Treatment of acromegaly and gigantism

Treatment of acromegaly should be comprehensive and conducted taking into account the form, stage and phase of disease activity. First of all, it is aimed at reducing the level of growth hormone in the blood serum by suppressing, destroying or removing the active STG-secreting tumor, which is achieved with the help of radiological, surgical, pharmacological methods of treatment and their combination. The correctness of the choice of the method of treatment and its adequacy are the prevention of the development of subsequent complications. In the presence of complications associated with the loss of tropic functions of the pituitary gland, a violation of the functional activity of various organs and systems, the means that correct neurological, endocrine and metabolic disorders are connected to treatment.

The most common methods of treating the disease include various types of external exposure (X-ray therapy, tele-u-therapy of the interstitial-pituitary region, irradiation of the pituitary with a proton beam). Less commonly used implantation in the pituitary gland of radioactive isotopes - gold ( ¹⁹⁸ AU) and yttrium ⁹⁰ I) - for the destruction of tumor cells, as well as cryodestruction of the tumor with the help of liquid nitrogen. Irradiation of the pituitary gland causes perivascular hyalinosis, which occurs 2 or more months after irradiation. Among the listed methods, the most promising is the irradiation of the pituitary with a proton beam (at a dose of 45 Gy to 150 Gy, depending on the tumor volume). Irradiation is shown with the active phase of acromegaly and the absence of rapid development of visual and neurologic disorders, expressed cephalgic syndrome, as well as ineffectiveness of previous surgical treatment or contraindications to it.

Indications for surgical treatment are now significantly expanded. If the pituitary tumor is small and does not go beyond the Turkish saddle, selective transnasal transsphenoidal adenomectomy is the method of choice, which provides a direct effect on the pituitary tumor with minimal traumatization of surrounding tissues. Complications associated with the operation (liquorrhea, meningitis, hemorrhage), are rare (less than 1% of cases). With significant pituitary tumor size and extrasellar growth, adenomectomy is performed by transfrontal access. Indication for this operation is a progressive narrowing of the fields of vision, neurological disorders, persistent headaches, as well as a suspicion of a malignant tumor.

Early signs of clinical remission include the disappearance of sweating, a decrease in the thickness of the skin fold and the size of soft tissues, a decrease in edema, a normalization of blood pressure and carbohydrate metabolism. An objective criterion of the adequacy of the treatment is a decrease in the level of somatotropic hormone in the blood serum, loss of the initial paradoxical sensitivity of the growth hormone to thyroidiberin, L-dofa, parlodel. The described methods are the only adequate for control of somatotropic secretion in patients with pituitary form of acromegaly. The positive effect of irradiation is noted in 60% of cases. Reduction of the level of growth hormone in the blood and remission of the disease are usually observed 1-2 years after irradiation. In the case of surgical intervention, the positive effect is revealed much earlier. The optimal option here is a combination of surgical treatment followed by radiotherapy.

The idea of the central origin of acromegaly promoted the introduction into clinical practice of drugs that selectively affect certain monoaminergic systems of the brain and correct the growth hormone secretion. A positive effect with acromegaly of alpha-adrenoblockers (phentolamine) and antiserotonergic drugs (cyproheptadine, metisergide) is described.

The positive effect of stimulants of dopaminergic receptors (L-dopa, apomorphine, bromocriptine and its analogs - abergin, pergolide, norprolac) is positive in the disease. The most promising of these drugs is parlodel (2-bromo-a-ergocryptin, bromocriptine), a semisynthetic ergot alkaloid that has a selective, prolonged action that blocks the growth hormone secretion. Normally, the drug helps to increase the level of growth hormone in the blood, while in acromegaly, according to different authors, approximately in 40-60% of cases there is a paradoxical reaction to the administration of the drug, expressed in a significant decrease in the level of growth hormone. The manifestation of this phenomenon is associated with a change in the receptor activity of adenomatous cells, which is characteristic of the hypothalamic form of acromegaly. The use of parlodel helps improve the clinical state, restore impaired functions and correlates with the normalization of biochemical and hormonal parameters. Under the influence of the parlodel, which causes a reversible blockade of the hypersecretion of the somatotropic hormone, an increase in the number of electronically dense granules in the cytoplasm of tumor cells and the violation of exocytosis are observed, which indicates changes in the secretion of the hormone, rather than the synthetic abilities of tumor cells.

