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Progressive weakness, anemia, hypoglycemia, and
hyperpigmentation of the skin. Vomiting, apneic spells, cyanosis, vascular
collapse, and cardiovascular shock may be consequential.
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Addison Disease; Adrenal Insufficiency; Adrenal
Hypoplasia/Aplasia.
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First described in 1849 by Thomas Addison, the English
physician, in patients suffering from tuberculosis with suprarenal
involvement.
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Most cases are sporadic, but depending on the
etiology solid evidence exists for autosomal recessive and X-linked
recessive forms.
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Complete or partial deficit of mineralocorticoids
and glucocorticoid hormones, excreted by the zonae fasciculata (aldosterone)
and glomerulosa (glucocorticoids) of the adrenal cortex, caused by different
mechanisms. Autoimmune mechanisms (which may be associated with other
autoimmune diseases, e.g. chronic lymphocytic thyroiditis, hyperthyroidism,
diabetes mellitus, celiac disease), adrenal aplasia, X-linked congenital
adrenal hypoplasia, cytomegalic adrenocortical hypoplasia, familial
hypoadrenocorticism, pituitary gland hypoplasia, isolated ACTH deficiency,
X-linked adrenoleukodystrophy, and Waterhouse Friderichsen Syndrome
(fulminant form caused by meningococcemia). Dysfunction of the adrenal
cortex leads to interrupted hypothalamic and anterior pituitary gland
feedback inhibition, resulting in continuous and uninhibited secretion of
ACTH. Cleavage of the prohormone pro-opiomelanocortin in the adenohypophysis
results in simultaneous secretion of ACTH and melanocyte-stimulating hormone
(MSH). The elevated MSH level is responsible for the typical bronze
hyperpigmentation in patients with primary adrenal insufficiency.
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Vomiting, cyanosis, apneic spells, hypoglycemia,
seizures, and vascular collapse are the usual presenting symptoms of an
adrenal crisis. Cardiovascular collapse may occur. Plasma and urinary
concentrations of all adrenal steroids are low. Serum glucose level usually
is low. Sodium plasma concentrations are decreased (but rarely <120 mmol/l)
but potassium plasma concentrations are increased (but rarely >7.0 mmol/l).
Moderate metabolic acidosis with plasma bicarbonate levels between 15 and 20
mmol/l is common. BUN typically is elevated. Urinary excretion of sodium and
chloride is increased, whereas potassium excretion is decreased. Plasma
cortisol levels—if measured before treatment—are low. However, the
final diagnosis of adrenocortical insufficiency is based on the
finding of an absent or decreased response in adrenal steroid synthesis to
stimulation with external (intravenous or intramuscular) ACTH. Increased
serum concentrations of cortisol and aldosterone are signs of a functional
adrenal cortex. Under normal conditions, cortisol synthesis increases by a
factor of two to five times above normal levels after administration of
ACTH. Failure of aldosterone serum level to double within 30 minutes of ACTH
administration indicates a problem with mineralocorticoid synthesis. A
normal ACTH stimulation test result excludes the diagnosis of primary
adrenocortical insufficiency. The adrenal glands may appear enlarged on
abdominal CT scan or sonography in patients with Addison disease secondary
to infection, hemorrhage, or malignancies involving the adrenals. Primary
adrenal insufficiency results in atrophic adrenal glands secondary to
inactivity. Idiopathic autoimmune adrenocortical insufficiency usually resulting from
autoimmune lymphocytic infiltration of the adrenal cortex is the most common
cause of Addisonian syndrome, accounting for approximately 80% of cases.
Another significant percentage results from adrenal cortex destruction by
tuberculosis.
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Idiopathic autoimmune Addison disease may occur in isolation or in
combination with other autoimmune diseases, such as diabetes mellitus type
I, systemic lupus erythematosus, Hashimoto thyroiditis, ...