Endocrinology Flashcards
A patient has a large goitre with possibly some nodules, how should it be investigated?
TFTs
Ultrasound (cystic or solid? Aka typically benign or malignant)
Fine needle aspiration
Consider a radioiodine isotope scan to determine cause of hyperthyroidism- absent isotope uptake suggests inflammation or destroyed tissue
Which diseases put patients at risk of thyroid disease?
Hyperlipidaemia Diabetes mellitus Those on amiodarone (arrhythmia) or lithium (bipolar) Down's or Turner's Addison's
Signs of thyrotoxicosis not specific to Graves:
Underdressed for temperature Warm moist skin Fine tremor Palmar erythema Thin hair Lid lag- eyelids lag behind the eye's descent Lid retraction
3 Signs of Grave’s disease specifically:
1 Eye: opthalmaplegia, proptosis (exopthalmus is Grave’s is cause)
2 Pretibial myxoedema
3 Thyroid acropachy- clubbing, painful fingers and toes (Extreme manifestation)
Cause of Grave’s disease:
Circulating IgG autoantibodies that activate G-protein coupled thyrotropin) receptors
= smooth thyroid enlargement and increased hormone production
Causes of thyrotoxicosis:
Graves’ (2/3rds)
Toxic multinodular goitre (related to gene mutations, nodules secrete hormones)
Toxic adenoma (solitary nodule producing T4/3, rest of gland is supressed)
Ectopic thyroid tissue- metastatic follicular cancer
Exogenous- iodine excess, levothyroxine
Subacute De Quervain’s Thyroditis- postviral self limiting
How can you try to differentiate between Graves and multinodular goitre or toxic adenoma on palpation of the gland?
Graves- smooth diffuse enlargement
Toxic adenoma or multinodular goitre- more palpable nodules
Other nodular:
Carcinoma
Other diffuse enlargement:
Hashimoto’s, subacute De Quervain’s
Drug treatment of thyrotoxicosis:
- Propranolol
- Carbimazole (agranulocytosis SE) ± levothyroxine
Inhibits the thyroid peroxidase enzyme iodinating the hormones
Risk of thyroidectomy? (Things to look for if someone has a thyroid placed scar)
Recurrent laryngeal nerve damage- hoarse voice
Hypoparathyroidism- tingling, burning sensation, muscle cramps
In which diseases might anti-thyroid peroxidase antibodies be present?
Graves disease
Or Hashimoto’s (chronic autoimmune hypothyroidism)
Signs of Graves eye disease:
I- Exopthalmus- appearance of protruding eye
Proptosis- eyes protrude beyond the orbit
Conjunctival oedema
Corneal ulceration
F- Papilloedema
A- Loss of colour plates
CNIII- opthalmaplegia from muscle swelling and fibrosis restricting movement
How is Graves eye disease treated?
Caused by lymphocyte infiltration and periorbital swelling:
Mild- symptomatic (artificial tears, sunglasses, avoid dust, elevate head at night, prisms on glasses for diplopia)
Severe- with opthalmaplegia or gross oedema:
IV methylprednisolone
Surgical decompression
What are the symptoms of hypothyroidism:
BRADYCARDIC
Bradycardia Reflexes relaxing slowly Ataxia (cerebellar) Dry skin/hair Yawning/drowsy Cold hands + low T Ascites ± non-pitting oedema ± pleural/pericardial effusion Round puffy face Defeated demeanor Immobile CCF
Neuropathy, myopathy
Causes of primary hypothyroidism:
Autoimmune- atrophic or Hashimoto’s (lymphocytic)
Iodine deficiency
Iatrogenic- thyroidectomy, radioiodine therapy, amiodarone, lithium
Subacute De Quervain’s- postviral (temporary)
What does POEMS syndrome stand for:
Polyneuropathy Organomegaly Endocrinopathy M-protein band (plasmacytoma) Skin tethering/pigmentation
How can amiodarone cause thyrotoxicosis and why may thyroid problems persist once stopped?
Has a cytotoxic effect on thyroid follicular cells, may cause a thyroiditis causing thyroid release
Amiodarone has a half life of 80 days
What effect does excess cortisol have?
In excess, it acts like aldosterone
Salt retention at the expense of H+ and K+
= hypokalaemic hypertensive alkalosis
Ie in Cushing’s, adrenal hyperplasia, ectopic ACTH
Patient has the signs of Grave’s disease but is euthyroid, what could the cause be?
