Endocrinology bits Flashcards
What are the main regulators of calcium homoestasis in the body?
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)
What are the actions of PTH?
- 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
What are the actions of 1, 25 dihydroxycholecalciferol (calcitriol)?
- increases plasma calcium and plasma phosphate
- increases renal tubular reabsorption and gut absorption of calcium
- increases osteoclastic activity
- increases renal phosphate reabsorption
Which nerve is most likely to be damaged by a total thyroidectomy?
right recurrent laryngeal nerve
What step is essential fo the synthesis of all steroid hormones?
conversion of cholesterol to pregnenolone
Why is pregnenolone?
Precursor to all steroid hormones Its formation (in mitochondria) represents the rate-limiting step of steroid synthesis
Which schizophrenia treatment can cause agranulocytosis?
Clozapine
important cause of drug-induced agranulocytosis
What is endothelin?
potent, long acting vasoconstrictor and bronchoconstrictor
secreted at vascular endothelium and then converted to ET-1 by endothelin converting enzyme
How does endothelin cause calcium release/
Activated/cleaved endothelin binds to GPCR (Gaq/11) linked to PLC to stimulate Ca2+ release
What are the actions of endothelin?
promotes release of:
- angiogensin II
- ADH
- hypoxia
- mechanical shearing forces
inhibits:
- NO release
- prostacyclin release
In which conditions are endothelin levels likely to be elevated?
MI heart failure acute renal failure asthma primary pulmonary hypertension
In which diseases is endothelin proposed to be involved in the pathogenesis?
primary pulmonary hypertension
cardiac failure
hepatorenal syndrome
Raynaud’s syndrome
What investigation is used to distinguish pituitary-dependent from pituitary independent causes of Cushing’s syndrome?
high dose dexamethasone suppression test (Synacthen)
Why can’t serum ACTH be used to identify whether the pituitary is dysfunctional or not in Cushing’s syndrome?
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
Why does Cushing’s disease cause increased BP?
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
What are the ACTH-dependent causes of Cushing’s syndrome?
- Cushing’s disease (80%) pituitary tumour secreting too much ACTH -> adrenal hyperplasia
- ectopic ACTH production (5-10%): e.g. small cell lung cancer
What are the ACTH independent causes of Cushing’s syndrome?
- iatrogenic: steroids
- adrenal adenoma
- adrenal carcinoma
- Carney complex:
- micronodular adrenal dysplasia
What is Pseudo-Cushing’s syndrome?
- mimics Cushing’s
- often due to EtOH excess or severe depression
- causes false positive in DMSO suppression test or 24hr urinary free cortisol
How can Pseudo-Cushing’s syndrome be distinguished from true Cushing’s disease?
insulin stress test
What is the enzymatic deficiency that causes congenital adrenal hyperplasia?
21-hydroxylase
What are the consequences of a deficiency of 21-hydroxylase?
- low cortisol production
- compensatory adrenal hyperplasia
Causes:
- increased androgen production
- ambiguous genitalia
What enzymes may be implicated in congenital adrenal hyperplasia?
- 21-hydroxylase
- 17-hydroxylase
- 11-beta hydroxylase
What are the main clinical features of 21 hydroxylase deficiency?
- virilisation of female genitalia
- precocious puberty in males
- salt-losing crisis at 1-3 wks age (occurs in 60-70% pts)
What are the main clinical features of 17 hydroxylase deficiency?
- non-virilising in females
- inter-sex in boys
- hypertension
