Endocrinology Flashcards
(46 cards)
Parathyroid hormone plays a central role in calcium and phosphate regulation. What is the primary target of PTH in the bone?
A. Osteoclast B. Osteoblast C. Osteocyte D. Mesenchymal stem cell E. Adipocyte
Answer: b - Osteoblast
The primary function of PTH is to maintain extracellular calcium within a narrow range. It acts directly on the bone and kidney plus indirectly on the GIT through its effects on vitamin D synthesis.
Osteoblasts have PTH receptors whereas osteoclasts do not. PTH mediated bone break down is indirect, and likely related to osteoblast signalling to the osteoclasts.
Intermittent PTH increases osteoblast numbers and prolongs their survival. This is important for the use of PTH analogues as anabolic treatment for osteoporosis (Teriparitide). Continuous exposure increases osteoclast mediated bone resorption.
Which of the following hormones leads to decreased food intake?
A. Ghrelin B. Glucagon C. Neuropeptide Y D. Leptin E. Cortisol
Answer: D - Leptin
Leptin is produced in adipose tissue and leads to suppression of appetite. It acts on the hypothalamus where it inhibits appetite by counteracting neuropeptide Y (a potent appetite stimulant) and promotes aplha-melanocyte-stimulating-hormone (suppressant).
Ghrelin stimulates appetite and is produces by the G cells of the stomach/pancreas.
Diuretics can alter calcium homeostasis. Which one of the following effects is most likely?
A. Thiazide diuretics increase GIT calcium absorption
B. Thiazide diuretics reduce urinary calcium excretion
C. Thiazides reduce serum calcium concentration
D. Loop diuretics reduce urinary calcium excretion
E. Loop diuretics increase serum calcium concentration
Answer: B - Thiazide diuretics reduce urinary calcium excretion
Thiazides reduce urinary calcium excretion. This can be therapeutically helpful in treatment of recurrent stone formation (calcium based). The fall in calcium excretion tends to increase serum calcium (mostly in older patients), usually in the setting of co-existing hyperparathyroidism.
Which protein is involved in glucose reabsorption at the brush border membrane of tubular epithelial cells in the kidney?
A. Glucose transporter (GLUT) type 1
B. GLUT 2
C. Sodium dependent glucose co transporter (SGLT)
D. Peroxisome proliferator activated receptor gamma (PPAR-gamma)
E. Hepatocyte nuclear factor (HNF)
Answer: C - SGLT Sodium dependent glucose co transporter
SGLT1 absorbs about 10% and SGLT2 about 90% of glucose in the proximal convoluted tubule.
HNFs are transcription factors in the liver, pancreatic islets, kidneys and genitals. In pancreatic beta-cells, they regulate insulin gene expression and proteins for glucose transport. HNF mutations are found in patients with MODY - mature onset diabetes of the young.
Which one of the following inhibits the formation of 1,25-OH2-vitamin D?
A. Circulating fibroblast growth factor 23 B. PTH C. Low serum phosphate level D. Pregnancy E. Sun exposure
Answer: A - Circulating fibroblast growth factor 23
1,25OH-vit D is activated by 1-a-hydroxylase in the proximal tubule of the kidneys –> 1,25-OH2-vit D.
Vitamin D stimulates uptake of calcium and phosphate in the GIT and also stimulates phosphate absorption from the renal tubules.
Formation of 1,25-OH2-vit D is stimulated by PTH and low phosphate levels, and it is inhibited by circulating FGF-23.
FGF-23 binds to its receptor and requires the protein Klotho as a cofactor. Active vitamin D up-regulates both FGF-23 and Klotho, as well as inhibiting PTH secretion. Thereby it reduces serum PTH and reduces renal phosphate loss and increasing FGF-23 increases serum phosphate loss.
What is the first physiological response to hypoglycaemia in an individual without diabetes mellitus?
A. Increased adrenaline B. Increased glucagon C. Decreased insulin D. Increased growth hormone E. Increased cortisol
Answer: C - Decreased insulin
Response to hypoglycaemia:
- Reduced insulin secretion
- Glucagon secretion
- Adrenaline secretion
- Delayed increase in growth hormone and cortisol
Insulin secretion begins to decrease as BGL approaches the lower limit of normal. It is the first defence against hypoglycaemia.
