Dexamethasone suppression test versus selective ovarian and adrenal vein catheterization in identifying virilizing tumors in postmenopausal hyperandrogenism - a systematic review and meta-analysis.

OBJECTIVE: The diagnostic accuracy of tests in identifying virilizing tumors in postmenopausal hyperandrogenism is limited. This systematic review compares the dexamethasone suppression test against selective ovarian and adrenal vein sampling of androgens in distinguishing neoplastic from non-neoplastic causes of postmenopausal hyperandrogenism. METHODS: Diagnostic test accuracy studies on these index tests in postmenopausal women were selected based on pre-established criteria. The true positive, false positive, false negative, and true negative values were extracted and meta-analysis was conducted using the hierarchical summary receiver operator characteristics curve method. RESULTS: The summary sensitivity of the dexamethasone suppression test is 100% (95% CI 0-100%) and that for selective venous sampling is 100% (95% CI 0-100%). The summary specificity of the dexamethasone suppression test is 89.2% (95% CI 85.3-92.2%) and that for selective venous sampling is 100% (95% CI 0.3-100%). CONCLUSION: There is limited evidence for the use of dexamethasone suppression test or selective venous sampling in identifying virilizing tumors in postmenopausal hyperandrogenism.

Treatment for hepatorenal syndrome in people with decompensated liver cirrhosis: a network meta-analysis.

BACKGROUND: Hepatorenal syndrome is defined as renal failure in people with cirrhosis in the absence of other causes. In addition to supportive treatment such as albumin to restore fluid balance, the other potential treatments include systemic vasoconstrictor drugs (such as vasopressin analogues or noradrenaline), renal vasodilator drugs (such as dopamine), transjugular intrahepatic portosystemic shunt (TIPS), and liver support with molecular adsorbent recirculating system (MARS). There is uncertainty over the best treatment regimen for hepatorenal syndrome. OBJECTIVES: To compare the benefits and harms of different treatments for hepatorenal syndrome in people with decompensated liver cirrhosis. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, Science Citation Index Expanded, World Health Organization International Clinical Trials Registry Platform, and trial registers until December 2018 to identify randomised clinical trials on hepatorenal syndrome in people with cirrhosis. SELECTION CRITERIA: We included only randomised clinical trials (irrespective of language, blinding, or publication status) in adults with cirrhosis and hepatorenal syndrome. We excluded randomised clinical trials in which participants had previously undergone liver transplantation. DATA COLLECTION AND ANALYSIS: Two authors independently identified eligible trials and collected data. The outcomes for this review included mortality, serious adverse events, any adverse events, resolution of hepatorenal syndrome, liver transplantation, and other decompensation events. We performed a network meta-analysis with OpenBUGS using Bayesian methods and calculated the odds ratio (OR), rate ratio, hazard ratio (HR), and mean difference (MD) with 95% credible intervals (CrI) based on an available-case analysis, according to National Institute of Health and Care Excellence Decision Support Unit guidance. MAIN RESULTS: We included a total of 25 trials (1263 participants; 12 interventions) in the review. Twenty-three trials (1185 participants) were included in one or more outcomes. All the trials were at high risk of bias, and all the evidence was of low or very low certainty. The trials included participants with liver cirrhosis of varied aetiologies as well as a mixture of type I hepatorenal syndrome only, type II hepatorenal syndrome only, or people with both type I and type II hepatorenal syndrome. Participant age ranged from 42 to 60 years, and the proportion of females ranged from 5.8% to 61.5% in the trials that reported this information. The follow-up in the trials ranged from one week to six months. Overall, 59% of participants died during this period and about 35% of participants recovered from hepatorenal syndrome. The most common interventions compared were albumin plus terlipressin, albumin plus noradrenaline, and albumin alone.There was no evidence of a difference in mortality (22 trials; 1153 participants) at maximal follow-up between the different interventions. None of the trials reported health-related quality of life. There was no evidence of differences in the proportion of people with serious adverse events (three trials; 428 participants), number of participants with serious adverse events per participant (two trials; 166 participants), proportion of participants with any adverse events (four trials; 402 participants), the proportion of people who underwent liver transplantation at maximal follow-up (four trials; 342 participants), or other features of decompensation at maximal follow-up (one trial; 466 participants). Five trials (293 participants) reported number of any adverse events, and five trials (219 participants) reported treatment costs. Albumin plus noradrenaline had fewer numbers of adverse events per participant (rate ratio 0.51, 95% CrI 0.28 to 0.87). Eighteen trials (1047 participants) reported recovery from hepatorenal syndrome (as per definition of hepatorenal syndrome). In terms of recovery from hepatorenal syndrome, in the direct comparisons, albumin plus midodrine plus octreotide and albumin plus octreotide had lower recovery from hepatorenal syndrome than albumin plus terlipressin (HR 0.04; 95% CrI 0.00 to 0.25 and HR 0.26, 95% CrI 0.07 to 0.80 respectively). There was no evidence of differences between the groups in any of the other direct comparisons. In the network meta-analysis, albumin and albumin plus midodrine plus octreotide had lower recovery from hepatorenal syndrome compared with albumin plus terlipressin. FUNDING: two trials were funded by pharmaceutical companies; five trials were funded by parties who had no vested interest in the results of the trial; and 18 trials did not report the source of funding. AUTHORS' CONCLUSIONS: Based on very low-certainty evidence, there is no evidence of benefit or harm of any of the interventions for hepatorenal syndrome with regards to the following outcomes: all-cause mortality, serious adverse events (proportion), number of serious adverse events per participant, any adverse events (proportion), liver transplantation, or other decompensation events. Low-certainty evidence suggests that albumin plus noradrenaline had fewer 'any adverse events per participant' than albumin plus terlipressin. Low- or very low-certainty evidence also found that albumin plus midodrine plus octreotide and albumin alone had lower recovery from hepatorenal syndrome compared with albumin plus terlipressin.Future randomised clinical trials should be adequately powered; employ blinding, avoid post-randomisation dropouts or planned cross-overs (or perform an intention-to-treat analysis); and report clinically important outcomes such as mortality, health-related quality of life, adverse events, and recovery from hepatorenal syndrome. Albumin plus noradrenaline and albumin plus terlipressin appear to be the interventions that should be compared in future trials.

