Adrenal Gland Disorders

Addison’s Disease, also called primary adrenal insufficiency, is a rare condition in which the adrenal glands fail to produce enough cortisol and often aldosterone. Cortisol is vital for stress response, metabolism, and inflammation control, while aldosterone helps regulate sodium, potassium, and blood pressure. The most common cause is autoimmune destruction of the adrenal cortex. Other causes include infections (e.g., tuberculosis), metastatic cancers, or adrenal hemorrhage. Symptoms are often vague and develop gradually: fatigue, weight loss, loss of appetite, abdominal pain, nausea, low blood pressure (especially on standing), salt craving, darkening of the skin (especially in creases), and mood disturbances. During times of stress, illness, or injury, patients may experience an Addisonian crisis, characterized by severe hypotension, vomiting, dehydration, confusion, and even coma — a medical emergency. Diagnosis involves measuring low cortisol levels, high ACTH (adrenocorticotropic hormone), and abnormal ACTH stimulation test results. Electrolyte abnormalities like low sodium and high potassium are common. Treatment involves lifelong hormone replacement with hydrocortisone or prednisolone for cortisol, and fludrocortisone for aldosterone. During illness or surgery, “stress doses” of steroids are needed to prevent adrenal crisis. With regular monitoring and adherence to treatment, patients can live healthy and active lives.

Cushing’s Syndrome is a hormonal disorder caused by prolonged exposure to high levels of cortisol. It can result from endogenous overproduction (due to adrenal tumors or excess ACTH secretion from the pituitary or ectopic sources) or exogenous use of corticosteroids. The clinical features develop gradually and include central obesity, moon-shaped face, fat accumulation around the neck and upper back (buffalo hump), purple stretch marks (striae) on the abdomen, muscle weakness, easy bruising, and slow wound healing. Other signs include high blood pressure, diabetes, osteoporosis, mood swings, irregular menstruation, and reduced libido. In children, Cushing’s may present as obesity with growth retardation. Pituitary-driven cases (Cushing’s disease) often have a gradual onset, while adrenal tumors or ectopic ACTH may present more acutely. Diagnosis involves confirming elevated cortisol levels via 24-hour urinary free cortisol, latenight salivary cortisol, or low-dose dexamethasone suppression tests, followed by imaging studies (MRI or CT) to localize the source. Treatment depends on the cause: surgical removal of the pituitary or adrenal tumor, radiation therapy, or medication to control cortisol production (e.g., ketoconazole, metyrapone). In steroid-induced cases, gradual tapering of the medication is essential. If left untreated, Cushing’s Syndrome can lead to severe complications like cardiovascular disease, fractures, infections, and psychological disturbances. Early detection and targeted therapy offer a good prognosis.

Congenital Adrenal Hyperplasia (CAH) refers to a group of inherited genetic disorders affecting adrenal steroid hormone production. The most common form, 21-hydroxylase deficiency, leads to decreased cortisol and, in some cases, aldosterone production, while androgen levels become abnormally elevated. CAH typically presents in infancy or early childhood. In classic CAH, symptoms include saltwasting (vomiting, dehydration, low blood pressure, failure to thrive) and ambiguous genitalia in females due to excess androgens. Males may appear normal at birth but develop early signs of puberty, such as rapid growth, body hair, and deepening of the voice (precocious puberty). Non-classic CAH, a milder form, may emerge in adolescence or adulthood with features like irregular menstrual cycles, acne, excessive body hair (hirsutism), and infertility in women. Untreated CAH can result in adrenal crisis, impaired growth, infertility, and psychosocial distress. Diagnosis is confirmed with elevated 17-hydroxyprogesterone levels, along with abnormal serum electrolytes and ACTH levels in classic cases. Genetic testing helps in confirming the mutation. Treatment involves lifelong glucocorticoid therapy (such as hydrocortisone or dexamethasone) to suppress excess androgen production and mineralocorticoids (like fludrocortisone) for saltwasting forms. Stress dosing during illness is essential. Surgical correction may be considered in females with genital ambiguity. With early diagnosis, education, and hormonal therapy, individuals with CAH can lead healthy and fulfilling lives

