Gigantism and acromegaly - symptoms and signs, diagnosis, treatment
Gigantism and acromegaly - symptoms and signs, diagnosis, treatment of acromegaly.
Gigantism and acromegaly
Gigantism and acromegaly are hypersecretion syndromes of GH (hypersomatotropism), almost always a consequence of the development of pituitary adenoma. In the case of the development of the tumor process before the closure of the epiphyseal growth zones, the result is the development of gigantism. If the tumor begins to develop after the closure of the growth zones, the result will be acromegaly with the emergence of characteristic external clinical signs. The diagnosis is made clinically, confirmed by radiography of the skull and hands, as well as the level of GH. Treatment consists in surgical removal or destruction of the adenoma that caused pathological changes.
Many adenomas secreting GH contain mutated Gs protein, which is an adenylate cyclase stimulator.Cells containing the mutant form of the Gs protein are able to secrete GH even in the absence of secretion of the releasing growth hormone factor (RFGR). Several cases of ectopic RFGR-secreting tumors have been described, mostly with localization in the pancreas and lungs.
Symptoms and signs of gigantism and acromegaly
Pituitary gigantism.This is a rather rare condition, it develops in the case of the onset of hypersecretion of GH in childhood, before the epiphyseal growth zones are closed. The growth rate of the skeleton in length and the maximum achievable growth are increased, but with small deformations of the bone tissue. Nevertheless, there is hypertrophy of soft tissues and an increase in peripheral innervation. Delayed puberty or hypogonadtropic hypogonadism is also often present, forming a characteristic eunuchoid physique.
Acromegaly. In acromegaly, hypersecretion of GH begins between the ages of 20 and 40 years. When hypersecretion of GH begins after the closure of the epiphyseal growth zones, the earliest clinical manifestations include a change in facial features and soft tissues (in the direction of expansion and thickening) of the arms and legs.The appearance of these changes in patients causes the need to increase the size of clothing and accessories (rings, gloves) and shoes. Photographing patients in dynamics is an important point in documenting the progress of the disease over time.
In adults with acromegaly, there is a slight increase in body hair and thickening and thickening of the skin and often darkening. The size and function of the sweat and sebaceous glands increase to such an extent that patients often complain of excessive sweating and unpleasant body odor. Hypertrophy of the lower jaw leads to its protrusion and the formation of abnormal bite. Proliferation of laryngeal cartilage leads to a low, hoarse voice. The tongue is enlarged, has a groove-like shape and is often coated. With a long course of acromegaly, pathological hypertrophied bone growth leads to the formation of a barrel-shaped chest. The proliferation of articular cartilage is an early clinical sign of hypersecretion of GH with the possible development of their erosion and necrosis. Often, articular symptoms progress, and degenerative arthritis may occur, leading to disability.
Compression of the nerve trunks, due to the growth of connective tissue and the development of endoneural fibrosis, often leads to the development of peripheral neuropathy. Patients often complain of headaches due to tumor growth. With supra-specific tumor growth and mechanical compression of the area of optic chiasm, a bitemporal hemianopsia can be observed. The heart, liver, spleen, thyroid and parathyroid glands and pancreas are enlarged. Approximately in patients the development of cardiovascular pathology and a doubly increased risk of cardiac death can occur. Hypertension develops in patients. The risk of malignant neoplasms, especially gastrointestinal localization, is doubled. GH enhances tubular reabsorption of phosphates and leads to moderate hyperphosphatemia. Impaired glucose tolerance occurs in almost 50% of patients with acromegaly and gigantism, but overt diabetes develops in only 10% of patients.
Galactorrhea occurs in some women with acromegaly and is usually associated with hyperprolactinemia.Nevertheless, lactation can also occur with isolated hypersecretion of GH, since the stimulant of lactation is the GH itself. In patients with GH secreting tumors, gonadotropin secretion is often reduced. At about1/ s men with acromegaly develop erectile dysfunction and almost all women have a menstrual disorder or amenorrhea.
Diagnosis of gigantism and acromegaly
The diagnosis is based on a characteristic clinical symptomatology. CT, MRI or radiography of the skull can help confirm the diagnosis when cortical swelling is detected, the frontal sinuses are enlarged, and the size and erosion of the Turkish saddle is increased. On the radiograph of the hands noticeable thickening of the terminal phalanges of the fingers and hypertrophy of soft tissues. As a rule, there is a violation of glucose tolerance and an increase in blood serum phosphates.
