Sheehan Syndrome: What every woman should know
Submitted by Josephine Kamera RN, EdD
Sheehan Syndrome (SS) is a disease of the pituitary gland. SS is a rare but a life threatening complication of post-partum hemorrhage. SS is associated with postpartum decreased functioning of the pituitary. During pregnancy, the body mechanism changes, including the pituitary gland that increases in size and becomes highly vasculature. In some cases, severe postpartum hemorrhage results in decreased blood supply to the pituitary. This blood loss causes necrosis of the pituitary gland.
In pregnancy, SS refers to post partum hypopituitarism due to adenohypophysis necrosis occurring during severe hypotension or shock secondary to massive hemorrhage during or after delivery (Meregildo-RodrÃguez, 2018). Its incidence was very high in underdeveloped and developing countries due to lack of adequate prenatal care. However, frequency of SS has decreased because of recent advances in obstetrical care (Arora & Sahni, 2020; Matsuzaki et al., 2018). Marked improvement in care of pregnant mothers has reduced the prevalence of the syndrome and all complications associated with it including death.
The endocrine system is one of the most essential systems in the human body. It plays a vital role in producing hormones that are needed for maintaining homeostasis within the body. These hormones are crucial in normal functioning of the body; promote growth, and development of sexual characteristics. Any interruption to this hormonal production leads to malfunctioning of the body. One of the main glands within the endocrine system is the pituitary gland.
SS was first described by H. L. Sheehan in 1937 (Sheikh, 2018; Schury & Adigun, 2017). Sheehan described the syndrome as adrenal pituitary insufficiency from hypovolemia secondary to excessive blood loss during or after delivery and if sustained for several hours, tissue necrosis occurs. Further studies have since expanded on this theory. Current research maintains that this syndrome is associated with severe post-partum hemorrhage, and is responsible for some of the maternal problems (Arora & Sahini, 2020; Meregildo-RodrÃguez, 2018). As Matsuzaki et al., 2018 point out "this condition can present with chronic symptoms after a relatively long latent period, including failure to lactate, mild headache, fatigue, nausea, and amenorrhea. (page2).
This paper will discuss the underlying pathophysiology, diagnosis and treatment of SS.
The pituitary gland is located below the hypothalamus. It sits in the sella turcica, a small bony structure at the base of the brain, and is divided into two lobes, the anterior and posterior pituitary. The anterior pituitary gland also called the adenohypophysis is responsible for SS. Hormones secreted by the anterior pituitary are adreno cortico trophin hormone (ACTH), melanocyte-stimulating hormone (MSH), luteinizing hormone (LH), gonadotrophin, prolactin, follicle stimulating (FSH), and thyroid stimulating (TSH). These hormones have varied functions and are responsible for maintaining balance within the body. Blood supply to the pituitary gland is through the hypophyseal portal system. This system is different from all the other circulatory systems in that releasing hormones from the hypothalamus are carried through the hypophyseal system directly to the adenohypophysis. When blood supply is decreased through vasospasm, necrosis can occur.
The pituitary gland is highly susceptible to necrosis due to its rich blood supply (Karaca et al., 2016; Schury & Adigun, 2017). The first reaction of the pituitary gland after necrosis is edema. This edema initiates malfunctioning of the pituitary. In SS, excessive fibrin is deposited in the pituitary vessels, clogging the vessels, resulting in decreased blood supply and infarction of the pituitary (McCance & Huether, 2006; Schury & Adigun, 2017). Thus pituitary insufficiency leads to hypopituitarism, and subsequent decreased pituitary hormones.
Deficiency of pituitary hormones results in a host of disorders. Signs and symptoms of SS usually appear slowly although, in some cases they can appear soon after delivery. In breast feeding mothers one of the first signs of SS is failure to lactate, fatigue, loss of pubic and axillary hair, decreased libido, breast atrophy, and amenorrhea (Sethuran et al., 2020; Waters, 2020). Additionally, patients can present with "hoarseness of voice, dry skin, thinning of hair, facial puffiness, non-pitting pedal edema, and a delayed ankle jerk" Dosi et al., 2013, page 318). It is therefore relevant to conclude that SS can cause high morbidity in women.
SS has traditionally been linked to hypopituatarism. In a quest to conclude if post partum hemorrhage is the only cause of hypopituitarism in SS, (De Bellis et al., 2008) investigated if anti-pituitary antibodies (APAs) and anti-hypothalamus antibodies (AHAs) are also involved. The authors evaluated a group of 20 women with an established diagnosis of SS of duration of three to forty years. Findings revealed 40% of the women with AHA, and 35% with APA. Results confirmed that an autoimmune pituitary process could be involved in this syndrome, inducing late hypopituitarism following post partum hemorrhage (De Bellis et al., 2008). From this study, it can be concluded that patients with SS, even after many years of the syndrome, still produce anti-pituitary and anti-hypothalamus antibodies. The authors suggest future research using a larger cohort to better clarify their assumption.
