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]

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

• Asymptomatic

  Endothelial dysfunction and increased carotid intima-media thickness in the cardiovascularly asymptomatic growth hormone naive patients of Sheehan’s syndrome. [healio.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]

  It is also possible to be asymptomatic with Sheehan’s syndrome depending on the degree of damage to the pituitary gland. [syndromespedia.com]

  […] initial event of hypovolemia and shock.[2] The acute presenting condition of Sheehan syndrome is usually evident when the mother of the newborn had difficulty with breastfeeding or cannot produce milk at all (agalactorrhea).[6] However, many women are asymptomatic [statpearls.com]

  That's weird considering most adenomas are asymptomatic, but that's the USMLE for you I guess. I suspect it isn't a simple answer, or probably completely understood beyond the association. What is, in medicine? Thanks for looking that up though. [forums.studentdoctor.net]

• Hypothermia

  It is thought to be related to trauma on bony prominences during delivery, hypothermia, asphyxia, or maternal diabetes; it usually resolves spontaneously by 2 to 4 weeks with no scarring. [medical-dictionary.thefreedictionary.com]

  She was found to have hypotension, hypoglycemia, and hypothermia. Her AM cortisol and ACTH were low, concerning for a non-primary adrenal insufficiency. [jhltonline.org]

  Physical examination revealed the following: Mild hypothermia (axillary temperature, 35.8°C), low blood pressure (74/49 mmHg) and a pulse rate of 40 beats/min. [spandidos-publications.com]

  Hypothermia can result. Endocrine deficiencies, which can result from destruction of adenohypophyseal tissue. [patient.info]

• Falling

  Once there, Vincent falls in love with an anorexic woman named Marie. Together, they steal Dr. Rose's car, and end up having to kidnap his OCD roommate, Alex, when he threatens to tell on them. With Robert and Dr. [imdb.com]

  Graef, �ber einen Fall einer Gravidit�t bei isoliertem Ausfall von ACTH Coexistent fregnancy and isolated ACTH deficiency: Case report, Klinische Wochenschrift, 10.1007/BF01468320, 51, 21, (1062-1065), (1973). [doi.org]

• 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]

• Muscle Weakness

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

  weakness Muscular weakness 0001324 Obesity Having too much body fat 0001513 Palpitations Missed heart beat Skipped heart beat [ more ] 0001962 Poor appetite Decreased appetite 0004396 Sensorineural hearing impairment 0000407 Thunderclap headache 0030907 [rarediseases.info.nih.gov]

  She was given hormone replacement therapy, which led to a significant improvement in lethargy, anorexia, muscle weakness, and episodes of hypoglycemia. [omicsonline.org]

• Joint Stiffness

  Side effects might include joint stiffness and fluid retention. Your endocrinologist is likely to test your blood regularly to make sure that you're getting adequate — but not excessive — amounts of hormones. [drugs.com]

  Side effects may include joint stiffness and fluid retention.Streptococcus pyogenes is the bacteria responsible for strep throat. [findatopdoc.com]

• Loss of Axillary Hair

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

• Agalactia

  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]

  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]

  Regardless, agalactia and prolonged postpartum amenorrhea should prompt a diagnosis of SS until proven otherwise. [liebertpub.com]

• 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]

  Patients present with amenorrhea, failure of lactation, weakness, weight loss, dry skin, loss of axillary and pubic hair, breast atrophy, and psychiatric disturbance ( ). [fertstert.org]

• Meningism

  We report the case of a patient who had headaches and meningitis signs few hours after a post-partum haemorrhage. Magnetic Resonance Imaging (MRI) performed at day 2 showed a specific hypophysitis. [jhu.pure.elsevier.com]

  Examination findings There may be rapid progression to coma, suggesting stroke, subarachnoid haemorrhage and with accompanying meningism, even meningitis. Careful and early examination may detect a variety of findings. [patient.info]

  […] underarm hair [ more ] 0002215 Sparse pubic hair Decreased sexual hair 0002225 5%-29% of people have these symptoms Antinuclear antibody positivity 0003493 Arthralgia Joint pain 0002829 Bradycardia Slow heartbeats 0001662 Chills 0025143 Chronic lymphocytic meningitis [rarediseases.info.nih.gov]

  There was no history of meningitis, head injury, tuberculosis or diabetes mellitus in the past. [pubs.sciepub.com]

  Other causes of severe headache that are specific to the postpartum phase include pre-eclampsia, postdural headache, meningitis, cerebral venous sinus thrombosis, and acute pituitary apoplexy.6,7 Our patient's headache was managed as a migraine in the [liebertpub.com]

• Amenorrhea

  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]

  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 incidence in developing and low-income countries is as high as 5 in 100,000 births 5. pituitary failure 1 may be silent and present with delayed hypopituitarism agalactorrhoea amenorrhea oligomenorrhea adrenal insufficiency hyponatremia (diabetes [radiopaedia.org]

  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]

• 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]

• Sexual Dysfunction

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

  Dysfunction in Sheehan Syndrome. 62 Mandal S...Ghosh S 34311117 2021 36 Sheehan's syndrome as a mimic of premature ovarian insufficiency: need for advocacy. 62 Kalra S...Bhattacharya S 33830850 2021 37 Management of a patient with Sheehan's syndrome [malacards.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.

• Hypercholesterolemia

  Multi-center study on the prevalence of hypothyroidism in patients with hypercholesterolemia[J]. Endocr J, 2011, 58(6): 449-457. DOI: 10.1507/endocrj.k11e-012. [5] GJEDDE S, GORMSEN LC, RUNGBY J, et al. [lcgdbzz.org]

  Case report A 39-year-old woman was referred to the endocrinology outpatient clinic by severe hypercholesterolemia. [elsevier.es]

• Cortisol Decreased

  Lab Finding GH Decreased PRL Decreased FSH Decreased LH Decreased ACTH Normal or elevated TSH Normal or elevated E2 (serum) Undetectable IGF-1 Decreased Free T4 Decreased Cortisol Decreased Table 4. Diagnostic Criteria [3]. [oatext.com]

• Cortisol Decreased

  Lab Finding GH Decreased PRL Decreased FSH Decreased LH Decreased ACTH Normal or elevated TSH Normal or elevated E2 (serum) Undetectable IGF-1 Decreased Free T4 Decreased Cortisol Decreased Table 4. Diagnostic Criteria [3]. [oatext.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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