Clinical Spectrum of Sheehan's Syndrome

Abstract

Brief ReportsClinical Spectrum of Sheehan's Syndrome Abdul Hamid Zargar, DM Shariq Rashid Masoodi, MD Bashir Ahmad Laway, MD Nissar Ahmad Shah, MD Mohammad Salahuddin, PhD Mushtaq Ahmed Siddiqi, and PhD Sharnagat KourMSc Abdul Hamid Zargar Address reprint requests and correspondence to Dr. Zargar: Associate Professor and Head, Department of Endocrinology, Institute of Medical Sciences, Soura, Srinagar - 1909011, Post Bag No. 27, Kashmir, India. From the Department of Endocrinology, Institute of Medical Sciences, Soura, Srinagar, Kashmir Search for more papers by this author , Shariq Rashid Masoodi From the Department of Endocrinology, Institute of Medical Sciences, Soura, Srinagar, Kashmir Search for more papers by this author , Bashir Ahmad Laway From the Department of Endocrinology, Institute of Medical Sciences, Soura, Srinagar, Kashmir Search for more papers by this author , Nissar Ahmad Shah From the Department of Endocrinology, Institute of Medical Sciences, Soura, Srinagar, Kashmir Search for more papers by this author , Mohammad Salahuddin From the Department of Immunology, Institute of Medical Sciences, Soura, Srinagar, Kashmir Search for more papers by this author , Mushtaq Ahmed Siddiqi From the Department of Immunology, Institute of Medical Sciences, Soura, Srinagar, Kashmir Search for more papers by this author , and Sharnagat Kour From the Department of Immunology, Institute of Medical Sciences, Soura, Srinagar, Kashmir Search for more papers by this author Published Online:1 May 1996https://doi.org/10.5144/0256-4947.1996.338SectionsPDF ToolsAdd to favoritesDownload citationTrack citations ShareShare onFacebookTwitterLinked InRedditEmail AboutIntroductionIn 1937, Sheehan described the syndrome of pituitary insufficiency following postpartum hemorrhage in women of child-bearing age. He estimated that over 50% of patients experiencing shock following postpartum hemorrhage would eventually suffer from hypopituitarism.1 Due to improvement in obstetric care, Sheehan's syndrome is rarely seen in developed countries.2 This disorder is more frequently seen in areas where home deliveries are common and obstetric care is not optimal.3The valley of Kashmir is witnessing a gradual improvement in its health care system, but home deliveries are still very common. With the increased awareness about the existence of Sheehan's syndrome in recent years, more and more clinicians refer cases with suspected Sheehan's syndrome to the Department of Endocrinology, Institute of Medical Sciences (IMS), Srinagar, Kashmir. This study is a retrospective analysis of clinical and hormonal data of patients with Sheehan's syndrome who were diagnosed over a period of 10 years (1985-1994) at IMS Srinagar, Kashmir.MATERIAL AND METHODSThe case records of all patients with Sheehan's syndrome (SS) seen between January 1985 and December 1994 at IMS Srinagar were reviewed. The presence of symptoms or signs of partial or complete pituitary insufficiency against a background of previous obstetrical injury was considered to be clinical evidence of SS. Information concerning the parity of patients, site of delivery, nature of the obstetrical insult and history of blood transfusion was particularly sought. Physical signs of ovarian, thyroid, and adrenal hypofunction, as indicated by the loss or absence of axillary/pubic hair, atrophy of breasts, dryness of skin, bradycardia and hypotension, were also noted.Laboratory data included: 1) complete hemogram, serum urea nitrogen, serum creatinine, glucose and electrolytes; 2) basal hormonal levels of serum triiodothyronine (T3), thyroxine (T4), thyroid-stimulating hormone (TSH), luteinizing hormone (LH), follicle-stimulating hormone (FSH), growth hormone (GH) and Cortisol (8 a.m.); and 3) GH and Cortisol levels after insulin-induced hypoglycemia.4 All the hormone measurements were done using specific radioimmunoassay. Because of irregular availability of assay reagents in between, not