Bone mineral density, turnover, and microarchitecture assessed by second-generation high-resolution peripheral quantitative computed tomography in patients with Sheehan's syndrome.

Sheehan's syndrome (SS) is a rare but well-characterized cause of hypopituitarism. Data on skeletal health is limited and on microarchitecture is lacking in SS patients. PURPOSE: We aimed to explore skeletal health in SS with bone mineral density (BMD), turnover, and microarchitecture. METHODS: Thirty-five patients with SS on stable replacement therapy for respective hormone deficiencies and 35 age- and BMI-matched controls were recruited. Hormonal profile and bone turnover markers (BTMs) were measured using electrochemiluminescence assay. Areal BMD and trabecular bone score were evaluated using DXA. Bone microarchitecture was assessed using a second-generation high-resolution peripheral quantitative computed tomography. RESULTS: The mean age of the patients was 45.5 ± 9.3 years with a lag of 8.3 ± 7.2 years prior to diagnosis. Patients were on glucocorticoid (94%), levothyroxine (94%), and estrogen-progestin replacement (58%). None had received prior growth hormone (GH) replacement. BTMs (P1NP and CTX) were not significantly different between patients and controls. Osteoporosis (26% vs. 16%, p = 0.01) and osteopenia (52% vs. 39%, p = 0.007) at the lumbar spine and femoral neck (osteoporosis, 23% vs. 10%, p = 0.001; osteopenia, 58% vs. 29%, p = 0.001) were present in greater proportion in SS patients than matched controls. Bone microarchitecture analysis revealed significantly lower cortical volumetric BMD (vBMD) (p = 0.02) at the tibia, with relative preservation of the other parameters. CONCLUSION: Low areal BMD (aBMD) is highly prevalent in SS as compared to age- and BMI-matched controls. However, there were no significant differences in bone microarchitectural measurements, except for tibial cortical vBMD, which was lower in adequately treated SS patients.

Sheehan's syndrome presenting with panhypopituitarism and central diabetes insipidus: a case report.

BACKGROUND: Sheehan's syndrome is a rare condition, which is classically characterized by anterior pituitary hypofunction following postpartum shock or hemorrhage. While diabetes insipidus (DI) is not commonly associated with Sheehan's syndrome, we present a rare case of a multiparous female developing rapid-onset panhypopituitarism and DI following severe postpartum hemorrhage. CASE PRESENTATION: A previously healthy 39-year-old woman, gravida 5, para 4, presented with hypovolemic shock after vaginal delivery, attributed to severe postpartum hemorrhage, necessitating emergent hysterectomy. Although her shock episodes resolved during hospitalization, she developed intermittent fever, later diagnosed as adrenal insufficiency. Administration of hydrocortisone effectively resolved the fever. However, she subsequently developed diabetes insipidus. Diagnosis of Sheehan's syndrome with central diabetes insipidus was confirmed through functional hormonal tests and MRI findings. Treatment consisted of hormone replacement therapy, with persistent panhypopituitarism noted during a ten-year follow-up period. CONCLUSIONS: Sheehan's syndrome is a rare complication of postpartum hemorrhage. Central diabetes insipidus should be suspected, although not commonly, while the patient presented polyuria and polydipsia. Besides, the potential necessity for long-term hormonal replacement therapy should be considered.

Impact of vortioxetine on psychosocial functioning moderated by symptoms of fatigue in post-COVID-19 condition: a secondary analysis.

INTRODUCTION: Fatigue is a prominent symptom in post-COVID condition (PCC) sequelae, termed "long COVID." Herein, we aim to ascertain the effect of fatigue on psychosocial function in persons living with PCC. METHODS: This post hoc analysis evaluated the effects of vortioxetine on measures of fatigue as assessed by the Fatigue Severity Scale (FSS) in psychosocial function as measured by the Sheehan Disability Scale (SDS) in persons with PCC. We also evaluated the change in FSS on psychosocial functioning as measured by the Sheehan Disability Scale (SDS). This post hoc analysis obtained data from a recently published placebo-controlled study evaluating vortioxetine's effect on objective cognitive functions in persons living with PCC. RESULTS: One hundred forty-four participants meeting World Health Organization (WHO) criteria for PCC were included in this analysis. At the end of 8 weeks of vortioxetine treatment, significant improvement of all domains was observed for psychosocial functioning. There was a significant between-group difference at treatment endpoint in the family, social, and work SDS subcategories (p < 0.001). There was a statistically significant interaction effect between the treatment condition time point and FSS effect on the SDS social (χ2 = 10.640, p = 0.014) and work (χ2 = 9.342, p = 0.025) categories but a statistically insignificant effect on the family categories ((χ2 = 5.201, p = 0.158)). DISCUSSION: This post hoc analysis suggests that vortioxetine treatment significantly improves psychosocial function in persons with PCC. Our results also indicate that the improvement in psychosocial function was significantly mediated by improvement in measures of fatigue. Our results provide empirical support for recommendations to identify therapeutics for fatigue in persons living with PCC with a broader aim to improve psychosocial function in this common and severely impaired population.

