| Value | Reference range | |
|---|---|---|
| 8 am plasma cortisol (nmol/L) | 800 | 200–650 |
| 8 am plasma adrenocorticotrophic hormone (ACTH) (ng/L) | 68 | <50 |
| Urine free cortisol (nmol/24 h) | 850 | 100–300 |
| Low-dose dexamethasone suppression test (2 mg/day): urine free cortisol (nmol/24 h) | 575 | |
| High-dose dexamethasone suppression test (8 mg/day): urine free cortisol (nmol/24 h) | 400 |
A. Bilateral adrenal vein sampling
B. Inferior petrosal sinus sampling
C. Midnight salivary free cortisol
D. Computed tomography of the abdomen
E. Refer the patient to a neurosurgeon
17. Which one of the following observations is correct regarding type 2 diabetes in the Australian indigenous population compared to the non-indigenous population?
A. Age of onset of type 2 diabetes in the indigenous and non-indigenous population is the same
B. There is an earlier average age of onset of macrovascular complications in the indigenous population
C. There is a later age of onset of microvascular complications in the indigenous population
D. Body mass index is not a predictor of the development of type 2 diabetes in the indigenous population
E. The prevalence of type 2 diabetes is higher in the non-indigenous population
18. Which one of the following statements is true concerning subclinical hypothyroidism?
A. Thyroid stimulating hormone (TSH) levels are suppressed but thyroxine levels are normal
B. TSH levels are increased but thyroxine levels are 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
19. A 34-year-old man has been concerned about a change in facial appearance, headaches, hypertension and excessive sweating. Which one of the following tests should be undertaken to investigate possible acromegaly?
A. Growth hormone-releasing hormone levels following a 75-g oral glucose load
B. 24-h urinary insulin-like growth factor 1 (IGF-1) levels
C. Growth hormone-releasing hormone suppression test
D. Growth hormone (GH) levels following insulin stimulation test
E. Insulin-like growth factor I (IGF-1) and growth hormone (GH) levels during a 2-h period after a 75-g oral glucose load
20. Which one of the following is the most important reason to measure thyroid stimulating hormone receptor antibodies during pregnancy in a woman with Graves disease?
A. To detect fetal goitre
B. To predict the risk of thyrotoxic storm
C. To titrate dose of anti-thyroid therapy
D. To predict the risk of neonatal thyrotoxicosis
E. To predict the risk of post-partum hypothyroidism
21. An 18-year-old man presents for investigation of delayed puberty. On examination, his height is 1.85 m and weight is 80 kg. He has a complete loss of the sense of smell and small testes. The results of investigations are shown below. What is the likely diagnosis?
| Value | Reference ranges | |
|---|---|---|
| Prolactin (mU/L) | 350 | 50–450 |
| Testosterone (nmol/L) | 4 | 11–36 |
| Luteinising hormone (LH) (IU/L) | <0.1 | 0.5–9.0 |
| Follicular stimulating hormone (FSH) (IU/L) | 0.5 | 1.0–8.0 |
| Serum cortisol at 9.00 am (nmol/L) | 165 | 200–700 |
A. Hypopituitarism
B. Kallman syndrome
C. Klinefelter syndrome
D. Noonan syndrome
E. Turner syndrome
22. A 28-year-old woman with type 1 diabetes 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 blood pressure (BP) is 120/70 mmHg. Her most recent HbA1c is 8.3%. Which one of the following should be included in her management plan?
A. HbA1c level should be monitored every 3 months
B. Intensify her insulin treatment to achieve a pre-prandial glucose level of 5.6–6.5 mmol/L
C. Intensify her insulin treatment to achieve a post-prandial glucose level at 1 h of less than 8 mmol/L
D. Intensify her insulin treatment to lower her HbA1c level to a target of 7.5%
E. Commence angiotensin converting enzyme (ACE) inhibitor
23. A 50-year-old woman presents with a sudden onset of severe headache associated with vomiting for the preceding 24 h. She has previously been healthy and does not take any medications. On examination, her temperature is 37 ° C, pulse is 100 beats/min and blood pressure is 85/50 mmHg. There is also a partial right-sided third nerve palsy present. The results of her investigations are shown below. What is the most likely diagnosis?
