Hypothalamic-hypophysial insufficiency (panhypopituitalism) is a clinical syndrome that develops as a result of destruction of the adenohypophysis, followed by a persistent decrease in the production of tropic hormones and impaired activity of the peripheral endocrine glands.
One of the forms of hypothalamic-hypophysial insufficiency is Simmonds disease, which implies postpartum septic-embolic necrosis of hypertension, leading to severe cachexia and involution of organs and tissues. Skien disease is the most common and more benign current variant of postpartum panhypopituitarism.
Etiology. The most frequent cause of hypopituitarism is circulatory disorders in the hypothalamic-hypophysial region (hemorrhage, ischemia), developing after childbirth, complicated by massive (more than 1 l) blood loss, thromboembolic disease, sepsis.
Hypertrophy of the anterior lobe of the pituitary gland during pregnancy, followed by its involution after birth, contributes to the fact that all of these complications lead to impaired blood circulation in the pituitary, angiospasm, hypoxia and necrosis.
Repeated and frequent pregnancies and childbirth as factors of the functional tension of the pituitary gland predispose to the development of hypopituitarism. Ischemic changes in the pituitary gland, although rare, can occur in men after gastrointestinal, nasal bleeding. In recent years, hypothalamic-hypophysial failure in women with severe toxicosis in the second half of pregnancy has been associated in some cases with the development of an autoimmune process in the pituitary gland — lymphocytic hypophitis.
The rarer causes of panhypopituitism are tumors of the hypothalamic-hypophysial region, tumor metastases in the hypothalamic-hypophysial region, injuries (severe head injuries with separation of the pituitary stalk, radiation and operative interventions on the pituitary gland), granulomatous processes (irradiation) and granulomatous processes on the pituitary gland, irradiation and surgical intervention on the pituitary gland), granulomatous processes (irradiation) and granulomatous processes on the pituitary gland, irradiation and surgical intervention on the pituitary gland), granulomatous processes (irradiation) and granulomatous processes on the pituitary gland, irradiation and surgical intervention on the pituitary gland), granulomatous processes (radiation). ).
Pathogenesis
The pathogenesis of panhypopituitarism is based on the deficit of tropic hormones and growth hormone. Depending on the localization, vastness and intensity of the destructive process, the decline or reduction of hormone formation in the pituitary gland can be uniform and complete (panhypopituitarism) or partial, in which the production of one or several hormones is preserved.
Although necrotic processes in the pituitary gland are noted in 1.1–8.8% of all autopsies, partial hormonal insufficiency develops with a lesion of 60–70% of the anterior lobe, and panhypopituitism – with a lesion of 90% or more. This leads to the development of secondary hypofunction of the adrenal glands, as well as the thyroid and sex glands.
More rarely, with simultaneous involvement of the posterior lobe or pituitary legs in the pathological process, vasopressin levels may decrease with the development of diabetes insipidus.
A decrease in the production of growth hormone with its universal effect on protein synthesis leads to progressive atrophy of smooth and skeletal muscles and internal organs (splanchnomicry). Severe weight loss occurs in about 25% of patients. Prolactin production loss leads to agalactia. In the case of partial hypopituitarism, gonadotropic and somatotropic functions are most often affected, and the production of ACTH and TSH is significantly less frequently impaired.
Clinic
Manifestations of panhypopituitarism are determined by the speed of development and the volume (preservation of individual triple functions) of the destruction of the adenohypophysis.
The disease is much more common (65%) in women of young and middle age (20–40 years), but there are cases of the disease both in old and in earlier age. The development of Scien syndrome in a girl 12 years after juvenile maternal bleeding has been described. In most cases, the disease develops slowly over several years.
Most often, the somatotropic and gonadotropic activity decreases first, then thyrotropic and adrenocorticotropic functions. Sometimes in the clinical picture is dominated by the increasing loss of body weight, the average component of 2-6 kg per month, with severe reaches 25-30 kg. The depletion is usually uniform, the muscles atrophy, the internal organs decrease in volume.
Characteristic changes in the skin are observed: thinning and dryness give the skin a look of tissue paper, wrinkling, peeling in combination with a pale yellow, wax-like color is noted. Hair disappears in the armpits and pubic. General view of patients rather peculiar. Sometimes, against the background of general pallor, there are areas of dirty pigmentation on the face and in the natural folds of the skin, acrocyanosis. As a result of a decrease in melanin synthesis, the nipples and skin in the perineum region are depigmented.
Sweating and secretion of the sebaceous glands weaken. Fragility and loss of hair, their early graying, decalcification of bones develop, the lower jaw atrophies, teeth collapse and fall out. The phenomena of marasmus and senile involution are growing rapidly.
Characterized by very general weakness apathy, adynamia up to complete immobility, hypothermia, orthostatic collapse and coma, which, without specific therapy, lead to the death of the patient.
