The presentations of SS arise from pituitary injury leading to a diminished levels of one or more hormones secreted by the pituitary gland, such as prolactin, ADH, thyroid stimulating hormone (TSH) and cortisol [6] [7]. Women with SS most commonly present with difficulty or inability to lactate (agalactorrhea). After delivery, if the menstrual cycle doesn’t return (amenorrhea) or is very light (oligomenorrhea), this may also be a sign of SS. Milder symptoms may go unnoticed in patients for years: fatigue, constipation, hair loss, bradycardia, hypotension and cold intolerance, which are all associated with hypothyroidism, may indicate SS. Due to the reliance of the adrenal gland on hormones produced by the pituitary gland, patients may also experience symptoms of adrenal deficiency, which is usually due to decreased circulating cortisol, causing anemia, low blood glucose and sodium, fatigue and weight loss. Furthermore, since cortisol is important for maintaining homeostasis, especially during stress, patients may experience attacks during high stress events, such as surgery or infection, leading to symptoms that correspond to an Addison crisis, which may be life threatening and should be treated immediately. Rarely, acute SS may occur following delivery and is primarily associated with hyponatremia. Loss of hormones is SS may follow a general pattern that starts with GH, followed by FSH, LH, ACTH and finally TSH.

• Weight Gain

  Review of systems is positive for fatigue, lightheadedness, and a 3-pound weight gain over the last 3 weeks. Her delivery was complicated by placenta accreta with postpartum blood loss. Her newborn infant is doing well on formula. [step1.medbullets.com]

  gain Difficulty staying warm 7. [de.slideshare.net]

  Symptoms of hypothyroidism such as fatigue, bradycardia, hypotension, weight gain, and constipation may occur months later along with the loss of axillary and pubic hair. Adrenal insufficiency can also occur with symptoms of fatigue and weight loss. [statpearls.com]

  Symptoms of hypothyroidism such as fatigue, bradycardia, hypotension, weight gain, and constipation may occur months later along with the loss of axillary and pubic hair. The skin is dry, the eyebrows thin. The thyroid may be impalpable. [accessanesthesiology.mhmedical.com]

  Adjustments in dosage may also be necessary during pregnancy or with marked weight gain or weight loss. [knowyourdisease.com]

• Weakness

  Patients may present with amenorrhea, lactation failure, weakness, weight loss, dry skin, loss of axillary and pubic hair, breast atrophy, and psychiatric disturbance. [pulsus.com]

  […] disorder resulting from pituitary necrosis following peri- or postpartum hemorrhage characterized by various symptoms depending on resulting hormone decrease (e.g. failure or difficulty with lactation, oligo- or amenorrhea, hot flashes, decreased libido, weakness [orpha.net]

  She was commenced on appropriate hormone replacement therapy, which led to significant improvement in lethargy, anorexia, muscle weakness, and episodes of hypoglycemia. [tandfonline.com]

  Agalactia is the first and foremost most sign Amenorrhea Evidence of Hypothyroidism Decreased insulin tolerance- Hypoglycemia Signs of Adreno-cortical failure:- (axillary sweating absent, loss of axillary and pubic hair, decrease in skin pigmentation) Weakness [de.slideshare.net]

  A case of Sheehan Syndrome with chronic diffuse muscle pain and weakness. Medical Science and Discovery, 6(11), 310–312. https://doi.org/10.36472/msd.v6i11.315 Received 2019-09-24 Accepted 2019-10-27 Published 2019-10-28 References Shivaprasad C. [medscidiscovery.com]

• Pain

  Seek emergency medical treatment if you experience the following signs and symptoms: Severe weakness Confusion Pain in your lower back or legs Severe abdominal pain, vomiting and diarrhea, leading to dehydration Reduced consciousness or delirium In an [mayoclinic.org]

  In March 1998, she started to have mild chest pain on exertion. Investigations confirmed patent previous grafts with progression of atheromatous disease in all her native coronary arteries. [academic.oup.com]

