fatigue, depression, hyperlipidemia)

No need to replace if asymptomatic - associated with familial longevity

Monitor - may become hypothyroid later

Question 151

What imaging is used in hypothyroidism?

Answer 151

Not usually necessary.

May get enlargement of pituitary gland due to hyperplasia which could be mistaken for pituitary adenoma as often have concomitant hyperprolactinaemia.

May get thymic enlargement in autoimmune thyroiditis.

Question 152

What is Reverse T3?

What is the order of appearance in the body of the other thyroid hormones?

Answer 152

Third-most common iodothyronine the thyroid gland releases into the bloodstream

T4 constitutes 90% and T3 is 9%.

However, 95% of rT3 in human blood is made elsewhere in the body, as enzymes remove a particular iodine atom from T4.

Question 153

What are the features of euthyroid sick syndrome?

Answer 153

The most common hormone pattern in sick euthyroid syndrome is a low total and unbound T3 levels with normal T4 and TSH levels.

Affected patients may have normal, low, or slightly elevated TSH depending on the spectrum of illness. Total T4 and T3 levels may be altered by binding protein abnormalities, and medications. Reverse T3 levels are generally increased signifying inhibition of normal Type 1 enzyme or reduced clearance of reverse T3. Generally the levels of Free T3 will be lowered, followed by the lowering of Free T4 in relation to severity of the disease.

Low serum T4 (very low = poor prognosis), low levels of free T4
Accelerated metabolism of T4 to rT3

Increased levels of rT3 due to stable production and decreased clearance

May have normal or low TSH

Critically ill patients have a circulating inhibitor to thyroxine binding globulin resulting in computed levels of protein-bound T3 and T4 to be low.

Question 154

What is the important differential of sick euthyroid in a severely ill patient?

Answer 154

A low serum T4 with no elevation in TSH may also be due to pituitary insufficiency however without a prior brain lesion or hypopituitarism, it’s unlikely to suddenly develop it.

If suspected hypopituituarism, DI or CNS endocrine lesion, can give T4 empirically.

Some antiseizure medications will call low serum FT4 by accelerating hepatic conversion of T4 to T3 and will also have normal TSH levels

Dopamine may suppress TSH in prolonged dopamine infusion.

Question 155

What infectious disease are patients with severe hypothyroidism more at risk of?

Answer 155

• bacterial pneumonia

Question 156

What is myxedema crisis?

What population is it seen in?

What drug do you need to be wary about?

Answer 156

Severe life threatening hypothyroidism
Impaired cognition to coma

Seizures

Severe hypothermia & hypoventilation

Hyponatraemia, hypoglycaemia and hypotension

Rhabdo and AKI

Hyponatraemia may be severe and refractory

Myxedema coma - elderly women who have had a stroke or stopped taking their meds

Also if underlying illness

Unusually sensitive to opioids - regular dosing may cause death.

Question 157

What must you assess for in a hypothyroid patient prior to starting levothyroxine?

Answer 157

Adrenal insufficiency and angina as these must be treated first.

Question 158

What is the target TSH in treated hypothyroidism?

Who needs a higher dose?

When should you take it?

Answer 158

Aim to keep between 0.4 and 2.0 and maintain clinical response

Pregnant women

After an overnight fast as food interferes a little with absorption

Question 159

What are the considerations for levothyroxine treatment in patients with heart disease or over age 60?

Answer 159

Smaller initial doses

If known IHD, should have angio or bypass first.

Question 160

How is myxedema crisis treated?

Answer 160

High dose IV levothyroxine since myxedema interferes with intestinal absorption of PO

Hypothermia - warming blankets only as faster can precipitate cardiovascular collapse.

Hydrocort if concomitant adrenal insufficiency

Question 161

In treated hypothyroidism, what does an elevated TSH indicate?

Which test should be maintained within the reference range?

Answer 161

Usually indicates the need for higher levo dose.

Serum T3.

Normal serum TSH and FT4 levels do not determine euthyroid status.

Question 162

Which drugs increase hepatic metabolism and conversion T4 to T3?

Answer 162

Anticonvulsants: Carbamazepine, phenytoin

Antibiotics: Rifampicin

TKIs: Sunitinib and Glivec

Question 163

Which drugs cause malabsorption of levothyroxine and worsening of hypothyroidism?

Answer 163

Iron (beware multivitamins!)

Calcium

Mag

Aluminium

Sevelamer

Fibre

Raloxifene

Cholestyramine

PPIs by reducing gastric acidity

Question 164

Which two states require an increased levothyroxine dose for hypothyroidism?

Answer 164

Pregnancy or on oral estrogen therapy

Requirements decrease after delivery and menopause

Question 165

What are the principles of hypothyroidism in pregnancy?

Answer 165

Fetus is partly dependent on maternal T4 for CNS development especially in the third trimester with requirement starting very early in pregnancy.

Levo should be increased by approx 30 as soon as pregnancy is confirmed. This increases to nearly 50% by mid pregnancy.

Question 166

What are the mechanisms of increased FT4 requirement of pregnancy?

Answer 166

1. Rising estrogen –> increases thyroxine binding globulin concentration –> free T4 reduced
2. Placental deiodinase promotes turnover of T4
3. Prenatal multivitamins (containing iron and Ca) binds to oral T4 and reduces intestinal absorption

Question 167

Why do serum TSH levels drop while T4 rises during the first trimester of pregnancy?

Answer 167

Probably due to high levels of HCG (structurally homologous to TSH) stimulating thyroid hormone production.

Low TSH patients in first trimester are euthyroid.

Question 168

In short bowel syndrome and resultant malabsorption of thyroxine, what can be given to improve it?

Answer 168

Medium chain triglyceride oil

Question 169

What can cause transient or false elevations in TSH?

Answer 169

• psych illness or recovery from a nonthyroidal illness
• autoimmune disease can interfere with an assay
• thyrotropin secreting tumors
• increased by phenothiazines and atypical antipsychotics

Question 170

In hypothyroid patients who have a normal serum TSH but still feel unwell, what might the reason be?

Answer 170

Suboptimal T3 - may need to increase levo dose

Question 171

What is a low TSH?

Suppressed?

Answer 171

0.4-4 is low

<0.03 is suppressed

Question 172

In a patient with a low serum TSH and no signs of hyperthyroidism, what should you consider?

Answer 172

Hypopituitarism or severe nonthyroidal illness

Medications: NSAIDS, opioids, nifedipine, verapamil and short term high dose steroids

Question 173

What illnesses can mimic hypothyroidism in a hypothyroid patient who has a low TSH controlled on levo?

What test is most helpful?

Answer 173

Adrenal insufficiency

Hypogonadism

Anaemia

Coeliac disease

depression

Serum T3

Question 174

When should you do a free T3 instead of a serum T3?

Answer 174

Pregnancy and in women receiving oral oestrogens

Question 175

What is the long term risk of a hypothyroid patient with a low TSH (0.04-0.4) on replacement thyroxine?

What about if they’re suppressed? (<0.03)

Answer 175

No long term increased risk of cardiovascular disease, dysrhythmia or fractures.

Suppressed - increased risk of all of the above - need monitoring for atrial arrhythmias and osteoporosis

Question 176

What is the mortality rate of myxedema crisis?

Answer 176

20-50%

Untreated hypothyroidism progresses to this

Question 177

What are the general symptoms of Graves disease?

Answer 177

Palpitations, anxiety, weight loss, loose stools, heat intolerance, fatigue, menstrual irregularity

Question 178

What are the general signs of hyperthyroidism?

Answer 178

Tachycardia, warm moist skin, stare and tremor.

In Graves: Goiter with bruit, opthalmopathy

Question 179

What are the general lab findings of hyperthyroidism?

Answer 179

Suppressed TSH in primary hyperthyroidism’; increased T4, FT4, T3, and FT3

Question 180

What is the other name for Graves disease?

Answer 180

Basedown disease

Question 181

What is the pathophysiology of Graves disease?

Answer 181

Autoantibodies bind TSH receptor in thyroid cell membranes and stimulate the gland to hyperfunction –> increase in synthesis and release of thyroid hormones

Thymus gland is typically enlarged and serum ANA are usually elevated

Question 182

What signs are commonly associated with Graves disease?

Answer 182

Infiltrative opthalmopathy (Graves exopthalmos)

Less commonly - infiltrative dermopathy (pretibial myxoedema)

Question 183

What are the genetic associations with Graves disease?

Answer 183

Familial tendency

HLA-B8 and HLA-DR3 association

Question 184

What can trigger Graves disease?

Answer 184

Dietary iodine supplementation

Potassium iodide reatment

Amiodarone

Question 185

What diseases are people with Graves disease also at risk of getting?

Answer 185

Sjogren syndrome

Perncious anaemia

Addison disease

Alopecia

Vitiligo

Coeliac disease

DM Type 1

Hypopth

Myasthenia gravis

Cardiomyopathy

Question 186

What is Jod-Basedow disease?

Answer 186

Iodine-induced hyperthyroidism

May occur in large multinodular goiters after large intake of dietary iodine, IV contrast, amiodarone

Not associated with opthalmolpathy or dermopathy

Question 187

What are the features of subacute (de quervain) thyroiditis?

Answer 187

• enlarged tender thyroid and hyperthyroidism
• due to a viral infection
• followed by hypothyroidism

Question 188

What is Struma Ovarii?

Answer 188

• hyperthyroidism due to autonomously secreting thyroid tissue
• found in 3% of ovarian dermoid tumours and teratomas
• may secrete in concert with toxic nodule, MNG, or Graves

Question 189

What are the laboratory features of hyperthyroidism due to a pituitary tumour?

Answer 189

• elevated or normal serum TSH in the presence of true thyrotoxicosis
• diminished feedback effect of T4 on the pituitary
• rare

Question 190

What are the causes of hyperthyroid thyroiditis?

Answer 190

Hashimotos will cause transient hyperthyroidism during the initial destructive phase

IFN-A, IFN-B, interleukin-2

Postpartum thyroiditis = Hashimoto’s within first 6 months of delivery

Question 191

What are the features of hyperthyroidism in pregnancy?

Answer 191

Increased neonatal risk of IUGR, prematurity and transient thyrotoxicosis from transplacental transfer of thyrotropin receptor antibody (TRab)

• very high serum levels of HCG may cause sufficient receptor activation to cause thyrotoxicosis in spite of their low affinity for the thyroid receptor

Question 192

When does mild gestational hyperthyroidism occur?

Why?

Answer 192

First 4 months of pregnancy

Due to very high HCG levels

Question 193

When are pregnant women more likely to have thyrotoxicosis and hyperemesis gravidarum?

Answer 193

If they have high serum levels of asialo-HCG, a subfraction of HCG with greater affinity for TSH receptors

Question 194

What type of damage does iodinated IV contrast do to the thyroid?

Answer 194

Induces a destructive subacute thyroiditis that may be painful and similar to type 2 amiodarone-induced thyrotoxicosis

Question 195

When can hyperthyroidism occur with amiodarone?

Answer 195

4 months to 3 years after initiation

Question 196

What are the general features of type 1 amiodarone-induced thyrotoxicosis?

Answer 196

• may cause toxic MNG in setting of iodine deficiency w/ autonomous thyroid nodules
• excess free iodine can trigger immunologic attack on thyroid resulting in Graves disease
• diffuse thyroid enlargement and antithyroid peroxidase antibodies (70%)

Question 197

What are the differences on imaging between type 1 and 2 amiodarone thyrotoxicosis?

Answer 197

Type 1 - diffuse enlargement, color flow doppler –> increased vascularity and blood flow velocity. Thyroidal radioiodine uptake can be low/normal/increased

Type 2 - no enlargement, no increase in vascularity, and very low thyroidal radioiodine uptake

Question 198

What is type 2 amiodarone induced thyrotoxicosis?

Answer 198

• Due to destructive thyroiditis
• Stored thyroid hormone released from damage cells
• Can last 1-3 months and may be followed by hypothyroidism

Question 199

What are the features of chronic thyrotoxicsois?

