Hypopituitarism

Previously, one of the main causes of hypopituitarism was ischemic necrosis of the pituitary gland (necrosis of the pituitary gland, which developed as a result of massive postpartum hemorrhage and vascular collapse - Shikhen syndrome, pituitary necrosis due to postpartum sepsis - Simmonds syndrome, recently often used the term "Simmonds syndrome - Shihena "). In recent decades, due to the improvement in obstetric care, this cause of hypopituitarism occurs significantly in voyage. Ischemic necrosis of the pituitary gland can also develop against diseases such as diabetes mellitus, temporal arteritis, sickle cell anemia, eclampsia, severe avitaminosis. However, in these patients, as a rule, the phenomena of hypopituitarism are of an eroded nature and rarely develop.

One should also 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 the deposition of iron in the pituitary gland. Rarely, the cause of hypopituitarism can be immunological disorders, as in malignant anemia. One of the frequent causes of hypopituitarism is the volumetric processes affecting the pituitary gland. These are primary tumors localized in the Turkish saddle (chromophobic adenoma, craniopharyngioma); parasellar tumors (meningiomas, gliomas of the optic nerve); aneurysms of the intracranial branches of the internal carotid artery. Therefore, a doctor who meets with the clinic of hypopituitarism should first of all exclude the volumetric process and determine its nature. The appearance of signs of hypopituitarism is possible even with a hemorrhage in the pituitary gland against the background of the tumor process. One of the most common reasons for the development of panhypopituitarism is the previous radiotherapy of the nasopharynx and the Turkish saddle, as well as neurosurgical intervention.

Extremely rare at the present time are such previously classical causes of hypopituitarism, such as tuberculosis and syphilis. The phenomena of hypopituitarism can occur in chronic renal failure. However, they are rare, not pronounced, and usually appear only as a decrease in gonadotropin function. It is often not possible to identify the specific cause of hypopituitarism, and then use the term "idiopathic hypopituitarism". In these cases autosomal or X-linked recessive variants of primary hypopituitarism are sometimes encountered, but sporadic cases are also possible.

Syndrome of the "empty" Turkish saddle is also attributed to the causes of primary hypopituitarism. However, we consider this interpretation too unambiguous. With the syndrome of the "empty" Turkish saddle, as a rule, hormonal changes depend not so much on the pituitary as suffering, but rather as a result of a deficiency in the stimulating effects of the hypothalamus. From our point of view, hypopituitarism in this syndrome can be both primary and secondary.

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

1. Destruction of the pituitary foot in traumas (fracture of the base of the skull), when it is compressed by a parasellar tumor or an aneurysm, if it is damaged as a result of neurosurgical intervention.
2. Defeat of the hypothalamus and other parts of the central nervous system.

Rarely, tumor causes of secondary hypopituitarism (primary, metastatic, lymphoma, leukemia) are rare, but they should be excluded first. It should also be borne in mind such rare diseases as sarcoidosis, infiltrative lesions of the hypothalamus in diseases of lipid deposition, traumatic lesions - severe trauma of the skull; as a rule, in patients with prolonged coma; toxic lesions (vincristine). Much more often the doctor meets hypopituitarism caused by the previous use of hormonal drugs, primarily long-term treatment with glucocorticoids and sex steroids, prolonged 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, quite frequent, there is a constitutional biochemical defect of the hypothalamic-pituitary region, decompensated under the influence of various external 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 may 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 anorexia nervosa. However, signs of hypothalamic dysfunction that existed before the onset of the disease or occurred before significant weight loss, as well as the absence of recovery of the menstrual cycle in a number of patients after normalization of body weight indicate that in anorexia nervosa some of the manifestations of hypopituitarism are not associated with weight loss but have a different genesis . Perhaps these patients have a constitutional pre-preparedness for hypothalamic dysfunction.

The manifestations of hypothalamic hypopituitarism in obesity are also not related solely to excess body weight. In particular, amenorrhea does not always correlate with the increase in body weight and often precedes obesity.

[1], [2], [3]

Pathogenesis of hypopituitarism

Distinguish primary hypopituitarism, which is a consequence of the lack or weakening of the secretion of hormonal cells of the pituitary gland, and secondary hypopituitarism, caused by a deficiency of stimulating effects of the hypothalamus on the secretion of pituitary hormones.

Violation of stimulating influences on the pituitary gland occurs as a result of disturbance of vascular or nervous connections with the brain at the level of the pituitary foot, hypothalamus or extrahypothalamic areas of the central nervous system.

Consequently, with secondary hypopituitarism, the inadequate secretion of hormones in the anterior pituitary gland is the result of a lack or corresponding decrease in releasing factors, and a decrease in secretion of hormones in the posterior lobe of the pituitary is a result of the lack of synthesis and axonal transport of the hormone from the place of their formation in the anterior hypothalamus.

Symptoms of hypopituitarism

Symptoms of hypopituitarism are extremely diverse and range from erased forms that have virtually no clear clinical manifestations to pronounced panhypopituitarism. Within hypopituitarism, there are forms with an isolated deficit of a hormone, which is accordingly reflected in clinical symptoms.

Symptoms of panhypopituitarism are determined by the deficiency of gonadotropins with hypogonadism; the state of thyroid insufficiency, caused by a decrease in secretion of TSH; insufficiency of ACTH, manifested by a decrease in the function of the adrenal cortex; decrease in the function of STH, which is manifested by a violation of tolerance to carbohydrates as a result of hypoinsulinemia and growth retardation in children; hypoprolactinemia, which is manifested by the absence of postpartum lactation.

