Sheehan Syndrome: Definition, Causes, Risk Factors, Symptoms, Diagnosis, Treatment and Prognosis

It is a type of hypopituitarism, which can occur when a woman has severe bleeding during delivery.

With the onset of Sheehan syndrome, deficiencies may develop in some or all of the hormones regulated by the pituitary gland .

What leads to hypocortisolism, hypothyroidism , hypogonadism and there is no production of growth hormone and prolactin.

The onset of diseases such as diabetes is rare.

The Sheehan syndrome mainly affects the endocrine system and the reproductive system.

Causes of Sheehan syndrome

Sheehan syndrome is a rare disorder of postpartum panhypopituitarism, which occurs as a result of ischemia and subsequent necrosis of the pituitary gland, and is classically a secondary condition after severe postpartum hemorrhage.

Postpartum hemorrhage produces a decrease in intravascular volume and hypotension , which results in the ischemia of several organs, including the pituitary gland.

Ischemia of the pituitary gland produces a necrosis and dysfunction.

The pituitary gland is at the base of the brain.

Hormones that normally depend on the synthesis and regulation of the pituitary, such as glucocorticoids, thyroid hormone, growth hormone, prolactin and gonadotropins.

Like luteinizing hormone and follicle-stimulating hormone, these hormones become deficient and that is when the clinical syndrome occurs.

Risk factor’s

Sheehan syndrome is associated with severe postpartum hemorrhage that can occur in women without any risk factors.

Risk factors for primary postpartum hemorrhage include the following:

  • The first pregnancy (primogesta patients).
  • The obesity.
  • The large size of the baby (macrosomia).
  • In cases of multiple gestation (twins, triplets, among others).
  • The prolonged labor.
  • A hemorrhage before childbirth.
  • In cases of placental retention.
  • In the cases of attached placenta.
  • When there are soft tissue lacerations.
  • Blood disorders of the maternal blood called fetal erythroblastosis.
  • Intrapartum intervention.
  • Hypertensive disorders, including preeclampsia .
  • Detachment of the placenta.
  • Asian or Hispanic ethnicity.
  • Epidural anesthesia.
  • Chorioamnionitis or infection of the amniotic fluid.
  • Intrapartum hemorrhage.

Postpartum hemorrhage is associated with obstetric interventions such as an increase in labor, episiotomy, forceps, and cesarean section.

Unnecessary interventions should be avoided where possible and addressing or limiting risk factors that are modifiable and associated with postpartum hemorrhage.

symptom

The pituitary gland is the gland that produces the hormones necessary to stimulate growth, stimulate the production of breast milk, regulate reproductive functions, function of the thyroid and adrenal glands.

The absence of these hormones can cause a variety of symptoms.

Symptoms that occur with Sheehan syndrome may include:

  • The inability to produce milk to breastfeed the baby.
  • The patient presents fatigue.
  • The absence of menstrual bleeding.
  • The loss of pubic hair and axillary hair.
  • Decreased blood pressure.

It is possible that the symptoms that occur with Sheehan syndrome do not develop until several years after delivery.

Diagnosis

Medical record:

In the medical history reference will be made to the symptoms that the postpartum patient presents, such as the impossibility to produce breast milk, presents problems such as low blood pressure levels.

Low levels of sugar in the blood, absence of menstruation ( Amenorrhea ), or delays (Oligomenorrhea), the patient has intolerance to cold, constipation , generalized weakness, alopecia, among others.

However, it is possible that a patient can not become symptomatic until years after inciting the postpartum event, caused by a subsequent adrenal crisis or secondary to a stressor.

Physical exam:

The vital signs may be initially consistent with the shock.

The findings of the physical examination are mainly due to individual hormonal deficiencies.

It may include decreased muscle strength, dry wrinkled skin, paleness, loss of pubic and axillary hair, atrophy of the breasts and decreased vaginal secretions.

Mental examination may show mental decline, apathy, and psychiatric disorders.

Differential diagnosis:

Other causes of hypopituitarism, more common is pituitary neoplasia.

Rarer causes include diseases such as autoimmune lymphocytic hypophysitis, increased intracranial pressure, accidental trauma, acute pituitary apoplexy, diabetes mellitus, among others.