Glucagon stimulates gluconeogenesis and glycogenolysis.
Which of the following best describes the biological action of glucagon like peptide 1?
A. Glucose dependent inhibition of insulin secretion B. Suppression of glucagon secretion C. Decreased synthesis of proinsulin D. Accelerated gastric emptying E. Stimulation of appetite
Answer: B - Suppression of glucagon secretion
GLP-1 is an incretin that stimulates insulin, suppresses glucagon, inhibits gastric emptying and reduces appetite/food intake.
In addition to its effects on glucose homeostasis, which of the following is an effect of increased glucagon level?
A. Decreased energy expenditure B. Decreased ketogenesis C. Decreased bile acid synthesis D. Decreased thermogenesis E. Decreased food intake
Answer: E - Decreased food intake
In addition to its glucose metabolism effects. Glucagon does the following:
- Increased lipolysis
- Increased fatty acid oxidation and ketogenesis
- Increased satiety and decreased food intake
- Increased thermogenesis and energy expenditure
- Increased bile acid synthesis
Hyponatraemia is a frequent manifestation of primary adrenal insufficiency. Which one of the following hormone changes explains this manifestation?
A. Increased corticotrophin releasing hormone
B. Increased prolactin
C. Increased thyroid stimulating hormone
D. Reduced anti-diuretic hormone release
E. Reduction in adrenocorticotropic hormone
Answer: A - Increased corticotrophin releasing hormone
Hyponatraemia is common in adrenal insufficiency as many as 78%.
Cortisol deficiency causes low sodium via increased CRH which stimulates ADH release. CRH is high due to loss of negative feedback.
Whereas aldosterone deficiency causes low sodium because of renal loss, hypovolaemia and baroreceptor mediated ADH release.
Which one of the following is an effect of Amiodarone on thyroid function?
A. Decreased sensitivity of pituitary to thyroxine (T4) and T3
B. Inhibition of conversion of T4 to T3
C. Inhibition of thyroid stimulating hormone TSH release
D. Stimulation of T3 synthesis
E. Inhibition of thyrotropin-releasing hormone (TRH) secretion
Answer: B - Inhibition of conversion of T4 to T3
In 15% of patients treated with Amiodarone there is overt thyroid dysfunction.
Amiodarone has several effects including a high iodine load and inhibition of conversion of T4 to T3.
Amiodarone induced hypothyroidism results from an inability to escape the Wolff-Chaikoff effect.
Amiodarone induced thyrotoxicosis has 2 forms.
- Type 1 AIT results from iodine excess induced thyroid hormone synthesis (Jod Basedow effect)
- Usually occurs on background pre-existing multinodular goitre or latent Graves’ disease - Type 2 AIT is a destructive thyroiditis from release of excess pre-formed T4 and T3
Treatment for AIT is with anti-thyroid drugs (treats type 1) and glucocorticoids (type 2).
EMQ
A. TSH B. TSH receptor antibody C. Thyroxine binding globulin D. Thyroglobulin E. Thyroid peroxidase antibody F. Reverse T3 G. Thyrotropin releasing hormone (TRH) H. Thyroxine
- An increase of which one occurs in normal maternal thyroid physiology during pregnancy as a result of reduced hepatic clearance and increased synthesis?
- Which one of the above is produced only by normal or neoplastic thyroid follicular cells and is helpful for monitoring for thyroid cancer recurrence?
- Which one of the above is metabolised by de-iodinase to generate T3?
- Which one of the above is a tripeptide hormone released by the hypothalamus?
- Answer: C - Thyroxine binding globulin
- The best recognised alteration in maternal thyroid physiology is the increase in TBG, beginning early in 1st trimester, plateaus mid-gestation and persists until shortly after delivery. Expands the extra-thyroidal pool of thyroid hormone. - Answer : D - Thyroglobulin is produced by follicular cells and should not be present following thyroid ablation.
- Thyroglobulin assays can be falsely positive in the setting of anti-thyroglobulin antibodies (seen in 15% of thyroid carcinoma) so should be checked as well.
