Adrenal Disorders Flashcards
Effects of angiotensin II on the adrenals
Activation of the following enzymes Side Chain Cleavage 3 Hydroxysteroid dehydrogenase 21 hydroxylase 11 hydroxylase 18 hydroxylase
Effects of ACTH on the adrenals
Activation of the following enzymes Side Chain Cleavage 3 Hydroxysteroid dehydrogenase 21 hydroxylase 11 hydroxylase 17 hydroxylase
Cholesterol to aldosterone pathway
progesterone 21 11-deoxy corticosterone 11 corticosterone 18 aldosterone
Cholesterol to cortisol pathway
progesterone 17 17-OH prog 21 11-deoxy deoxycortisol 11 cortisol
Addison’s disease
Primary adrenal failure
Autoimmune disease where the immune system decides to destroy the adrenal cortex (UK)
Tuberculosis of the adrenal glands (commonest cause worldwide)
Pituitary starts secreting lots of ACTH and hence MSH
Addison’s disease presentation
Increased pigmentation
Autoimmune vitiligo may coexist
No cortisol or aldosterone, so low blood pressure
Weight loss
Good tan?
Addison’s disease
POMC is a large precursor protein that is cleaved to form a number of smaller peptides, including ACTH, MSH and endorphins
Thus people who have pathologically high levels of ACTH may become tanned
Causes of adrenocortical failure
Adrenal glands destroyed
Enzymes in the steroid synthetic pathway not working
Tuberculous Addison’s disease (commonest worldwide)
Autoimmune Addison’s disease (commonest in UK)
Congenital adrenal hyperplasia
Consequences of adrenocortical failure
Fall in blood pressure
Loss of salt in the urine
Increased plasma potassium
Fall in glucose due to glucocorticoid deficiency
High ACTH resulting in increased pigmentation
Eventual death due to severe hypotension
Tests for Addison’s
9am cortisol = low
ACTH = high
Short synACTHen test
Give 250 ug synacthen IM
Measure cortisol response - no increase suggest Addison’s
Treatment for Addison’s
Aldosterone half life too short for once a day administration
Thus fludrocortisone used instead - does not exist naturally, so take longer to biodegrade
Cortisol is diurnal
Oral hydrocortisol has too short a half life - late peaks are harmful due to hypertension
Prednisolone - longer half life
Congenital Adrenal Hyperplasia
Commonest is caused by 21-hydroxylase deficiency
Can be complete or partial
Complete 21-hydroxylase deficiency
Aldosterone and cortisol completely absent
Survive for less than 24 hours
Sex steroids and testosterone especially in excess
As a neonate with a salt losing Addisonian crisis
Before birth, (while in utero), foetus gets steroids across placenta
Girls might have ambiguous genitalia (virilised by adrenal testo)
Hyperplasia of adrenal glands
Hypotension and high K
Partial 21-hydroxylase deficiency
Aldosterone and cortisol deficient
Sex steroids and especially testosterone in excess
Present any age they survive
Main problem in later life is hirsutism and virilisation in girls and early puberty in boys due to adrenal testosterone
Hyperplasia of adrenal glands
Hypotension and high K