Answer 199

Osteoporosis

Clubbing

Swelling of the fingers (acropachy)

Question 200

What are the cardiopulmonary manifestations of hyperthyroidism?

Answer 200

• Tachycardia
• AF w/ RVR
• reversible pulmonary hypertension (mainly PaH)

Question 201

What are the eye manifestations that can occur with hyperthyroidism of any aetiology?

Answer 201

Upper eyelid retraction (Dalrymple sign)

Lid lag with downward gaze (von Graefe sign)

Staring appearance (Kocher sign)

Question 202

What eye manifestation is exclusive to Graves disease and type-1 amiodarone induced thyrotoxicosis?

Answer 202

• opthalmopathy
• conjunctival oedema (chemosis)
• conjunctivitis
• mild exopthalmos (proptosis)

Question 203

What are the manifestations of severe exopthalmos of Graves?

Answer 203

• increased retro-orbital and eye muscles that have been thickened by lymphocytic infiltration
• diplopia from extraocular muscle entrapment
• weakness of upward gaze (Stellwag sign)
• optic nerve compression –> progressive loss of colour vision, fields, and acuity

Question 204

How does thyroid eye disease correlate with thyrotoxicosis?

Answer 204

It doesn’t - some patients with Graves opthalmopathy are clinically euthyroid

Question 205

What extra test should be performed on all patients with confirmed Graves disease and why?

Answer 205

Exopthalmometry

Document degree of exopthalmos and detect progression of orbitopathy

Question 206

What is the differential diagnosis for Graves opthalmopathy?

What are it’s features?

Answer 206

Coexistent ocular myasthenia gravis

More common in Graves

Usually mild with selective eye involvement

ACHr Abs only elevated in 40%

Thymoma in 9%

Question 207

What are the features of Graves dermopathy (pre-tibial myxoedema)?

Answer 207

• more common with high levels of TSH-stiulating Ig and in severe Graves opthalmopathy
• glycosaminoglycan accumulation and lymphoid infiltration occurs in infected skin which becomes erythematous with a thickened rough texture

Question 208

What is thyroid acropachy?

Answer 208

• extreme and rare
• digital clubbing, swelling of fingers and toes and periosteal reaction of extremity bones
• most patients are smokers
• indicates severity of autoimmunity - high titres of thyroid-stimulating Ig

Question 209

What are the features of hyperthyroidism related tetany?

Answer 209

• rare
• due to incresaed renal excretion of magnesium
• severe depletion causes hypoparathyroidism that results in hypocalcaemia

Question 210

What effect does Graves disease have on pregnancy and vice versa?

Answer 210

• Increased risk of thyroid storm, eclampsia, CCS, prem, abruption
• TSHrAb crosses the placenter - if maternal serum TSHrab levels >500% in third tri –> risk of transient neonatal graves

Question 211

Which weird disease no one’s ever heard of occurs with thyrotoxicosis? What are the features?

Answer 211

• Hypokalemic periodic paralysis - Asians and Native American men
• symmetric flaccid paralysis often after oral carbs, vigorous exercise or IV dextrose
• attacks last 7-72 hours

Question 212

What is ‘subclinical hyperthyroidism’?

Answer 212

• asymptomatic individual
• low serum TSH w/ normal FT4 and T3
• risk of progression higher with MNG

Question 213

What are the other lab findings in hyperthryoidism generally?

Answer 213

Hypercalcaemia

Increased ALP

Anaemia

Agranulocytosis

Thyrotoxic periodic paralyisis: Hypokalemia and hypophosphataemia

Question 214

What are the general lab findings in Graves disease?

Answer 214

Detectable TSHRabs (65%)

Antithyroglobulin or anti TPO can be elevated by not specific

Elevated ANA/dsDNA w/o evidence of lupus or collagen-vascular disease

Question 215

What are the general lab findings in subacute thyroiditis?

Answer 215

Increased ESR

No anti-thyroid antibodies

TSHRaBs are negative

Question 216

What are the general lab findings in iodine induced hyperthyroidism?

Answer 216

Undetectable TSHrAbs

No anti TPO antibodies

Elevated urinary iodine concentration

Question 217

How do you distinguish thyrotoxicosis factitia from other causes of hyperthyroidism?

Answer 217

Serum thyroglobulin levels will be low

Question 218

What are the lab findings of hyperthyroidism during pregnancy?

Answer 218

Elevated FT4

Suppressed TSH - although failure to suppress may be due to misidentification of HCG

T3 resin uptake is low because of high TBG concentration

In Graves - beneficial effect, decreasing antibody tires and decreasing FT4 as pregnancy progresses

Question 219

What must be present along with the elevated T4 of amiodarone induced hyperthyroidism?

Answer 219

Suppressed TSH - patients taking amiodarone will have high T4 and FT4 levels regardless of whether or not they’re hyperthyroid.

Question 220

What findings are diagnostic of type 1 amiodarone induced thyrotoxicosis?

Answer 220

Proptosis and TSH Ig

Question 221

What interleukin is markedly elevated in type 2 amiodarone induced hyperthyroidism?

Answer 221

Il-6

Question 222

In which thyroid conditions will you get a high radioactive iodine uptake?

Answer 222

Graves

Toxic nodular goitre

Question 223

In which thyroid conditions will you get a normal-low radioactive iodine uptake?

Answer 223

Type 1 amiodarone-induced thyrotoxicosis - usually detectable but low

Question 224

In which thyroid conditions will you get a low radioactive iodine uptake?

Answer 224

Subacute thyroiditis

Iodine induced hyperthyroidism

Type 2 amiodarone induced thyrotoxicosis

Question 225

When is radioactive iodine imaging helpful?

Answer 225

• determine the cause of hyperthyroidism
• not necessary if obvious Graves (TSHrabs or associated Graves opthalmopathy)
• never in pregnant women

Question 226

When should a radioactive iodine scan be extended to include the abdomen?

Answer 226

Screen for concomitant struma ovarii in women with Graves

Question 227

When is thyroid ultrasound useful?

Answer 227

Hyperthyroid patients particularly with palpable nodules

Question 228

When is thyroid color flow doppler u/s useful?

Answer 228

Distinguish between type-1 amiodarone induced thyrotoxicosis (increased blood flow velocity and vascularity) and type 2 (reduced vascularity)

Question 229

When it orbital imaging indicated in thyroid disease and why?

Answer 229

MRI or CT visualises Graves opthalmopathy affecting the extraocular muscles

Required in severe or unilateral cases, or in euthyroid exopthalmos that must be distinguished from orbital pseudotumor, tumors, and other lesions

Question 230

What is the ddx of thyrotoxicosis?

Answer 230

• hypermetabolic states ie anaemia, leukaemia, polycythaemia dn cancer
• Pheo
• Acromegaly
• cardiac disease suggests possibility of ‘apathetic’ hyperthyroidism
• other causes of opthalmoplegia ie MG and exopthalmos ie tumor
• must consider thyrotoxicosis in ddx of muscle weakness and thyrotoxicosis
• may have concomitant DM or Addison disease

Question 231

What are some complications of hyperthyroidism?

Answer 231

Hypercalcaemia

Osteoporosis

Nephrocalcinosis

Decreased libidio, gynecomastia , erectile dysfunction and sperm motility

Dysrhythmia

Thyrotoxic hypokalemic periodic paralysis

Question 232

What is the role of Propranolol in Graves diseae?

Answer 232

• symptomatic relief of tachycardia, tremor, sweats anxiety
• initial treatment of choice for thyroid storm
• treatment for periodic paralysis

Question 233

What is the role of thiourea drugs in hyperthyroidism?

Answer 233

• methimazole/carbimazole or PTU
• young patients with mild thyrotoxicosis, small goiters or fear of isotopes
• elderly respond well
• presurgical preparation
• no permanent thyroid damage, assoc w/ lower chance of posttreatment hypothyroidism (c/w surgery or RAI)
• contraindicated in breastfeeding

Question 234

What affects long term remission in patients with hyperthyroidism?

Answer 234

• better likelihood if:
  1. small goiter or mild hyperthyroidism
  2. requiring small doses of thiourea
  3. high tpo and tg antibodies 2 years after therapy only have a 10% relapse rate

Question 235

What is the main notable side effect of methimazole and PTU?

Answer 235

Agranulocytosis

Genetic link

Reversible

Not improved by G-CSF

Also: pruritus

Question 236

If a patient has a major allergic reaction to carbimazole, can you give them PTU?

Answer 236

No - because they’re too similar

Question 237

What are the features of carbimazole?

Answer 237

1st line for thyrotoxicosis - induction of permanent remission, prethyroidectomy, before and after radioactive iodine

• less likely to cause fulminant hepatic necrosis and I¹³¹ treatment failure
• risk of fetal anomalies, switch to PTU

Question 238

What are the features of propylthiouracil?

Answer 238

Drug of choice for breastfeeding

Favored in pregnancy

Complications: Arthritis, lupus, aplastic anaemia, thrombocytopaenia, hypoprothrombinaemia

In pregnancy: can be switched to carbimazole in second tri

Question 239

What is the role of iodinated contrast agents as a treatment for thyrotoxicosis?

Answer 239

• effective temporary treatment for thyrotoxicosis of any cause
• Graves: blocked with carbimazole then replaced with iodinated agent
• useful for symptomatic thyrotoxicosis
• option for T4 overdose, subacute thyroiditis, amiodarone-induced thyrotoxicosis, intolerance to thiorureas and newborns with thyrotoxicosis secondary to maternal Graves

Question 240

What is the role of radioactive iodine in treatment of hyperthyroidism?

Answer 240

• destruction of overactive thyroid tissue (diffue or toxic nodular goiter)
• no increased risk of subsequent thyroid cancer, leukaemia or other malignancy
• normal rates of congenital abn
• should not be given to pregnant women due to fetal radiation being harmful

Question 241

What affects treatment success of radioactive I¹³¹?

Answer 241

• Graves + a thiourea of any sort
• can improve effectiveness if discontinue at least 4 days prior and if I¹³¹ dose is adjusted up

Question 242

What is a noteable side effect of I¹³¹ therapy in Graves disease?

Answer 242

Grave opthalmopathy - much more likely if patient a smoker.

Pre-existent opthalmopathy worsens unless you give prophylactic prednisone 2 months prior esp if severe orbital involvement. Smoking decreases effectiveness of pred

Question 243

What happens to the lab results of a thyrotoxic patient treated with I^131?

Answer 243

FT4 levels may drop within 2 months then go up to thyrotoxic levels during which time RAI uptake is low

• due to release of stored thyroid hormone from injured cells, not treatment failure –> FT4 will eventually fall abruptly to hypothyroid levels

Question 244

What increased risks are there for patients with Graves disease treated with I^131?

Answer 244

• increased lifetime risk of hyperparathyroidism particularly if radioidine given in childhood/adolescence
• need lifetime followup with serum TSH, FT4 and calcium

Question 245

What are the indications for thyroidectomy in thyrotoxic patients?

Answer 245

Pregnant women with thyrotoxicosis not controlled with low doses of thioureeas

Women who want to get pregnant in vvery near future

Option for nodular goiters when there is a suspicion of malignancy

Question 246

What are the types of thyroid surgery?

Answer 246

Hartley-Dunhill - treatment of choice for Graves having surgery

• total resection of one lobe and a subtotal resection of the other lobe
• subtotal thyroidectomy of both lobes - but 9% recurrence rate
• total thyrodectomy - increased risk of hypoparathyroidism and damage to the recurrent laryngeal nerves

Question 247

What is the perioperative management for thyrotoxic patients undergoing thyroid surgery?

Answer 247

• rendered euthyroid preop with a thiourea
• propranolol is given until euthyroid
• may given iodine to reduce vascularity
• if thyrotoxic during surgery –> needs higher doses of propranolol

Question 248

What is the morbidity associated with thyroidectomy?

Answer 248

• recurrent laryngeal nerve palsy and vocal cord paralysis
• if both damages –> airway obstruction –> intubation –> trache

Question 249

What is the general management of a toxic solitary thyroid nodule?