Before the start of treatment should establish a degree of sensitivity to the drug by a single injection of 2.5 mg (1 tablet) of parlodel. Reduction of the level of somatotropic hormone in blood serum by 50% or more from the initial for 4 hours after taking the drug is a criterion of its effectiveness with subsequent long-term use. The initial dose of the drug is 2.5 mg with a gradual increase. Parlodel is administered 6 hours (4 times a day) after meals. The optimal therapeutic dose is 20-30 mg per day. The effectiveness of therapy is not affected by the initial level of growth hormone, pre-treatment, as well as gender and age differences. With prolonged use, there may be a "slippage" syndrome, that is, loss of sensitivity to the drug, which requires an increase in dose or a change in the method of treatment.

The use of the drug in the presence of sensitivity to it is indicated in combination with routine methods of treatment. Parlodel is recommended to be used as a means of preoperative preparation, as well as in the period after completion of radiation treatment before the appearance of the clinical effect of irradiation. As a monotherapy, it can be used with ineffectiveness or contraindications to routine methods of treating acromegaly. In this case, therapy with parlodel should be carried out for life, since even with the long-term use of the drug, its withdrawal leads to a repeated increase in the level of growth hormone and an exacerbation of the disease.

Somatostatin is a promising tool that allows to control somatotropic secretion in acromegaly, but the short duration of its action limits the wide clinical use of the drug. At present, analogs of somatostatin with a duration of up to 9 hours have appeared. The introduction of prolonged forms of somatostatin will allow for effective physiological correction of somatotropic function in forms associated with hypersecretion of growth hormone. The following somatostatin analogues are currently used: octreotide (200-300 μg / day), depot-octreotide-sandostatin-LAR (3-30 mg IM once every 28 days), intranasal form of octreotide (500 μg / day).

Symptomatic treatment of acromegaly is associated primarily with the correction of existing endocrine and somatic disorders. Because diabetes mellitus is characterized by pronounced insulin resistance in acromegaly, it is preferable to use oral hypoglycemic drugs, mainly from the biguanide group. In the presence of secondary hypothyroidism of the thyroid gland, adrenal glands, gonads, compensatory hormone replacement therapy is performed.

Prognosis, prevention of acromegaly and gigantism

The prognosis for acromegaly is determined primarily by the severity of the tumor syndrome and the peculiarity of the course of the disease. With a benign course, the prognosis regarding life and work capacity is favorable. Adequate treatment contributes to long-term multi-year remission. In malignant course, the prognosis is determined by the timeliness of tumor removal. Lethal outcome, as a rule, is a consequence of cardiovascular and pulmonary insufficiency, as well as cerebral disorders and diabetes mellitus. The ability to work of patients depends on the stage and course of the disease. In benign acromegaly, the ability to work persists for a long time. A persistent loss of capacity for work is associated with the development of panhypopituitarism, visual and neurological disorders, pronounced changes in the osteoarticular apparatus, progression of cardiopulmonary insufficiency, and a severe course of diabetes mellitus.

Patients with acromegaly need constant follow-up at the endocrinologist, neurologist, and ophthalmologist.

There are no clear data on the effectiveness of acromegaly prophylaxis. The appearance of transient acromegaloid changes in women during puberty or during pregnancy is a relative contraindication for subsequent pregnancies. Such patients should abstain from abortion, castration. From these positions, the correct treatment of hypergonadotropic hypogonadism, climacteric syndrome is the prevention of acromegaly. Prevention of complications associated with the disease is reduced to the timely diagnosis of acromegaly and the adequacy of the treatment.