An objective way to predict remission and relapse in Cushing disease using Bayes' theorem of probability.

OBJECTIVE: In this study on patients with Cushing disease, post-transsphenoidal surgery (TSS), we attempt to predict the probability of remaining in remission, at least for a year and relapse after that, using Bayes' theorem and the equation of conditional probability. The number of parameters, as well as the weightage of each, is incorporated in this equation. DESIGN AND METHODS: The study design was a single-centre ambispective study. Ten clinical, biochemical, radiological and histopathological parameters capable of predicting Cushing disease remission were identified. The presence or absence of each parameter was entered as binary numbers. Bayes' theorem was applied, and each patient's probability of remission and relapse was calculated. RESULTS: A total of 145 patients were included in the study. ROC plot showed a cut-off value of the probability of 0.68, with a sensitivity of 82% (range 73-89%) and a specificity of 94% (range 83-99%) to predict the probability of remission. Eighty-one patients who were in remission at 1 year were followed up for relapse and 23 patients developed relapse of the disease. The Bayes' equation was able to predict relapse in only 3 out of 23 patients. CONCLUSIONS: Using various parameters, remission of Cushing disease can be predicted by applying Bayes' theorem of conditional probability with a sensitivity and a specificity of 82% and 94%, respectively. This study provided an objective way of predicting remission after TSS and relapse in patients with Cushing disease giving a weightage advantage to every parameter.

GIANT MEDIASTINAL PARATHYROID ADENOMAS AND MULTIPLE ENDOCRINE NEOPLASIA TYPE 1: A DIAGNOSTIC CONUNDRUM.

Context: Giant parathyroid adenoma (GPA) is a rare entity that is rarer with Multiple endocrine neoplasia type 1 (MEN1) syndrome. Objectives: Describe the clinical presentation, diagnostic difficulties, and management strategy for GPA in MEN1. Methods: We searched Pubmed, SCOPUS and EMBASE for GPA in MEN1 for GPA in association with MEN1. Hereby, we describe index case of largest ever reported GPA. Results: We identified 7 cases of GPA reported till date in association with MEN1. The mean adenoma weight was 7.1 gram. The index case is largest-ever reported GPA (weight 97 gram) in MEN1 presenting with compressive symptoms and mediastinal mass. Incidentally, she was found to have hypercalcemia with increased parathyroid hormone, suggesting primary hyperparathyroidism. The possibilities of an ectopic parathyroid tumor and thymic carcinoid were considered. She also had acromegaloid features, and was found to have a sellar tumor. Subsequently, MENIN gene mutation was identified confirming MEN1 syndrome. Patient underwent trans-sternal excision of the mass weighing 97 grams and confirmed as parathyroid adenoma on histopathologic examination. Conclusion: Despite rarity of ectopic mediastinal parathyroid tumors, calcium profile should be considered as part of work-up of considering varied etiologies of anterior mediastinal mass.

Unravelling a novel, promising and convenient tool for differential diagnosis of delayed puberty: GnRHa-stimulated inhibin B (GnRH-iB).

