ADDISON’S DISEASE
Addison’s disease (chronic primary adrenocortical insufficiency) occurs when the adrenal gland has lost most of its functional capacity. Addison’s disease can be caused by many different disease states that inhibit the functioning of the adrenal gland. The adrenal gland has a massive reserve capacity, and clinical manifestations of chronic adrenal insufficiency are not seen until the bilateral glands have lost at least 90% of their ability to produce adrenal hormones. Autoimmune destructive atrophy of the adrenal glands is the most common cause of Addison’s disease. Infectious processes can cause destruction of the adrenal gland, with tuberculosis one of the more common causes of chronic adrenal gland insufficiency. Most cases of acute adrenal gland destruction are caused by bacteria (i.e., meningococcal disease).
Clinical
Findings: Males and females are equally affected. The first symptoms are lethargy
and generalized malaise. These symptoms may not be apparent until the affected
patient undergoes a major stressful event, such as infection, which can lead to
a prolonged disease course and a prolonged convalescence. Patients have
excessive nervousness and may show emotional lability superimposed on periods
of depression. Fatigue and weakness can be severe, to the point where even
speaking causes fatigue. Weight loss and evidence of dehydration are present in
most cases. Hypotension is frequently seen, and a small heart shadow is seen on
chest radiography.
Cutaneous
effects are always found in chronic primary adrenal insufficiency. Pigmentation
is seen in many regions of the body and appears to occur in areas of friction,
such as along the waist line and on elbows and knees. This is typically a
generalized “bronze pigmentation,” but it is accentuated in the groin,
nipples, and scrotum. The palmar and plantar creases are accentuated.
Hyperpigmentation may be prominent within previous scars. Vitiligo may be
present in conjunction with autoimmune adrenal insufficiency. Increased pigmentation of hair is seen, but this may be subtle and may occur slowly. Pigmentary
alterations of the gingival and labial mucosa may also be seen. Pigmentary
anomalies are not seen in secondary adrenal insufficiency, which is caused by
pituitary deficiency.
Body hair is
dramatically decreased, with near loss of axillary and pubic hair. The hair
loss is more pronounced in females, because males still produce androgens,
primarily in the unaffected testes. Serum testing shows hyperkalemia and
hyponatremia, with a low cortisol level. The diagnosis is confirmed by
intravenously injecting a synthetic corticotropin and evaluating the adrenal
gland’s response by measuring cortisol levels after the injection. In patients
with Addison’s disease, the serum cortisol level is not increased by
stimulation testing.
Histology:
Skin
biopsies are not helpful in making the diagnosis and are rarely performed. A
normal number of melanocytes are present, with an increased amount of melanin
pigment in the epidermis.
Pathogenesis:
The
adrenal glands are responsible for making cortisol, aldosterone, and the 17-ketosteroiods.
When the adrenal glands no longer are able to produce these molecules,
Addison’s disease sets in. In the presence of low circulating levels of
cortisol, the pituitary responds by increasing production of
adrenocorticotrophic hormone (ACTH, corticotropin) and melanocyte-stimulating
hormone (MSH). ACTH and MSH are derived from the same precursor protein, pro-opiomelanocortin (POMC). The pigmentary anomalies seen in Addison’s disease are directly related to
increased release of MSH. The increase in MSH causes pigment production by
melanocytes in skin, hair, and mucous membranes. Pubic and axillary hair loss
is related to the lack of 17-ketosteroids, whereas hypotension is caused by the
lack of aldosterone. The lack of aldosterone causes a decreased blood volume
and decreased serum sodium. The lack of cortisol production is responsible for
weakness, fatigue, weight loss, and decreased mentation.
Addison’s
disease is seen frequently in association with other autoimmune endocrine
disorders such as diabetes and autoimmune thyroiditis.
Treatment: Treatment requires the clearing of infection or treatment of the underlying cause of adrenal gland dysfunction. Supplemental hydrocortisone and fludrocortisone are used as replacement therapy for those with inadequate adrenal function. Hydrocortisone is used primarily to replace the missing cortisol, and fludrocortisone is used to replace aldosterone.