| Value | Reference ranges | |
|---|---|---|
| Haemoglobin (g/L) | 120 | 115–155 |
| White cell count (cells/L) | 14.5 × 109 | 4.0–11.0 × 109 |
| Platelet count (cells/L) | 240 × 109 | 150–450 × 109 |
| C-reactive protein (g/L) | 32 | 0–10 |
| Sodium (mmol/L) | 126 | 137–145 |
| Potassium (mmol/L | 4.3 | 3.2–4.3 |
| Urea (μmol/L) | 6.8 | 2.7–8.0 |
| Creatinine (μmol/L) | 110 | 60–100 |
| Thyroid-stimulating hormone (mIU/L) | 1.3 | 0.4–4.5 |
| Free thyroxine (T4) (pmol/L) | 7 | 10–22 |
| Serum cortisol at 9.00 am (nmol/L) | 165 | 200–700 |
A. Brainstem ischaemic stroke
B. Encephalitis
C. Meningitis
D. Pituitary apoplexy
E. Subarachnoid haemorrhage
24. You are referred a 19-year-old woman with newly diagnosed diabetes. She has no symptoms, but had a random glucose of 17 mmol/L. A subsequent fasting glucose was 5.8 mmol/L and HbA1c was 6.8%.
Her medical history is significant for cystic fibrosis diagnosed as an infant. She has had numerous hospitalisations over the years for pulmonary infections. Her current medications include salbutamol inhaler 200 μg four times a day, pancreatic enzymes of variable dose three times a day, ciprofloxacin 500 mg twice a day, and one multi-vitamin tablet daily. Her weight is 55 kg (BMI 17.5 kg/m2).
You arrange for her to be taught home blood glucose monitoring by a diabetic educator. What is the best therapeutic option at this point?
Her medical history is significant for cystic fibrosis diagnosed as an infant. She has had numerous hospitalisations over the years for pulmonary infections. Her current medications include salbutamol inhaler 200 μg four times a day, pancreatic enzymes of variable dose three times a day, ciprofloxacin 500 mg twice a day, and one multi-vitamin tablet daily. Her weight is 55 kg (BMI 17.5 kg/m2).
You arrange for her to be taught home blood glucose monitoring by a diabetic educator. What is the best therapeutic option at this point?
A. Acarbose three times a day with meals
B. Metformin twice daily with meals
C. Gliclazide slow release once daily
D. Once-daily basal insulin
E. Rapid-acting insulin with meals
25. Regarding diagnosis and management of prolactinoma, which one of the following is INCORRECT?
A. There is an increased risk of cardiac valve regurgitation with the use of cabergoline in patients with Parkinson disease
B. Patients with bitemporal hemianopia and severe headache should have transphenoidal surgery
C. Elevated prolactin levels can be observed in patient with hepatic or renal failure
D. Anti-depressants and anti-psychotic medications are associated with elevated prolactin levels
E. In patients with a pituitary macroadenoma, prolactin level can be greatly underestimated with immunoradiometric assays
26. A 45-year-old man was diagnosed to have hypergastrinaemia due to Zollinger–Ellison syndrome associated with multiple endocrine neoplasia syndrome type 1. Which one the following findings can be observed?
A. Decrease in lower oesophageal sphincter (LES) pressure
B. Decrease in pepsinogen secretion
C. Increase in gastric motility
D. Increase in ileo-caecal sphincter pressure
E. Inhibition of gastric mucosa growth
27. A 65-year-old woman has had a total thyroidectomy and radioactive iodine for treatment of papillary thyroid carcinoma. She is on an appropriate dose of thyroxine therapy. Six months later she has a neck ultrasound which shows no residual thyroid disease. What other test should be considered at this time?
A. Anti-thyroperoxidase antibody
B. Thyroid-stimulating hormone
C. Free thyroxine (free T4)
D. Thyroglobulin
E. Anti-thyroid stimulating hormone receptor antibody
28. A 39-year-old woman with a history of primary hyperparathyroidism treated with subtotal parathyroidectomy presents with episodic headaches and palpitations. She is found to be hypertensive. Further investigations reveal that her 24-h urinary norepinephrine (noradrenaline) and epinephrine (adrenaline) are 600 nmol/L (0–450) and 752 nmol/L (0–100), respectively. In addition her serum calcitonin is also elevated at 1355 ng/L (0–5.5). Which one of the following genes should be considered for mutational analyses?