High prevalence of coronary artery calcification and increased risk for coronary artery disease in patients with Sheehan syndrome-A case-control study.

OBJECTIVE: Patients with Sheehan syndrome (SS) are predisposed to coronary artery disease (CAD) due to risk factors like abdominal obesity, dyslipidemia and chronic inflammation. In addition to estimate CAD risk enhancers like high sensitive C reactive protein (hsCRP), apolipoprotein B (ApoB) and lipoprotein A [Lp(a)], this study applies Framingham risk score (FRS) and coronary artery calcium (CAC) score to compute a 10-year probability of cardiovascular (CV) events in SS patients. DESIGN: Case-control study Sixty-three SS patients, on a stable hormonal replacement treatment except for growth hormone and 65 age, body mass index and parity-matched controls. MEASUREMENTS: Measurement of serum hsCRP, ApoB and Lp(a) and estimation of CAC with 16-row multislice computed tomography scanner. RESULTS: The concentrations of hsCRP, ApoB and Lp(a) were significantly higher in SS patients than in controls (p < .01). After calculating FRS, 95.2% of SS patients were classified as low risk, 4.8% as intermediate risk and all controls were classified as low risk for probable CV events. CAC was detected in 50.7% SS patients and 7.6% controls (p = .006). According to the CAC score, 26.9% SS patients were classified as at risk (CAC > 10) for incident CV events as against 1.6% controls. The mean Multi-Ethnic Study of Atherosclerosis (MESA) score was significantly higher in patients with SS than controls. CAC corelated significantly with fasting blood glucose (r = .316), ApoB (r = .549), LP(a) (r = .310) and FRS (r = .294). CONCLUSION: Significant number of asymptomatic SS patients have high coronary artery calcium score and are classified at risk for CAD.

Assessment of health-related quality of life and health status in patients with treatment-resistant depression treated with esketamine nasal spray plus an oral antidepressant.

BACKGROUND: Patients with treatment-resistant depression (TRD) report significant deficits in physical and mental health, as well as severely impaired health-related quality of life (HRQoL) and functioning. Esketamine effectively enhances the daily functioning in these patients while also improving their depressive symptoms. This study assessed HRQoL and health status of patients with TRD, who were treated with esketamine nasal spray and an oral antidepressant (ESK + AD) vs. placebo nasal spray and an AD (AD + PBO). METHODS: Data from TRANSFORM-2, a phase 3, randomized, double-blind, short-term flexibly dosed study, were analyzed. Patients (aged 18-64 years) with TRD were included. The outcome assessments included the European Quality of Life Group, Five Dimension, Five Level (EQ-5D-5L), EQ-Visual Analogue Scale (EQ-VAS), and Sheehan Disability Scale (SDS). The health status index (HSI) was calculated using EQ-5D-5L scores. RESULTS: The full analysis set included 223 patients (ESK + AD: 114; AD + PBO: 109; mean [SD] age: 45.7 [11.89]). At Day 28, a lower percentage of patients reported impairment in the ESK + AD vs. AD + PBO group in all five EQ-5D-5L dimensions: mobility (10.6% vs. 25.0%), self-care (13.5% vs. 32.0%), usual activities (51.9% vs. 72.0%), pain/discomfort (35.6% vs. 54.0%), and anxiety/depression (69.2% vs. 78.0%). The mean (SD) change from baseline in HSI at Day 28 was 0.310 (0.219) for ESK + AD and 0.235 (0.252) for AD + PBO, with a higher score reflecting better levels of health. The mean (SD) change from baseline in EQ-VAS score at Day 28 was greater in ESK + AD (31.1 [25.67]) vs. AD + PBO (22.1 [26.43]). The mean (SD) change in the SDS total score from baseline to Day 28 also favored ESK + AD (-13.6 [8.31]) vs. AD + PBO (-9.4 [8.43]). CONCLUSIONS: Greater improvements in HRQoL and health status were observed among patients with TRD treated with ESK + AD vs. AD + PBO. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02418585.

