Acromegaly and gigantism are neuroendocrine syndromes resulting from excessive production or increased biological activity of growth hormone.
These two diseases should be considered as age-related variations of the same pathological process, the specific clinical manifestations of which are determined by the degree of completion of osteogenesis.
In children and adolescents with an incomplete growth, chronic hyperproduction of growth hormone is manifested by gigantism, characterized by excessive, exceeding the physiological limits, relatively proportional to the growth of epiphyseal and periostal bones, an increase in soft tissues and organs.
In adults, since after ossification of the epiphyseal cartilage, further growth is impossible, acromegaly develops. With this pathology, there is an accelerated growth of the body, but not in length, but in width due to soft tissues, which manifests itself as a disproportionate periosteal growth of the bones of the skeleton, an increase in the mass of internal organs and a characteristic metabolic disorder.
Etiology
Based on the classical scheme of the hypothalamic – hypophysial regulation of somatotropic function, a number of possible mechanisms can be distinguished that contribute to its hyperfunction and characteristic clinical manifestations:
1) an initial dysregulation at the level of the hypothalamus or the overlying sections of the central nervous system, which is realized in the excessive formation of somatoliberin or insufficient secretion of somatostatin;
2) the initial occurrence of a tumor process in the hypophysis with impaired hypothalamic control and autonomous hypersecretion of growth hormone or its active forms;
3) an increase in the formation and activity of somatomedins, which directly affect the growth of the osteo-articular apparatus. The most common cause of the development of acromegaly and gigantic
MA is an autonomous production of growth hormone by adenoma hypophysis.
In most cases, macromega adenoma is detected in acromegaly. By their origin, somatotropinomas (tumors from somatotrophs of the adenohypophysis) are monoclonal tumors that develop as a result of somatic mutations of somatotrophs.
In acromegaly, pituitary adenomas secreting growth hormone are detected in 99% of cases. Immunohistochemically, along with pure somatotropic adenomas (about 45%), mixed prolactosomotropinomas (about 30%) are isolated. The remaining 25% of adenomas, in addition, produce other adeno-pituitary hormones (TSH, LH, FSH).
Ectopic growth hormone production with the development of acromegaly is rare in lung cancer, breast cancer, pancreatic and ovarian tumors.
Pathogenesis
Changes in the organs during acromegaly are reduced to their true hypertrophy and hyperplasia (splanchnomegaly), which is associated with the predominant growth of mesenchymal tissues. Increased parenchyma and stroma of all internal organs (lungs, heart, liver, pancreas, intestine, spleen). With the progression of the disease due to proliferation of the connective tissue, sclerotic changes occur in all organs, accompanied by the progressive development of their insufficiency. In parallel, there is an increase in the risk of benign and malignant tumors in all tissues and organs, including endocrine ones.
Clinic
In most cases, acromegaly develops between the ages of 30 and 50, is more common in women, since both pregnancy itself and its non-physiological interruption are factors that activate somatotropic function. The overwhelming majority of cases of gigantism and acromegaly are sporadic. Acromegaly occurs with a frequency of 3-4 cases per 1 million population.
Acromegaly is clinically manifested by an increase in hands, feet, changes in appearance, carbohydrate metabolism disorders, the menstrual cycle, and other symptoms.
Intracranial hypertension syndrome: an increase in intracranial pressure or compression of the diaphragm of the Turkish saddle by a growing tumor causes the development of headaches with acromegaly. In the latter case, headaches are the most stubborn character, driving the patient to a frenzy.
Syndromes associated with the effect of growth hormone on organs and tissues are manifested by a progressive pathological increase in linear growth and body size, hands, feet, nose, mandible, because of which patients are often forced to change shoes and gloves. The change in appearance, which is manifested by the deification of the facial features, is associated with an increase in the superciliary arches, zygomatic bones, and mandible. There is hypertrophy of the soft tissues of the face (nose, lips, ears).
An increase in the mandible leads to a change in the bite due to the divergence of the interdental spaces. The tongue is enlarged (makoglossiya), teeth are imprinted on it.
An increase in the quantity and an increase in the functional activity of the sweat glands leads to significant sweating. Activation and hypertrophy of the sebaceous glands, thickening of the skin lead to its characteristic appearance (it becomes dense thickened, with deep folds, more pronounced on the hairy part of the head. In the area of skin folds and areas of increased friction, hyperpigmentation is noted.
Hypertrichosis is often detected.
The effect of growth hormone on the muscles and internal organs at the initial stages of the disease is hardly noticeable, and sometimes, especially among athletes and physical workers, is perceived positively, as working capacity and physical activity increase, but as the disease progresses, the muscle fibers degenerate ( due to proliferation of the connective tissue and the relative lag in the growth of blood vessels from an increase in mass), causing an increasing weakness, a progressive decrease in efficiency.
