Sheehan's syndrome

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Postpartum hypopituitarism caused by pituitary ischemic necrosis after severe childbirth bleeding

Sheehan's syndrome
Pituitary_gland-optic_chiasm-sella_turcica.jpg
Synonyms	Postpartum pituitary necrosis, postpartum hypopituitarism, postpartum pituitary insufficiency
Pronounce	N/A
Specialty	Endocrinology, Obstetrics, Gynecology
Symptoms	Lactation failure, amenorrhea, fatigue, hypotension, hypoglycemia, hyponatremia, cold intolerance
Complications	Adrenal crisis, central hypothyroidism, infertility, hypopituitarism, panhypopituitarism
Onset	Usually after severe postpartum hemorrhage; symptoms may be acute or delayed for months to years
Duration	Long-term
Types	N/A
Causes	Ischemic injury or necrosis of the pituitary gland after severe childbirth-related hemorrhage, hypovolemia, and shock
Risks	Postpartum hemorrhage, severe hypotension, placenta previa, uterine atony, retained placenta, uterine rupture, disseminated intravascular coagulation
Diagnosis	Obstetric history, pituitary hormone testing, cortisol, ACTH, TSH, free thyroxine, prolactin, gonadotropins, IGF-1, and MRI
Differential diagnosis	Lymphocytic hypophysitis, pituitary apoplexy, empty sella syndrome, pituitary adenoma, Addison disease, primary hypothyroidism
Prevention	Prompt recognition and treatment of postpartum hemorrhage and hypovolemic shock
Treatment	Lifelong hormone replacement therapy and emergency treatment of adrenal insufficiency when present
Medication	Hydrocortisone, prednisone, levothyroxine, estrogen, progesterone, desmopressin, growth hormone
Prognosis	Usually good with early diagnosis and appropriate hormone replacement
Frequency	Rare in high-resource settings; more common where severe postpartum hemorrhage is not rapidly treated
Deaths	Rare with treatment; possible from untreated adrenal crisis

Sheehan's syndrome is a form of hypopituitarism caused by ischemic injury or necrosis of the pituitary gland after severe postpartum hemorrhage, hypovolemia, and shock during or after childbirth. It is also known as postpartum pituitary necrosis or postpartum hypopituitarism. The disorder occurs because the anterior pituitary enlarges during pregnancy and becomes more vulnerable to reduced blood flow during severe maternal blood loss.Sheehan Syndrome(link). StatPearls, National Center for Biotechnology Information.

The condition may present soon after delivery with lactation failure, severe fatigue, hypotension, hypoglycemia, or hyponatremia. In many patients, however, diagnosis is delayed for months or years because symptoms can be subtle, chronic, and gradually progressive.Sheehan Syndrome(link). National Organization for Rare Disorders.

Overview

The pituitary gland is a small endocrine gland located at the base of the brain in the sella turcica. It produces hormones that regulate the adrenal glands, thyroid gland, ovaries, growth hormone activity, prolactin production, and lactation.

In Sheehan's syndrome, damage to the anterior pituitary reduces secretion of one or more pituitary hormones. When most or all anterior pituitary hormones are deficient, the condition is called panhypopituitarism.

Important affected hormone systems include:

• ACTH - A pituitary hormone that stimulates the adrenal glands to produce cortisol.

• Cortisol - A glucocorticoid hormone needed for blood pressure, glucose metabolism, and stress response.

• TSH - A pituitary hormone that stimulates the thyroid gland.

• Free thyroxine - A thyroid hormone used to assess central hypothyroidism.

• Prolactin - A pituitary hormone needed for breast milk production and lactation.

• Luteinizing hormone - A gonadotropin involved in ovulation and ovarian hormone production.

• Follicle-stimulating hormone - A gonadotropin important for ovarian function and fertility.

• Growth hormone - A pituitary hormone involved in metabolism, body composition, and IGF-1 production.

• Antidiuretic hormone - A posterior pituitary hormone involved in water balance, rarely affected in Sheehan's syndrome.

Signs and symptoms

Symptoms depend on the degree of pituitary gland injury and which hormone pathways are affected.

Early symptoms after delivery

Early signs may include:

• Lactation failure - Failure to produce enough breast milk after childbirth.

• Agalactorrhea - Complete absence of milk production after delivery.