Sheehan's Syndrome unmasked by dengue fever: A case report and review of literature.

Sheehan's syndrome is a pituitary disease resulting from severe postpartum hemorrhage and can present with varying degrees of pituitary insufficiency. Although its incidence is decreasing in developed countries, it continues to be one of the most common causes of hypopituitarism in underdeveloped and developing countries. Here, we report a case of Sheehan's syndrome which was diagnosed following an episode of severe dengue infection, in a 38-year-old female.

Allotriophagy And Allotriodipsia In Endocrinology.

Allotriophagy is defined as food cravings that are different from the expected or the norm. It gives clinical pointers to an underlying diagnosis. We propose a new term, allotriodipsia which suggests a preference for beverages that are different from the norm. Taken together, these two entities may point towards certain endocrinological abnormalities and iatrogenic sequelae. In this communication we highlight the clinical relevance of allotriophagy and allotriodipsia.

Long-term hepatic and cardiac health in patients diagnosed with Sheehan's syndrome.

PURPOSE: Sheehan's syndrome (SS) is characterised by chronic pituitary insufficiency following a vascular insult to the pituitary in the peripartum period. There is a lack of substantial evidence on the long-term hepatic and cardiac consequences in these patients, following hormone replacement. METHODS: Patients with a diagnosis of SS were recruited for the study. Detailed clinico-biochemical and radiological evaluation were performed in all patients (n = 60). Hepatic and cardiac complications were assessed using fibroscan and echocardiography (2D speckle-tracking) respectively, in a subset of patients (n = 29) as well as age-and BMI-matched controls (n = 26). Controlled attenuation parameter (for steatosis) and liver stiffness measurement (for fibrosis) were used to define non-alcoholic fatty liver disease (NAFLD). Diastolic cardiac function was evaluated using standard criteria and systolic function by ejection fraction and global longitudinal strain (GLS). RESULTS: The mean age of the cohort was 42.7 ± 11.6 years. Multiple (≥ 2) hormone deficiencies were present in 68.8% of patients, with hypothyroidism (91.4%), hypocortisolism (88.3%), and growth hormone (GH) deficiency (85.7%) being the most common. At a mean follow-up of 9.8 ± 6.8 years, NAFLD was present in 63% of patients, with 51% having severe steatosis, which was predicted by the presence of GH deficiency and higher body mass index. Though the ejection fraction was similar, increased left ventricular GLS (18.8 vs. 7.7%) was present in a significantly higher number of patients versus controls. CONCLUSION: NAFLD, especially severe hepatic steatosis, is highly prevalent in SS. Subclinical cardiac systolic dysfunction (impaired GLS) is also more common, but of mild intensity.

Acute Sheehan's syndrome manifesting initially with diabetes insipidus postpartum: a case report and systematic literature review.

PURPOSE: Acute Sheehan's syndrome is a rare, but potentially life-threatening, obstetric event that can be complicated by diabetes insipidus. Little information on the diagnosis and treatment of Sheehan's syndrome with diabetes insipidus is available. We report on a 28-year-old patient who developed acute Sheehan's syndrome with diabetes insipidus after giving birth, and on a systematic review of similar cases. METHODS: We performed a systematic review of the literature cataloged in PubMed and Google Scholar using the keywords "Sheehan syndrome" OR "Sheehan's syndrome" AND "diabetes insipidus" to identify relevant case reports published between 1990 and 2021. Eight Reports met the inclusion criteria (English-language abstracts available, onset in the puerperium, information about the day of the onset). RESULTS: In the present case, postpartum curettage was necessary to remove the residual placenta. The total amount of blood loss was severe (2500 ml). On the second day postpartal, the patient developed polyuria. Laboratory analysis revealed hypernatremia with increased serum osmolality and decreased urinary osmolality. Hormone analysis showed partial hypopituitarism involving the thyroid, corticotropic, and gonadotropic axes. The prolactin level was elevated. Brain magnetic resonance imaging showed pituitary gland infarction. Desmopressin therapy was initiated and resolved the polyuria. Hormone replacement therapy was administered. Four months later, the patient was well, with partial diabetes insipidus. The literature review indicated that this case was typical in terms of symptoms and disease onset. Most reported cases involve hypotension and peripartum hemorrhage, but some patients without hemorrhage also develop Sheehan's syndrome. Elevated prolactin levels are uncommon and associated with poor prognosis in patients with Sheehan's syndrome. CONCLUSION: Acute Sheehan's syndrome with diabetes insipidus involves nearly all pituitary hormone axes, indicating severe disease. Prolactin elevation could suggest that a case of Sheehan's syndrome is severe.

