|Year : 2014 | Volume
| Issue : 2 | Page : 82-86
Sheehan's syndrome: A clinical, biochemical, hormonal, radiological, bone mineral density and quality of life assessment
Manish Gutch1, Sukriti Kumar2, Sanjay Saran1, Keshav Kumar Gupta1, Syed Mohd Razi1, Jaideep Tomar3, Kamlendra Verma4
1 Department of Endocrinology, Lala Lajpat Rai Memorial Medical College, Meerut, Uttar Pradesh, India
2 Department of Radiodiagnosis, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India
3 Consultant Radiologist, Om Imaging, Meerut, Uttar Pradesh, India
4 Department of Endocrinology Medicine, Lala Lajpat Rai Memorial Medical College, Meerut, Uttar Pradesh, India
|Date of Web Publication||11-Jun-2014|
D 15, Lala Lajpat Rai Memorial Medical College, Meerut 250 004, Uttar Pradesh
Source of Support: None, Conflict of Interest: None
Background: Sheehan's syndrome (SS) or postpartum pituitary necrosis though rare, still remains one of the commonest causes of hypopituitarism in the Indian subcontinent. The clinical presentation is often variable with abrupt or insidiously onset pituitary insufficiency after heavy intrapartum or postpartum hemorrhage. Aims: To study the demographic profile, hormonal profile, as well as the quality of life of patients of SS, and the effect of hormonal replacement therapy on outcome. Materials and Methods: All patients previously diagnosed with Sheehan's syndrome or newly admitted during the study period of 2011-2013 were enrolled in the study after obtaining informed consent. Their clinical, biochemical, hormonal, radiological and bone mineral density (BMD) data were collected. The quality of life (QoL) was assessed using the disease-specific questionnaire both before and after hormone replacement therapy. Result: Twenty three patients were enrolled in the study, the mean age of diagnosis was 43.4 ± 14.2 years; mean diagnostic delay was 13.2 ± 7.4 years. Secondary amenorrhea and lactation failure were the most common clinical presentations. The mean total tetraiodothyronine (T4), peak stimulated cortisol, stimulated growth hormone (GH), and prolactin (PRL) levels were low. The gonadotropins [follicle stimulating hormone (FSH) and luteinizing hormone (LH)] were inappropriately normal in the presence of amenorrhea. Anemia was the most common hematological abnormality seen in 69.5% of patients, while 39.1% of patients had hyponatermia. BMD assessment (n = 23) was suggestive of low bone mass. The QoL improved significantly (P < 0.05) in patients after one year of hormonal replacement therapy. Conclusion: Sheehan's syndrome resulted in multiple pituitary hormone deficiencies in all patients. Anemia, hyponatremia, and low bone mass were frequently seen in patients with Sheehan's syndrome. The QoL improved significantly (P < 0.05) after hormonal replacement therapy.
Keywords: Bone mineral density, empty sella, multiple pituitary hormone deficiency, quality of life, Sheehan′s syndrome
|How to cite this article:|
Gutch M, Kumar S, Saran S, Gupta KK, Razi SM, Tomar J, Verma K. Sheehan's syndrome: A clinical, biochemical, hormonal, radiological, bone mineral density and quality of life assessment. CHRISMED J Health Res 2014;1:82-6
|How to cite this URL:|
Gutch M, Kumar S, Saran S, Gupta KK, Razi SM, Tomar J, Verma K. Sheehan's syndrome: A clinical, biochemical, hormonal, radiological, bone mineral density and quality of life assessment. CHRISMED J Health Res [serial online] 2014 [cited 2017 May 25];1:82-6. Available from: http://www.cjhr.org/text.asp?2014/1/2/82/134266
| Introduction|| |
Sheehan's syndrome (SS), a post partum pituitary necrosis first described by HL Sheehan in 1937 classically refers to adenopituitary insufficiency during severe hypotension or shock, secondary to massive blood loss during or just after delivery.  Although the pathogenesis of SS is not clear, it is clear that the basic event is infarction in the anterior pituitary due to decreased blood volume.  It is not clear whether this infarct is due to vasospasm, thrombosis or a vascular compression. 
