Hypopituitarism

Previously, one of the main causes of hypopituitarism was considered to be ischemic necrosis of the pituitary gland (pituitary necrosis that developed as a result of massive postpartum hemorrhage and vascular collapse - Sheehan syndrome; pituitary necrosis that occurred as a result of postpartum sepsis - Simmonds syndrome; recently, the term "Simmonds-Sheehan syndrome" is often used). In recent decades, due to the improvement of obstetric care, this cause of hypopituitarism occurs significantly more often. Ischemic necrosis of the pituitary gland can also develop against the background of such diseases as diabetes mellitus, temporal arteritis, sickle cell anemia, eclampsia, severe vitamin deficiencies. However, in these patients, as a rule, the phenomena of hypopituitarism are erased and develop rarely.

It is also necessary to remember such a possible cause of hypopituitarism as hemochromatosis, in which the function of the adenohypophysis decreases in almost half of the cases and is the result of iron deposition in the pituitary gland. Quite rarely, hypopituitarism can be caused by immunological disorders, as in pernicious anemia. One of the common causes of hypopituitarism is volumetric processes affecting the pituitary gland. These are primary tumors localized in the sella turcica (chromophobe adenoma, craniopharyngioma); parasellar tumors (meningiomas, gliomas of the optic nerve); aneurysms of the intracranial branches of the internal carotid artery. Therefore, a doctor encountering a clinical picture of hypopituitarism must first exclude a volumetric process and determine its nature. The appearance of signs of hypopituitarism is also possible with hemorrhage in the pituitary gland against the background of a tumor process. One of the most common causes of panhypopituitarism is previous radiation therapy of the nasopharynx and sella turcica, as well as neurosurgical intervention.

Such previously classical causes of hypopituitarism as tuberculosis and syphilis are extremely rare at present. Hypopituitarism may occur in chronic renal failure. However, they are rare, not clearly expressed and usually manifest only by a decrease in the function of gonadotropins. Quite often it is not possible to identify a specific cause of hypopituitarism, and then the term "idiopathic hypopituitarism" is used. In these cases, autosomal or X-linked recessive variants of primary hypopituitarism are sometimes encountered, but sporadic cases are also possible.

The syndrome of the "empty" sella turcica is also attributed to the causes of primary hypopituitarism. However, we believe that such an interpretation is too unambiguous. In the syndrome of the "empty" sella turcica, as a rule, hormonal changes depend not so much on the pituitary gland, but are the result of a deficiency of the stimulating influences of the hypothalamus. From our point of view, hypopituitarism in this syndrome can be of both primary and secondary nature.

The causes of secondary hypopituitarism should be divided into two groups, the first of which is less common.

1. Destruction of the pituitary stalk due to trauma (fracture of the base of the skull), when it is compressed by a parasellar tumor or aneurysm, or when it is damaged as a result of neurosurgical intervention.
2. Damage to the hypothalamus and other parts of the central nervous system.

Tumor causes of secondary hypopituitarism (primary, metastatic, lymphomas, leukemia) are quite rare, but they should be excluded first. It is also necessary to keep in mind such rare diseases as sarcoidosis, infiltrative lesions of the hypothalamus in lipid deposition disease, traumatic lesions - severe head injuries; as a rule, in patients with prolonged coma; toxic lesions (vincristine). Much more often, the doctor encounters hypopituitarism caused by previous use of hormonal drugs, primarily long-term treatment with glucocorticoids and sex steroids, long-term use of oral contraceptives.

Idiopathic forms of secondary hypopituitarism are observed, often congenital or familial, often affecting the secretion of one or two hormones, often transient. Most likely, in such cases, which are quite common, there is a constitutional biochemical defect of the hypothalamic-pituitary region, decompensating under the influence of various environmental influences. Often, the clinical picture of hypothalamic hypopituitarism can be a consequence of both acute and chronic stress and be reversible. One of the variants of chronic stress can be one or another neurotic condition, often occurring with a decrease in body weight and anorexic reactions. With a significant change in body weight, as a rule, signs of hypopituitarism appear. This is also noted in the cachectic stage of nervous anorexia. However, signs of hypothalamic dysfunction that were present before the onset of the disease or occurred before significant weight loss, as well as the lack of restoration of the menstrual cycle in a number of patients after normalization of body weight indicate that in nervous anorexia, some manifestations of hypopituitarism are not associated with weight loss, but have a different genesis. Perhaps such patients have a constitutional predisposition to hypothalamic dysfunction.

