Symptoms of acromegaly and gigantism

Typical complaints of acromegaly include headache, changes in appearance, and enlargement of the hands and feet. Patients are bothered by numbness in the hands, weakness, dry mouth, thirst, joint pain, and limited and painful movements. Due to the progressive increase in body size, patients are forced to frequently change shoes, gloves, hats, underwear, and clothes. Almost all women experience menstrual irregularities, and 30% of men develop sexual weakness. Galactorrhea is observed in 25% of women with acromegaly. These abnormalities are caused by hypersecretion of prolactin and/or loss of the gonadotropic function of the pituitary gland. Complaints of irritability, sleep disturbances, and decreased performance are common.

Headaches may vary in nature, localization, and intensity. Occasionally, persistent headaches are observed, combined with lacrimation, driving the patient to frenzy. The genesis of headaches is associated with increased intracranial pressure and/or compression of the sella turcica diaphragm by a growing tumor.

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

The change in appearance is associated with coarsening of facial features, enlargement of the brow ridges, cheekbones, lower jaw with malocclusion (prognathism) and widening of interdental spaces (diastema). Enlargement of the feet and hands, hypertrophy of the soft tissues of the face - nose, lips, ears - is noted. The tongue is enlarged (macroglossia), with imprints of teeth.

Acromegaly is often characterized by hyperpigmentation of the skin, most pronounced in the area of skin folds and areas of increased friction. The skin is moist and oily (due to increased function of the sweat and sebaceous glands, which are enlarged both in size and quantity), dense, thickened, with deep folds that are more pronounced on the scalp. Hypertrichosis is noted. Skin changes in acromegaly are the result of connective tissue proliferation and accumulation of intracellular matrix. Increased levels of acidic mucopolysaccharides lead to interstitial edema.

The increase in muscle tissue volume occurs not so much due to hypertrophy of muscle fibers, but due to the proliferation of connective tissue formations. At the onset of the disease, physical strength and performance significantly increase, but as it progresses, muscle fibers become sclerotic and degenerate, and electromyography and biopsy data indicate the progression of proximal myopathy. The development of acromegalic arthropathy is the result of hypertrophy of cartilaginous tissue. Proliferation of laryngeal cartilage contributes to the formation of a low hoarse voice in patients.

The functional state of the enlarged internal organs is practically not affected at the initial stages of the disease. However, as the disease progresses, signs of cardiac, pulmonary and hepatic failure develop. Patients develop atherosclerotic changes in the vessels quite early, and blood pressure increases. The heart in acromegaly is enlarged due to the proliferation of connective tissue and hypertrophy of muscle fibers, but the valve apparatus does not increase, which contributes to the development of circulatory failure. Myocardial dystrophy develops, and cardiac conduction disorders are possible. Pronounced morphological changes in the respiratory organs are observed, leading to respiratory disorders. Patients in the active phase of the disease often experience sleep apnea syndrome, which is caused by obstruction of the airways.

In 30% of patients, acroparesthesia of varying degrees was observed, resulting from compression of nerves by bone structures or hypertrophied soft tissues. The most common is carpal tunnel syndrome, which 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.

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

On average, 50-60% of patients have impaired glucose tolerance. Overt diabetes mellitus occurs in approximately 20% of cases. The diabetogenic effect of somatotropic hormone is due to its counterinsular action, which consists in stimulating glycogenolysis, inhibiting the activity of hexokinase and glucose utilization by muscle tissue, and increasing the activity of liver insulinase. An increase in the level of free fatty acids due to the lipolytic effect of the hormone has an inhibitory effect on the activity of glycolytic enzymes in peripheral tissues, preventing normal glucose utilization. The islets of Langerhans are enlarged and even in severe diabetes mellitus, beta cells contain insulin granules. Disturbances in the insular apparatus are characterized by two dominant effects of growth hormone: resistance to the hypoglycemic effect 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 observed rarely.

There are also disturbances in mineral metabolism. Somatotropic hormone directly affects kidney function, promoting increased excretion of inorganic phosphorus, sodium, potassium, and chlorides with urine. Disturbances in phosphorus-calcium metabolism are characteristic of acromegaly. An increase in the level of inorganic phosphorus in the blood and accelerated excretion of calcium with urine are indicators of disease activity. Loss of calcium with urine is compensated by accelerated absorption through the gastrointestinal tract due to increased parathyroid hormone activity. A combination of acromegaly with tertiary hyperparathyroidism and parathyroid adenoma has been described.

