Sheehan syndrome is a neuroendocrine disorder caused by the death of pituitary cells due to complicated childbirth or abortion. It is manifested by a decrease in milk secretion up to complete cessation, oligomenorrhea and amenorrhea, swelling of the body, brittle hair and nails, dizziness, fainting, weakness, fatigue, hyperpigmentation of the skin. For diagnosis, analysis of the level of hormones of the pituitary gland, thyroid gland, ovaries, adrenal glands, targeted radiography of the skull, CT, MRI are used. The treatment regimen for Sheehan syndrome involves the appointment of hormone replacement therapy, symptomatic antianemic and anabolic agents.
Sheehan’s syndrome is the second most common cause of hypopituitarism in adulthood. The disease was first described at the end of the XIX century, named after the British scientist Harold Leeming Sheehan, who established a link between adenohypophysis necrosis and severe blood loss in childbirth in 1937. The prevalence of clinically expressed disease does not exceed 0.1%, in poor and developing countries this indicator is higher, for example, in India, postpartum hypopituitarism is detected in 2.7-3.9% of women over 20 years of age. Mild forms of the disorder may not be recognized, often regarded as hypofunction of the thyroid gland or vegetative vascular dystonia of the hypotonic type. With massive bleeding after childbirth and abortions, signs of hypopituitarism are detected in 40-45% of women. Sheehan’s disease develops in 25% of patients who have lost up to 800 ml of blood in childbirth, in 50% of women in labor with blood loss of up to 1 liter and in 65-67% — with loss of more than 1 liter of blood.
The morphological basis for the development of postpartum hypopituitarism is the death of adenohypophysis cells with the subsequent development of hormonal insufficiency. Destructive necrotic processes in the pituitary tissue are usually associated with impaired blood supply to the gland, which compensatorily increases during pregnancy. The immediate causes of arterial hypotension, leading to irreversible damage to pituitary cells, are:
- Massive blood loss. The volume of lost blood is considered critical for the development of the syndrome, 800-1000 ml. Threatening obstetric bleeding is observed in ectopic pregnancy, premature detachment, presentation or increment of the placenta, uterine hypotension, birth trauma (rupture of the uterus or its cervix, vagina, perineum).
- Infectious-toxic shock. Pronounced microcirculatory disorders in septic shock occur under the action of endo- and exotoxins of microbial agents. Significant bacterial contamination is possible with a prolonged anhydrous period as a result of premature discharge of amniotic fluid, chorioamnionitis, postpartum endometritis, peritonitis, sepsis.
- DIC syndrome. Generalized intravascular coagulation with vascular thrombosis and coagulopathic bleeding causes severe ischemic disorders in various organs, including the pituitary gland. DIC develops against the background of blood loss, shock conditions, amniotic fluid embolism and immune conflicts, aggravates their course.
Predisposing factors to the occurrence of Sheehan’s disease are gestosis, occurring with high blood pressure and impaired renal function, idiopathic and secondary thrombocytopenia, arterial hypertension and symptomatic arterial hypertension, severe renal insufficiency. The risk group also includes patients with multiple pregnancies and rapid childbirth.
The key link in the development of Sheehan syndrome is the discrepancy between the pituitary gland’s need for blood supply and the volume of incoming blood. Pregnant women have a physiological increase in the size of pituitary tissue by 120-136%, associated with the need to carry the fetus and prepare the woman’s body for childbirth. First of all, lactotropocytes are hypertrophied and hyperplasized — cells that secrete the hormone prolactin, under the influence of which the tissue of the mammary glands develops and prepares for the production of milk. At the same time, the blood flow in the organ remains unchanged, so the pituitary gland becomes especially sensitive to circulatory disorders. Hypovolemic and coagulopathic bleeding that occurs during childbirth leads to a shortage of blood supply to glandular tissue, which is accompanied by vasoconstriction and subsequent white infarction with coagulation necrosis. As a result of cell death, the production of hormones of the anterior pituitary gland stops, which forms a typical clinical picture of Sheehan disease.
The systematization of the forms of postpartum hypopituitarism is carried out taking into account the severity of the clinical picture and the degree of damage to the adenohypophysis. According to the severity of symptoms, the disease can be mild, moderate and severe. Based on the depth of glandular tissue lesion, modern specialists in the field of obstetrics and gynecology distinguish the following variants of Sheehan syndrome:
- Global. Due to irreversible damage, there is no or sharply reduced secretion of thyroid-stimulating hormone, gonadoliberins, ACTH with loss of corresponding functions.
- Partial. The secreting tissue is partially preserved, due to its destruction, thyroid-stimulating, gonadotropic and adrenocorticotropic insufficiency is noted.
