Zona Glomerulosa Zona Fasiculata Zona Reticularis

4 Steroid Hormones Glucocorticoids –CHO, lipid & fat metabolism –Increases blood glucose levels & gluconeogenesis –Increases protein breakdown –Inhibits protein synthesis Mineralcorticoids –Elecrolyte & fluid balance –Increases sodium & water retention –Regulated by renin & andiotensin Sex Steroids –Low synthesis in adrenals compared to gonads –Virilising hormones may be secreted

5 Conditions Affecting Adrenal Cortex Adrenocortical Hyperfunction Cushing’s syndrome –Increased glucocorticoid levels Hyperaldosterone –Excessive water retention  Ht Adrenogenital syndromes –Excess androgens (testosterone) in peripheral tissue Dehydroepiandrosterone Androstentendione Adrenocortical Insufficiency Acute Adrenocortical Insufficiency Chronic Adrenocortical Insuffeciency (Addison’s)

6 Acute Adrenocortical Insufficiency Aetiology & pathogenesis Sepsis  Waterhouse-Friderichsen syndrome –Neisseria meningitidis (classic) –Pseudonomas; pneumococci; H. influenzae (others) –Unclear pathogenesis  endotoxin induced vascular injury (massive haemorrhage) with associated DIC Sudden withdrawal of long term corticosteroid treatment –Inability of atrophic adrenals to produce glucocorticoids Stress with underlying chronic adrenal insufficiency –Acute adrenal crises on limited physiological reserves

Massive adrenal haemorrhage, resulting in primary acute adrenal insufficiency Metastatic breast carcinoma affecting the adrenal gland and causing primary chronic adrenal insufficiency

8 Chronic Adrenocortical Insufficiency “Addison’s Disease” Aetiology & pathogenesis Primary  Addison’s disease Secondary causes –Tuberculosis  caseous necrosis of adrenal cortex –Autoimmune adrenalitis Ass with e.g. pernicious anaemia; thyroiditis; IDDM –AIDS –Metastatic disease –Systemic amyloidosis –Fungal infections –Haemochromatosis –Sarcoidosis

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10 Morphology Primary autoimmune adrenitis –Irregularly shrunken glands TB; fungi; sarcoidosis –Granulomas in adrenals Metastatic Ca –Adrenals enlarged –achitecture obscured Secondary hypoadrenalism –Adrenals small & flattened –Atrophy of corticol cells

11 Clinical Features Insidious onset –Progressive weakness & fragiability –Non-specific complaints (anorexia; N/V; WL) Primary adrenal disease –Hyperpigmentation (increased ACTH) Hyperkalaemia & hyponatraemia Hypotension (volume depletion) & dehydration Hypoglycaemia Sexual dysfunction Adrenal crises –Infections; trauma; sugery  intractable vomiting; abdominl pain; hypotension; vascular collaspe  death Diagnosis –Low plasma cortisol

Laboratory findings. 1.A low serum Na level and a high serum P level together with a characteristic clinical picture suggest the possibility of Addison’s disease. 2.Adrenal insufficiency can be specifically diagnosed by: low levels of plasma glucocorticoids and mineralocorticoids, or urinary 17 – hydroxycorticosteroid (17 – OHCS) or 17 – ketogenic steroid (17 – KGS); demonstrating failure to increase plasma cortisol levels, or urinary 17 – OHCS or 17 – KGS excretion, upon administration of ACTH (in patients with primary adrenal insufficiency, those with secondary adrenocortical insufficiency will have a significant increase in plasma cortisol or 24 - h urinary corticosteroid levels.) 3.To distinguish between primary and secondary adrenal insufficiency, me have to find the level of plasma ACTH: primary shows increased, and secondary shows decreased level.

Features of Addison’s d.

14 This is a caseating granuloma of tuberculosis in the adrenal gland. Tuberculosis used to be the most common cause of chronic adrenal insufficiency. Now, idiopathic (presumably autoimmune) Addison's disease is much more often the cause for chronic adrenal insufficiency.

16 The pair of adrenals in the center are normal. Those at the top come from a patient with adrenal atrophy (with either Addison's disease or long-term corticosteroid therapy). The adrenals at the bottom represent bilateral cortical hyperplasia. This could be due to a pituitary adenoma secreting ACTH (Cushing's disease), or Cushing's syndrome from ectopic ACTH production, or idiopathic adrenal hyperplasia.

Case Discussion

A 26-year old man is admitted to the Intensive Care Unit 3 days vomiting – hourly Drowsy BP 60/30 Deeply pigmented Na+125 mmol/l(N ) K+5.4 mmol/l(N )

Questions Diagnosis Pathogenesis What hormone is deficient Diagnostic test Treatment Complications

Addison’s disease Pathogenesis Destruction of adrenal glands  Autoimmune  Tuberculosis  Tumour/infiltration  Infective (meningococcus) Hormone deficiency Cortisol Aldosterone

Diagnostic test Synacthen test Treatment Cortisol replacement  Hydrocortisone/Cortisone Aldosterone replacement  Fludrocortisone Complications Adrenal crisis – intercurrent illness

Synacthen test Pituitary Cortisol Adrenal gland Synacthen (=synACTHen) Baseline cortisol may be normal in Addison’s disease Synacthen test: uses synthetic ACTH analogue Normal response: rise in cortisol