Symptoms of acromegaly and gigantism

Typical complaints for acromegaly include headache, changes in appearance, an increase in the size of brushes, feet. Patients are concerned about numbness in the hands, weakness, dry mouth, thirst, joint pain, limitation and painful movements. In connection with the progressive increase in body size, patients are often forced to change shoes, gloves, hats, underwear and clothing. Almost all women are disrupted by the menstrual cycle, 30% of men develop sexual weakness. Galactorrhea is noted in 25% of women with acromegaly. These abnormalities are due to hypersecretion of prolactin and / or loss of gonadotropic pituitary gland function. Complaints of irritability, sleep disturbances, and reduced capacity for work are frequent.

Headache can be different in nature, localization and intensity. Occasionally, persistent headaches are observed, combined with lacrimation, leading the patient to frenzy. The genesis of headaches is associated with increased intracranial pressure and / or compression of the diaphragm of the Turkish saddle with a growing tumor.

Weakness (in the absence of adrenal insufficiency) is due to the development of myopathy, as well as peripheral neuropathy resulting from soft tissue edema and peri- or endoneural fibrotic proliferation.

The change in appearance is associated with coarsening of facial features, an increase in the superciliary arches, zygomatic bones, the lower jaw with violation of the occlusion (prognathism) and the widening of the interdental spaces (diastema). There is an enlargement of feet and brushes, hypertrophy of the soft tissues of the face - nose, lips, ears. The tongue is enlarged (macroglossia), with the impressions of the teeth.

With acromegaly often hyperpigmentation of the skin, most pronounced in the area of skin folds and places of increased friction, is noted . Skin moist and oily (which is associated with increased function of sweat and sebaceous glands, which are enlarged both in size and quantity), dense, thickened, with deep folds that are more pronounced on the scalp. There is hypertrichosis. Skin changes in acromegaly are the result of the proliferation of connective tissue and the accumulation of intracellular matrix. An increase in the content of acidic mucopolysaccharides leads to interstitial edema.

The increase in the volume of muscle tissue occurs not so much due to hypertrophy of muscle fibers, but rather because of the proliferation of connective tissue formations. At the onset of the disease, physical strength and performance increase significantly, but as it develops, the muscle fibers are sclerosed and degenerated, and electromyography and biopsy data indicate the progression of proximal myopathy. The development of acromegaly arthropathy is the result of hypertrophy of the cartilaginous tissue. Proliferation of the cartilages of the larynx promotes the formation of low-pitched voice in patients.

The functional state of the enlarged internal organs at the initial stages of the disease is practically unaffected. However, as the disease progresses, signs of cardiac, pulmonary and hepatic insufficiency develop. Patients develop early atherosclerotic changes in the vessels, blood pressure rises. The heart with acromegaly is increased due to proliferation of connective tissue and hypertrophy of muscle fibers, however, the valve apparatus does not increase, which contributes to the development of circulatory failure. Myocardial dystrophy develops, cardiac conduction abnormalities are possible. There are pronounced morphological changes in the respiratory organs, leading to respiratory disorders. Often in patients in the active phase of the disease there is a syndrome of respiratory arrest during sleep, which is caused by violation of airway patency.

In 30% of patients, acroparesthesia of varying degrees was observed, resulting from the compression of the nerves by bone structures or hypertrophied soft tissues. The most common carpal syndrome is the result of compression of the median nerve in the carpal tunnel and is manifested by numbness and loss of tactile sensitivity of the fingers.

The metabolic disturbances are directly related to the pathological effect of hypersecretion of the growth hormone. It has been established that somatotropic hormone possesses a number of basic biological properties: anabolic, lipolytic and anti-insular (diabetogenic), and also regulates growth, anabolic and adaptive processes in the body. The influence of growth hormone on protein metabolism is primarily manifested in the enhancement of protein synthesis, increasing nitrogen retention by increasing the incorporation of amino acids into proteins, accelerating the synthesis of all types of RNA, and enhancing the mechanisms of translation. With acromegaly, activation of lipolysis processes, a decrease in the content of deposited fats in the liver, an increase in their oxidation in peripheral tissues are noted. These changes are manifested by increased serum levels of unesterified fatty acids (NEFC), ketone bodies, cholesterol, lecithin, beta-lipoproteins, and the more active the disease, the higher the level of NEFLC in the blood.

On average, 50-60% of patients experience impaired glucose tolerance. Explicit diabetes mellitus occurs in about 20% of cases. The diabetic effect of the growth hormone is due to its counterinsular effect, which consists in stimulating glycogenolysis, inhibiting the activity of hexokinase and utilizing glucose by muscle tissue, increasing the activity of liver insulinase. An increase in the level of free fatty acids due to the lipolytic action of the hormone acts depressingly on the activity of glycolytic enzymes in peripheral tissues, preventing normal utilization of glucose. The islets of Langerhans are enlarged in size and even with expressed diabetes, beta cells contain insulin granules. Violation of the insular apparatus is characterized by two dominant effects of growth hormone: resistance to hypoglycemic action of insulin and acceleration of insulin secretion, the level of which correlates with the activity of the disease. The phenomena of diabetic angioretinopathy in acromegaly and diabetes mellitus are rare.

There are also violations of the mineral metabolism. The growth hormone directly affects the function of the kidneys, promoting increased urinary excretion of inorganic phosphorus, sodium, potassium, and chlorides. Characteristic for acromegaly is a violation of phosphorus-calcium metabolism. The increase in the level of inorganic phosphorus in the blood and the acceleration of calcium excretion in the urine are indicators of the activity of the disease. The loss of calcium in the urine is compensated by the acceleration of its absorption through the gastrointestinal tract due to increased activity of parathyroid hormone. A combination of acromegaly with tertiary hyperparathyroidism and parathyroid adenoma is described.