All of these manifestations are present simultaneously with panhypopituitarism. Previously, there was a decrease in the function of STH, then hypogonadism. Deficiency of ACTH and TSH develops in later stages of the disease. Earlier it was believed that the leading sign of panhypopituitarism is cachexia. It has now been established that cachexia is not only not a basic symptom, but also not necessarily a symptom.

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

In the study of internal organs, splanchnomycria are revealed, therefore the liver and spleen, as a rule, are not palpable. Gonads and external genital organs atrophy in patients of both sexes. In men prostate gland is atrophied, in women - mammary glands. Characteristic amenorrhea, impotence in men, decreased sexual desire in patients of both sexes.

Often develops moderate anemia, usually normocytic, but sometimes hypochromic or macrocytic. Often there is relative leukopenia. Changes in the mental sphere are characterized by mental retardation, apathy, reduced motivation. A tendency to hypoglycemic reactions has been found. Within the framework of panhypopituitarism, a clinical picture of diabetes insipidus is often found.

The isolated deficiency of ACTH is manifested by symptoms characteristic of a decrease in the function of the adrenal cortex. General weakness, postural hypotension, dehydration, nausea, propensity to hypoglycemic conditions are expressed. In patients with ACTH deficiency, hypoglycemia may be the only sign of swelling. Unlike the primary hypofunction of the adrenal glands, hyperpigmentation is extremely rare. Moreover, depigmentation and a decrease in the degree of sunburn during solar irradiation are characteristic. ACTH secretion usually does not completely disappear, and the corresponding symptoms of the disease at the onset of the disease can appear only during periods of various types of stress. Liked libido, hair falling in the armpits and pubic hair.

Isolated thyroid-stimulating hormone deficiency (with a deficiency of TSH - secondary hypothyroidism, with the initial deficiency of thyrotropin-releasing factor - tertiary hypothyroidism). Clinical manifestations: a picture of hypothyroidism in the form of violation of tolerance to cold, the appearance of constipation, dryness and pallor of the skin, slowing of mental processes, bradycaria, hoarseness of voice. True miksedema is extremely rare; possibly both strengthening and reducing menstrual bleeding. Sometimes pseudohypoparathyroidism is observed.

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

Isolated deficiency of growth hormone in adults is not accompanied by significant clinical symptoms. There is only a violation of tolerance to carbohydrates. The lack of growth hormone in children is accompanied by a delay in growth. At any age, clinical manifestations of the state of hypoglycaemia on an empty stomach are frequent, which becomes a permanent syndrome with a concurrent deficit of ACTH.

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

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

Differential diagnosis is carried out primarily with hormonal deficiency, caused by the primary hypofunction of peripheral endocrine glands. In this case, it is very important to determine the initial levels of secretion of a particular tropic hormone, conduct samples with stimulation and suppression of its secretion. At a young age, a differential diagnosis with anorexia nervosa is very important. Anorexia nervosa is characterized by the presence of dysmorphophobic experiences, measures aimed at reducing body weight. With anorexia nervosa, as a rule, patients have a considerable time (before the stage of pronounced cachexia) are active, do not complain of asthenic nature, are very mobile, active, workable. They have preserved hair in the armpits and pubic region. Characterized by palpitation, increased sweating, vegetative paroxysms of various nature, including sympathoadrenal, are noted. Significant difficulties in the differential diagnosis are available at the stage of cachexia. However, a thorough analysis of the course of the disease, the identification of its stages help diagnosis. In most cases, with pronounced cachexia and exclusion of primary somatic suffering and hypofunction of the peripheral endocrine glands, psychiatrist consultation is necessary.

Treatment of hypopituitarism

The tactics of the therapeutic approach must first be determined 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 this or that tropic hormone of the pituitary gland. So, with ACTH deficiency, glucocorticoids are used - cortisone and hydrocortisone. Prednisone or prednisone may be used. Sometimes hormone replacement therapy becomes necessary only during periods of stress. The question of the appropriateness of the appointment of glucocorticoid therapy is decided on the basis of the degree of decrease in the initial level of cortisol or when the reaction to stimulation is impaired.

Treatment for phenomena of diabetes insipidus. Patients with a deficiency of TSH should be treated in the same way as patients with primary hypothyroidism. Usually, triiodothyronine and thyroxine are used. A good therapeutic effect can be given by the introduction of TRH. When hypogonadism occurs, estragen therapy is used.

Deficiency of growth hormone is treated only with pronounced growth retardation in children in the puberty period, usually using somatotropin.

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

Treatment of erased and benignly current forms of hypopituitarism should not begin with hormone replacement therapy. In the initial stage of therapy, it is desirable to prescribe drugs that, acting through neurotransmitters, affect the level of releasing factors and inhibitory factors of the hypothalamus, and reduce the stress of the body. Means such means as nootropilum, obzidan, clonidine are meant. There have been reports of a normalizing effect on the hypothalamic-pituitary system of phenobarbital and neuroleptics. It should not be forgotten that neurotic disorders, mainly anxious and depressive, may be accompanied by anorectic reactions, nausea, vomiting; this leads sometimes to a significant decrease in body weight. As a rule, in the anamnesis, these patients can be traced signs of hypothalamic insufficiency. A significant decrease in body weight and the formation of a psychopathological syndrome can lead to the formation of complete or partial hypopituitarism, against which the underlying neurotic disease proceeds. 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 can 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.