Other possible areas of research include investigating whether conditions like hypovolumea, diabetes insipidus, preexisting psychosis or malignancy of the pituitary are associated with SS. For example, pituitary adenomas also cause malfunctioning of the gland by reducing the amount of hormones the pituitary produces. Use of imaging studies will aid in making a differential diagnosis between malignancy and SS. The pituitary gland releases antidiuretic hormone (ADH). Lack of ADH in the body system may lead to diabetes insipidus. In this case, research will be beneficial to rule out SS as the cause of diabetes insipidus.
Diagnosis and Treatment
In most cases, the onset of SS is slow in progression. It can take years before signs and symptoms of SS appear but at times onset can be acute and fatal (Matsuzaki et al., 2018). Diagnosis of SS can be difficult because after delivery, it is common for a woman to experience symptoms like headache, fatigue, and reduced lactation post delivery; therefore many women will not seek medical attention. In those women with symptoms that appear immediately post partum, prompt treatment is vital to prevent further complications. To the experienced obstetrician, the patient's history and physical examination usually leads to a diagnosis of SS. Other cases of SS have been found to develop psychosis-like features. Women with history of severe post partum hemorrhage can present with changes in mental status (Chandra et al, 2020; Reddy et al, 2017).
A recent discovery indicated that SS is linked to altered mental status and COVID 19 infection (Gundluru et al., 2021). The authors report a case of a 38 year old woman who presented with altered mental status, shortness of breath, cough, hypotension, and tachycardia. The woman tested positive for COVID 19 infection. Further review of past medical history revealed that the woman had delivered twins 17 years ago. She suffered massive post-partum hemorrhage and had 8 units of blood transfusion. A diagnosis of SS was made through imaging studies. Patient was discharged home on prednisone and endocrinology follow-up. Extensive review of medical history is crucial to rule out complications that increase the risk of SS.
Some research has suggested that imaging studies should be performed early in pregnancy to rule out neurological disorders already present before delivery. As noted by Zak et al., 2007, some clinicians are reluctant to perform imaging studies during pregnancy, yet it is important to rule out conditions that can be fatal to the woman after delivery. The authors carried out a study to examine cerebrovascular complications (post partum cerebral angiopathy), neuroendocrine disorders of the pituitary gland (SS), and neoplastic disorders (pituitary adenomas). Imaging studies were performed for each condition. In some of these cases abnormalities were detected. The findings supported the argument that preexisting conditions in pregnancy can contribute to complications after delivery. The conclusion from these studies is that earlier use of imaging will result in fewer delayed diagnoses. Use of imaging studies is increasingly being performed "making definitive diagnosis that can save a patient's life," (Zak et al., 2007, p. 106).
Cimino-Fiallos et al., 2018 present the benefits of using magnetic resonance imaging studies to rule out SS. The authors discuss a case of a 54 year old that was found responsive with a blood sugar level of 17 mg/dl. The woman had past histories of hypothyroidism, anemia and Cesarean section 17 years prior, which was complicated by postpartum hemorrhage. A brain Magnetic Resonance Imaging was performed, which revealed an empty sella turcica, thus SS diagnosis was made. The patient was treated with steroids and levothyroxine and, scheduled endocrinology follow-up.
Overall, treatment involves replacing the hormones that the pituitary is failing to produce. Estrogen and progesterone hormonal replacement therapy, and adrenal cortical hormones will be administered for the remainder of the woman's life. Sodium chloride and hydrocortisone are also administered in addition to hormonal therapy to treat hyponatremia. Iron treatment is given for anemia. It is important to educate the patient on the importance of hormonal therapy as interruption in treatment can be detrimental to her health. In addition, according to Anderson and Etches (2007) "hysterectomy is the definitive treatment in women with severe, intractable hemorrhage" (p. 881).
This paper has explored the underlying causes, effects and management of SS. Severe circulatory failure has been proven to be the cause of SS. Prevention of post partum hemorrhage is therefore crucial. Post partum hemorrhage is a life threatening condition. Although it may be arrested immediately after delivery, it can be a leading cause of other complications that can develop well after pregnancy.
SS continues to be one of the most threatening complications of pregnancy due to inability of the pituitary gland to produce hormones essential for normal body function. Lack of these hormones may lead to total failure of the body and eventually death. SS is difficult to detect because its onset is slow, nonspecific, and often times signs and symptoms can mimic other disorders.
Prevention of SS starts from providing pregnant mothers with the best obstetrical care. Obstetricians need to be aware of dangers of post partum hemorrhage, and exercise extreme caution during the third stage of labor to prevent unnecessary uterine rupture and vaginal lacerations. Post partum hemorrhage requires prompt intervention.
Studies have supported benefits of screening preexisting conditions during pregnancy that can exacerbate SS. Adequate obstetrical care include screening for eclampsia and preeclampsia as these conditions can lead to placenta previa and shock. Women need to be educated on signs and symptoms of SS so that they seek treatment as soon as possible. For those women diagnosed with SS, they need to be aware that they will be on hormonal therapy for the remainder of their lives.
Although SS is a challenging disorder, technological improvement is helping in early diagnosis. Women are now able to receive treatment much earlier preventing further complications. The good news is that SS is no longer much of a threat due to improved obstetrical care particularly in developing countries.
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