Endocrinology bits

Question 1

What are the main regulators of calcium homoestasis in the body?

Answer 1

PTH
calcitriol (active form of vitamin D = 1, 25 OH-vitamin D)
(calcitonin plays a part but it is not a major regulator in calcium metabolism)

Question 2

What are the actions of PTH?

Answer 2

• increases plasma calcium, decreases plasma phosphate
• increases renal tubular reabsorption of calcium
• increases osteoclastic activity (works indirectly)
• increases renal conversion of 25-hydroxycholecalciferol to 1,25-dihydroxycholecalciferol
• decreases renal phosphate reabsorption

Question 3

What are the actions of 1, 25 dihydroxycholecalciferol (calcitriol)?

Answer 3

• increases plasma calcium and plasma phosphate
• increases renal tubular reabsorption and gut absorption of calcium
• increases osteoclastic activity
• increases renal phosphate reabsorption

Question 4

Which nerve is most likely to be damaged by a total thyroidectomy?

Answer 4

right recurrent laryngeal nerve

Question 5

What step is essential fo the synthesis of all steroid hormones?

Answer 5

conversion of cholesterol to pregnenolone

Question 6

Why is pregnenolone?

Answer 6

Precursor to all steroid hormones
Its formation (in mitochondria) represents the rate-limiting step of steroid synthesis

Question 7

Which schizophrenia treatment can cause agranulocytosis?

Answer 7

Clozapine

important cause of drug-induced agranulocytosis

Question 8

What is endothelin?

Answer 8

potent, long acting vasoconstrictor and bronchoconstrictor

secreted at vascular endothelium and then converted to ET-1 by endothelin converting enzyme

Question 9

How does endothelin cause calcium release/

Answer 9

Activated/cleaved endothelin binds to GPCR (Gaq/11) linked to PLC to stimulate Ca2+ release

Question 10

What are the actions of endothelin?

Answer 10

promotes release of:

• angiogensin II
• ADH
• hypoxia
• mechanical shearing forces

inhibits:
- NO release
- prostacyclin release

Question 11

In which conditions are endothelin levels likely to be elevated?

Answer 11

MI
heart failure
acute renal failure 
asthma
primary pulmonary hypertension

Question 12

In which diseases is endothelin proposed to be involved in the pathogenesis?

Answer 12

primary pulmonary hypertension
cardiac failure
hepatorenal syndrome
Raynaud’s syndrome

Question 13

What investigation is used to distinguish pituitary-dependent from pituitary independent causes of Cushing’s syndrome?

Answer 13

high dose dexamethasone suppression test (Synacthen)

Question 14

Why can’t serum ACTH be used to identify whether the pituitary is dysfunctional or not in Cushing’s syndrome?

Answer 14

there is a ~10% overlap in serum ACTH levels for patients who have pituitary dependent or independent Cushing’s syndrome
Therefore, it cannot be used to distinguish the causal organ

Question 15

Why does Cushing’s disease cause increased BP?

Answer 15

upregulation of alpha-adrenoreceptors on vascular smooth muscle

smooth muscle is therefore more sensitive to catecholamines

resulting in hypertension

Also high ACTH causes increased aldosterone and therefore will activate RAAS

Question 16

What are the ACTH-dependent causes of Cushing’s syndrome?

Answer 16

• Cushing’s disease (80%) pituitary tumour secreting too much ACTH -> adrenal hyperplasia
• ectopic ACTH production (5-10%): e.g. small cell lung cancer

Question 17

What are the ACTH independent causes of Cushing’s syndrome?

Answer 17

• iatrogenic: steroids
• adrenal adenoma
• adrenal carcinoma
• Carney complex:
• micronodular adrenal dysplasia

Question 18

What is Pseudo-Cushing’s syndrome?

Answer 18

• mimics Cushing’s
• often due to EtOH excess or severe depression
• causes false positive in DMSO suppression test or 24hr urinary free cortisol

Question 19

How can Pseudo-Cushing’s syndrome be distinguished from true Cushing’s disease?

Answer 19

insulin stress test

Question 20

What is the enzymatic deficiency that causes congenital adrenal hyperplasia?

Answer 20

21-hydroxylase

Question 21

What are the consequences of a deficiency of 21-hydroxylase?

Answer 21

• low cortisol production
• compensatory adrenal hyperplasia

Causes:

• increased androgen production
• ambiguous genitalia

Question 22

What enzymes may be implicated in congenital adrenal hyperplasia?

Answer 22

• 21-hydroxylase
• 17-hydroxylase
• 11-beta hydroxylase

Question 23

What are the main clinical features of 21 hydroxylase deficiency?

Answer 23

• virilisation of female genitalia
• precocious puberty in males
• salt-losing crisis at 1-3 wks age (occurs in 60-70% pts)

Question 24

What are the main clinical features of 17 hydroxylase deficiency?

Answer 24

• non-virilising in females
• inter-sex in boys
• hypertension

Question 25

What is virilisation?

Answer 25

development of male pattern body features
due to excess androgen production
e.g. muscle bulk, genitalie etc

Question 26

What are the clinical features of 11-beta hydroxylase deficiency?

Answer 26

• virilisation of female genitalia
• precocious puberty in males
• hypertension
• hypokalaemia

Question 27

What is the function of somotostatin?

Answer 27

• inhibits growth and hormone secretion
• inhibits INS and GCG secretion
• decreases gastric acid, pepsin, gastrin and pancreatic enzyme acid secretion
• inhibits gastric trophic effects
• stimulates production of gastric mucosa

Question 28

Where is somatostatin found?

Answer 28

SST = growth hormone inhibiting hormone (GHIH)

found in the DELTA cells of:

• pancreas
• pylorus
• duodenum

Question 29

What are the main causes of metabolic alkalosis?

Answer 29

• vomiting/aspiration
• diuretics
• hypokalaemia
• primary hyperaldosteronism
• Cushing’s syndrome