  Fingerprint Diabète insipide Diabetes insipidus Imagerie par résonance magnétique Insuffisance anté-hypophysaire du post-partum Magnetic resonance imaging Post-partum hypopituitarism Sheehan syndrome Syndrome de Sheehan Anesthesiology and Pain Medicine [jhu.pure.elsevier.com]

• Weight Loss

  loss (Hypophyseal Cachexia)  Treatment:- Antibiotic Therapy or Surgery [de.slideshare.net]

  The dosage of corticosteroid medications may also require adjustments during months of pregnancy or when the patient has undergone marked weight loss or weight gain. [hxbenefit.com]

  Symptoms of hypothyroidism such as fatigue, bradycardia, hypotension, weight gain, and constipation may occur months later along with the loss of axillary and pubic hair. Adrenal insufficiency can also occur with symptoms of fatigue and weight loss. [statpearls.com]

  Adjustments in dosage may also be necessary during pregnancy or with marked weight gain or weight loss. [knowyourdisease.com]

  Signs and symptoms may include: Extreme fatigue Weight loss and decreased appetite Darkening of your skin (hyperpigmentation) Low blood pressure, even fainting Salt craving Low blood sugar (hypoglycemia) Nausea, diarrhea or vomiting (gastrointestinal [mayoclinic.org]

• Collapse

  If a woman suffers severe hemorrhage, collapse, or shock at the time of delivery or during the early postpartum period, she should be observed closely for several months for subsequent signs and symptoms indicating pituitary necrosis. [iss.ndl.go.jp]

  Sheehan, English pathologist, 1900-1988 a postpartum condition of pituitary necrosis and hypopituitarism after circulatory collapse resulting from uterine hemorrhaging. Lactation may not develop, and loss of pubic and axillary hair may occur. [medical-dictionary.thefreedictionary.com]

  We report a 38-year-old Syrian woman who presented with progressive breathlessness, hypotension and circulatory collapse. Echocardiogram revealed a large pericardial effusion with evidence of cardiac tamponade. [ncbi.nlm.nih.gov]

  Management is focused on identifying missing or deficient hormones and replacing them, to ensure that patients with hypopituitarism do not succumb to circulatory collapse. Growth hormone deficiency should also be corrected. [news-medical.net]

  It is necessary to consider this diagnosis in all patients having presented with a cardiovascular collapse during childbirth, whatever the cause, and in the presence of the classic signs of pituitary insufficiency. [pubs.sciepub.com]

• Hypertension

  Abstract Intracranial hypertension (IH) has been associated with hypocortisolism caused by either primary adrenocortical insufficiency or corticosteroid withdrawal. [ncbi.nlm.nih.gov]

  In addition to the endocrinopathy, all of our patients had significant comorbidities, i.e. hypertension, diabetes, obesity, previous MI, etc. [academic.oup.com]

  Prolonged or augmented labor Placental disorders: abruption, accreta, previa Retained placenta Soft tissue lacerations Maternal blood disorders Hypertensive disorders including preeclampsia Chorioamnionitis Obesity Lack of access to adequate obstetric [unboundmedicine.com]

  […] typically about 0.2.5 Dysbetalipoproteinemia accounts for 1.0% of the lipid disorders associated with myocardial infarction.10 Thus, a careful history should be obtained to find out other modifiable risk factors for atherosclerosis, such as smoking and hypertension [elsevier.es]

• Dry Skin

  The most common findings on physical examination were absence of axillary hair in 56 (93%) and pubic hair in 56 (93%), dry skin in 49 (82%), and pallor in 42 (70%). [ncbi.nlm.nih.gov]

  She showed signs of hoarseness of voice, dry skin, thinning of hair, facial puffiness, non-pitting pedal edema, and a delayed ankle jerk all of which point to a clinical diagnosis of myxedema. [jpgmonline.com]

