Endocrinology Flashcards
What effect does biotin have on thyroid function?
Can cause spurious results on TFTs, as it interferes with assay.
Can cause false positive Graves-like appearance
Patients taking biotin should hold the supplement for two days prior to assessing thyroid function and longer if they are taking more than 10 mg a day.
What are the main associations with MEN2 syndrome?
WHat is the main difference between MEN2A and MEN2B?
MEN2A = medullary thyroid cancer, pheochromocytoma, and primary parathyroid hyperplasia
MEN2B = MTC + pheochromocytoma but not hyperparathyroidism
What are the main associations with MEN1 syndrome?
3Ps
Tumours of
- parathyroid glands
- anterior pituitary
- enteropancreatic endocrine cells
2011B40
A 52 year old male presents with flushing, watery diarrhoea and wheezing. Urinary 5HIAA is 120mg/dL (2-8). A CT of the abdomen shows multiple liver metastases.
What is the site of primary tumour? A. colon B. oesophagus C. rectum D. small intestine E. stomach
Small intestine
Distribution frequency =
GIT – 55%
- Small intestine – 45%, most commonly in the ileum
- Rectum 20%, Appendix 16%, Colon 11%, Stomach 7%
Bronchopulmonary system – 30%
What is the most common clinical presentation of carcinoid syndrome?
Chronic flushing (85%) & diarrhea (80%)
Result of serotonin (and other vasoactive substances) secretion into the systemic circulation
What test has >90% sensitivity and specificity for carcinoid syndrome diagnosis?
24-hour urinary excretion of 5-hydroxyindoleacetic acid (5-HIAA)
- Values >100 md/day indicative of carcinoid syndrome (normal 2-8mg/day)
5-HIAA is an end product of serotonin metabolism
5-HIAA is most useful in patients with primary midgut (jujunoileal, appendiceal, ascending colon) carcinoid tumours, which produce the highest levels of serotonin
What the effect of SGLT2 inhibitors on glucagon and insulin levels?
It decrease glucose levels, which leads to reduction in insulin and increase in glucagon
What is the main orexigenic hormone from the stomach that promotes hunger?
Ghrelin
What are the main hunger-promoting hormones from the arcuate nucleus of the hypothalamus?
Agouti-related peptide (AgRP) Neuropeptide Y (NPY)
Where is leptin secreted from?
What are its main effects?
Secreted by adipocytes
Acts as the body’s marker of fat stores
An increase will stimulate melanocortin, which suppresses appetite
What is the main difference between Roux-en-Y and Sleeve gastrectomy in terms of weight loss mechanism?
Both are restrictive, but Roux-en-Y is also malabsorptive
What is the most effective treatment for morbid obesity?
Bariatric surgery
What is the proven most effective T2DM prevention strategy?
Intensive lifestyle program with diet and exercise
What are the effects of insulin on glucose utilisation, proteins and fats?
Glucose utilisation
- Stimulates uptake of glucose by skeletal muscle and fat
- Inhibits hepatic gluconeogenesis by decreasing free fatty acids to liver -> decreased gluconeogenesis
Fat
- Promotes storage of triglycerides in adipose tissue
- Inhibits lipolysis of stored triglycerides from adipose tissue
Protein
- Increases protein synthesis
What are incretins?
What is their function?
They are insulin secretagogues.
- Amplification effect -> determines up to 70% of post-prandial insulin production
- After meal, GLP1 / GIP peptide hormones bind to pancreas -> production of insulin
- DPP4 cleaves GLP1, rendering it inactive
- Incretin effect is impaired in DM
Which transporter in the kidney is responsible for up to 90% of PCT reabsorption of glucose?
SGLT2 - Sodium glucose co-transporter 2
Which hypoglycaemic agents promote weight loss?
Metformin
GLP-1 agonists
SGLT2 inhibitors
Which hypoglycaemic agent can improve BP?
SGLT2 inhibitors via weak diuretic affect
Which hypoglycaemic agents have shown to reduce CV death?
