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Introduction
Sheehanβs syndrome is a complication of severe post-partum haemorrhage (PPH) and hypovolaemic shock, in which there is ischaemic necrosis of the anterior pituitary gland.
Sheehanβs syndrome is extremely rare, seen in around 5/100,000 births.1
Aetiology
The pituitary gland is located within a depression of theΒ sphenoid bone, called theΒ pituitary (hypophyseal) fossa or sella turcica.
The blood supply to the anterior pituitary gland is from the hypothalamo-hypophyseal portal system, which is a low-pressure system. This means that it is vulnerable to rapid blood pressure reductions.
In contrast, the posterior pituitary gland has a rich blood supply from various arteries, so it is not susceptible to ischaemia during drops in blood pressure.2
The hormones that the anterior pituitary releases are:
- Follicle-stimulating hormone (FSH)
- Luteinising hormone (LH)
- Thyroid-stimulating hormone (TSH)
- Growth hormone (GH)
- Adrenocorticotropic hormone (ACTH)
- Prolactin
The hormones that the posterior pituitary gland releases (which are typically not affected by Sheehanβs syndrome) are:
- Antidiuretic hormone (ADH)
- Oxytocin
Risk factors
Risk factors for Sheehanβs syndrome include:
- Pregnancy, particularly multiple pregnancy
- Placental abruption
- Placenta praevia
- Pre-eclampsia
- Severe PPH
- History of autoimmune disease
Clinical features
The clinical features seen in Sheehanβs syndrome are associated with the lack of hormone production by the anterior pituitary gland.
Patients can present acutely or chronically. Commonly, women present months to years after the initial event.3
Clinical features of Sheehanβs syndrome include:
- Reduced milk production (agalactorrhea): due to the lack of prolactin
- Amenorrhoea: due to lack of FSH and LH
- Hypothyroidism: due to lack of TSH
- Adrenal insufficiency and adrenal crisis: due to lack of ACTH
History
The first and most common symptom of Sheehanβs syndrome is agalactorrhea, and another common symptom is amenorrhea.
Symptoms typically reflect which anterior pituitary hormones are affected and to what degree. These symptoms would relate to deficiencies of thyroid hormones, prolactin, gonadotrophins, adrenals, and growth hormone.
Symptoms of hypothyroidism include:
- Fatigue
- Weight gain
- Constipation
- Depression
- Loss of libido
- Cold intolerance
Symptoms of adrenal insufficiency include:
- Fatigue
- Muscle cramps & weakness
- Thirst and craving salt
- Dizziness and fainting
- Abdominal pain
Clinical examination
Clinical findings of hypothyroidism on examination include:
- Bradycardia
- Dry skin
- Stiff muscles
- Cold peripheries
- Hair loss
Clinical signs of adrenal insufficiency include:
- Hypotension (particularly postural hypotension)
- Bronze pigmentation of the skin, commonly in skin creases
Other signs on clinical examination may include:
- Breast tissue atrophy
- Decreased axillary and pubic hair growth
Differential diagnoses
Differential diagnoses of Sheehanβs syndrome include:
- Addisonβs disease: patients will present with adrenal insufficiency alone
- Pituitary tumour:Β patients will present very similar to those with Sheehan’s syndrome
- Hypothyroidism: patients will present with symptoms of hypothyroidism alone
- Menopause: patients will present with amenorrhoea alone
Investigations
Laboratory investigations
Relevant laboratory investigations include:
- Blood tests for the hormones produced by the anterior pituitary: TFTs, FSH, LH, ACTH, prolactin
- Plasma cortisol level
- Serum IGF-1: low in hypothyroidism and GH deficiency
- GH provocation test: GH level is measured after clonidine and arginine are administered, which stimulates GH secretion
- Pituitary hormone stimulation tests: metoclopramide and clomiphene citrate stimulation tests
Imaging
Relevant imaging investigations include:
- MRI scan: may show acute changes of ischaemia or an empty sella turcica, also to rule out other causes of the symptoms (e.g. a pituitary tumour)
- CT scan: if the MRI scan is inconclusive
Management
Management of Sheehanβs syndrome will be guided by a specialist endocrinologist, and it will be lifelong.
Medical management
The main aim is to replace the missing hormones:
- HRT including oestrogen and progesterone for female sex hormones until menopause
- Growth hormone
- Levothyroxine for hypothyroidism
- Hydrocortisone for adrenal insufficiency
Complications
Complications of Sheehanβs syndrome include:
- Hypothyroidism
- Addisonian crisis
- Death
Key points
- Sheehanβs syndrome is ischaemic necrosis of the anterior pituitary gland, commonly due to a severe postpartum haemorrhage
- The anterior pituitary gland produces many hormones including TSH, LH, FSH, ACTH, GH and prolactin
- Common symptoms include amenorrhea and agalactorrhea
- Common clinical findings include postural hypotension and hair loss
- Primary investigations are blood tests for the hormones produced by the anterior pituitary gland
- Mainstay treatment is medications that replace those lost hormones, this includes, HRT, levothyroxine and hydrocortisone
- Complications can include hypothyroidism and Addisonian crisis.
Reviewer
Mr Obinna Mba
Obstetrics and Gynaecology consultant
References
- Schury MP, Adigun R. Sheehan Syndrome. Treasure Island (FL): StatPearls Publishing. January 2024. Available from: [LINK]
- Karaca, Z., Laway, B., Dokmetas, H.Β et al. Sheehan syndrome. Nat Rev Dis Primers. December 2016.Β
- Diri, H., Karaca, Z., Tanriverdi, F.Β et al. Sheehanβs syndrome: new insights into an old disease. Endocrine. January 2016.