• Fatigue - Severe tiredness that is out of proportion to ordinary postpartum recovery.

• Hypotension - Low blood pressure, often worsened by adrenal insufficiency.

• Hypoglycemia - Low blood glucose caused by impaired cortisol response.

• Hyponatremia - Low sodium level that may occur with cortisol deficiency or hypothyroidism.

• Dizziness - Lightheadedness due to low blood pressure, low glucose, or electrolyte disturbance.

• Syncope - Fainting caused by severe hypotension or adrenal insufficiency.

• Amenorrhea - Absence of menstrual periods after the affected pregnancy.

• Oligomenorrhea - Infrequent menstrual periods due to gonadotropin deficiency.

Delayed symptoms

Delayed symptoms may appear months or years after the childbirth event.

• Amenorrhea - Absent menstrual periods caused by low LH, low FSH, and low estrogen.

• Infertility - Difficulty becoming pregnant due to impaired ovarian stimulation.

• Cold intolerance - Sensitivity to cold due to central hypothyroidism.

• Constipation - A common symptom of low thyroid hormone.

• Weight gain - Possible effect of hypothyroidism or altered metabolism.

• Weight loss - Possible effect of chronic adrenal insufficiency.

• Dry skin - A symptom associated with hypothyroidism.

• Hair loss - Loss of scalp, axillary, or pubic hair due to hormone deficiency.

• Reduced libido - Reduced sexual desire due to low estrogen or broader hypopituitarism.

• Muscle weakness - May occur with cortisol deficiency or growth hormone deficiency.

• Depression - Mood symptoms may occur with chronic endocrine deficiency.

• Cognitive impairment - Slowed thinking or poor concentration may occur with hypothyroidism or adrenal insufficiency.

• Anemia - May be associated with chronic endocrine dysfunction.

Adrenal insufficiency symptoms

Deficiency of ACTH causes secondary adrenal insufficiency. This is one of the most dangerous features of Sheehan's syndrome.

• Fatigue - Severe and persistent tiredness.

• Hypotension - Low blood pressure, especially during illness or dehydration.

• Hypoglycemia - Low blood glucose caused by inadequate cortisol response.

• Nausea - A common symptom of adrenal insufficiency.

• Vomiting - A warning sign when associated with weakness or low blood pressure.

• Abdominal pain - May occur during adrenal crisis.

• Weight loss - Can occur with chronic cortisol deficiency.

• Hyponatremia - Low serum sodium due to impaired water handling.

• Dizziness - May occur with hypotension or dehydration.

• Adrenal crisis - A life-threatening emergency caused by severe cortisol deficiency.

Central hypothyroidism symptoms

Damage to pituitary production of thyroid-stimulating hormone may cause central hypothyroidism.

• Fatigue - Common symptom of low thyroid hormone.

• Cold intolerance - Feeling unusually cold.

• Constipation - Slowed bowel function.

• Dry skin - Skin dryness due to reduced thyroid activity.

• Weight gain - May occur with reduced metabolic rate.

• Bradycardia - Slow heart rate.

• Hoarseness - Voice change sometimes seen in hypothyroidism.

• Depression - Mood changes may occur with low thyroid hormone.

• Cognitive slowing - Slow thinking or poor concentration.

In central hypothyroidism, free thyroxine is low, while TSH may be low, normal, or only mildly abnormal.

Gonadotropin deficiency symptoms

Deficiency of luteinizing hormone and follicle-stimulating hormone affects ovarian function.

• Amenorrhea - Absent menstrual periods.

• Oligomenorrhea - Infrequent menstrual periods.

• Infertility - Difficulty becoming pregnant.

• Estrogen deficiency - Low estrogen due to inadequate ovarian stimulation.

• Hot flashes - Vasomotor symptoms caused by low estrogen.

• Vaginal dryness - A symptom of estrogen deficiency.

• Reduced libido - Reduced sexual desire.

• Osteopenia - Reduced bone density over time.

• Osteoporosis - Increased risk of fragile bones with prolonged estrogen deficiency.

Growth hormone deficiency symptoms

• Growth hormone deficiency in adults may cause nonspecific symptoms.

• Fatigue - Low energy and reduced stamina.

• Reduced muscle mass - Loss of lean body mass.

• Increased body fat - Change in body composition.

