bubble_chart Overview

Hypopituitarism (Simmonds-Sheehan syndrome) is clinically characterized primarily by insufficient secretion of hormones from the anterior pituitary, leading to secondary hypofunction of its target glands (gonads, thyroid, adrenal cortex).

The disease causes include postpartum hemorrhage, intracranial tumors, infections, granulomas, trauma, pituitary radiotherapy, surgery, and autoimmune disorders. This chapter focuses on postpartum hypopituitarism.

Postpartum hypopituitarism was first identified by Sheehan in 1937 as being caused by anterior pituitary necrosis due to postpartum hemorrhage, and is later referred to as Sheehan syndrome.

bubble_chart Etiology

This disease is primarily caused by massive bleeding during childbirth due to conditions such as placenta previa, placental abruption, retained placenta, cervical laceration, uterine rupture, or uterine atony. This leads to a sudden decrease in effective blood flow to the anterior pituitary, resulting in spasm and infarction of the pituitary arterioles, ischemic necrosis of the anterior pituitary, followed by fibrosis and atrophy, reduction of parenchymal cells, and diminished function, ultimately leading to secondary hypofunction of the target glands. Additionally, a few cases may result from postpartum infections causing embolism of the pituitary arterioles or disseminated intravascular coagulation, thereby inducing the disease.

bubble_chart Pathogenesis

During pregnancy, the pituitary gland undergoes physiological hypertrophy, and the anterior pituitary is supplied by its portal system. Therefore, when the effective blood flow decreases sharply due to the above factors during childbirth, this disease is prone to occur. The blood supply to the posterior pituitary does not rely on the pituitary portal system, so postpartum metrorrhagia generally does not cause its necrosis, and diabetes insipidus is rare.

According to general estimates, symptoms appear when more than 60% of the anterior pituitary tissue is destroyed, become obvious when more than 75% is destroyed, and become severe when more than 95% is destroyed. Due to the uneven nature of anterior pituitary lesions, the degree of reduction in various tropic hormones varies, and sometimes only a single tropic hormone deficiency is manifested.

bubble_chart Clinical Manifestations

The onset is mostly gradual, with a history of postpartum hemorrhage, syncope, or puerperium infection. The manifestations of insufficient secretion of multiple anterior pituitary hormones usually appear progressively. Generally, symptoms of promoting lactation hormone, gonadotropin, and growth hormone deficiency occur first, followed by manifestations of thyrotropin and adrenocorticotropic hormone deficiency. Sometimes, symptoms of adrenal cortical insufficiency may precede those of hypothyroidism.

1. Promoting lactation hormone deficiency: After childbirth, it manifests as lack of breast engorgement and absence of milk secretion.
2. Growth hormone deficiency: In adults, it primarily presents as susceptibility to hypoglycemia, as growth hormone has a hyperglycemic effect.
3. Gonadotropin deficiency: Patients exhibit amenorrhea, decreased or absent libido, significant atrophy of the breasts and genitalia, and infertility. Hair loss is common, particularly in the axillary and pubic regions, with sparse eyebrows. The amenorrhea in these patients typically lacks paroxysmal facial flushing and other vasomotor disturbances, distinguishing it from menopausal women.
4. Thyrotropin deficiency: Complexion is pale with a prematurely aged appearance. The skin is dry, thin, and atrophic, or may show edema, though rarely myxedema; patients appear apathetic, with slow reactions, a low-pitched voice, intellectual decline, and a tendency to curl up due to fear of cold. Hallucinations, delusions, mental disturbances, or even mania may occur. The heart rate is slow, and electrocardiograms show low voltage, with possible flat or inverted T waves. The heart is often not enlarged and may even shrink, distinguishing it from primary hypothyroidism.
5. Adrenocorticotropic hormone deficiency: Mainly affects glucocorticoid secretion. Patients experience weakness, lack of strength, poor appetite, nausea, vomiting, epigastric pain, weight loss, low blood pressure, intolerance to hunger, and susceptibility to hypoglycemia, hyponatremia, or dehydration. Reduced resistance increases susceptibility to infections, which may lead to shock or unconsciousness.
6. Melanocyte-stimulating hormone deficiency: Both melanocyte-stimulating hormone and adrenocorticotropic hormone promote skin pigmentation. Due to the deficiency of these hormones, patients exhibit lighter skin tones, with no significant darkening even after sun exposure. Normally pigmented areas, such as the areola and midline of the abdomen, become notably lighter. This contrasts with the increased pigmentation seen in primary chronic adrenal cortical insufficiency.

Based on the above symptoms, the condition can be clinically classified into the following four types:

1. Gonadal hypofunction type, common;
2. Secondary myxedema type, less common;
3. Paroxysmal hypoglycemia type, least common but most severe;
4. Mixed type, most common.

Anterior pituitary hypofunction crisis is often triggered by various stressors such as infection, diarrhea, vomiting, dehydration, hunger, cold exposure, excessive fatigue, trauma, surgery, anesthesia, and reactions to sedatives, hypnotics, or hypoglycemic drugs. Clinical manifestations include severe weakness, vomiting, high fever or hypothermia, delirium, drowsiness, unconsciousness, convulsions, etc. Based on the predominant symptoms, it can be categorized into hyperpyrexic type (>40°C), hypoglycemic type, circulatory failure type, or water intoxication type.

bubble_chart Auxiliary Examination

Metabolic disorders and other changes

1. often present with anemia, mostly normochromic and normocytic anemia;
2. fasting blood glucose is low, prone to hypoglycemia, with a flat glucose tolerance curve;
3. serum sodium and chloride may be low, while blood potassium is mostly normal;
4. water load capacity is reduced, which can be corrected with corticosteroids.