Comparative efficacy of pharmacological treatments on measures of self-rated functional outcomes using the Sheehan Disability Scale in patients with major depressive disorder: a systematic review and network meta-analysis.

OBJECTIVE: More than 50% patients with major depressive disorder (MDD) have severe functional impairment. The restoration of patient functioning is a critical therapeutic goal among patients with MDD. We conducted a systematic review and network meta-analysis to evaluate the efficacy of pharmacological treatments on self-rated functional outcomes using the Sheehan Disability Scale in adults with MDD in randomized clinical trials. METHODS: PubMed, EMBASE, PsycINFO, Cochrane Library, and ClinicalTrials.gov were searched from inception to December 10, 2019. Summary statistics are reported as weighted mean differences with 95% confidence intervals. Interventions were ranked using the surface under the cumulative ranking probabilities. RESULTS: We included 42 randomized controlled trials (RCTs) (n = 18 998) evaluating the efficacy of 13 different pharmacological treatments on functional outcomes, as measured by the Sheehan Disability Scale (SDS). Duloxetine was the most effective pharmacological agent on functional outcomes, followed by (ranked by efficacy): paroxetine, levomilnacipran, venlafaxine, quetiapine, desvenlafaxine, agomelatine, escitalopram, amitriptyline, bupropion, sertraline, vortioxetine, and fluoxetine. Serotonin and norepinephrine reuptake inhibitors were more effective than other drug classes. Additionally, the comparison-adjusted funnel plot suggested the publication bias between small and large studies was relatively low. CONCLUSIONS: Our results indicate that there may be differences across antidepressant agents and classes with respect to self-reported functional outcomes. Validation and replication of these findings in large-scale RCTs are warranted. Our research results will be clinically useful for guiding psychiatrists in treating patients with MDD and functional impairment. PROSPERO registration number CRD42018116663.

Sexual Dysfunction in Sheehan Syndrome.

OBJECTIVE: The study was done to objectively document the sexual function in Sheehan syndrome (SS). SS is not an uncommon cause of hypopituitarism in developing countries. The lack of sex steroids from both ovaries and adrenal glands could lead to sexual dysfunction in SS. Sexual function is a neglected aspect of health in women in developing countries, although it greatly contributes toward the quality of life and feeling of well-being. Objective documentation of sexual function in SS is limited. METHODS: Thirty-two subjects with SS on conventional therapy (except growth hormone) were evaluated. SS was diagnosed as per standard criteria. Sexual function was assessed by validated questionnaires using the Female Sexual Function Index (FSFI). Thirty healthy women of a similar age range and socioeconomic background were included as comparators. RESULTS: The mean age (±SD) of the study population and healthy controls was 39.9 (±8.6) years and 38.2 (±6.8) years, respectively. The median interval between inciting events and diagnosis of SS was 8.3 years (interquartile range, 5.2-13.5 years). Thirty subjects were sexually active. Of the 30 subjects, 28 (93%) had sexual dysfunction, that is, an FSFI score of ≤26.55. The median total FSFI scores of subjects with SS and controls were 20.8 and 29.05, respectively, (P = .001). There was a statistically significant difference for individual parameters of sexual function, including desire, arousal, lubrication, orgasm, and satisfaction, between those with SS and controls. However, the pain during intercourse was not different. FSFI score in subjects with SS was not correlated with any endocrine parameter or duration of the disease since diagnosis. CONCLUSION: Sexual dysfunction is very common, affecting >90% of subjects with SS.

