User:Burkin202/Sheehan's syndrome

Article Draft

Lead

Sheehan's syndrome, also known as postpartum pituitary gland necrosis, occurs when the pituitary gland is damaged due to of significant blood loss and hypovolemic shock (ischemic necrosis) usually during or after childbirth leading to decreased functioning of the pituitary gland (hypopituitarism). The pituitary gland is an endocrine organ, meaning it produces certain hormones and is involved in the regulation of various other hormones. This gland is located in the brain and sits in a pocket of the sphenoid bone known as the sella turcica. The pituitary gland works in conjunction with the hypothalamus, and other endocrine organs to modulate numerous bodily functions including growth, metabolism, menstruation, lactation, and even the "fight-or-flight" response. Hence, damage to the pituitary gland can have downstream effects on any of these bodily functions.

Signs and symptoms

The various signs and symptoms of Sheehan's syndrome are caused by damage to the pituitary, thereby causing a decrease in one or more of the hormones it normally secretes. Because the pituitary controls many glands in the endocrine system, partial or complete loss of a variety of functions may result. Many of the signs and symptoms of Sheehan's are considered "nonspecific" in the medical community; in other words these signs and symptoms are seen in a number of different disease processes, and are not specific to a singular disease or syndrome.

In some cases, a woman with Sheehan syndrome may be relatively asymptomatic initially; therefore, the diagnosis would not be made until years later when features of hypopituitarism become evident. Hypopituitarism can cause secondary hypothyroidism (hypothyroidism due to pituitary dysfunction), adrenal insufficiency due to glucocorticoid deficiency, sex hormone deficiency (gonadotropin deficiency), prolactin deficiency (a hormone responsible for lactation), growth hormone deficiency, or rarely central diabetes insipidus (Anti-diuretic hormone deficiency). The most common initial symptoms of Sheehan's syndrome are difficulties with or total absence of lactation (agalactorrhea). Another common sign is infrequent menstrual cycles (oligomenorrhea) or absent menstrual cycles (amenorrhea) following delivery. In addition to menstrual irregularities other signs of gonadotropin deficiency are hot flashes, decreased libido, and breast involution.

Symptoms of secondary hypothyroidism are exactly the same as primary hypothyroidism: tiredness, intolerance to cold, constipation, weight gain, hair loss and slowed thinking, as well as a slowed heart rate and low blood pressure. Adrenal insufficiency can present acutely or chronically. In a more chronic case, it is similar to Addison's disease with symptoms including fatigue, weight loss, hypoglycemia (low blood sugar levels), low hemoglobin levels (anemia) and hyponatremia (low sodium levels) that develop over several months or years. Acute adrenal insufficiency is referred to as an adrenal crisis, which can be life-threatening, and occurs very shortly after the inciting event i.e. significant blood loss post-partum in the context of Sheehan's syndrome. Adrenal crisis signs and symptoms include hypoglycemia, hypotension, weakness, fatigue, and seizures from severe hyponatremia. "Uncommonly, [Sheehan's syndrome] can present acutely with circulatory collapse, congestive cardiac failure or psychosis".

Growth hormone deficiency is one of the most common hormone deficiencies of hypopituitarism seen in Sheehan’s syndrome. Low levels of growth hormone may present with low energy, body aches, or subtle wrinkling of the skin around the eyes or mouth. The symptoms of diabetes insipidus are increased thirst, excessive urination, headache, and fatigue. Hematological changes might be seen as well such as (anemia) or low platelets (thrombocytopenia). Hyponatremia is seen in many cases of Sheehan's syndrome because it can result from multiple etiologies. Drops in thyroid hormones and glucocorticoid/adrenal hormones can indirectly lead to hyponatremia through water retention, while blood loss can trigger hyponatremia through ADH secretion. The development of Syndrome of Inappropriate Anti-Diuretic Hormone in patients with Sheehan's syndrome has been documented in the literature, although the mechanism is not well understood.

Causes

As stated, Sheehan's syndrome is caused by damage to the pituitary, thereby causing a decrease in one or more of the hormones it normally secretes. Sheehan's syndrome typically occurs because of excessive blood loss after delivery (post-partum hemorrhage), although there appear to be several risk factors that may contribute to its development. This syndrome does not appear to be exclusively linked to childbirth, as Sheehan's syndrome has been reported in pregnant patients that experienced massive hemorrhage from non-obstetrical causes. The pituitary gland grows and has a higher metabolic demand during pregnancy, resulting in an increased demand for blood flow. One cause of pituitary growth in pregnancy is the proliferation of lactotroph cells which produce prolactin, the hormone responsible for milk production. Other hormone-secreting cells of the pituitary undergo rapid growth in pregnant women as well, which contribute to the gland's enlargement.

Thus, if the body enters a state of shock from excessive blood loss in post-partum delivery, the pituitary gland is more susceptible to injury. Although the vast majority of cases of Sheehan's syndrome occur in the setting of massive blood loss, cases have been documented of acute Sheehan's syndrome occurring with blood loss volumes that do not qualify as "massive". Some possible predisposing factors to Sheehan’s syndrome may include: disseminated blood coagulation (DIC), hypotension, small sella turcica size, and blood clots from a pre-existing hypercoagulable disorder. Atony of the uterus is a leading cause of post-partum hemorrhage, therefore uterine atony could induce Sheehan’s syndrome.