Initial tests:

Complete loss of pituitary function is life-threatening and requires immediate treatment.

Computed tomography or magnetic resonance imaging can help evaluate pituitary injury due to infarction or hemorrhage, but images are rarely needed in a classic clinical setting.

An empty Turkish chair can be seen in the images if a pituitary necrosis has occurred, and particularly if it has been prolonged.

The pituitary gland increases in size during pregnancy, up to 136% of the average size it has under normal conditions, so it becomes more dependent on blood flow and is susceptible to ischemia .

Pituitary hormones must be analyzed individually to make the diagnosis.

The first hormones lost are prolactin and growth hormone.

Serum studies should be done in the early hours of the morning when the daytime cortisol level is at its maximum level.

Laboratory tests may show:

  • A decrease in serum cortisol, free T4 and estradiol.
  • Luteinizing hormone and follicle-stimulating hormone should only be analyzed in cases where the patient is amenorrheic, normal, and low levels.
  • The level of prolactin is generally low.
  • TSH levels may be normal, low or paradoxically high but biologically less active.
  • The levels of growth hormone are unmistakably low.
  • Most patients are deficient in the adrenocorticotropic hormone.
  • A complete blood count or blood count may show normocytic and normochromic anemia or pancytopenia.

Hyponatremia is the most frequent electrolyte alteration and occurs in 33% to 69% of cases.

Serum glucose may be consistent with hypoglycemia .

If the pituitary stalk is affected, the patient may have central diabetes insipidus (decreased or absent antidiuretic hormone) and hypernatremia .

Interpretation:

Chronic findings may show replacement of the necrotic anterior pituitary gland with hypocellular connective tissue.

Treatment

First line:

In the case of hypocortisolism:

Hydrocortisone is replaced first to prevent the adrenal crisis from replacing T4.

This should be given 15 to 25 mg per day (this is the standard dose for adults).

The treatment is usually 2 to 3 daily doses, but recent studies suggest that 5 mg twice a day is adequate and prevents excessive replacement.

The monitoring is mainly clinical due to the lack of objective parameters.

Within considerations of pregnancy, cortisol-binding globulin and free cortisol levels increase during pregnancy, so the hydrocortisone replacement should be increased by 50% in the third trimester of pregnancy.

Second line:

The hormones must be replaced according to the individual deficiencies observed in the laboratories.

In the case of Hypothyroidism:

The replacement of thyroid hormone tetraiodothyronine is adjusted to the individual requirements of each patient.

The administration of an exogenous thyroid hormone such as levothyroxine (T4), in doses of 1.5 μg per kg of body weight per day.

The levels of thyroid hormone increase during pregnancy.

Substitution of thyroid hormone should be increased during pregnancy by 30%.

In the case of Hypogonadism :

The replacement of the gonadotropin must be adjusted to the individual requirements of each patient, according to the results of laboratory studies or clinical symptoms.

Estrogen and progesterone must be replaced to mimic physiological secretion in women.

Treatment should be recommended to premenopausal women with an oral contraceptive containing 20 to 35 μg of estrogen.

Treatment with transdermal estradiol can also be considered.

In the case of growth hormone deficiency:

Patients with severe growth hormone deficiency can undergo replacement.

This replacement is controversial in adults and there are no standard recommendations.

In cases where the replacement is performed, the recommended therapy is to start with low doses such as 0.15 to 0.3 mg per day, with constant monitoring and titration that will allow adjustment at the individual level, depending on the patient’s response.

In cases of prolactin deficiency:

Currently, there are no treatments available for prolactin deficiency.

In these cases, breastfeeding is not feasible and babies will need to be fed with infant formulas.

Forecast

When the patient enters a state of shock, with an adrenal crisis or in a state of shock secondary to a postpartum hemorrhage.

For patients in shock, the guidelines of advanced cardiac life support are used, replacing fluids intravenously.

Once stabilized with first-line treatment, hormone replacement can be initiated and controlled in an outpatient setting.

The prognosis is rarely fatal, but requires lifelong hormone replacement.

The greatest danger is presented in the event that glucocorticoids or thyroid hormones are not replaced.

The prognosis with early diagnosis and treatment is excellent.

Complications

Sheehan syndrome is a condition that can be essentially dangerous and even lethal if it is not treated in time.