Endocrine function tests

1. Anterior pituitary function assessment: FSH, LH, TSH, ACTH, PRL, and GH plasma levels are below normal. To evaluate anterior pituitary reserve function or differentiate hypothalamic causes, relevant stimulation tests such as TRH test or LRH test may be selected.
2. Target gland function assessment
   1. Gonadal function shows low levels of estrogen and progesterone, vaginal mucosal smear reveals reduced keratinized cells, and basal body temperature measurement indicates an anovulatory curve.
   2. Thyroid function shows a reduced basal metabolic rate, mostly below 20%. Blood T3, T4, and thyroid ¹³¹I uptake rates are below normal.
   3. Adrenal cortical function shows 24-hour urinary 17-OHCS and 17-KS levels below normal. The ACTH stimulation test shows a delayed response, indicating adrenal cortical dysfunction secondary to anterior pituitary lesions. Plasma cortisol and 24-hour urinary free cortisol are often below normal.

bubble_chart Diagnosis

The diagnosis is relatively straightforward in cases with a history of postpartum massive hemorrhage, shock, or puerperal infection, accompanied by clinical symptoms of gonadal, thyroid, and adrenal cortex hypofunction, along with signs and laboratory evidence. However, for a minority of patients with atypical early symptoms or an uneven progression of hypofunction in the three target glands, the diagnosis can be more challenging.

bubble_chart Treatment Measures

General Treatment

Patients should consume a high-calorie, high-protein, and high-vitamin diet, maintain a regular lifestyle, stay warm, prevent infections, and avoid excessive fatigue and emotional stress. Narcotic analgesics like morphine, sedatives like barbiturates, central nervous system depressants like chlorpromazine, and various hypoglycemic agents should be prohibited or used with caution to prevent inducing unconsciousness.

Hormone Replacement Therapy

Supplementing anterior pituitary hormones seems ideal, but it requires injections for efficacy, is inconvenient to administer, expensive, and some preparations may induce antibody production after long-term use. When target glands are severely atrophied, pituitary tropic hormones often prove ineffective. Currently, target gland hormones are widely used in clinical practice for replacement therapy due to their reliable efficacy, low cost, and ease of administration.

1. Adrenocortical Hormones: These should be administered before thyroid hormone therapy to avoid inducing a crisis. The drug of choice is hydrocortisone, with the dose individualized. Severe cases may require full replacement, approximately 30mg daily (equivalent to 37.5mg cortisone or 7.5mg prednisone). The dosing regimen involves administering two-thirds of the daily dose at 8 AM and one-third at 2 PM. The dose should be reduced for maintenance once the condition improves. During stress conditions like infections, surgery, or trauma, the dose should be increased as needed. Since aldosterone secretion may not be significantly reduced, deoxycorticosterone is rarely required.
2. Thyroid Hormones: These are usually started 3–5 days after initiating adrenocortical hormone therapy or concurrently. Treatment must begin with a small dose, starting with 15–30mg of desiccated thyroid daily, then increasing by 15–30mg every 4–7 days, with a maintenance dose of approximately 60–120mg daily. Alternatively, levothyroxine (T4) can be initiated at 25μg daily and gradually increased to a maintenance dose of 100–200μg daily. Larger doses may be divided into two oral administrations, and heart rate changes should be monitored to avoid overdose.
3. Sex Hormones: Routine use is unnecessary. For middle-aged and older women, sex hormones may be omitted or used in small doses. Younger patients may undergo artificial menstruation by taking 0.5–1.0mg of diethylstilbestrol orally at bedtime for 20 days, with the addition of 10mg progesterone intramuscularly or 4–8mg megestrol orally daily during the last 5 days. Menstruation may resume 3–5 days after stopping the medication, helping to maintain secondary sexual characteristics and sexual function while improving mental and physical well-being. Subsequent cycles can be repeated after menstruation ceases. If pregnancy occurs during this cyclic therapy, it may sometimes alleviate the condition, but care must be taken to prevent postpartum hemorrhage, which could worsen the disease.

Crisis Management

1. For suspected hypoglycemia, first administer 40–60ml of 50% glucose intravenously.
2. Follow with 200–300mg hydrocortisone in 5% glucose saline via intravenous drip over 24 hours. After improvement, reduce the dose of adrenocortical hormones and switch to oral preparations.
3. Administer thyroid hormone preparations orally or via nasogastric tube if oral intake is not possible. Desiccated thyroid can be given at 30–60mg every 6 hours; triiodothyronine is more effective at 20μg every 6 hours. For severe hypothermic unconsciousness, intravenous injection may be used, with dose reduction after improvement.
4. For patients with peripheral circulatory failure, add anti-shock medications.
5. For concurrent infections, promptly administer sufficient antibiotics to control the infection.
6. For high fever, apply appropriate antipyretic treatment.
7. For hypothermic patients, provide warmth but avoid burns.
8. For water intoxication, immediately administer 40–80mg hydrocortisone or 10–20mg prednisone orally. If oral administration is not possible, slowly inject 25mg hydrocortisone in 40ml of 25% glucose intravenously, followed by 100mg hydrocortisone in 250ml of 10% glucose via intravenous drip. Adjust the dose based on the patient's condition.

bubble_chart Prevention

Actively conduct prenatal examinations and carefully observe and manage the childbirth process. Strictly prevent postpartum hemorrhage and puerperal fever to avoid the occurrence of this disease.

bubble_chart Differentiation

In the differential diagnosis, the following two groups of diseases should be excluded:

1. Multiple target gland hypofunction, the main basis is the elevation of related tropic hormones, and a weak or absent response to ACTH and TRH tests, which differs from anterior pituitary hypofunction.
2. Chronic wasting diseases or psychogenic anorexia; the former has symptoms of the primary disease, while the latter has psychological factors, and generally, axillary and pubic hair remain normal.