An adrenal incidentaloma is an unexpected mass found in one of the adrenal glands during imaging performed for unrelated reasons. These lesions are surprisingly common, especially in older adults, and are found in up to 5% of abdominal CT scans. Most adrenal incidentalomas are benign, non-functioning adenomas that require no treatment. However, a critical evaluation is necessary to determine whether the mass is: 1. Functioning (hormonally active) 2. Non-functioning 3. Malignant Functioning tumors may secrete hormones such as cortisol (leading to Cushing’s syndrome), aldosterone (causing primary aldosteronism), or catecholamines (suggesting pheochromocytoma). Hence, every incidentaloma must be assessed for hormonal activity and potential malignancy. Clinical symptoms depend on the hormone secreted. Many patients are asymptomatic, but some may present with hypertension, weight gain, muscle weakness, or palpitations depending on the tumor type. Evaluation involves a combination of hormonal testing (for cortisol, aldosterone, renin, and catecholamines) and imaging features (size, shape, density on CT or MRI). Features suggestive of malignancy include large size (>4 cm), irregular borders, and rapid growth. Non-functioning and small benign-appearing lesions are monitored periodically. Surgery is recommended for tumors that are functional, larger than 4–6 cm, or show suspicious characteristics. Most incidentalomas are benign and stable, but accurate assessment is crucial to avoid missing a hormonally active or malignant lesion.

Primary Aldosteronism, also known as Conn’s Syndrome, is a hormonal disorder in which the adrenal glands produce excessive amounts of aldosterone — a hormone that helps regulate blood pressure by controlling sodium and potassium balance. The most common causes include aldosterone-producing adenoma (benign tumor) and bilateral adrenal hyperplasia. The excess aldosterone leads to sodium retention, increased blood volume, and suppression of renin, resulting in hypertension and hypokalemia (low potassium). Clinically, patients may present with resistant high blood pressure, muscle weakness, cramps, numbness, fatigue, or even periodic paralysis due to low potassium. However, many remain asymptomatic apart from the hypertension. Diagnosis begins with screening tests showing elevated aldosterone levels and suppressed plasma renin activity, followed by confirmatory testing (like saline infusion or captopril challenge tests). CT scan of the adrenal glands helps identify unilateral or bilateral lesions, and in selected cases, adrenal venous sampling is done to determine the exact source of hormone overproduction. Treatment depends on the underlying cause: • Unilateral adenoma: managed surgically (adrenalectomy), often resulting in significant improvement or resolution of hypertension. • Bilateral hyperplasia: treated with mineralocorticoid receptor antagonists like spironolactone or eplerenone. Primary aldosteronism is underdiagnosed but is one of the most treatable causes of secondary hypertension. Early detection and appropriate therapy can prevent long-term cardiovascular and renal complications.

Pheochromocytoma is a rare tumor of the adrenal medulla that produces excessive amounts of catecholamines — mainly epinephrine and norepinephrine. These hormones trigger the body’s fight-or-flight response, leading to sudden and severe spikes in blood pressure. The classic triad of symptoms includes: 1. Headaches 2. Palpitations 3. Sweating These may occur in episodic attacks, often accompanied by anxiety, tremors, flushing, chest pain, and weight loss. Some patients may present with sustained or paroxysmal hypertension, and in rare cases, the tumor can cause a hypertensive crisis, arrhythmia, stroke, or heart failure. Pheochromocytomas may occur sporadically or as part of inherited syndromes like MEN2, von Hippel-Lindau, and neurofibromatosis type 1. About 10% of tumors are bilateral, malignant, or extra-adrenal (paragangliomas). Diagnosis is made by detecting elevated catecholamines or their metabolites (e.g., plasma-free metanephrines or 24-hour urinary metanephrines). Imaging studies like CT or MRI localize the tumor, while MIBG scans help identify metastatic or extra-adrenal disease. The primary treatment is surgical removal, but preoperative preparation with alpha-blockers (like phenoxybenzamine) and sometimes beta-blockers is essential to avoid intraoperative hypertensive crises. With early diagnosis and expert surgical care, the prognosis is excellent. However, long-term follow-up is required due to risk of recurrence or metastasis.