Androgen Deficiency, Associations and Survival of Men With Stage 4 and 5 Chronic Kidney Disease: A Cohort Study.

OBJECTIVES: Anaemia is a key cause of morbidity in chronic kidney disease (CKD). Androgen deficiency (AD) in males can contribute to anaemia of all causes, including in CKD. We sought to examine the prevalence of AD in men with CKD, the extent to which it contributed to anaemia and whether it was independently associated with long-term survival. METHODS: This cross-sectional observational study was conducted among males aged 18 years and over with CKD stages 4 and 5. The study analysed morning blood samples with regard to their full blood count, urea and electrolytes, albumin, lipids, testosterone (T) and sex hormone binding globulin, with calculation of free testosterone by mass action equation. Mortality data were obtained 15 years later for survival analysis. RESULTS: Among 322 patients with a mean age of 63 years, the overall prevalence of AD was 68.9%. There was a statistically significant negative correlation between erythropoiesis stimulating agent (ESA) dose and testosterone concentrations (Pearson correlation -0.193, p = 0.05). There was a positive correlation between haemoglobin (Hb) and free testosterone level among patients not on ESA therapy (Pearson correlation 0.331, p < 0.001). Kaplan-Meier plots showed p < 0.001 on log-rank analysis, indicating that AD was significantly associated with worse survival. However, in Cox regression analysis, free testosterone was not associated with survival (95% CI for free testosterone 0.997-1.000). CONCLUSIONS: AD is highly prevalent among this population, and increases further with older age and more severe CKD warranting haemodialysis. Association of lower Hb and higher ESA dose with lower T concentration might be causative, which has important pharmaco-economic as well as clinical implications. Lower survival in men with low T, more likely reflects overall poor health rather than causation. A properly constituted randomised controlled study evaluating the effect of native T replacement is warranted in men with CKD and AD.

Cardiovascular disease and testosterone therapy in male hypogonadism.

This review assesses the evidence of the physiological effects of testosterone on cardiovascular health, the association between male hypogonadism and cardiovascular health, and the effects of testosterone therapy on cardiovascular health in male hypogonadism. Preclinical studies suggest complex effects of testosterone on cardiovascular risk by acting on skeletal muscle, cardiomyocytes, vasculature, adipocytes, insulin action, and erythropoiesis. Furthermore, low testosterone has a bi-directional association with cardiometabolic risk. Observational studies have reported worse metabolic profiles in men with organic hypogonadism. However, a consistent association between major cardiovascular events and male hypogonadism has not been established. Hematocrit increases with testosterone therapy; however, most studies do not report an increase in venous thromboembolism risk. Although some observational studies and a small randomized controlled study reported an increased risk of cardiovascular disease, recent data confirm the medium-term cardiovascular safety of testosterone therapy in middle-aged and older men with low testosterone.

Male hypogonadism: pathogenesis, diagnosis, and management.

Organic male hypogonadism due to irreversible hypothalamic-pituitary-testicular (HPT) pathology is easily diagnosed and treated with testosterone-replacement therapy. However, controversy surrounds the global practice of prescribing testosterone to symptomatic men with low testosterone and non-gonadal factors reducing health status, such as obesity, type 2 diabetes, and ageing (ie, functional hypogonadism), but without identifiable HPT axis pathology. Health optimisation remains the gold-standard management strategy. Nevertheless, in the last decade large clinical trials and an individual patient data meta-analysis of smaller clinical trials confirmed that testosterone therapy induces modest, yet statistically significant, improvements in sexual function without increasing short-term to medium-term cardiovascular or prostate cancer risks in men with functional hypogonadism. Although testosterone improves bone mineral density and insulin sensitivity in these men, trials from the last decade suggest insufficient evidence to determine the safety and effectiveness of use of this hormone for the prevention of fractures or type 2 diabetes. This Review discusses the pathogenesis and diagnosis of male hypogonadism and appraises the evidence underpinning the management of this condition.

Metabolic and cardiovascular risks of hormone treatment for transgender individuals.

