Why Addison's disease can tan skin that never sees the sun
In Addison's disease the adrenal glands stop making enough cortisol, and the pituitary responds by shouting louder, pumping out a hormone that shares its parent molecule with a skin-darkening signal. The result can be dusky creases on the palms, darkened old scars and pigment inside the cheeks, a strange outward clue to a hidden hormone failure.
The condition, also called primary adrenal insufficiency, occurs when the outer layer of the adrenal glands produces too little cortisol and often too little aldosterone. In industrialised countries the usual cause is autoimmune: between 68 and 94 per cent of cases involve the immune system attacking an adrenal enzyme called 21-hydroxylase, a target identified in 1992. Tuberculosis, bleeding into both glands, cancer spread and rare genetic faults account for others. Many patients also have another autoimmune illness, most commonly thyroid disease, found in about 40 per cent.
The pigment clue comes from shared chemistry. The pituitary makes a large precursor protein, pro-opiomelanocortin, which is cut into ACTH, the hormone that prods the adrenals, and into melanocyte-stimulating hormone. When cortisol falls, ACTH rises and pigment-stimulating fragments rise with it. That is why darkening appears only when the adrenals themselves have failed, not when the problem lies in the pituitary.
Symptoms creep in over months and mimic other illnesses: fatigue, weight loss, aching muscles, nausea and abdominal pain. Low aldosterone can cause salt cravings and dizziness on standing, and blood tests often reveal low sodium and high potassium. A review of delayed diagnoses notes that this slow, varied presentation makes the disease easy to miss. Confirmation comes from a stimulation test in which synthetic ACTH fails to drive cortisol up normally.
Stress from injury, surgery or infection can tip a patient into an adrenal crisis, with plunging blood pressure, vomiting and collapse, a genuine emergency. Treatment replaces the missing hormones for life, and with it most people live fairly normal lives. The disease affects about 9 to 14 in 100,000 people in the developed world, most often middle-aged women, and takes its name from Thomas Addison, who described it in 1855. A small study of 19 patients found lower bone density and weaker bone microstructure than in matched controls.
Source: Addison's disease
