•Zona Glomerulosa•Zona Fasiculata

•Zona Reticularis

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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

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Conditions Affecting Adrenal CortexAdrenocortical 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)

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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

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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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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

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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.

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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.

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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 Unit3 days vomiting – hourlyDrowsyBP 60/30Deeply pigmentedNa+ 125 mmol/l (N 135-145)K+ 5.4 mmol/l (N 3.5-5.0)

QuestionsDiagnosisPathogenesisWhat hormone is deficientDiagnostic testTreatmentComplications

Addison’s diseasePathogenesis Destruction of adrenal glands

Autoimmune Tuberculosis Tumour/infiltration Infective (meningococcus)

Hormone deficiency Cortisol Aldosterone

Diagnostic test Synacthen testTreatment Cortisol replacement

Hydrocortisone/Cortisone Aldosterone replacement

FludrocortisoneComplications Adrenal crisis – intercurrent illness

Synacthen testPituitary

Cortisol

Adrenalgland

Synacthen(=synACTHen)

•Baseline cortisol may be normal in Addison’s disease•Synacthen test: uses synthetic ACTH analogue•Normal response: rise in cortisol