Pathophysiology

This syndrome seems to arise when certain factors compound each other to cause pituitary injury. The physiologic enlargement of the pituitary gland in conjunction with an interference in its blood supply ultimately result in pituitary ischemia and necrosis. One cause of pituitary growth associated with the risk of Sheehan’s syndrome is the hyperplasia of lactotrophs. The anterior pituitary is supplied by a low pressure portal venous system. It has been suggested that the arrangement of the pituitary's blood supply contribute to its susceptibility for injury. "The highly vascularized pituitary tissue involves one of the most rapid blood flow in the human body and probably, therefore, has a tendency to infarction because even small degrees of change in the pituitary intravascular pressure cause an arrest of blood flow". Ischemia may occur as a result of vasospasm from shock, hypotension, thrombosis, or direct vascular compression of the hypophyseal artery from the enlarged pituitary gland itself. The presence of disseminated intravascular coagulation (i.e., in amniotic fluid embolism or HELLP syndrome) also appears to be a factor in its development.

The anterior pituitary is more commonly affected in Sheehan's syndrome because of the structure of the portal venous system. Posterior pituitary involvement leading to central diabetes insipidus is much rarer, and typically reflects more extensive damage to the organ and more severe disease.

At present, the part that autoimmunity plays in the development of Sheehan's syndrome is uncertain. Several case reports have identified anti-pituitary antibodies in patients diagnosed with Sheehan's. Some patients also tested positive for anti-hypothalamus antibodies. Given that many patients that have developed Sheehan's syndrome do not have detectable levels of these antibodies, it is unclear whether these antibodies cause this syndrome or result from it.

Diagnosis

Typically an important clue that leads to a diagnosis of Sheehan's syndrome is identifying a deficiency in one or more of the hormones produced directly, or indirectly, by the pituitary gland. The extent of hormone deficiency, and which hormones are affected depends on the extent of the damage to the pituitary. Hormonal assays measure the levels of these hormones which include but are not limited to T4, TSH, estrogen, gonadotropin, cortisol, and ACTH. It might be difficult to detect damage to these hormone pathways if hormone levels are at the borderline of the abnormal range. In this case, stimulation tests will be done to determine if the pituitary is responsive to hypothalamic hormones.

MRI is useful in diagnosing Sheehan's syndrome since it examines the structure of the pituitary and may identify any anatomical damage. MRI findings will vary based on how early or late in the disease process the test is being conducted. If an MRI is conducted early enough in the disease process the pituitary may appear larger than normal, and show changes that are consistent with damage from lack of blood supply . Later in the disease process of this syndrome the damage imposed on the pituitary gland will cause it to shrink, and leave a partially empty or totally empty sella turcica on MRI .

Treatment

The mainstay of treatment is hormone replacement therapy for the hormones that are missing. Treatment plans and dosages should be individualized by an endocrinologist. Glucocorticoids may be administered to address or prevent an adrenal crisis, a potential serious complication of Sheehan syndrome.

Epidemiology

In a study of 1,034 symptomatic adults, Sheehan’s syndrome was found to be the sixth-most frequent etiology of growth hormone deficiency, being responsible for 3.1% of cases (versus 53.9% due to a pituitary tumor).

Sheehan syndrome is more prevalent in developing countries than developed countries. Additionally, it was found that the majority of women who experienced Sheehan syndrome gave birth at home rather than in a hospital.

History

The specific association with postpartum shock or hemorrhage was described in 1937 by the British pathologist Harold Leeming Sheehan (1900–1988). The initial distinction was made in the research article “Post-Partum Necrosis of the Anterior Pituitary”. In his research, Dr. Sheehan reviewed (through autopsy) the effects of pituitary necrosis on 12 cases of patients that experienced postpartum necrosis. He observed cases where lesions and death occurred during or after pregnancy, as well as cases where death occurred in the late stage of necrosis (years later). This started the initial distinction of Sheehan’s syndrome from Simmonds’ disease (also known as hypopituitarism). Dr. Sheehan noted that significant feature of these patients' cases was hemorrhaging, which in his experience was most commonly caused by either: placenta Previa (low placenta), uterine rupture, cervical or uterine tears, post-partum atony, or retained placenta. Simmonds' disease, however, occurs in either sex due to causes unrelated to pregnancy.

However, in his 1939 publication: “Simmonds’ Disease due to Post-partum Necrosis of the Anterior Pituitary”, Dr. Sheehan displays post-partum necrosis as a cause of Simmonds’ disease, thus establishing the relationship between the two conditions. According to Sheehan in 1939 approximately 41% of survivors of severe postpartum hemorrhage (PPH) and/or hypovolemic shock experienced severe or partial hypopituitarism.

Society and Culture

In the developed world Sheehan’s Syndrome is a rare complication of pregnancy; although this syndrome is more prevalent in developing countries "it is still a worldwide health problem".

A retrospective study in Turkey found that the prevalence of Sheehan’s syndrome was directly proportional to the amount of at-home deliveries each decade. This may be due to previously limited obstetric techniques present in a home environment.