Answer 249

Usually benign if no surgery –> FNA

Symptomatic: Propranolol ER and carbi/PTU as for Graves

• keep TSH slightly suppressed so stimulated growth of the nodule is reduced
• under 40: surgery
• over 40/poor health: I¹³¹ , keeping TSH suppressed prior in order to reduce I¹³¹ uptake by the normal thyroid

Question 250

How is toxic MNG treated?

Answer 250

• propranolol and carbi but 95% recurrence rate if stopped
• definitive: surgery - either to release pressure or cosmetic
• I¹³¹ - must stop carbimazole 4 days prior and follow low iodine diet to enhance RAI uptake

Question 251

How does carbimazole work?

Answer 251

Carbimazole is a pro-drug as after absorption it is converted to the active form, methimazole. Methimazole prevents the thyroid peroxidase enzyme from coupling and iodinating the tyrosine residues on thyroglobulin, hence reducing the production of the thyroid hormones T3 and T4 (thyroxine).

Question 252

How does PTU work?

Answer 252

Central - inhibits thyroperoxidase whichhelps iodine addition onto thyroglobulin - an essential step in T4 production

Peripheral: PTU also acts by inhibiting the enzyme 5’-deiodinase (tetraiodothyronine 5’ deiodinase), which converts T4 to the active form T3. (This is in contrast to methimazole, which shares propylthiouracil’s central mechanism, but not its peripheral one.)

Question 253

What side effect is peculiar to I¹³¹ therapy for diffusely nodular toxic goiter?

Answer 253

May induce Graves and Graves eye disease.

Question 254

What is the management of subacute thyroiditis?

Answer 254

Propranolol for symptom relief if thyrotoxic

NSAID or aspirin for pain

Pred if severe

Thioureas and RAI are unhelpful as thyroid production is actually low

May have hypothyroidism afterward, need to monitor

Question 255

What is the management of hyperthyroidism during pregnancy and lactation?

Answer 255

• PTU in first tri then switch to lower risk of foetal abnormalities
• both cross the placenta and can induce fetal hypothyroidism and TSH hypersecretion
• T3 and T4 do not cross the placenta but fetal hypothyroidism is rare if mothers hyperthyroidism is controlled with small doses of thioureas

Question 256

What are the trimester specific thyroid function tests?

Answer 256

First tri

• lower TSH
• higher FT3
• normal FT4

Second tri

• TSH should return to normal, may not
• higher FT3
• lower later

Third tri

• as for second
• higher FT3
• lower FT4

Question 257

How is type 2 amiodarone induced thyrotoxicosis managed?

Answer 257

Propranolol for sx

Prednisone

May be able to continue amiodarone

Carbimazole is ineffective

Question 258

What is the management when the diagnosis of amiodarone types 1 and 2 is unclear?

Answer 258

Propranolol

1 month trial of carbimazole

Pred if severe or when carbi fails to correct

Amiodarone is discontinued if possible

Question 259

Why isn’t PTU first line anymore?

Answer 259

Higher risk of fulminant hepatic necrosis

Question 260

Which drugs can aggravate Graves opthalmopathy?

Answer 260

Thiazolidinediones (glitazones)

Question 261

What is the treatment for acute progressive exopthalmos of Graves?

Answer 261

IV methyl pred (superior to oral)

Doesn’t work as well for smokers

Can also give retrorobulbar radiation with oral pred - although response less good if chronic proptosis and orbital muscle restriction.

• orbital decompression if severe and may save vision but diplopia often persists

Question 262

What is the role of Digoxin in the AF of hyperthyroidism?? Why not a B-Blocker?

Answer 262

Slows RVR

Need larger than normal doses due to increased clearence and increased number of cardiac sodium pumps needing inhibition

Dose reduces as AF does

B-blockers second line as negative inotropic effect may precipitate CHF

Question 263

When are anticoagulants used in hyperthyroidism?

Answer 263

• LA enlargement on TTE
• global LV dysfunction
• recent CHF
• hypertension
• recurrent AF
• hx prev VTE
• smaller doses of Warfarin needed because there is an accelerated clearance of vitamin-K dependent clotting factors

Question 264

How does apathetic hyperthyroidism present?

Answer 264

• angina pectoris
• reverse hyperthyroidism and reverse angina, thus avoiding the need for angioplasty

Question 265

What are the features of a thyroid storm?

Answer 265

• triggered by stress, surg or RAI admin
• severe delirium, tachy, vomiting, high fever
• high mortality rate
• Give hydrocort
• avoid aspirin
• delay definitive treatment until euthyroid

Question 266

Why must you avoid aspirin in a thyroid storm?

Answer 266

Displaces T4 from TBG raising FT4 levels.

Question 267

How is the hyperthyroidism of postpartum thyroiditis managed?

Answer 267

Propranalol during hyperthyroid phase, levo during hypothyroid phase

Question 268

How is Graves dermopathy managed?

Answer 268

• topical corticosteroid with nocturnal plastic occlusive dressings

Question 269

What is the management of thyrotoxic hypokalemic periodic paralysis?

Answer 269

Propranolol - normalise potassium and phosphate, reverses paralysis within 2-3 hours

Avoid IV dextrose and oral CHO - aggravates

Treat underlying hyperthyroidism

No potassium or phosphate replacement usually required

Question 270

What is the long term risk to women with treated Graves disease?

Answer 270

Increased long-term risk of death from thyroid disease, cardiovascular disease, stroke, and fracture of the femur.

Post-treatment hypothyroidism is common

Question 271

What is the prognosis of Graves disease that presents in early pregnancy?

Answer 271

30% chance of spontaneous remission before the third tri

Question 272

What impact on bone physiology does subclinical hyperthyroidism have?

Answer 272

• most don’t have accelerated bone loss but if there is osteopenia, need to do regular followup BMDs.

Question 273

How is an asymptomatic person with subclinical hyperthyroidism managed?

Answer 273

People with very low TSH are closely monitored but are not treated unless AF or other manifestations of hyperthyroidism appear

Question 274

What are the general features of Hashimoto thyroiditis?

Answer 274

• most common
• b-lymphocytic invasian
• Anti-TPO and antithyroglobulin antibodies

Question 275

What is the epidemiology of Hashimoto thyroiditis?

Answer 275

Familial

Women 6x

Childhood/occ exposure to head/neck external beam radiation

Question 276

What predicts long term hypothyroidism after Hashimoto thyroiditis?

Answer 276

smokers

High serum thyroid peroxidase levels

Question 277

What are the disease associations with Hashimoto thyroiditis?

Answer 277

Polyglandular autoimmunity

Celiac disease

Turner Syndrome

Hep-C

Question 278

What are the features of painless postpartum thyroiditis?

Answer 278

• occurs soon after delivery
• may be due to accumulation of fetal cells in the maternal thyroid during pregnancy (microchimerism)
• 70% chance of recurrence in subsequent pregnancies
• occurs mostly if high levels of anti-TPO antibodies in first tri, or immediately after delivery

Question 279

What is de Quervain thyroiditis?

Answer 279

• also known as subacute, granulomatous or giant cell thyroiditis
• usually post viral URTI
• incidence peaks in summer
• young and middle aged women

Question 280

What is the rarest form of thyroiditis?

Answer 280

Riedel or fibrous thyroiditis. Usually found in elderly women as a manifestation of systemic fibrosis.

Question 281

What are the clinical findings in Hashimoto thyroiditis?

Answer 281

• diffusely enlarged, firm, and finely nodular thyroid, sometimes with lobular assymmetry
• absence of pain
• may be assoc w/ mild myasthenia gravis affecting extraocular muscles with low detectable AChR Ab or thymic disease

Question 282

What are the clinical findings of postpartum thyroiditis?

Answer 282

• hyperthyroidism 1-6 months after delivery
• persists for 1-2 months
• hypothyroidism develops 4-8 months after delivery

Question 283

What are the clinical findings of subacute thyroiditis?

Answer 283

Acute and painful enlarged thyroid gland

Low grade fever and fatigue

Thyrotoxicosis in 50% and lasts several weeks followed by hypothyroidism that lasts 4-6 months

Question 284

What are the lab findings of Hashimoto thyroiditis?

Answer 284

Increased anti-TPO antibodies

Increased anti-thyroglobulin antibodies

No need to monitor once diagnosed

Antibodies decline during pregnancy and are undetectable by third tri.

Question 285

What additional tests should you do after confirming Hashimoto thyroiditis?

Answer 285

Coeliac workup:

Serum IgA endomysial aB or TTG

Serum IgA

Must not be on a gluten-free diet at thet ime

Question 286

What are the lab findings in subacute thyroiditis?

Answer 286

Markedly elevated ESR

Low antithyroid antibody titres

(Leuks elevated in suppurative thyroiditis)

Question 287

How do thyroid hormone levels differ between the thyrotoxicosis of thyroiditis and Graves?

Answer 287

Thyroiditis - serum FT4 levels proportinally higher than T3 since the hyperthyroidism is due to passive release of stored thyroid hormone (predominantly T4).

Graves/toxic NG –> T3 is relatively more elevated and hyperthyroidism more severe as T3 more active

Question 288

What are the findings of imaging of Hashimoto thyroiditis?

Answer 288

U/S - diffuse hetergenous density and hypogenecity - distuingishes thyroiditis from MNG or suss nodules, guides FNA

Color flow doppler - distuingishes from Graves (hypervascular) as normal or reduced vascularity

RAI - very low in subacute thyroiditis but otherwise unhelpful in making dx of Hashimoto

Question 289

What is the role of FNA in Hashimoto thyroiditis?

Answer 289

Do it if they have a thyroid nodule

RIsk of papillary cancer about 8%

Not required for deQuervain (subacute) thyroiditis)

Question 290

What is the risk to perimenopausal women with Hashimoto thyroiditis?

Answer 290

Higher relative risk of depression if high serum anti-TPO antibodies

Question 291

What is the role of antibody-specific tests in Hashimoto thyroiditis?

Answer 291

Sensitive but not specific (If negative you’ve ruled it out, if positive it could be other stuff)

Also positive in MNG, malignancy and concurrent Graves

Question 292

What is the treatment of Hashimoto thyroiditis?

Answer 292

• levo if hypothyroid
• if large goitre –> lots of levo to drive down TSH and shrink the goiter
• if euthyroid - monitor, may become hypothyroid years later
• simvastatin and selenium may have a role but no long term data

Question 293

What is the mx of subacute thyroiditis?

Answer 293

Aspirin - relieves pain and inflammation

Propranolol if thyrotoxic and symptomatic

Iodinated contrast causes prompt fall in serum T3 and thyrotoxic symptoms

Question 294

What is the treatment of the really really rare fibrosing Riedel thyroiditis?

Answer 294

Tamoxifen

Question 295

What is the prognosis of Hashimoto?

Answer 295

Excellent - even if they become hypothyroid, it’s easily treated

Question 296

What is the prognosis of postpartum thyroiditis?

Answer 296

80% return to normal

50% develop permanent hypothyroidism within 7 years

More common if multiparous or spontaneous abortion

Papillary cancer plus Hashimoto has a good prognosis

Question 297

What are the general features of thyroid nodules?

Answer 297

Common and mostly benign

Same cancer risk if multiple compared with one

Higher risk if hx head-neck radiation, total body radiation for bone marrow transplant/exp to fallout, FHx, hx malignancy

Question 298

What are the general clinical features of a goitre?

Answer 298

Cosmetic embarassment

If retrosternal –> dyspnoea due to tracheal compression

Large substernal –> SVC syndrome

Question 299

What are the general lab findings for thyroid nodules?

Answer 299

If abnormal TSH –> need imaging to determine if hyperfunctioning (and if so, they are rarely malignant)

Antibody tests –> very high if Hashimoto

If thyroiditis must check for malignancy as often coexists

Question 300

In a patient with a thyroid nodule and a family member with familial medullary thyroid carcinoma or MEN2, what test should be performed?