- Combined. The destruction of the pituitary tissue led to disruption of a pair of endocrine glands (adrenal glands and thyroid or genital and thyroid).
The severity of the syndrome is directly related to the severity of pituitary damage: a mild form of the disorder occurs when 60-70% of adenohypophysis cells are destroyed, moderate clinical damage becomes noticeable with the destruction of more than 80% of pituitary tissue, the death of 90% of cells is accompanied by severe pituitary insufficiency.
Depending on the depth of destructive processes, the disease debuts immediately or within a few months after delivery. Often, the first sign of postpartum hypopituitarism is the involution of the mammary glands and a violation of milk secretion (hypogalactia, agalactia). Subsequently, the clinical picture of the syndrome is supplemented by other manifestations of neuroendocrine insufficiency. With a mild course of the disease, the amount of secreted milk is not enough to meet the nutritional needs of the baby. A woman periodically experiences headaches, complains of fatigue, dizziness, which occur against the background of a drop in blood pressure.
Shihan’s disease of moderate severity is manifested by a complete lack of milk, constant loss of strength, drowsiness, memory loss, a tendency to fainting. The patient has swelling, body weight increases, constipation occurs. Despite the absence of breastfeeding, the monthly cycle does not recover immediately, menstruation becomes scarce and shortened to 2-3 days (oligomenorrhea). In severe cases, the clinic is aggravated by persistent amenorrhea, generalized edema of the whole body, weight loss. The mammary glands and external genitalia are hypotrophic. Women complain of brittle nails, hair loss. The skin acquires an even bronze hue.
A characteristic consequence of the moderate and severe forms of Sheehan syndrome is therapeutically resistant anemia. In the most severe cases, hormonal insufficiency that occurs during postpartum hypopituitarism is complicated by deep depression of the functions of the nervous, respiratory, cardiovascular and other systems due to hypopituitic or hypothyroid coma, the development of Waterhouse-Friederiksen syndrome (acute adrenal insufficiency). Violation of the gonadotropic function of the pituitary gland leads to premature involution of the mammary glands, early menopause, persistent infertility.
The appearance of signs of neuroendocrine insufficiency after recent complicated childbirth or abortion is the basis for a detailed study of the pituitary gland function. The diagnostic search for suspected Sheehan syndrome is aimed at assessing the condition and functionality of the pituitary tissue. The most informative for the diagnosis of postpartum hypopituitarism are:
- The study of the content of hormones. A decrease in the concentration of TSH, ACTH, FSH, LH, prolactin indicates a violation of the secretory function of the adenohypophysis. An indirect sign of insufficient synthesis of tropic hormones is a low level of estriol, triiodothyronine (T3), thyroxine (T4), cortisol.
- Methods of medical imaging. A targeted X-ray of the Turkish saddle reveals a decrease in the size of the gland. More detailed information about the structure and changes of the organ is provided by tomographic techniques (MRI, computed tomography).
As additional examinations, a urine test for 17-ketosteroids and a glucose tolerance test are recommended (after a sugar load, a hypoglycemic curve is noted). The disease is differentiated with pituitary tumors, encephalitis, neurosarcoidosis, hypocorticism (Addison’s disease), hypothyroidism, secondary ovarian hypofunction. If necessary, the patient is consulted by an endocrinologist, neurologist, neurosurgeon, oncologist.
The main objectives of therapy for postpartum hypopituitarism are the restoration of normal hormonal background and correction of possible symptomatic disorders. The course of pathogenetic treatment is prescribed taking into account the form and severity of the disease. The standard treatment regimen provides for the use of such methods and approaches as:
- Hormone replacement therapy. Taking into account the deficiency of tropic hormones, patients are prescribed glucocorticoids, thyroid preparations on a regular basis or in courses. Up to 45 years of age, oral contraceptives are cyclically used in violation of the menstrual cycle.
- Symptomatic remedies. Since Sheehan’s disease often manifests itself as therapy-resistant anemia, periodic use of iron preparations under the control of a general blood test is indicated. Anabolics are recommended to ensure physiological protein metabolism.
Prognosis and prevention
Early diagnosis and adequate treatment (in most cases, lifelong) can significantly improve the quality of life of the patient and exclude the development of dangerous complications. For the prevention of Sheehan syndrome, pregnancy planning and refusal of abortions are recommended. Timely registration in the antenatal clinic, regular scheduled examinations by an obstetrician-gynecologist ensure timely detection of pregnancy complications, genital and somatic pathology that can lead to massive obstetric bleeding, DIC syndrome, etc.