all the hormone estimations were available in all the patients.Criteria for inclusion in this study was the presence of clinical features of SS, which included evidence of failure of two or more pituitary-dependent endocrine glands in the context of previous delivery and absence of any symptoms or signs suggestive of pituitary tumor. This was to be confirmed by hormonal assays, proving secondary failure of one or more pituitary-dependent endocrine glands.RESULTSOne hundred and three patients were evaluated for possible SS during the 10-year-period under study. Diagnoses were not established in three of these patients, and they were excluded from the study. Adequate records were not available for 14 out of 100 patients and so they were also excluded. The remaining 86 patients were considered definite cases of SS and only data from these patients were analyzed further.Analysis of the data revealed that the age at onset of the symptoms of hypopituitarism ranged between 17 and 45 years (mean 29.21 ± 6.06, median 29.5 years). The ages at the time of diagnosis ranged between 21 and 50 years (mean 35.13 ± 7.69, median 35 years). The interval between the start of symptoms and ultimate diagnosis ranged between one week and 20 years (mean 5.94 ±5.05, median 4 years). Parity of the patients ranged between one and eight (mean 4.14 ± 2.11, median 5). Out of the 77 patients for whom this information was available, 64 had a history of postpartum hemorrhage, three had antepartum hemorrhage and the remaining 10 denied any history of excessive bleeding. Nineteen (24.7%) were hospital deliveries, while 58 (75.3%) were home deliveries. Normal delivery had occurred in 48 (68.6%) patients, 18 (25.7%) had stillbirths, three had retained placenta and one patient had an abortion at 25 weeks. This information was lacking in others. Amenorrhea with failure of lactation at last delivery (69.77%) and amenorrhea alone (17.44%) were the two most common reasons for referral in these patients. Two patients reported because of lactation failure, two patients presented with psychosis, two with coma, two with anemia, one with infertility and one patient was admitted in shock through the accident emergency. The most common clinical manifestation was menstrual abnormality (amenorrhea/oligomenorrhea), which was present in all except one patient, who presented just one week after delivery. Lactation failure was ultimately found in 81 (94.19%) patients. Other clinical features included weakness and weight loss (87.14%), dryness of skin (85.71%), sparse axillary and pubic hair (79.71%), breast atrophy (71.50%), hypotension (47.06%) and psychiatric abnormalities (10%). Psychiatric abnormalities included indifference, lethargy, personality changes or frank psychosis. Even though none of the patients was cachexic, most of the patients were underweight, mean body weight being 44.02 ± 6.88 kg (range 35-65) with a mean body mass index of 18.7 ± 3.0. Mean blood pressure (diastolic + 1/3 pulse pressure) of these patients ranged from 57 to 103 mmHg (mean 77.37 ± 10.84). Heart rate ranged from 40 to 110 beats/minute (mean 72.73 ± 12.94). Anemia (hemoglobin <120 g/L) without any other obvious cause was present in 49 (71.0%) patients. In 26 (37.7%) of these patients, hemoglobin was less than 100 g/L. Significant hyponatremia3 (serum Na+ <129 mmol/L) was seen in seven (12.7%) patients, while mild hyponatremia (Na+ 130-134 mmol/L) was seen in 14 (25.5%) patients at the time of presentation.Basal hormone estimations (Table 1) revealed low T3 in 37 (47.43%), low T4 in 49 (62.82%), inappropriately low-normal TSH in 51 (69.86%) and subnormal prolactin in 24 (54.54%) patients. Basal LH and FSH were subnormal or inappropriately normal in 42 (91.30%) and 25 (92.59%) patients, respectively. Basal GH and Cortisol levels were subnormal in 75 (100%) and 40 (71.42%) patients, respectively. Insulin tolerance test (Figure 1) revealed GH deficiency in 72 (100%) patients and corticotroph loss in 38 (84.44%) patients. A peak value of >10 μg/L for GH and >550 nmol/L for Cortisol was taken as normal.4 Patients who did not have corticotroph loss had a mean interval (between onset of disease and its diagnosis) of 2.21 ± 2.23 years as compared to a mean interval of 7.38 ± 4.21 years in those who had corticotroph loss. This was statistically significant (P<0.01).Figure 1. Growth hormone and Cortisol response to insulin-induced hypoglycemia in patients with SS. Patients with normal Cortisol response are excluded.Download FigureTable 1. Thyroid hormone, gonadotropin and prolactin levels in patients with SS.Table 1. Thyroid hormone, gonadotropin and prolactin levels in patients with SS.Two of the patients developed central diabetes insipidus confirmed by water restriction vasopressin administration test. One patient was in a persistently stuporous state for six weeks until she was taken from the hospital. It is possible that she had developed anoxic-ischemic encephalopathy following protracted hypotension before she was hospitalized.Follow-up was available in 70 patients and they were doing well on 150-200 μg/day of levothyroxine and 5.0-7.5 mg/day of prednisolone. Two cases of diabetes insipidus were treated with nasal desmopressin.DISCUSSIONHypopituitarism following postpartum pituitary necrosis (Sheehan's syndrome) may involve a deficiency of one, several, or all of the pituitary tropic hormones.5 Sheehan and Davis6 proposed two possible mechanisms for the development of disease: 1) local vascular spasm, and 2) a generalized Swartzman phenomenon. A possible pathogenetic role for autoimmunity has also been postulated.7A long delay in arriving at a diagnosis is not uncommon in SS.8 In our study, the average interval between the onset of disease and the diagnosis was approximately six years. The unfolding of the syndrome is notoriously slow; in Sheehan's own experience, the full-blown picture often took 15 to 20 years to develop.9 The median age at the onset of symptoms was 29.5 years and most of our patients were multiparous with a mean parity of five. These observations are in agreement with others.3 The relative young age of our patients could be because of marriage at a younger age and multiparity, which are common here. Similar observations have been made in African women because of “premature” marriage and multiparity.9 A history of peripartum hemorrhage was present in 67 (87%) patients, which is similar to observations of other workers.6,10 However, in one series,8 peripartum hemorrhage was reported in 100% of patients.The clinical features of hypopituitarism vary from partial to panhypopituitarism.2 In this series, 98.84% of patients were amenorrheic or oligomenorrheic (suggesting gonadotroph failure), 94.19% had failure of lactation (suggesting lactotroph failure) 87.14% had weakness, weight loss and/or hypotension (suggesting corticotroph failure), 85.71% had dryness of the skin, lethargy and/or bradycardia (suggesting thyrotroph failure). A wide spectrum of psychiatric disorders have been reported, including disorientation, hallucinations, restlessness, depression, confusion and insomnia.3 In this series, seven patients were found to have neuropsychiatric disturbances which included indifference, lethargy, personality changes or frank psychosis. Three of these patients were first seen by psychiatrists before Sheehan's syndrome was diagnosed. All these disturbances improved with treatment (steroid therapy).11Anemia (Hb <120 g/L) without any other obvious cause was present in 71% of patients. Anemia is known to occur in hypopituitarism, and may be microcytic, normocytic or macrocytic. The mechanisms by which these anemias are produced are not well understood, however, they seem to be related to pituitary hypothyroidism.9 Significant hyponatremia was seen in seven patients, while 14 had mild hyponatremia. Hyponatremia in patients with Sheehan's syndrome is due to deficient quantities of total sodium in the body, water retention, and transfer of