Plasma GH levels, usually measured by the radioimmunoassay method, are usually elevated, and the results of the simplest tests to evaluate its secretion are in favor of GH hypersecretion. Blood sampling should be performed in the patient on an empty stomach, before breakfast (basal level), in healthy people it is less than 5 ng / ml.A transient increase in the level of GH is normal and should be differentiated from its pathological secretion. The degree of suppression of GH secretion after glucose load should be determined in patients with elevated levels of GH in plasma as a mandatory standard of management. However, the test results significantly depend on the adherence to the test procedure, and it is difficult to distinguish the result from the normal suppression of GH in response to glucose administration. The secretion of GH in healthy people is suppressed to less than 2 ng / ml (less than 1 ng / ml is often taken as the norm) in the 90th minute after the administration of 75 g of oral glucose. Most patients with acromegaly have levels of GH that are significantly higher than those indicated. The level of basal GH in plasma is also important in the monitoring process to assess the effectiveness of therapy.
Plasma insulin-like factor (IGF-1) should be determined in patients with a presumptive diagnosis of acromegaly; IGF-1 levels are usually steadily elevated (3–10 times). IGF-1 level monitoring can be used to control therapy. To detect a tumor, CT or MRI of the head is performed.If the tumor is not visualized, hypersecretion of GH can be a consequence of tumor growth with localization of the process outside the CNS, with significant secretion of ectopic releasing factor of growth hormone (RFGR). A proven high plasma RFGR level can confirm the diagnosis. If you suspect the presence of ectopic sources of RFGR secretion (capabilities), the lungs and pancreas should be investigated first.
Treatment of gigantism and acromegaly
As a rule, radical therapy is prescribed using surgical methods or radiation therapy. It is preferable to perform transsphenoidal resection of the pituitary gland, however, the options for a therapeutic approach vary greatly depending on the capabilities of the institution. Stereotactic high-voltage irradiation of the pituitary at a dose of about 5,000 cGy) is used, however, the level of GH may not be reduced to the norm over several years. Treatment using accelerated protons (irradiation with heavy particles) allows the pituitary gland to act with a higher dose of radiation (equivalent to a dose of up to 10,000 cGy); however, this tactic of therapy determines the high risk of damage to the cranial nerves and hypothalamus and is used only in a few clinical centers.As a rule, within a few years, a decrease in the function of the pituitary gland develops. Due to the cumulative effect of radiation exposure, proton beam therapy is not performed after the previous traditional gamma therapy. Patients with progressive extrasselar tumor growth and patients who cannot be, for any reason, complete resection of the tumor, which is quite common, are prescribed combined (surgical and radiotherapy) treatment.
Pegvisomant, a receptor blocker for GH, has been shown to level its tissue effects and reduce the level of IGF-1 in patients with acromegaly without an apparent increase in the size of the pituitary tumor. This drug can find its therapeutic niche in patients with partial or complete resistance to treatment with somatostatin analogues.
Surgical removal of the tumor, apparently, can be considered successful only if the level of GH after the test for glucose tolerance and the level of IGF-1 returns to normal values. If one of these parameters or both differ from the norm, then, as a rule, the patient needs further therapy.If the reduction in the level of GH is not enough and it remains high, arterial hypertension develops, heart failure and the risk of death will increase by 2 times. If the level of GH is less than 5 ng / ml, mortality does not increase.
As a rule, drug therapy is prescribed if surgical treatment and radiation therapy are contraindicated, or if they have not brought the desired therapeutic effect, or if the mode of radiation therapy temporarily deprives the patient of work capacity (does not allow time to work) . In such situations, bromocriptine mesylate (1.25–5 mg orally is currently the first line of treatment — somatostatins analogues 2 times a day), which in a small number of patients reduces GH levels. With the ineffectiveness of bromocriptine, an analogue of somatostatin octreotide is prescribed at a dose of 0.05–0.15 mg subcutaneously, after 8– hours, which makes it possible to effectively reduce the level of GH in patients resistant to bromcriptine, surgical treatment or radiation therapy. Long-acting somatostatin analogues, such as manni-tol-modified form of octreotide (octreotide LAR),prescribed 10-30 mg intramuscularly, for a course of 4 to 6 weeks and lanreotide in a dose of 30 mg intramuscularly, after 10- days, are more suitable for prolonged therapy.