Fructosamine and HbA1c: A Correlational Study in a Southeast Asian Population.

Objectives: Fructosamine correlates well with glycated haemoglobin (HbA1c) in Caucasians. This study investigates this correlation and whether fructosamine can reliably estimate glycated haemoglobin in Southeast Asians. Methods: We recruited 193 participants based on 4 HbA1c bands (<6.0%; 6.0 - 7.9%; 8.0- 9.9%; ≥10%) from a secondary hospital in Singapore between August 2017 and December 2021. Blood samples for fructosamine, glycated haemoglobin, albumin, haemoglobin, thyroid stimulating hormone and creatinine were drawn in a single setting for all participants. Scatter plot was used to explore correlation between fructosamine and glycated haemoglobin. Strength of linear correlation was reported using Pearson's correlation coefficient. Simple linear regression was used to examine the relationship between fructosamine and glycated haemoglobin. Results: We performed simple linear regression to study the relationship between fructosamine and HbA1c in the research participants (R2 = 0.756, p<0.01). Further analysis with natural logarithmic transformation of fructosamine demonstrated a stronger correlation between HbA1c and fructosamine (R2 = 0.792, p<0.01). Conclusions: Fructosamine is reliably correlated with HbA1c for the monitoring of glycaemic control in Southeast Asians.

Macroprolactinoma with secondary resistance to dopamine agonists: a case report and review of the literature.

BACKGROUND: Resistance to dopamine agonists is not uncommonly seen in prolactinomas. However, development of resistance to dopamine agonists after an initial period of robust treatment response is rare, and only 39 cases have been reported in the past four decades. We describe a Chinese man with this rare condition and explored the postulated mechanisms that may explain this phenomenon. We compiled similar cases that were previously reported and compared their etiology, progress, and response to treatment. On the basis of these cases, we derived a list of differential diagnoses to consider in patients with secondary resistance to dopamine agonists. CASE PRESENTATION: A 63-year-old Chinese man presented with blurred vision and was subsequently diagnosed with a macroprolactinoma. He had initial response to cabergoline but developed secondary resistance to it after 5 years. The prolactinoma continued to grow, and his serum prolactin remained markedly elevated despite adherence to escalating dosages of cabergoline up to 6 mg/week. The patient finally underwent transsphenoidal surgery and was found to have a sparsely granulated lactotroph tumor with Ki-67 index of 5%. Postoperatively, there was improvement in his serum prolactin level, although he still required treatment with cabergoline at 6 mg/week. CONCLUSIONS: Surgery can facilitate disease control in patients with prolactinomas that develop secondary resistance to dopamine agonists. Malignant prolactinoma is an important differential diagnosis in this group of patients, especially when serum prolactin remains markedly elevated despite resolution or stability of the primary pituitary lesion, suggesting a metastatic source of prolactin secretion.