  She also complained of multiple symptoms including headaches, apathy, vaginal dryness, and dry skin, which were considered to be constitutional and not investigated further. [liebertpub.com]

  Examination revealed pulse rate of 60 per minute, blood pressure of 100/66 mm Hg with pale and dry skin. [casereports.in]

• Loss of Axillary Hair

  There was a loss of axillary hairs and only sparse pubic hairs. Examination of other systems was unremarkable. [omicsonline.org]

• Suggestibility

  The present case suggests that rhabdomyolysis could occur in a patient with Sheehan syndrome without other precipitating factors. [ncbi.nlm.nih.gov]

  There was a correlation between the diagnostic delay and the clinical sign suggesting hypopituitarism. [eje.bioscientifica.com]

  To our knowledge, this is the first case report of acute Sheehan's syndrome presenting with both hyponatremia and suggestive hypoglycemia. Pituitary necrosis is an uncommon complication of peripartum hemorrhagic shock. [dx.doi.org]

• Agalactia

  These four patients could not be thus evaluated for agalactia. Of 35 patients evaluated, four (n=4/35 or 11%) had been diagnosed with agalactia. [eje.bioscientifica.com]

  In this case report of Sheehan's syndrome in the post-partum period, the signs were characterized by agalactia, severe hypoglycemia, and low serum levels of thyroid hormones, cortico-adrenal hormones, and gonadotrophin (FSH, LH). [ncbi.nlm.nih.gov]

  The presentation is frequently amenorrhea and agalactia; hypoglycemia as a solitary presentation is uncommon. Case report: 68-year-old female with a history of postpartum hemorrhage 35 years ago. She had two episodes of hypoglycemia. [investigadores.unison.mx]

• Breast Atrophy

  Clinical examination including breast atrophy, diminished hairs in pubic and axillary regions were noted. [pulsus.com]

  Objective Data The patient exhibits many of the classic physical exam elements with the exception of breast atrophy and her normal Glasgow Coma Score. [oatext.com]

  Breast atrophy and sparse axillary and pubic hair were striking features. [spandidos-publications.com]

  atrophy) and more specific symptoms of SS (agalactia and amenorrhea). [eje.bioscientifica.com]

• Asthenia

  Fifteen patients (38.4%) had consulted for a major complaint of asthenia. SS was suspected in one patient (patient no. 16) by a dermatologist on a diagnosis of dry skin, with associated amenorrhea and asthenia since the last delivery. [eje.bioscientifica.com]

  The most common symptoms included asthenia and adynamia in 51 (85%), amenorrhea in 44 (73%), loss of axillary or pubic hair in 40 (67%), and agalactia in 40 (67%). [ncbi.nlm.nih.gov]

  The onset of asthenia, loss of weight, polyuro-polydipsy, persistent amenorrhoea and absence of lactation led to hormonal investigation. This permitted to diagnose global antehypopituitarism associated with diabetes insipidus. [jhu.pure.elsevier.com]

  In a study from France analyzing 28 patients with Sheehan's syndrome, 50% presented with agalactia, 25% had headaches in the postpartum period, 27.3% presented with amenorrhea, 25% had hypothyroidism, and 42.8% had asthenia since delivery [4]. [cureus.com]

  Symptoms of hypothyroidism may occur months after childbirth, and the patient may complain of fatigue, asthenia or weakness, hair loss, constipation, weight gain, problems with focusing or with their attention span, and cold intolerance. [statpearls.com]

• Lethargy

  There is failure of milk production, loss of body hair, absence of menstruation, lethargy and other effects of underaction of the endocrine glands. (Professor Harold Leeming Sheehan, 1900–86, English physician). [medical-dictionary.thefreedictionary.com]

  She was commenced on appropriate hormone replacement therapy, which led to significant improvement in lethargy, anorexia, muscle weakness, and episodes of hypoglycemia. [tandfonline.com]

