MRI of the pituitary gland (sagittal section); arrows indicate the sella turcica: A, T1-weighted image showing a low homogenous signal in the sella turcica. B, T2-weighted image showing a highly homogenous signal in the sella turcica. C, Gadolinium-enhanced image showing peripheral enhancement of the pituitary gland. These findings are diagnostic of an empty sella | Taniguchi, J, Sugawara, H, Yamada, H, et al. Adrenal crisis precipitated by influenza A led to the diagnosis of Sheehan's syndrome 18 years after postpartum hemorrhage. Clin Case Rep. 2020; 8: 3081– 3086. https://doi.org/10.1002/ccr3.3355
Contents
Postpartum hypopituitarism caused by necrosis of the pituitary gland.
Type of Pituitary apoplexy (infarction or haemorrhage of pituitary gland)
History:
The specific association with postpartum shock or haemorrhage was described in 1937 by the British pathologist Harold Leeming Sheehan (1900–1988). The initial distinction was made in the research article “Post-Partum Necrosis of the Anterior Pituitary”. In his research, Dr Sheehan reviewed (through autopsy) the effects of pituitary necrosis on 12 cases of patient’s that experienced postpartum necrosis. He observed cases where lesions and death occurred during or after pregnancy, as well as cases where death occurred in the late stage of necrosis (years later). This started the initial distinction of Sheehan’s syndrome from Simmonds’ disease (also known as hypopituitarism). Dr Sheehan noted that significant features of these patient cases were haemorrhaging, which in his experience was most commonly caused by either: placenta Previa (low placenta), uterine rupture, cervical or uterine tears, post-partum atony, or retained placenta. Simmonds’ disease, however, occurs in either sex due to causes unrelated to pregnancy.
Harold Leeming Sheehan FRCP FRCOG FRCPath TD (1900–1988) was a British physician, pathologist, and professor of pathology.
However, in his 1939 publication: “Simmonds’ Disease due to Post-partum Necrosis of the Anterior Pituitary”, Dr Sheehan displays post-partum necrosis as a cause of Simmonds’ disease, thus establishing the relationship between the two conditions. According to Sheehan in 1939 approximately 41% of survivors of severe postpartum haemorrhage (PPH) and/or hypovolemic shock experienced severe or partial hypopituitarism.
Aetiology
Genetics
Small sella turcica
Autoimmunity
Severe PPH
Coagulopathies
Pathophysiology
Anatomy of pituitary gland:
Anatomy and vascularization of the pituitary gland: a) The pituitary gland is located in the sphenoid bone (sella turcica) and is composed of the anterior lobe (adenohypophysis) and the posterior lobe (neurohypophysis). The anterior lobe is composed of three parts: the pars distalis, which is the main component of adenohypophysis that secretes anterior pituitary hormones; the pars intermedia, which is suppressed in humans; and the pars tuberalis, which surrounds the infundibulum. The optic chiasma (where the optic nerves cross) is located on top of the superior part of the pituitary gland. b) The infundibulum, median eminence, pars tuberalis and posterior lobe are supplied by the internal carotid artery, whereas the pars distalis receives most of its blood supply from venous drainage from the infundibulum and the posterior lobe of the pituitary gland. The venous blood supply makes the anterior pituitary gland vulnerable to disturbances in blood supply. | Karaca, Z., Laway, B. A., Dokmetas, H. S., Atmaca, H., & Kelestimur, F. (2016). Sheehan syndrome, 2, 16092. Retrieved from http://dx.doi.org/10.1038/nrdp.2016.92
Hypothalamic-pituitary-adrenal axis:
Regulation of the hypothalamic–pituitary– adrenal axis: Glucocorticoid secretion is regulated by adrenocorticotropic hormone (ACTH) secretion from the pituitary gland, which is stimulated by corticotropin releasing hormone (CRH) secretion from the hypothalamus. CRH is suggested to be regulated from the upper centres of the brain. Glucocorticoids have negative-feedback effects on the upper centres of the brain, the hypothalamus and the pituitary gland. ACTH not only stimulates glucocorticoids but also stimulates adrenal androgens and mineralocorticoids. However, given that aldosterone secretion is primarily regulated by the renin– angiotensin system, ACTH deficiency does not result in mineralocorticoid deficiency, but leads to glucocorticoid deficiency and adrenal androgen deficiency in women. | Karaca, Z., Laway, B. A., Dokmetas, H. S., Atmaca, H., & Kelestimur, F. (2016). Sheehan syndrome, 2, 16092. Retrieved from http://dx.doi.org/10.1038/nrdp.2016.92
Pathology:
Adenohypophyseal ischaemic necrosis following hypoperfusion
At least 75% of pituitary must be destroyed before clinical manifestations become evident.