- Useful for follicular and papillary thyroid carcinoma - Answer: H - Thyroxine
- Answer: G - TRH
A 36 year old woman has an abdominal CT performed for abdominal pain. A 1.9cm mass in her right adrenal gland with an attenuation value of <10 Hounsfield units was the only abnormality. She has no significant past medical history. She is normotensive and overnight dexamethasone suppression test, urinary fractionated metanephrines and plasma aldosterone/renin ration and electrolytes are all normal. What should be the further management plan?
A. MRI adrenal glands B. Selective adrenal venous sampling for aldosterone C. Arrange for surgical resection D. Repeat CT at 6, 12 and 24 months E. 24 hour urinary cortisol levels
Answer: D - Repeat CT at 6, 12 and 24 months
Adrenal incidentaloma which is non-secretory. Should have regular follow-up with repeat imaging.
Incidentalomas should be assessed with an overnight dexamethasone suppression test, urinary fractionated metanephrines and plasma aldosterone : renin ratio
Imaging findings of concern include large size (>4cm is 90% sensitive for adrenal carcinoma). <10 Hounsfield units suggests lipid content and is most likely an adenoma.
A 30 year old woman with Cushing syndrome returns for her recent investigation results which are below. MRI pituitary did not show any mass. What would be the next appropriate step?
8am plasma cortisol 800 (200 - 650)
8am plasma ACTH 68 (<50)
Urine free cortisol 850/24hr (100 - 300)
Low dose dexamethasone suppression (2mg/day) cortisol - 575
High dose dexamethasone suppression test (8mg/day)
cortisol - 400
A. Bilateral adrenal vein sampling B. Inferior petrosal sinus sampling C. Midnight salivary free cortisol D. CT abdomen E. Refer patient to neurosurgeon
Answer: B - Inferior petrosal sinus sampling
Cushing syndrome:
- Establish presence of high cortisol
- Establish if ACTH dependent or ACTH independent
- If ACTH dependent is it Cushing disease (pituitary adenoma) or ectopic
Failure to suppress to 8mg/high dose dexamethasone = Ectopic ACTH (will not suppress)
Suppression of cortisol after high dose dexamethasone = Cushing disease/pituitary adenoma
In adrenal cushing, ACH will be low.
Which of the following is correct regarding type 2 diabetes in indigenous population compared to non-indigenous?
A. Age of onset is the same
B. Earlier average age of macrovascular complications in indigenous Australians
C. Lateral age of onset of microvascular complications in indigenous Australians
D. BMI is not a predictor of T2DM in indigenous Australians
E. Prevalence of type 2 diabetes is higher in non-indigenous Australians
Answer: B - Earlier average age of macrovascular complications in indigenous Australians
Which of the following is true regarding subclinical hypothyroidism?
A. TSH suppressed but thyroxine normal
B. TSH increased but thyroxine normal
C. It does not progress to overt hypothyroidism
D. Thyroxine replacement should be initiated if TSH is elevated
E. Population screening for subclinical hypothyroidism is of proven benefit
Answer: B - TSH increased but thyroxine normal
Subclinical hypothyroidism is an elevated TSH with normal thyroid hormone levels. 4-18% may progress to overt hypothyroidism each year.
Thyroxine treatment has no benefit on Cochrane review.
Most experts advocate treatment when the TSH is greater than 10.
A 34 year old man has been concerned about a change in facial appearance, headaches, hypertension and excessive sweating. Which one of the following test should be undertaken to investigate possible acromegaly?