BACKGROUND: Etiological diagnosis of delayed puberty is difficult. Despite availability of various basal and stimulation tests differentiation between constitutional delay in puberty and hypogonadotropic hypogonadism is still challenging. OBJECTIVE: To elucidate the role of GnRH agonist-stimulated inhibin B (GnRH-iB) for the differential diagnosis of delayed puberty. STUDY DESIGN: Participants were recruited into "exploratory cohort" (n = 39) and "validation cohort" (n = 16). "Exploratory cohort" included children with spontaneous puberty and patients with hypogonadotropic hypogonadism. "Validation cohort" constituted children who presented with delayed puberty. INTERVENTION AND OUTCOME: GnRHa (Triptorelin) stimulation test along with measurement of inhibin B level at 24 h after GnRHa injection was performed in all the study participants. Cut-offs for GnRH-iB were derived from the "exploratory cohort". These cut-offs were applied to the "validation cohort". Basal LH, basal inhibin B(INH-B), GnRHa-stimulated LH at 4 h (GnRH-LH) and GnRH-iB were evaluated for the prediction of onset of puberty on prospective follow-up. RESULTS: GnRH-iB at a cut-off value of 113.5 pg/ml in boys and 72.6 pg/ml in girls had 100% sensitivity and specificity for the documentation of puberty. In the "validation cohort" basal LH, basal INH-B, GnRH-LH, and GnRH-iB had a diagnostic accuracy of 68.75%, 81.25%, 68.75% and 93.75% respectively, for the prediction of onset of puberty. Basal LH, basal INH-B and GnRH-LH used alone or in combination were inferior to GnRH-iB used alone. CONCLUSION: GnRHa-stimulated inhibin B (GnRH-iB) is a convenient and easily employable test for the differentiation of constitutional delay in puberty from hypogonadotropic hypogonadism. CTRI REGISTRATION NO: CTRI/2019/10/021570.

Vitamin D supplementation and clinical outcomes in COVID-19: a systematic review and meta-analysis.

PURPOSE: To provide a precise summary and collate the hitherto available clinical evidence on the effect of vitamin D supplementation on clinical outcomes in COVID-19 patients. METHODS: PubMed/MEDLINE, Scopus, and Web of Science databases were systematically searched using appropriate keywords till June 8, 2021, to identify observational studies and randomized controlled trials (RCTs) reporting adverse clinical outcomes (ICU admission and/or mortality) in COVID-19 patients receiving vitamin D supplementation vs. those not receiving the same. Both prior use and use of vitamin D after COVID-19 diagnosis were considered. Unadjusted/adjusted pooled odds ratio (OR) with 95% confidence intervals (CI) were calculated (PROSPERO registration number CRD42021248488). RESULTS: We identified 13 studies (10 observational, 3 RCTs) pooling data retrieved from 2933 COVID-19 patients. Pooled analysis of unadjusted data showed that vitamin D use in COVID-19 was significantly associated with reduced ICU admission/mortality (OR 0.41, 95% CI: 0.20, 0.81, p = 0.01, I2 = 66%, random-effects model). Similarly, on pooling adjusted risk estimates, vitamin D was also found to reduce the risk of adverse outcomes (pooled OR 0.27, 95% CI: 0.08, 0.91, p = 0.03, I2 = 80%, random-effects model). Subgroup analysis showed that vitamin D supplementation was associated with improved clinical outcomes only in patients receiving the drug post-COVID-19 diagnosis and not in those who had received vitamin D before diagnosis. CONCLUSIONS: Vitamin D supplementation might be associated with improved clinical outcomes, especially when administered after the diagnosis of COVID-19. However, issues regarding the appropriate dose, duration, and mode of administration of vitamin D remain unanswered and need further research.

Fracture risk in hypoparathyroidism: a systematic review and meta-analysis.

In this meta-analysis, we analyzed 7 observational studies for assessing the fracture risk in patients with hypoparathyroidism (hypoPT). We found that the risk of vertebral fractures is increased by almost 2-fold, especially those with nonsurgical hypoPT. PURPOSE: Patients with hypoPT have higher bone mineral density than age- and sex-matched controls. This would theoretically translate into a lower risk of fractures, although available clinical evidence is contradictory. Hence, the present systematic review and meta-analysis was undertaken to collate and provide a precise summary of fracture risk in hypoPT. METHODS: PubMed, Scopus, and Web of Science databases were systematically searched using appropriate keywords till March 8, 2021, to identify observational studies reporting the rate of occurrence of fractures among hypoPT patients (nonsurgical and/or postsurgical) compared to non-hypoPT subjects (controls). Study quality was assessed using Newcastle-Ottawa Scale. Pooled odds ratio (OR) with 95% confidence intervals (CI) was calculated. Subgroup analyses of nonsurgical and postsurgical hypoPT patients were also conducted. RESULTS: We identified 7 observational studies of high-quality pooling data retrieved from 1470 patients with hypoPT. When stratified based on the skeletal site, pooled analyses showed that hypoPT patients were at an increased risk of vertebral fractures compared to non-hypoPT controls (OR 2.22, 95% CI: 1.23, 4.03, p = 0.009, I2 = 49%, random-effects model). The increased risk of vertebral fractures was seen only in patients with nonsurgical hypoPT (OR 2.31, 95% CI: 1.32, 4.03, p = 0.003, I2 = 3%, random-effects model) but not in those with postsurgical hypoPT. hypoPT patients were not at an increased or decreased risk of any, humerus, or proximal femur/hip fractures than controls. CONCLUSIONS: Nonsurgical hypoPT patients are at an almost 2-fold increased risk of vertebral fractures and thus need to be actively screened irrespective of the underlying BMD.