• Exercise intolerance - Reduced ability to exercise.

• Dyslipidemia - Abnormal blood lipid levels.

• Reduced quality of life - General decline in well-being.

Posterior pituitary symptoms

Most cases affect the anterior pituitary. Rarely, the posterior pituitary may be involved.

• Polydipsia - Excessive thirst.

• Polyuria - Excessive urination.

• Diabetes insipidus - A disorder of water balance due to deficient antidiuretic hormone.

• Hypernatremia - High sodium level caused by excessive free-water loss.

Causes

Sheehan's syndrome is caused by reduced blood flow to the pituitary gland during or after childbirth. The classic trigger is severe postpartum hemorrhage with hypovolemic shock.

Common obstetric causes include:

• Postpartum hemorrhage - Severe bleeding after childbirth.

• Uterine atony - Failure of the uterus to contract properly after delivery.

• Placenta previa - A placenta that partially or completely covers the cervix.

• Placental abruption - Premature separation of the placenta from the uterus.

• Retained placenta - Placental tissue remaining in the uterus after delivery.

• Uterine rupture - Tearing of the uterus during pregnancy or labor.

• Cervical tear - Trauma to the cervix that may cause bleeding.

• Vaginal tear - Birth-related injury that may contribute to hemorrhage.

• Disseminated intravascular coagulation - Abnormal clotting and bleeding disorder.

• HELLP syndrome - A severe pregnancy complication associated with hemolysis, liver enzyme elevation, and low platelets.

• Amniotic fluid embolism - A rare obstetric emergency that may cause shock and coagulopathy.

• Hypovolemic shock - Shock due to severe blood or fluid loss.

During pregnancy, the anterior pituitary enlarges because of increased lactotroph cells that produce prolactin. This increases oxygen demand. Severe blood loss and low blood pressure can reduce pituitary blood flow, causing ischemia, infarction, and necrosis.Generalized Hypopituitarism(link). Merck Manual Professional Edition.

Risk factors

Risk factors include:

• Postpartum hemorrhage - The most important risk factor.

• Hypotension - Severe low blood pressure during or after childbirth.

• Hypovolemic shock - Circulatory collapse from blood loss.

• Placenta previa - A cause of severe obstetric bleeding.

• Placental abruption - A cause of maternal bleeding and shock.

• Retained placenta - A cause of prolonged postpartum bleeding.

• Uterine atony - A common cause of postpartum hemorrhage.

• Uterine rupture - A serious obstetric emergency.

• Severe anemia - Reduced oxygen-carrying capacity.

• Disseminated intravascular coagulation - A clotting disorder that can worsen bleeding.

• Blood transfusion delay - Delayed replacement of blood volume.

• Home birth without emergency backup - A risk when severe bleeding cannot be treated promptly.

• Emergency obstetric care delay - Delayed access to surgery, transfusion, and intensive care.

Pathophysiology

The anterior pituitary receives much of its blood supply from a low-pressure hypophyseal portal system. During pregnancy, pituitary size and metabolic demand increase. Severe maternal blood loss may reduce perfusion of the enlarged gland.

The sequence may include:

• Pregnancy - Physiologic enlargement of the pituitary gland.

• Lactotroph hyperplasia - Expansion of prolactin-producing cells.

• Postpartum hemorrhage - Severe loss of circulating blood volume.

• Hypotension - Reduced pressure needed to perfuse the pituitary gland.

• Ischemia - Inadequate oxygen delivery to pituitary tissue.

• Pituitary infarction - Tissue injury from lack of blood supply.

• Pituitary necrosis - Death of hormone-producing pituitary cells.

• Hypopituitarism - Deficiency of one or more pituitary hormones.

• Panhypopituitarism - Deficiency of most or all anterior pituitary hormones.

Hormone deficiencies may include:

• Adrenocorticotropic hormone deficiency - Causes secondary adrenal insufficiency.

• Thyroid-stimulating hormone deficiency - Causes central hypothyroidism.

• Prolactin deficiency - Causes lactation failure.

• Gonadotropin deficiency - Causes amenorrhea, infertility, and estrogen deficiency.

• Growth hormone deficiency - Causes metabolic and quality-of-life symptoms.

Diagnosis

Diagnosis is based on obstetric history, symptoms, hormone testing, and pituitary imaging.

