Symptoms of ectopic ACTH production 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.

These symptoms are caused by hypokalemia, which is a consequence of increased excretion of potassium under the influence of excess cortisol production. The potassium content in plasma is usually 3 mmol/l. Its excretion in the syndrome of ectopic ACTH production sometimes reaches large sizes and leads to the development of the so-called potassium diabetes. In this case, the level of potassium in the muscles, heart decreases, which is expressed by characteristic changes in the ECG, the alkaline reserve of the blood and the level of bicarbonates increases. As a result of the excretion of large quantities of this substance from the cells and its replacement with sodium and hydrogen ions, hypokalemic alkalosis develops, which is combined with a compensatory decrease in chlorine; most patients have hypochloremia. An increase in blood volume contributes to the development of hypertension in patients.

Hyperpigmentation of the skin and mucous membranes is a characteristic manifestation of the syndrome of ectopic ACTH production. The shades of pigmentation may be different (smoky, chocolate, brown, almost black with a blue tint). Sometimes, an increase in skin coloration for a long time may be the only sign of an ectopic tumor. In some patients, hyperpigmentation develops simultaneously with symptoms of hypercorticism.

The development of increased pigment deposition in the skin depends on the secretion of ACTH by the ectopic tumor. Moreover, its properties may differ from ACTH of pituitary origin. Therefore, the hormone has different effects on skin color and stimulation of the adrenal glands. Melasma, which develops with the syndrome of ectopic secretion of adrenocorticotropic hormone, can be compared with hyperpigmentation of the skin in patients with a pituitary tumor, with Nelson syndrome and with Addison's disease.

For most patients, the clinical picture of hypercorticism is uncharacteristic. They do not have specific obesity; on the contrary, cachexia often develops. The predominant symptoms are progressive muscle weakness, hyperpigmentation of the skin and mucous membranes, hypokalemic alkalosis, hypertension, impaired carbohydrate tolerance, and emotional lability.

In some patients, ACTH and CRF were detected in tumors, but clinical manifestations of their presence were not observed. The reason for this is either the low activity of the compounds secreted by the tumor or the lack of time for the development of hypercorticism symptoms. Thus, clinical manifestations in patients with ectopic ACTH production syndrome may be typical of Itsenko-Cushing syndrome or partial.

The symptoms of the disease may develop quickly (over several months) or slowly (over several years). In addition to the changes characteristic of hypercorticism, patients with ectopic ACTH secretion syndrome exhibit signs characteristic of a tumor process. They often experience intoxication, manifestations of metastasis to various organs, and symptoms of compression of the vascular-nerve plexuses. Clinical manifestations of ectopic ACTH production syndrome depend not only on hypercorticism, but also on other hormones that the tumor may secrete.

Patients with oat cell tumor of the bronchi have been described, in whom, along with the production of ACTH, secretion of ADH was detected. The combined action of these hormones masked the development of hypokalemia. It is believed that asymptomatic increase in ADH secretion occurs quite often.

Cases of combination of ectopic production of ACTH and growth hormone are very rare. A 37-year-old patient with clinical manifestations of acromegaly, hypercorticism is described; malignant bronchial carcinoid contained ACTH and STH

There is data on an 18-year-old patient with gigantism, Itsenko-Cushing syndrome. After autopsy, ACTH and STH were isolated from carcinoid metastases in the liver. In addition, somatotropinoma was detected.

Cases of tumor secretion of vasopressin, oxytocin, and neurophysin along with ACTH have been published. The authors rely on the determination of serum and urine osmolarity. The presence of vasopressin is detected by reducing the ability of patients to respond to water loading.