Could still be Graves, before thyroid disease has occurred yet
There are TSH-receptors in the eye
Rx for grave’s
Carbimazole
Propylthiouracil
SE: agranulocytosis- rash, fever, sore throat
Features of MEN1?
Pituitary tumours
Pancreatic neuroendocrine tumours (VIPoma)
Parathyroid tumours- all 4 glands may be affected
What test can determine whether a patient has high Ca2+ because of a familial kidney condition?
Urine calcium should be low if they have benign hypocalciuric hypercalcaemia
Secondary causes of diabetes:
Drugs: steroids, thiazides, atypical antipsychotics (olanzepine)
PMH: CF, chronic pancreatitis, haemochromotosis, Cushing’s/phaeochromocytoma, acromegaly
MODY, gestational, DIDMOAD
Patient has random glucose of 10, what would your next line of investigation be?
Between 7-11 do a fasting glucose test
If fasting glucose is >7 do an oral glucose tolerance test
+ve if above 11
How long do you fast for before taking a fasting blood glucose?
8 hours
How is an oral glucose tolerance test performed?
Fast for 8 hours
75mg of glucose
Measure at 2 hours
Complications of diabetes:
Macrovascular: Stroke, peripheral arterial disease, MI
Microvascular: Nerve, eyes, kidneys
Acute: hypoglycaemic crisis, DKA
Types of thyroid carcinoma
Please Feel My Airway Lightly
Papillary (commonest- orphan annie nuclei on histology)
Follicular (female, favourable prognosis, faraway mets)
Medullary (calcitonin, Men2 associated, Ca low)
Anaplastic (old, poor survival)
Lymphoma (A with Hashitomo’s thyroiditis)
Tumour markers for thyroid cancers
Thyroglobin: follicular + papillary
Calcitonin
What are the electrolyte abnormalities classically associated with Cushing’s?
Mineralocorticoid effect: low K+, high Na+
Glucocorticoid effect: hyperglycaemia
Causes of Cushing’s that are ACTH-dependent and independent
ACTH dependent: Pituitary adenoma (Cushing’s disease) or hyperplasia, ectopic source
ACTH independent: Adrenal hyperplasia, adrenal adenoma, exogenous
Pseudo-Cushing’s: severe depression, alcoholism
Tests for Cortisol if suspected:
- Best: Urinary 24hr cortisol
But often: Midnight cortisol - Low dose Dexamethasone test = confirms
Dexamethasone at midnight, measure in AM - Measure ACTH = dependent or independent
High- dependent
Low- adrenal cause (CT or adrenal vein sampling) - High dose Dexamethasone = ?ectopic
Low Cortisol- Cushing’s disease in pituitary
High Cortisol- Ectopic ACTH
Rx of Cushing’s:
Pituitary adenoma:
Ketoconazole then transphenoidal excision
Adrenal site:
Ketoconazole then adrenalectomy
Which is the more potent suppresser of TSH- T3 or T4?
T3
In someone taking levothyroxine, is it more important to measure T3 or T4?
T4 as this acts as the thyroid store, each cell converts as much of T4 as it needs into T3
What is Sheehan’s syndrome?
Pituitary necrosis after postpartum haemorrhage hypovolaemia
What basal tests can be performed to look for hypopituitarism?
Low: LH and FSH Testosterone, oestradiol TSH, T4 IGF-1 (measures GH axis) Cortisol
High from disinhibition:
Prolactin
What dynamic tests of pituitary function can be performed?
- Short synacthen test: ACTH given and cortisol measured
2. Insulin tolerance test: IV insulin, measure GH and cortisol increase
Which hormones are produced by the anterior and posterior pituitary gland?
