Sheehan’s syndrome, or postpartum pituitary necrosis, is usually associated with massive hemorrhage and shock in the postpartum period. Since the original report by Sheehan¹⁾ in 1937, the prevalence of Sheehan’s syndrome has decreased in many parts of the world due to improved obstetrical care. However, in the developing countries, it is still a major medical problem. Especially in Korea, where many women had previously delivered babies at home without adequate obstetric care, a number of them have Sheehan’s syndrome.

The onset of symptoms and signs of pituitary hormonal insufficiency in Sheehan’s syndrome varies from patient to patient due to the extent of the infarction and the rate of regeneration of the pituitary^2,3). Therefore, it is difficult to predict the time needed to replace deficient hormones, especially cortisol and thyroid hormones which are essential in maintaining life.

CT has emerged as a major noninvasive tool for the diagnosis of intracranial lesions, including those in and around the pituitary⁴⁾. Coronal sections of pituitary fossa demonstrate that the common findings in Sheehan’s syndrome are varying degrees of emptiness of sella turcica and completely and partially empty sella according to the amounts of the pituitary remnants⁵⁾.

In this study, we performed high resolution CT and pituitary stimulation tests in order to correlate the emptiness of sella turcica on CT evaluation with the preservation of pituitrary function.

Acute ischemic necrosis of the pituitary associated with blood loss during delivery was described first by Sheehan in 1937¹⁾, following considerable research and a number of reports^7–9). However, it is regarded as a rare complication in modern obstetrics. A failure of lactation is an early indication that pituitary function has been impaired. Typically, however, the additional clinical features of pituitary insufficiency appear much later. Although the natural history of postpartum pituitary necrosis is unknown, late-onset myxedema and adrenal insufficiency resulting in death have been reported^7,10). Therefore, the detection of impairment in endocrine function early in the course of the disease, before gross evidence of endocrine insufficiency develops, is of clinical importance. According to Jialal et al.²⁾, measurement of PRL concentration following challenge with TRH is a convenient and suitable screening test for the detection of Sheehan’s syndrome. However, insulin hypoglycemia test is necessary in order to determine the deficient hormone needed for replacement therapy. Insulin hypoglycemia test is potentially dangerous and impractical for use on an outpatient basis. So, a simple and reliable test is needed to predict the pituitary function.

Computed tomography, one of the modern radiological techniques, has been used for documenting morphologic manifestation of the pituitary gland. Empty sella is the common CT finding of Sheehan’s syndrome when the patients have symptoms of hormonal insufficiency^5,11). Sheehan’s studies on women undergoing autopsy within the first month after delivery showed that reduction in pituitary volume did not occur immediately after the pituitary necrosis¹⁾. In an early stage of Sheehan’s syndrome, homogeneous or inhomogeneous pituitary tissue might have been detected by CT. In addition, by his autopsy studies on women surviving more than one year, Sheehan observed scarring atrophy and shrinkage of the pituitary gland⁹⁾. Accordingly, after the necrosis, the pituitary gland shrinks gradually and evolutes to empty sella. Loss of pituitary tissue creates an empty space within the fossa with subsdequent herniation of the arachnoid, entrance of CSF into the sella and appearance of the so-called secondary empty sella on CT scans. Similarily, secondary empty sella occurs after surgical removal¹²⁾, radiation therapy¹²⁾ or spontaneous infarction¹³⁾ of pituitary tumors and represents replacement of tumor mass with fluid. In such patients, the sella is enlarged. however, in Sheehan’s syndrome, the sella is not enlarged. In this study, the time intervals between CT studies and postpartum bleeding were more than 6 years in all cases except one (patient 3), and the results revealed that of the 26 patients one showed normal sella, 4 PES and 21 CES.

The most common endocrine abnormality found in all patients was deficiency in the ability of the pituitary gland which produces GH in response to insulin hypoglycemia and prolactin in response to TRH. It means that the observation of poor GH and prolactin reserve is possibly a result of the anatomic situation of GH and prolactin cells in the lower lateral regions of the adenohypophysis, which are the most susceptible to damage by ischemic necrosis¹⁴⁾.