The pituitary is one of the highly vascularized tissues in the body. Pituitary volume increases two-folds during pregnancy; mostly due to the hyperplasia of prolactin secreting cells or lactotrophs as a result of an elevated concentration of estrogen.  As the pituitary enlarges, it undergoes ischemic necrosis and is replaced by the scarred tissues.  At least 75-80% of pituitary is destroyed before clinical manifestations become evident. The extent of anterior pituitary hormone deficiency varies in different studies. The main setback was the secretion of growth hormone (GH) and prolactin (90-100%), while deficiencies in cortisol secretion, gonadotropins and thyroid stimulating hormone (TSH) ranged from 50 to 100%. ,,
History of postpartum hemorrhage, failure to lactate and cessation of menses are important clues to the diagnosis. The frequency of Sheehan's syndrome has gradually decreased in developed countries. This decrement can be attributed to improved obstetric care including treatment of hemodynamic complications with rapid blood transfusion and/or fluid replacement.
The prevalence of SS in India is estimated to be 2.7-3.9% among parous women older than 20 years.  Hence, in developing countries like India, where home deliveries are widely practised and obstetric care is poor, it is one of the leading causes of hypopituitarism. 
No data on SS is available from western Uttar Pradesh located in northern India, and no case series have been published so far.
| Materials and Methods|| |
The present study was conducted in the Department of Endocrinology at a tertiary care center in the northern part of India, during the 2 year period of from July 2011 to Dec 2013. The diagnosis of Sheehan's syndrome was based on patient history (profound bleeding during or following the delivery, absence of postnatal lactation etc), physical examination, deficiency of one or more pituitary hormone and a magnetic resonance imaging (MRI) evaluation of the pituitary. Routine biochemical examinations, complete blood counts (CBC), thyroid function tests and basal hormone levels (for FSH, LH, prolactin, cortisol and GH) were performed for diagnosis.
For the insulin tolerance test (ITT), regular insulin was used at a dose of 0.1 U/kg. A blood glucose level of 40 mg/dl or less was considered as a criterion of hypoglycemia and the moment at which blood glucose level fell below this limit was accepted as the 0 time point and accordingly blood samples for cortisol and GH determination were taken at 0, 30, 60, 90 and 120 minutes. An increase of more than 21 μg/dl in cortisol levels and increase in more than 10 μg/dl in GH levels during the ITT test was consider significant. An MRI (1.5T; Symphony Maestro, Siemens-Germany) of pituitary was done. At the time of the diagnosis of SS, the patients were evaluated by dual energy x-ray absorptiometry (DEXA) to determine BMD, T-score and Z-score using the Asian BMD database. Measurements included DEXA of femoral neck, and lumbar spine (postero-anterior projection L1-4). The quality of life assessment was done with the help of Burckhardt questionnaire;  sixteen questions were asked of each patient both before and after hormonal replacement therapy for one year (Prednisolone, levothyroxine and estrogen/progesterone in appropriate dosage). All results were expressed as mean ± SD. Informed consent was taken from every patient before being included in the study. The study was approved by the local ethical committee.
Continuous data were summarized as Mean ± SD while discrete (categorical) values as numbers and percentages. Continuous two independent groups were compared by parametric independent student's test and the significance of parametric t test was also validated with nonparametric alternative. Two-sided (α =2) P values less than 0.05 (P < 0.05) was considered statistically significant. All analyses were performed on STATISTICA software (Windows version 6.0).
| Results|| |
The results are summarized in the tables below.
[Table 1] shows the baseline parameters of the patients, the mean age at diagnosis was 43.4 ± 14.2 years, mean diagnostic delay was 13.2 ± 7.4 years, the most common electrolytic abnormality was found to be hyponatermia, rest of the indices are given in [Table 1].
[Table 2] and [Figure 1] shows the common clinical manifestations found in the patients, these are secondary amenorrhea in 95.6% of patients, followed by postpartum hemorrhage in 86.9% of patients, lactation failure in 82.6% of patients, asthenia in 60.8% of patients, anemia in 69.5% of patients, hyponatermia in 39.1% of patients, shock in 21.7% of patients, and hypoglycemia in 17.4% of patients.
[Table 3] and [Figure 2] shows the hormonal assessment of patients with Sheehan's syndrome; the most common abnormality was found to be gonadotropins deficiency (LH and FSH) in 95.6% of patients, followed by growth hormonal and prolactin deficiency in 91.3% of patients, ACTH deficiency in 78.2% and TSH deficiency in 69.5% of patients.
[Table 4] shows the bone mineral characteristics of patients with Sheehan's syndrome, T-score, were found to be significantly reduced in lumbar spine (−2.8 ± 0.6) and femoral neck (−2.9 ± 0.8) as also the Z score; these were −1.6 ± 0.6, -1.4 ± 0.6 respectively. Severe osteoporosis (osteoporosis with fracture) was found in three patients (13%), osteoporosis in four patients (17.3%), osteopenia in six patients (26%), while the rest of the 10 patients had normal BMD.