  However, she complained of persistent fatigue and lethargy, and a glucagon stimulation test (GST) revealed no rise in serum GH and a blunted increase in serum cortisol (Table 1). [liebertpub.com]

  Case Presentation A 30 years young lady, married for 15 years having 3 child, from Satbaria, Chandanaish presented to OPD clinic with lethargy, lossof weight and appetite for a duration of eight months. [pubs.sciepub.com]

  On eliciting a detailed history she was found to have episodes of recurrent loss of consciousness since 6 months accompanied by symptoms of generalized fatigue, weakness, lethargy, and anorexia. [jpgmonline.com]

• Reduced Consciousness

  Seek emergency medical treatment if you experience the following signs and symptoms: Severe weakness Confusion Pain in your lower back or legs Severe abdominal pain, vomiting and diarrhea, leading to dehydration Reduced consciousness or delirium In an [mayoclinic.org]

• Amenorrhea

  The most common symptoms included asthenia and adynamia in 51 (85%), amenorrhea in 44 (73%), loss of axillary or pubic hair in 40 (67%), and agalactia in 40 (67%). [ncbi.nlm.nih.gov]

  CLINICAL CHARACTERISTICS Signs and Symptoms • Secondary amenorrhea • Secondary hypothyroidism • Adrenal insufficiency (the degree of pituitary damage and resultant loss is highly variable; as a result, the reduction of adrenal and thyroid hormone production [clinicalgate.com]

  Second, we evaluated the patients for the presence of amenorrhea. Among the 39 patients, only 29 could be evaluated for amenorrhea because ten patients had undergone hysterectomy. [eje.bioscientifica.com]

  Though most common and early symptoms are lactation failure and amenorrhea, some cases might be relatively asymptomatic which are diagnosed in later years when features of hypothyroidism and adrenal insufficiency predominate. [ejgm.co.uk]

• Secondary Amenorrhea

  A 25-year-old woman presented with lactation failure, secondary amenorrhea, features of hypothyroidism and a hypocortisol state following severe postpartum hemorrhage after her last child birth. She also had smear positive pulmonary tuberculosis. [ncbi.nlm.nih.gov]

  CLINICAL CHARACTERISTICS Signs and Symptoms • Secondary amenorrhea • Secondary hypothyroidism • Adrenal insufficiency (the degree of pituitary damage and resultant loss is highly variable; as a result, the reduction of adrenal and thyroid hormone production [clinicalgate.com]

  After this episode she started having acyclic menses, occurring after prolonged periods of time, followed by secondary amenorrhea. She had periods once following a course of medroxy progesterone acetate. [austinpublishinggroup.com]

  On pelvic exam and sonogram she was found to have normal uterus and ovaries and the low follicle stimulating hormone and luteinizing hormone values, which further proved hypogonadotrophic hypogonadism as a cause of her secondary amenorrhea. [jpgmonline.com]

  Some of the possible reasons that had contributed to this delay are; [ 1 ] inadequate counseling on discharge after her eventful delivery and postpartum hemorrhage, and [ 2 ] lack of awareness to seek help for secondary amenorrhea for many. [omicsonline.org]

• Cesarean Section

  We report the case of a 23-year-old Saudi Arabian woman who presented to the medical intensive care unit with severe hyponatremia and hypoglycemia following a Cesarean section delivery complicated by hemorrhage due to disseminated intravascular coagulopathy [dx.doi.org]

  To balance the maternal risk of expectant management and neonatal risk of prematurity, considering her history of cesarean section and preciousness of the baby, a selective cesarean section was conducted at 37+6 weeks of gestation with the help of a neonatologist [rs.yiigle.com]

  section), consistent with good obstetric practice. [unboundmedicine.com]

  In order to save the other twin, emergency cesarean section was performed, and the 2 nd twin was delivered alive. The PPH was surgically managed, with 2 units of whole blood transfusion. [ruralneuropractice.com]