Anterior: TSH, Prolactin, FSH, LH, ACTH
Posterior: ADH, GH
Features of polycystic ovarian syndrome:
Oligomenorrhoea/amenorrhoea
Infertility
Obesity, acne, hirsutism
Causes of gynaecomastia
Oestrogens may be increased by:
Tumours- testicular, adrenal, bronchial HCG producing
Failure to convert them
Hypogonadism
Liver cirrhosis
Hyperthyroidism
Causes of erectile dysfunction:
Big 3: smoking, alcohol and diabetes
Endocrine: hypogonadism, high prolactin or thyroid, kidney/liver dysfunction
Neurological: prostate or bladder surgery damage, MS, cord lesions, autonomic neuropathy
Penile abnormalities: Peyronie’s, post-priaprism
Drugs: F DDAB (can’t properly F)
digoxin, diuretics, antidepressants, antipsychotics, b blocker, finasteride
Management of erectile dysfunction:
LFTs, U+Es, glucose, TFTs, LH, FSH, lipids, testosterone, prolactin
- PDE5 inhibitor- sildenafil
Inhibition prevents break down of cGMP, which activates Ca+ activated K+ channels to hyperpolarise and relax smooth muscle cells (= engorgement)
Vacuum aids
Intracavernosal injections
Inflatable prostheses
Bioengineered tissue engineering
CI to PDE5 inhibitors like sildenafil
PC: bleeding from peptic ulcer
PMH: unstable angina, MI in 3 months, stroke
Renal or liver impairment, hypertension, retinal disorders (PDE in the eye affected)
DHx: concurrent nitrates
Causes of primary hypogonadism in males:
Chromosomal- XXY (Klinefelter’s)
Post orchitis- mumps, HIV, leprosy
Local trauma- torsion, chemo
Systemic- Renal failure, liver cirrhosis, alcohol excess (toxic to Leydig cells)
Causes of secondary hypogonadism:
Low LH and FSH:
Hypopituitarism, Prolactinaemia
Kallman’s syndrome- isolated GnRH deficiency ± colour blind
Systemic- COPD, HIV, DM, Age
Patient with end-stage renal failure, polydactyly and low IQ?
Other features?
Laurence Moon syndrome
Autosomal recessive- obesity, hypogenitalism, reduced body hair, azoospermia
Retinitis pigmentosa
Kidney- calyceal clubbing, cysts, diverticula
What affects does high aldosterone have?
Sodium and water retention
Leading to reduced renin release from juxtaglomerular cells
Renin release is stimulated by:
- Sympathetic action (B1-adrenorecptors)
- Low Na+ at DCT
- Renal artery hypotension
Patient has a BP of 160/95
U+Es:
K+ 3mmol
Na+ 144mmol
What endocrine cause is there?
Primary aldosteronism:
Acts on ENaC to increase Na/K exchange at collecting duct
Stimulates a proton-ATPase increasing proton excretion leading to a metabolic alkalosis
Causes of primary aldosteronism:
66% solitary adenoma of adrenals (Conn’s syndrome)
33% adrenocortical hyperplasia
Rarely: adrenal carcinoma
Glucocorticoid-remediable aldosteronism
What is the pathophysiology and Rx of glucocorticoid-remediable aldosteronism?
The ACTH regulatory element fuses with the aldosterone synthase gene, bringing aldosterone under control of ACTH + increasing production.
Rx: Dexamethasone normalises biochemistry but perhaps not BP
By suppressing ACTH release
Tests if suspecting primary aldosteronism:
- U+Es, venous blood gas- hypokalaemic alkalosis
- Plasma Renin- normally low due to dilutional effects of salt + water retention
Plasma aldosterone to renin ratio- high aldosterone vs renin
Drugs may interfere- diuretics, steroids, antihypertensives, laxatives
- CT or MRI to localise cause
- Adrenal vein sampling- identify adenoma
How are the common causes of aldosteronism (Conn’s, adrenal hyperplasia) managed differently?
Conn’s: spironolactone for 4 weeks then laparoscopic adrenalectomy
Hyperplasia: medical management- spironolactone, amiloride, eplerenone
Causes of secondary hyperaldosteronism?
High renin and high aldosterone
Reduced renal perfusion (renin release stimulated by low pressure, lack of salt in DCT or sympathetic input) from:
Renal artery stenosis
Accelerated hypertension
Diuretics, CCF, hepatic failure
What is Bartter’s syndrome and what U+Es findings would you expect?
Autosomal recessive salt wasting
Sodium chloride leak in the loop of Henle via a defective channel
Sodium loss > aldosteronism > low K+ and alkalosis
PC: polydipsia, polyuria and failure to thrive in childhoos
What is a phaeochromocytoma?
Catecholamine-producing tumour
Arising from sympathetic paraganglionic cells (chromaffin cells) in the adrenal medulla
10% rule
10% malignant
10% extra-adrenal (by aortic bifurcation)
10% bilateral
10% inheritable (MEN2a, MEN2b, neurofibromatosis, von Hippel Lindau)
What is the classic triad of phaeochromocytoma?
- Episodic headache
- Sweating
- Tachycardia
Tests for phaeochromocytoma?
