adrenals Flashcards
congenital adrenal hyperplasia: explain the hormonal consequences of specific adrenal enzyme deficiencies, explain the clinical features and investigation of congenital adrenal hyperplasia with reference to specific enzyme deficiencies
what is the precursor for all steroid hormones, and number of carbons
cholesterol (27 C)
what are the 3 classes of steroid hormone synthesised from cholesterol
mineralocorticoid, glucocorticoid, sex hormones/precursors
main mineralocorticoid and zone produced in
aldosterone, zona glomerulosa in cortex
main glucocorticoid and zone produced in
cortisol, zona fasciculata in cortex
2 main sex streroids (androgens) and zone produced in; where are most produced
testosterone and oestrodiol (very structurally similar; testosterone to oestrodiol is catalysed by aromatase enzyme), zona reticularis in cortex; most produced in gonads
what is the main family of enzymes involved in converting cholesterol to these steroid hormones
cytochrome P450; most are hydroxylase enzymes
effect of circadian stimuli or stress on cortisol production (hypothalamo-pituitary-adrenal) pathway
increased stress on cerebral cortex -> hypothalamus -> neurosecretions of corticotropin-releasing hormone (CRH) -> adenohypophysis -> ACTH -> adrenals -> cholesterol to cortisol -> regulatory inhibition on CRH and ACTH
effect of stress on aldosterone and sex hormones
as more ACTH released, production of aldosterone and sex hormones in adrenals also increases
pathway of cholesterol to aldosterone [with relevant critical enzymes in cytochrome P450 complex]
cholesterol -> progesterone -> 11 deoxycrticosterone [21] -> corticosterone [11] -> aldosterone [18]
pathway of cholesterol to cortisol [with relevant enzymes critical in cytochrome P450 complex]
cholesterol -> progesterone -> 17 OH progesterone [17] -> 11 deoxycortisol [21] -> cortisol [11]
pathway of cholesterol to sex steroids [with relevant critical enzyme in cytochrome P450 complex]
cholesterol -> progesterone -> 17 OH progesterone [17] -> sex steroids
3 causes of adrenocortical failure
tuberculous Addison’s disease (adrenal glands destroyed e.g. by granulomas/other metastases), autoimmune Addison’s disease (adrenal glands destroyed), congenital adrenal hyperplasia (enzymes in steroid synthetic pathway not working)
3 consequences of adrenocortical failure: mineralocorticoid deficiency
fall in blood pressure (apparent as postural hypotension), loss of salt in urine (hyponatraemic), increased plasma potassium (hyperkalaemic); eventual death due to severe hypotension
consequence of adrenocortical failure: glucocorticoid deficiency
fall in glucose as used to mobilise glucose
consequence of adrenocortical failure: high ACTH (no negative feedback)
increased pigmentation (incl. in scars and buccal mucosa) as increased POMC (ACTH precursor) is broken down to ACTH and MSH (melanocyte stimulating hormone), which increases melanin synthesis; vitiligo (autoimmune predisposition causing melanocyte destruction)
effect on medulla, aldosteorne, cortisol and sex steroids if entire adrenal cortex atrophied or destroyed
medulla has no change as unaffected; aldosteorne, cortisol and sex steroids absent or very low
what else is POMC broken down to
endorphins, enkephalins, other peptides
commonest cause of congenital adrenal hyperplasia (large adrenals as high ACTH causes large growth)
21-hydroxylase deficiency (complete or partial) - most important as most common
hormones affected by 21-hydroxylase deficiency in congenital adrenal hyperplasia
aldosterone and cortisol
hormones totally absent if complete 21-hydroxlase deficiency in congenital adrenal hyperplasia, impact on survival; hormones in excess
aldosterone and cortisol, so as severe hypotension and low plasma glucose, survival time of less than a few weeks resulting in death; sex steroids (incl. testosterone) will be in excess as no feedback to pituitary or hypothalamus so excessive stimulation and production
age of presentation of complete 21-hydroxlase deficiency in congenital adrenal hyperplasia
as a neonate with salt losing Addisonian crisis
in complete 21-hydroxlase deficiency in congenital adrenal hyperplasia, how does the foetus get steroids before birth (while in utero)
across placenta
effect of complete 21-hydroxlase deficiency in congenital adrenal hyperplasia on girls
might have ambiguous genitalia (virilisation by adrenal testosterone)
hormones deficient if partial 21-hydroxlase deficiency in congenital adrenal hyperplasia; hormones in excess; age of presentation
aldosterone and cortisol; sex steroids and testosteorne will be in excess; age of presentation will be any as they survive
main problem in later life of partial 21 hydroxylase deficiency (congenital adrenal hyperplasia) in girls
hirsutism (male-pattern hair growth) and virilisation (clitoral enlargement appearing as male genitalia)
main problem in later life of partial 21 hydroxylase deficiency in congenital adrenal hyperplasia in boys
precocious puberty (adrenal testosterone)
hormones deficient if 11-hydroxlase deficiency in congenital adrenal hyperplasia, and hormones in excess
aldosterone and cortisol deficient; sex steroids, testosterone and 11-deoxycorticosterone in excess (cannot be converted to corticosterone)
what does 11 deoxycorticosterone in aldosterone synthesis pathway behave like, and effect if in excess
behaves like aldosterone, so in excess can cause hypertension and hypokalaemia
effect of high testosterone in 11-hydroxlase deficiency in congenital adrenal hyperplasia
virilisation
hormones deficient if 17-hydroxlase deficiency in congenital adrenal hyperplasia, and hormones in excess
cortisol and sex steroids deficient, with 11-deoxycorticosterone and aldosterone (mineralocorticoids) in excess
problems of 17-hydroxlase deficiency in congenital adrenal hyperplasia
hypertension, hypokalaemia, sex steroid deficiency, glucocorticoid deficiency (low glucose)