A. Growth hormone release hormone level following an OGTT (oral glucose tolerance test)
B. 24 hour urinary IGF-1 levels
C. GHRH suppression test
D. GH levels following insulin stimulation test
E. Insulin-like growth factor 1 (IGF-1) and GH levels during a 2 hour period after a 75 g oral glucose load
Answer: E - Insulin-like growth factor 1 (IGF-1) and GH levels during a 2 hour period after a 75 g oral glucose load
Acromegaly = growth hormone excess
- GH is under dual inhibitory (somatostatin) and stimulatory (GHRH) control
- GH strongly stimulated by hypoglycaemia. Also stimulated by sleep, exercise, sepsis
- Acts via IGF-1 which gives negative feedback
Diagnosis:
- Elevated IGF-1 level
- 75g OGTT with FAILED SUPPRESSION of GH
Management: 1st line surgery
- Early cure 80-90% microadenomas, <50% macroadenomas
Medical management: (if post-operative IGF remains elevated or not amenable to surgery)
- Somatostain analogues
- Dopamine agonists can be trialled (often fails) - particularly if co-prolactin secreting
- Pegvisomant = GH receptor antagonist
Which one of the following is the most important reason to measure thyroid stimulating receptor antibodies during pregnancy in a women with Graves’ disease?
A. To detect foetal goitre
B. To predict risk of thyrotoxic storm
C. To titrate anti-thyroid therapy
D. To predict risk of neonatal thyrotoxicosis
E. To predict risk of post partum hypothyroidism
Answer: D - To predict risk of neonatal thyrotoxicosis
Because maternal thyroid receptor antibodies freely cross the placenta and can stimulate the foetal thyroid, they should be measured by 22 weeks with mothers with active Graves, previous Graves or if previously elevated TRAb.
If the TRAb is elevated >2-3x normal range then regular US screening should be done. PTU can be used if thought to endanger the pregnancy.
An 18 year old man presents for investigation of delayed puberty. On examination his height is 1.85cm and weight is 80kg. He has a complete loss of smell and small testes. The results of investigations are below. What is the likely diagnosis?
Prolactin 350 (50 - 450) Testosterone 4 (11 - 36) LH <0.1 (0.5 - 9) FSH 0.5 (1.0 - 8.0) Serum cortisol at 9am 165 (200 - 700)
A. Hypopituitarism B. Kallman syndrome C. Klinefelter syndrome D. Noonan syndrome E. Turner syndrome
Answer: B - Kallman syndrome
Hypothalamic gonadotropin release hormone deficiency - hence low testosterone and sex hormones - and deficient olfactory sense. It is usually X-linked inheritance or autosomal recessive.
Remember that Klinefelter syndrome causes a hypergonadotrophic hypogonadism with high LH/FSH and low testosterone
A 28 year old woman with T1 diabetes mellitus is 13 weeks pregnant. She is on a basal-bolus insulin treatment. She is seen in the high risk pregnancy clinic for the first time. Her BP is 120/70mmHg. Her most recent HbA1c is 8.3%. Which one of the following should be included in her management plan?
A. HbA1c every 3 months
B. Intensify her insulin treatment to achieve pre-prandial glucose level of 5.6 -6.5
C. Intensify her insulin treatment to achieve a post-prandial glucose at 1 hour of less than 8
D. Intensify her insulin treatment to lower her HbA1c to a target of 7.5%
E. Commence an ACE inhibitor
Answer: C - Intensify her insulin treatment to achieve a post-prandial glucose at 1 hour of less than 8
Diabetes in pregnancy is associated with increased risk of pre-eclampsia, preterm delivery and perinatal mortality.
Strict glycaemic control is important in pregnancy and pre-eclampsia is more frequent in poorly controlled diabetes.
STRICT TARGETS:
Recommended glycaemic targets are pre-prandial 4-5.5 and post prandial less than 8
HbA1c should be measured every 4-8 weeks (is normally lower in pregnancy)
A 50 year old woman presents with sudden onset of severe headache associated with vomiting for the last 24 hours. She has previously been healthy on no regular medications. Examination shows her temperature 37 degrees, HR 100bpm, BP 85/50. She has a partial right sided third nerve palsy present and investigations as below. What is the most likely diagnosis?
Hb 120 WCC 14.5 Platelets 240 CRP 32 Na 126 K 6.8 Urea 6.8 Creatinine 110 TSH 1.3 (0.4 - 4.5) T4/thyroxine 7 (10 - 22) Serum am cortisol 165 (200 - 700)
A. Brainstem ischaemic stroke B. Encephalitis C. Meningitis D. Pituitary apoplexy E. Subarachnoid haemorrhage
Answer: D - Pituitary apoplexy
Pituitary apoplexy characterised by sudden onset of headache, visual symptoms, altered mental state and hormonal dysfunction for haemorrhage or infarction of the pituitary.