The determination of impairment in the ACTH reserve in patients with Sheehan’s syndrome is of clinical importance because of possible life-threatening cortisol deficiency. So, it is necessary to study ACTH reserve under stress. Although the insulin induced hypoglycemia is a specific stress test, its relationship to other stressful situations, such as a surgical procedure, has not been proved. Hypoglycemia followed by an abnormal cortisol response is a reflection of poor ACTH reserve¹⁵⁾. Deaths due to adrenal insufficiency in patients with postpartum hypopituitarism have been reported previously^7,10). Consequently, it is recommended that the patients with Sheehan’s syndrome showing a deficient cortisol response to hypoglycemia should be treated with cortisol replacement¹⁵⁾.

Three (75%) with PES had normal basal cortisol levels, more frequent than 2(9.6%) with CES. This result indicates that the reduction in pituitary ACTH reserve capacity was more severe in CES than in PES. However, most of the patients with PES and CES demonstrated blunted cortisol responses to hypoglycemic stimulation. Therefore, cortisol replacement therapies are needed.

According to Dizerega et al¹⁵⁾, use of thyroid hormone replacement should be dependent upon the free thyroxine index, not on the TSH response to TRH administration. The fact that most of the patients with CES had low thyroxine levels and blunted TSH responses to TRH administration indicates the need for thyroid hormone replacement.

It is interesting that normal thyroxine levels were observed in 3 of 4 with PES. The TSH reserve in the pituitary of the patients with PES appeared sufficient to maintain normal thyroid funciton without clinical symptoms of hypothyroidism. Accordingly these patients do not, at present, need thyroid hormone replacement. T4 and FT4 should be measured twice a year in order to detect deterioration and determine subsequent for therapy⁷⁾.

Basal gonadotrophin levels were normal in all patients with PES and gonadotropin responses to LH-RH administration were adequate in 2 of 4 with PES. These results indicate that considerable numbers with PES have the pituitary reserve-function necessary to maintain the normal basal gonadotropin and to release gonadotropin in response to gonadotropin releasing hormone.

Sheehan¹⁶⁾ reported that, even in the presence of massive necrosis, there is some residual tissue at the pars tuberalis and the lateral poles of the pituitary gland. Therefore, those areas are able to respond to exogenous gonadotropin releasing hormone. So, it is anticipated that gonadotropin reserve function is preserved more or lee even in those patients with CES who have the pituitary volume less than 10%. Contrary to Sheehan’s report, however, only one of 21 with CES showed normal gonadotropin response to the administration of the gonadotropin releasing hormone.

Fleckman et al.⁵⁾ had found no correlation between the presence of pituitary tissue in CT evaluation and preservation of the function in the study on 13 patients with Sheehan’s syndrome. In their study, some preservation of pituitary function was observed not only with PES but also in considerable numbers with CES. In our study, panhypopituitarisms occurred in 21 patients. Twenty of them showed CES. The remaining five patients had some preservation of pituitary function. Only one (patient 9) of the five was revealed to have CES. The pituitary function of the patients having considerable amounts of pituitary remnants visualized by CT were relatively preserved for TSH, cortisol, FSH and LH. Considering the above results, it might be predicted that the changes in the amounts of pituitary remnants detected by CT correlate with hormonal secretory capacity in patients with Sheehan’s syndrome who had a history of postpartum massive bleeding. This result contrasts to that of Fleckman’s study. However, it will be necessary to study further the numbers with PES in order to detect deficient hormone according to the region of remaining tissue. Also, the continuous observation of changes in the pituitary function and remaining tissue in patients with PES is required for defining the natural course of Sheehan’s syndrome.

It is noteworthy that patient 4 showed a panhypopituitarism in spite of the remaining pituitary tissue occupying 50% of sella turcica. She was 70 years old, and the age at the postpartum bleeding was 42. We thought her hypopituitarism developed due to senility or the long interval between CT study and postpartum bleeding. However, her pituitary remnant was possibly composed of mainly scarred tissue.

In summary, CT scannings in patients with Sheehan’s syndrome revealed 21 CES, 4 PES and 1 normal. Most of the patients with CES showed panhypopituitarisms. The pituitary reserve capacity for TSH, cortisol, FSH and LH was preserved more or less in patients having considerable amounts of pituitary remnants visualized by CT. We recommend sella CT for the patient with Sheehan’s syndrome in order to determine the degree of hormonal insufficiency.