Sheehan's syndrome
Sheehan's syndrome | |
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Other names | Simmond's syndrome, postpartum hypopituitarism, postpartum pituitary gland necrosis |
Anatomy of normal pituitary gland and surrounding structures | |
Empty sella turcica on MRI as seen in severe cases of Sheehan's syndrome | |
Specialty | Endocrinology, obstetrics and gynaecology |
Sheehan's syndrome, also known as postpartum pituitary gland necrosis, occurs when the
Signs and symptoms
The various signs and symptoms in Sheehan's syndrome are caused by damage to the pituitary, thereby causing a decrease in one or more of the hormones it normally secretes. Since the pituitary controls many glands in the endocrine system, partial or complete loss of a variety of functions may result.[4] 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.[5]
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.[6] In rare instances this syndrome can present acutely with unstable vital signs, dangerously low blood glucose levels, heart failure, or even psychosis.[7][8] Hypopituitarism can lead to an interruption in any of the following hormone pathways: thyroid disorder (secondary hypothyroidism), adrenal gland (adrenal insufficiency due to glucocorticoid deficiency), sex hormone (gonadotropin deficiency), prolactin (a hormone responsible for lactation), growth hormone, or rarely anti-diuretic hormone deficiency (central diabetes insipidus).[2] Since damage to the pituitary can cause a deficiency in more than one of these hormone pathways simultaneously, it is possible to have a mix of any of the signs or symptoms listed below.[8]
Sheehan's syndrome's most common initial symptoms are difficulties with or total absence of lactation (
Growth hormone deficiency is one of the most common hormone deficiencies of hypopituitarism seen in Sheehan's syndrome.[9] Low levels of growth hormone may present with low energy, body aches, or subtle wrinkling of the skin around the eyes or mouth.[5][7] The symptoms of anti-diuretic hormone deficiency are increased thirst, excessive urination, headache, and fatigue.[12] Hematological changes might be seen as well such as anemia or low platelets (thrombocytopenia).[9] 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.[7] 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.[7]
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 are several risk factors that may contribute to its development.[8] 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.[8] The pituitary gland grows and has a higher metabolic demand during pregnancy because the pituitary needs to rev up the production of certain hormones associated with pregnancy.[8][4] This higher metabolic demand, in turn, leads to higher demand for blood flow.[4]
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.
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.[8] One cause of pituitary growth associated with the risk of Sheehan's syndrome is the hyperplasia of lactotrophs which produce prolactin, the hormone responsible for milk production.[4] Other hormone-secreting cells of the pituitary undergo rapid growth in pregnant women as well, which contribute to the gland's enlargement.[9]
The anterior pituitary is supplied by a low pressure portal venous system.[14] 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.[12] 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".[8] 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.[8][4][14] The presence of disseminated intravascular coagulation (i.e., in amniotic fluid embolism or HELLP syndrome) also appears to be a factor in its development.[8]
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
MRI is useful in diagnosing Sheehan's syndrome since it examines the structure of the pituitary and may identify any anatomical damage.[4] 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.[15] 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.[7]
Treatment
The mainstay of treatment is hormone replacement therapy for the hormones that are missing.
Epidemiology
The exact prevalence of this syndrome is difficult to define because the incidence varies so much from country to country. Sheehan syndrome is more prevalent in developing countries than developed countries.[14] In a study from the United Kingdom in 2001 only 1.4% of patients with hypopituitarism were diagnosed with Sheehan's syndrome.[5] Just a few years earlier in 1996 the World Health Organization estimated that 3 million women were effected by Sheehan's syndrome.[8] 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).[7] Additionally, it was found that the majority of women who experienced Sheehan syndrome gave birth at home rather than in a hospital.[14]
History
The specific association with postpartum shock or hemorrhage was described in 1937 by the British pathologist
However, in his 1939 publication, "Simmonds' Disease due to Post-partum Necrosis of the Anterior Pituitary", Sheehan displays post-partum necrosis as a cause of Simmonds' disease, thus establishing the relationship between the two conditions.[19] According to Sheehan in 1939 approximately 41% of survivors of severe postpartum hemorrhage (PPH) and/or hypovolemic shock experienced severe or partial hypopituitarism.[14]
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 continues to effect women around the world.[8] 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.[7] This may be due to previously limited obstetric techniques present in a home environment. Blood loss associated with episiotomy and forceps exacerbating blood loss when the placenta separates from the wall of the uterus, particularly in mothers with low blood pressure, even in obstetric setting, namely hospital, caused a more subtle Sheehan's syndrome of Growth Hormone, Anti-Duretic Hormone, ACTH deficiency, which may be life threatening if missed; PubMed.gov Sheehan's in modern times:a nationwide retrospective study Iceland 2011, where every mother gives birth in hospital, with full obstetric care available.
Research
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.[4] Some patients also tested positive for anti-hypothalamus antibodies.[20] 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.[8]
References
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