Adrenal Insufficiency: Aetiology, Clinical Presentation

Adrenal Insufficiency: Aetiology, Clinical Presentation, and Laboratory Findings Aetiology Adrenal insufficiency, or Addison's disease, is a condition where the adrenal glands fail to produce sufficient hormones, primarily cortisol and aldosterone. The causes can be broadly categorized into primary, secondary, and tertiary. 1. Primary Adrenal Insufficiency (Addison’s Disease): o Autoimmune Adrenalitis: The most common cause, where the immune system attacks the adrenal cortex. o Infections: Tuberculosis, HIV, fungal infections (e.g., histoplasmosis). o Adrenal Hemorrhage: Often due to sepsis (Waterhouse-Friderichsen syndrome) or anticoagulant therapy. o Genetic Disorders: Congenital adrenal hyperplasia, adrenoleukodystrophy. o Metastatic Disease: Cancers that spread to the adrenal glands. 2. Secondary Adrenal Insufficiency: o Pituitary Disorders: Tumors, surgery, radiation, or inflammation affecting ACTH production. o Exogenous Glucocorticoid Use: Prolonged use of corticosteroids suppresses ACTH production, leading to adrenal atrophy. 3. Tertiary Adrenal Insufficiency: o Hypothalamic Dysfunction: Tumors, trauma, or radiation affecting the hypothalamus, leading to decreased CRH production. Clinical Presentation The clinical manifestations of adrenal insufficiency vary depending on the severity and duration of hormone deficiency. 1. Chronic Symptoms: o Fatigue and Weakness: Persistent and progressive. o Weight Loss: Unintentional and often significant. o Hyperpigmentation: Especially in primary adrenal insufficiency due to high ACTH levels stimulating melanocytes. Commonly seen in the palmar creases, gums, and scars. o Hypotension: Particularly postural hypotension, due to low aldosterone. o Salt Craving: Due to hyponatremia. o Gastrointestinal Symptoms: Nausea, vomiting, abdominal pain, and diarrhea. 2. Acute Adrenal Crisis: o Severe Hypotension: Can progress to shock. o Dehydration: Due to aldosterone deficiency leading to salt and water loss. o Hypoglycemia: Often severe. o Confusion or Coma: Severe cases may present with altered mental status. Laboratory Findings Laboratory tests are essential for diagnosing adrenal insufficiency and determining its etiology. 1. Primary Adrenal Insufficiency: o Electrolyte Imbalances: Hyponatremia, hyperkalemia due to aldosterone deficiency. o Cortisol Levels: Low morning serum cortisol. o ACTH Levels: Elevated in primary adrenal insufficiency. o Renin and Aldosterone: Elevated plasma renin activity and low aldosterone levels. o Adrenal Antibodies: Positive in autoimmune adrenalitis. o ACTH Stimulation Test: Measures cortisol response to synthetic ACTH (cosyntropin). In primary adrenal insufficiency, cortisol fails to rise significantly. 2. Secondary Adrenal Insufficiency: o Cortisol Levels: Low. o ACTH Levels: Low or inappropriately normal. o ACTH Stimulation Test: May show a subnormal increase in cortisol, depending on the duration of ACTH deficiency. o Pituitary Imaging: MRI may reveal pituitary pathology. o Other Pituitary Hormones: May be involved, suggesting panhypopituitarism. 3. Tertiary Adrenal Insufficiency: o Cortisol and ACTH Levels: Both may be low. o CRH Stimulation Test: Helps differentiate between secondary and tertiary causes; reduced ACTH response indicates tertiary insufficiency. o Hypothalamic Imaging: To identify structural lesions. Conclusion Adrenal insufficiency is a life-threatening condition if not diagnosed and managed promptly. It presents with a range of symptoms from chronic fatigue and weight loss to acute adrenal crisis with severe hypotension and shock. Diagnosis involves careful assessment of hormone levels and response to stimulation tests, alongside imaging to identify underlying causes. Understanding the aetiology, clinical presentation, and laboratory findings is crucial for effective management and treatment of this endocrine disorder.