Answer 300

Serum calcitonin

Question 301

What are the features of imaging with thyroid nodules?

Answer 301

U/S - do to see if palpable nodule is part of MNG

RAI - limited usefulness - only to determine if ‘hot’ or ‘cold’ but can’t differentiate malignancy

CT - larger nodules, degree of tracheal compression and mediastinal extension

Question 302

What are the concerning features of a thyroid nodule on ultrasound?

Answer 302

• irregular or distinct margins
• heterogenous nodule echogenecity
• intranodular vascularity
• microcalcifications
• diameter >1cm

Question 303

How are thyroid nodules with suspicious findings on ultrasound assessed?

Answer 303

FNA - best method

Can be done on anticoagulation/aspirin

Four largest (>1cm) in MNG should be biopsied so you don’t miss it

Question 304

For a solitary thyroid nodule, when is FNA biopsy indicated?

Answer 304

• >5mm with suspicious appearance
• assoc w/ abnormal lymph nodes
• >1cm and solid or have microcalcifications
• mixed cystic-solid nodules >1.5cm in diameter with any suspicious features on U/s
• >2cm and benign on U/S
• spongiform and 2cm

Question 305

What is the management of a thyroid nodule that is found to be cystic on u/s?

Answer 305

Observe - pure cystic nodules are benign and don’t need biopsy.

Question 306

What is the risk of a thyroid nodule being malignant when the FNA cytology reads “suspicious follicular lesion”?

Answer 306

• about 20-25%
• higher if much younger or older than age 50
• bloody aspirate higher chance of malignancy
• surgery usually indicated on suspicious cytology

Question 307

What happens if you give someone with MNG iodinated contrast or IV iodine?

Answer 307

Toxic MNG!

Question 308

What is the role of levothyroxine suppression therapy in patients with nodular goitres?

Answer 308

• replaced if elevated TSH
• suppression most therapy in iodine deficient ares of the world
• long term tx keeps nodules from enlarging and may reduce emergence of new nodules

Question 309

When is levothyroxine suppression therapy for goitre not used?

Answer 309

Cardiac disease - increases risk for angina and AF

Also causes a small lose in BMD in post-menopausal women if serum TSH is suppressed

Low baseline TSH because that means there is autonomous thyroid secretion, meaning levo won’t work and will cause thyrotoxicosis instead

Question 310

What is the role of percutaneous ethanol in treating thyroid nodules?

Answer 310

Shrinks benign cysts quite well as if you suck out the fluid it just comes back. Needs to be repeated but has 80% success rate.

Question 311

What is the role of I¹³¹ therapy in patients with thyroid nodules?

Answer 311

Option for hyperthyroid patients with toxic adenoma, MNG or Graves

Can be used to shrink benign nontoxic nodules

May be used for MNG but may induce Graves

Risk of hypothyroidism years after therapy

Question 312

What is the prognosis of thyroid nodules?

Answer 312

90% will increase in size over 5 years, cystic ones remain fairly stable

MNGs persist or grow slowly

Small incidentalomas require u/s followup ever 1-2 years but low risk

Question 313

What are the general features of thyroid cancer?

Answer 313

Painless swelling

Normal thyroid function tests

Past history of irradiation to head and neck

Positive thyroid needle aspiration

Question 314

What is the most common thyroid cancer?

Answer 314

Papillary carcinoma

Question 315

What are the general features of papillary carcinoma?

Answer 315

Usually from a single nodule but can come out of an MNG - commonly multifocal within the gland

Slow growing, may be more aggressive in older patients with local invasion and spread to the lungs

Hx of head and neck irradiation, medical, Chernobyl etc.

Question 316

What is the underlying pathophysiology of papillary thyroid carcinoma?

Answer 316

• activating mutation of ras oncogene can cause benign adenoma or nodular goiter
• additional activation mutation in BRAF or TRK genes can lead to papillary carcinoma
• 45% caused by overexpression of RET oncogene (medical radiation - retPTC-1, nuclear fallout retPTC-3)

Question 317

What can cause progession of papillary thyroid carcinoma to anaplastic thyroid carcinoma?

Answer 317

Additional loss of p53 tumor suppressor gene in presence of activation mutation of ret oncogene and BRAF/TRK mutations

Question 318

What are the disease associations for papillary thyroid ca?

Answer 318

Autosomal dominant familial syndromes

• familial thyroid ca
• familial polyposis
• Gardner & Turcot syndromes

Question 319

Which is the least aggressive thyroid malignancy?

Answer 319

Papillary carcinoma

• 80% have microscopic mets but no increased mortality rate
• if lymph nodes, only the risk of local recurrence increases

Question 320

What is the second most common thyroid cancer?

Answer 320

Follicular thyroid ca and it’s variants (i.e. Hurthle cell ca)

Generally more aggressive than papillary

Question 321

What are the features of follicular thyroid ca?

Answer 321

• avidly absorb iodine so v treatable
• mets to nodes, bones and lungs
• high risk of poorly differentiated or Hurthle cell variants (both don’t take up RAI)

Question 322

What mutations cause benign follicular adenomas?

Answer 322

• aberrant DNA methylation
• ras oncogene
• MEN1 gene

Question 323

What are the features of medullary thyroid Ca?

Answer 323

• 3% of thyroid cancer
• 1/3 sporadic, 1/3 familial, 1/3 MEN2
• ret oncogene mutation on chromosome 10

Question 324

What additional mandatory testing should be performed in a patient with confirmed medullary thyroid Ca?

Answer 324

Genetic analysis of peripheral white blood cells for the germline mutation of ret oncogene in exon 16.

If positive - related family members must be tested for that gene defect.

If no mutation, can still identify gene carriers with family linkage analysis, or if no defect at all, 6 monthly thyroid surveillance is required.

Question 325

What is the pathophysiology of medullary thyroid ca?

Answer 325

• arise from parafollicular thyroid cells that secrete calcitonin, prostaglandins, serotonin, ACTH, CRH and more
• can be used as tumor markers
• metastasises and does not concentrate iodine

Question 326

What are the features of anaplastic thyroid ca?

Answer 326

Rarest

Older patients with rapidly enlarging mass in a MNG

Most aggressive and metastasizes early

Does not concentrate iodine

Question 327

What are the clinical features peculiar to medullary thyroid ca?

Answer 327

Flushing and persistent diarrhoea - may be the initial clinical features

Cushing syndrome in about 5% due to secretion of ACTH or CRH

Question 328

What is the role of serum thyroglobulin in thyroid ca?

Answer 328

• high in most papillary and follicular tumours making it a marker for recurrent or metastatic disease
• MUST measure antithyroglobulin antibodies as elevation of these can affect the test
• may be misleadingly elevated in thyroiditis which can coexist with Ca
• some assays falsely report elevated levels after total thyroidectomy and tumor resection causing unneeded concern about mets.

Question 329

What considerations must be taken when using calcitonin as a tumour marker for medullary thyroid ca?

Answer 329

• may also be elevated in thyroiditis, pregnancy, azotemia, hypercalcemia and other malignancies
• measure with CEA pre-op, then postop every 4 months for 5 years, then every 6 months for life
• if extensive mets, need to do it with serial dilutions
• the best indication for recurrence is a rising level of calcitonin, not simply a high one as may remain elevated.

Question 330

What is the role of RAI scanning in thyroid Ca?

Answer 330

Thyroid and whole body used post thyroidectomy for surveillance along with U/s

Question 331

What is the role of CT and MRI in thyroid Ca?

Answer 331

CT - particularly good for localising and monitoring lung mets but not good for neck mets

MRI - particularly useful for bone mets. Medullary ca calcified in thyroid, nodes and liver but lung mets rarely do.

Question 332

What is the role of PET scanning in thyroid Ca?

Answer 332

• mets that don’t have good iodine uptake on RAI
• enhanced if hypothyroid or on thyrotropin which increases metabolic activity of differentiated thyroid ca
• low SUV = better prognosis

Question 333

What are the complications of thyroid ca?

Answer 333

1/3 of medullary secrete serotonin and prostaglandins –> flushing and diarrhoea and have coexistent phaeo or hyperparathyroidism

• risks of radical neck surgery inc hypoPTH, vocal cord palsy
• permanent hypothyroidism is expected post-op and should be treated

Question 334

What is the treatment of differentiated thyroid Ca?

Answer 334

Surgical removal with preop neck u/s for LN involvement as may need neck dissection (esp if >1cm diameter)

Question 335

What is the surgical mx of an indeterminate thyroid nodule?

Answer 335

Thyroid lobectomy if <4cm progressing to complete if malignancy detected

Bilateral thyroidectomy as initial surg if >4cm

Question 336

In what circumstance would you do a lobectomy over a total/near total thyroidectomy for confirmed thyroid malignancy?

Answer 336

Ppillary thyroid ca >1cm in diameter under age 45 who have no hx of irradiation or mets.

Question 337

When would you perform a lateral neck dissection in thyroid Ca?

Answer 337

• biopsy proven lateral cervical lymphadenopathy
• muscle resection is usually avoided

Question 338

How do you treat thyroid ca mets to the brain?

Answer 338

Surgically - radiation or RAI doesn’t work.

Question 339

What are the features of hypoparathyroidism postoperatively after thyroidectomy?

Answer 339

Happens in 20%, permanent in 2%

Incidence reduced if accidentally resected parathyroids are immediately autotransplanted into neck muscles.

Watch for tetany

Question 340

What is the management of pregnant women with thyroid cancer?

Answer 340

• delay surg until after delivery unless fast growing then after 24 weeks
• no difference in recurrence or survival if done during or after pregnancy
• higher risk comes from thyroid surg, not cancer

Question 341

What is the general management of the serum TSH in thyroid cancer post thyroidectomy?

Answer 341

Suppress to < 0.1 with stage II disease

Suppress to <0.05 for higher stages

Risk is lower bone density but relatively minor if euthyroid

Question 342

What is the treatment option for thyroid ca resistant to chemo?

Answer 342

Sorafenib and sunitib have partial response.

Question 343

What are the reasons for treatment with I¹³¹ after thyroidectomy?

Answer 343

1- thyroid remnant ablation

2- tx of known or suspected thyroid ca

Question 344

What is a low iodine diet and when would you use it?

Answer 344

• iodised salt, fish and seaweed, commercial bread, dairy, processed meats, canned/dried fruit and juice, black tea, instant coffee, red dye # 3 and MVs.

2 weeks before I¹³¹ so the radioactive form gets taken up instead

Must also avoid amiodarone and iodinated contrast

Question 345

What is the role of RAI therapy in metastatic thyroid Ca?

Answer 345

Improves survival and reduces recurrence rates in Stage III-IV and in II with gross extension or a distant met

Question 346

Which population of patients should have a prophylactic thyroidectomy?

Answer 346

Patients with a ret protooncogene mutation should have a prophylactic total thyroidectomy, ideally by age 6 years (MEN 2A) or at age 6 months (MEN 2B).

Question 347

What is the role of recombinant TSH stimulated I¹³¹ therapy?

Answer 347

Thyrogen (rTSH) is given to increase the sensitive of serum thyroglobulin for residual ca and increase uptake of I¹³¹ into remant tissue or cancer.

• should NOT Be given to patients with an intact thyroid gland as will cause swelling and hyperthyroidism - and can cause this in patients with significant mets or residual normal thyroid
• Nausea and headache are SEs, can cause neurologic deterioration in CNS mets

Question 348

What is the role of external radiation therapy in thyroid ca?

Answer 348

• anaplastic thyroid ca
• brain mets with gamma knife radiosurgery

Question 349

In suppressing TSH for thyroid Ca, the serum T4 may be slightly elevated by the thyroxine dose. How can you ensure the patient is not hyperthyroid?

Answer 349

Serum T3 or FT3 level

Question 350

When is serum thyroglobulin a useful tumour marker?

Answer 350

Only after total or near-total thyroidectomy or I¹³¹ ablation and particularly when there are no serum anti-thyroglobulin antibodies.

