Lecture 19

Question 1

What does hyperactivity of the adrenal cortex cause?

Answer 1

Increased secretion of cortisol: Cushing’s Syndrome

Question 2

Why may you get Cushing’s syndrome?

Answer 2

• primary cortisol producing adrenal adenoma
• disorders in secretion of ACTH by a pituitary adenoma: Cushing’s Disease
• ectopic secretion of ACTH from a tumour at a site remote from the pituitary

Question 3

What are the signs and symptoms of excess cortisol?

Answer 3

• increased muscle proteolysis: wasting of proximal muscles= thin arms and leg and weakness
• increased hepatic gluconeogenesis: hyperglycaemia with polyuria and polydipsia
• increased lipogenesis in adipose tissue leading to depositions of fat in abdomen, neck and face: moon shaped face
• purple striae: catabolic effects on protein structures in skin leading to easy bruising due to thinning of skin
• mineralcorticoid effects of excess cortisol may produce hypertension due to sodium and fluid retention
• disturbances to calcium metabolism: osteoporosis
• immunisuppressive, anti-inflammatory, anti-allergic reactions of cortisol leading to bacterial infections and acne

Question 4

What patients experience the symptoms of Cushing’s syndrome?

Answer 4

Patients receiving long term treatment with glucocorticoids for chronic inflammatory conditions
e.g. hydrocortisone, prednisone

Question 5

Difference between Cushing’s disease and syndrome?

Answer 5

Syndrome refers to collection of symptoms due to excessive exposure to cortisol (more common)
Disease refers to a benign ACTH secreting pituitary adenoma

Question 6

What is it called when you have too little cortisol and what causes it?

Answer 6

Addison’s Disease

• diseases of adrenal cortex (autoimmune destruction)
• disorders in pituitary/hypothalamus leading to decreased secretion of ACTH/CRF

Question 7

What does autoimmune destruction of adrenal gland cause?

Answer 7

Loss of cortisol and mineralcorticoids

May present as a clinical emergency: Addisonian Crisis or Addison’s Disease

Question 8

What are the symptoms of Addison’s disease?

Answer 8

• hypoglycaemic episodes
• postural hypotension
• decreased BP due to sodium and fluid depletion
• increased skin pigmentation in exposed areas of body, buccal mucosa, scars, palmar creases due to increase in ACTH as well as other products of POMC which stimulate melanocytes to produce more melanin
• extreme muscular weakness/anorexia
• dehydration
• weight loss

Question 9

How do you treat Addison’s Disease?

Answer 9

Intravenous cortisol

Fluid replacement

Question 10

What clinical tests can be used to diagnose adrenocortical disease?

Answer 10

• measurement of plasma cortisol and ACTH levels, and 24 urinary excretion of cortisol
• dynamic function tests (dexamethasone suppression/ACTH stimulation)

Question 11

How do dynamic function tests work to diagnose adrenocortical disease?

Answer 11

Dexamethasone: synthetic steroid given orally suppresses secretion of ACTH and therefore cortisol

• suppression of cortisol is characteristic of Cushing’s disease because the diseased pituitary retains some sensitivity to synthetic steroids
• suppression does not normally occur in adrenal tumours/ectopics

Syncathen intramuscularly (synthetic analogue of ACTH)
-normally increase plasma cortisol, normal response excludes Addison disease

Question 12

What is congenital adrenal hyperplasia?

Answer 12

Genetic defect in an enzyme required for synthesis of corticosteroid hormones from cholesterol
-lack of cortisol= more ACTH via negative feedback causing hyperplasia of adrenal cortex
= deficiency in enzyme 21-hydroxylase: less glucocorticoid and mineralcorticoid production and more androgen synthesis resulting in genital ambiguity and salt-wasting crises (unable to retain enough salt) due to high rate of sodium in urine because of lack of aldosterone

Question 13

What is Conn’s syndrome?

Answer 13

Primary hyperaldosteronism: hyperactivity of one/both adrenal glands
Unilateral form: adenoma
Bilateral form: rare genetic syndromes

Question 14

What are the symptoms of Conn’s syndrome?

Answer 14

• high BP
• muscular weakness/spasms
• excessive urination
• tingling sensations

Question 15

What effect does excess aldosterone have on the kidney?

Answer 15

Increases sodium reabsorption and potassium secretion via Na/K ATPase, resulting in increased BP and volume
-increase in blood volume and renal perfusion causes a decrease in renin release
In Conn’s disease, decreased renin levels does not lead to a decrease in aldosterone

Question 16

What receptors does cortisol bind to?

Answer 16

Glucocorticoid receptors
Mineralcorticoid and androgen receptors with a low affinity: this becomes significant when high levels of cortisol are present

Question 17

What do androgens stimulate in men and women?

Answer 17

Men: male genital tract, male secondary characteristics (height, body shape, facial and body hair, lower pitch voice), anabolic actions on muscle protein
Women: female genital tract, breasts, female secondary characteristics (broad hips, accumulation of fat in breasts and buttocks, body hair distribution), anabolic, decrease circulating cholesterol levels

Question 18

What does oversecretion of adrenal androgens in females cause?

Answer 18

Excessive body hair growth (hirsutism)
Acne
Menstrual problems 
Virilisation (development of male physical characteristics)
Increased muscle
Deepened voice