Sheehan Syndrome 

Sheehan syndrome is a postpartum hypopituitarism caused by ischemic necrosis of the anterior pituitary gland following severe postpartum hemorrhage (PPH) and hypovolemic shock.


Historical Background

The condition is named after British pathologist: Harold Leeming Sheehan

He first described postpartum pituitary necrosis in 1937 while studying women who died after severe obstetric hemorrhage.


Why Pregnancy Predisposes to Pituitary Injury

Physiological Changes in Pregnancy

During pregnancy:

  • Pituitary gland enlarges by 120–150%
  • Enlargement mainly due to:
    • Lactotroph hyperplasia (prolactin-producing cells)
  • Blood supply does NOT proportionally increase

👉 Result → Pituitary becomes highly vulnerable to ischemia.


Pituitary Blood Supply (Key Pathophysiology)

Anterior Pituitary Supply

  • Supplied mainly by:
    • Superior hypophyseal arteries
    • Portal venous system

👉 Low pressure vascular network
👉 Highly vulnerable to hypotension


Posterior Pituitary Supply

  • Supplied by inferior hypophyseal arteries
  • Direct arterial blood supply
  • Therefore:

✅ Usually spared in Sheehan syndrome


Definition

Sheehan syndrome is:

Ischemic necrosis of anterior pituitary occurring after severe postpartum hemorrhage causing hypopituitarism.


Epidemiology

More common in:

  • Developing countries
  • Areas with:
    • Poor obstetric care
    • Delayed hemorrhage control

Incidence:

  • Rare in developed settings
  • Still seen in rural obstetric practice


Etiology

Primary Trigger

Severe postpartum hemorrhage

Usually due to:

  • Uterine atony (most common)
  • Placental abruption
  • Placenta previa
  • Retained placenta
  • Obstetric trauma
  • Disseminated intravascular coagulation


Pathophysiology (Step-by-Step)

Stage 1 – Pregnancy Pituitary Enlargement

  • Increased metabolic demand
  • Lactotroph hypertrophy


Stage 2 – Obstetric Hemorrhage

  • Massive blood loss
  • Hypovolemic shock
  • Reduced portal circulation flow


Stage 3 – Pituitary Infarction

  • Anterior pituitary ischemia
  • Necrosis and fibrosis


Stage 4 – Hormonal Failure

Sequential loss typically follows order:

  1. Growth hormone
  2. Prolactin
  3. Gonadotropins (LH/FSH)
  4. ACTH
  5. TSH

 ACTH deficiency = Most life-threatening


Clinical Presentation

Presentation varies from:

  • Acute life-threatening crisis
  • Delayed chronic endocrine failure (years later)


Acute Presentation (Immediately Postpartum)

Classic Early Clues

1️⃣ Failure of Lactation (Earliest Sign)

  • Due to prolactin deficiency
  • Very important exam point


2️⃣ Postpartum Hypotension

  • Secondary adrenal insufficiency


3️⃣ Hypoglycemia

  • Cortisol deficiency
  • GH deficiency


4️⃣ Hyponatremia

  • Cortisol deficiency → increased ADH


5️⃣ Shock Resistant to Fluids

  • Due to cortisol deficiency


Chronic Presentation (Months to Years Later)

Very commonly missed.

Reproductive Symptoms

  • Amenorrhea
  • Infertility
  • Loss of libido
  • Breast atrophy


Hypothyroidism Features

  • Fatigue
  • Weight gain
  • Cold intolerance
  • Bradycardia


Adrenal Insufficiency

  • Chronic fatigue
  • Hypotension
  • Recurrent hypoglycemia


GH Deficiency

  • Decreased muscle mass
  • Increased fat
  • Poor quality of life


Physical Examination Findings

General:

  • Pale appearance
  • Loss of axillary and pubic hair
  • Dry skin
  • Hypotension


Breast:

  • Failure of lactation
  • Breast involution


Hormonal Profile

Hormone

Finding

ACTH

↓

Cortisol

↓

TSH

↓ or normal (central hypothyroidism)

Free T4

↓

LH/FSH

↓

Estrogen

↓

Prolactin

↓

GH

↓


Laboratory Findings

Electrolytes

  • Hyponatremia
  • Hypoglycemia


Dynamic Endocrine Testing

  • Insulin tolerance test
  • ACTH stimulation test


Radiological Diagnosis

MRI Pituitary

Early Phase:

  • Pituitary swelling
  • Infarction

Late Phase:

👉 Empty sella (classic)


Differential Diagnosis

  • Lymphocytic hypophysitis
  • Pituitary adenoma apoplexy
  • Infiltrative diseases
  • Craniopharyngioma
  • Sarcoidosis
  • Tuberculosis


Sheehan Syndrome vs Lymphocytic Hypophysitis

Feature

Sheehan

Hypophysitis

Cause

Ischemic

Autoimmune

Timing

Postpartum hemorrhage

Late pregnancy/postpartum

Prolactin

Low

Often high

MRI

Empty sella later

Pituitary enlargement


Emergency Presentation in ICU

Critically ill patient may present with:

  • Refractory shock
  • Unexplained hypoglycemia
  • Hyponatremia
  • Coma

👉 Always consider Sheehan in postpartum women.


Acute Management (Life-Saving)

Step 1 – Treat Adrenal Crisis

Hydrocortisone is FIRST priority

  • IV Hydrocortisone 100 mg bolus
  • Followed by 50–100 mg every 6 hours

 NEVER start thyroid hormone before steroids


Step 2 – Correct Hypoglycemia

  • IV dextrose


Step 3 – Fluid Resuscitation

  • Isotonic saline


Chronic Hormone Replacement

Replacement Order (Exam Favourite)

👉 Always replace cortisol first


1️⃣ Glucocorticoid Replacement

  • Hydrocortisone 15–25 mg/day in divided doses


2️⃣ Thyroid Replacement

  • Levothyroxine after steroid stabilization


3️⃣ Gonadal Hormones

  • Estrogen/progesterone therapy
  • Fertility induction if required


4️⃣ Growth Hormone

  • Selected cases


Fertility Management

  • Ovulation induction
  • Assisted reproductive techniques

Pregnancy is possible with proper endocrine replacement.


Complications

  • Chronic adrenal crisis
  • Osteoporosis
  • Infertility
  • Cardiovascular risk
  • Reduced quality of life


✅ ACTH deficiency = most dangerous
✅ Steroids BEFORE thyroid replacement
✅ May present decades later


Critical Care Perspective (NEET-SS / INI-SS Focus)

Always suspect in:

  • Postpartum shock not responding to fluids/vasopressors
  • Unexplained recurrent hypoglycemia
  • Hyponatremia postpartum
  • Lactation failure history


Recent Guideline & Evidence Concepts

Modern endocrine recommendations stress:

  • Lifelong endocrine follow-up
  • Stress-dose steroids during illness
  • Pregnancy planning under specialist care