Empagliflozin
Liraglutide
What are the main auto-abs in T1DM? (4)
GAD
IA2
Insulin
ZnT8
What is the duration of action of Ryzodeg 70/30?
42 hours
What are 4 key advantages of insulin pumps over injections?
Reduced HbA1c
Reduced severe hypos
Improved QoL
May decrease mortality (CV and overall)
What is the role of RANK Ligand in bone?
Cytokine which is essential for development and survival of osteoclasts -> promotes bone resorption
Is bone mineral density a more sensitive or specific marker of fracture risk?
Specific
Low sensitivity
At what BMD range do most fractures occur?
Osteopenic range -> -1 -> -2.5
What is the biggest risk factor for fracture in osteoporosis?
Previous fracture
Which type of bone is most affected in steroid-induced OP?
Trabecular (cancellous)
What is the PBS criteria for bone health treatment in long-term steroid use?
> 7.5mg/day of prednisolone for over 3 months + T-score <1.5
What are the three ways in which PTH acts to increase serum calcium?
- Promotes formation of calcitriol in kidneys, which increases GIT absorption of Ca and Phos
- Mobilises calcium from bone by promoting resorption
- Increases renal calcium reabsorption
What is the best way to distinguish between factitious hypoglycaemia and insulinoma?
C-peptide level
- will be high in insulinoma
What diagnosis is consistent with diffusely increased uptake on Thyroid Uptake Scan?
Graves Disease
What are the indications for treating subclinical hypothyroidism? (3 definitive)
Treat if ->
- TSH >10 - Symptomatic - Pregnant (TSH >4)
Consider if:
- Age <65 - Heart failure - TPO / Tg ab positive - Dyslipidaemia
What are the indications for treating subclinical hyPERthyroidism? (5)
Treat if =
- TSH <0.1 - Symptoms - AF - Heart failure - Osteoporosis
Why is there hyperpigmentation in primary adrenal insufficiency?
Due to increased production of proopiomelanocortin (POMC), a prohormone that is cleaved into the biologically active hormones -> ACTH, MSH, and others.
The elevated MSH results in increased melanin synthesis, causing hyperpigmentation.
What is the most common cause of primary adrenal insufficiency?
What are the other common causes?
Autoimmune adrenalitis is responsible for 70 to 90%
Remainder =
- infectious diseases
- replacement by metastatic cancer or lymphoma
- adrenal hemorrhage / infarction
- drugs
What are the tests to diagnosis primary adrenal insufficiency?
Early morning cortisol and ACTH
Short Synacthen to detect response to ACTH stimulation
Check plasma renin levels (will be elevated)
When is ongoing mineralocorticoid replacement required in adrenal insufficiency?
In primary only
-> adrenal insufficiency secondary to hypopituitarism only requires glucocorticoid replacement; mineralocorticoid replacement is not required because the renin–angiotensin–aldosterone axis remains intact
What should be done to the mineralocorticoid dosing for a patient with primary adrenal insufficiency who is acutely unwell?
Nothing ->
Acute adjustment of the mineralocorticoid dose is not required for stress or intercurrent illness.
How is primary adrenal insufficiency treatment monitored?
What is the role of ACTH?
At each review, measure serum sodium and potassium and plasma renin concentrations.
Plasma renin concentration in the upper-normal reference range indicates optimal mineralocorticoid replacement.
Clinically, assess for features of glucocorticoid/mineralocorticoid excess/deficiency
ACTH does not correlate well with appropriateness of replacement, so is not used
Acute treatment for adrenal crisis?
Hydrocortisone 100 mg intravenously, initially, then 50 mg intravenously, every 6 hours until stable and tolerating oral intake.
Hypovolaemia -> IV NaCl 0.9%
Correction of hypoglycaemia
Severe hyperkalaemia -> usually responds to IV fluids and hydrocortisone therapy —do not use intravenous insulin and glucose.
What dose of prednisolone would be expected to lead to adrenocortical suppression?
Oral prednis(ol)one at a dose of 10 mg or more daily for more than 3 weeks
What is the most common cause of adrenal dysfunction in children?