electrolytes between tissues and plasma.1Hormonal analysis of the patients who had undergone evaluation revealed somatotroph failure in 100%, gonadotroph failure (subnormal or inappropriate normal gonadotropins) in 92.6%, corticotroph failure in 84.4%, thyrotroph failure in 69.9% and lactotroph failure in 54.5% of patients. Loss of GH reserve, as indicated by insulin tolerance test, represents an early sign of pituitary failure.3 Gonadotroph failure was second only to somatotroph failure. Patients who did not have corticotroph deficiency had a significantly shorter interval between the onset of disease and time of diagnosis. This observation has also been made by others.3 Hypothyroidism, which was suggested clinically in 85.71% of patients, was documented in only 69.86% of patients by hormonal data. This value is much lower than that observed by others,3,10 who have reported a thyrotroph loss of 84.6% to 100%. Similarly, 94.2% of our patients had a history of lactation failure, but only 54.5% of these patients had low basal prolactin. It would have been ideal to perform TRH and other stimulatory tests to document the actual thyrotroph and lactotroph reserve, but unfortunately the resources were not available. Two of our patients developed diabetes insipidus. Another study reported diabetes insipidus in 1% of patients with SS.9 Development of diabetes insipidus in SS is perhaps indicative of a hypothalamic lesion.9We believe that obstetric care being still far from optimal (particularly in rural areas) in Kashmir, postpartum hemorrhage will be common, so consequently, Sheehan's syndrome will continue to be a considerable diagnostic and therapeutic challenge.ARTICLE REFERENCES:1. Bethune IE, Nelson DH. "Hyponatremia in hypopituitarism" . N Engl J Med. 1965; 272: 771–6. Google Scholar2. Sheehan HL, Davis JC. Postpartum hypopituitarism. Springfield, IL: Charles C. Thomas, 1982; 1–453. Google Scholar3. Al-Nuaim A, Shetty UP, Fumuyiwa OO, Mathur RP, Sherbeeni SM. "Sheehan's syndrome: a retrospective review of 50 cases seen in Riyadh, Saudi Arabia" . Ann Saudi Med. 1990; 10: 500–3. Google Scholar4. Wass JAH, Besser M. Tests of pituitary function. In: DeGroot LJ, ed. Endocrinology, 3rd ed. Philadelphia: W. B. Saunders, 1995: 487–96. Google Scholar5. Cohen BL, Baillie P. "Sheehan's syndrome followed by successful pregnancy" . S Afr Med J. 1980; 57: 838–40. Google Scholar6. Sheehan HL, Davis JC. "Pituitary necrosis" . Br Med Bull. 1968; 24: 59–70. Google Scholar7. Asa SL, Bilbao JM, Kovacs K, et al. "Lymphocytic hypophysitis of pregnancy resulting in hypopituitarism. A distinct clinicopathologic entity" . Ann Intern Med. 1981; 95: 165–72. Google Scholar8. Abdelaziz MA, Kassimi MA, Saleem MS. "Postpartum pituitary necrosis (Sheehan's syndrome) in Saudi Arabia" . Saudi Med J. 1986; 7: 26–32. Google Scholar9. Christy NP, Warren MP. Other clinical syndromes of the hypothalamus and anterior pituitary, including tumor mass effects. In: DeGroot LJ, ed. Endocrinology. Philadelphia: W. B. Saunders, 1989: 419–53. Google Scholar10. Jayakumar RV, Mekki MO, Sulimani RS, Subesinghe N. "Pituitary gland involvement in Sheehan's syndrome" . Ann Saudi Med. 1988; 8: 457–60. Google Scholar11. Bahemuka M, Reese PH. "Sheehan's syndrome presenting with psychosis" . East Afr Med J. 1981; 58: 324–9. Google Scholar Previous article Next article FiguresReferencesRelatedDetailsCited byLaway B, Alai M, Gojwari T, Ganie M and Zargar A (2010) Sheehan syndrome with reversible dilated cardiomyopathy, Annals of Saudi Medicine, 30:4, (321-324), Online publication date: 1-Jul-2010. Volume 16, Issue 3May 1996 Metrics History Received7 March 1995Accepted3 December 1995Published online1 May 1996 ACKNOWLEDGMENTSWe would like to thank Mr. Mohammad Shafi, Senior Technologist, Department of Immunology, IMS, Srinagar for his help in data collection and Mr. Farooq Ahnmad Nadaf for his assistance in the preparation of this manuscript.InformationCopyright © 1996, Annals of Saudi MedicinePDF download