• Detectable != recurrence
• baseline is NOT helpful, stimulated measurements should be used and always w/ neck U/S

Question 351

How should neck ultrasound be used in patients with thyroid Ca?

Answer 351

Supplements palpation

Perform pre-op

3 months post-op

Then as followup

Better than CT or MRI for local LN mets.

Question 352

What is the role of I¹³¹ RAI scanning in thyroid Ca surveillance?

Answer 352

High risk

Persistant antithyrglobulin antibodies that make serum thyroglobulin determination unreliable

Must be used <2 weeks before scheduled I¹³¹ treatment to avoid stunning the mets (or can use I123 as does not stun tumors and better for SPECT)

Performed 2-4 months post op in differentiated disease

May not need repeat scanning if clear post op and low serum thyroglobulin, but continue ultrasounds

Question 353

What do you do if there is persistent radioiodine uptake in the neck on diagnostic RAI scanning but no visible tumor on neck ultrasound post thyroidectomy?

Answer 353

No additional therapy, especially if serum thyroglobulin is very low

Question 354

What is the role of PET scanning as surveillance in thyroid ca?

Answer 354

• useful for detecting mets when high serum thyroglobulin who have a normal whole-body RAI scan and unrevealing neck-ultrasound
• avoid sweets and in diabetics, BSL <20
• better sensitivity if done as a fusion scan with CT
• poor specificity

Question 355

What can cause false positives on PET scans?

Answer 355

Benign hepatic tumours

Sarcoidosis

Radiation therapy

Suture granulomas

Reactive LNs

Inflammation

Muscles

Brown fat

Question 356

What role does PET scanning have in prognosticating thyroid disease?

Answer 356

Predicts survival better than standard staging - number, location and SUV of mets are all factors.

Question 357

What is the prognosis of papillary thyroid Ca?

Answer 357

• few mets, low SUV on PET = better
• under 40 even with mets = good
• over 45, male, bone or brain mets, >1cm, pulmonary mets or lack I131 = bad

Question 358

What papillary ca histology is assoc w/ worse prognosis?

Answer 358

tall cell

columnar cell

diffuse sclerosing

brain mets reduce survival to 12 months but improves with resection

Question 359

What increases mortality in papillary thyroid ca?

Answer 359

• tumor >1cm and only limited thyroid surgery (subtotal or lobectomy)
• no I131 ablation
• higher in men
• multifocal tumors

Question 360

What are the prognostic features of medullary thyroid Ca?

Answer 360

• 90% 10 year survival when confined to the thyroid, drops to 20% with distant mets
• if LN involvement, modified radical neck dissection helps
• MEN2A associated less agressive, also women under 40
• more aggressive in MEN2B, younger in age, M918T mutation

Question 361

What antigenic stain finding increases the mortality of medullary thyroid Ca x4.5?

What is associated with prolonged survival even if there are significant mets?

Answer 361

Myelomonocytic antigen M-1

Heavy immunoperoxidase stain for calcitonin

Question 362

What is the survival rate of anaplastic thyroid ca?

Answer 362

1 year survival of about 10%

5 year survival of 5%

Fully localised tumor on MRI has a better prognosis

Question 363

What is the prognosis of thyroid lymphoma?

Answer 363

100% at 5 years

Outside the thyroid, 63%

Better if MALT

Stridor, pain, palsy, mediastinal extension = worse

Question 364

What are the features of iodine deficiency disorder and endemic goitre?

Answer 364

• low iodine diet
• high rate of congenital hypothyroidism and cretinism
• goiters may become multinodular and enlarge
• most are euthyroid

Question 365

What impact does iodine deficiency have on children?

Answer 365

Increased risk of miscarriage and stillbirth

Congenital hypothyroidism –> deafness, short stature, lower IQ

Full blown cretinism

Question 366

What aggravates iodine deficiency or can themselves, cause goiter?

Answer 366

Sorghum/millet/maize/cassava

Selenium, iron

Water pollution

Smoking

Pregnancy

Question 367

What are the lab findings in iodine-deficient endemic goiter?

Answer 367

Normal serum T4 and TSH

If TSH falls and hyperthyroidism –> MNG has become autonomous in presence of sufficient amounts of iodine

• Thyroid RAI uptake usually elevated but may be normal if iodine intake has improved
• antithyroid antibodies either undetectable or low
• eleavted serum thyroglobulin

Question 368

What is the treatment of endemic goiter?

Answer 368

• iodised table salt reduces prevalence but doesn’t shrink goiter
• Concurrent vitamin A and iodine deficiency increases risk of endemic goiter, concurrent repletion reduces
• large multinodular goiter –> thyroidectomy for cosmesis, compressive sx or thyrotoxicosis
• high recurrence rate if subtotal + iodine deficient area, total is preferred

Question 369

What are the complications associated with endemic goiter?

Answer 369

Iodine supplementation increases risk of autoimmune transformation

Excess supplementation increases risk of goiter particularly if autonomonous MNG - avoid thyroxine suppression if low TSH

Rarely - Graves post I131 in MNG

Question 370

What are the essentials of diagnosis for male hypogonadism?

Answer 370

• diminished libido and erections
• low serum or free testosterone
• LH and FSH low/normal in hypogonadotropic hypogonadism
• increased in testicular failure (hypergonadotropic hypogonadism)

Question 371

How is male hypogonadism classified?

Answer 371

• insufficient gonadotropin secretion by the pituitary (hypogonadotropic)
• pathology in the testes (hypergonadotropic)
• both

Question 372

What are the features of hypogonadotropic hypogonadism?

Answer 372

• FSH and LH deficiency due to pituitary failure, either in isolation or with other hormone deficiencies
• can be primary
• main causes are functional; obesity, poor health, normal aging - spermatogenesis preserved

Question 373

What is the natural history of testosterone secretion in men?

Answer 373

After age 40, declines by 1-2% per year

Free testosterone levels decline even faster due to increasing SHBG with age

No concomitant increase in LH until after age 70, at which point it starts to rise, suggesting primary gonadal dysfunction with age

Question 374

What should the diagnosis of testosterone deficiency in older men include?

Answer 374

Low serum testosterone

At least 3 of the following 6:

Erectile dysfunction

Poor morning erection

Low libido

Depression

Fatgiue

Inability to perform vigorous activity

These men are most likely to benefit from testosterone replacement

Question 375

What are the general features of hypergonadotropic hypogonadism?

Answer 375

• failure of testicular secretion of testosterone
• can be caused by viruses (i.e. mumps), irradiation, ca, autoimmunity, myotonic dystrophy, genetics, andropause, single testicle failure, 17-hydroxylase deficiency, 17-ketosteroid reductase deficiency

Question 376

What are the features of Klinefelter syndrome?

Answer 376

47, XXY

Most common male chromosomal abnormality

Gynecomastia and tall stature

Dx on karyotype of RNA for X-inactive-specific transcriptase on peripheral leukocyte PCR

Azoospermia (although some produce sperm)

Question 377

What are the features of XY gonadal dysgenesis?

Answer 377

• failure of normal testicular development
• mutation in SRY gene
• no testosterone –> sex reversal
• external female genitalia w/o uterus, have intra-abdominal gonads
• raised as girls, upon puberty, amenorrhea
• resect intrabdominal testes, risk of malignancy
• considered women, give estrogen

Question 378

What are the clinical findings of hypogonadism?

Answer 378

Delayed puberty if congenital or acquired during childhood

Decreased libido

Decreased man hair (after years)

Low muscle mass

Weight gain

Question 379

What are the lab findings in hypogonadism?

Answer 379

Morning serum or free testosterone (declines throughout day) will be low

• free testosterone esp important in elderly men due to high SHBG
• should be confirmed with repeat assay and low LH and FSH
• check for hyperprolactinaemia
• mild anaemia as testosterone stimulates RBC production
• BMD if longstanding as may have osteoporosis

Question 380

What are the lab findings in hypogonadotropic hypogonadism?

Answer 380

• serum PRL may be elevated
• normal/low LH/FSH
• if gynecomastia, screen for partial 17-ketosteroid reducatse deficiency plus androstenedione and estrone which are elevated in this condition.
• serum estradiol may be elevated if cirrhotic and if rare estrogen secreting tumour

Question 381

What screening test should be done in a man with hypogonatropic hypogonadism with no definite cause?

Answer 381

Screen for hemochromatosis and MRI the pituitary and hypothalamus looking for a lesion

Question 382

What are the lab findings in hypergonadtropic hypogonadism?

Answer 382

• low serum testosterone with high FSH and LH
• karyotype or PCR leukocyte XIST for Klinefelters
• testicular bx in young guys if no cause found

Question 383

What are the general principles of testoserone replacement?

Answer 383

• boys who have not start puberty by age 14
• men with hypergonadtropic hypogonadism or severe hypogonadtropic hypogonadsim
• hypogonadic symptoms (at least 3), with low serum or free testosterone

Question 384

In whom is testosterone therapy contraindicated?

Answer 384

Active prostate or breast ca

Erythrocytosis

Need DRE and PSA prior to commencing

Untreated OSA
CHF

Question 385

What special considerations need to be made in testostereone replacement?

Answer 385

Must improve cardiac risk factors and give low-dose aspirin

If on Warfarin –> can increase INR and risk of bleeding

Will increase cyclosporine and tac levels

Hypoglycaemia in diabetic men on insulin or oral hypoglycaemics

Question 386

What are the features of testosterone replacement formulations?

Answer 386

Topical administration is best - more stable sterum testosterone

Skin acts as reservoir of slow release - 10% gets into the blood, steady state in 1-3 days

Transdermal is inconvenient and expensive

Avoid breast or genitals

Oral forms can cause liver tumors or peliosis hepatis

Question 387

Who benefits from testosterone therapy?

Answer 387

Low serum testosterone and at least 3 manifestations of hypogonadism

Question 388

What are the risks associated with testosterone replacement therapy?

Answer 388

• increases risk of cardiovascular events in age over 65 with risk factors or pre-existing angina
• may be due to decrease in HDL associated with testosterone therapy
• aggravates BPH but not voiding sx
• erythrocytosis with IM but no increased risk of thromboembolic events
• aggravates sleep apnoea
• acne
• gynecomastia that resolves spontaneously, better with gel

Question 389

What are the general features of male gynecomastia?

Answer 389

60% of pubertal boys - spontaneously resolves, common in tall oor overweight

Half of athletes who abuse

HIV on HAART - esp efavirenz of didanosine - spontaneously resolves

Question 390

What are the concerning characteristics in a man with gynecomastia?

Answer 390

• asymmetry
• location not immediately below the areola
• unusual firmness
• nipple retraction, bleeding or discharge

Question 391

What are the lab findings to consider in male gynecomastia?

Answer 391

PRL

B-subunit of HCG suggest a testicular tumor (germ cell or Sertoli) or other malignancy (lung or liver)

• low serum free testosterone and high LH –> primary hypogonadism
• high testosterone plus high LH –> partial androgen resistance
• estradiol increased from testicular tumours, increased B-HCG, liver disease and obesity

Question 392

In a man with new gynecomastia and no clear cause - what test should be performed?

Answer 392

CXR for metastatic or bronchogenic ca

Question 393

What is the role of selective estrogen receptor modulator therapy (SERM) in gynecomastia?

Answer 393

Works for lumpy ‘glandular’ gynecomastia rather than diffuse fatty kind.

Give raloxifene

Question 394

When is surgical correction used for gynecomastia?

Answer 394

If persistent or severe

Question 395

What is the genetic abnormality of Turner’s syndrome?

Answer 395

Turner’s syndrome is a chromosomal disorder affecting around 1 in 2,500 females. It is caused by either the presence of only one sex chromosome (X) or a deletion of the short arm of one of the X chromosomes. Turner’s syndrome is denoted as 45,XO or 45,X

Question 396

What are the phenotypical features of Turner syndrome?