Development of the Asia Pacific Consortium on Osteoporosis (APCO) Framework: clinical standards of care for the screening, diagnosis, and management of osteoporosis in the Asia-Pacific region.

Guidelines for doctors managing osteoporosis in the Asia-Pacific region vary widely. We compared 18 guidelines for similarities and differences in five key areas. We then used a structured consensus process to develop clinical standards of care for the diagnosis and management of osteoporosis and for improving the quality of care. PURPOSE: Minimum clinical standards for assessment and management of osteoporosis are needed in the Asia-Pacific (AP) region to inform clinical practice guidelines (CPGs) and to improve osteoporosis care. We present the framework of these clinical standards and describe its development. METHODS: We conducted a structured comparative analysis of existing CPGs in the AP region using a "5IQ" model (identification, investigation, information, intervention, integration, and quality). One-hundred data elements were extracted from each guideline. We then employed a four-round Delphi consensus process to structure the framework, identify key components of guidance, and develop clinical care standards. RESULTS: Eighteen guidelines were included. The 5IQ analysis demonstrated marked heterogeneity, notably in guidance on risk factors, the use of biochemical markers, self-care information for patients, indications for osteoporosis treatment, use of fracture risk assessment tools, and protocols for monitoring treatment. There was minimal guidance on long-term management plans or on strategies and systems for clinical quality improvement. Twenty-nine APCO members participated in the Delphi process, resulting in consensus on 16 clinical standards, with levels of attainment defined for those on identification and investigation of fragility fractures, vertebral fracture assessment, and inclusion of quality metrics in guidelines. CONCLUSION: The 5IQ analysis confirmed previous anecdotal observations of marked heterogeneity of osteoporosis clinical guidelines in the AP region. The Framework provides practical, clear, and feasible recommendations for osteoporosis care and can be adapted for use in other such vastly diverse regions. Implementation of the standards is expected to significantly lessen the global burden of osteoporosis.

Remission in Cushing's disease is predicted by cortisol burden and its withdrawal following pituitary surgery.

AIM: To ascertain the predictors of remission and relapse in patients of Cushing's disease (CD) undergoing pituitary transsphenoidal surgery (TSS). METHODS: Patients with CD subjected to TSS over 35 years at a tertiary care center were included. Patients were grouped into remission and persistent disease at 1 year after surgery, and were further followed up for relapse. Demographic, clinical, biochemical, histological, radiological and post-operative follow-up parameters were analyzed. RESULTS: Of the 152 patients of CD, 145 underwent TSS. Remission was achieved in 95 (65.5%) patients at 1 year. Patients in remission had shorter duration of symptoms prior to presentation (p = 0.009), more frequent presence of proximal myopathy (p = 0.038) and a tumor size of < 2.05 cm (p = 0.016) in comparison to those with persistent disease. Post-TSS, immediate post-operative 0800-h cortisol (< 159.85 nmol/L; p = 0.001), histological confirmation of tumor (p = 0.045), duration of glucocorticoid replacement (median 90 days; p = 0.001), non-visualization of tumor on MRI (p = 0.003), new-onset hypogonadism (p = 0.001), 3-month 0800-h cortisol (< 384.9 nmol/L; p = 0.001), resolution of diabetes (p = 0.001) and hypertension (p = 0.001), and recovery of hypothalamic-pituitary-adrenal axis (p = 0.018) favored remission. In logistic regression model, requirement of glucocorticoid replacement (p = 0.033), and resolution of hypertension post-TSS (p = 0.003) predicted remission. None of the parameters could predict relapse. CONCLUSION: The study could ascertain the predictors of remission in CD. Apart from the tumor characteristics, surgical aspects and low post-operative 0800-h cortisol, the results suggest that baseline clinical parameters, longer glucocorticoid replacement, and resolution of metabolic complications post-TSS predict remission in CD. Long-term follow-up is essential to look for relapse.