3 x 24 hour urine samples- metadrenalines and normetadrenalines
Localisation: Abdo CT/MRI
or MIBG chromaffin seeking isotope scan
Rx of phaeochromocytoma:
a-adrenoreceptor blockade- phenoxybenzamine
as unopposed a-stimulation will cause vasoconstriction (b adrenorecptors dilate vessels to skeletal muscle)
b-blockers if tachycardic
Surgical removal
What parts of the adrenal gland make the different hormones?
Medulla- noradrenaline (phaeochromacytoma)
Cortex- GFR
GFR Miner GA:
Glomerulosa- mineralcorticoid
Fasciculata- glucocorticoids
Reticularis- androgens
What is Takotsubo cardiomyopathy?
Stress or catecholamine-induced cardiomyopathy (broken heart syndrome)
Sudden chest pain, mimicking an MI
ECG shows ST elevation
Echo- Apical ballooning during catecholamine surges
Can occur with phaeochromocytoma
Causes of primary adrenocortical insufficiency (Addison’s disease):
Vascular: Waterhouse-Friderichsen’s syndrome of bilateral adrenal haemorrhage from meningococcal sepsis where endotoxin activates inflammatory and clotting cascades (DIC) or SLE, antiphospholipid syndrome
Infection: TB (commonest cause worldwide), opportunistic HIV (T) Autoimmune: 80% on UK (M) Iatrogenic Neoplasia: mets, lyphoma
How does Addison’s present?
PC:
Tired, weak, dizzy, myalgia, arthralgia
Depression, psychosis
N+V, abdo pain, constipation or diarrhoea
EHx:
Hands- pigmented palmar creases, vitiligo, pigmented skin
Shock- hypotensive, tachycardic, pyrexial, coma
Patient has low Na+, high K+, low glucose, high Ca+, low Hb
What needs to be excluded and how?
Low Na+ and high K+ is lack of aldosterone
Low glucose may be due to low cortisol
So Addison’s disease:
Short ACTH stimulation test (synACTHen test)- check cortisol levels in response to ACTH, will remain low as no ability to make cortisol.
9am ACTH level (high if primary adrenocortical insufficiency)
Test for Addison’s?
Primary adrenocortical insufficiency
- U+E: low Na, high K, high Ca, low glucose
- Short ACTH synacthen test- cortisol low after ACTH
- 9am ACTH level- low = secondary cause (ACTH-dependent cause)
- Plasma renin and aldosterone- measure mineralocorticoid status
Which antibody is raised in autoimmune Addison’s disease?
Responsible for 80% of Addison’s in the UK
21-hydroxylase adrenal autoantibodies
Rx of Addison’s disease?
Hydrocortisone in 2-3 doses- may cause insomnia if given late
Fludrocortisone OD
Steroid rules apply- no stopping suddenly, double in illness, extra for exercise, IM if vomiting, have steroid card or bracelet
How does secondary adrenal insufficiency differ from Addison’s disease (primary adrenal insufficiency)?
Mineralocorticoid production remains intact- U+Es normal
ACTH is low rather than high
No hyperpigmentation- no excess ACTH
Commonly due to suppression of pituitary-adrenal axis from exogenous steroids
Which hormones does ACTH stimulate production of?
Cortisol- fasciculata
Androgens- reticularis (GFR minerGA)
Rarely in glucocorticoid-remediable aldosteronism it can stimulate aldosterone release due to gene fusion
What’s the difference between Cushing’s syndrome and Cushing’s disease?
Cushing’s syndrome- clinical state produced by chronic glucocorticoid excess and loss of normal feedback mechanisms in the axis.
Primarily due to exogenous steroids.
Cushing’s disease- pituitary adenoma secreting ACTH leads to bilateral adrenal hyperplasia, a specific and rare cause of Cushing’s syndrome
What are the ACTH dependent and independent causes of Cushing’s syndrome?
ACTH dependent:
Pituitary adenoma (Cushing’s disease)
Ectopic ACTH production- small cell lung cancer, carcinoid tumours
Ectopic CRF (Corticotrophin Releasing Factor)- medullary and prostate cancers
ACTH independent:
Oral exogenous steroids
Adrenal nodular hyperplasia
Adrenal adenoma/cancer
Carney complex (pigmented, myxoma, schwannoma, endo tumours)
McCune-Albright syndrome (fibrous dysplasia of bone, pigmented)
What type of cancer’s produce ectopic ACTH and which rarely can produce CRF?
