1001 - The Adrenal Gland

Question 1

What are the embryonic origins of the adrenal gland?

Answer 1

90% mesoderm - becomes cortex

10% ectoderm (neural crest) - becomes medulla and is a part of SY nervous system.

Question 2

Describe the location of the adrenal glands

Answer 2

Retro-peritoneal, immediately inferior to the diaphragm and at the superior pole of the kidney. Approx 3-5cm in lengh and weighing 3-5 grams. Triangular (R) and semilunar (L) in shape, consisting of an outer capsule, cortex, and medulla.

Question 3

What are the three layers of the adrenal cortex? What is their function?

Answer 3

Superficial to the medulla
Zona Glomerulosa - synthesise and release aldosterone and other mineralocorticoids (MCC).
Zona Fasiculata - synthesise and release cortisol and other glucocorticoids (GCC)
Zona Reticularis - synthesise and release androgens - DHEA and androstenedione.

Remember - GFR

Question 4

What is the function of the adrenal medulla?

Answer 4

Deep to the cortex.
Synthesise (from tyrosine) and release catecholamines (adrenaline, noradrenaline, dopamine) - directly linked to SY nervous system.

Question 5

What are the key points of the pathways of adrenal steroid synthesis?

Answer 5

All derived from cholesterol (giving adrenal cortex yellow colour), converted to pregnenolone.
3 branches, mineralocorticoid (aldosterone), glucocorticoid (cortisol), ‘sex hormones’. Not totally independent - linked up to and including progesterone.
Given the common cholesterol backbone - great deal of potential for any steroid to bind to any steroid receptor if concentration high enough.

Question 6

How is adrenal hormone secretion regulated?

Answer 6

Mineralocorticoid (aldosterone) - predominantly regulated by extracellular K+ and renin, also partial pituitary.
Glucocorticoid (cortisol) - under control of pituitary gland.
Cortisol feeds back on hypothalamus and pituitary to give negative feedback - limit ACTH release.

Question 7

Briefly outline the effects of cortisol (hydrocortisone)

Answer 7

Hits all cells and organs - response depends on individual tissue.
Has metabolic effects and anti-inflammatory/immune effects.

Question 8

What are the metabolic effects of glucocorticoids (cortisol)?

Answer 8

Carbs - stimulate gluconeogenisis, reduce glucose utilisation, leading to ⇡ plasma glucose concentration.
Protein - + liver synthesis, but - in other tissues, which become catabolic. Aa’s are transported to liver where they are gluconeogenic substrates.
Lipids - Fatty acid mobilised from peripheral tissue and deposited centrally.

Question 9

What are the anti-inflammatory and immune effects of glucocorticoids (cortisol)?

Answer 9

Anti-inflammatory - Reduce production of cytokines with reduced chemotaxis locally.

Immune - reduced clonal amplification of lymphocytes (also from change in cytokine synthesis)
Ultimate consequence - risk of infection if excessive.

Question 10

What is the regulation of mineralocorticoid (aldosterone) release?

Answer 10

Primarily by RAA system (hypovolaemia/drop in BP). Increased K+ also a major stimulus, but ACTH is only a minor stimulus.

Question 11

What is the effect and fate of adrenal mineralocorticoids (aldosterone)?

Answer 11

Effect - Limit sodium excretion through DT of kidney.

Fate - Aldosterone metabolised in both liver and kidney - very little excreted unchanged.

Question 12

What is the mechanism of action for adrenal medullary hormones (specifically adrenaline/noradrenaline)?

Answer 12

Very short half-life (1-2 minutes)

Act via cell surface receptors - adrenaline predominantly beta 1 and 2, noradrenaline alpha and beta 1.

Question 13

What is the effect of alpha 1, and beta 1 and 2 receptors?

Answer 13

alpha 1 - vasoconstrict and increase BP (noradrenaline)
Beta 1 - positive inotrope (cardiac) - (noradrenaline and adrenaline)
Beta 2 - vasodilation (adrenaline)

Question 14

What are the major pathologies of the adrenal gland?

Answer 14

Glucocorticoid (cortisol) excess - Cushing’s syndrome
Glucocorticoid deficiency - Addison’s disease
Mineralocorticoid (aldosterone) excess - Conn’s syndrome
Congenital adrenal hyperplasia
Adrenal medulla catecholamine hypersecretion

Question 15

What are the causes of glucocorticoid excess (Cushing’s Syndrome)?

Answer 15

1. Iatrogenic (brought on by steroid treatment) - most common
2. Increased pituitary production of ACTH (Cushing’s Disease)
3. Primary adrenal gland pathology
4. Ectopic production of ACTH due to malignancy

Question 16

How can glucocoticoid deficiency (Addison’s Disease) present?

Answer 16

1. Iatrogenic (following steroid therapy)
2. Autoimmune (Australia/NZ most common)
3. Tuberculosis destruction of adrenals (Asia)
4. Non-specific findings (tiredness/fatigue) or emergency (hypotension, dehydreation, hyperkalemia, metabolic acidosis)
5. May have vitiligo associated with increased ACTH secretion.