Congenital adrenal hyperplasia
What enzyme is most commonly deficient in CAH?
What hormonal imbalances does this lead to?
21-hydroxylase
Leads to cortisol and aldosterone deficiency, with androgen excess
What is the usual presentation of Nonclassical congenital adrenal hyperplasia?
What is it (usually) caused by?
Androgen excess without glucocorticoid deficiency.
Females -> hirsutism and menstrual irregularity; may be clinically indistinguishable from PCOS.
Can be asymptomatic
In men often very subtle, hard to pick up
Caused by a PARTIAL deficiency of the 21-hydroxylase enzyme, leading to androgen excess without symptoms of glucocorticoid deficiency
Most common cause of hypopit in adults?
PItuitary adenoma
Why can thyroxine not be commenced in hypopit until cortisol is corrected?
Levothyroxine increases the clearance of cortisol, and can precipitate adrenal crisis in a patient with low glucocorticoid reserve.
In adults with growth hormone deficiency who can receive recombinant GH replacement, how is dose titrated / monitored?
Titrate the somatropin dose to achieve a plasma IGF-1 concentration in the middle of the age-adjusted reference range.
What is the effect of oestrogen therapy on GH levels in GH deficiency?
Oral oestrogen decreases sensitivity to growth hormone, increasing the dose requirement if on replacement.
How is diabetes insipidus diagnosed?
Water deprivation test -> measures response of plasma and urine osmolality to water deprivation. In DI, fluid restriction does not lead to appropriate concentrating of urine (which would appear as increased urine osmolality >600)
Differentiating between central and nephrogenic -> give desmopressin
- urine osmolality will increase in response to desmopressin if the patient has central diabetes insipidus, but not nephrogenic diabetes insipidus
Management of central diabetes insipidus?
Drink to thirst
Oral Desmopressin, adjusted to electrolytes
What is the difference between micro and macro prolactinoma?
Micro <10mm diameter
Macro >10mm
What are 1st line treatment options for prolactinoma?
Dopamine agonists -
- cabergoline
- bromocriptine
What is the management of prolactinoma during pregnancy?
Prolactinomas can enlarge in pregnancy
- risk depends on size of the prolactinoma before pregnancy.
Smaller masses -> stop dopamine agonist therapy when pregnancy is confirmed.
Monitor - assess the woman regularly throughout pregnancy for signs of prolactinoma enlargement (eg headache, visual disturbance).
Macro
- Formal assessment of visual fields is recommended each trimester
- MRI if the patient becomes symptomatic
- If enlargement on MRI -> treatment with Bromocriptine
Large mass -> Consider surgical debulking before pregnancy.
Use bromocriptine pre-emptively
What is the 1st line treatment for acromegaly?
Surgery -> Trans-sphenoidal microadenomectomy
What is the 2nd line Rx for acromegaly, after surgery?
Somatostatin analogue
- lanreotide
- octreotide
- Pasireotide if non-responsive to the 1st two options
Adjunct if required -> dopamine agonist
What is Pegvisomant?
3rd line agent for acromegaly
GH receptor antagonist
PBS approved for refractory IGF-1 to somatostatin analogue
Initial screening test for suspected primary aldosteronism?
Plasma aldosterone-to-renin ratio (elevated)
Which anti-hypertensives do NOT interfere with plasma aldosterone-to-renin ratio, and can be taken by the patient when tested?
Diltiazem, verapamil
Prazosin
Hydralazine
After initial screening, how is Conn’s dx confirmed?
- Aldosterone suppression test to confirm
- Oral sodium load for 3 days OR IV NaCL load for 4 hours
- Aldosterone should be suppressed <140 - Adrenal CT
- Tumour on CT and aged <40 -> reliably the cause
- May be incidentaloma in age >40 - Adrenal vein sampling -> To check for lateralisation
What is the medical management of Conn’s?
MRA ->
- Spironolactone
- Eplerenone (less effective but better tolerated)
Screening tests for Phaeo?
