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Causes and pathogenesis of acute adrenal insufficiency

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Last reviewed: 06.07.2025
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Adrenal or Addisonian crises develop more often in patients with primary or secondary adrenal disease. They are less common in patients without previous adrenal disease.

Decompensation of metabolic processes in patients with chronic adrenal insufficiency, resulting from inadequate replacement therapy against the background of acute infections, injuries, operations, climate change and heavy physical exertion, is accompanied by the development of an acute form of the disease. The development of an Addisonian crisis is sometimes the first manifestation of the disease in latent and undiagnosed Addison's disease, Schmidt's syndrome. Acute adrenal insufficiency constantly threatens patients with bilateral adrenalectomy performed in patients with Itsenko-Cushing's disease and other conditions.

Diseases of the adrenal glands that may cause Addisonian crises include adrenogenital syndrome and isolated aldosterone secretion deficiency. Acute adrenal insufficiency occurs in children with the salt-wasting form of adrenogenital syndrome and in adults during intercurrent diseases and extreme conditions. Its development is possible with secondary adrenal insufficiency: diseases of hypothalamic-pituitary origin and non-endocrine diseases due to exogenous administration of corticosteroids. With hypothalamic-pituitary insufficiency accompanied by a deficiency of ACTH and other tropic hormones, with Simonds syndrome, Sheehan syndrome, etc., surgical removal of pituitary adenomas and radiation therapy for acromegaly, Itsenko-Cushing disease, prolactinomas during stressful situations, there is a possibility of adrenal crises.

A special group consists of patients previously treated with glucocorticoids for non-endocrine diseases. As a result of long-term use of glucocorticoid drugs, their hypothalamic-pituitary-adrenal system function decreases, most often during surgical or infectious stress, adrenal cortex function failure is revealed - an Addisonian crisis develops. Withdrawal syndrome, occurring as acute adrenal insufficiency, occurs in patients with rapid withdrawal of hormones, with their long-term use in various diseases, most often of autoimmune origin. Manifestations of acute adrenal insufficiency develop even without a preceding pathological process in the adrenal glands. The disease caused by thrombosis or embolism of the adrenal veins is called Waterhouse-Friderichsen syndrome. Hemorrhagic infarction of the adrenal glands in this syndrome occurs against the background of meningococcal (classical variant), pneumococcal or streptococcal bacteremia, but can also be observed in cases of poliovirus infection. Waterhouse-Friderichsen syndrome occurs at any age. In newborns, the most common cause of adrenal apoplexy is birth trauma, followed by infectious and toxic factors.

Acute hemorrhages in the adrenal glands have been described in various stresses, major surgeries, sepsis, burns, during treatment with ACTH and anticoagulants, in pregnant women, and in AIDS patients. Severe stress situations lead to bilateral hemorrhages in the adrenal glands in military personnel. Acute infarctions occur during heart surgery for stomach and esophageal cancer. Sepsis and septic conditions in peritonitis and bronchopneumonia may be accompanied by hemorrhages in the adrenal glands. In burn disease, both acute infarctions and decreased hormone secretion by the adrenal cortex occur as a result of prolonged stress.

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Pathogenesis of acute adrenal insufficiency

The pathogenesis of acute hypocorticism is based on decompensation of all types of metabolism and adaptation processes associated with the cessation of secretion of hormones of the adrenal cortex.

In the case of the disease, due to the lack of synthesis of gluco- and mineralocorticoid hormones by the adrenal cortex, the body loses sodium and chloride ions with urine and their absorption in the intestine decreases. Along with this, fluid is excreted from the body. In case of untreated acute adrenal insufficiency, dehydration occurs due to the loss of extracellular fluid and the secondary transition of water from the extracellular space into the cell. Due to the sharp dehydration of the body, the blood volume decreases, which leads to shock. Fluid loss also occurs through the gastrointestinal tract. The onset of uncontrollable vomiting, frequent loose stools are a manifestation of severe electrolyte imbalance.

Potassium metabolism disorder also takes part in the pathogenesis of acute adrenal insufficiency. In the absence of adrenal cortex hormones, its level increases in the blood serum, in the intercellular fluid and in the cells. In conditions of adrenal insufficiency, potassium excretion in the urine decreases, since aldosterone promotes potassium excretion by the distal parts of the convoluted tubules of the kidneys. Excess potassium in the heart muscle leads to a violation of the contractility of the myocardium, local changes may occur, and the functional reserves of the myocardium decrease. The heart is unable to adequately respond to increased stress.

In the acute form of the disease, carbohydrate metabolism is disrupted in the body: blood sugar levels decrease, glycogen reserves in the liver and skeletal muscles decrease, and insulin sensitivity increases. With insufficient secretion of glucocorticoids, glycogen synthesis and metabolism in the liver are disrupted. In response to hypoglycemia, the liver does not increase glucose release. The administration of glucocorticoids by enhancing gluconeogenesis in the liver from proteins, fats, and other precursors leads to the normalization of carbohydrate metabolism. Clinical manifestations of hypoglycemia accompany acute adrenal insufficiency, but in some cases, a hypoglycemic coma develops as a result of a sharp glucose deficiency in the tissues.

With a deficiency of glucocorticoids, the level of urea, the end product of nitrogen metabolism, decreases. The effect of glucocorticoids on protein metabolism is not only catabolic or anti-anabolic. It is much more complex and depends on many factors.

Pathological anatomy of acute adrenal insufficiency

Adrenal lesions in Waterhouse-Friderichsen syndrome may be focal and diffuse, necrotic and hemorrhagic. The most typical for this syndrome is the mixed form - necrotic-hemorrhagic. Changes are more often observed in two adrenal glands, less often - in one.

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