Alex Edwards ae11g11@soton.ac.uk Adrenal Disease Alex Edwards ae11g11@soton.ac.uk

DAPSICAMP Definition Aetiology Pathophysiology Signs and Symptoms Investigations Complications Alternative Diagnosis Management Prognosis

Anatomy – Arterial Blood Supply Inferior Phrenic Artery Superior Suprarenal Artery Adrenal Gland! Middle Suprarenal Artery Inferior Suprarenal Artery Aorta Renal Artery

Anatomy – Venous Drainage Right Suprarenal Vein Left Suprarenal Vein Left Renal Vein Inferior Vena Cava

Blood Supply - Summary Arterial Supply (same on both sides) Superior Suprarenal Artery (from inferior phrenic) Middle Suprarenal Artery (from aorta) Inferior Suprarenal Artery (from renal artery) Venous Drainage LEFT Suprarenal Vein – into left renal vein RIGHT Suprarenal Vein – into inferior vena cava

Adrenal Structure Cortex – secretes steroid hormones Medulla – secretes cathecholamines

The Medulla Contains Chromaffin cells Secrete Adrenaline (80%) Secrete Noradrenaline (20%) Secretion in response to stimulation by sympathetic nerve fibres from thoracic segments Pre-ganglionic fibres release Ach that binds to Nicotinic type 1 receptors on adrenal medulla NA/A secreted into circulation

The Medulla - effects of cathecholamines Sympathetic Fight or Flight response Cause of excess catecholamines: PHEOCHROMOCYTOMA – tumour of the adrenal medulla Tachycardia, hypertension, tremor, sweating High plasma glucose NA/A cause an increase in lipolysis, gluconeogenesis and glycogenolysis

The Cortex – GFR! Zona Glomerulosa Mineralocorticoids ALDOSTERONE Zona Fasciculata Glucocorticoids CORTISOL Zona Reticularis Androgens TESTOSTERONE

The Key Step Progesterone Mineralocorticoids (ALDOSTERONE) Cholesterol Progesterone Mineralocorticoids (ALDOSTERONE) Zona Glomerulosa 17α hydroxylase Glucocorticoids (CORTISOL) Zona Fasciculata

Aldosterone - released by ZG in response to Angiotensin II Angiotensinogen Blood pressure Renal blood flow Catecholamines Renin from Kidney JGA Angiotensin I ACE from surface of pulmonary and renal endothelium Angiotensin II ALDOSTERONE Vasoconstriction

Aldosterone - effects Increases renal Na+ retention in the late DCT Increases renal water retention in the early collecting ducts Increases blood volume and blood pressure

Hyperaldosteronism - aetiology Conn’s Syndrome (>80%) Adrenal adenoma that secretes excess aldosterone Bilateral Adrenal Hyperplasia (15%) Other Familial Adrenal carcinoma (rare) 17α hydroxylase deficiency

Hyperaldosteronism - pathophysiology Aldosterone acts on principle cells in the late DCT/early collecting ducts causing: Expression of Na+ and K+ channels in luminal membrane Activity of Na+/K+ pump on basolateral membrane Therefore signs and symptoms include: Hypernatremia Hypokalemia Hypertension INTERSTITIUM ALDOSTERONE

Hyperaldosteronism - investigations Blood tests U&Es Spot renin and aldosterone levels ECG – arrhythmias from electrolyte imbalance CT/MRI Special tests Lying and standing aldosterone/renin levels Salt loading and aldosterone/renin levels

Cortisol - released by ZF in response to ACTH HPA axis: Hypothalamus Corticotropin Releasing Factor (CRF) Anterior Pituitary Gland -Corticotrophs Adenocorticotropic Hormone (ACTH) Adrenal Cortex (Zona Fasciculata) CORTISOL

Cortisol - effects Cortisol is a catabolic stress hormone Anti-insulin – increases plasma glucose Increases muscle protein degradation Increases lipolysis and fat deposition Anti-inflammatory Immunosuppressant

Hypercorticism (Cushing’s Syndrome) - aetiology ACTH dependent (80-85%) Secondary pituitary adenoma (80%) – Cushing’s Disease Secondary ectopic tumour Small cell lung cancer Carcinoid tumour of the lung Most endocrine tumours ACTH independent Primary adrenal adenoma (60%) Primary adrenal carcinoma (40%) Iatrogenic Corticosteroids

Hypercorticism (Cushing’s Syndrome) - Signs and Symptoms Anti-insulin and increased plasma glucose - HYPERGYLCAEMIA Muscle protein degradation – MUSCLE WASTING Lipolysis and fat deposition – BUFFALO HUMP and CENTRAL OBESITY Anti-inflammatory and Immunosuppressant effects – EASY BRUISING

Hypercorticism (Cushing’s Syndrome) - investigations U&Es 24 hour urinary free cortisol (3 collections) Dexamethasone suppression test Dexamethasone supressed corticotropin releasing hormone (CRH) test

Adrenal Insufficiency ADDISON’S DISEASE Adrenal cortex destruction Rare 90% autoimmune Aldosterone deficiency Hypotension (postural) Hyponatremia and hyperkalaemia Cortisol deficiency Hypoglycaemia Skin pigmentation Caused by increased ACTH from negative feedback ACTH precursor causes pigmentation

Adrenal insufficiency - investigations U&Es Blood cortisol levels ACTH stimulation (Synacthen) test Fails to produce cortisol in adrenal failure Managed by synthetic hormonal replacement

Summary

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