Pangypopituitarism is a functional insufficiency of the adenohypophysis, characterized by a persistent deficiency of all tropic hormones and hypofunction of the peripheral endocrine glands. With pangypopituitarism, there is a delay in growth and development in children, sharp weight loss, severe weakness, sexual dysfunction, signs of hypothyroidism and hypocorticism, neuropsychiatric disorders, pituitary coma. Diagnosis of panhypopituitarism includes the study of basal levels of tropic hormones, estradiol, testosterone, T4, cortisol in blood and urine, various provocative tests, neuroradiological examination. The treatment depends on the genesis of the disease, consists in carrying out appropriate hormone replacement therapy, surgical removal of the pituitary tumor.
Meaning
Hormones of the anterior pituitary gland (ACTH, LH, STH, TSH, FSH and prolactin) are the main regulators of the activity of peripheral endocrine glands (thyroid gland, adrenal cortex, ovaries and testes), have an indirect effect on almost all vital functions of the body. A total decrease or cessation of the secretion of tropic hormones in pangypopituitarism leads to secondary insufficiency of the corresponding endocrine target glands and the development of symptoms of hypothyroidism, hypocorticism, hypogonadism, stunting, agalactia, etc.
Primary hypopituitarism develops due to congenital or acquired destructive lesions of the anterior pituitary gland. In secondary pangypopituitarism, deficiency of adenohypophysial hormones is caused by damage to the nuclei of the hypothalamus and a decrease or absence of secretion of hypothalamic releasing hormones. Clinical signs of panhypopituitarism are found, as a rule, with damage (pronounced subcapsular atrophy and scar transformation) of at least 90-95% of functionally active pituitary tissue. Progressive atrophy and pronounced fibrosis with violation of all functions is observed in internal organs, smooth and skeletal muscles. Most often (in 65% of cases) panhypopituitarism occurs in young and middle-aged women (from 20 to 40 years).
Causes
Various pathological conditions of the anterior pituitary gland and hypothalamus can lead to insufficient secretion of tropic hormones in pangypopituitarism. Most often, panhypopituitarism occurs with circulatory disorders of the hypothalamic-pituitary region (ischemic necrosis, pituitary tissue infarction, pituitary apoplexy, vascular thrombosis, aneurysms of the internal carotid artery).
Women with massive (more than 1 liter) blood loss during childbirth, abortions (Simmonds—Skien syndrome, hypothalamic-pituitary cachexia) leading to hypovolemia, arterial hypotension, shock and circulatory hypoxia of the pituitary gland are at increased risk for the development of pangypopituitarism. Repeated and frequent pregnancies and childbirth, causing functional tension of the pituitary gland, predispose to the development of panhypopituitarism.
Ischemic changes in the pituitary gland in men can occur as a result of copious gastrointestinal and nasal bleeding. There is a high probability of developing panhypopituitarism in benign tumors of the pituitary gland and hypothalamus (adenoma, craniopharyngioma, cyst, meningioma, angioma of the pituitary pedicle) or metastases of malignant tumors in the hypothalamic-pituitary region.
Severe traumatic brain injuries with intracerebral hemorrhages, surgical interventions and radiation therapy for hypothalamic and pituitary tumors can cause damage to the cells of the adenohypophysis and/or hypothalamus.
More rare causes of panhypopituitarism include Hand–Schuller–Christian disease, sarcoidosis, hemochromatosis. Some infections (tuberculosis, malaria, syphilis, encephalitis, influenza) can cause inflammatory and destructive changes that destroy the pituitary tissue. Severe toxicosis of the second half of pregnancy can also provoke an autoimmune lesion of the gland – lymphocytic pituitary with infiltration and replacement of pituitary tissue with lymphoid with the development of its functional insufficiency. In some cases, the causes of panhypopituitarism cannot be identified (idiopathic panhypopituitarism).
Symptoms
The clinical picture of panhypopituitarism includes specific symptoms of combined polyendocrine insufficiency and a variety of neurovegetative manifestations. The severity of the symptoms of panhypopituitarism depends on the degree of destructive damage to the adenohypophysis. Usually the disease develops gradually, in rare cases it has an acute onset and can lead to the death of the patient in a short time. Somatotropic and gonadotropic functions are usually the first to decrease, followed by thyrotropic and adrenocorticotropic activity.
Partial or complete insufficiency of gonadotropins (LH and FSH) in pangypopituitarism leads to a violation of the regulation of the sex glands. In men, testosterone levels, libido and potency decrease, secondary sexual characteristics gradually disappear (hair on the chin, in the armpits, on the pubis), atrophy of the prostate gland, testicles, seminal vesicles and penis, oligoazoospermia develops. In women, signs of estrogenic activity disappear, amenorrhea and hypotrophy of the internal and external genitalia, mammary glands, depigmentation of the areola of the nipples, postpartum agalactia (Skien’s syndrome) occur.