On the part of the functional activity of the peripheral endocrine glands in acromegaly, there is a two-phase reaction, manifested in an increase and subsequent decrease in functional activity. The first phase is directly related to the anabolic effect of growth hormone, which promotes the activation of hypertrophic and hyperplastic processes in the endocrine organs. Approximately half the cases with the disease noted the presence of diffuse or nodal euthyroid goiter, one of the reasons for the development of which is an increase in renal clearance for iodine. In a number of cases, the appearance of goiter is due to the combined hypersecretion of tumor cells of somatotropic and thyroid-stimulating hormones. Despite the increase in basal metabolism, basal levels of thyroxine and triiodothyronine in the blood serum are usually within normal limits.

In case of tumor genesis, as the tumor grows beyond the Turkish saddle, the symptom of the violation of the function of the cranial nerves and the mesencephalon is added to the clinical picture of the disease. Progressive compression of the tumor by the intersection of the optic nerves is manifested by bitemporal hemianopsia, decreased acuity and narrowing of the visual fields. The hemianopsia can be predominantly one-sided, with the earliest sign being a violation of the perception of red. On the eyeground, swelling, stasis and atrophy of the optic nerves are consistently observed. In the absence of adequate treatment, these violations inevitably lead to complete blindness. With the growth of the tumor towards the hypothalamus, patients have drowsiness, thirst, polyuria, sudden temperature rises; with frontal growth - epilepsy, in case of defeat of the olfactory tract - anosmia; with temporal growth - epileptic seizures, homonymous hemianopsia, hemiparesis; III, IV, V, VI pairs of cranial nerves are affected when the tumor develops towards the cavernous sinuses. This is manifested by ptosis, diplopia, ophthalmoplegia, facial analgesia, and hearing loss.

The development of acromegaly includes a number of stages: pre-acromegaly, hypertrophic, tumor and cachectic. The first stage is characterized by the earliest signs of the disease, which are usually difficult to diagnose. The hypertrophic stage is registered in the presence of hypertrophy and hyperplasia of tissues and organs characteristic of the disease in patients. In the tumor stage, the signs dominate the clinical picture, mediated by the pathological effect of the pituitary tumor on the surrounding tissues (increased intracranial pressure, ocular and neurological disorders). The cachectic stage, caused, as a rule, by a hemorrhage into the pituitary tumor, is the logical outcome of the disease with the development of panhypopituitarism.

According to the degree of activity of the pathological process, the active phase of the disease and the phase of remission are distinguished. The active phase is characterized by progressive enlargement of the limbs, deterioration of the eye fundus and narrowing of the visual fields, the presence of severe cephalgic syndrome, a violation of carbohydrate metabolism, an increase in the content of somatotropic hormone in the blood, inorganic phosphorus, NEFLC, a decrease in somatostatin, an increase in calcium excretion in the urine, the presence of a paradoxical sensitivity to acute hyper- and hypoglycemia, the effect of central dopaminergic drugs (L-dofa, parlodel).

According to the anatomical and physiological character, the central forms of acromegaly are conventionally divided into pituitary and hypothalamic. It is established that the pathogenesis of both forms is associated with primary damage to the hypothalamus and / or overlying sections of the central nervous system. The pituitary form is distinguished by a disorder of the hypothalamic-pituitary interaction, which leads to the release of somatotrophs from the inhibitory effect of the hypothalamus and promotes their uncontrolled hyperplasia. The pituitary form is characterized by the autonomy of the development of the tumor, which is characterized by the resistance of the secretion of growth hormone to artificial fluctuations in glycemia (hyper-, hypoglycemia) and to the effect of drugs affecting the central nervous system (thyreoliberin, parlodel), and the absence of increase in growth hormone in the initial phase of sleep. With this form of the disease in the blood there is a significant increase in the level of growth hormone. For the hypothalamic form of acromegaly, the central regulation of the somatotropic function is characteristic. The main criteria are the sensitivity of the growth hormone to the introduction of glucose, including a paradoxical reaction, the presence of a reaction to a stimulating test with insulin hypoglycemia, the appearance of paradoxical sensitivity to centrally acting drugs and neuropeptides (tiroliberin, lyuliberin, parlodel), and the preservation of rhythmic secretion of growth hormone.

Most authors distinguish between two variants of acromegaly flow: benign and malignant. The first is more often observed in patients older than 45 years. The disease develops slowly, without marked clinical and laboratory signs of the activity of the process (including the level of growth hormone) and with a relatively small increase in the size of the Turkish saddle. Without treatment, this form of acromegaly can last from 10 to 30 years or more. In malignant acromegaly, the disease occurs at a younger age, is characterized by a rapidly progressive development of clinical symptoms, significant rigidity of the process, a more pronounced increase in the size of the pituitary tumor with its exit beyond the Turkish saddle and visual impairment. In the absence of timely and adequate treatment, the life expectancy of patients is 3-4 years. Returning to the above classification of the forms of acromegaly, it should be emphasized that the first, benign variant of the flow is more characteristic of the hypothalamic form of acromegalia, whereas the second one is for the pituitary form with rapid autonomic growth of the pituitary tumor and a more pronounced clinical picture of the disease.

[1], [2], [3], [4], [5], [6]