ACTH- small cell lung cancer and carcinoid tumours
CRF- medullary thyroid and prostate cancer
How does ectopic ACTH production in Cushing’s syndrome cause a hypokalaemic metabolic alkalosis?
Very high cortisol mimics mineralocorticoid activity = hyperaldosteronism
So more K+ exchanged for Na+ and more activation of proton ATPase leading to proton excretion
How to investigate suspected Cushing’s syndrome:
- Late night cortisol
- Overnight Dexamethasone suppression test
Dex at midnight, serum cortisol at 8am, no suppression - 48 hour high dose Dex suppression test
(halves cortisol in pituitary adenoma, Cushing’s disease) - Plasma ACTH= dependent or independent cause
How are ACTH dependent causes of Cushing’s syndrome investigated differently from independent causes once the ACTH dependency is established?
So after plasma cortisol,overnight dex test, high dose suppression test, ACTH levels
ACTH high:
Suppressed by high dose dex (pituitary cause) > head MRI
Not suppressed > CT chest, abdo, pelvix with contrast ± MRI
ACTH low:
CT adrenal glands
No mass > adrenal vein sampling or adrenal scintigraphy
Rx of Cushing’s disease or ectopic ACTH production:
Pituitary adenoma secreting ACTH: transphenoidal removal of adenoma
Ectopic ACTH production: excision of tumour, ketoconazole and fluconazoe reduce cortisol pre-op if high
If ACTH causing psychosis may need cortisol receptor antagonist (mifespristone)
Effects of PTH?
Secreted in response to low ionised Ca+ Increases osteoclast activity Increases Ca+ reabsorption in the kidney Reduced PO4 reabsorption by kidney Increases active Vit-D3 production
Causes of primary hyperparathyroidism?
80% parathyroid adenoma
19% hyperplasia
0.5% cancer
What can cause a high calcium and high or inappropriately normal PTH?
Primary hyperparathyroidism- adenoma, hyperplasia
Thiazides + lithium
Familial hypocalciuric hypercalcaemia (check 24hr urine Ca+)
Tertiary hyperparathyroidism (autonomous production of PTH after long period of secondary PTHism)
Management of primary hyperparathyroidism?
Conservative: Increase fluid (prevents stones) Avoid thiazides Ensure good vit D + calcium intake
Medical:
2nd post surgery Cinacalcet reduces PTH glands sensitivity to Ca+
Surgical:
US or MIBG might isolate a adenoma for removal
Or parathyroid gland excision if high Ca+, osteoporosis or renal damage
SEs: reccurent laryngeal nerve damage, low Ca+
If secondary/tertiary hyperparathyroidism is caused by CKD how will this look different from primary parathyroidism?
Secondary has low Ca and high PTH
low Vit D means low Ca absorption in gut and low Ca
Primary would have high Ca and high PTH
Tertiary has high Ca and very high PTH because glands are acting autonomously without any feedback
Which type of cancer rarely produces PTH related peptide?
Squamous cell lung cancers
Breast + renal cell carcinomas
Patient has short 4th and 5th metacarpals, low IQ, high PTH and short stature. Cause?
Pseudohypoparathyroidism
Genetic loss of target cell response to PTH
Differences between MEN1, MEN2a and MEN2b?
MEN1 - 3P’s
Parathyroid, Pituitary (prolactinoma or GH), Pancreas (VIPoma,
insulinoma)
MEN2a - 2P, 1M
Parathyroid, Phaeochromocytoma, Medullary thyroid
MEN2b- 1P, 2M
Phaeochromocytoma, Medullary thyroid, Marfanoid appearance/ mucosa neuroma
Name 7 Multiple Endocrine Neoplasia syndromes and their characteristic features:
Autosomal dominant syndromes A with hormone-producing tumours
- Neurofibromatosis
Type 1- cafe au lait spots, skin fold freckling, neurofibromas, Lisch nodules in eyes
Type 2- cafe au lait spots, schwannoma causing acoustic neuroma - MEN1: Parathyroid, Pancreas (VIPoma, insulinoma etc), Pituitary (prolactinoma, GH-producing)
- MEN2a: Parathyroid, phaeochromocytoma, medullary thyroid
- EN2b: Phaeochromocytoma, medullary thyroid, Marfainoid
- Von Hippel Lindau: renal cysts, phaeo, cerebellar haemangioma
- Peutz Jeghers: lip, mucosa, hand + feet freckling, GI polyps
- Carney complex: pigmentation, myxoma, schwannoma, adrenal and pituitary tumours
In MEN1 syndrome, what types of pancreatic hormonal tumours may arise and their symptoms?