A. Adenomatous polyposis coli (APC) gene
B. Breast cancer type 1 (BRCA1) gene
C. K-ras oncogene
D. RET oncogene
E. Von Hippel–Lindau (VHL) gene
29. A 27-year-old woman presented with amenorrhoea since stopping her oral contraceptive pill 4 months ago. She has no significant past medical problems. The results of investigations are shown below. What is the most likely cause of her amenorrhoea?
| Value | Reference range | |
|---|---|---|
| Prolactin (ng/mL) | 24 | 5–20 |
| Oestrogen (pmol/L) | 28676 | 100–2400 |
| Testosterone (nmol/L) | 2.9 | 0.5–2.5 |
| Luteinising hormone (LH) (IU/L) | <1.0 | 3.0–12.0 |
| Follicle stimulating hormone (FSH) (IU/L) | <1.0 | 2.0–10.0 |
A. Prolactinoma
B. Pregnancy
C. Congenital adrenal hyperplasia (CAH)
D. Premature ovarian failure
E. Polycystic ovary syndrome (PCOS)
30. A 59-year-old man has chronic kidney disease secondary to diabetic nephropathy. His estimated glomerular filtration rate is 45 mL/min/1.73 m2. Which one of the following glucose-lowering agents poses the highest risk of hypoglycaemia in the setting of the renal impairment?
A. Acarbose
B. Exenatide
C. Glimepiride
D. Metformin
E. Sitagliptin
Theme: Endocrine investigations (for Questions 31–34)
A. 24-h urinary catecholamines and metanephrines
B. Plasma catecholamines
C. Blood renin-to-aldosterone ratio
D. Insulin-like growth factor-I
E. Saline suppression test
F. Thyroid function test
G. Urinary sodium and osmolality
H. Water deprivation test
31. The hypertension in a 40-year-old woman is known to be difficult to control. She is currently taking three anti-hypertensive medications. She also complains of recurrent anxiety attacks and episodes of palpitations. Which one of the above is the next most appropriate investigation?
32. A 76-year-old woman presents with confusion. Her family reports her being constipated and gaining weight in recent months. On examination, she is alert but disoriented in time and place. Her heart rate is 52 beats/min and blood pressure is 138/95 mmHg. There is non-pitting oedema in both legs. The chest X-ray reveals cardiomegaly and bilateral small pleural effusions. Apart from mild hyponatraemia (serum sodium level 133 mmol/L), other biochemistry results are unremarkable. What is the next most appropriate investigation?
33. A 40-year-old man presents with recent changes in his vision and headaches. He reports that he has had two near-miss traffic accidents because he failed to spot cars approaching him at a T-junction. His medical history is unremarkable though his wife reports the recent onset of severe snoring and he recently had bilateral carpal tunnel release. On examination, he is hypertensive with a blood pressure of 160/95 mmHg and he is tanned from a recent holiday. The rest of his cardiovascular, respiratory and abdominal examination is normal. What is the next investigation to undertake?
34. A 68-year-old woman presents after a 2-day history of vomiting. She is found to have hypernatraemia but her elevated serum sodium concentration did not improve despite adequate fluid replacement. She has a history of bipolar disorder and has been taking lithium for the past 8 years. What is the appropriate investigation after stabilising this patient clinically?
Answers
Basic Science
1. Answer B
The primary function of parathyroid hormone (PTH) is to maintain the extracellular fluid calcium concentration within a narrow normal range. The hormone acts directly on bone and the kidney and indirectly on the intestine through its effects on synthesis of 1, 25-dihydroxy-vitamin D to increase serum calcium concentration (Kousteni and Bilezikian, 2008).
Osteoblasts (or stromal cell precursors), which have PTH receptors, are crucial to the bone-forming effect of PTH; osteoclasts, which appear to lack PTH receptors, mediate bone breakdown. PTH-mediated stimulation of osteoclasts is thought to be indirect, acting in part through cytokines released from osteoblasts to activate osteoclasts. In in vitro experiments, osteoblasts must be present for PTH to activate osteoclasts to reabsorb bone. Intermittent PTH treatment increases osteoblast numbers, induces differentiation of committed osteoblast precursors and prolongs osteoblast survival. Understanding the cell biology of PTH is important in appreciating the mechanism of action of PTH analogues in the treatment of osteoporosis (Kraenzlin and Meier, 2011). Continuous exposure to elevated levels of PTH for days leads to increased osteoclast-mediated bone reabsorption, but intermittent administration leads to a net stimulation of bone formation rather than bone breakdown.
The primary function of parathyroid hormone (PTH) is to maintain the extracellular fluid calcium concentration within a narrow normal range. The hormone acts directly on bone and the kidney and indirectly on the intestine through its effects on synthesis of 1, 25-dihydroxy-vitamin D to increase serum calcium concentration (Kousteni and Bilezikian, 2008).
