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Extensive Investigation of 114 Patients with Sheehan's Syndrome: A H Diri and others Sheehan’s syndrome 171:3 311–318 Clinical Study Extensive investigation of 114 patients with Sheehan’s syndrome: a continuing disorder 1 1 1 2 1 Halit Diri , Fatih Tanriverdi , Zuleyha Karaca , Serkan Senol , Kursad Unluhizarci , Correspondence Ahmet Candan Durak2, Hulusi Atmaca3 and Fahrettin Kelestimur1 should be addressed to F Kelestimur Departments of 1Endocrinology and 2Radiology, Erciyes University Medical School, 38039 Kayseri, Turkey and Email 3Department of Endocrinology, Ondokuz Mayis University Medical School, Samsun, Turkey [email protected] Abstract Objective: Sheehan’s syndrome (SS) is a well-known cause of hypopituitarism resulting from postpartum pituitary necrosis. Because of its rarity in Western society, its diagnosis is often overlooked. We aimed to investigate the clinical, laboratory, and radiological aspects of SS in a large number of patients. Study design: A retrospective assessment of the medical records of 114 patients with SS was conducted. In addition, sella turcica volumes of 29 healthy women were compared with those of patients by magnetic resonance imaging examinations. Results: The mean period of diagnostic delay was 19.7 years in patients with SS. It was found that 52.6% of patients had nonspecific complaints, 30.7% had complaints related to adrenal insufficiency, and 9.6% had complaints related to hypogonadism when diagnosed. At the time of diagnosis, 55.3% of the patients had panhypopituitarism, while 44.7% had partial hypopituitarism. The number of deficient hormones was found to be increased over the years. None of the patients whose basal prolactin was below 4.0 ng/ml had adequate prolactin responses to TRH test, while all patients whose basal prolactin was above 7.8 ng/ml had adequate responses. Mean sella volume was found to be significantly lower in the SS group (340.5G214 mm3) than that in the healthy group (602.5G192 mm3). Conclusions: SS is a common cause of hypopituitarism in underdeveloped and developing countries. The main reasons for diagnostic delay seem to be the high frequency of patients with nonspecific complaints and neglect of SS. In addition, the TRH stimulation test was found to have a high sensitivity and specificity to recognize PRL deficiency. Furthermore, European Journal of Endocrinology small sella size may have an important contributing role in the etiopathogenesis of SS. European Journal of Endocrinology (2014) 171, 311–318 Introduction Sheehan’s syndrome (SS) can be defined as partial or carried out in Turkey has shown that the frequency of SS complete hypopituitarism occurring due to massive was 13.8% among 773 patients with hypopituitarism (4). postpartum uterine hemorrhage that leads to pituitary The main reason for diagnostic delay of SS seems to be infarction (1). It is a common disorder particularly in nonspecific and thus unnoticed symptoms, such as fatigue, underdeveloped and developing regions of the world. weakness, and anorexia. For this reason, there may be a It was estimated by the World Health Organization (WHO) great number of patients with SS who remain undiagnosed in 1996 that SS was taking the lives of 100 000 women and thereby untreated. However, it should be kept in mind a year, and at that time affected more than 3 million that SS may also develop acutely and lead to coma and women in the world (2). In one cohort study, the pre- even death due to severe hypopituitarism (5). Furthermore, valence of SS was estimated to be 3.1% among women clinical and laboratory findings vary according to whether who were older than 20 years in Kashmir, India (3). pituitary deficiency is partial or complete (6, 7, 8). SS is not rare in developing countries; even so, delay The etiopathogenesis of SS is also not clear. Physio- in diagnosis has been a common problem. A recent study logical enlargement of the pituitary gland during www.eje-online.org Ñ 2014 European Society of Endocrinology Published by Bioscientifica Ltd. DOI: 10.1530/EJE-14-0244 Printed in Great Britain Downloaded from Bioscientifica.com at 09/29/2021 03:38:47PM via free access Clinical Study H Diri and others Sheehan’s syndrome 171:3 312 pregnancy makes it more vulnerable to ischemic necrosis; Hormonal assessment however, some other factors have also been suggested to Basal levels of hormones and, if indicated, dynamic tests have a contributing role. Thrombosis in the pituitary were carried out to determine hormonal failures in all arteries due to hypercoagulation, arterial vasospasm due patients. During the last 30 years, different methods and to severe hypotension during delivery, pituitary auto- commercial kits have been used to measure hormone immunity, and smaller sella turcica size have been levels. Hence, reference ranges of hormones were taken hypothesized for the etiopathogenesis of the disease according to the values suggested by commercial kits used (9, 10, 11, 12). Herein, we aimed to investigate the initial at that time. clinical and laboratory findings with subsequent course Diagnosis of gonadotropin deficiency was established in patients with SS. In addition, we