Psychometric evaluation of the Swedish self-rated 36-item version of WHODAS 2.0 for use in psychiatric populations - using classical test theory.

AIM: The aim of this study was to evaluate the reliability and validity of the Swedish version of the self-rated 36-item WHODAS 2.0 in patients from Swedish psychiatric outpatient settings, using classical test theory. METHODS: The 36-item WHODAS 2.0, together with the Sheehan Disability Scale (SDS), was filled in by a sample of 780 participating psychiatric patients: 512 (65.6%) women, 263 (33.7%) men, and 5 (0.6%) who did not report any sex. RESULTS: The internal consistency, measured by Cronbach's alpha, for the different domains of functioning were between 0.70 and 0.94, and interpreted as good. The confirmatory factor analysis (CFA) revealed two levels: the first level consisted of a general disability factor, while the second level consisted of the six domains of the scale, respectively. The model had borderline fit. There was a significant correlation between WHODAS 2.0 36-item and SDS (n = 395). The WHODAS 2.0 differed significantly between diagnostic groups. CONCLUSION: The present study demonstrates that the Swedish self-rated 36-item version of WHODAS 2.0, within a psychiatric outpatient population, showed good reliability and convergent validity. We conclude that the self-rated 36-item Swedish version of WHODAS 2.0 can be used for valid interpretations of disability in patients with psychiatric health conditions.

Sheehan syndrome.

Sheehan syndrome is an underestimated cause of hypopituitarism, which can be either partial or complete. It results from ischaemic necrosis of anterior pituitary during peripartum period leading to loss of one or more pituitary cell lines. Hyperplasia of pituitary gland during pregnancy increases demand for blood supply and at the same time compresses the pituitary gland. Severe postpartum haemorrhage leads to hypovolaemia and vasospasm of supplying vessels resulting in infarction of pituitary tissue. Congenital or acquired thrombophilia and autoimmunity exaggerate this phenomenon. Presentation is usually delayed by many years. It presents with symptoms of anterior pituitary hormone loss after a delay of many years. Rarely presentation may be acute or involve posterior pituitary as well. Low basal or stimulated pituitary hormones along with classic clinical setting clinches the diagnosis. Replacement of deficient hormones is the mainstay of treatment, however emphasis on better obstetric care to common masses would help to eradicate the disease in future.

Anesthetic management of a patient with Sheehan's syndrome and twin pregnancy while undergoing a cesarean section.

Sheehan's syndrome (SS) is caused by infarction of the pituitary gland usually precipitated by hypotension due to massive uterine hemorrhage during the peripartum period. Once SS develops, it becomes a major comorbidity for the young females and predisposes them to further medical, obstetric, and anesthetic complications. Herein, we report the perioperative anesthetic management of a 28-year-old female, already diagnosed with SS precipitated by urosepsis and septicemic shock in a previous pregnancy, now presenting with twin pregnancy for elective cesarean section. Her magnetic resonance imaging brain revealed pituitary apoplexy and she had hypothyroidism with gestational diabetes mellitus. The overall successful perioperative management of the patient is described along with an emphasis on aggressive management of hypotension due to any cause in the peripartum period to prevent infarction/necrosis of anterior pituitary gland.

Clinical evaluation of pituitary insufficiency in adult population

Background/aim: This retrospective study aimed to investigate the clinical profile of pituitary insufficiency (PI) in adult population. Materials and methods: One hundred and fifty patients who were diagnosed as having PI between 2012 and 2018 (53.3% female, mean age 48.13 ± 15.83 years) were retrospectively analyzed. Results: Age at diagnosis was higher in females as compared with males (51.13 ± 15.95 vs. 44.70 ± 15.08 years, P = 0.012). The most frequent presenting signs were headache (29.4%) and visual disturbance (19.6%) in general. Females frequently presented with headache (33.3%), whereas males presented with sexual dysfunction (34.4%). The most frequent cause of PI was nonfunctional pituitary adenoma (28.8%) in general population. A frequent cause of PI was Sheehan's syndrome (33.8%) among females and nonfunctional pituitary adenoma (38.6%) among males. Pituitary macroadenoma (75.8%) was frequent in pituitary tumors with PI. 55.3 % of the patients had 4 pituitary hormones deficiencies and 26.0% of patients had 3 pituitary hormones deficiencies. Gonadotropin deficiency was the leading pituitary hormone deficiency. The frequency of posttraumatic PI was 4.7% in the general population. Conclusion: Nonfunctional pituitary adenoma was the most common cause of PI among males and Sheehan's syndrome was a major etiologic factor in females. Sheehan's syndrome remains an important health problem in Turkey although obstetric care has improved. Posttraumatic PI should be considered in the differential diagnosis of idiopathic PI.