Gastrinoma (Zollinger Ellison): multiple + distal peptic ulcers, chronic diarrhoea as pancreatic enzymes are inactivated
Insulinoma: hypoglycaemia- faint, sweaty, tremor, palpitations
Somatostatinoma: DM, steatorrhoea, gallstones
VIPoma: diarrhoea and low K+, acidosis, high Ca+, low Mg+
Glucagonoma: migrating rash, glossitis, anaemia, weight loss
Symptoms of hypothyroidism
Tired, sleepy, lethargic, depressed, reduced memory, dementia
Weight gain, constipation
Myalgia, cramps, neuropathy, myopathy, weakness
Menorrhagia, hoarse voice
Causes of hypothyroidism:
Primary autoimmune:
Atrophic
Hashimoto’s- goitre from lymphocyte infiltration
Iodine deficiency
Iatrogenic- radioiodine or thyroidectomy
Drugs- Amiodarone, lithium, antithyroid drugs
Post viral- Subacute de Quervain’s
Secondary- very rare, pituitary insufficiency
Rx of hypothyroidism, and things to watch out for with treatment:
Levothyroxine
Half life 7ds, so wait to check effects when changing dose
Susceptible to more metabolism when enzyme inducers given
What is subacute hypothyroidism and how is it managed?
TSH raised, T4 normal
Risk of progression to hypothyroidism
Can try a trial of medication if TSH >4 to see if patient functions better
Signs specific to Graves disease:
Eye disease- exopthalmos, opthalmoplegia
Pretibial myxoedema
Thyoid acropachy
Bruit, mild neutropenia
What type of antibodies are associated with Graves disease?
TSH R antibody (Graves)
Thyroid peroxidase antibody (Graves or Hashimoto’s)
Thyroglobulin antibody (Hashimoto’s or thyroid cancer)
If someone has hyperthyroidism and you give them contrast for a CT scan, what happens?
Thyroid storm
Causes of hyperthyroidism and how they differ on isotope scan?
Graves- autoantibodies, global uptake of isotope
Toxic multinodular goitre- in elderly or iodine deficient, focal nodules
Toxic adenoma- hot nodule, rest supressed
Ectopic thyroid tissue- follicular thyroid cancer or ovarian
Iodine excess, amiodarone, levothyroxine
Subacute de Quervain’s- low isotope uptake (NSAIDs help)
Post-partum
Management of hyperthyroidism:
Propranolol for symptoms
Carbimazole- either titrated up or block completely + give thyroxine
For 1-1.5 years, then withdraw.
Thyroidectomy or radio iodine (CI: pregnancy) if relapse.
Main risk factor for Graves eye disease?
Smoking
Symptoms of Graves eye disease?
Grittiness, tear production
Discomfort, photophobia
Diplopia, reduced acuity, afferent pupillary defect*
*optic nerve compression eek!
Exopthalmos = appearance of protruding eye, proptosis = eye extends beyond orbit
Management of Graves eye disease
Conservative: if mild, artificial tears, sunglasses, elevate bed at night, Fresnel prism for diplopia
Medical: if severe, high dose steroids
Surgical: if sight threatening, decompression or cosmetic
A painful goitre amounts to what typically:
Subacute De Quervain’s thyroiditis (viral)
What is sick euthyroidism?
TSH and T4 all low
Following a systemic illness, TFTs may become deranged temporarily
If repeated when recovered, should not see this
What test can you do if suspecting self-induced hyperthyroidism in a patient?
(Administering levothyroxine)
Thyroglobulin- the thyroid protein precursor to T4 will be low as endogenous T4 production is suppressed
Which patients should be screened for thyroid abnormality?
AF Hyperlipidaemia DM, Addison's disease Type 1 DM + pregnant Down's, Turner's syndrome
When is surgery warranted for a thyroid problem?
Refractory hyperthyroidism (have withdrawn carbimazole after 1.5 years and still hyperthyroid)
Nodule is too big >3cm or compression
Rapid growth
Dominant nodule on scintigraphy, hypoechoic nodule
Causes of hypoglycaemia:
EXPLAIN
EXogenous drugs- insulin, oral hypoglycaemics
Alcohol, ACEi, aspirin poisoning, bblockers, insulin (body builders)
Pituitary insufficiency
Liver failure
Addison’s disease
Islet cell tumours- insulinoma, anti-insulin R abs in Hodgkins
Non-pancreatic neoplasms
Post-prandial hypoglycaemia:
After gastric or bariatric surgery IHx: prolonged OGTT
Tests if a patient has hypoglycaemia?