Identifying metabolic and cardiovascular risks of gender-affirming hormone therapy (GAHT) is challenging due to other confounding variables that affect patient outcomes and the diversity of treatment regimes. Masculinising hormone therapy produces atherogenic lipid profiles, while effects on other metabolic parameters are not consistent. There is insufficient evidence to conclude if cardiovascular disease risk among transmen is increased. The effects of feminising hormone therapy on metabolic parameters do not demonstrate a consistent pattern in the available literature. However, the risk of venous thromboembolism is greater in transwomen than in cis-gender men and women with a possible increase in cardiovascular disease risk. It is recommended to discuss the potential effects of GAHT on cardiovascular health and encourage patients seeking GAHT to adopt a healthy lifestyle. Performing baseline and periodic assessments of cardiovascular risk factors would enable early identification and interventions. In high-risk individuals, the cardiovascular effects of hormonal regimes might impact the treatment decision.

Cost-effectiveness of testosterone treatment utilising individual patient data from randomised controlled trials in men with low testosterone levels.

BACKGROUND: Testosterone is safe and highly effective in men with organic hypogonadism, but worldwide testosterone prescribing has recently shifted towards middle-aged and older men, mostly with low testosterone related to age, diabetes and obesity, for whom there is less established evidence of clinical safety and benefit. The value of testosterone treatment in middle-aged and older men with low testosterone is yet to be determined. We therefore evaluated the cost-effectiveness of testosterone treatment in such men with low testosterone compared with no treatment. METHODS: A cost-utility analysis comparing testosterone with no treatment was conducted following best practices in decision modelling. A cohort Markov model incorporating relevant care pathways for individuals with hypogonadism was developed for a 10-year-time horizon. Clinical outcomes were obtained from an individual patient meta-analysis of placebo-controlled, double-blind randomised studies. Three starting age categories were defined: 40, 60 and 75 years. Cost utility (quality-adjusted life years) accrued and costs of testosterone treatment, monitoring and cardiovascular complications were compared to estimate incremental cost-effectiveness ratios and cost-effectiveness acceptability curves for selected scenarios. RESULTS: Ten-year excess treatment costs for testosterone compared with non-treatment ranged between £2306 and £3269 per patient. Quality-adjusted life years results depended on the instruments used to measure health utilities. Using Beck depression index-derived quality-adjusted life years data, testosterone was cost-effective (incremental cost-effectiveness ratio <£20,000) for men aged <75 years, regardless of morbidity and mortality sensitivity analyses. Testosterone was not cost-effective in men aged >75 years in models assuming increased morbidity and/or mortality. CONCLUSIONS AND FUTURE RESEARCH: Our data suggest that testosterone is cost-effective in men <75 years when Beck depression index-derived quality-adjusted life years data are considered; cost-effectiveness in men >75 years is dependent on cardiovascular safety. However, more robust and longer-term cost-utility data are needed to verify our conclusion.

Global Barriers to Accessing Off-Patent Endocrine Therapies: A Renaissance of the Orphan Disease?

CONTEXT: Clinical endocrinology encompasses many diseases requiring long-term drug therapy. Prohibitive pricing of some endocrine drugs classified as essential by the World Health Organization has created suboptimal care of patients with endocrine disorders. EVIDENCE ACQUISITION: This review is based on evidence obtained from several databases and search engines including PubMed, Google, and Google Scholar; reference searches; manual searching for web pages of international regulatory bodies; and the authors' experience from different healthcare settings. EVIDENCE SYNTHESIS: After the expiry of a patent, generic versions with the opportunity for increased availability and a price reduction are expected. There are access barriers worldwide for many off-patent endocrine drugs. The high price is the main issue for several medicines including insulin, hydrocortisone, testosterone, and gonadotropins. This is caused by several factors including the market monopoly due to the lack of registered generics or suppliers limiting the benefit of competition and a complex supply chain. Additionally, the lack of some medicines has been concerning due to market factors such as the relatively small number of patients, making it less attractive for the manufacturers. Commissioning of nonprofit manufacturers and state manufacturing as well as strict price control measures could alleviate this situation. CONCLUSION: Lack of availability and disproportionate price inflation affecting essential off-patent endocrine therapies is common due to several interrelated factors. Global collaboration among healthcare organizations with the support of policymaking bodies might be needed to mitigate this.