The dominant symptom of panhypopituitarism is a sharp decrease in body weight with loss of the subcutaneous fat layer, muscle atrophy and a decrease in the volume of internal organs up to cachexia. On the part of the skin with pangypopituitarism, there is a decrease in sweating, peeling and wrinkling, the development of a waxy hue with areas of dirty-earthy pigmentation on the face and in the skin folds, acrocyanosis. Trophic disorders contribute to bone decalcification, the development of osteoporosis, tooth decay, hair loss.
With hapothalamic-pituitary tumors, there is an increase in intracranial pressure, headache, decreased visual acuity. TSH deficiency in panhypopituitarism leads to signs of hypothyroidism: lethargy, drowsiness, bradycardia, decreased blood pressure, atony of the gastrointestinal tract.
ACTH deficiency causes secondary hypocorticism, exacerbating malaise and hypotension, reducing the body’s resistance to intercurrent infections and stressful situations, contributing to the development of hypoglycemia, severe dyspeptic disorders. Patients with panhypopituitarism experience severe weakness, adynamia, violation of thermoregulation, neurological disorders (polyneuritis, polyradiculoneuritis with severe pain syndrome). Insufficiency of growth hormone (STH) and thyrotropin in children with panhypopituitarism causes growth retardation (pituitary dwarfism), lagging sexual development, cognitive impairment.
With all variants of panhypopituitarism, there is a violation of mental health: decreased emotional activity, apathy, depression, the phenomena of senile involution. With panhypopituitarism, there is a high risk of developing orthostatic collapse and a comatose state due to a combination of acute adrenal insufficiency and progressive hypothyroidism. Pituitary coma can develop suddenly, with an increase in adynamia (up to complete immobility), signs of hyponatremia and hypoglycemia, tetanic syndrome, hypothermia.
Diagnostics
The diagnosis of panhypopituitarism is based on the analysis of anamnestic data, clinical picture, results of hormonal, neuroradiological, ophthalmological examination and radiography.
To assess the dysfunction of target organs in pangypopituitarism , the levels of endocrine gland hormones are examined: TSH and T4, ACTH, 17-OX, LH and FSH, STH, prolactin, testosterone, estradiol, cortisol in blood and urine. To clarify the reserves of pituitary hormones, diagnostic tests are carried out (stimulation tests with the introduction of releasing hormones, taking methirapone, hypoglycemic test with insulin, etc.). Often in laboratory diagnostics, the determination of the content of somatomedin-C (insulin-like growth factor – IGF-1) in the blood, reflecting the level of STH, is used.
The presence of hypochromic and normochromic anemia, sometimes leukopenia with eosinophilia and lymphocytosis, low glucose levels and elevated cholesterol in the blood have an important diagnostic value in pangypopituitarism. To visualize structural anomalies of the pituitary-hypothalamic region in pangypopituitarism, MRI or CT, positron emission tomography (PET) of the brain, cone lateral craniography of the Turkish saddle, and cerebral angiography is performed to detect vascular anomalies or aneurysms. Chest x-ray, skull, spine, and arm bones are also shown to determine bone age in children and the presence of osteoporosis in adults, as well as the study of visual fields.
Differential diagnosis of panhypopituitarism in endocrinology is carried out with primary endocrinopathies, polyendocrine autoimmune syndrome, diseases leading to severe weight loss and exhaustion (malignant neoplasms, tuberculosis, enterocolitis, tropical diarrhea (sprue), porphyria, psychogenic anorexia, dystrophic myotonia).
Treatment
With panhypopituitarism, appropriate hormone replacement therapy with individual selection of doses and drug regimens is prescribed to compensate for the lost functions of the peripheral endocrine glands. In the therapy of panhypopituitarism, somatotropin is used to stimulate linear growth in children; thyroid hormones (levothyroxine sodium) are used to eliminate the symptoms of hypothyroidism, prednisone, hydrocortisone (sometimes in combination with mineralocorticoids) for adrenal insufficiency.
In the treatment of manifestations of hypogonadism, sex hormones are indicated: in women, estrogen and progesterone preparations to restore menstrual function, gonadotropins (gonadoliberin) in infertility, in men – testosterone – to normalize sexual desire and potency.
In the case of panhypopituitarism of tumor genesis, in parallel with replacement therapy, adequate treatment of the tumor is carried out: with small tumor sizes, transsphenoidal microsurgical removal in combination with radiation therapy, with prolactinomas, taking dopamine agonists (bromocriptine, cabergoline), supplemented by surgical intervention or radiation therapy, according to indications. With pituitary apoplexy, urgent decompression of the pituitary gland by transsphenoidal access is justified, as well as the use of high doses of glucocorticoids.
Prognosis and prevention
The prognosis for panhypopituitarism is determined by the root cause that caused the functional insufficiency of the adenohypophysis and the adequacy of therapeutic measures (surgical treatment, HRT). After the treatment of panhypopituitarism, it is necessary to assess the hormonal status of the patient (after 3, 6, 12 months and further annually), with the development of visual defects, radiography of the Turkish saddle area and pituitary gland visualization are shown (every 2 years for 10 years).
Preventive measures include the prevention of massive postpartum and other bleeding, TBI, neuroinfections, etc. factors damaging the pituitary gland.