Answer 396

short stature

shield chest, widely spaced nipples

webbed neck

bicuspid aortic valve (15%), coarctation of the aorta (5-10%)

primary amenorrhoea

cystic hygroma (often diagnosed prenatally)

high-arched palate

short fourth metacarpal

multiple pigmented naevi

lymphoedema in neonates (especially feet)

There is also an increased incidence of autoimmune disease (especially autoimmune thyroiditis) and Crohn’s disease

Question 397

What is the source, stimulus, and action of gastrin?

Answer 397

G cells in antrum of the stomach

Distension of stomach, vagus nerves (mediated by gastrin-releasing peptide), luminal peptides/amino acids

Inhibited by: low antral pH, somatostatin

Increase HCL, pepsinogen and IF secretion, increases gastric motility, stimulates parietal cell maturation

Question 398

What is the source, stimulus, and action of CCK?

Answer 398

I cells in upper small intestine

Partially digested proteins and triglycerides

Increases secretion of enzyme-rich fluid from pancreas, contraction of gallbladder and relaxation of sphincter of Oddi, decreases gastric emptying, trophic effect on pancreatic acinar cells, induces satiety

Question 399

What is the source, stimulus, and action of secretin?

Answer 399

S cells in upper small intestine

Acidic chyme, fatty acids

Increases secretion of bicarbonate-rich fluid from pancreas and hepatic duct cells, decreases gastric acid secretion, trophic effect on pancreatic acinar cells

Question 400

What is the source, stimulus, and action of VIP?

Answer 400

Small intestine, pancreas

Neural

Stimulates secretion by pancreas and intestines, inhibits acid secretion

Question 401

What is the source, stimulus, and action of somatostatin?

Answer 401

D cells in the pancreas & stomach

Fat, bile salts and glucose in the intestinal lumen

Decreases acid and pepsin secretion, decreases gastrin secretion, decreases pancreatic enzyme secretion, decreases insulin and glucagon secretion

inhibits trophic effects of gastrin, stimulates gastric mucous production

Question 402

What are the hormones secreted by the adrenals and where?

Answer 402

Adrenal cortex (mnemonic GFR - ACD)

zona glomerulosa (on outside): mineralocorticoids, mainly aldosterone

zona fasciculata (middle): glucocorticoids, mainly cortisol

zona reticularis (on inside): androgens, mainly dehydroepiandrosterone (DHEA)

Question 403

Where does parathyroid hormone act?

Answer 403

PTH acts to increase the concentration of calcium in the blood by acting upon the parathyroid hormone 1 receptor (high levels in bone and kidney) and the parathyroid hormone 2 receptor (high levels in the central nervous system, pancreas, testis, and placenta).

Question 404

Describe the regulation of parathyroid hormone

Answer 404

Secretion of parathyroid hormone is controlled chiefly by serum [Ca2+] through negative feedback. Calcium-sensing receptors located on parathyroid cells are activated when [Ca2+] is elevated.

In the parathyroid gland, high concentrations of extracellular calcium result in activation of the Gq G-protein coupled cascade through the action of phospholipase C.

Hypermagnesemia also results in inhibition of PTH secretion.

While low levels of magnesium stimulate parathyroid hormone secretion, very low serum concentrations induce a paradoxical block.

Question 405

Name the stimulators and inhibitors of parathyroid hormone release

Answer 405

Stimulators

Decreased serum [Ca2+].

Mild decreases in serum [Mg2+].

An increase in serum phosphate (increased phosphate causes it to complex with serum calcium, forming calcium phosphate, which reduces stimulation of Ca-sensitive receptors (CaSr) that do not sense calcium phosphate, triggering an increase in PTH).

Inhibitors

Increased serum [Ca2+].

Severe decreases in serum [Mg2+], which also produces symptoms of hypoparathyroidism (such as hypocalcemia).[13]

Calcitriol

Question 406

What is the cause of most hyperfunctioning thyroid nodules?

Answer 406

Activating TSH receptor mutations

Activating mutations in either the TSH-R or the Gs subunit genes are identified in >90% of patients with solitary hyperfunctioning nodules

Thyrotoxicosis is usually mild

Disorder is suggested by the presence of the thyroid nodule and by the absence of clinical features suggestive of Graves’ disease or other causes of thyrotoxicosis

A thyroid scan provides a definitive diagnostic test, demonstrating focal uptake in the hyperfunctioning nodule and diminished uptake in the remainder of the gland, as activity of the normal thyroid is suppressed

Question 407

What impact do fibrates have on blood cholesterol?

Answer 407

Decrease TGL

Decrease VLDL

Decrease total chol

Increase HDL

Question 408

How do fibrates work?

Answer 408

Stimulate lipoprotein lipase by inducing PPAR-alpha receptors which induce the transcription of genes that facilitate lipid metabolism

ApoCIII (a VLDL protein) is decreased as a result which increases LPL activity

VLDL catabolism is enhanced which generates surface remnants, these are then taken up by HDL, helped by PPAR driven transcription of APoA1 and ApoA2

End result is increased HDL-mediated reverse chol transport, reduction in hepatic VLDL secretion, increased size and removal of LDL partiles, and reduced plasminogen activator inhibitor type 1 levels.

Question 409

What is the role of:

Chylomicron

VLDL

LDL

HDL

Answer 409

Chylomicrons carry diet-derived lipids to body cells

VLDLs carry lipids synthesized by the liver to body cells

LDLs carry cholesterol around the body

HDLs carry cholesterol from the body back to the liver for breakdown and excretion.

Question 410

Describe the ‘non-HDL’ pathway of lipid transport

Answer 410

1. ApoB (VLDL) secreted by liver
2. Connects to muscle and liver via surface APO-CIII which activates lipoprotein lipase
3. Core TGLs hydrolysed to FAs and cross capillary membrane, VLDL now ILDL (APO-B100)
4. ApO-B100 further freed of FAs by hepatic lipaseand becomes LDL (stil APO-B100) which expresses Apo CIII
5. ILDL and LDL shed APO-E and APOCIII remnants as they shrink, which get taken up by HDL
6. LDL or remnants reuptaken by LDLr or LRP

OR - the remnants or chylomicron remnants get taken up by peripheral cells for cholesterol content or by capillary macrophages which have LDLr’s –> foam cells –> atheroma.

Question 411

Describe the ‘HDL’ or ‘reverse cholesterol’ pathway of lipid metabolism

Answer 411

1. Poorly lipidated APoA1 secreted by liver and intestine into the plasma
2. Cholesterol filled cell (inc macrophages) upregulate the ABCA transporter which converts cholesterol ester to free cholesterol from the lipid pool and delivers it to the cell membrane.
3. APOA1 collects this cholesterol and forms nascent HDL. ABCA keeps shuttling.
4. Lecithin cholesterol athyltransferase (LCAT) esterifies cholesterol on nascet HDL surface –> chol ester moves to lipoprotein core –> HDL3 is formed.
5. HDL collects more cholesterol from cell membranes via the FRB receptor, becomes HDL2.
6. HDL2 via cholesterol ester transfer protein (CETP) exchanges cholesterol for triglycerides with TGL-rich lipoproteins (VLDL and LDL)
7. HDL2 can then have it’s TGLs hydrolysed by hepatic lipase and then become HDL3 again OR return to the liver where scavenger receptor SRB1 extracts cholesterol –> HDL3, or HDL2 gets catabolised by the liver.

Question 412

What are the non-iatrogenic causes of hypervitaminosis-D?

Answer 412

Remember - excess calcitriol (aka D3)

• hyperparathyroidism –> upregulated 1-alpha hydroxylase in the kidney
• Tumor production of calcitriol:
• Predominant cause of hypercalcemia in Hodgkin’s disease and in 1/3 of patients with NHL
• Sarcoidosis and sarcoma
• Usually responds to corticosteroid administration

Question 413

What are the endocrine and exocrine features of sarcoidosis?

Answer 413

Increased prolactin –> amenorrhea, galactorrhoea, non peurpeural mastitis

Granuloma’s secrete 1-alpha hydroxylase –> increased 1,25OHD –> hypervitaminosis D –> hypercalcemia

Question 414

What is the major cause of the hypercalcemia of malignancy?

What is it’s significance?

Answer 414

PTH-rP is the leading cause of hypercalcemia in malignancy (80% of cancer pt.’s with hypercalcemia have PTH-rP-related hypercalcemia).

Hypercalcemia in malignancy occurs abruptly, is se

vere, and portends a very poor prognosis (median

survival only six weeks).

Question 415

Which cancers are associated with hypercalcemia?

Answer 415

Breast, lung, and multiple myeloma

Question 416

What are the threen main mechanisms of hypercalcemia in malignancy?

Answer 416

PTHrp

Osteolytic mets

Tumor production of calcitriol

Question 417

What are the features of PTH related protein? (PTH-rp)

Answer 417

PTH-rP is the leading cause of hypercalcemia in malignancy (80% of cancer pt.’s with hypercalcemia have

PTH-rP-related hypercalcemia).

• Also known as HHM (humoral hypercalcemia of malignancy)
• PTH-rP is produced by a number of cells (neuro

endocrine, epithelial, mesoderm-derived tissues)

• Can be associated with any solid tumor (most commonly breast cancer) and occasionally humoral

malignancy.

Question 418

Which cancers have osteolytic mets?

Answer 418

Remember the pneumonic BLT with a Kosher Pickle, Mustard & Mayo

:

Breast,Lung,Lymphoma,Thyroid,

Kidney, Prostate, Multiple Myeloma

• Most commonly caused by breast cancer and NSCLC

Question 419

Describe the follicular phase of the female menstrual cycle.

Answer 419

Beginning of menstrual cycle

Hypothalamus releases GNRH

Pituitary releases FSH

FSH stimulates follicle (1 egg, oestrogen secretion) growth and maturation

Follicle releases oestrogen

Uterine endometrium proliferates via oestrogen

Increasing GnRH results in LH secretion –> luteal phase

Question 420

Describe the luteal phase of the female menstrual cycle.

Answer 420

Midpoint of cycle

Ever increasing GnRH acts on pituitary to spike LH secretion

Egg is released from follicle - takes 5-6 days to travel to uterus

Follicle becomes corpus luteum which secretes progesterone

Progesterone acts on endometrium to become secretory (favorable for egg)

Continues to secrete progesterone

No fertilisation –> corpus luteum dies and in presence of both falling oestrogen and progesterone –> sheds, period

Fertilisation –> corpus luteum keeps secreting progesterone for first 12 weeks of pregnancy.

Question 421

Describe the gonadal production of testosterone

Answer 421

Hypothalamus releases GnRH

Ant pituitary releases LH & FSH

LH goes to the Leydig Cells in the interstitial space

Leydig cells secrete testosterone

Testosterone and dihydroxytestosterone negatively feedback on the anterior pituitary to reduce LH release and drop testosterone production.

Question 422

Describe the hormonal control of spermatogenesis

Answer 422

Hypothalamus releases GnRH

GnRH stimulates LH & FSH release

LH –> Leydig cells (interstitium) –> testosterone

FSH –> Sertoli cells (seminiferous tubules) –> ABP (androgen binding protein) release

Testosterone binds ABP –> stimulates sperm growth (spermiogenesis and spermatogenesis)

Sertoli cells secrete inhibin –> negative feedback to pituitary –> reduced production of FSH.

Question 423

What are the general features of the male gonads?

Answer 423

• approx 3 degrees cooler than body (for sperm)
• can drop away from body via spermatic cord if body gets too hot
• tunica albuginea protects teste, and extends inside to form septa –> dividing teste into lobules containing interstitium and seminiferous tubules

Question 424

What are the active areas of the male teste and what do they do?

Answer 424

Seminferous tubule form sperm

Interstitial cells form male hormones (androgens)

Question 425

Describe the process of sperm production

Answer 425

FSH –>

Spermatogonium undergo mitosis forming a daughter spermatogonium (for later) and a primary spermatocyte with 46 chromosomes.

Primary Spermatocyte undergoes meiosis 1

Secondary spermatocyte is generated in which the DNA is not replicated beforehand, leaving it with only 23 chromosomes.