Effect of oestrogen modulation on semen parameters in men with secondary hypogonadism: Systematic review and meta-analysis.

BACKGROUND: Selective oestrogen receptor modulators and aromatase inhibitors stimulate endogenous gonadotrophins and testosterone in men with hypogonadism. There are no systematic reviews/meta-analyses assessing the effects of selective oestrogen receptor modulators/aromatase inhibitors on semen parameters in men with secondary hypogonadism. OBJECTIVES: To assess the effect of monotherapy or a combination of selective oestrogen receptor modulators/aromatase inhibitors on sperm parameters and/or fertility in men with secondary hypogonadism. MATERIALS AND METHODS: A systematic search was conducted in PubMed, MEDLINE, Cochrane Library and ClinicalTrials.gov. Study selection and data extraction were performed by two reviewers independently. Randomised controlled trials and non-randomised studies of interventions reporting effects of selective oestrogen receptor modulators and/or aromatase inhibitors on semen parameters or fertility in men with low testosterone with low/normal gonadotrophins were selected. The risk of bias was assessed using ROB-2 and ROBINS-I tools. The results of randomised controlled trials were summarised using vote counting while summarising effect estimates where available. Non-randomised studies of intervention meta-analysis were conducted using the random-effect model. The certainty of evidence was assessed using GRADE. RESULTS: Five non-randomised studies of interventions (n = 105) of selective oestrogen receptor modulators showed an increase in sperm concentration (pooled mean difference 6.64 million/mL; 95% confidence interval 1.54, 11.74, I2  = 0%) and three non-randomised studies of interventions (n = 83) of selective oestrogen receptor modulators showed an increase in total motile sperm count (pooled mean difference 10.52; 95% confidence interval 1.46-19.59, I2  = 0%), with very low certainty of evidence. The mean body mass index of participants was >30 kg/m2 . Four randomised controlled trials (n = 591) comparing selective oestrogen receptor modulators to placebo showed a heterogeneous effect on sperm concentration. Three included men with overweight or obesity. The results were of very low certainty of evidence. Limited pregnancy or live birth data were available. No studies comparing aromatase inhibitors with placebo or testosterone were found. DISCUSSION AND CONCLUSION: Current studies are of limited size and quality but suggest that selective oestrogen receptor modulators may improve semen parameters in those patients, particularly when associated with obesity.

Rathke's cleft cyst discovered with ruptured anterior communicating artery aneurysm: a case report.

INTRODUCTION: Rathke's cleft cysts are thought to have a benign clinical outcome apart from associated hypopituitarism and visual defects. Synchronous central nervous system lesions, including pituitary adenoma and intracerebral aneurysms, are rarely reported. Diagnosis of Rathke's cleft cyst after presenting with a subarachnoid hemorrhage due to a ruptured arterial aneurysm is reported only once before. CASE PRESENTATION: A 33-year-old Sri Lankan female presented with a subarachnoid hemorrhage due to a ruptured anterior communication artery aneurysm. She underwent pterional craniotomy and aneurysm clipping. She was found to have partial cranial diabetes insipidus and hypogonadotropic hypogonadism. She had a cystic lesion occupying enlarged sella turcica with characteristics of a Rathke's cleft cyst. Subsequently, she underwent trans-sphenoidal excision of the sellar lesion. Histology confirmed the diagnosis of Rathke's cleft cyst. CONCLUSIONS: Rare co-occurrence of a Rathke's cleft cyst and an anterior communicating artery aneurysm would have been missed if subtle manifestations atypical for subarachnoid hemorrhage were not further pursued. This could have led to progressive visual deterioration and hypopituitarism.

Standardising the biochemical confirmation of adult male hypogonadism; a joint position statement by the Society for Endocrinology and Association of Clinical Biochemistry and Laboratory Medicine.