Osteoblasts (or stromal cell precursors), which have PTH receptors, are crucial to the bone-forming effect of PTH; osteoclasts, which appear to lack PTH receptors, mediate bone breakdown. PTH-mediated stimulation of osteoclasts is thought to be indirect, acting in part through cytokines released from osteoblasts to activate osteoclasts. In in vitro experiments, osteoblasts must be present for PTH to activate osteoclasts to reabsorb bone. Intermittent PTH treatment increases osteoblast numbers, induces differentiation of committed osteoblast precursors and prolongs osteoblast survival. Understanding the cell biology of PTH is important in appreciating the mechanism of action of PTH analogues in the treatment of osteoporosis (Kraenzlin and Meier, 2011). Continuous exposure to elevated levels of PTH for days leads to increased osteoclast-mediated bone reabsorption, but intermittent administration leads to a net stimulation of bone formation rather than bone breakdown.
Kousteni, S. and Bilezikian, J.P. (2008). The cell biology of parathyroid hormone in osteoblasts. Curr Osteoporos Rep 6, 72–76.
Kraenzlin, M.E. and Meier, C. (2011). Parathyroid hormone analogues in the treatment of osteoporosis. Nat Rev Endocrinol 7, 647–656.
2. Answer D
Leptin is a circulating peptide hormone that is produced primarily in adipose tissue and leads to suppression of appetite.
Leptin acts on receptors in the hypothalamus where it inhibits appetite by counteracting the effects of neuropeptide Y (a potent appetite stimulant) and promotes the synthesis of α-melanocyte-stimulating hormone, an appetite suppressant. Genetic deficiency of leptin or the leptin receptor leads to severe obesity.
Ghrelin is an appetite-stimulating hormone that is produced mainly by the stomach and pancreas. Its secretion increase with starvation or reduced food intake and it stimulates secretion of growth hormone, increases appetite and leads to weight gain. Reduced ghrelin production may partially account for the effectiveness of some bariatric surgery.
Glucagon is a counter-regulatory hormone to hypoglycaemia and it increases glucose production in the liver by increasing both gluconeogenesis and glycogenolysis.
Leptin is a circulating peptide hormone that is produced primarily in adipose tissue and leads to suppression of appetite.
Leptin acts on receptors in the hypothalamus where it inhibits appetite by counteracting the effects of neuropeptide Y (a potent appetite stimulant) and promotes the synthesis of α-melanocyte-stimulating hormone, an appetite suppressant. Genetic deficiency of leptin or the leptin receptor leads to severe obesity.
Ghrelin is an appetite-stimulating hormone that is produced mainly by the stomach and pancreas. Its secretion increase with starvation or reduced food intake and it stimulates secretion of growth hormone, increases appetite and leads to weight gain. Reduced ghrelin production may partially account for the effectiveness of some bariatric surgery.
Glucagon is a counter-regulatory hormone to hypoglycaemia and it increases glucose production in the liver by increasing both gluconeogenesis and glycogenolysis.
3. Answer B
Thiazide diuretics tend to lead to a reduction in urinary calcium excretion. This effect can be therapeutically helpful in the treatment of recurrent stone formers with hypercalciuria. The fall in calcium excretion also tends to induce positive calcium balance or to minimise the degree of negative calcium balance that is commonly seen in older patients. This may be manifested clinically by an increase in bone density, possibly by a reduction in the incidence of hip fracture. Chronic use of a loop diuretic may have the opposite effect as it tends to promote calcium loss and negative calcium balance may enhance the risk of hip fracture. Thiazide diuretics can be associated with hypercalcaemia, but usually in the presence of co-existing hyperparathyroidism.
Thiazide diuretics tend to lead to a reduction in urinary calcium excretion. This effect can be therapeutically helpful in the treatment of recurrent stone formers with hypercalciuria. The fall in calcium excretion also tends to induce positive calcium balance or to minimise the degree of negative calcium balance that is commonly seen in older patients. This may be manifested clinically by an increase in bone density, possibly by a reduction in the incidence of hip fracture. Chronic use of a loop diuretic may have the opposite effect as it tends to promote calcium loss and negative calcium balance may enhance the risk of hip fracture. Thiazide diuretics can be associated with hypercalcaemia, but usually in the presence of co-existing hyperparathyroidism.