Blood glucose- laboratory (monitors may not be reliable at low values)
Insulin level
C peptide- waste product of endogenous insulin production
Plasma ketones
What causes hypoglycaemia, low insulin and no excess ketones?
Rarely
Anti-insulin receptor antibodies (in Hodgkin’s lymphoma)
Non-pancreatic neoplasms- fibrosarcoma, secreting an peptide downstream from insulin with a similar effect like insulin growth factor
A patient has hypoglycaemia, how does the level of insulin determine the likely cause?
High insulin:
Insulinoma, sulphonylurea, insulin injection
Low insulin, high ketones:
Alcohol, pituitary insufficiency, Addison’s disease
Patient has had a gastric bypass and has been found to be hypoglycaemic after meals, what specific test do they require?
Prolonged oral glucose tolerance test lasting 5 hours
Rx of hypoglycaemia?
- Sugar or long-acting carb if possible
2a. 200mL glucose 10% IV (less vein damage than 50% glucose)
2b. Glucagon IM in no IV access
What are Whipple’s triad of symptoms for fasting hypoglycaemia:
Occurs in insulinomas (sporadic or part of MEN1)
- Symptoms associated with fasting or exercise
- Recorded hypoglycaemia with symptoms
- Symptoms relieved with glucose
Different tests if suspecting insulinoma?
Screening: Insulin level and glucose level during a fast
Suppressing: IV insulin + measure C-peptide
Normally exogenous peptide suppresses C peptide production
Imaging: CT/MRI
Which signs distinguish ischaemia from peripheral neuropathy on the foot exam?
Ischaemia: critical toes (ulcers, gangrene), absent dorsalis pedis
Peripheral neuropathy: injury or infection over pressure points (like metatarsal head)
NB: most patients have both
Signs of peripheral neuropathy in the diabetic foot:
Inspect:
Charcot foot- absent pes cavus, claw toes, loss of transverse arch, rocker bottom sole
Absent ankle jerks
Reduced sensation in a stocking distribution
Points to educate someone with a diabetic/ischaemic foot on:
- Daily foot inspection
- Good shoes- soft leather, increased depth, no barefoot walking, cushioning insoles
- Regular chiropody- remove calluses
- Fungal infection treatment
- Surgery referral potentially
What are the 4 things to examine or investigate with a diabetic foot ulcer?
Assess degree of:
- Neuropathy- clinically
- Ischaemia- clinically, doppler ± angiography
- Bony deformity(Charcot joint)- clinically + xray
- Infection- swabs, blood culture, ulcer probe (depth) + xray (osteomyelitis)
Rx of diabetic neuropathy of the feet
Bed rest to relieve high pressure areas
Therapeutic shoes
Regular chiropody
Abs for infection- benzylpenicillin, flucloxacillin, metronidazole
Considerations for surgery
What are the 4 types of neuropathy someone with diabetes might get?
- Peripheral sensory neuropathy- glove + stocking
- Mononeuritis multiplex- if sudden or severe, immunosupression can be tried
- Amyotrophy- painful wasting of quadraceps
- Autonomic- postural BP drop, gastroparesis, urine retention, ED
How should gastroparesis be proved in a diabetic patient who is experiencing early satiety, post-prandial N+V and bloating?
99-technetium labelled meal
Rx: antiemetics, erythromycin or gastric pacing
Complications of diabetes:
Macrovascular- MI, stroke, peripheral arterial disease
Statin advised + clopidogrel if PAD
Microvascular- nephropathy, neuropathy, retinopathy
ACEi i microproteinuria
Stages of diabetic retinopathy:
Nonproliferative retinopathy: mild, moderate and severe
Mild- dots + blots
Moderate- dots, blots, hard exudates
Severe- blots, cotton wool spots, venous beading + loops
Proliferative retinopathy:
New vessel formation (floaters, visual loss)
Maculopathy:
Exudate (from vessel leaks) or retinal thickening within an optic disc
Rx of maculopathy?
Sudden vision loss-
Intravitreal steroids
Laser photo-coagulation (to destroy peripheral ischaemic vessels releasing anti-VEGF)
Anti- angiogenic agents
What is the stepwise approach to oral glycaemic agents in T2DM?