investigated the by reduced basal estradiol levels with reduced or difference between SS patients and healthy women with inappropriately normal gonadotropin levels. Menstrual regard to sella volumes. irregularities, amenorrhea in particular, in addition to biochemical data were also taken into account for the diag- nosis of gonadotropin deficiency. Thyroid-stimulating hormone (TSH) deficiency was diagnosed by low free Subjects and methods thyroxine levels with normal or decreased TSH levels. Study design Adrenocorticotropic hormone (ACTH) deficiency was determined as low serum cortisol level (%3.0 mg/dl) in The medical records of 114 SS patients who were followed the presence of a low or normal ACTH level. Blood samples up in the Endocrinology Department of Erciyes University were taken at 0800 h for analyzing ACTH and cortisol Medical School between 1985 and 2013 were assessed in levels. The 1 mg ACTH stimulation test was carried out in this retrospective study after obtaining approval from the 49 patients to confirm the diagnosis of secondary adrenal Local Ethics Committee. The diagnosis of SS was based insufficiency. Adrenal failure was defined as peak cortisol on the criteria proposed previously: i) typical obstetrical levels below 18 mg/dl (14).ThebasalPRLleveland history of severe postpartum vaginal bleeding; ii) severe responses to the thyrotropin-releasing hormone (TRH) hypotension or shock for which blood transfusion or stimulation test were evaluated together to detect PRL postpartum fluid replacement is necessary; iii) failure of deficiency. Patients with peak PRL values that did not lactation; iv) failure to resume regular menses after deli- double according to baseline values were accepted as very; v) varying degree of anterior pituitary failure, partial European Journal of Endocrinology having PRL deficiency in TRH test (15). Growth hormone or panhypopituitarism; and vi) empty sella discovered on (GH) deficiency was diagnosed by low insulin-like growth computed tomography (CT) scan or magnetic resonance factor 1 level in the presence of greater than or equal to imaging (MRI) (13). three pituitary-deficient hormones or insulin tolerance The demographic data, clinical findings at diagnosis test (ITT). ITT was carried out in 52 patients. A peak GH and during follow-up, obstetric histories, endocrinological level of !3 mg/l after ITT was accepted as GH deficiency investigations, pituitary MRI, and CT findings of the (16). The diagnosis of antidiuretic hormone (ADH) patients were recorded from their hospital files. The initial deficiency was established by measuring serum and urine complaints of patients at diagnosis were classified into osmolalities in patients with polyuria (O3 l/day) and four groups: i) nonspecific complaints (fatigue, weakness, confirmed by the response to desmopressin therapy in anorexia, arthralgia, and headache); ii) adrenal insuffi- patients with low urine osmolality. ciency (hypoglycemia, hyponatremia, hypotension, fever, loss of consciousness, nausea, vomiting, and diarrhea); Radiological evaluation iii) hypothyroidism (somnolence, edema, cold intolerance, and constipation); and iv) hypogonadism (amenorrhea). Three dimensional volumetric MRI (Philips, Gyroscan In addition, 29 healthy women were enrolled in the Intera 1.5 Tesla; Eindhoven, The Netherlands) was used study as a control group to compare their sella turcica to evaluate pituitary gland and sella turcica volumes at volumes with the patients with SS. The demographic data the Radiology Department of Erciyes University and past medical and obstetric histories of the healthy Medical School. The same MRI scan was performed women were also recorded. The obstetric and reproductive for both the control and the SS groups. Sella turcica histories of all healthy women were normal. volumes (mm3) were measured by using the www.eje-online.org Downloaded from Bioscientifica.com at 09/29/2021 03:38:47PM via free access Clinical Study H Diri and others Sheehan’s syndrome 171:3 313 DiChiro formula (0.5!(length!width!depth)) (17). (1.8%) did not have a history of live birth. Twenty-seven Two experienced neuroradiologists evaluated the images (23.7%) patients had a history of stillbirth, 54 (47.4%) had (A C Durak and S Senol). a history of miscarriage, and nine (7.9%) had a history of curettage during their lives. One patient became pregnant through induction of ovulation after the diagnosis of Statistical analysis SS, and had a healthy baby. All statistical analyses were performed with the SPSS 15.0 Obstetric histories of the last delivery revealed that Software. Descriptive data are presented as meanGS.D., 89 (78.1%) patients had delivered at home. Eight (9%) percentages, and occasionally as a range of minimum– out of these 89 patients were subsequently admitted to a maximum. Distribution of data was tested by the hospital and given a blood transfusion because of severe Kolmogorov–Smirnov test before comparison and corre- postpartum hemorrhage. On the other hand, 25 (21.9%) lation tests. The independent samples t-test was used for patients reported that they had delivered at a hospital, normally distributed data.
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