Evaluation of bone texture imaging parameters on panoramic radiographs of patients with Sheehan's syndrome: a STROBE-compliant case-control study.

Sheehan's syndrome (SHS) is a rare condition related to the risk of osteoporosis and evaluation of bone texture imaging features on panoramic radiographs would be suitable for this condition, which was the aim of the present study. Fractal dimension, lacunarity, and trabecular morphologic aspects were significantly altered in these patients. INTRODUCTION: SHS is an important public health problem particularly in developing countries. It is characterized as postpartum hypopituitarism secondary to obstetric complications-related ischemic pituitary necrosis that shows significant systemic metabolic repercussions. Thus, this study aimed to evaluate bone texture parameters in digital panoramic radiographs of patients with SHS. METHODS: A case-control study was conducted with 30 SHS patients from an Endocrinology and Diabetology Service of reference in Brazil, and 30 age- and sex-matched healthy controls. A custom computer program measured fractal dimension, lacunarity, and some morphologic features in the following mandibular regions of interest (50 × 50 pixels): below the mental foramen (F1), between the first and second molars (M1), and at the center of the mandibular ramus (R1). RESULTS: The fractal analysis showed a statistically significant difference between the studied groups in all regions of interest. The fractal dimension in F1 (p = 0.016), M1 (p = 0.043), and R1 (p = 0.028) was significantly lower in SHS group, as well as lacunarity in R1 (p = 0.008). Additionally, several morphologic features were statistically significant in the SHS group (p < 0.05). CONCLUSION: Therefore, individuals with SHS showed altered imaging texture parameters on panoramic radiographs, which reflect a smaller spatial organization of the bone trabeculae and, possibly, a state of reduced mineral bone density.

Adjunctive Brexpiprazole and Functioning in Major Depressive Disorder: A Pooled Analysis of Six Randomized Studies Using the Sheehan Disability Scale.

BACKGROUND: Patients with major depressive disorder and inadequate response to antidepressant treatments may experience a prolonged loss of functioning. This post hoc analysis aimed to determine the effect of adjunctive brexpiprazole on functioning in such patients. METHODS: A pooled analysis of data from the 6-week, randomized, double-blind treatment phases of 6 studies of adjunctive brexpiprazole (2 and 3 mg/d in fixed-dose studies; 1-3 mg/d in flexible-dose studies) vs placebo in patients with major depressive disorder and inadequate response to antidepressant treatments (NCT01360645, NCT01360632, NCT02196506, NCT01727726, NCT00797966, NCT01052077). Functioning was measured by change in Sheehan Disability Scale score from baseline to week 6. RESULTS: Considering Sheehan Disability Scale mean score across all 6 studies (n = 2066 randomized), the least squares mean difference between antidepressant treatments + brexpiprazole and antidepressant treatments + placebo at week 6 was -0.40 (95% CI: -0.56, -0.23; P < .0001). Antidepressant treatments + brexpiprazole showed a greater benefit than antidepressant treatments + placebo on the social life (-0.45; -0.63, -0.27; P < .001) and family life (-0.50; -0.70, -0.31; P < .001) items but not on the work/studies item (-0.16; -0.38, 0.06; P = .16). Pooled analyses of just the (1) fixed-dose, (2) flexible-dose, and (3) Phase 3 studies showed the same pattern of benefits for antidepressant treatments + brexpiprazole. CONCLUSIONS: Brexpiprazole, as adjunct to antidepressant treatments, improved functioning in patients with major depressive disorder and inadequate response to antidepressant treatments.

Decreased bone mineral density in women with Sheehan's syndrome and improvement following oestrogen replacement and nutritional supplementation.

