Adrenocorticotropic hormone in blood

Reference values for ACTH concentration in blood serum: at 8:00 a.m. - less than 26 pmol/l, at 10:00 p.m. - less than 19 pmol/l.

Adrenocorticotropic hormone is a peptide consisting of 39 amino acid residues with a molecular weight of approximately 4500. ACTH secretion into the blood is subject to circadian rhythms, the concentration is maximum at 6 am, and minimum - approximately at 10 pm. A strong stimulator of ACTH is stress. Half-life in the blood is 3-8 minutes.

Itsenko-Cushing's disease is one of the most severe and complex neuroendocrine diseases of hypothalamic-pituitary genesis with subsequent involvement of the adrenal glands and the formation of total hypercorticism syndrome and associated disorders of all types of metabolism. The pathogenetic basis of Itsenko-Cushing's disease is a feedback disorder in the functional system hypothalamus → pituitary gland → adrenal cortex, characterized by constantly increased activity of the pituitary gland and hyperplasia of corticotrophs or, much more often, the development of ACTH-producing pituitary adenomas and hyperplasia of the cortex of both adrenal glands. In most cases of Itsenko-Cushing's disease, pituitary adenomas are detected (macroadenomas - in 5%, microadenomas - in 80% of patients).

Cushing's disease is characterized by a simultaneous increase in the blood levels of ACTH and cortisol, as well as increased daily excretion of free cortisol and 17-OCS in the urine. Determination of ACTH in the blood is necessary for differential diagnosis of the disease and various forms of Cushing's syndrome. ACTH secretion is significantly reduced in patients with corticosteroma and adrenal cortex cancer (Cushing's syndrome). In individuals with Cushing's disease and ectopic ACTH syndrome (pathological secretion of ACTH by a tumor of non-pituitary origin, most often bronchial cancer or thymoma), the concentration of ACTH in the blood is increased. A CRH test is used for differential diagnosis between the latter two diseases. In Cushing's disease, ACTH secretion after CRH administration increases significantly. ACTH-producing cells of non-pituitary tumors do not have CRH receptors, so the concentration of ACTH does not change significantly during this test.

The syndrome of ectopic ACTH secretion most often develops in lung cancer, carcinoid and bronchial cancer, malignant thymomas, primary thymus carcinoids and other mediastinal tumors. Less often, the syndrome accompanies tumors of the parotid glands, urinary and gall bladder, esophagus, stomach, colon, melanoma, lymphosarcoma. Ectopic ACTH production is also detected in tumors of the endocrine glands: islet cell cancer of Langerhans, medullary thyroid cancer, pheochromocytoma, neuroblastoma, ovarian cancer, testicular cancer, prostate cancer. As a result of prolonged elevated concentration of ACTH in the blood, hyperplasia of the adrenal cortex develops and the secretion of cortisol increases.

The concentration of ACTH in the blood can be from 22 to 220 pmol/l and more. In diagnostic terms, in the syndrome of ectopic ACTH production, ACTH concentrations in the blood above 44 pmol/l are considered clinically significant.

The best method for distinguishing between pituitary and ectopic sources of ACTH is a simultaneous bilateral study of blood from the inferior cavernous sinuses for ACTH content. If the concentration of ACTH in the cavernous sinuses is significantly higher than in the peripheral blood, then the source of ACTH hypersecretion is the pituitary gland. If a gradient between the ACTH content in the cavernous sinuses and peripheral blood is not observed, the source of increased hormone production is most likely a carcinoid tumor of another localization.

Primary adrenal insufficiency (Addison's disease). In primary adrenal insufficiency, as a result of destructive processes in the adrenal cortex, the production of GC, mineralocorticoids and androgens decreases, which leads to disruption of all types of metabolism in the body.

The most common laboratory signs of primary adrenal insufficiency are hyponatremia and hyperkalemia.

In primary adrenal insufficiency, the ACTH concentration in the blood is significantly increased - 2-3 times or more. The secretion rhythm is disrupted - the ACTH content in the blood is increased both in the morning and in the evening. In secondary adrenal insufficiency, the ACTH concentration in the blood decreases. To assess the residual ACTH reserve, a CRH test is performed. In pituitary insufficiency, there is no reaction to CRH. If the process is localized in the hypothalamus (absence of CRH), the test may be positive, but the response of ACTH and cortisol to the introduction of CRH is slow. Primary adrenal insufficiency is characterized by a decrease in the concentration of aldosterone in the blood.

Secondary and tertiary adrenal insufficiency occur as a result of brain damage with subsequent decrease in ACTH production and development of secondary hypoplasia or atrophy of the adrenal cortex. Usually, secondary adrenal insufficiency develops simultaneously with panhypopituitarism, but sometimes isolated ACTH deficiency of congenital or autoimmune origin is also possible. The most common cause of tertiary adrenal insufficiency is long-term use of glucocorticosteroids in high doses (treatment of inflammatory or rheumatic diseases). Suppression of CRH secretion with subsequent development of adrenal insufficiency is a paradoxical consequence of successful treatment of Itsenko-Cushing syndrome.

Nelson syndrome develops after total removal of the adrenal glands in Itsenko-Cushing disease; it is characterized by chronic adrenal insufficiency, hyperpigmentation of the skin, mucous membranes and the presence of a pituitary tumor. Nelson syndrome is characterized by an increase in the concentration of ACTH in the blood. When conducting differential diagnostics between Nelson syndrome and ectopic ACTH secretion, it is necessary to conduct a simultaneous bilateral study of blood from the inferior cavernous sinuses for ACTH content, which allows for clarification of the localization of the process.

After surgical treatment (transsphenoidal surgery with removal of corticotropinoma), determination of the concentration of ACTH in the blood plasma allows one to assess the radicality of the surgery.

In pregnant women, the concentration of ACTH in the blood may be increased.

Diseases and conditions that may alter serum ACTH concentrations

Increased concentration	Decreased concentration
Itsenko-Cushing's disease Paraneoplastic syndrome Addison's disease Post-traumatic and post-operative conditions Nelson's syndrome Adrenal virilism Use of ACTH, insulin, vasopressin Ectopic ACTH production	Adrenal cortex hypofunction Adrenal cortex tumor Tumor secreting cortisol Use of glucocorticosteroids

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