Secondary spermatocyte undergoes meiosis 2, generating 4 spermatids each with 23 chromosomes.

Spermatids then differentiate to form their own heads and tails –> mature spermatozoa

In summary: spermatogenesis forms 4 x spermatozoa (sperm cells) each with only 23 chromsomes from one primary spermatocyte (46 chromosomes). Female ova supply the other 23 chromosomes.

Question 426

Describe the components of sperm

Answer 426

Head –> contains nucleus and chromsomes. Tip (acrosome) contains penetrative enzymes

Body –> mitochondria for ATP and swimming energy

Tail –> flagellum

Lives for hours to 3 days.

Question 427

Describe the passage of sperm from the testes

Answer 427

Seminefrous tubule

Epididymus (coiled tube) –> mature on way through here

Emptied into vas deferens then passes through the inguinal canal, loops over then down the side of the bladder to the seminal vesicle

Seminal vesicle supplies nutrition and most of the ejaculatory fluid and joins with the vas deferens to become the ejaculatory duct which passes through the prostate.

Prostate - contracts and provides the alkaline fluid to neutralise vaginal acidity, supplies more of the ejaculatory fluid

Sperm then travels through the bulbourethral glands which also provide alkali fluid to counteract urethral acidity and lubrication.

Sperm then exits the urethra.

Question 428

Describe the different parts of the penis

Answer 428

Anterior - corpus cavernosa (does the erection)

Posterior - corpus spongiosum (has the urethra and forms the glans)

Distal end - glans

Foreskin - prepuce

Question 429

What stimulates the release of human growth hormone?

Answer 429

GH is stimulated in response to stress, exercise, malnutrition and anorexia during the day (i.e. in response to a catabolic state - hypoglycacemia, low FFAs and high circulating amino acid concentrations).

Question 430

In a normal person, which of the following is most likely to cause a decrease in circulating growth

hormone concentration?

A. Slow wave sleep.

B. Hyperglycaemia.

C. Protein meal.

D. Exercise.

E. Sepsis.

Answer 430

B.

C, D, E are all potentially catabolic states which will increase circulating growth hormone concentration. At baseline physiology, growth hormone release is highest in sleep stage III and IV (deep sleep). B is the only option

Question 431

What are the features of human growth hormone?

Answer 431

Also known as ‘somatotropin’.

‘Stress hormone’ that stimulates lipolysis, gluconeogenesis and also increases protein synthesis.

Normally pulsatile secretion, highest during sleep stages III and IV, lowest in early morning

Peaks in teenage years and declines after that, diminished further in heart failure patients.

Stimulated by slow wave sleep, ghrelin, the ‘hunger’ hormone released by the stomach and a catabolic state (hypoglycaemia, stress, exercise).

Question 432

What are the effects of human growth hormone?

Answer 432

Stress hormone

Hepatic IGF-1 release (growth promoter)

Gluconeogenesis

Lipolysis –> FFA release

Protein synthesis

Increases T4 to T3 deoiodination

Cakcium retention and mineralisaton of bone

Stimulates internal organ growth

Homeostasis

Question 433

What is IGF-1?

Answer 433

Growth factor released by the liver in response to growh hormone.

Responsible for human growth in general, and growth-effects of human growth hormone.

Receptor number is regulated by GH and thyroxine.

Question 434

What are the inhibitors of human growth hormone?

Answer 434

Somatostatin

TRH –> somatostatin release (which suppresses TSH, in turn, hypothyroidism suppresses somastostatin)

B-agonists –> somatostatin release

Exogenous glucocorticoids (at hypothalamus)

High circulating FFAs

Leptin (released by fat cells when there’s lots of fat)

Hyperglycaemia

Question 435

Where is somastatin secreted from and what does it do?

Answer 435

Also known as GHIH - it’s an inhibitory system

In the anterior pituitary (secreted by hypothalamus):

• inhibits GH (opposes GHRH)
• inhibits TSH
• inhibits prolactin release
• always paracrine (not in blood)

In the GI system (secreted by stomach, intestine and pancreatic delta cells)

• suppresses all the GI hormones (gastrin, CCK, secretin, VIP, GIP, secretin, motilin)
• decreases gastric emptying and reduces sm contractions in the intestine
• suppresses pancreatic hormone (endocrine and exocrine) release inc insulin and glucagon.

Question 436

How is acromegaly diagnosed?

Answer 436

IGF-1 most sensitive, so good screening test.

If positive - GH suppression testing following oral glucose load - specific. Failure of suppression = acromegaly)

Single GH value NOT useful.

Question 437

What are the complications of acromegaly?

Answer 437

Arthritis and carpal tunnel

Myocardial hypertrophy

DM due to insulin resistance

Hypertension

Heart and renal failure

Colorectal ca

Question 438

What laboratory parameter is most suggestive of psychogenic polydipsia?

Answer 438

Hyponatraemia - in true diapetes insipidus, the patients are dehydrated from excessive water loss

Question 439

What will a water deprivation test show for

Psychogenic polydipsia

Central DI

Nephrogenic DI?

Answer 439

Psychogenic: Concentrated urine both before and after desmopressin

Central DI: Dilute urine before DDAVP, concentrated after

Nephrogenic: Dilute urine before and after DDAVP

Question 440

What is desmopressin and what is it used for?

Answer 440

Man made vasopressin or ADH with little effect on BP as compared with vasopressin

Used to treat central DI (bind renal collecting duct V2 receptors –> aquoporin channels to apical membrane of duct)

Promotes release of vWF (also on V2 receptor) and increases factor VIII survival thanks to this –> used in VW disease, mild hemophilia A, and thrombocytopaenia. Can also be used with uremic induced platelet dysfunction. Not for haemophilia B or severe haemophilia A.

Question 441

Describe the state of renin, aldoserone and cortisol for

Conn’s

Secondary hyperaldosteronism (or renovascular ht)

Addison’s disease

Cushing’s disease

Answer 441

Primary hyperaldosteronism (also known as Conn’s syndrome): high aldosterone, normal cortisol, low renin

Secondary hyperaldosteronism: high aldosterone, normal cortisol, high renin

Addison’s disease (also known as adrenal insufficiency): low aldosterone, low cortisol, high renin

Cushing’s syndrome: low-normal aldosterone, high cortisol, low renin

Question 442

Which drugs should be avoided prior to perform an aldosterone:renin ratio?

Answer 442

Diuretics including spironolactone which raises plasma renin levels, thereby reducing the ratio.

Hypokalemia should be corrected before testing as low potassium suppresses aldosterone secretion.

Question 443

What is the effect of hypothyroidism on lipid physiology?

Answer 443

Decreased tissue and hepatic LDL receptors

Hyperlipidaemia of LDL origin - even in subclinical hypothyroidism

Question 444

What is the dyslipidemia characteristic of protease inhibitors?

Answer 444

Hypertriglyceridaemia (as well as increase in total chol and LDL)

Mainly Ritonavir

Question 445

What are the characteristic features of a type 2 diabetic dyslipidemia?

Answer 445

High triglycerides

Low HDL

Increased small dense LDL cholesterol

Question 446

What are the characteristics of atherogenic dyslipidemia?

Answer 446

Elevated small dense LDL

Low HDL

Increased TGL

Question 447

What does excessive alcohol intake do to lipid levels?

Answer 447

Raises TGLs

Raises HDL

Minimal effect on LDL

• not recommended for prevention of coronary disease! ;)

Question 448

What are the contraindications to bisphosphonates?

Answer 448

Delayed oesophageal emptying eg stricture, achalasia; (they can cause serious oesophageal erosions)

inability to stand, sit upright for greater than or equal to 30 min;

hypocalcaemia

renal impairment (mainly w/ IV therapy)

(Zoledronate)

recent uveitis incl bisphosphonate assoc history; pregnancy, lactation

Question 449

How do you differentiate between:

Exogenous glucocorticoids

Pseudo Cushing’s

Cushing’s disease

Ectopic Cushing’s syndrome

Cortisol producting adrenal adenoma?

Answer 449

Exogenous and cortisol producing-adrenal adenoma (both are forms of primary hypercortisolism) –> ACTH suppressed (negative feedback depends on cortisol)

Pseudo Cushings - cortisol and ACTH normal

Cushing’s disease (pituitary dependent) - normal/somewhat elevated (not in hundreds) ACTH (pituitary source) and high cortisol suppressed by high dexamethasone doses (tumour still sensitive somewhat)

Ectopic Cushing’s syndrome (pituitary independent) - high ACTH as it is ectopic production of ACTH driving the hypercortisolaemia, wouldn’t matter if pituitary productions was suppressed - elevated in hundreds. Cortisol not suppressed at all by dex suppression test. Look in adrenals or lungs.

Question 450

How do you differentiate between an adrenal crisis and a glucocorticoid insufficiency due to hypopituitarism crisis?

Answer 450

Both:

Hypotension / collapse

Coma

Hypothermia or hyperthermia

Hypoglycaemia (unless diabetic!)

Low T4

Adrenal only

Hyperkalemia and hyponatraemia (these are ok in hypopituitarism because renin is not affected - only production of aldosterone by the adrenals)

Question 451

What are the general features of an adrenal crisis?

Answer 451

Severe lethargy

Convulsions

Fever

Hyperkalemia (elevated potassium level in the blood)

Hypercalcemia (elevated calcium level in the blood): the etiology of hypercalcemia is a combination of increased calcium input into the extracellular space and reduced calcium removal by the kidney, this last caused by decreased glomerular filtration and increased tubular calcium reabsorption. Both renal factors are secondary to volume depletion and, in fact, improve rapidly during rehydration with saline infusion.[3]

Hypoglycemia (reduced level of blood glucose)

Hyponatremia (low sodium level in the blood)

Hypotension (low blood pressure)

Hypothyroid (low T4 level)

Severe vomiting and diarrhea, resulting in dehydration

Question 452

What are the clinical features of CAH?

Answer 452

Due to inadequate mineralocorticoids:

vomiting due to salt-wasting leading to dehydration and death

Due to excess androgens:

functional and average sized penis in cases involving extreme virilization (but no sperm)

ambiguous genitalia, in some females, such that it can be initially difficult to identify external genitalia as “male” or “female”.

early pubic hair and rapid growth in childhood

precocious puberty or failure of puberty to occur (sexual infantilism: absent or delayed puberty)

excessive facial hair, virilization, and/or menstrual irregularity in adolescence

infertility due to anovulation

enlarged clitoris and shallow vagina

Question 453

What is the most predictive marker of PCOS in patients who have evidence of hyperandrogenism?

Answer 453

Approximately three-quarters of patients with PCOS (by the diagnostic criteria of NIH/NICHD 1990) have evidence of hyperandrogenism, with free testosterone being the single most predictive marker with ~60% of patients demonstrating supranormal levels

Question 454

Describe what happens to hormone levels in pregnancy

Answer 454

HCG - peaks in first tri then drops until birth

Progesterone and oestrogen climb consistently into third tri.

Question 455

What is the mechanism and causes of SIADH?

Answer 455

Excessive ADH secretion and inappropriate water reabsoprtion

Caused by:

Ectopic - SCLC

Drugs - sulfonylurea

Lesion of baroreceptor pathway

Question 456

What are the consequences of SIADH?

Answer 456

Water retention and increased ANP leading to euvolaemic hyponatraemia

Urine osmolarity greater than plasma osmolarity

Elevated urinary sodium

Question 457

What is the mechanism of sodium wasting in SIADH?

Answer 457

ADH activity effectively dilutes the blood (decreasing the concentrations of solutes such as sodium), causing hyponatremia; this is compounded by the fact the body responds to water retention by decreasing aldosterone, thus allowing even more sodium wasting. For this reason, a high urinary sodium excretion will be seen.

Question 458

What causes hypovolaemic hyponatraemia?

Answer 458

Diuretics

Diarrhoea

Vomiting

Question 459

What causes euvolaemic hyponatraemia?