Background: Inter-assay variation between different immunoassays and different mass spectrometry methods hampers the biochemical confirmation of male hypogonadism. Furthermore, some laboratories utilis eassay manufacturer reference ranges that do not necessarily mirror assay performance characteristics, with the lower limit of normality ranging from 4.9 nmol/L to 11 nmol/L. The quality of the normative data underlying commercial immunoassay reference ranges is uncertain.Design: A working group reviewed published evidence and agreed upon standardised reporting guidance to augment total testosterone reports. Results: Evidence-based guidance on appropriate blood sampling, clinical action limits, and other major factors likely to affect the interpretation of results are provided. Conclusions: This article aims to improve the quality of the interpretation of testosterone results by non-specialist clinicians. It also discusses approaches for assay harmonisation which have been successful in some but not all healthcare systems.

Hyperpyrexia in a previously healthy pregnant female with COVID pneumonia: a case report and review of the literature.

BACKGROUND: Infection due to the SARS-CoV-2 virus can have a wide range of presentations from asymptomatic/mildly symptomatic to severe disease with multiorgan failure. Fever is a common symptom. But hyperpyrexia defined as temperature > 41.5 °C is not usual in COVID-19. CASE PRESENTATION: A 24-year-old previously well Sri Lankan female in the 24th week of gestation of her first pregnancy presented with fever and shortness of breath. She was confirmed to have coronavirus disease-2019 (COVID-19). History was suggestive of late presentation on approximately the eighth day of the illness. She had rapidly deteriorating hypoxia due to COVID pneumonia requiring mechanical ventilation two days after the admission. There was evidence of cytokine storm without any secondary bacterial infection. She received glucocorticoids, tocilizumab, and intravenous antibiotics. Although she initially showed mild improvements, she subsequently developed high-grade fever with the axillary temperature rising to 41.7 °C starting from the seventh day of admission. There were no causative medicines or risk factors to explain hyperpyrexia. She died on the ninth day of admission. CONCLUSIONS: There are no reports of patients developing this complication during pregnancy. The pathophysiology of this rare life-threatening complication remains elusive. Detailed reporting and in-depth analysis of such patients will facilitate the understanding of the associations and successful management of these patients.

Primary hyperparathyroidism in an adolescent presenting with genu valgus progressing to extensive bone disease; a case report.

BACKGROUND: Primary hyperparathyroidism which is rare in adolescents presents commonly with non-specific symptoms and systemic complaints. Though there are few reported cases of genu valgus, genu valgus progressing to extensive bone disease despite mildly elevated calcium had not been reported before. CASE PRESENTATION: A 12-year-old male had been evaluated for bilateral (left > right) genu valgus and short stature. Serum calcium and phosphate levels had been normal. X-ray of the femora and pelvic bones had not shown additional abnormalities. Valgus deformity progressed despite left femoral plating, and a left distal femoral medial closed wedge osteotomy had been performed at 15 years. Plain imaging at that time had shown localised osteopaenia. At the age of 17 years, he developed multiple fragility fractures of his left hip rendering him wheelchair-bound. Further evaluation revealed a serum PTH level of 2571 (10-65) pg/mL with calcium of 2.82 (2.2-2.6) mmol/L and inorganic phosphate of 1.7 (2.2-4.7) mg/dL. The lumbar spine DXA scan showed a Z-score of -5.8. A left parathyroid adenoma was localised and there was evidence of hyperparathyroid bone disease including brown tumours. He underwent left parathyroidectomy and left thyroid lobectomy after which his PTH level dropped to 4.03 pg/mL. He developed hypocalcaemia which was managed successfully with calcium and alfacalcidol replacement. CONCLUSIONS: Primary hyperparathyroidism can present with genu valgus in adolescents. Initial normocalcaemia which could be due to concomitant vitamin D deficiency could mask this leading to delayed diagnosis until severe irreversible bone disease ensues.

Sexual dysfunction among men with diabetes; a cross-sectional study at a specialised diabetes clinic in Sri Lanka.