HbA1c >48: lifestyle measures
HbA1c
>48: metformin
>58: meformin + other drug* (Aim <53)
> 58: metformin + 2 other drugs (often 1 sulfonylurea) or insulin
*sulfonylurea, gliptin, SGLT2i, pioglitazone
Under what circumstances is a GLP-2 mimetic indicated? (Exenatide)
If triple therapy of metformin + 2 other drugs is not tolerated
AND BMI >35
= metformin + sulfonylurea + GLP1 mimetic
What is needed to diagnose diabetes?
Symptoms + fasting glucose >6.9 Symptoms + random glucose >11 2 occasions of abnormal glucose HbA1c >48 1 abnormal glucose + abnormal OGTT (>11 at 2 hours)
Which HLA groups is diabetes mellitus type 2 associated with?
HLA DR3 (3 little pigs and a straw shack)-
HLA DR4- rheum for dad and mum (DM)
What are the untypical forms of type 1 and 2 DM?
Latent autoimmune diabetes of adults- T1DM onsetting later in life
Mature onset diabetes of the young- T2DM onsetting earlier in life (autosomal D)
Features of metabolic syndrome:
Central obesity (waist circumference or BMI >30) + 2 of:
1. Hypertension >130/85 2. Insulin resistance DM or fasting glucose >5.5 3. Low HDL levels 4. Hypertriglyceridaemia >1.6 mmol
How does tubular dysfunction cause a difference in U+Es results than low eGFR?
Tubular dysfunction: low K+, low urate, low phosphate, high H+
May be polyuric with all sorts in the urine
Low eGFR: high K+, high urate, high phosphate, low H+
May be oliguric
What pattern of U+Es do thiazides and loop diuretics cause?
Low Na+, low K+, high bicarbonate
Thiazide- high Ca in blood (the-HIGH-azide)
Loop diuretics- low Ca (Lowoop)
How quickly can potassium be given in a peripheral line?
20mmol an hour
But 40mmol per bag max
how does ma differ depending on whether someone has osteopenia or osteoporosis?
Osteopenia (T score from -2.5 to -1): lifestyle advice
Stop smoking, reduce alcohol
Weight bearing exercise, tai chi, calcium rich diet, OT input at home
Osteoporosis (T score below -2): lifestyle and Rx
Causes of osteomalacia:
Vit D deficiency or resistance (inheritable)
Renal osteodystrophy
Liver failure- needed to convert Vit D also
Drug induced- anticonvulsants
What is Paget’s disease and the complications of it?
Increased numbers of osteoclasts and osteoblasts + remodelling causing bone enlargement + deformity.
Asymptomatic 70%
Bony pain + deformity > pathological fractures, osteoarthritis
High Ca
Nerve compression from bone overgrowth (deafness)
High output CCF
Osteosarcoma <1%
Rx of Paget’s disease:
Analgesia
Bisphosphonates
Commonest type of porphyria and how it manifests:
Acute intermittent porphyria- autosomal dominant
Neurovisceral symptoms:
Abdo pain, vomiting, constipation, fever, WCC
Peripheral neuropathy, seizures, psychosis
High BP + HR, low BP
How do acute and chronic porphyrias present differently?
Acute: neurovisceral symptoms with photosensitivity in the less common type (variegate prophyria)
Chronic: cutaneous photosensitivity alone- may have increased facial hair or hyperpigmentation (prophyria cutanea tarda, erythropoeitic protoporphyria)
What is the inheritance and cause of primary hyperlipidaemia?
Autosomal dominant
Mutations in LDL receptors impairs exchange of LDLs
Heterozygotes- cardiovascular disease
What are the four types of primary hypertriglyceridaemia?
- Familial hypertriglyceridaemia
Xantomata, high VLDLs - Familial dysbetalipoproteinemia
Elevated intermediate DLs + chylomicrons - Lipoprotein lipase deficiency
Chylomicron metabolism - Apo CII deficiency
Needed to activate lipoprotein lipase
What are secondary causes of elevated LDLs?
Hypothyroidism
Liver disease
Nephrotic syndrome
Thiazides, glucocorticoids, ciclosporin
What are secondary causes of elevated triglycerides?
Obesity, diabetes, proegesterone, acute hepatitis
Alcohol, oestrogens, antifungals
What are eruptive xanthomata and what do they occur in?
Itchy crops of lipid nodules found in primary hypertriglyceridaemia
MEN2A+ 2B patients with medullary thyroid cancer have what gene mutation?
RET gene mutation- gain of function
