Ectopic ACTH Production Syndrome: A Review of Information

For the first time WH Brown in 1928 described a patient with ovarian cell lung cancer who had clinical manifestations of hypercorticism: characteristic obesity, striae, hirsutism, glucosuria. An autopsy was found at the autopsy. Evidence that different tumors can release ACTH-like substances was obtained later. In 1960, peptides with adrenocorticotropic activity were detected in lung tumors. This was the reason to identify a new disease called "syndrome of ectopic AKTH production.

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

The causes of the syndrome of ectopic production of ACTH

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

Causes and pathogenesis of the syndrome of ectopic production of ACTH

Symptoms of the syndrome of ectopic production of ACTH

Symptoms of the syndrome of ectopic production ACTH is a different degree of hypercorticism. In the case of rapid progression of the tumor process and high production of hormones, the adrenal cortex develops a typical Itenko-Cushing syndrome. In patients, excessive deposition of subcutaneous fat in the face, neck, trunk, abdomen is noted. The face acquires the form of a "full moon". The limbs are thin, the skin becomes dry, acquires a purplish-cyanotic color. Appear red-violet strips of "stretching" on the skin of the abdomen, thighs, inner surfaces of the shoulders. There is a general, and in places of friction, hyperpigmentation of the skin. On the skin of the face, chest, back appears hypertrichosis. There is a tendency to furunculosis and development of erysipelas. The arterial pressure is increased. The skeleton has been osteoporotically changed, with a severe course there are fractures of the ribs and vertebrae. Steroid diabetes is characterized by insulin resistance. Hypokalemia of varying degrees depends on the degree of hypercortisy. The development of his symptoms depends on the biological activity and the amount of hormones secreted by the tumor and secreted by the cortex of the adrenals of cortisol, corticosterone, aldosterone and androgens.

One of the characteristic and persistent symptoms of the syndrome of ectopic production of ACTH is a progressive muscle weakness. It is expressed by fast fatigue, pronounced fatigue. To a greater degree this is observed in the lower limbs. The muscles become flabby and soft. Patients can not get up from the chair or climb the stairs without help. Often, physical asthenia in these patients is accompanied by mental disorders.

Symptoms of the syndrome of ectopic production of ACTH

Diagnosis of the syndrome of ectopic production of ACTH

The presence of the syndrome of ectopic production of ACTH can be suspected with the rapid growth in patients of muscle weakness and peculiar hyperpigmentation. The syndrome often develops between 50 and 60 years of life with equal frequency in men and women, while Itenko-Cushing's disease begins between 20 and 40 years, and in women is 3 times more likely than in men. She is in most cases sick of women after childbirth. The syndrome of ectopic AKTG production, caused by ovine cell carcinoma, on the contrary, is more common in young smokers. It is not often that the syndrome of ectopic production of ACTH is observed in children and people of advanced age.

A rare case of the syndrome of ectopic production of adrenocorticotropic hormone, caused by nephroblastoma, was described in a Japanese girl of 5 years. Within 2 months the child developed cushingoid obesity, roundness of the face, darkening of the skin, sexual development was consistent with age. Arterial blood pressure rose to 190/130 mm Hg. The potassium content in the plasma was 3.9 mmol / l. A significant increase in 17-ACS and 17-CS in daily urine was found. Intravenous pyelography showed a violation of the configuration of the left kidney, and in selective renal arteriography, a violation of the blood circulation of its lower part was detected. The operation removed the tumor - nefroblastoma, 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 hypercorticosis regressed, and the function of the adrenal glands normalized.

Diagnosis of ectopic syndrome of ACTH

[1], [2], [3], [4], [5], [6]

Treatment of the syndrome of ectopic production of ACTH

Treatment of the syndrome of ectopic production ACTH can be pathogenetic and symptomatic. The first is to remove the tumor - the source of ACTH and in the normalization of the function of the adrenal cortex. The choice of a method of treatment in the syndrome of ectopic production of ACTH depends on the location of the tumor, the vastness of the tumor process and the general condition of the patient. Radical tumor removal is the most successful type of treatment for patients, but often can not be done because of late topical diagnosis of the ectopic tumor and the widespread tumor process or extensive metastasis. In cases of inoperability of the tumor, radiotherapy, chemotherapeutic treatment, or a combination thereof is used. Symptomatic treatment is aimed at compensating metabolic processes in patients: elimination of electrolyte imbalance, protein dystrophy and normalization of carbohydrate metabolism.

The vast majority of tumors that cause the syndrome of ectopic AKTH production are malignant, therefore, after their prompt removal, radiation treatment is prescribed. M.O. Tomer et al. Described a patient at the age of 21 with a rapid clinical development of hypercorticism caused by thymus carcinoma. The results of the examination made it possible to exclude the pituitary source of hypersecretion of ACTH. Using a computed tomography of the chest, a tumor in the mediastinum was found. Before the operation to reduce the function of the adrenal cortex, methopyron (750 mg every 6 hours), dexamethasone (0.25 mg after 8 hours) was treated. The operation removed the thymus tumor with a mass of 28 g. After the operation, an external irradiation of the mediastinum in a dose of 40 Gy for 5 weeks was prescribed. As a result of the treatment, the patient underwent clinical and biochemical remission. Combination of surgical and radiation methods in mediastinal tumors is considered by many authors to be the best method for treating ectopic tumors.

Treatment of the syndrome of ectopic production of ACTH

Prevention of the syndrome of ectopic production of ACTH

Syndrome of ectopic products ACTH is much more common in men who smoke and is caused by lung, bronchial, mediastinal cancer. In this regard, the fight against smoking can play a positive role in the prevention of the disease.

Prognosis in the syndrome of ectopic production of ACTH

The prognosis in most cases is poor, depends on the degree of malignancy of the process, its distribution, the severity of hypercorticism and the time of diagnosis. The disability in most patients is lost.