Answer 459

SIADH - brain, lung ca, pain, psych meds

Pseudo SIADH - hypothyroidism, hypoaldosteronism

Thiazides

Characterised by high urine osmolality

Question 460

What causes hypervolaemic hyponatraemia?

Answer 460

CHF

Cirrhosis

Question 461

How do you differentiate refractory essential hypertension from

Conn’s

Renal artery stenosis

Cushing’s syndrome

Phaeo?

Answer 461

Essential hypertension tends to have no electrolyte derangement, can have a bruit.

Hyperaldosteronism seen in Conn’s and renal artery stenosis will predispose to hypokalemia and alkalosis

Phaeo tends to present young to mid age and can be paroxysmal with tachycardias.

Question 462

When do you worry about an adrenal incidentaloma?

Answer 462

When it’s over 4cm or there’s evidence of hormonal overactivation

Question 463

What drug should you never give to someone with bilateral renal artery stenosis and why?

Answer 463

ACEIs

In renal artery stenosis, the afferent pressure is reduced by the narrowed vessel, hence autoregulation is almost exclusively dependent on changes in post-glomerular arteriolar tone.

Because ACE inhibitors interfere with the production of angiotensin II, autoregulation is impaired, glomerular perfusion falls, renal ischaemic nephropathy develops and renal failure ensues.

Angiotensin II forms part of the renal autoregulation of glomerular perfusion mechanism. The preglomerular arteriolar tone is reduced when renal perfusion falls, increasing glomerular blood flow and maintaining glomerular filtration.

If this response is inadequate, renin is released, activating the RAAS cascade, leading to angiotensin II mediated constriction of the post-glomerular arteriole. Pressure within the glomerulus is therefore increased and filtration restored.

Question 464

What are the indications for ambulatory blood pressure recording?

Answer 464

• Suspected white-coat hypertension (including in

pregnancy)

• Suspected masked hypertension (untreated subject

with normal clinic BP and elevated ABP)

• Suspected nocturnal hypertension or no night time reduction in BP (dipping)
• Hypertension despite appropriate treatment
• Patients with a high risk of future cardiovascular events (even if clinic BP is normal)
• Suspected episodic hypertension.

Ambulatory BP monitoring may also be useful for:

• titrating antihypertensive therapy
• borderline hypertension
• hypertension detected early in pregnancy
• suspected or confirmed sleep apnoea
• syncope or other symptoms suggesting orthostatic hypotension, where this cannot be demonstrated in

the clinic.

Question 465

What are the most common pituitary tumors?

Answer 465

The common tumours secrete growth hormone (15%), prolactin (30%), ACTH (15%), gonatroophic (10% - asymptomatic) mixed secretions or no secretion at all.

Question 466

What is the most common long-term side effect of radiation for pituitary tumors?

Answer 466

Hypopituitarism

Question 467

What is the role of long acting insulin in type 1 diabetes?

Answer 467

The aim of the basal aspect of insulin administration is to provide a constant level of insulin between meals without increasing the risk of hypoglycaemia, particularly at night (nocturnal hypoglycaemia).

Question 468

Why is insulin glargine preferred over NPH insulin?

Answer 468

NPH activity peaks 3–5 hours after administration; its duration of action is only 14 ± 3 hours and hence it has to be injected twice daily. With NPH administered at bedtime, peak insulin activity is reached while the glucose levels are low, which increases the risk of nocturnal hypoglycaemia. Nocturnal hypoglycaemia is accepted to be an important barrier to the achievement of optimal glucose control, as users tend to lower the insulin dose to prevent hypoglycaemia.

Question 469

What is the normal value for urine osmolality?

Answer 469

The normal 24-hour urine osmolality is, on average, 500-800 mOsm/kg of water.

Random urine osmolality should average 300-900 mOsm/kg of water.

After 12-14 hours of fluid intake restriction, the urine osmolality should exceed 850 mOsm/kg of water.

Question 470

What is the reference range for urine sodium?

Answer 470

The reference range for urine sodium is 40-220 mEq/L/24 hours

Question 471

Serum osmolality should be higher than urine osmolality.

True

False

Answer 471

False

Question 472

Which conditions cause low urine osmolality?

Answer 472

Diabetes insipidus

Excess fluid intake

Acute renal insufficiency

Glomerulonephritis

Question 473

Which conditions cause high urine osmolality?

Answer 473

Dehydration

Syndrome Inappropriate ADH secretion (SIADH)

Adrenal insufficiency

Glycosuria

Hypernatremia

High protein diet

Question 474

How do you differentiate an insulinoma from exogenous insulin administration?

Answer 474

Insulinoma –> high c-peptide and high fasting insulin

Exogenous –> high fasting insulin, low c-peptide

Question 475

What are the types of cells of the pancreas and what do they secrete?

Answer 475

the A cells (20%) secrete glucagon,

the B cells (70%) secrete insulin

the D cells (5%) secrete somatostatin or gastrin.

F cells secrete “pancreatic polypeptide.”

Question 476

What are the general features of insulinomas?

Answer 476

Insulinomas are usually benign (about 90%) and secrete excessive amounts of insulin that causes hypoglyce- mia. Insulinomas also produce proinsulin and C-peptide. Insulinomas are solitary in 95% of sporadic cases but are multiple in about 90% of cases arising in MEN 1.

Question 477

What are the general features of gastrinomas?

Answer 477

Gastrinomas secrete excessive quantities of the hor- mone gastrin (as well as “big” gastrin), which stimulates the stomach to hypersecrete acid, thereby causing hyper- plastic gastric rugae and peptic ulceration (Zollinger– Ellison syndrome).

About 50% of gastrinomas are malignant and metastasize to the liver.

Gastrinomas are typically found in the duodenum (49%), pancreas (24%), or lymph nodes (11%).

Sporadic Zollinger–Ellison syn- drome is rarely suspected at the onset of symptoms; typi- cally, there is a 5-year delay in diagnosis. About 22% of patients have MEN 1. In patients with MEN 1, gastrinomas usually present at a younger age; hyperparathyroidism may occur from 14 years preceding the Zollinger–Ellison diag- nosis to 38 years afterward.

Question 478

What are the general features of carcinoid tumours?

Answer 478

Carcinoid pancreatic neuroendocrine tumors secrete serotonin and can produce an atypical carcinoid syndrome manifested by pain, diarrhea, and weight loss; skin flushing occurs in 39% of patients. typi- cally indolent but usually metastasize to local and distant sites, particularly to other endocrine organs.

Question 479

What is a VIPoma?

Answer 479

VIPomas are rare pancreatic neuroendocrine tumors that produce vasoactive intestinal polypeptide (VIP), a substance that causes profuse watery diarrhea and pro- found hypokalemia (Verner-Morrison syndrome).

Question 480

What are the general features of

MEN-1

MEN-2A

MEN - 2B?

Answer 480

MEn 1: tumors of the parathyroid glands, endocrine pancreas and duodenum, pituitary, adrenal, thyroid; lipomas and facial angiofibromas.

MEn 2a: medullary thyroid cancers, pheochromo-

cytomas, Hirschsprung disease.

MEn 2B: medullary thyroid cancers, pheochromo- cytomas, Marfan-like habitus, mucosal neuromas, intestinal ganglioneuroma, delayed puberty.

Question 481

What does vasoactive intestinal peptide do?

Answer 481

Smooth muscle relaxation (LES, stomach, GB)

Stimulates water and electrolyte secretion into pancreatic juice and bile

Inhibits gastric acid secretion and absorption

Stimulats enteric smooth muscle contraction

Overall –> increased motility

Stimulates pepsinogen secretion by chief cells

Question 482

How do you differentiate Graves from thyroiditis on radioactive imaging?

Answer 482

During the hyperthyroid phase, iodine uptake is suppressed, while during the hypothyroid phase, uptake is increased.

This situation contrasts greatly with the elevated iodine uptake found in patients with Graves’ disease

Question 483

What is the most common cause of diminished tendon reflexes?

Answer 483

Diabetic neuropathy

Question 484

What is the most affected nerve of diabetic autonomic neuropathy?

Answer 484

Diabetic autonomic neuropathy manifests first in longer nerves. The vagus nerve (the longest of the ANS nerves) accounts for ~75% of all parasympathetic activity; as such, even early affects of diabetic autonomic neuropathy are widespread.

Question 485

What are the factors that contribute to hypoglycaemic unawareness?

Answer 485

a) there may be autonomic neuropathy Since epinephrine release is a function of the autonomic nervous system, the presence of autonomic neuropathy (i.e., a damaged autonomic nervous system) will cause the epinephrine release in response to hypoglycemia to be lost or blunted.
b) the brain may have become desensitized to hypoglycemia. If a person has frequent episodes of hypoglycemia (even mild ones), the brain becomes “used to” the low glucose and no longer signals for epinephrine to be released during such times. More specifically, there are glucose transporters located in the brain cells (neurons). These transporters increase in number in response to repeated hypoglycemia (this permits the brain to receive a steady supply of glucose even during hypoglycemia). As a result, what was once the hypoglycemic threshold for the brain to signal epinephrine release becomes lower. Epinephrine is not released, if at all, until the blood glucose level has dropped to even lower levels. Clinically, the result is hypoglycemic unawareness.
c) the person may be using medicines which mask the hypoglycemic symptoms - i.e. beta blockers

Question 486

A 30 year old woman presents with a 4cm solitary thyroid nodule - what tests would you do and why?

Answer 486

>1cm is a concerning feature

Start with a serum TSH - if it is a hyperfunctioning nodule it is less likely to be malignant so if TSH is suppressed and it’s hot on imaging, less need to worry.

If TSH is normal, then an ultrasound to see if it’s cystic or has other concerning features should be considered.

Question 487

In a 53 woman with suspected pathological fractures and severe osteoporosis on dexa scan whose serum electrophoresis shows decreased Ig but no paraprotein, what should you do and why?

Answer 487

When hypogammaglobulinemia is observed without a coincident paraprotein in the serum, the MLT should investigate the cause of hypogammaglobulinemia. If there is no known cause (immune disorder, chemotherapy, etc) for the patient’s lack of antibody production, the lab should request the collection of a urine sample. It is possible that the patient has an overproduction of free light chains that is reducing the production of normal antibodies. The free light chains may be filtering through the kidneys and therefore, only observed in the patient’s urine. The presence of free light chains is a clinically significant finding.

Question 488

What is the role of demeclocycline in SIADH?

Answer 488

It is widely used (though off-label in many countries) in the treatment of hyponatremia (low blood sodium concentration) due to the syndrome of inappropriate antidiuretic hormone (SIADH) when fluid restriction alone has been ineffective.[3] Physiologically, this works by reducing the responsiveness of the collecting tubule cells to ADH.

Question 489

What is the first line treatment for prolactinoma?

Answer 489

Dopamine agonist - usually bromocriptine or cabergoline (however long T1/2, may cause difficulties if low BP as hypotension is an SE)

Dopamine antagonises prolactin and shrinks the tumor in 80% of cases.

Surgery if refractory

Question 490

What are the symptoms of prolactinoma?

Answer 490

The symptoms due to a prolactinoma are broadly divided into those that are caused by increased prolactin levels or mass effect.

Those that are caused by increased prolactin levels are:[3]

Amenorrhea

Galactorrhea (infrequent in men)

Loss of axillary and pubic hair

Hypogonadism, gynecomastia, erectile dysfunction (in males)

Those that are caused by mass effect are:

Bitemporal hemianopsia (due to pressure on optic chiasm)

Vertigo

Nausea, vomiting

Question 491

What causes hyperreninaemic hypertension?

Answer 491

Renovascular hypertension

Question 492

What HLA testing can you do in coeliac disease?

Answer 492

Over 99% of people affected by coeliac disease have the HLA DQ2, HLA DQ8, or parts of these genes. Therefore, a negative test for these genes effectively rules out coeliac disease. The gene test on its own cannot diagnose coeliac disease – only 1 in 30 people who have HLA DQ2 or HLA DQ8 will develop coeliac disease. A gluten free diet should only be started after confirmation of coeliac disease by small bowel biopsy.