Treatment of acromegaly and gigantism

Treatment of acromegaly should be comprehensive and carried out 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 STH-secreting tumor, which is achieved using radiological, surgical, pharmacological methods of treatment and their combination. The correct choice of treatment method 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, disruption of the functional activity of various organs and systems, agents that correct neurological, endocrine and metabolic disorders are added to the treatment.

The most common methods of treating the disease include various types of external irradiation (X-ray therapy, tele-y-therapy of the interstitial-pituitary region, proton beam irradiation of the pituitary gland). Less commonly used are implantation of radioactive isotopes into the pituitary gland - gold ( ¹⁹⁸ Au) and yttrium ⁹⁰ I) - in order to destroy tumor cells, as well as cryodestruction of the tumor using 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 irradiation of the pituitary gland with a proton beam (at a dose of 45 Gy to 150 Gy depending on the tumor volume). Irradiation is indicated in the active phase of acromegaly and the absence of rapid development of visual and neurological disorders, severe cephalgic syndrome, as well as in cases of 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 extend beyond the sella turcica, the method of choice is selective transnasal transsphenoidal adenomectomy, which provides direct impact on the pituitary tumor with minimal trauma to the surrounding tissues. Complications associated with surgery (liquorrhea, meningitis, hemorrhage) are rare (less than 1% of cases). With significant pituitary tumor sizes and extrasellar growth, adenomectomy is performed using a transfrontal approach. Indications for such surgery are progressive narrowing of the visual fields, neurological disorders, persistent headaches, and suspicion of a malignant tumor.

Early signs of clinical remission include disappearance of sweating, reduction in skin fold thickness and soft tissue size, decreased swelling, normalization of blood pressure and carbohydrate metabolism indices. An objective criterion for 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 somatotropic hormone to thyroliberin, L-dopa, and parlodel. The described methods are the only ones adequate for controlling somatotropic secretion in patients with the pituitary form of acromegaly. A positive effect of irradiation is observed in 60% of cases. A decrease in 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, a positive effect is revealed much earlier. The optimal option in this case is a combination of surgical treatment with subsequent radiation therapy.

The idea of the central origin of acromegaly contributed to the introduction into clinical practice of drugs that selectively affect certain monoaminergic systems of the brain and correct somatotropic secretion. The positive effect of alpha-adrenoblockers (phentolamine) and antiserotonergic drugs (cyproheptadine, methysergide) in acromegaly has been described.

The positive effect of dopaminergic receptor stimulants (L-dopa, apomorphine, bromocriptine and its analogues - abergin, pergolide, norprolac) in the disease has been proven. The most promising of the drugs in this series is parlodel (2-bromo-a-ergocryptine, bromocriptine) - a semi-synthetic ergot alkaloid, which has a selective, prolonged effect, blocking somatotropic secretion. Normally, the drug promotes an increase in the level of growth hormone in the blood, while in acromegaly, according to various authors, in approximately 40-60% of cases there is a paradoxical reaction to the administration of the drug, expressed in a significant decrease in the level of somatotropic 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 improves the clinical condition, restores impaired functions and correlates with the normalization of biochemical and hormonal parameters. Under the influence of parlodel, which causes a reversible blockade of hypersecretion of somatotropic hormone, an increase in the number of electron-dense granules in the cytoplasm of tumor cells and a violation of exocytosis are observed, which indicates changes in the secretion of the hormone, and not the synthetic capabilities of tumor cells.

Before starting treatment, the degree of sensitivity to the drug should be established by a single administration of 2.5 mg (1 tablet) of parlodel. A decrease in the level of somatotropic hormone in the blood serum by 50% or more from the initial level within 4 hours after taking the drug is a criterion for 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 of the drug per day. The effectiveness of therapy is not affected by the initial level of somatotropic hormone, prior treatment, as well as gender and age differences. With long-term use, an "escape" syndrome may be observed, i.e. loss of sensitivity to the drug, which requires an increase in the dose or a change in the treatment method.

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

A promising agent for controlling somatotropic secretion in acromegaly is somatostatin, but its short duration of action limits its widespread clinical use. Currently, somatostatin analogues with a duration of action of up to 9 hours have appeared. The introduction of prolonged forms of somatostatin will allow for effective physiological correction of the somatotropic function in forms associated with hypersecretion of growth hormone. The following somatostatin analogues are currently used: octreotide (200-300 mcg/day), depot-octreotide - sandostatin-LAR (3-30 mg intramuscularly once every 28 days), intranasal form of octreotide (500 mcg/day).

Symptomatic treatment of acromegaly is primarily associated with the correction of existing endocrine and somatic disorders. Since diabetes mellitus in acromegaly is characterized by pronounced insulin resistance, it is preferable to use oral hypoglycemic drugs, mainly from the biguanide group. In the presence of secondary hypofunction of the thyroid gland, adrenal glands, and sex glands, 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 characteristics of the disease. In the benign course, the prognosis for life and ability to work is favorable. Adequate treatment promotes long-term remission for many years. In the malignant course, the prognosis is determined by the timeliness of tumor removal. A fatal outcome is usually a consequence of cardiovascular and pulmonary insufficiency, as well as cerebral disorders and diabetes mellitus. The ability to work depends on the stage and course of the disease. In the benign course of acromegaly, ability to work is maintained for a long time. Persistent loss of working capacity is associated with the development of panhypopituitarism, visual and neurological disorders, pronounced changes in the musculoskeletal system, progression of cardiopulmonary insufficiency, and severe diabetes mellitus.

Patients with acromegaly require constant medical supervision by an endocrinologist, neurologist, and ophthalmologist.

There is no clear data on the effectiveness of acromegaly prevention. The occurrence of transient acromegaloid changes in women during puberty or pregnancy is a relative contraindication for subsequent pregnancies. Such patients should refrain from abortions and castration. From this standpoint, proper treatment of hypergonadotropic hypogonadism and climacteric syndrome is a prevention of acromegaly. Prevention of complications associated with the disease comes down to timely diagnosis of acromegaly and the adequacy of the treatment.