Because of the impaired blood supply and sclerotherapy of hypertrophied internal organs, pulmonary and cardiac failure develops, causing the death of patients.
Sleep apnea syndrome develops in 80% of patients with acromegaly. This is due to the proliferation of soft tissues of the upper respiratory tract and damage to the respiratory centers. Uncompensated long-term hyperproduction of growth hormone leads to the development of concentric myocardial hypertrophy, which is replaced by hypertrophic myocardiodystrophy, and in advanced cases of the disease it becomes dilated, leading to progressive heart failure.
The syndrome of reproductive disorders associated with concomitant hyperproduction of prolactin, or with prolactin-like effects of growth hormone, is manifested in a menstrual disorder up to amenorrhea, and often in galactorrhea in women, and impotence in men.
The syndrome of endocrine disorders associated with the effect of growth hormone on various types of metabolism, as well as changes in the activity of other endocrine glands, manifests as impaired glucose tolerance and obvious diabetes mellitus, changes in calcium phosphate metabolism, impaired fat metabolism, an increase in thyroid gland . As the tumor progresses, the clinical picture of hypothalamic-hypophysial insufficiency develops, including the formation of secondary hypothyroidism, hypocorticism, hypogonadism.
Cranial nerve dysfunction syndrome: chiasmatic syndrome (bitemporal hemianopia, narrowing of the visual fields); changes in the fundus include swelling and atrophy of the visual nerve disc; compression of the hypothalamus and violation of cerebrospinal fluid dynamics lead to drowsiness, sometimes to polyuria, there may be temperature rises, epileptiform syndrome, anosmia, ptosis, double vision, decreased sensitivity of the skin, hearing loss.
Diagnostics
Laboratory diagnostics of acromegaly is based on the study of growth hormone levels. In many patients, it is sharply elevated, and in this case, with the expanded clinical picture, the diagnosis can be considered established. However, in a number of patients, the level of growth hormone is only slightly elevated or corresponds to normal (0.5–5.0 ng / ml). In this regard, a number of functional tests were proposed. The glucose tolerance test implies a study of the plasma level of growth hormone initially, as well as in blood samples every 30 minutes for 2.5-3 h after administration of 75 g of glucose. Normally, with a glucose load, the level of growth hormone decreases. In the active phase of acromegaly, the level of growth hormone does not decrease below 2 × ng / ml, or a paradoxical increase in the level of growth hormone is detected. In 60% of cases with acromegaly, a pathological increase in growth hormone levels (by 50–100% from baseline and more) is determined 30–60 minutes after administration of tyroliberin (500 μg intravenously). Normally, there is no reaction to thyroliberin.
With clinically manifest and hormonally confirmed acromegaly, topical diagnosis of pituitary adenoma is usually not a problem. In macroadenomas, characteristic changes on the craniogram are detected; MRI is the method of choice for imaging adenoma.
Treatment
The goal of treating acromegaly is the elimination of autonomous hyperproduction of growth hormone, normalization of the level of IGF-1 in the blood and the absence of an increase in the plasma level of growth hormone in the glucose tolerance test (75 g glucose) above 1 ng / ml. These criteria correspond to the remission of the disease. This goal is achieved by removing a pituitary tumor or reducing the tumor mass.
The method of choice in treating patients with acromegaly is transsphenoidal removal of pituitary adenoma. In 85% of cases of microadenomas, the level of growth hormone after surgery returns to normal. In the case of small encapsulated adenomas, surgical treatment usually results in a persistent disease remission. In macroadenomas, full recovery after the first operation is achieved in 30% of cases. Tumors with extracellular growth have the worst prognosis. With the help of proton therapy on the pituitary gland in most patients, it is possible to achieve a decrease in the level of growth hormone rez 1 year after the course of treatment. However, 10 years after proton therapy in 70% of patients, the spontaneous level of growth hormone does not exceed 10 ng / ml on average.
For drug therapy, which can only be regarded as temporary or palliative, dofaminomimetics and somatostatin analogues are currently used.
When treating with dopaminomimetics (bromocryptic, parlodel), 54% of patients have a decrease in growth hormone levels below 10 ng / ml, and only 20% have less than 5 ng / ml. A reduction in tumor size is noted in no more than 20% of patients. Treatment with somatostatin analogues (octreotide, sandostatin) is much more effective. In 90% of patients, a decrease in the level of GH is determined, in 53% of patients the level of GH is reduced below 5 ng / ml. There is evidence of a greater percentage of radically performed adenomectomies if the operation was preceded by treatment with octreotide.