Reduced production of thyroid-stimulating hormone leads to rapid or gradual development of hypothyroidism. Chilliness, drowsiness, lethargy, weakness, mental and physical activity decrease. The number of heart contractions decreases, heart sounds become deaf, blood pressure decreases. Atony of the gastrointestinal tract and constipation develop.
Fluid retention characteristic of hypothyroidism is manifested differently in patients with hypopituitarism. With marked emaciation, there is usually no edema, and in patients with a predominance of symptoms of hypogonadism and hypothyroidism in the absence of ACTH deficiency, there is usually no large loss of body weight.
One of the leading places in the clinical symptomatology is occupied by disorders of the sexual sphere, caused by a decrease or complete loss of gonadotropic regulation of the sex glands. Genital disorders are often preceded by the appearance of all other symptoms. The sexual inclination is lost, the potency decreases. External and internal genital organs gradually atrophy. There are no signs of estrogenic activity in vaginal smears. In women, menstruation stops, the breast glands are reduced in volume. With the development of the disease after childbirth, agalactia and amenorrhea are characteristic (menstruation is not resumed). In rare cases of a prolonged and erased course of the disease, the menstrual cycle, although broken, remains, and even pregnancy is possible. In men, secondary sexual characteristics (pubic, axillary hair growth, mustache, bovine) disappear, the testes atrophy, prostate gland, seminal vesicles, penis. As a result of canalicular and interstitial insufficiency of the testes, oligozozoospermia occurs and testosterone levels decrease.
Acute adeno-pituitary insufficiency (pituitary coma) is a combination of acute adrenal insufficiency and hypothyroid coma.
Diagnostics
In typical cases, the diagnosis of panhypopituitarism is not difficult. The appearance of a complex of symptoms of insufficiency of the adrenal cortex, thyroid and genital glands after complicated births or in connection with another reason is in favor of hypothalamic-pituitary insufficiency. In severe forms (in Simmonds disease), weight loss, muscle, skin, subcutaneous tissue atrophy, hair loss, hypothermia, hypotension, osteoporosis, apathy, mental insanity dominate.
In case of Sciena’s disease, the clinical picture develops gradually, in some cases reaching the manifest stage after many years after giving birth, manifesting itself in the loss of not all, but individual adenohypophysical functions.
In a typical case, the syndrome is “7 A” (amenorrhea, agalactia, loss of axillary hair distribution, areola depigmentation, pallor and hypotrophy of the skin, apathy, adynamia).
In patients with a sluggish disease, the diagnosis is made late, although the absence of lactation after childbirth complicated by hemorrhage, a prolonged decline in working ability and menstrual dysfunction should suggest hypopituitarism. Hypochromic and normochromic anemia are frequent laboratory findings in hypopituitarism, especially in severe hypothyroidism, sometimes leukopenia with eosinophilia and lymphocytosis. The glucose level in the blood is low, the glycemic curve with glucose load is flattened.
Cholesterol
blood terina increased.
When hormonal research is determined by the combination
low levels of hormones from peripheral endocrine glands (T4, testosterone, estradiol, daily excretion of free cortisol in urine) with reduced or low levels of tropic hormones and growth hormone.
To clarify the reserves of pituitary hormones, stimulating tests with releasing hormones (thyroliberin, gonadotropin-releasing hormones) are shown. In the secondary (as opposed to the primary) hypocorticoidism (Addison’s disease), mineralocorticoid secretion does not occur, since the secretion of the latter is regulated mainly independently of the effects of ACTH. However, with prolonged ACTH deficiency, which, in addition to the secretory, has on the adrenal cortex and a trophic effect, in addition to the tubercular and reticular zone, the glomerular zone of the adrenal cortex can undergo atrophy, which will correspond to a decrease in plasma alsterone and an increase in activity renin in the blood plasma. For the diagnosis of secondary hypocorticism, a test with ACTH in combination with the determination of the level of ACTH in plasma, as well as a test with metyrapone and insulin hypoglycemia, is used.
Treatment
For panhypopituitarism, treatment should be aimed at compensating for hormonal deficiency and, if possible, at eliminating the cause of the disease. A tumor or cyst that causes destructive processes in the pituitary or hypothalamus is subject to radical treatment (surgical, radiation).
Hormone replacement therapy begins with the compensation of secondary hypocorticism with corticosteroids. Appointment of thyroid hormones to compensate for hypocorticism can lead to the development of acute adrenal insufficiency. The insufficiency of the sex glands is compensated for by the use of estrogen and progestin in women, androgenic drugs in men.
After preliminary treatment with sex hormones and a decrease in atrophic processes in the genitals, gonadotropins are prescribed if restoration of fertility is desired.
Thyroid insufficiency is eliminated by thyroid hormone preparations. Treatment begins with L-thyroxin in a daily dose of 12.5-25 µg, followed by an increase. In connection with the impairment of somatotropic function, the appointment of growth hormone has been shown to patients with hypothalamic-hypophysial insufficiency. Treatment for a hypopituitary coma is similar to that for acute adrenal insufficiency.