Endocrinology · Adrenal Disorders
The facts most likely to be tested
Primary adrenal insufficiency is characterized by the simultaneous deficiency of cortisol and aldosterone, leading to hyperpigmentation due to elevated ACTH and MSH levels.
The cosyntropin stimulation test is the gold standard diagnostic test, showing a failure of serum cortisol to rise after the administration of synthetic ACTH.
Patients typically present with hyponatremia, hyperkalemia, and non-anion gap metabolic acidosis due to the loss of mineralocorticoid activity.
Autoimmune adrenalitis is the most common cause of primary adrenal insufficiency in developed countries, often associated with polyglandular autoimmune syndromes.
Adrenal crisis is a life-threatening emergency presenting with refractory hypotension and shock that requires immediate IV hydrocortisone and aggressive fluid resuscitation.
In patients with suspected adrenal insufficiency, serum morning cortisol and plasma ACTH levels should be obtained to establish the diagnosis before initiating treatment.
Chronic management of Addison disease requires glucocorticoid replacement (hydrocortisone) and mineralocorticoid replacement (fludrocortisone) to maintain electrolyte balance.
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A 34-year-old woman presents to the clinic with a 3-month history of progressive fatigue, weight loss, and salt cravings. Physical examination reveals hyperpigmentation of the palmar creases and buccal mucosa. Laboratory studies demonstrate hyponatremia, hyperkalemia, and a low morning serum cortisol level. A cosyntropin stimulation test is performed, and the patient's serum cortisol fails to increase 60 minutes after injection.
What is the most appropriate long-term pharmacologic management for this patient?
Hydrocortisone and fludrocortisone
The patient exhibits classic signs of primary adrenal insufficiency (Addison disease), which requires both glucocorticoid (hydrocortisone) and mineralocorticoid (fludrocortisone) replacement to address the combined deficiency of cortisol and aldosterone.
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Etiology / Epidemiology
Most common cause in developed nations is autoimmune destruction of the adrenal cortex. Suspect in patients with hyperpigmentation and unexplained hypotension.
Clinical Manifestations
Classic presentation includes hyperpigmentation (palmar creases/buccal mucosa) and salt craving. Adrenal crisis presents as refractory shock.
Diagnosis
Gold standard is the Cosyntropin stimulation test; failure to increase serum cortisol >18 mcg/dL confirms diagnosis.
Treatment
First-line replacement is Hydrocortisone plus Fludrocortisone. Do not delay treatment in suspected adrenal crisis.
Prognosis
Patients require lifelong replacement therapy. Adrenal crisis is a life-threatening emergency requiring immediate IV fluids and steroids.
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Epidemiology & Etiology
In the US, autoimmune adrenalitis accounts for >80% of cases. Globally, tuberculosis remains a leading infectious cause. It is frequently associated with Autoimmune Polyglandular Syndromes (APS).
Pertinent Anatomy
The adrenal cortex is divided into three zones: the zona glomerulosa (aldosterone), zona fasciculata (cortisol), and zona reticularis (androgens). Primary insufficiency involves destruction of all three layers, leading to combined mineralocorticoid and glucocorticoid deficiency.
Pathophysiology
Loss of cortisol leads to impaired gluconeogenesis and increased insulin sensitivity, causing hypoglycemia. Loss of aldosterone results in hyponatremia and hyperkalemia. Elevated pro-opiomelanocortin (POMC) levels stimulate melanocytes, causing characteristic skin darkening.
Clinical Manifestations
Patients present with insidious fatigue, weight loss, and hyperpigmentation of skin folds and mucous membranes. Salt craving is a classic symptom due to mineralocorticoid loss. Adrenal crisis manifests as sudden, severe hypotension, abdominal pain, and vomiting unresponsive to vasopressors.
Diagnosis
The Cosyntropin stimulation test is the gold standard; a post-stimulation cortisol level <18 mcg/dL confirms primary insufficiency. Elevated ACTH levels distinguish primary from secondary causes. Obtain a baseline morning cortisol and ACTH level prior to stimulation.
Treatment
Replace glucocorticoids with Hydrocortisone and mineralocorticoids with Fludrocortisone. Stress dose steroids (increased dosage) are required during illness, surgery, or trauma to prevent crisis. Do not delay life-saving IV fluids and high-dose steroids if adrenal crisis is suspected.
Prognosis
With adherence to lifelong hormone replacement, life expectancy is near normal. Adrenal crisis remains the primary cause of mortality if triggers are not managed with appropriate dose adjustments.
Differential Diagnosis
Secondary Adrenal Insufficiency: No hyperpigmentation (low ACTH)
Congenital Adrenal Hyperplasia: Virilization and early onset
Hypothyroidism: Fatigue without electrolyte abnormalities
Hemochromatosis: Hyperpigmentation without hypotension
Sepsis: Hypotension without chronic history