[Table 5] shows the quality of life of patients with Sheehan's syndrome before and after hormonal replacement therapy for one year. The score was 25 ± 8 before the start of therapy and it increased to 59.4 ± 8.6 after one year of hormonal replacement therapy.
| Discussion|| |
This is a prospective study done in the Department of Endocrinology at a tertiary health center of western UP, during the study period of 2 years. Twenty three patients were diagnosed and enrolled in the study; patients were evaluated for the baselines parameters, clinical presentation, hormonal assessment, bone mineral density and quality of life assessment during the study. The prevalence among women of reproductive age with suspected SS in the Kashmir valley (Indian subcontinent) was estimated at 3.2%. 
Presentation of Sheehan's syndrome may be acute or chronic. The acute form is very rare and diagnosis of the chronic form may be delayed for many years. This interval may be as long as 15 to 20 years.  Among our patients, the diagnostic delay was 13.2 ± 7.4 years, with the earliest detection after 5.8 years and the longest being a duration of 20 years. The delay in diagnosis is because most of the patients don't show symptoms or lack symptoms suggestive of pituitary involvement. Also, the lack of awareness about Sheehan's syndrome among physicians is another contributing factor in the delay in diagnosis.
The common presentations of patients with Sheehan's syndrome in our study were secondary amenorrhea in 95.6% of patients, followed by postpartum hemorrhage in 86.9% of patients, lactation failure in 82.6% of patients, asthenia in 60.8% of patients, shock in 21.7% of patients, and hypoglycemia in 17.4% of patients. Our data corresponds to various studies done previously. ,,,,,,,
Anemia was found in 69.5% of patients, and it is believed to be due to deficient anterior pituitary hormones or absence of some other yet unidentified factors normally secreted from the pituitary. The most common electrolyte abnormality was hyponatremia which was present in 39.1% of patients, almost corresponds to the study done by Dokmetas et al. 
The most common cells involved in Sheehan's syndrome are the somatotropes (GH) and lactotrophs (PRL) followed by the gonadotrophs (LH and FSH), corticotrophs and thyrotopes. Various studies reported Complete pituitary insufficiency in 70-90% of the patients and partial insufficiency in 10-30% of the patients. , Posterior pituitary involvement although rare may be present in small number of patients. , Among our patients, the most common hormone deficiency was of gonadropins in 95.6% of patients. Prolactin, GH, ACTH, and thyrotropes were involved in 91.3%, 91.3%, 78.2% and 69.5% of patients. None of our patients had diabetes insipidus.
The BMD of the enrolled patients was recorded during the study period, and patients were found to have significantly reduced BMD at both the side lumbar spine and femoral neck. Severe osteoporosis (osteoporosis with fracture) was found in three patients (13%), osteoporosis in four patients (17.3%), osteopenia in six patients (26%), and the rest of the 10 patients had normal BMD. The results of our study are comparable to the study done by Gokalp et al. 
Radiological imaging provides the supportive role in the diagnosis of Sheehan's syndrome; Fleckman et al. suggested that an empty sella was a typical feature of Sheehan's syndrome.  Various studies have shown that sella volumes decrease in patients with Sheehan's syndrome compared to the normal controls.  All of our patients underwent a MRI of the pituitary. Fourteen patients had an empty sella while nine patients had a partially empty sella.
The quality of life assessment was done with the help of Burckhardt questionnaire;  sixteen questions were asked to each patient both before and after hormonal replacement therapy for one year. The score improved significantly after one year from 25 ± 8 to 59.4 ± 8.6. However, an improvement in score has been previously reported only with GH replacement therapy, , while in our study, patient's scores for quality of life improved significantly after substitution with levothyroxine, prednisolone, and estrogen/progesterone without GH replacement therapy.
