Pituitary gland present in the sella turcica of the brain, is divided into anterior and posterior pituitary. The blood supply of the posterior pituitary comes from the inferior hypophyseal artery while the anterior pituitary is supplied indirectly by portal vessels coming from hypothalamus and posterior pituitary [9]. This low pressure system feeding the anterior pituitary makes it more susceptible to ischemia after any vascular insult [10].
During pregnancy, this gland undergoes hyperplasia, increasing the nutritional and metabolic demands of the gland. In case of a massive PPH, this gland undergoes ischemic necrosis in 1–2% of women who lose 1–2 L of blood with associated hypotension [2].This condition is known as Sheehan syndrome.
Sheehan syndrome or postpartum pituitary necrosis, is a rare complication of PPH, indicating that there are other factors responsible for its causation apart from the compromised blood supply to the gland. These include enlargement of the pituitary gland, small size of the sella, disseminated intravascular coagulation and autoimmunity [11].
The clinical manifestations associated with this condition can result from selective loss of pituitary function or even panhypopituitarism. There is often a delay of months to years in the diagnosis of the condition due to the late presentation of vague and non-specific symptoms including fatigue, weakness and anemia after the initial vascular insult [12]. Our patient presented six years after her last obstetric event because the signs of adenohypophyseal insufficiency are often delayed and subtle [13]. She gave birth to a still born and thus could not provide a history of failure to lactate. Her amenorrhea and gradual deterioration after the delivery was, to most extent, neglected until she was hospitalized.
Owing to pituitary dysfunction and hypoprolactinemia, failure to lactate can occur along with low serum level of prolactin as seen in this patient. In our patient, the history was also notable for six years of amenorrhea and low serum levels of follicle stimulating hormone (FSH) and luteinizing hormone (LH) compared to the post-menopausal levels, indicating pituitary dysfunction as the cause of early menopause. Another less frequent cause of panhypopituitarism is Lymphocytic Hypophysitis, which needs to be ruled out in the diagnosis of Sheehan syndrome. Lymphocytic Hypophysitis is an autoimmune condition leading to impaired pituitary hormonal secretion and is also associated with other autoimmune diseases, such as Hashimoto's thyroiditis, autoimmune polyglandular syndrome type 2, Grave's disease, and systemic lupus erythematosus [6]. Low serum prolactin level in this patient along with a history of PPH makes Sheehan syndrome a more likely diagnosis.
Hypothyroidism from the deficiency of thyroid stimulating hormone (TSH) secreted by the anterior pituitary is responsible for a majority of clinical manifestations in our patient. Fatigue, loss of appetite, edema, hair loss and dry wrinkling skin seen here, can be explained by the deranged thyroid profile. A major cause of pericardial effusion is hypothyroidism, which usually gets corrected on achieving a euthyroid state [14]. Pericardiocentesis was performed to rule out infectious and malignant effusion.
Pituitary dysfunction leads to disruption of normal adrenocorticotropic hormone (ACTH)-cortisol axis seen as adrenocortical insufficiency. Common features of adrenal insufficiency like weight loss, anorexia, nausea, vomiting, lethargy and fatigue along with skin pigmentation over the elbows, knuckles, lips and gingival mucosa, and loss of axillary and pubic hair have been observed in people with primary adrenal failure [15]. Hypotension, tachycardia and hyponatremia, accompanied by impaired consciousness at the time of admission of our patient, indicate that she was in a state of adrenal crisis secondary to ACTH deficiency which was confirmed by low serum levels of ACTH and cortisol on analysis (Table 2).
According to a cohort study in Costa Rica, approximately 50% of patients with Sheehan syndrome develop panhypopituitarism, whereas only adrenal insufficiency is seen in around 33% patients and the remaining present with just hypothyroidism [16].
Confirmation of diagnosis of Sheehan Syndrome is done by imaging of pituitary gland and sella turcica where an empty sella is present in about 70% of patients, and a partially empty sella is present in about 30% of patients on MRI [17].
After the establishment of diagnosis, the aim of the treatment is to correct the endocrine imbalances such as hypoglycemia and adrenal insufficiency that warrant urgent care [18]. Normal function of the thyroid, adrenals and ovaries can be maintained by hormone substitution for life. It is important to have regular follow ups for response assessment and dose regulation of the medications.
Though the occurrence of Sheehan syndrome has slowly declined over time with better management of labour and delivery, in the resource poor healthcare settings of developing countries, its cases are still witnessed owing to neglected blood loss during delivery and poor management. The late presentation of this condition can result in a delay in diagnosis. It is important to note that mild hyponatremia should not be missed as a presenting sign of adrenal failure secondary to ACTH deficiency in a patient with Sheehan syndrome as in this case. The condition can be fatal and warrants an early diagnosis through recognition of symptoms as well as blood workup in a female with massive PPH.