Manifestations of hypothalamic hypopituitarism in obesity are also not associated exclusively with excess body weight. In particular, amenorrhea does not always correlate with weight gain and often precedes obesity.

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Pathogenesis of hypopituitarism

A distinction is made between primary hypopituitarism, which is a consequence of the absence or weakening of the secretion of hormonal cells of the pituitary gland, and secondary hypopituitarism, caused by a deficiency of the stimulating effects of the hypothalamus on the secretion of pituitary hormones.

Disruption of the stimulating effects on the pituitary gland occurs as a result of disruption of vascular or neural connections with the brain at the level of the pituitary stalk, hypothalamus, or extrahypothalamic areas of the central nervous system.

Consequently, in secondary hypopituitarism, the insufficiency of secretion of hormones of the anterior pituitary gland is the result of the absence or corresponding decrease in releasing factors, and the decrease in secretion of hormones of the posterior pituitary gland is the result of the absence of synthesis and axonal transport of the hormone from the site of their formation in the anterior hypothalamus.

Symptoms of hypopituitarism

Symptoms of hypopituitarism are extremely diverse and range from latent forms, which have virtually no clear clinical manifestations, to pronounced panhypopituitarism. Within the framework of hypopituitarism, there are forms with isolated deficiency of one or another hormone, which is accordingly reflected in clinical symptoms.

Symptoms of panhypopituitarism are determined by gonadotropin deficiency with hypogonadism; thyroid insufficiency caused by decreased TSH secretion; ACTH deficiency, manifested by decreased adrenal cortex function; decreased STH function, which manifests itself as impaired carbohydrate tolerance due to hypoinsulinemia and growth retardation in children; hypoprolactinemia, which manifests itself as the absence of postpartum lactation.

All of the listed manifestations of panhypopituitarism are present simultaneously. The first to be observed is a decrease in the function of STH, then hypogonadism. Deficiency of ACTH and TSH develops at later stages of the disease. Previously, it was believed that the leading sign of panhypopituitarism is cachexia. It has now been established that cachexia is not only not the main, but also not necessarily occurring symptom.

It should be remembered that panhypopituitarism may occur against the background of normal and even slightly increased body weight (in the presence of severe cachexia, it is necessary to exclude somatic diseases, diseases of the primary endocrine glands, and in young patients - nervous anorexia). The clinical picture is characterized by the senile appearance of patients, the Mongoloid character of the face attracts attention, the skin loses turgor, the hair on the head turns gray early and falls out quickly; pubic hair and hair in the armpits are significantly reduced or completely disappears. Brittle nails are noted, acrocyanosis often develops. A tendency to bradycaria, decreased blood pressure is revealed, cases of orthostatic hypotension are not uncommon.

When examining the internal organs, splanchnomycosis is revealed, so the liver and spleen are usually not palpated. The gonads and external genitalia atrophy in patients of both sexes. In men, the prostate gland atrophies, and in women, the mammary glands. Amenorrhea, impotence in men, and decreased sexual desire in patients of both sexes are characteristic.

Moderate anemia often develops, usually normocytic, but sometimes hypochromic or macrocytic. Relative leukopenia is often observed. Mental retardation, apathy, and decreased motivation are characteristic of changes in the mental sphere. A tendency to hypoglycemic reactions has been detected. Within the framework of panhypopituitarism, the clinical picture of diabetes insipidus is often detected.

Isolated ACTH deficiency manifests itself with symptoms characteristic of decreased adrenal cortex function. General weakness, postural hypotension, dehydration, nausea, and a tendency to hypoglycemic states are expressed. In patients with isolated ACTH deficiency, hypoglycemia may be the only sign of the disease. Unlike primary adrenal hypofunction, hyperpigmentation is extremely rare. Moreover, depigmentation and a decrease in the degree of tanning with solar radiation are characteristic. ACTH secretion usually does not completely disappear, and the corresponding symptoms of the disease at the onset of the disease may appear only during periods of various types of stress exposure. Libido decreases, hair falls out in the armpits and pubis.

Isolated deficiency of thyroid-stimulating hormone (with TSH deficiency - secondary hypothyroidism, with initial deficiency of thyrotropin-releasing factor - tertiary hypothyroidism). Clinical manifestations: hypothyroidism picture in the form of impaired tolerance to cold, constipation, dry and pale skin, slowing of mental processes, bradycaria, hoarseness. True myxedema is extremely rare; both increase and decrease of menstrual bleeding are possible. Pseudohypoparathyroidism is sometimes observed.