Lateral extension can cause 3,4,5, 6 cranial nerve palsies.
Hypopituitarism is evident (usually all or most hormones) in the majority of patients.
You are referred a 19 year old woman with newly diagnosed diabetes. She has no symptoms but a random glucose of 17mmoL. A subsequent glucose was 5.8 and HbA1c 6.8%.
Her history is significant for cystic fibrosis diagnosed as an infant with numerous hospitalisations over the years for pulmonary infections. Her current medications include salbutamol QID, pancreatic enzymes TDS with meals, Ciprofloxacin 500mg BD and a multivitamin.
Her weight is 55kg (BMI 17.5)
You arrange for her to be taught home blood glucose monitoring by a diabetes educator. Which is the best therapeutic option?
A. Acarbose TDS with meals B. Metformin BD with meals C. Gliclazide slow release daily D. Once daily basal insulin E. Rapid acting insulin with meals
Answer: E - Rapid acting insulin with meals
CF-related diabetes (CFRD) is common in CF - up to 50% have impaired glucose tolerance.
CFRD is unique in that these patients have other factors affecting glucose metabolism including high energy expenditure, acute and chronic infection, glucagon deficiency, liver dysfunction, decreased intestinal transit time and increased work of breathing, as well as islet fibrosis leading to insulin deficiency.
Insulin sensitisers are unlikely to be effective.
They tend to be very sensitive to insulin due to pancreatic glucagon deficiency. Supplemental insulin to prevent post-prandial hyperglycaemia is the usual treatment and most do not require overnight insulin unless receiving nocturnal nasogastric of gastrostomy feeding.
Regarding diagnosis and management of prolactinoma, which is INCORRECT?
A. There is increased risk of cardiac valve regurgitation with use of cabergoline in patients with Parkinson disease
B. Bitemporal hemianopia and severe headache should have transphenoidal surgery
C. Elevated prolactin levels can be observed in patients with hepatic or renal failure
D. Anti-depressants and antipsychotic medications are associated with elevated prolactin
E. In patients with a pituitary macroadenoma, prolactin level can be greatly underestimated with immunoradiometric asssays
Answer: B - Bitemporal hemianopia and severe headache should have transphenoidal surgery
Dopamine agonists are the 1st line therapy for patients with prolactin secreting adenomas - micro or macro.
A 45 year old man is diagnosed with hypergastrinaemia due to Zollinger-Ellison syndrome with multiple endocrine neoplasia type 1. Which of the following findings can be observed?
A. Decreased lower oesophageal sphincter pressure
B. Decreased pepsinogen secretion
C. Increased gastric motility
D. Increased ileo-caecal sphincter pressure
E. Inhibition of gastric mucosal growth
Answer: C - Increased gastric motility
Gastrin has the main functions of:
- Increased HCl secretion via parietal cells
- Stimulate gastric mucosa growth
- Increased gastric motility
- Increase lower oesophageal sphincter pressure (preventing reflux)
- Lower ileo-caecal sphincter pressure
- Increase pepsinogen secretion
GIT neuroendocrine tumours are rare.
Gastrinomas are in the main sporadic. 12-20% are associated with MEN1 (MEN1 tumour suppressor gene)
MEN 1 = 3 Ps - Pituitary adenoma/Prolactinoma, Parathyroid hyperplasia/adenoma, pancreatic tumours (insulinoma 10%)
A 65 year old woman has had a total thyroidectomy and radioactive iodine for treatment of papillary thyroid carcinoma. She is on appropriate dose of thyroxine therapy. 6 months later she has a neck ultrasound which shows no residual thyroid disease. What other test should be considered at this time?
A. Anti-TPO antibody B. TSH C. T4 level D. Thyroglobulin E. Anti-TSHR antibody
Answer: D - Thyroglobulin
Thyroglobulin is used as a tumour marker or marker of residual disease/recurrence of papillary or follicular thyroid carcinoma.
Should be measured with serum anti-thyroglobulin antibodies at the same time.