BACKGROUND: Male sexual dysfunction in diabetes is often an unrevealed clinical issue. Though many publications report the prevalence, there is limited data on its associations, impact, and health-seeking behaviour. The objectives were to assess the prevalence of male sexual dysfunction, its associations, impact and treatment-seeking among men with diabetes in a selected tertiary care Diabetes Clinic. METHODS: A cross-sectional study was conducted at the Diabetes Clinic, National Hospital of Sri Lanka, from January to September 2020. Men with diabetes aged 18 to 70 years undergoing annual assessment were recruited consecutively. Socio-demographic and clinical information were collected using an interviewer-administered questionnaire. Erectile dysfunction (ED), premature ejaculation, mental health and quality of life were assessed using validated self-administered questionnaires. Cardiovascular autonomic reflex tests and total testosterone levels were performed. Penile colour Doppler ultrasonography was performed on consenting participants with erectile dysfunction. Associations were assessed using the chi-square test or Fisher's exact for dichotomous variables and independent sample t-test for continuous variables. RESULTS: Two hundred and twelve participants were recruited with a mean age of 54.1 (SD = 10.1) years. Erectile dysfunction was present in 168 (79.2%), (mild: 45, mild-moderate: 56, moderate: 26, severe: 41). Premature ejaculation was present in 26 (18.7%). Libido was low among 16%. Sexual dysfunction was not revealed to a health provider by 85.6% despite 60.5% experiencing psychological and/or relationship effects. Out of 18 who sought treatment, only 4 achieved a good response. Mean age (55.4 ± 9.5 vs 48.7 ± 10.6 years, p < 0.001) and duration of diabetes (10.9 ± 7.6 vs 5.8 ± 4.6 years, p < 0.001) were higher while eGFR was lower (73.9 ± 27.7 vs 100.51 ± 28.08 years, p < 0.008) among those with ED compared to those without. Diabetic retinopathy (4% vs 42%, p < 0.001), peripheral neuropathy (17.9% vs 38.4%, p = 0.041) and lower limb arterial disease (0% vs 12.2%, p = 0.04) were associated with ED. Arterial insufficiency was seen among 50% of the participants who underwent penile colour Doppler ultrasonography. CONCLUSIONS: Male sexual dysfunction is a pervasive yet underappreciated problem in diabetes care despite its effect on the individual. Patient and disease characteristics would guide the identification of high-risk individuals for targeted screening in clinical practice.

Postmenopausal hyperandrogenism due to an ovarian sex cord-stromal tumour causing elevated dehydroepiandrosterone sulphate: a case report.

BACKGROUND: The source of excess androgen can be obscure in postmenopausal women with new-onset hyperandrogenism. If serum dehydroepiandrosterone sulphate (DHEAS) is raised, it is presumed to be of adrenal origin because DHEAS is exclusively produced from adrenal cortical cells. This reports an elderly female presenting with new-onset hyperandrogenism due to an ovarian sex cord-stromal tumour, associated with increased serum DHEAS levels. CASE DESCRIPTION: A 76-year-old female with long-standing diabetes and hypertension presented with hirsutism and male type alopecia for six months. She had menopause at 55 years of age. There was a pelvic mass on examination. Total testosterone was 6.106 ng/ml (0.124-0.357) and DHEAS was > 1000 µg/dL (35-430). Contrast-enhanced computed tomography of the abdomen and pelvis showed a heterogeneously enhancing complex mass measuring 11 × 8 cm in the left adnexal region. Adrenal glands were normal. She underwent total abdominal hysterectomy, bilateral salphingo-oophorectomy, and omentectomy. Both testosterone and DHEAS normalised following surgery. Histology revealed a sex cord-stromal tumour, likely a steroid cell tumour with malignant potential. Fluorodeoxyglucose-Positron emission tomography did not show any additional lesions. CONCLUSIONS: Due to the lack of sulfotransferase in ovarian tissue, markedly elevated DHEAS originating from an ovarian neoplasm is unusual. This phenomenon has not been described except in a patient with a steroid cell tumour causing Cushing syndrome and hyperandrogenism. The mechanism of this rare occurrence remains elusive. Knowledge of this unusual presentation would enable the clinicians to be cautious in localising the androgen source in women with hyperandrogenism.

Prognostic and Therapeutic Role of Vitamin D in COVID-19: Systematic Review and Meta-analysis.