| References|| |
|1.||Sheehan HL. Postpartum necrosis of anterior pituitary. J Pathol Bact 1937;45:189-214. |
|2.||Scheithauer BW, Sano T, Kovacs KT, Young WF Jr, Ryan N, Randall RV. The pituitary gland in pregnancy: A clinicopathologic and immunohistochemical study of 69 cases. Mayo Clin Proc 1990;65:461-74. |
|3.||Kovacs K. Sheehan syndrome. Lancet 2003;361:520-2. |
|4.||Sert M, Tetiker T, Kirim S, Kocak M. Clinical report of 28 patients with Sheehan's syndrome. Endocr J 2003;50:297-301. |
|5.||Dokmetas HS, Kilichi F, Korkmaz S, Yonem O. Characteristic features of 20 patients with Sheehan's syndrome. Gynaecol Endocrinol 2006;22:279-83. |
|6.||Banzal S, Ayoola EA, Banzal S. Sheehan's syndrome in Saudi Arabia. Int J Gynaecol Obstet 1999;66:181-2. |
|7.||Zargar AH, Singh B, Laway BA, Masoodi SR, Wani AI, Bashir MI. Epidemiologic aspects of postpartum pituitary hypofunction (Sheehan's syndrome). Fertil Steril 2005;84:523-8. |
|8.||Chatterjee P, Mukhopadhyay P, Pandit K, Roychowdhury B, Sarkar D, Mukherjee S, et al. Profile of hypopituitarism in a tertiary care hospital of eastern India-is quality of life different in patients with growth hormone deficiency? J Indian Med Assoc 2008;106:384-5, 388. |
|9.||Burckhardt CS, Woods SL, Schultz AA, Ziebarth DM. Quality of life of adults with chronic illness: A psychometric study. Res Nurs Health 1989;12:347-54. |
|10.||De Groot LJ. Textbook of endocrinology. 2 nd ed. Philadelphia: Saunders; 1989. p. 431-2. |
|11.||Collins ML, O'Brien P, Cline A. Diabetes insipidus following obstetric shock. Obstet Gynecol 1979;53:16S-7. |
|12.||Wang SY, Hsu SR, Su SL, Tu ST. Sheehan's syndrome presenting with early postpartum congestive heart failure. J Chin Med Assoc 2005;68:386-91. |
|13.||Weston G, Chaves N, Bowditch J. Sheehan's syndrome presenting post-partum with diabetes insipidus. Aust N Z J Obstet Gynaecol 2005;45:249-50. |
|14.||Kale K, Nihalani N, Karnik N, Shah N. Postpartum psychosis in a case of sheehan's syndrome. Indian J Psychiatry 1999;41:70-2. |
|15.||Boulanger E, Pagniez D, Roueff S, Binaut R, Valat AS, Provost N, et al. Sheehan syndrome presenting the early post-partum hyponatraemia. Nephrol Dial Transplant 1999;14:2714-5. |
|16.||Sas AM, Meynaar IA, Laven JS, Bakker SL, Feelders RA. Irreversible coma following hypoglycemia in Sheehan syndrome with adrenocortical insufficiency. Ned Tijdschr Geneeskd 2003;147:1650-3. |
|17.||Bunch TJ, Dunn WF, Basu A, Gosman RI. Hyponatremia and hypoglycemia in acute Sheehan's syndrome. Gynecol Endocrinol 2002;16:419-23. |
|18.||Haddock L, Vega LA, Aguilo F, Rodriguez O. Adrenocortical, thyroidal and human growth hormone reserve in Sheehan's syndrome. Johns Hopkins Med J 1972;131:80-99. |
|19.||Bayram F, Ünlühýzarcý K, Keleþtimur F. A retrospective investigation of the patients with sheehan's syndrome seen in erciyes university medical school hospital during the last 7 years. Tur JEM 1996;6:279-91. |
|20.||Briet JW. Diabetes insipidus, Sheehan's syndrome and pregnancy. Eur J Obstet Gynecol Reprod Biol 1998;77:201-3. |
|21.||Gokalp D, Tuzcu A, Bahceci M, Arikan S, Ozmen CA, Cil T. Sheehan's syndrome and its impact on bone mineral density. Gynecol Endocrinol 2009;25:344-9. |
|22.||Fleckman AM, Schubart UK, Danziger A, Fleischer N. Empty sella of normal size in Sheehan's syndrome. Am J Med 1983;75:585-91. |
|23.||Bakiri F, Bendib SE, Maoui R, Bendib A, Benmiloud M. The sella turcica in Sheehan's syndrome: Computerized tomographic study in 54 patients. J Endocrinol Invest 1991;14:193-6. |
|24.||Gilchrist FJ, Murray RD, Shalet SM. The effect of long-term untreated growth hormone deficiency (GHD) and 9 years of GH replacement on the quality of life (QoL) of GH-deficient adults. Clin Endocrinol (Oxf) 2002;57:363-70. |
|25.||Hoffman AR, Kuntze JE, Baptista J, Baum HB, Baumann GP, Biller BM, et al. Growth hormone (GH) replacement therapy in adult-onset gh deficiency: Effects on body composition in men and women in a double-blind, randomized, placebo controlled trial. J Clin Endocrinol Metab 2004;89:2048-56. |
[Figure 1], [Figure 2]
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5]