Describe the function of the adrenal cortex and the adrenal medulla?
Cortex: steroid hormone synthesis and function (glucocorticoids and mineralocorticoids)
Medulla: catecholamine synthesis and function (adrenaline and noradrenaline)
Describe the disease states associated with the adrenal cortex and the adrenal medulla?
Cortex: Cushing's and Addison's
Describe the structure of the adrenal cortex?
What is secreted form each layer?
Zona glomerulosa: mineralocorticoids (aldosterone)
Zona fasiculata: glucocorticoids (cortisol)
Zona reticularis: sex steroid, androgens
Describe the difference between cortisol, hyrdrocortisone and cortisone?
Cortisol = hydrocortisone
Cortisone is an inactive metabolite of cortisol (can be metabolised back to cortisol in liver), very weak glucocorticoid
What are steroid hormones synthesised from?
Describe the three basic pathways from cholesterol to steroid hormone synthesis?
Mineralocorticoid pathway (aldosterone)
Glucocorticoid pathway (cortisol)
Sex hormone pathway (oestrogen and testosterone)
Describe the actions of glucocorticoids?
Stimulation of gluconeogenesis in liver
Mobilisation of amino acids in muscle
Stimulation of lipolysis in adipose tissues
(maintain homeostasis in face of physiological challenge)
Describe the effects of excess cortisol?
Wasting of muscle, skin and bone
Inhibiiton of linear growth
Describe why hyperglycaemia and hypertension occur in the presence of excess cortisol?
Hyperglycaemia: muscle amino acid > glucose
Hypertension: salt retention
Describe the two types of hypercortisolism and their causes?
ACTH-dependent: Cushing's disease
Due to pituitary adenoma or ectopic ACTH syndrome
ACTH-indepedent: Cushing's syndrome
Due to adrenal adenoma or carcinoma, ACTH-independent nodular hyperplasia or administration of glucocorticoids
Describe the features of Cushing's disease?
Muscle wasting, thin skin
Metabolic derangements (diabetes)
Describe the rationale behind the dexamethasone suppression test?
What is it used to test for?
Used to test for suspected Cushing's
Dexamethasone feeds back to piuitary and switches off cortisol production
Describe how suspected Cushing's disease can be investigated?
24 hour urine free cortisol
Check diurnal variation: serum cortisol and plasma at 8am and midnight
Dexamethasone suppression test (check negative feedback is working)
Imaging as indicated
Describe the effects of cortisol deficiency?
GI symptoms: anorexia, nausea, vomiting, diarrheoa, weight loss
Darkening of skin
Increased susceptibility to infection
Why does darkening of the skin occur with cortisol deficiency?
ACTH stimulated > MSH stimulated > melanocytes produce melanin
Describe the causes of adrenocortical insufficiency?
Enzyme defect in cortisol biosynthesis
Autoimmune adrenal destruction (most common)
Infectious disease > adrenal destruction
What is the most common cause of adrenocortical insufficiency?
Autoimmune destruction : Addison's disease
What is Addison's disease?
Adrenal insufficiency due to destruction of adrenals, usually autoimmune destruction
Describe the electrolyte imbalance that occurs in Addison's disease?
Salt-wasting state > low Na, high K
Describe the treatment for Addison's disease?
Cortisol and fludrocortisone (aldosterone analogue)
Describe the common sites of Addisonian pigmentation?
Gums and oral mucosa
Describe the effects of excess androgens?
Premature pubic hair
Enlargement of penis or clitoris
Linear growth spurt
Rapid epiphyseal fusion
Muscular body type
Deepening of voice
Describe the cause of congenital adrenal hyperplasia?
21-hydroxylase deficiency in 90% > no cortisol secreted > increased ACTH >adrenal hyperplasia > increased sex hormone production
Describe the presentation of congenital adrenal hyperplasia?
Females: infantile ambiguous genitalia, premature pubic hair and enlarged clitoris or adolescent hirsutism and acne
Males: adrenal crisis in newborn or premature sexual development at 2-3yo
Describe the treatment for congenital adrenal hyperplasia?
Replace cortisol and aldosterone as early as possible
Describe the clinical uses of glucocorticoids?
Replacement therapy if inadequately produced
Anti-inflammatory and immunosuppressive effects
What regulates mineralocorticoid (aldosterone) secretion?
Increased K in ECF
(salt and water deficit)
Describe the actions of mineralocorticoids?
Increased resorption of Na
Increased resorption of water
Increased excretion of K from kidney DT
Describe the effects of aldosterone excess and insufficiency?
Excess: hypertension, weakness
Deficiency: dehydration, salt depletion, postural hypotension, cardiac arrhythmias
Why does weakness occur in aldosterone excess?