Derm Dx: Hyperpigmentation in a white female with fatigue, dizziness and nausea - Clinical Advisor

Derm Dx: Hyperpigmentation in a white female with fatigue, dizziness and nausea

Slideshow

  • CA0711Addison_Face

  • CA0711Addison_Elbow

  • CA0711Addison_Axilla

  • CA0711Addison_Oral

A 40-year old white female presents to her primary care health care provider with a chief complaint of fatigue, dizziness, nausea and vomiting. She has hyperpigmented skin on her face, oral mucosa, elbow and axillae.

The patient reports a 10 lb weight loss and pubic hair alopecia during the past month. Her BP is 93/60 mm Hg lying down, and systolic BP drops to 80 mm Hg standing. What’s your diagnosis?

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Addison's disease is a disorder involving adrenal insufficiency caused by damage to the adrenal cortex. Primarily affecting adults aged 30 to 50 years, US incidence is five to six cases per million population annually.First described in 1855 by Thomas Addison,...

Submit your diagnosis to see full explanation.

Addison’s disease is a disorder involving adrenal insufficiency caused by damage to the adrenal cortex. Primarily affecting adults aged 30 to 50 years, US incidence is five to six cases per million population annually.

First described in 1855 by Thomas Addison, the etiology of Addison’s disease in developed countries has shifted. Once a disorder primarily caused by tuberculosis (TB) infection, nonspecific autoimmune destruction has eclipsed TB as the most prevalent cause in developed countries. Other causes include neoplastic, vascular, metabolic and traumatic events.

When the adrenal cortex is damaged, corticotropin and melanocyte-stimulating hormone (MSH) are secreted continuously, resulting in the characteristic bronze hyperpigmentation that occurs in 95% of patients with Addison’s disease. Clinical findings are usually only noted after 90% of the adrenal cortex has been destroyed.

Signs & symptoms

Nonspecific Addison’s disease symptoms include fatigue, weakness, anorexia, nausea, abdominal pain, gastroenteritis, diarrhea and mood swings.

Approximately 90% of patients experience nausea, vomiting and diffuse abdominal pain. Diarrhea is less common, occurring in about 20% of patients. Mood changes include depression, irritability and decreased concentration.

Physical symptoms include skin and mucosa hyperpigmentation, loss of androgen-stimulated hair in women, dehydration, hypotension (systolic BP lower than 110 mm Hg) and vitiligo. Hyperpigmentation is generally most pronounced on the nipples, axillae, perineum and buccal mucosa.

Autoimmune causes

Autoimmune destruction of the adrenal cortex occurs in polyglandular autoimmune syndrome type I (PGAD I), and autoimmune-mediated adrenal insufficiency occurs in polyglandular autoimmune syndrome type II (PGAD II).

PGAD I may involve type 1 diabetes, hypogonadism, chronic hepatitis, immunoglobulin A (IgA) deficiency, chronic atopic dermatitis, keratoconjunctivitis, vitiligo and alopecia. PGAD II may involve autoimmune-mediated thyroiditis and/or autoimmune-mediated type 1 diabetes. Less than 1% of patients with type 1 diabetes develop Addison’s disease.

People without symptoms of Addison’s disease that have antibodies to the adrenal cortex (ACAs) — particularly to steroid 21-hydroxylase (21-OH), steroid 17-hydroxylase (17-OH) and cytochrome P-450 — are at risk of adrenal insufficiency and progression to Addison’s disease.

Diagnosis

The first step in diagnosing Addison’s disease is identifying adrenal insufficiency and the site of the defect in the hypothalamic-pituitary axis.

Clinicians should perform a blood test to measure serum cortisol levels from samples obtained between 6 and 8 am, when cortisol levels are highest.

Cortisol values less than 3 mcg/dL are indicative of Addison’s disease; patients with values in the 3 to 19 mcg/dL require further evaluation before a definitive diagnosis is made. Cortisol values greater than 19 mcg/dL rule out Addison’s disease.

Other tests to determine adrenal insufficiency include the corticotropin-releasing hormone (CHR) stimulation test  (Cortrosyn, Amphastar Pharmaceuticals), the insulin tolerance test and the metyrapone test.

Corticotropin sampling, corticotropin provocative testing and CRH provocative testing are options for determining whether the adrenal insufficiency is hypothalamic-mediated or pituitary-mediated.

Initial diagnostic evaluations should also include a work up for adrenal antibodies and TB. Computed tomography (CT) and magnetic resonance imaging (MRI) may be useful in identifying diminished adrenal glands in patients in whom Addison’s disease is autoimmune in nature, or enlarged adrenal glands in patients with an infectious etiology.

CT may reveal calcification in patients with adrenal insufficiency caused by TB. Clinicians can identify adrenal hemorrhages using either CT or MRI.

Treatment

The primary goal of treatment for Addison’s disease is adequate glucocorticoid and mineralocorticoid replacement with medications including cortisone, hydrocortisone, fludrocortisone and dexamethasone.

Dosing varies from patient to patient and achieving optimal medication levels can be challenging. Underdosing results in continued adrenal insufficiency and overdosing may cause weight gain, hypertension and osteoporosis.

Patients with hypovolemia and hyponatremia should be treated with intravenous fluid and sodium replacement until stable. Admit those with systemic symptoms to the hospital immediately.

Clinicians should avoid diuretics to prevent excessive sodium loss and pay special attention to potential adverse drug interactions. Also, be sure to advise patients about the potential for salt loss during vigorous exercise.

Depending on the cause of adrenal insufficiency, referral to an endocrinologist, rheumatologist or infectious disease specialist for consultation may be warranted.

Jabbour SA. Cutaneous manifestations of endocrine disorders: a guide for dermatologists. Am J Clin Dermatol. 2003;4:315-331.

Luken KK. Clinical manifestations and management of Addison’s disease. J Am Acad Nurse Pract. 1999;11:151-154.

Nieman LK, Chanco Turner ML. Addison’s disease. Clin Dermatol. 2006;24:276-80.

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