Primary hyperparathyroidism in pregnancy: observations from the Indian PHPT registry.

PURPOSE: To present the data on primary hyperparathyroidism (PHPT) in pregnancy from India obtained from a large database maintained over 15 years. METHODS: We retrieved data of all women with gestational PHPT from the Indian PHPT registry between July 2005 and January 2020, and compared their clinical, biochemical, and other characteristics with age-matched non-pregnant women with PHPT. RESULTS: Out of 386 women, eight had gestational PHPT (2.1%). The common presenting manifestations were acute pancreatitis (50%) and renal stone disease (50%); two were asymptomatic. Five women (62.5%) had a history of prior miscarriages. Seven patients (88%) had preeclampsia during the present gestation. Serum calcium and intact parathyroid hormone (iPTH) were not statistically different from the age-matched non-pregnant PHPT group. Six patients with mild-to-moderate hypercalcemia were medically managed with hydration with/without cinacalcet while one patient underwent percutaneous ethanol ablation of the parathyroid adenoma; none underwent surgery during pregnancy. Mean serum calcium maintained from treatment initiation till delivery was 10.5 ± 0.4 mg/dl. One patient had spontaneous preterm delivery at 36 weeks; the remaining patients had normal vaginal delivery at term. None had severe preeclampsia/eclampsia. Fetal outcomes included low birth weight in three newborns (37.5%); two of them had hypocalcemic seizures. CONCLUSION: The prevalence of gestational PHPT was 2.1% in this largest Indian PHPT cohort, which is higher than that reported from the West (< 1%). Gestational PHPT can lead to preeclampsia and miscarriage. Pregnant PHPT patients with mild-to-moderate hypercalcemia can be managed with hydration/cinacalcet; however, long-term safety data and large-scale randomized controlled trials are required.

IQ driving QI: the Asia Pacific Consortium on Osteoporosis (APCO): an innovative and collaborative initiative to improve osteoporosis care in the Asia Pacific.

Asia Pacific Consortium on Osteoporosis (APCO) comprises of clinical experts from across the Asia Pacific region, uniting to develop solutions to problems facing osteoporosis management and care. The vision of APCO is to reduce the burden of osteoporosis and fragility fractures in the Asia Pacific region. INTRODUCTION: The Asia Pacific (AP) region comprises 71 countries with vastly different healthcare systems. It is predicted that by 2050, more than half the world's hip fractures will occur in this region. The Asia Pacific Consortium on Osteoporosis (APCO) was set up in May 2019 with the vision of reducing the burden of osteoporosis and fragility fractures in the AP region. METHODS: APCO has so far brought together 39 clinical experts from countries and regions across the AP to develop solutions to challenges facing osteoporosis management and fracture prevention in this highly populous region of the world. APCO aims to achieve its vision by engaging with relevant stakeholders including healthcare providers, policy makers and the public. The initial APCO project is to develop and implement a Framework of pan-AP minimum clinical standards for the screening, diagnosis and management of osteoporosis. RESULTS AND CONCLUSIONS: The Framework will serve as a platform upon which new national clinical guidelines can be developed or existing guidelines be revised, in a standardised fashion. The Framework will also facilitate benchmarking for provision of quality of care. It is hoped that the principles underlying the formation and functioning of APCO can be adopted by other regions and that every health care facility and progressively every country in the world can follow our aspirational path and progress towards best practice.