Prolactin and growth hormone: M/C hormones affected by selective pituitary necrosis and hypofunction
Pathogenesis of Sheehan syndrome: The pituitary gland is physiologically enlarged during pregnancy as a result of massive hyperplasia of the lactotroph cells, which are stimulated by oestrogens produced by the placenta. The vascular structure of the pituitary gland might become compressed because of pituitary gland enlargement and/or small sella turcica size. Vasospasm (caused by massive postpartum haemorrhage) and/or thrombosis (associated with pregnancy, genetic predisposition or disorders of blood coagulation) might result in ischaemia. Autoimmunity might worsen hypopituitarism over the years. | Solid arrows indicate the well-known mechanisms; dashed arrows indicated mechanisms that have not yet been proven. | ACTH, adrenocorticotropic hormone; FSH, follicle-stimulating hormone; GH, growth hormone; LH, luteinizing hormone; PRL, prolactin; TSH, thyroid-stimulating hormone. | Karaca, Z., Laway, B. A., Dokmetas, H. S., Atmaca, H., & Kelestimur, F. (2016). Sheehan syndrome, 2, 16092. Retrieved from http://dx.doi.org/10.1038/nrdp.2016.92
Presentation
Characteristic manifestations include failure to lactate or to resume menses, genital and axillary hair loss, asthenia and weakness, fine wrinkles around the eyes and lips, signs of premature aging, dry skin, hypopigmentation and other evidence of hypopituitarism.
Usually present in the postpartum period with lactation failure or after many months to years following the inciting delivery.
Agalactorrhoea (lack of prolactin) or amenorrhoea (lack of LH & FSH)
Lack of growth hormone:
Asthenia and weakness
Dry skin, hypopigmentation
Signs of premature ageing
Genital and axillary hair loss
Fine wrinkles around the eyes and lips
Complications
Hypothyroidism
2° Adrenal insufficiency:
Addisonian crisis
Hyponatremia, hypoglycaemia
Death
Diagnosis
Pituitary hormone levels:
MRI, CT-scan
Pituitary ring sign: Ring enhancement or halo around sella turcica
Radiological characteristics of Sheehan syndrome: a,b) Acute phase: Post-contrast MRI scans of the pituitary gland in a patient 2 months after postpartum haemorrhage showing gland atrophy and non-haemorrhagic central infarction characterized by central hypointensity on T1-weighted images (part a) and hyperintensity on T2-weighted images (part b). c,d) Chronic phase: Coronal (part c) and sagittal (part d) T1-weighted MRI scans showing an empty sella turcica. Sella turcica size is normal in all images. | Arrows indicate the pituitary gland. | Karaca, Z., Laway, B. A., Dokmetas, H. S., Atmaca, H., & Kelestimur, F. (2016). Sheehan syndrome, 2, 16092. Retrieved from http://dx.doi.org/10.1038/nrdp.2016.92
Differential diagnosis:
Addison syndrome
Lymphocytic hypophysitis
Pan-hypopituitarism
Pituitary apoplexy
Management
Prevention:
Aggressive management of PPH & other causes of blood loss
Treatment:
Hormone Replacement Therapy (HRT)
Summary
Overview of Sheehan syndrome | Karaca, Z., Laway, B. A., Dokmetas, H. S., Atmaca, H., & Kelestimur, F. (2016). Sheehan syndrome, 2, 16092. Retrieved from http://dx.doi.org/10.1038/nrdp.2016.92