PURPOSE: Vitamin D deficiency/insufficiency may increase the susceptibility to coronavirus disease 2019 (COVID-19). We aimed to determine the association between vitamin D deficiency/insufficiency and susceptibility to COVID-19, its severity, mortality, and role of vitamin D in its treatment. METHODS: We searched CINAHL, Cochrane library, EMBASE, PubMED, Scopus, and Web of Science up to May 30, 2021, for observational studies on association between vitamin D deficiency/insufficiency and susceptibility to COVID-19, severe disease, and death among adults, and, randomized controlled trials (RCTs) comparing vitamin D treatment against standard care or placebo, in improving severity or mortality among adults with COVID-19. Risk of bias was assessed using Newcastle-Ottawa scale for observational studies and AUB-KQ1 Cochrane tool for RCTs. Study-level data were analyzed using RevMan 5.3 and R (v4.1.0). Heterogeneity was determined by I2 and sources were explored through prespecified sensitivity analyses, subgroup analyses, and meta-regressions. RESULTS: Of 1877 search results, 76 studies satisfying eligibility criteria were included. Seventy-two observational studies were included in the meta-analysis (n = 1 976 099). Vitamin D deficiency/insufficiency increased the odds of developing COVID-19 (odds ratio [OR] 1.46; 95% CI, 1.28-1.65; P < 0.0001; I2 = 92%), severe disease (OR 1.90; 95% CI, 1.52-2.38; P < 0.0001; I2 = 81%), and death (OR 2.07; 95% CI, 1.28-3.35; P = 0.003; I2 = 73%). The 25-hydroxy vitamin D concentrations were lower in individuals with COVID-19 compared with controls (mean difference [MD] -3.85 ng/mL; 95% CI, -5.44 to -2.26; P ≤ 0.0001), in patients with severe COVID-19 compared with controls with nonsevere COVID-19 (MD -4.84 ng/mL; 95% CI, -7.32 to -2.35; P = 0.0001) and in nonsurvivors compared with survivors (MD -4.80 ng/mL; 95% CI, -7.89 to -1.71; P = 0.002). The association between vitamin D deficiency/insufficiency and death was insignificant when studies with high risk of bias or studies reporting unadjusted effect estimates were excluded. Risk of bias and heterogeneity were high across all analyses. Discrepancies in timing of vitamin D testing, definitions of severe COVID-19, and vitamin D deficiency/insufficiency partly explained the heterogeneity. Four RCTs were widely heterogeneous precluding meta-analysis. CONCLUSION: Multiple observational studies involving nearly 2 million adults suggest vitamin D deficiency/insufficiency increases susceptibility to COVID-19 and severe COVID-19, although with a high risk of bias and heterogeneity. Association with mortality was less robust. Heterogeneity in RCTs precluded their meta-analysis.

Plague Transmission from Corpses and Carcasses.

Knowing whether human corpses can transmit plague will inform policies for handling the bodies of those who have died of the disease. We analyzed the literature to evaluate risk for transmission of Yersinia pestis, the causative agent of plague, from human corpses and animal carcasses. Because we could not find direct evidence of transmission, we described a transmission pathway and assessed the potential for transmission at each step. We examined 3 potential sources of infection: body fluids of living plague patients, infected corpses and carcasses, and body fluids of infected corpses. We concluded that pneumonic plague can be transmitted by intensive handling of the corpse or carcass, presumably through the inhalation of respiratory droplets, and that bubonic plague can be transmitted by blood-to-blood contact with the body fluids of a corpse or carcass. These findings should inform precautions taken by those handling the bodies of persons or animals that died of plague.

Apoplexy of Crooke cell tumour leading to the diagnosis of severe Cushing disease; a case report.