Medical history

Important diagnostic clues include:

• Postpartum hemorrhage - History of severe childbirth bleeding.

• Blood transfusion - Need for transfusion after delivery.

• Shock - Very low blood pressure during or after childbirth.

• Intensive care unit admission - Severe postpartum illness requiring critical care.

• Lactation failure - Failure to produce breast milk after delivery.

• Amenorrhea - Failure of menstrual periods to return.

• Fatigue - Persistent exhaustion beginning after childbirth.

• Hyponatremia - Recurrent or unexplained low sodium.

• Hypoglycemia - Recurrent or unexplained low blood glucose.

• Infertility - Difficulty conceiving after the affected pregnancy.

Laboratory testing

Laboratory evaluation may include:

• Morning cortisol - Screening test for adrenal insufficiency.

• ACTH - Helps distinguish central from primary adrenal disease.

• TSH - Pituitary hormone used with free thyroxine to evaluate thyroid function.

• Free thyroxine - Key test for central hypothyroidism.

• Prolactin - Often low in lactation failure due to pituitary damage.

• Luteinizing hormone - Used to assess gonadotropin deficiency.

• Follicle-stimulating hormone - Used to assess ovarian axis function.

• Estradiol - Reflects ovarian estrogen production.

• IGF-1 - Screening marker for growth hormone deficiency.

• Serum sodium - Evaluates hyponatremia.

• Serum glucose - Evaluates hypoglycemia.

• Complete blood count - Evaluates anemia or other abnormalities.

• Comprehensive metabolic panel - Evaluates electrolytes, kidney function, and liver function.

Dynamic endocrine testing

Dynamic testing may be needed when hormone levels are borderline.

• ACTH stimulation test - Evaluates adrenal reserve.

• Insulin tolerance test - May assess growth hormone and ACTH reserve in selected settings.

• Glucagon stimulation test - May assess growth hormone reserve.

• Cosyntropin stimulation test - Common test for adrenal function.

• Water deprivation test - Used only when diabetes insipidus is suspected.

Imaging

• Magnetic resonance imaging of the pituitary is commonly used.

MRI findings may include:

• Empty sella syndrome - Partial or complete empty sella.

• Pituitary atrophy - Small or shrunken pituitary gland.

• Pituitary infarction - Evidence of previous ischemic injury.

• Pituitary necrosis - Tissue loss after infarction.

• Pituitary adenoma exclusion - Imaging helps rule out tumor.

• Sellar mass exclusion - Imaging helps rule out other lesions of the sella.

A normal MRI does not fully exclude Sheehan's syndrome if the obstetric history and hormone pattern strongly support the diagnosis.

Differential diagnosis

Conditions that may resemble Sheehan's syndrome include:

• Lymphocytic hypophysitis - Autoimmune inflammation of the pituitary, often associated with pregnancy or postpartum state.

• Pituitary apoplexy - Sudden bleeding or infarction in a pituitary tumor.

• Pituitary adenoma - Benign pituitary tumor that can cause hypopituitarism.

• Empty sella syndrome - Radiologic finding that may be associated with pituitary dysfunction.

• Addison disease - Primary adrenal insufficiency caused by adrenal gland disease.

• Primary hypothyroidism - Thyroid gland failure rather than pituitary disease.

• Postpartum thyroiditis - Thyroid inflammation after pregnancy.

• Hypothalamic disease - Disorders affecting pituitary regulation.

• Chronic fatigue syndrome - Chronic fatigue disorder that may mimic endocrine disease.

• Major depressive disorder - Mood disorder that may overlap with fatigue and cognitive symptoms.

• Anemia - Low red blood cell count causing fatigue and weakness.

• Chronic kidney disease - Kidney disease that may cause fatigue and electrolyte problems.

• Simmonds disease - Severe hypopituitarism from non-postpartum causes.

Treatment

Treatment consists of replacing deficient hormones and preventing adrenal crisis.

Emergency treatment

Suspected adrenal crisis requires immediate treatment.

• Hydrocortisone - First-line emergency glucocorticoid treatment.

• Intravenous fluids - Used to treat dehydration and shock.

• Dextrose - Used to correct severe hypoglycemia.

• Hyponatremia treatment - Correction of severe low sodium under medical supervision.

• Blood pressure support - Treatment of severe hypotension.

