adrenals

Question 1

what is the precursor for all steroid hormones, and number of carbons

Answer 1

cholesterol (27 C)

Question 2

what are the 3 classes of steroid hormone synthesised from cholesterol

Answer 2

mineralocorticoid, glucocorticoid, sex hormones/precursors

Question 3

main mineralocorticoid and zone produced in

Answer 3

aldosterone, zona glomerulosa in cortex

Question 4

main glucocorticoid and zone produced in

Answer 4

cortisol, zona fasciculata in cortex

Question 5

2 main sex streroids (androgens) and zone produced in; where are most produced

Answer 5

testosterone and oestrodiol (very structurally similar; testosterone to oestrodiol is catalysed by aromatase enzyme), zona reticularis in cortex; most produced in gonads

Question 6

what is the main family of enzymes involved in converting cholesterol to these steroid hormones

Answer 6

cytochrome P450; most are hydroxylase enzymes

Question 7

effect of circadian stimuli or stress on cortisol production (hypothalamo-pituitary-adrenal) pathway

Answer 7

increased stress on cerebral cortex -> hypothalamus -> neurosecretions of corticotropin-releasing hormone (CRH) -> adenohypophysis -> ACTH -> adrenals -> cholesterol to cortisol -> regulatory inhibition on CRH and ACTH

Question 8

effect of stress on aldosterone and sex hormones

Answer 8

as more ACTH released, production of aldosterone and sex hormones in adrenals also increases

Question 9

pathway of cholesterol to aldosterone [with relevant critical enzymes in cytochrome P450 complex]

Answer 9

cholesterol -> progesterone -> 11 deoxycrticosterone [21] -> corticosterone [11] -> aldosterone [18]

Question 10

pathway of cholesterol to cortisol [with relevant enzymes critical in cytochrome P450 complex]

Answer 10

cholesterol -> progesterone -> 17 OH progesterone [17] -> 11 deoxycortisol [21] -> cortisol [11]

Question 11

pathway of cholesterol to sex steroids [with relevant critical enzyme in cytochrome P450 complex]

Answer 11

cholesterol -> progesterone -> 17 OH progesterone [17] -> sex steroids

Question 12

3 causes of adrenocortical failure

Answer 12

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)

Question 13

3 consequences of adrenocortical failure: mineralocorticoid deficiency

Answer 13

fall in blood pressure (apparent as postural hypotension), loss of salt in urine (hyponatraemic), increased plasma potassium (hyperkalaemic); eventual death due to severe hypotension

Question 14

consequence of adrenocortical failure: glucocorticoid deficiency

Answer 14

fall in glucose as used to mobilise glucose

Question 15

consequence of adrenocortical failure: high ACTH (no negative feedback)

Answer 15

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)

Question 16

effect on medulla, aldosteorne, cortisol and sex steroids if entire adrenal cortex atrophied or destroyed

Answer 16

medulla has no change as unaffected; aldosteorne, cortisol and sex steroids absent or very low

Question 17

what else is POMC broken down to

Answer 17

endorphins, enkephalins, other peptides

Question 18

commonest cause of congenital adrenal hyperplasia (large adrenals as high ACTH causes large growth)

Answer 18

21-hydroxylase deficiency (complete or partial) - most important as most common

Question 19

hormones affected by 21-hydroxylase deficiency in congenital adrenal hyperplasia

Answer 19

aldosterone and cortisol

Question 20

hormones totally absent if complete 21-hydroxlase deficiency in congenital adrenal hyperplasia, impact on survival; hormones in excess

Answer 20

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

Question 21

age of presentation of complete 21-hydroxlase deficiency in congenital adrenal hyperplasia

Answer 21

as a neonate with salt losing Addisonian crisis

Question 22

in complete 21-hydroxlase deficiency in congenital adrenal hyperplasia, how does the foetus get steroids before birth (while in utero)

Answer 22

across placenta

Question 23

effect of complete 21-hydroxlase deficiency in congenital adrenal hyperplasia on girls

Answer 23

might have ambiguous genitalia (virilisation by adrenal testosterone)

Question 24

hormones deficient if partial 21-hydroxlase deficiency in congenital adrenal hyperplasia; hormones in excess; age of presentation

Answer 24

aldosterone and cortisol; sex steroids and testosteorne will be in excess; age of presentation will be any as they survive

Question 25

main problem in later life of partial 21 hydroxylase deficiency (congenital adrenal hyperplasia) in girls

Answer 25

hirsutism (male-pattern hair growth) and virilisation (clitoral enlargement appearing as male genitalia)

Question 26

main problem in later life of partial 21 hydroxylase deficiency in congenital adrenal hyperplasia in boys

Answer 26

precocious puberty (adrenal testosterone)

Question 27

hormones deficient if 11-hydroxlase deficiency in congenital adrenal hyperplasia, and hormones in excess

Answer 27

aldosterone and cortisol deficient; sex steroids, testosterone and 11-deoxycorticosterone in excess (cannot be converted to corticosterone)

Question 28

what does 11 deoxycorticosterone in aldosterone synthesis pathway behave like, and effect if in excess

Answer 28

behaves like aldosterone, so in excess can cause hypertension and hypokalaemia

Question 29

effect of high testosterone in 11-hydroxlase deficiency in congenital adrenal hyperplasia

Answer 29

virilisation

Question 30

hormones deficient if 17-hydroxlase deficiency in congenital adrenal hyperplasia, and hormones in excess

Answer 30

cortisol and sex steroids deficient, with 11-deoxycorticosterone and aldosterone (mineralocorticoids) in excess

Question 31

problems of 17-hydroxlase deficiency in congenital adrenal hyperplasia

Answer 31

hypertension, hypokalaemia, sex steroid deficiency, glucocorticoid deficiency (low glucose)