• Sexual Dysfunction

  dysfunction in women Acute adrenal failure (addisonian crisis) Sometimes the signs and symptoms of Addison's disease may appear suddenly. [mayoclinic.org]

Symptoms of SS vary widely, depending on which pituitary hormone is deficient, making diagnosis challenging. Women who present with symptoms possibly related to hypopituitarism and previously experienced hemorrhage during delivery are often diagnosed with SS. Specific symptoms may include dizziness, fatigue, weakness or hypoglycemia in women with ACTH deficiency, fatigue and decreased muscle mass and quality of life in women with GH deficiency and decreased libido, no or light menstrual cycle and hot flashes in women with FSH or LH deficiency. The hypopituitarism associated with SS often causes secondary hypothyroidism which is difficult to discern from primary hypothyroidism and leads to low levels of T3 and t$ hormones.

Women with SS that experience panhypopituitarism will have low levels of corticotropin, LH, thyrotropin, cortisol and thyroxine. To detect a partial hormone deficiency, stimulation tests are needed (metyrapone test and insulin hypoglycemia test). SS is suspected in mothers with low thyroid hormone and cortisol levels along with hyponatremia, especially if patients’ hormone levels are unchanged following insulin hypoglycemia tests.

Although radiographic imaging of the pituitary gland provides little help early on in SS disease progression, a smaller sella turcica may be observed in women in the more advanced stages of SS.

• Hyponatremia

  To our knowledge, this is the first case report of acute Sheehan's syndrome presenting with both hyponatremia and suggestive hypoglycemia. Pituitary necrosis is an uncommon complication of peripartum hemorrhagic shock. [dx.doi.org]

  Several mechanisms are responsible for hyponatremia. Hypothyroidism and glucocorticoid deficiency by decreasing free water clearance independent of vasopressin cause hyponatremia. [doi.org]

  Hyponatremia and hypoglycemia may also be present as well. [statpearls.com]

SS is addressed with the primary aim of replacing hormone deficiencies. If left untreated, the hormone imbalance associated with SS can be life threatening [8] [9] [10]. SS patients who have developed hypoadrenalism and hypothyroidism should be treated first with glucocorticoid replacement therapy before addressing thyroid deficiencies. Hormone replacement therapy is recommended for hypogonadism and GH deficiency. GH replacement must be individualized, started with low doses, tapered upward and closely monitored, so GH and insulin-like growth factor 1 levels remain within appropriate range. Body composition and cardiovascular risk should be considered with GH replacement therapy. Desmopressin should be administered to patients with diabetes insipidus. Patients hoping for a pregnancy should consult a fertility specialist.

SS is effectively treated with early diagnosis and care posing only a slight health risk for patients in developed countries. If untreated, SS is a life threatening condition.

SS arises from massive hemorrhage, vasospasm, compression of hypophyseal arteries and thrombosis during delivery that causes necrosis of the pituitary gland and subsequent hypopituitarism. The precise pathophysiology and etiology of SS remain unclear and the disease is rarely observed in developed countries because of optimal obstetrical care. However, SS is one of the leading sources of growth hormone (GH) deficiency in patients with GH-deficiency [4] [5].

SS prevalence is unclear due to the low number of diagnosed cases. One small study investigating causes of GH-deficiency indicated that SS was responsible for causing 3.1% of cases, rendering it the sixth most common cause of GH-deficiency. In that study, the most common cause of GH-deficiency was found to be pituitary cancer which was responsible for 53.9% of cases [4] [5].

The pituitary gland is particularly sensitive to ischemia during pregnancy and delivery due to 1) hyperplasia and hypertrophy of the lactotrophic cells in the anterior pituitary gland and 2) decreased portal pressure. Therefore, hypotension or a severe hemorrhage occurring during childbirth or in the period immediately after, will likely cause ischemia-induced necrosis of the anterior pituitary gland. The posterior pituitary remains unaffected because of the blood received from arterial vessels.

