Addison Hyperpigmentation

An endocrine disorder first described by the British Physician Thomas Addison in the mid 1800 s. The adrenal glands fail to produce sufficient amounts of glucocorticoid hormones (cortisol) and sometime mineralocorticoid (aldosterone). If left untreated it is life-threatening, the patient will show muscle weakness, hyperpigmentation and even depression. Typical treatment is hydrocortisone replacement therapy. 

Hyperpigmentation is common in Addison s disease and may involve exposed and nonexposed parts of the body. Hyperpigmentation is usually not seen in secondary adrenal insufficiency because of low amounts of melanocyte-stimulating hormone. 

Adrenal insufficiency may result from hypofunction of the adrenal cortex (primary adrenal insufficiency, Addison s disease) or from a malfunctioning of the hypothalamic-pituitary system (secondary adrenal insufficiency). In treating primary adrenal insufficiency, one should administer sufficient cortisol to diminish hyperpigmentation and abolish postural hypotension these are the cardinal signs of Addison s disease. 

Human ACTH is a single peptide chain of 39 amino acids. The amino terminal portion containing amino acids 1-24 is necessary for full biologic activity. The remaining amino acids (25-39) confer species specificity. Synthetic human ACTHi 24 is known as cosyntropin. The amino terminal amino acids 1-13 are identical to melanocyte-stimulating hormone (cr-MSH), which has been found in animals but not in humans. In states of excessive pituitary ACTH secretion (Addison s disease or an ACTH-secreting pituitary tumor), hyperpigmentation—caused by the -MSH activity intrinsic to ACTH—may be noted. 

A. Hyperpigmentation is a feature of Addison disease, the diagnosis in this case. Decreased plasma cortisol because of adrenal insufficiency releases feedback inhibition of ACTH secretion by the pituitary, resulting in elevation of ACTH biosynthesis. The ACTH precursor peptide is cleaved to also yield melanocyte-stimulating hormone, the factor responsible for hyperpigmentation even in areas not exposed to sunlight. 

Tyrosinase activity decreases after hypophysectomy, but can be restored by chronic administration of pituitary hormones like prolactin, MSH, and ACTH to a greater or lesser extent (131). Prolactin can promote in vivo melanin synthesis not only by stimulating tjn osinase activity, but also by increasing the supply of available substrate (131). However, it is still unknown which of the pituitary hormones is responsible for hyperpigmentation in Addison s disease in man. 

Addison s disease was described in 1855. In his original observation, Addison remarked that the disease is characterized by the now classical triad of symptoms— electrolyte imbalance, hypertension, and hyperpigmentation. Addison s disease is a rare disease that affects both sexes with the same frequency. Before the corticosteroid hormones were discovered, the disease was inevitably fatal. 

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