4. Answer C
The kidney contributes to glucose homeostasis through gluconeogenesis, glucose filtration, reabsorption and consumption. Under normal circumstances, up to 180 g/day of glucose is filtered by the renal glomerulus and virtually all of it is reabsorbed in the proximal convoluted tubule. This reabsorption is carried out by two sodium-dependent glucose co-transporter (SGLT) proteins, SGLT1 and SGLT2, which are present on the brush border membrane of epithelial tubular cells. SGLT1, situated in the S3 segment, is a high-affinity low-capacity transporter reabsorbing about 10% of filtered glucose. SGLT2, situated in the S1 segment, is a low-affinity high-capacity transporter reabsorbing the other 90%. In patients with type 2 diabetes mellitus, renal absorptive capacity is maladaptively increased. Once glucose has been reabsorbed and concentrated in the tubular epithelial cells, it diffuses into the interstitium across specific facilitative glucose transporters (GLUTs) located on the basolateral membrane of cells (Mather and Pollock, 2011).
SGLT2 inhibitors have been examined as a novel drug for treating diabetes. SGLT2 inhibitors enhance renal glucose excretion by inhibiting renal glucose reabsorption. Consequently, SGLT2 inhibitors reduce plasma glucose and improve insulin resistance in diabetes. To date, various SGLT2 inhibitors have been developed and evaluated in clinical studies.
Peroxisome proliferator-activated receptor γ (PPARγ) is expressed most abundantly in adipose tissue, but is also found in pancreatic beta cells, vascular endothelium and macrophages. PPARγ is essential for normal adipocyte differentiation and proliferation as well as fatty acid uptake and storage.
Hepatocyte nuclear factors (HNFs) are transcription factors found in the liver, pancreatic islets, the kidneys and genital tissues. In pancreatic beta cells, these transcription factors regulate the expression of the insulin gene and the expression of genes encoding proteins involved in glucose transport, metabolism and mitochondrial metabolism – all of which are linked to protein secretion. Mutation of HNFs is found in patients with mature-onset diabetes of the young (MODY). Patients with mutation of HNF-1β are associated with MODY 5, which is characterised by both diabetes mellitus and renal cysts. However, the role of HNF-1β in glucose transport is not known.
The kidney contributes to glucose homeostasis through gluconeogenesis, glucose filtration, reabsorption and consumption. Under normal circumstances, up to 180 g/day of glucose is filtered by the renal glomerulus and virtually all of it is reabsorbed in the proximal convoluted tubule. This reabsorption is carried out by two sodium-dependent glucose co-transporter (SGLT) proteins, SGLT1 and SGLT2, which are present on the brush border membrane of epithelial tubular cells. SGLT1, situated in the S3 segment, is a high-affinity low-capacity transporter reabsorbing about 10% of filtered glucose. SGLT2, situated in the S1 segment, is a low-affinity high-capacity transporter reabsorbing the other 90%. In patients with type 2 diabetes mellitus, renal absorptive capacity is maladaptively increased. Once glucose has been reabsorbed and concentrated in the tubular epithelial cells, it diffuses into the interstitium across specific facilitative glucose transporters (GLUTs) located on the basolateral membrane of cells (Mather and Pollock, 2011).
SGLT2 inhibitors have been examined as a novel drug for treating diabetes. SGLT2 inhibitors enhance renal glucose excretion by inhibiting renal glucose reabsorption. Consequently, SGLT2 inhibitors reduce plasma glucose and improve insulin resistance in diabetes. To date, various SGLT2 inhibitors have been developed and evaluated in clinical studies.
Peroxisome proliferator-activated receptor γ (PPARγ) is expressed most abundantly in adipose tissue, but is also found in pancreatic beta cells, vascular endothelium and macrophages. PPARγ is essential for normal adipocyte differentiation and proliferation as well as fatty acid uptake and storage.
Hepatocyte nuclear factors (HNFs) are transcription factors found in the liver, pancreatic islets, the kidneys and genital tissues. In pancreatic beta cells, these transcription factors regulate the expression of the insulin gene and the expression of genes encoding proteins involved in glucose transport, metabolism and mitochondrial metabolism – all of which are linked to protein secretion. Mutation of HNFs is found in patients with mature-onset diabetes of the young (MODY). Patients with mutation of HNF-1β are associated with MODY 5, which is characterised by both diabetes mellitus and renal cysts. However, the role of HNF-1β in glucose transport is not known.
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