Dysregulated mitogen-activated protein kinase pathway mediated cell cycle disruption in sporadic parathyroid tumors.

OBJECTIVES: The study was designed to evaluate expression profiling of mitogen-activated protein kinase (MAPK) signalling pathway genes in sporadic parathyroid adenoma. METHODS: Expression of MAPK signalling pathway genes including activated transcription factors and cell cycle regulatory genes was analysed by real-time PCR- based array in parathyroid adenoma (N = 20) and normal parathyroid tissue (N = 4). RESULTS: MAPK signalling pathway as studied by PCR array revealed that a total of 22 genes were differentially expressed (≥ twofold change, p ≤ 0.05) in parathyroid adenoma. Up-regulated genes were ARAF, MAPK12, CREBBP, MYC, HSPB1, HRAS, CDK4, CCND1, and E2F1, and down-regulated genes were MAP4K1, DLK1, MAP3K4, MAPK10, MAPK8, ATF2, SMAD4, MEF2C, LAMTOR3, FOS, CDKN2A CDKN2B, and RB1. The present study revealed that ERK1/2 signalling pathway with up-regulation of HRAS, ARAF, and MEK1 genes and up-regulation of positive regulators of cell cycle (CCND1, CDK4, and E2F1) and down-regulation negative regulators of cell cycle (CDKN2A, CDKN2B, and RB1) made highly dysregulated MAPK signalling pathway in parathyroid adenoma. Expression of CDK4 was positively associated with plasma PTH level (r = 0.60, p = 0.04) and tumor weight (r = 0.80, p = 0.02) of the adenoma patients, respectively. Expression of CDKN2A was correlated negatively with PTH level (r = - 0.52, p = 0.04) of the adenoma patients. CONCLUSION: The current study revealed that ERK pathway and associated cell cycle regulator genes are dysregulated in sporadic parathyroid adenoma.

Quantitative proteomics analysis of sporadic parathyroid adenoma tissue samples.

OBJECTIVE: Molecular pathogenesis of parathyroid tumors is incompletely understood. Identification of novel molecules and understanding their role in parathyroid tumorigenesis by proteomics approach would be informative with potential clinical implications. METHOD: Adenomatous (n = 5) and normal (n = 2) parathyroid tissue lysates were analyzed for protein profile by LC-MS/MS method and the proteins were classified using bioinformatics tools such as PANTHER and toppfun functional enrichment tool. Identified proteins were further validated by western blotting and qRT-PCR (n = 20). RESULT: Comparative proteomics analysis revealed that a total of 206 proteins (74 upregulated and 132 downregulated) were differentially expressed (≥ twofold change) in adenomas. Bioinformatics analysis revealed that 48 proteins were associated with plasma membrane, 49 with macromolecular complex, 39 were cytoplasm, 38 were organelle related, 21 were cell junction and 10 were extracellular proteins. These proteins belonged to a diverse protein family such as enzymes, transcription factors, cell signalling, cell adhesion, cytoskeleton proteins, receptors, and calcium-binding proteins. The major biological processes predicted for the proteins were a cellular, metabolic and developmental process, cellular localization, and biological regulation. The differentially expressed proteins were found to be associated with MAPK, phospholipase C (PLC) and phosphatidylinositol (PI) signalling pathways, and with chromatin organization. Western blot and qRT-PCR analysis of three proteins (DNAJC2, ACO2, and PRDX2) validated the LC-MS/MS findings. CONCLUSION: This exploratory study demonstrates the feasibility of proteomics approach in finding the dysregulated proteins in benign parathyroid adenomas, and our preliminary results suggest that MAPK, PLC and PI signalling pathways and chromatin organization are involved in parathyroid tumorigenesis.