• Infection treatment - Treatment of infection that may trigger adrenal crisis.

• Hospitalization - Monitoring in urgent or unstable cases.

If adrenal insufficiency is possible, glucocorticoid treatment should not be delayed in an unstable patient.

Glucocorticoid replacement

• Glucocorticoid therapy replaces deficient cortisol.

• Hydrocortisone - Common physiologic replacement for secondary adrenal insufficiency.

• Prednisone - Alternative glucocorticoid used in selected patients.

• Stress-dose steroids - Higher doses needed during fever, surgery, trauma, or severe illness.

• Medical identification - Bracelet, necklace, or card identifying adrenal insufficiency.

• Emergency hydrocortisone injection - Used when vomiting, collapse, or severe illness prevents oral dosing.

Thyroid hormone replacement

• Levothyroxine is used for central hypothyroidism.

• Levothyroxine - Replacement for low thyroid hormone.

• Free thyroxine monitoring - Main laboratory guide in central hypothyroidism.

• TSH - May be unreliable for dose adjustment in central hypothyroidism.

• Adrenal crisis prevention - Glucocorticoid deficiency should be treated before starting or increasing levothyroxine.

Sex hormone replacement

Premenopausal women with gonadotropin deficiency may need sex hormone replacement unless contraindicated.

• Estrogen - Replaces ovarian estrogen deficiency.

• Progesterone - Protects the uterus when estrogen is used in women with an intact uterus.

• Hormone replacement therapy - May improve symptoms and protect bone health.

• Bone density - Should be monitored when estrogen deficiency is prolonged.

• Reproductive endocrinology - Referral may be needed for pregnancy planning.

Fertility treatment

Women desiring pregnancy may need specialist care.

• Ovulation induction - Treatment to stimulate ovulation.

• Gonadotropin therapy - Fertility treatment using LH-like and FSH-like hormones.

• Reproductive endocrinologist - Specialist for infertility due to pituitary disease.

• High-risk obstetrics - Care for pregnancy after Sheehan's syndrome.

Growth hormone replacement

Selected adults with confirmed growth hormone deficiency may benefit from growth hormone replacement.

• Growth hormone - Replacement therapy considered in selected adults.

• IGF-1 - Used to monitor growth hormone replacement.

• Body composition - May improve with treatment in selected patients.

• Exercise tolerance - May improve in some treated patients.

• Quality of life - May improve with appropriate therapy.

Desmopressin

• Desmopressin is used only when central diabetes insipidus is present.

• Desmopressin - Replacement for deficient antidiuretic hormone activity.

• Diabetes insipidus - Rare in Sheehan's syndrome.

• Serum sodium - Must be monitored during treatment.

• Fluid balance - Important in patients with polyuria or polydipsia.

Monitoring and follow-up

Long-term follow-up with an endocrinologist is important.

• Endocrinology - Specialty care for pituitary hormone replacement.

• Blood pressure - Monitoring for hypotension or overtreatment.

• Serum sodium - Monitoring for hyponatremia or diabetes insipidus.

• Serum glucose - Monitoring for hypoglycemia.

• Free thyroxine - Monitoring of thyroid hormone replacement.

• Cortisol replacement - Clinical review of glucocorticoid adequacy.

• Menstrual history - Monitoring ovarian axis function.

• Bone density test - Screening for osteopenia or osteoporosis.

• Lipid profile - Metabolic monitoring, especially with growth hormone deficiency.

• Pituitary MRI - Follow-up imaging when clinically indicated.

• Sick day rules - Education for stress-dose steroid use during illness.

Complications

Possible complications include:

• Adrenal crisis - Life-threatening cortisol deficiency.

• Hyponatremia - Low sodium, sometimes severe.

• Hypoglycemia - Low blood glucose from cortisol deficiency.

• Central hypothyroidism - Thyroid hormone deficiency due to pituitary disease.

• Infertility - Impaired fertility due to gonadotropin deficiency.

• Amenorrhea - Absence of menstrual periods.

• Osteopenia - Reduced bone density.

• Osteoporosis - Fragile bone disease from prolonged sex hormone deficiency.

• Panhypopituitarism - Deficiency of most or all anterior pituitary hormones.

• Reduced quality of life - Chronic symptoms from untreated or undertreated hormone deficiency.

• Death - Rare but possible from untreated adrenal crisis.

