Layers of the adrenal gland

Glomerulosa: Salt: aldosterone

Fasiculata: Sugar: glucocorticoids

Reticularis: Sex hormones - dehydroepiandrosterone / oestradiol

Medulla - catecholamines

Mechanism of action of Steroid hormones

1. Intracellular receptor binding
2. Results in gene stimulation

Hormone release (RAS)

1. Glucocorticoids
   • ACTH
2. Aldosterone
   • Renin (stimulated by low BP, sympathetics); Low Na; Hyperkalaemia
   • Renin - activates Angiotensinogen
   • Angiotensinogen activates angiotensin I
   • Angiotensin I to Angiotensi II by ACE (in the lungs)
   • Stimulates aldosterone release

Cushing's syndrome / Disease

• Hypercortisolaemia (Cf disease - hypercortisolaemia secondary to pituitary adenoma secreting ACTH)

Causes:

1. ACTH - pituitary tumours, ectopic ACTH from oat cell, carcinoid, pancreas
2. Steroid secreting adenoma
3. iatrogenic steroids

• Cushingoid features (1) Head and neck - moon face from fat and oedema, acne from testosterone effects, male pattern baldness, hisutism in ladies (2) Chest and trunk - buffalo hump from fat distribution, central obesity, striae, ecchymoses from capillary fragility (4) Limbs - muscle wasting from cortisol effect
• Endocrine effects

1. Fat / salt handling
2. Diabetes
3. Secondary osteoporosis
4. Amenorrhoea from suppression

Hyperaldosteronism

1. Primary: Conn's syndrome - autonomic secretion from adenoma
   • Salt/water retention leads to hypertension
   • Hypernatraemia / hypokalaemia / metabolic alkalosis (in association with hypokalaemia)
   • Rx: Spironalactone (Aldosterone antagonist)
2. Secondary: RAS activation following dehydration

Adrenocortical insufficiency / Addison's disease

• Bilateral destruction of the layers of the adrenal gland

1. Infection - TB, fungi, Friederichsen-Waterhouse (meningococcal emboli)
2. Deposition - haemochromatosis, amyloid, malignancy
3. Auto-immune
4. Drugs - adrenolytic drugs (ketoconazole), steroid withdrawal
5. Iatrogenic- Adrenalectomy

• Clinical features

1. General: Weight loss, malaise
2. Skin: - Hyperpigmentation due to POMC (pro-opio melano cortin) from anterior pituitary with increase in MSH and ACTH
3. Biochemical: Hyponatraemia, hyperkalaemia, increased ACTH, decreased aldosterone and cortisol

Hormones produced

1. Catecholamines: produced from tyrosine (tyrosine hydroxylase)> DOPA (Dopa decarboxylase)> Norad (Dopamine B-hydroxylase)> Dopamine (Phenylethanolamine-N-methyl-transferase)> Adrenaline
2. From chromaffin cells: Dopamine, somatostatin, substance P, enkephalins

Innervation: Ach from pre-ganglionic sympathetic fibres

Effects of hormones:

1. Cardiovascular effects
   • Hypertension, tachycardia
2. Respiratory
3. GI:
4. Metabolic
   • Carbohydrate - cause hyperglycaemia (1) stimulates gluconeogenesis (2) glycolysis (3) inhibit release or insulin - mediated via alpha-receptors
   • Lipids - stimulates lipolysis