Hypopituitarism, Sheehan Syndrome

Sheehan syndrome is postpartum hypopituitarism resulting from ischaemic pituitary necrosis. It classically occurs in the setting of severe obstetric haemorrhage and associated hypotension.

It has historically been an important cause of hypopituitarism in regions with limited access to timely management of obstetric haemorrhage. It is now less common in well-resourced healthcare settings, given improvements in the prevention and management of major obstetric haemorrhage.

This entry provides the context relevant to this obstetric-related aetiology and its characteristic clinical presentation and diagnostic considerations.

Pathophysiology

• The anterior pituitary gland undergoes marked physiological hypertrophy during normal pregnancy, from increased lactotroph cell proliferation in preparation for postpartum lactation.
• This enlarged gland is believed to be particularly vulnerable to ischaemic injury in significant hypotension. Contributing factors are the vulnerable pituitary portal blood supply and the increased metabolic demand of the hypertrophied gland.
• Severe postpartum haemorrhage with significant, sustained hypotension produces ischaemic injury and, in more severe cases, frank necrosis of the anterior pituitary gland.
• The degree of hypopituitarism relates directly to the extent of glandular necrosis. It ranges from partial, single-axis hormonal deficiency to complete panhypopituitarism affecting all anterior pituitary hormone axes.
• The posterior pituitary is generally relatively spared because of its distinct blood supply. Arginine vasopressin deficiency is therefore a much less common feature than the anterior pituitary hormone deficiencies that dominate the presentation.

• Failure of postpartum lactation, from loss of functional lactotroph cells and resulting prolactin deficiency, is a classic and often early presenting feature. It is sometimes the first clue to the diagnosis in a woman who has had a significant peripartum haemorrhagic event.
• Failure to resume normal menstruation after delivery, with other features of gonadotropin deficiency, is a further common, early presenting feature. It reflects frequent, prominent involvement of this hormone axis.
• Recognition of the broader syndrome may be delayed, sometimes by months to years after the precipitating obstetric event. The additional hormone deficiencies (including thyroid stimulating hormone and adrenocorticotropic hormone deficiency) become apparent gradually and insidiously.
• A history of significant peripartum haemorrhage, even from some years previously, should therefore be sought proactively in any woman with features suggestive of hypopituitarism.
• The pattern and severity of presentation reflect the combination and severity of the individual anterior pituitary hormone deficiencies present.
• Adrenocorticotropic hormone deficiency is of critical significance because of the risk of life-threatening adrenal crisis if unrecognised.

• Diagnosis is established by a relevant clinical history (significant peripartum haemorrhage with associated hypotension) together with full anterior pituitary hormonal assessment showing the pattern of hormone deficiency present.
• Magnetic resonance imaging of the pituitary may show a small, atrophic or empty sella. This is a recognised, characteristic later finding, reflecting reduced pituitary tissue volume after the initial ischaemic necrotic event. It supports the diagnosis, particularly in a woman presenting some time after the precipitating event.
• Clinical recognition is frequently delayed and insidious. A high index of suspicion is therefore essential for timely diagnosis, with proactive enquiry about obstetric history in any woman with symptoms suggestive of hypopituitarism.

• Management comprises replacement of each identified deficient hormone axis.
• Adrenocorticotropic hormone deficiency needs particular priority and urgency, given the life-threatening potential of unrecognised or inadequately treated adrenal insufficiency. Educate the patient on sick day dose adjustment and emergency management planning.
• Lifelong, structured endocrinology follow up is required.
• Educate the patient about the diagnosis and its lifelong management requirements. Provide a medical alert bracelet or card given the risk of adrenal crisis.