Prevention

The best prevention is rapid recognition and treatment of severe postpartum bleeding.

• Skilled birth attendance - Trained care during labor and delivery.

• Postpartum hemorrhage prevention - Active management of the third stage of labor.

• Uterotonic medication - Treatment to help the uterus contract after delivery.

• Oxytocin - Common medication used to prevent or treat uterine atony.

• Blood transfusion - Timely replacement of severe blood loss.

• Intravenous fluids - Treatment of hypovolemia.

• Emergency obstetric surgery - Surgery when bleeding cannot be controlled medically.

• Intensive care - Critical care for severe shock or organ dysfunction.

• Postpartum follow-up - Screening after severe obstetric hemorrhage.

• Lactation assessment - Evaluation of failure to produce breast milk after hemorrhage.

Women with severe postpartum hemorrhage should be asked about lactation failure, amenorrhea, fatigue, dizziness, and symptoms of pituitary hormone deficiency.

Prognosis

The prognosis is usually good when Sheehan's syndrome is recognized and treated. Lifelong hormone replacement can restore metabolic stability and reduce the risk of adrenal crisis.

Delayed diagnosis is common because symptoms may be nonspecific. Some patients are diagnosed many years after the childbirth event.

Epidemiology

Sheehan's syndrome is rare in many high-resource countries because of improved obstetric care, blood transfusion availability, and emergency treatment of postpartum hemorrhage. It remains an important cause of hypopituitarism in areas where severe postpartum bleeding is not rapidly treated."Sheehan syndrome: a current approach to a dormant disease".Pituitary.2025;doi:10.1007/s11102-024-01481-1.

The true frequency is difficult to estimate because mild or chronic cases may remain undiagnosed.

History

The syndrome is named for Harold Leeming Sheehan, a British pathologist who described postpartum necrosis of the anterior pituitary in the 1930s. His work helped distinguish postpartum pituitary necrosis from other causes of hypopituitarism.

Historically, the condition was recognized at autopsy in women who died after severe childbirth hemorrhage or years after delivery with features of pituitary failure. Modern MRI and hormone testing now allow diagnosis during life.

Patient education

Patients with Sheehan's syndrome should understand that the condition is usually lifelong and requires regular medical follow-up.

• Medication adherence - Take hormone medicines exactly as prescribed.

• Glucocorticoid withdrawal - Do not stop steroid replacement suddenly.

• Sick day rules - Increase glucocorticoid dosing during significant illness as instructed.

• Emergency care - Seek urgent care for vomiting, fainting, severe weakness, fever, or shock.

• Medical identification - Wear a medical alert bracelet or carry a steroid emergency card.

• Surgery - Tell healthcare providers about adrenal insufficiency before procedures.

• Endocrinology follow-up - Keep regular appointments for hormone monitoring.

• Pregnancy planning - Discuss future pregnancy with endocrinology and obstetrics specialists.

When to seek urgent medical care

Urgent medical care is needed for symptoms of possible adrenal crisis.

• Severe weakness - Especially with low blood pressure or vomiting.

• Syncope - Fainting or near-fainting.

• Confusion - Possible severe electrolyte or glucose disturbance.

• Vomiting - Persistent vomiting can prevent oral steroid absorption.

• Abdominal pain - Severe pain may occur during adrenal crisis.

• Hypotension - Very low blood pressure is an emergency sign.

• Dehydration - May worsen adrenal insufficiency.

• Hypoglycemia - Severe low blood sugar needs urgent treatment.

• Hyponatremia - Severe low sodium can cause confusion or seizures.

• Shock - Collapse or circulatory failure requires emergency treatment.

See also

• Hypopituitarism

• Panhypopituitarism

• Pituitary gland

• Anterior pituitary

• Postpartum hemorrhage

• Adrenal insufficiency

• Adrenal crisis

• Central hypothyroidism

• Lymphocytic hypophysitis

• Pituitary apoplexy

• Empty sella syndrome

• Growth hormone deficiency

• Amenorrhea

• Infertility

• Endocrinology

• Obstetrics

• Gynecology

• Pregnancy complications

External links

• Sheehan Syndrome - StatPearls
• Sheehan Syndrome - National Organization for Rare Disorders
• Generalized Hypopituitarism - Merck Manual Professional Edition