BACKGROUND: Patients with Crooke cell tumours present with features of Cushing syndrome or mass effect. There are few reports of patients with Crooke cell tumours presenting due to apoplexy. All of them had silent tumours. Patients with Cushing syndrome caused by Crooke cell tumours have not been reported to present with apoplexy. CASE PRESENTATION: A 35-year-old female presented with sudden onset headache and visual loss for 1 week. She had secondary amenorrhoea for 10 years. There were features of Cushing syndrome including central obesity, multiple monomorphic acne, dorso-cervical and supraclavicular fat pads, hypertension, proximal weakness, pigmentation and refractory hypokalaemia. She was found to have markedly elevated serum cortisol, central hypothyroidism and hypogonadotropic hypogonadism. There was a mass in the sellar region (4.7 cm × 1.9 cm × 5.3 cm) suggestive of a pituitary tumour extending to the suprasellar region. Imaging showed evidence of bleeding and compression of the optic chiasm. She underwent urgent trans-sphenoidal excision of the tumour. Histology was compatible with a pituitary neuroendocrine tumour. There was margination of ACTH reactivity to the cell periphery and ring like positivity in most of the cells in the cytokeratin stain. Features were in favour of a Crooke cell tumour. After surgery she improved gradually and became eucortisolaemic. CONCLUSIONS: This is a unique presentation of an apoplexy of Crooke cell tumour causing Cushing syndrome. Delayed health seeking behaviour of this patient despite severe Cushing disease could have led to this presentation which has not been reported before.

Sheehan Syndrome Presenting with Psychotic Manifestations Mimicking Schizophrenia in a Young Female: A Case Report and Review of the Literature.

INTRODUCTION: Sheehan syndrome presents with features of multiple hormone deficiencies including lactation failure and amenorrhoea as well as with features of central hypothyroidism and adrenocorticotropic hormone deficiency. Psychiatric manifestations are mostly limited to cognitive impairment. Psychotic presentations are rare and limited to case reports. Case Presentation. A 32-year-old female was evaluated for fearfulness and delusions for one year. She had persecutory and bizarre delusions, delusion of thought possession, and elementary auditory hallucinations. These began four months after the birth of her third child. The delivery had been complicated with postpartum haemorrhage. Her symptoms caused the functional decline and progressively worsened, resulting in suicidal ideation. Cognitive assessment revealed mild impairment in attention. Further inquiry revealed lethargy, constipation, cold intolerance, and lactation failure. She was slow, having dry skin, puffy face, and bradycardia with a blood pressure of 80/60 mmHg (supine) and 70/50 mmHg (standing). She had hyponatraemia, elevated creatine phosphokinase, low thyroxine, prolactin, FSH, LH, and IGF-1. She had poor cortisol and growth hormone response to the insulin tolerance test. MRI-pituitary showed empty sella. A diagnosis of Sheehan syndrome was made. Her symptoms improved completely after the initiation of levothyroxine and hydrocortisone. CONCLUSIONS: Sheehan syndrome can present with psychotic symptoms mimicking schizophrenia with variable involvement of cognition. Detailed reporting of these patients would enhance better characterization of the clinical presentation and risk profile of these patients.

Hemostatic derangement in leptospirosis: A prospective cross-sectional study.

CONTEXT: Coagulation abnormalities have been observed among leptospirosis patients. However, coagulopathy in severe leptospirosis has not been further characterized. AIMS: The aim of this study was to evaluate conventional coagulation and rotational thromboelastometry (ROTEM®) parameters in leptospirosis patients. SETTINGS AND DESIGN: This prospective cross-sectional comparative study included patients presenting to a tertiary hospital in Sri Lanka with clinically and serologically confirmed leptospirosis (14 severe and 6 mild), dengue (6), sepsis (5), and 6 healthy individuals. SUBJECTS AND METHODS: Blood samples were collected between the 3rd and 10th days of illness for prothrombin time (PT), activated partial thromboplastin time (aPTT), thrombin time (TT), fibrinogen, lupus anticoagulant, factors VII and VIII, D-dimer, platelet count, and ROTEM. STATISTICAL ANALYSIS USED: ANOVA post hoc comparison using Bonferroni was applied to compare groups. RESULTS: PT and aPTT were prolonged in leptospirosis patients and were corrected with normal plasma. TT was not significantly prolonged in leptospirosis. Fibrinogen was significantly elevated in severe leptospirosis (P = 0.001) and sepsis (P = 0.001) compared with healthy controls and dengue. Thirty percent of leptospirosis patients had thrombocytopenia (17% in mild and 36% in severe). No significant differences were seen in inTEM clotting time (CT) and exTEM CT in leptospirosis when compared to the other three groups. inTEM clot formation time (CFT) and exTEM CFT in dengue were significantly higher compared to severe (P = 0.001) and mild (P = 0.005) leptospirosis. inTEM maximum clot firmness (MCF) (P = 0.001) and exTEM MCF (P = 0.001) were significantly lower in dengue than in leptospirosis. Only one patient with leptospirosis had bleeding manifestations. CONCLUSIONS: Abnormalities in conventional coagulation parameters occur in leptospirosis. However, ROTEM parameters in leptospirosis are not significantly altered.