Effect of Linagliptin on Incretin-axis and Glycaemic Variability in T1DM.

BACKGROUNDS AND OBJECTIVES: Short-term studies have demonstrated potential therapeutic efficacy of dipeptidyl peptidase 4 inhibitors (DPP4 inhibitors) in patients with poorly controlled T1DM. In this study we evaluated the effect of DPP4 inhibitor, linagliptin, on glycaemic control and variability, and incretinaxis in well controlled T1DM patients to mitigate the effect of glucotoxicity on incretin secreting cells. METHODS: Twenty T1DM patients were randomized to receive either linagliptin (10 patients, dose-5 mg/day) or placebo (10 patients), in addition to insulin for 3 months. HbA1C, continuous glucose monitoring (CGM) and mixed meal test (MMT) were performed before and at the end of the study period. RESULTS: HbA1C reduction and change in glycaemic variability and insulin requirement in the linagliptin group did not attain the level of statistical significance. The increase in AUC GLP1 (Area under curve for GLP1) and decrease in AUC glucagon (Area under curve for glucagon) during the MMT in linagliptin group were also statistically insignificant. INTERPRETATIONS AND CONCLUSIONS: Linagliptin is not effective in reducing HbA1C and glycaemic variability in relatively well controlled T1DM patients.

Deranged regulatory T-cells and transforming growth factor-ß1 levels in type 1 diabetes patients with associated autoimmune diseases.

AIM: This study was designed to enumerate regulatory T-cells (Tregs) and estimate transforming growth factor-ß1 (TGF-ß1) levels in type 1 diabetic (T1D) patients with respect to disease duration and associated autoimmune diseases. METHODS: One hundred and fifty patients and twenty healthy controls were recruited in the study. The patients were subcategorized into eight categories on the basis of disease duration (new onset [NO] and long standing [LS]) and associated diseases, i.e., celiac disease (CD) and autoimmune thyroid disease (AiTD). Treg cells were assessed as CD4+ CD25hi+, FOXP3+ cells and serum TGF-ß1 levels were assessed by ELISA. RESULTS: The frequency of Tregs and levels of TGF-ß1 were significantly increased in the patients compared to the healthy controls. Among the different categories of the patients, no significant differences were seen for TGF- ß1 levels, but for Tregs in patients with T1D and AiTD (P = 0.035). A significant correlation was also found between percentage count of Tregs and TGF-ß1 levels in NO cases in all disease subcategories, but not in LS patients. CONCLUSION: Thus, there was an increased percentage of Tregs and serum levels of TGF-ß1 in T1D patients, irrespective of the disease duration and associated autoimmune diseases. The significant correlation in these two parameters at the onset of the disease, but not in LS disease, indicates that the immunological milieu in LS autoimmune diseases is more complicated with disease-associated conditions such as prolonged hyperglycemia, insulin therapy, and/or continued gluten in diet. Treatment and modulation of these long-term complications for improving immunological parameters require further research.

Primary hyperparathyroidism: review and recommendations on evaluation, diagnosis, and management. A Canadian and international consensus.

The purpose of this review is to assess the most recent evidence in the management of primary hyperparathyroidism (PHPT) and provide updated recommendations for its evaluation, diagnosis and treatment. A Medline search of "Hyperparathyroidism. Primary" was conducted and the literature with the highest levels of evidence were reviewed and used to formulate recommendations. PHPT is a common endocrine disorder usually discovered by routine biochemical screening. PHPT is defined as hypercalcemia with increased or inappropriately normal plasma parathyroid hormone (PTH). It is most commonly seen after the age of 50 years, with women predominating by three to fourfold. In countries with routine multichannel screening, PHPT is identified earlier and may be asymptomatic. Where biochemical testing is not routine, PHPT is more likely to present with skeletal complications, or nephrolithiasis. Parathyroidectomy (PTx) is indicated for those with symptomatic disease. For asymptomatic patients, recent guidelines have recommended criteria for surgery, however PTx can also be considered in those who do not meet criteria, and prefer surgery. Non-surgical therapies are available when surgery is not appropriate. This review presents the current state of the art in the diagnosis and management of PHPT and updates the Canadian Position paper on PHPT. An overview of the impact of PHPT on the skeleton and other target organs is presented with international consensus. Differences in the international presentation of this condition are also summarized.