Plasma free metanephrines / normetanephrines
Urine total metanephrines
In Phaeo, why must alpha-adrenergic blockade be established prior to treatment with beta blockade?
Unopposed alpha receptor–mediated vasoconstriction can cause an extreme rise in blood pressure
Why is Phenoxybenzamine generally the preferred agent for alpha blockade in Phaeo?
Noncompetitive alpha-adrenergic blocker, so cannot be displaced from alpha receptors by a rise in concentration of endogenous catecholamines (unlike prazosin)
What are three genetic syndromes commonly associated with Phaeo?
Von Hippel-Lindau (VHL) syndrome
MEN2
Neurofibromatosis type 1 (NF1)
What percent of adrenal incidentalomas are functional?
20%
What is the general algorithm for evaluation of adrenal incidentalomas?
Test for hormonal hypersecretion
- if present, consider surgery
If non-functional
- assess risk based on imaging characteristics ->
- > over 4cm
- > over 10 Hounsfield units
- > delayed CT contrast washout
- if suspicious, consider surgery
If benign phenotype, monitor =
- repeat imaging in 12 months
- biochemical testing for 4-5 years
What is the 1st line medical management of Cushing’s syndrome, used when surgical management is not appropriate or unsuccessful?
1st line -> ketoconazole (inhibits the first step in cortisol biosynthesis - side-chain cleavage - and, to a lesser extent, the conversion of 11-deoxycortisol to cortisol
2nd line -> add Metarypone (11-beta-hydroxylase inhibitor that blocks the final step in cortisol biosynthesis
or IV Etomidate (blocks 11-beta-hydroxylation of deoxycortisol to produce cortisol)
What are the initial screening tests for Cushing’s syndrome?
24 hour urinary cortisol or late night salivary cortisol
Which medication can be used to achieve medical adrenalectomy in Cushings?
Mitotane
= Adrenolytic -> binds to important macromolecules in the mitochondria, causing mitochondrial destruction and necrosis of adrenocortical cells
Used in high doses for adrenal carcinoma
What are some contraindications to COCP? (8)
- current or previous venous thromboembolism (VTE)
- genetic thrombophilia
- coronary artery disease
- cerebrovascular disease
- uncontrolled hypertension
- severely impaired liver function
- malignancy of the breast or genital tract
- migraine with aura
Biochemically, how can we tell if a menstrual cycle if ovulatory?
Serum progesterone concentration is >20 nmol/L during the midluteal phase (5-10 days prior to menses)
For women taking HRT, when do you use cyclical and when do you use continuous?
Cyclical ->
- women still having spontaneous menses or LNMP under 2 years ago (may get withdrawal bleed on continuous)
Continuous
- 2 years post menopause
What are some non-hormonal options for treating vasomotor symptoms of menopause?
Venlafaxine (SNRI)
Paroxetine (SSRI)
Gabapentin
Clonidine
How is androgen deficiency diagnosed in men?
Must have both the following factors =
- Consistent symptoms and signs of androgen deficiency
- An unequivocally low early morning plasma testosterone concentration, confirmed by repeat measurement.
What effect does obesity have on SHBG?
What effect does age have on SHBG?
Obesity decreases SHBG concentrations, thereby decreasing the serum total testosterone concentration
Aging increases SHBG
Why should androgen levels not be evaluated in acute illness in men?
They are likely to have transient functional secondary hypogonadism
How can non-classical CAH be differentiated from PCOS biochemically?
NCCAH -> very elevated 17-hydroxyprogesterone level when tested in early morning at follicular phase
Can then be confirmed with ACTH stimulation test -> The Response to ACTH is exaggerated in NCCAH
What is the effect of licorice on
Inhibits enzyme ->
Gene in polyglandular autoimmune syndrome Type 1?
Triad?
AIRE gene
Hypoparathyroidism
Chronic mucocutaneous candidiasis
Later -> adrenal insufficiency
Common manifestations of polyglandular autoimmune syndrome Type 2?
Autoimmune thyroid disease
T1DM
Adrenal insufficiency