The Impact of SARS-Cov-2 Virus Infection on the Endocrine System.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus has spread across the globe rapidly causing an unprecedented pandemic. Because of the novelty of the disease, the possible impact on the endocrine system is not clear. To compile a mini-review describing possible endocrine consequences of SARS-CoV-2 infection, we performed a literature survey using the key words Covid-19, Coronavirus, SARS CoV-1, SARS Cov-2, Endocrine, and related terms in medical databases including PubMed, Google Scholar, and MedARXiv from the year 2000. Additional references were identified through manual screening of bibliographies and via citations in the selected articles. The literature review is current until April 28, 2020. In light of the literature, we discuss SARS-CoV-2 and explore the endocrine consequences based on the experience with structurally-similar SARS-CoV-1. Studies from the SARS -CoV-1 epidemic have reported variable changes in the endocrine organs. SARS-CoV-2 attaches to the ACE2 system in the pancreas causing perturbation of insulin production resulting in hyperglycemic emergencies. In patients with preexisting endocrine disorders who develop COVID-19, several factors warrant management decisions. Hydrocortisone dose adjustments are required in patients with adrenal insufficiency. Identification and management of critical illness-related corticosteroid insufficiency is crucial. Patients with Cushing syndrome may have poorer outcomes because of the associated immunodeficiency and coagulopathy. Vitamin D deficiency appears to be associated with increased susceptibility or severity to SARS-CoV-2 infection, and replacement may improve outcomes. Robust strategies required for the optimal management of endocrinopathies in COVID-19 are discussed extensively in this mini-review.

Carica papaya extract in dengue: a systematic review and meta-analysis.

BACKGROUND: Carica papaya (CP) extract is becoming popular as an unlicensed herbal remedy purported to hasten recovery in dengue infection, mostly based on observations that it may increase platelet counts. This systematic review and meta-analysis aims to critically analyze the evidence from controlled clinical trials on the efficacy and safety of CP extract in the treatment of dengue infection. METHODS: PubMed, LILACS and Google Scholar were searched for randomized or non-randomized trials enrolling patients with suspected or confirmed dengue where CP extract was compared, as a treatment measure, against standard treatment. Recovery of platelet counts as well as other clinical indicators of favourable outcome (duration of hospital stay, prevention of plasma leakage, life threatening complications, and mortality) were assessed. RESULTS: Nine studies (India-6, Pakistan-1, Indonesia-1, Malaysia-1) met the inclusion criteria. Seven studies showed an increase in platelet counts in patients receiving CP extract, while one study showed no significant difference between the two groups, and direct comparison was not possible in the remaining study. Serious adverse events were not reported. CP extract may reduce the duration of hospital stay (mean difference - 1.98 days, 95% confidence interval - 1.83 to - 2.12, 3 studies, 580 participants, low quality evidence), and cause improvement in mean platelet counts between the first and fifth day of treatment (mean difference 35.45, 95% confidence interval 23.74 to 47.15, 3 studies, 129 participants, low quality evidence). No evidence was available regarding other clinical outcomes. CONCLUSIONS: The clinical value of improvement in platelet count or early discharge is unclear in the absence of more robust indicators of favourable clinical outcome. Current evidence is insufficient to comment on the role of CP extract in dengue. There is a need for further well designed clinical trials examining the effect of CP on platelet counts, plasma leakage, other serious manifestations of dengue, and mortality, with clearly defined outcome measures.