Primary adrenal insufficiency (Addison’s disease) results from a dysfunction of the adrenal glands, which may be secondary to autoimmune diseases, genetic conditions, infections, and vasculopathies,or may be drug-induced (e.g. checkpoint inhibitors), among others . In contrast, secondary adrenal insufficiency results from pituitary dysfunction of low adrenocorticotropic hormone (ACTH). The most common cause of primary adrenal insufficiency in developed countries is autoimmune adrenalitis, which accounts for upwards of 90% of cases. Typically, 21-hydroxylase autoantibodies are identified and account for destruction of the adrenal cortex through cell-mediated and humoral immune responses.
Dr. Sophia M. Akhiyat
Palmar creases, subungual surfaces, sites of trauma, and joint spaces (including the knees, spine, elbows, and shoulders) are commonly affected. Hair depletes in the pubic area and axillary vaults. Nevi may also appear darker. In patients with autoimmune adrenalitis, vitiligo may be seen secondary to autoimmune destruction of melanocytes.
Diagnosis may be difficult in the early stages, but historical findings of fatigue and clinical findings of hyperpigmentation in classic areas may prompt appropriate lab screening workup. It is essential to determine whether adrenal insufficiency is primary or secondary. Evaluation of decreased cortisol production, determination of whether production is ACTH-dependent or -independent, and evaluation for the underlying causes of adrenal dysfunction are important. Lab screening includes morning serum cortisol, morning ACTH (cosyntropin) stimulation test, fasting CBC with differential, and CMP to evaluate for normocytic normochromic anemia, hyponatremia, hyperkalemia, hypoglycemia, plasma renin/aldosterone ratio, and 21-hydroxylase autoantibodies.
Dr. Sophia M. Akhiyat
Management strategies of primary adrenal insufficiency require corticosteroid supplementation and multidisciplinary collaboration with endocrinology. If untreated, primary adrenal insufficiency can be fatal. Adrenal crisis is a critical condition following a precipitating event, such as GI infection, fever, acute stress, and/or untreated adrenal or pituitary disorders. Clinical findings include acute shock with hypotension, nausea, vomiting, abdominal pain, back or leg pain, and a change in mental status. In this scenario, increasing the dose of corticosteroid supplementation is essential for reducing mortality.
Upon examining this patient’s new skin findings of hyperpigmentation and discussing her fatigue, primary adrenal insufficiency was suspected. With further prompting, the patient reported an ICU hospitalization several months prior because of sepsis originating from a peritonsillar abscess. With these clinical and historical findings, preliminary workup was conducted by dermatology, which included morning cortisol level, ACTH, CBC with differential, CMP, plasma renin-aldosterone ratio, and 21-hydroxylase autoantibodies. Work up demonstrated a low morning cortisol level of 1.3 mcg/dL, an elevated ACTH of 2,739 pg/mL, and positive 21-hydroxylase autoantibodies. The patient was urgently referred to endocrinology and started on oral hydrocortisone. Her fatigue immediately improved, and at 1-year follow-up with dermatology, her mucocutaneous hyperpigmentation had subsided dramatically.
Dr. Donna Bilu Martin
Dermatologists can play a major role in the early diagnosis of primary adrenal insufficiency, which is essential for reducing patient morbidity and mortality. Skin findings on full body skin exams can clue in dermatologists for ordering preliminary workup to expedite care for these patients.
The case and photos were submitted by Dr. Akhiyat, Scripps Clinic Medical Group, La Jolla, California. Donna Bilu Martin, MD, edited the column.
Dr. Bilu Martin is a board-certified dermatologist in private practice at Premier Dermatology, MD, in Aventura, Florida. More diagnostic cases are available at mdedge.com/dermatology. To submit a case for possible publication, send an email to dermnews@mdedge.com.
References
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