Isolated gonadotropin deficiency in women is manifested by amenorrhea, atrophy of the mammary glands, dry skin, decreased vaginal secretion, decreased libido; in men - by shrinkage of the testicles, decreased libido and potency, slow hair growth in the corresponding areas of the body, decreased muscle strength, eunuchoid appearance.

Isolated growth hormone deficiency in adults is not accompanied by significant clinical symptoms. Only impaired carbohydrate tolerance is noted. Growth hormone deficiency in children is accompanied by growth retardation. Clinical manifestations of fasting hypoglycemia are common at any age, which becomes a permanent syndrome with simultaneous ACTH deficiency.

Isolated prolactin deficiency is characterized by a single clinical manifestation - the absence of postpartum lactation.

Isolated deficiency of vasopressin (ADH) is characterized by the clinical picture of diabetes insipidus.

Differential diagnosis is carried out primarily with hormonal deficiency caused by primary hypofunction of the peripheral endocrine glands. In this case, the determined initial levels of secretion of a particular tropic hormone, conducting tests with stimulation and suppression of its secretion are very important. At a young age, differential diagnosis with nervous anorexia is very important. Nervous anorexia is characterized by the presence of dysmorphophobic experiences, measures aimed at reducing body weight. With nervous anorexia, as a rule, patients are active for a significant time (before the stage of severe cachexia), do not present asthenic complaints, are very mobile, energetic, and efficient. They retain hair in the armpits and pubis. Heart palpitations, increased sweating are characteristic, vegetative paroxysms of various natures are noted, including sympathoadrenal. Significant difficulties in differential diagnosis exist at the stage of cachexia. However, a thorough analysis of the course of the disease, identifying its stages helps in diagnosis. In most cases, with severe cachexia and exclusion of primary somatic suffering and hypofunction of the peripheral endocrine glands, a consultation with a psychiatrist is necessary.

Treatment of hypopituitarism

The tactics of the therapeutic approach should be determined first of all by the nature of the pathological process that caused primary or secondary hypopituitarism. Hormone replacement therapy is prescribed after mandatory consultation with endocrinologists; it is planned depending on the clinically detected deficiency of a particular pituitary tropic hormone. Thus, in case of ACTH deficiency, glucocorticoids are used - cortisone and hydrocortisone. Prednisolone or prednisone can be used. Sometimes, hormone replacement therapy becomes necessary only during periods of stress. The question of the advisability of prescribing glucocorticoid therapy is decided on the basis of the degree of decrease in the initial level of cortisol or in case of a violation of its response to stimulation.

Treatment for diabetes insipidus. Patients with TSH deficiency should be treated in the same way as patients with primary hypothyroidism. Triiodothyronine and thyroxine are usually used. TRH administration can have a good therapeutic effect. Estrogen therapy is used for hypogonadism.

Growth hormone deficiency is treated only in cases of severe growth retardation in children during puberty, usually using somatotropin.

Radiation therapy is used only when the tumor genesis of the disease is proven; it replaces or complements surgical treatment.

Treatment of latent and benign forms of hypopituitarism should not begin with hormone replacement therapy. At the initial stage of therapy, it is advisable to prescribe agents that, acting through neurotransmitters, affect the level of releasing factors and inhibitory factors of the hypothalamus, reducing the body's stress availability. This refers to such agents as nootropil, obzidan, clonidine. There are reports on the normalizing effect of phenobarbital and neuroleptics on the hypothalamic-pituitary system. It should not be forgotten that neurotic disorders, mainly of an anxious-depressive nature, can be accompanied by anorectic reactions, nausea, vomiting; this sometimes leads to a significant decrease in body weight. As a rule, signs of hypothalamic insufficiency can be traced in the anamnesis of these patients. Significant weight loss and the development of a psychopathological syndrome may lead to the development of complete or partial hypopituitarism, against the background of which the underlying neurotic disease occurs. In such cases, treatment should not begin with hormone therapy, since the normalization of psychopathological disorders and the increase in body weight as a result of psychotropic therapy may lead to a significant reduction in the phenomena of hypopituitarism. Psychotropic therapy should be selected individually; the criterion for choosing a drug should be the nature of the psychopathological syndrome.