Signs and symptoms of SS arise from a deficiency in the circulation of one or more hormones secreted or induced by the pituitary gland, which include prolactin, ADH, thyroid stimulating hormone (TSH), cortisol, GH, luteinizing hormone (LH), follicle-stimulating hormone (FSH) and adrenocorticotropic hormone (ACTH).

Prolactin deficiency results in inability to lactate, ADH deficiency may cause central diabetes insipidus, TSH deficiency can lead to hypothyroidism and low cortisol can cause mental ailments among other things. It is due to the diversity of symptoms that may arise in SS, that this condition is classified as a syndrome.

Placental issues or being pregnant with more than one child at once may increase the chances of hypotension and hemorrhage, therefore, these women have a higher risk of developing SS. Proper perinatal monitoring and care greatly decrease the chances of having both hemorrhage and SS.

Sheehan's syndrome (SS) is associated with reduced pituitary hormone secretions (hypopituitarism) which stems from the necrosis of the pituitary gland that is caused by massive postpartum hemorrhage, vasospasm, compression of hypophyseal arteries and thrombosis. The necrotic pituitary gland will display impaired function, atrophy and scarring. During delivery, the pituitary gland has a heightened sensitivity to ischemia due to its larger size and the presence of circulating vasoconstrictors may cause vasospasm and low portal pressure. Patients most commonly present with breast involution and prolactin deficiency, which prevents lactation, followed by the failure to re-establish menstruation and the inability to regrow pubic and axillary hair. Overtime, hypothyroidism may cause fatigue, malaise, joint aches, anorexia, decreased skin pigmentation, mental disturbances (with or without psychosis) and decreased insulin dependence in women with type 1 diabetes. In rare cases women with SS that experience stress may develop acute adrenal crises and hypotension which may be lethal.

The pathogenesis of SS is diverse and may involve pituitary gland enlargement, low pressure regional perfusion, autoimmunity and disseminated intravascular coagulation. One out of three women with postpartum hemorrhage may experience various levels of hypopituitarism and, although symptoms rarely arise, many patients show diminished neurohypophyseal function when tested. In developing and underdeveloped countries SS is the most common cause of hypopituitarism, but due to advanced obstetrical care, SS and hypopituitarism are rare in developed countries. Some suggested predisposing factors may include the presence of a previously unknown pituitary mass, smaller and more rigid sella turcica, type 1 diabetes and preexisting vascular disease.

Postmortem analysis often reveals neurohypophyseal scarring along with paraventricular nuclei and surpraoptic scarring, locations which secrete antidiuretic hormone (ADH). A lack of ADH may cause central diabetes insipidus (DI) [1] [2] [3].

Sheehan syndrome (SS) is a rare disorder, caused by severe bleeding of women during child delivery. The pituitary gland of pregnant women is particularly sensitive to decreased blood flow and extensive hemorrhage causes large areas of the pituitary gland to die, leading to a decreased hormone production. The pituitary gland produces a variety of hormones including those that stimulate milk production, growth, the adrenal gland, the thyroid gland and regulate menstruation. Women pregnant with multiple babies or those who have issues with their placenta have a higher risk of having severe hemorrhages during delivery and therefore a higher risk of developing SS.

The symptoms that accompany SS may appear right away or after several years and include inadequate breast milk production, low blood pressure, fatigue, hair loss (axillary and pubic) and absent or light menstrual cycle. There are a number of blood tests that can be done to assess the levels of circulating hormones in your blood. Imaging may be performed to assess the pituitary gland and exclude other causes.

Hormone replacement therapy, including estrogen and progesterone will be given until 48 to 55 years of age, and thyroid and adrenal hormone supplements will be given indefinitely to treat SS. With early diagnosis and modern treatments the prognosis is good, however, in underdeveloped and developing countries women often go undiagnosed and receive suboptimal treatments leading to severe complications and even death. Proper care during delivery may reduce the risk of severe bleeding and SS.

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