Ectopic ACTH production syndrome - Overview of information

In 1928, WH Brown first described a patient with oat cell lung cancer who had clinical manifestations of hypercorticism: characteristic obesity, striae, hirsutism, and glucosuria. An autopsy revealed enlarged adrenal glands. Evidence that various tumors can secrete ACTH-like substances was obtained later. In 1960, peptides with adrenocorticotropic activity were discovered in lung tumors. This led to the identification of a new disease called "ectopic ACTH production syndrome".

Tumors of endocrine glands and non-endocrine organs can secrete various biologically active substances and are accompanied by the appearance of certain clinical symptoms. Tumors producing ACTH, ADH, prolactin, parathyroid hormone, calcitonin, and various releasing hormones have been described. The frequency of ectopic hormonal secretion is still not well known. It has been shown that 10% of all patients with lung cancer have ectopic secretion of various hormones. One of the first to be described was the syndrome of ectopic ACTH production, and it is the most common among other similar syndromes.

Causes of ectopic ACTH production syndrome

Hypercorticism syndrome caused by ectopic ACTH production is found in tumors of both non-endocrine organs and endocrine glands. Most often, this syndrome develops in tumors of the chest (lung cancer, carcinoid and bronchial cancer, malignant thymomas, primary thymus carcinoids and other mediastinal tumors). Less often, the syndrome accompanies tumors of various organs: parotid, salivary glands, urinary and gall bladder, esophagus, stomach, colon. The development of the syndrome in melanoma and lymphosarcoma has been described. Ectopic ACTH production has also been found in tumors of the endocrine glands. ACTH secretion is often found in cancer of the islets of Langerhans. Medullary thyroid cancer and pheochromocytoma, neuroblastoma occur with the same frequency. Much less frequently, ectopic ACTH production is detected in cancer of the cervix, ovaries, testicles and prostate gland. It has also been found that in many malignant tumors that produce ACTH, clinical manifestations of hypercorticism are not observed. At present, the causes of ACTH production in cell tumors have not yet been found. According to Pearse's assumption in 1966, based on the concept of the APUD system, groups of cells formed from nervous tissue are present not only in the central nervous system, but also in many other organs: the lungs, thyroid and pancreas, the urogenital area, etc. The cells of tumors of these organs, under conditions of uncontrolled growth, begin to synthesize various hormonal substances.

Causes and pathogenesis of ectopic ACTH production syndrome

Symptoms of ectopic ACTH syndrome

Symptoms of ectopic ACTH production syndrome are various degrees of hypercorticism. In case of rapid progression of the tumor process and high production of hormones by the adrenal cortex, typical Itsenko-Cushing syndrome develops. Patients have excessive deposition of subcutaneous fat in the face, neck, trunk, abdomen. The face takes on the appearance of a "full moon". The limbs become thinner, the skin becomes dry, acquires a purple-cyanotic color. Red-violet "stretch" stripes appear on the skin of the abdomen, thighs, inner surfaces of the shoulders. Both general and friction hyperpigmentation of the skin is noted. Hypertrichosis appears on the skin of the face, chest, back. There is a tendency to furunculosis and erysipelas. Blood pressure is elevated. The skeleton is osteoporotic, with severe cases there are fractures of the ribs and vertebrae. Steroid diabetes is characterized by insulin resistance. Hypokalemia of varying degrees depends on the degree of hypercorticism. The development of its symptoms depends on the biological activity and amount of hormones secreted by the tumor and secreted by the adrenal cortex cortisol, corticosterone, aldosterone and androgens.

One of the characteristic and constant symptoms of the ectopic ACTH syndrome is progressive muscle weakness. It is expressed by rapid fatigability, severe fatigue. This is observed to a greater extent in the lower extremities. The muscles become flabby and soft. Patients cannot get up from a chair or climb stairs without assistance. Often, physical asthenia in these patients is accompanied by mental disorders.

Symptoms of ectopic ACTH syndrome

Diagnosis of ectopic ACTH production syndrome

The presence of ectopic ACTH production syndrome can be suspected by a rapid increase in muscle weakness and peculiar hyperpigmentation in patients. The syndrome most often develops between 50 and 60 years of age with equal frequency in men and women, while Itsenko-Cushing's disease begins between 20 and 40 years, and in women 3 times more often than in men. In most cases, women get sick after childbirth. Ectopic ACTH production syndrome caused by osseous cell carcinoma, on the contrary, is more common in young male smokers. Ectopic ACTH syndrome is rarely observed in children and the elderly.

A rare case of ectopic adrenocorticotropic hormone production syndrome caused by nephroblastoma was described in a 5-year-old Japanese girl. Within 2 months, the child developed Cushingoid obesity, facial roundness, darkening of the skin, and age-appropriate sexual development. Blood pressure rose to 190/130 mm Hg, plasma potassium content was 3.9 mmol/l. A significant increase in 17-OCS and 17-CS was detected in daily urine. Intravenous pyelography showed an abnormal configuration of the left kidney, and selective renal arteriography revealed impaired blood circulation in its lower part. The tumor, nephroblastoma, was removed during surgery, and metastases were not detected. The tumor synthesized "large" ACTH, beta-lipotropin, beta-endorphin, and corticotropin-releasing-like activity. After removal of the kidney tumor, the symptoms of hypercorticism regressed and adrenal function returned to normal.

Diagnosis of ectopic ACTH production syndrome

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Treatment of ectopic ACTH production syndrome

Treatment of ectopic ACTH production syndrome can be pathogenetic and symptomatic. The first involves removing the tumor - the source of ACTH and normalizing the function of the adrenal cortex. The choice of treatment for ectopic ACTH production syndrome depends on the location of the tumor, the extent of the tumor process and the general condition of the patient. Radical removal of the tumor is the most successful type of treatment for patients, but it often cannot be carried out due to late topical diagnosis of the ectopic tumor and the widespread tumor process or extensive metastasis. In cases of tumor inoperability, radiation therapy, chemotherapy or a combination of both are used. Symptomatic treatment is aimed at compensating for metabolic processes in patients: eliminating electrolyte imbalance, protein dystrophy and normalizing carbohydrate metabolism.

The vast majority of tumors causing ectopic ACTH production syndrome are malignant, so radiation therapy is prescribed after their surgical removal. M. O. Tomer et al. described a 21-year-old patient with rapid clinical development of hypercorticism caused by thymic carcinoma. The examination results allowed to exclude the pituitary source of ACTH hypersecretion. A tumor in the mediastinum was detected using chest computed tomography. Before the operation, metopirone (750 mg every 6 hours) and dexamethasone (0.25 mg every 8 hours) were administered to reduce the function of the adrenal cortex. A 28 g thymic tumor was removed during the operation. After the operation, external irradiation of the mediastinum was prescribed at a dose of 40 Gy for 5 weeks. As a result of the treatment, the patient achieved clinical and biochemical remission. Many authors consider the combination of surgical and radiation methods for mediastinal tumors to be the best method for treating ectopic tumors.

Treatment of ectopic ACTH production syndrome

Prevention of ectopic ACTH production syndrome

The syndrome of ectopic ACTH production is much more common in male smokers and is caused by cancer of the lungs, bronchi, and mediastinum. In this regard, the fight against smoking can play a positive role in preventing the disease.

Prognosis for ectopic ACTH syndrome

The prognosis in most cases is poor, depending on the degree of malignancy of the process, its spread, the severity of hypercorticism and the time of diagnosis. Most patients lose their ability to work.