In terms of the functional activity of the peripheral endocrine glands, acromegaly is characterized by 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. In approximately half of the cases, the disease is accompanied by diffuse or nodular euthyroid goiter, one of the causes of which is an increase in renal clearance for iodine. In some cases, the appearance of goiter is due to the combined hypersecretion of somatotropic and thyroid-stimulating hormones by tumor cells. Despite the increase in basal metabolism, basal levels of thyroxine and triiodothyronine in the blood serum are usually within normal limits.

In tumor genesis, as the tumor grows beyond the sella turcica, symptoms of dysfunction of the cranial nerves and diencephalon are added to the clinical picture of the disease. Progressive compression of the optic chiasm by the tumor is manifested by bitemporal hemianopsia, decreased visual acuity and narrowing of the visual fields. Hemianopsia can be predominantly unilateral, with the earliest sign being impaired perception of red color. Edema, stasis and atrophy of the optic nerves are consistently observed in the fundus. Without adequate treatment, these disorders inevitably lead to complete blindness. As the tumor grows towards the hypothalamus, patients experience drowsiness, thirst, polyuria, and sudden increases in temperature; with frontal growth - epilepsy, and in case of damage to the olfactory tract - anosmia; with temporal growth - epileptic seizures, homonymous hemianopsia, hemiparesis; When the tumor develops towards the cavernous sinuses, the III, IV, V, VI pairs of cranial nerves are affected. This is manifested by ptosis, diplopia, ophthalmoplegia, facial analgesia, and hearing loss.

The development of acromegaly includes a number of stages: preacromegalic, hypertrophic, tumoral and cachectic. The first stage is characterized by the earliest signs of the disease, which are usually difficult to diagnose. The hypertrophic stage is recorded when patients have the characteristic phenomena of hypertrophy and hyperplasia of tissues and organs. At the tumor stage, the clinical picture is dominated by signs mediated by the pathological effect of the pituitary tumor on the surrounding tissues (increased intracranial pressure, eye and neurological disorders). The cachectic stage, usually caused by hemorrhage into the pituitary tumor, is a logical outcome of the disease with the development of panhypopituitarism.

Depending on the activity of the pathological process, an active phase of the disease and a remission phase are distinguished. The active phase is characterized by progressive enlargement of the limbs, deterioration of the fundus and narrowing of the visual fields, the presence of pronounced cephalgic syndrome, impaired carbohydrate metabolism, increased blood levels of somatotropic hormone, inorganic phosphorus, NEFA, decreased somatostatin levels, increased urinary calcium excretion, paradoxical sensitivity to acute hyper- and hypoglycemia, and the action of central dopaminergic drugs (L-dopa, parlodel).

According to the anatomical and physiological features, the central forms of acromegaly are conventionally divided into pituitary and hypothalamic. It has been established that the pathogenesis of both forms is associated with the primary lesion of the hypothalamus and/or overlying parts of the central nervous system. The pituitary form is distinguished by a violation of the hypothalamic-pituitary interaction, which leads to the release of somatotrophs from the inhibitory influence of the hypothalamus and contributes to their uncontrolled hyperplasia. The pituitary form is characterized by the autonomy of tumor development, the signs of which are the resistance of the secretion of somatotropic hormone to artificial fluctuations in glycemia (hyper-, hypoglycemia) and to the influence of drugs affecting the central nervous system (thyroliberin, parlodel), as well as the absence of an increase in somatotropic hormone in the initial phase of sleep. With this form of the disease, a significant increase in the level of somatotropic hormone is noted in the blood. The hypothalamic form of acromegaly is characterized by the preservation of central regulation of the somatotropic function. The main criteria are the sensitivity of the somatotropic 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 (thyroliberin, luliberin, parlodel), and the preservation of rhythmic secretion of the somatotropic hormone.

Most authors distinguish two variants of acromegaly: benign and malignant. The first is more often observed in patients over 45 years of age. The disease develops slowly, without pronounced clinical and laboratory signs of process activity (including the level of somatotropic hormone) and with a relatively small increase in the size of the sella turcica. Without treatment, this form of acromegaly can last from 10 to 30 years or more. In the malignant course of acromegaly, the disease occurs at a younger age, is characterized by rapidly progressing 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 sella turcica 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 forms of acromegaly, it should be emphasized that the first, benign variant of the course is more characteristic of the hypothalamic form of acromegaly, while the second is for the pituitary form with rapid autonomous growth of the pituitary tumor and a more pronounced clinical picture of the disease.

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