Spectrum of cutaneous manifestations of type 1 diabetes mellitus in 500 South Asian patients.

BACKGROUND: Data on cutaneous manifestations of type 1 diabetes mellitus (DM) is scarce. OBJECTIVES: To study the spectrum of dermatoses in patients with type 1 DM and the effects of disease duration and long-term glucose control on these cutaneous manifestations. SUBJECTS AND METHODS: After prior consent, clinical examination and relevant investigations were done in 500 subjects with type 1 DM enrolled between July 2011 and June 2012. Statistical tests were performed using SPSS 16. The presence of various dermatoses was correlated with the duration of diabetes. RESULTS: Of five hundred subjects, 339 (67·8%) had one or more dermatoses. The mean age of the patients was 16·9 ± 6·9 years (range 1-25 years) and mean total duration of diabetes was 4·43 ± 4·4 years. Cutaneous adverse effects related to insulin injections (CAII), comprising lipohypertrophy (41%), post-inflammatory hyperpigmentation (3%), lipoatrophy (0·6%) and acanthosis nigricans (0·4%), were the most common findings, followed by limited joint mobility (LJM) (16·8%), xerosis (15·8%) and scleroderma-like skin changes (10%). Patients having long-duration DM (> 4·4 years) were significantly more likely to have lipohypertrophy (P = 0·000), LJM (P = 0·000), scleroderma-like skin changes (P = 0·000), diabetic dermopathy (P = 0·000), acanthosis nigricans (P = 0·005) and skin tags (P = 0·002). Lipohypertrophy, LJM and scleroderma-like skin changes also showed significant correlation with blood glucose level. CONCLUSIONS: Our study suggests that cutaneous changes are common in young Asian patients with type 1 DM. Information, education and counselling of patients and care givers, and awareness among physicians is essential for the prevention and early management of these dermatoses.

Congestive heart failure in acromegaly: A review of 6 cases.

BACKGROUND: Though cardiac involvement is common in acromegaly, overt congestive heart failure is uncommon. MATERIALS AND METHODS: This is retrospective analysis of hospital record between 1996 and 2007. We analyzed records of 150 consecutive patients with acromegaly. We included the patients with acromegaly those who had overt congestive heart failure either at presentation or during the course of illness for the present analysis. The diagnosis of acromegaly and congestive cardiac failure were based on standard criteria. RESULTS: Out of 150 patients with acromegaly, 6 patients had overt CHF (4.0%), of which 4 presented with the features of CHF and 2 developed during the course of illness. Three patients had hypertension and 1 had diabetes. Baseline echocardiography showed severe biventricular dysfunction and global hypokinesia in all. Angiography showed dilated hypokinetic left ventricle with normal coronaries in 3, it was confirmed at autopsy in 1. Three underwent trans-sphenoidal surgery, 1 received somatostatin analogue as primary treatment modality. Normalization of growth hormone and IGF-1 led to improvement in cardiac function in 1, 1 patient lost to follow up, and 4 died during the course of illness. In 1 patient, autopsy was performed and cardiac specimen revealed normal coronaries, concentric ventricular hypertrophy, and dilatation with myofibrolysis and interfascicular fibrosis. CONCLUSION: Prevalence of overt CHF is 4% in present series. Overt CHF carries poor prognosis and hence, this complication should be recognized at earliest, and medical management to normalized cardiac function should be given utmost priority.