Sheehan's syndrome (SS) is an important cause of pan-hypopituitarism in women. There is scanty information on bone mineral density (BMD) in this condition. We determined BMD and the changes in BMD after oestrogen (E2) replacement and nutritional supplementation in women with SS. In a cross-sectional study, BMD was measured by DEXA in 83 patients [age (mean ± SD) 42 ± 9.2 years] and compared with an equal number of matched controls. In a sub-set of 19 patients, we conducted an open-label, prospective study to determine changes in BMD after 1 year of replacement of E2, and calcium and vitamin D3 supplementation. All patients had low serum IGF-1 and E2, while 98% had ≥ 3 pituitary hormone deficiencies. Compared with Indian reference standards, 47% had decreased bone mass (Z-score ≤ - 2.0). BMD Z-scores were decreased at all sites, being most marked in the lumbar spine and femoral neck. At the lumbar spine, BMD was lowest among the age group 21-30 years. Women with SS also had significantly lower BMD Z-scores at all three sites on comparison with ethnic controls. On multivariate analysis, BMD Z-score was associated with weight, daily calcium intake and age (lumbar spine). In the prospective study, 1 year of therapy improved BMD Z-score at lumbar spine (- 1.4 ± 1.2 vs. - 1.1 ± 1.1, p = 0.02), but not at hip or femoral neck. In conclusion, patients with SS had significantly lower BMD compared to controls at all three sites. Replacement of E2 and supplementation with calcium/vitamin D3 lead to significant improvement in lumbar spine BMD.

Categorical improvement in functional impairment in depressed patients treated with desvenlafaxine.

OBJECTIVE: This post-hoc pooled analysis evaluated categorical change in functional impairment in patients with major depressive disorder (MDD) treated with desvenlafaxine versus placebo and examined whether early improvement in functioning predicted functional outcomes at study endpoint. METHODS: Data were pooled from eight randomized, double-blind, placebo-controlled studies of desvenlafaxine for the treatment of MDD, including adults who were randomly assigned to receive desvenlafaxine 50 or 100 mg/d or placebo (N=3,384). Shift tables were generated for categorical changes in functional impairment from baseline based on Sheehan Disability Scale (SDS) subscale scores. The categories were none/mild (0-3), moderate (4-6), and marked/extreme (7-10). Treatment comparisons for prespecified shifts of interest and predictive value of week 2 or 4 improvement in SDS subscale scores for functional outcome at week 8 were assessed using logistic regression. RESULTS: Greater proportions of patients receiving desvenlafaxine 50 and 100 mg achieved improvement from baseline to week 8 for each prespecified shift endpoint versus placebo (all p ≤ 0.02). Early improvement in SDS subscale scores was a statistically significant predictor of functional outcome at week 8, both overall and for each treatment group (all p<0.0001). CONCLUSIONS: Treatment with desvenlafaxine 50 or 100 mg/d led to significantly greater categorical improvement in functional impairment versus placebo, and improvement in SDS subscale scores significantly predicted functional outcome. Monitoring patient progress early in the course of antidepressant treatment using a functional assessment such as the SDS may help clinicians determine whether or not treatment adjustments are needed.

Hypopituitarism other than sellar and parasellar tumors or traumatic brain injury assessed in a tertiary hospital.

OBJECTIVE: Data regarding the etiology, clinical and biochemical patterns in hypopituitarism is scant for Pakistan. We describe the characteristics of patients with hypopituitarism other than sellar and parasellar tumors or traumatic brain injury from a tertiary care center in Pakistan. METHODS: We conducted a retrospective descriptive study in the Aga Khan University Hospital, Karachi, Pakistan. We studied all patients presenting with hypopituitarism, between January 2004 and December 2013. Clinical, hormonal and imaging data pertinent to the study was collected according to inclusion criteria. RESULTS: Forty-two patients presented to the endocrinology clinics at the Aga Khan University Hospital during the study period. Thirty-seven patients (88.1%) were females. Mean age ± standard deviation of the participants was 53.8 ± 14.7 years. Sixteen patients had secondary infertility and all were females; a majority of patients in this group had Sheehan's syndrome (n=8) followed by empty sella syndrome (n=3), partial empty sella syndrome (n=2), idiopathic cause (n=2) and tuberculoma (n=1). Eighteen females (48.6%) reported inability to lactate. CONCLUSIONS: Non-traumatic hypopituitarism was more common in women, with Sheehan syndrome being the most common cause of hypopituitarism in our study (35.7%). Secondary hypothyroidism was the most common hormonal deficiency. The most commonly reported symptom was weakness.