Myxedema Coma Precipitated by Iohexol: Case Report and Brief Literature Review on the Wolff-Chaikoff Effect.

Background: Failure to escape from the Wolff-Chaikoff effect (WCE) causes hypothyroidism. Methods: This is the first report of myxedema coma after iohexol administration. The failure of the escape phenomenon in this patient was longer than existing reports. Results: The patient received 42,000 mg of iodine in iohexol cumulatively and developed myxedema coma after 16 days. She was subsequently found to have pre-existing primary hypothyroidism that was treated with levothyroxine 50 µg daily, but had defaulted treatment. She was discharged with levothyroxine 100 µg daily and this was weaned to 50 µg daily over 12 months. Conclusions: Iodine-based contrast media (ICM) can aggravate primary hypothyroidism. In severe cases, it may precipitate myxedema coma. Patients with thyroid disorders should be informed to monitor for aggravation of their symptoms after ICM administration. Long-term follow-up of thyroid function may be needed in patients who fail to escape from the WCE.

Efficacy and safety of anticoagulation in thyrotoxic atrial fibrillation: a systematic review and meta-analysis.

Background: Evidence on the efficacy and safety of anticoagulation in preventing stroke and thromboembolic events in people with thyrotoxic atrial fibrillation is scarce. Objective: We evaluated the efficacy and safety of anticoagulation in people with thyrotoxic atrial fibrillation. Methods: Our study protocol was published in the International Prospective Register of Systematic Reviews (registration no. CRD42020222782). Four databases and two systematic review registers were searched through 25 November 2020 for interventional and observational studies comparing anticoagulation therapy with active comparators, placebo, or no treatment in people with thyrotoxic atrial fibrillation. Random-effects meta-analysis and sensitivity analysis were performed. Quality of evidence was described using the GRADE framework. Results: In the study, 23,145 records were retrieved. One randomized controlled trial and eight cohort studies were ultimately included. Effect estimates on the efficacy and safety of anticoagulation were extracted. Meta-analysis using the inverse variance and random-effects methods was conducted on four cohort studies with 3443 participants and 277 events. Anticoagulation in people with thyrotoxic atrial fibrillation reduced the risk of ischemic stroke and systemic thromboembolism by 3% (95% CI: 1-6%). Warfarin may prevent ischemic stroke in people with thyrotoxic atrial fibrillation if the CHA2DS2-VASc score exceeds 1 and when atrial fibrillation persists beyond 7 days. Direct oral anticoagulants may be associated with fewer bleeding events than warfarin. Conclusions: Anticoagulation prevents ischemic stroke and systemic thromboembolism in people with thyrotoxic atrial fibrillation. Direct oral anticoagulants may be associated with fewer bleeding events.

Gonadotropin-Releasing Hormone Analogue Stimulation Test Versus Venous Sampling in Postmenopausal Hyperandrogenism.

Postmenopausal hyperandrogenism can be due to excessive androgen secretion from adrenal or ovarian virilizing tumors or nonneoplastic conditions. The etiology of postmenopausal hyperandrogenism can be difficult to discern because of limited accuracy of current diagnostic tests. This systematic review compares the diagnostic accuracy of the gonadotropin-releasing hormone (GnRH) analogue stimulation test against selective ovarian and adrenal vein sampling of androgens in distinguishing neoplastic from nonneoplastic causes of postmenopausal hyperandrogenism. Diagnostic test accuracy studies on these index tests in postmenopausal women were selected based on preestablished criteria. The true positive, false positive, false negative, and true negative values were extracted and meta-analysis was conducted using the hierarchical summary receiver operator characteristics curve method. The summary sensitivity of the GnRH analogue stimulation test is 10% (95% confidence interval [CI], 1.1%-46.7%) and that for selective venous sampling is 100% (95% CI, 0%-100%). Both tests have 100% specificity. There is limited evidence for the use of either test in identifying virilizing tumors in postmenopausal hyperandrogenism.

The debate on treating subclinical hypothyroidism.

Subclinical hypothyroidism (SCH) represents a mild or compensated form of primary hypothyroidism. The diagnosis of SCH is controversial, as its symptoms are non-specific and its biochemical diagnosis is arbitrary. The treatment of SCH was examined among non-pregnant adults, pregnant adults and children. In non-pregnant adults, treatment of SCH may prevent its progression to overt hypothyroidism, reduce the occurrence of coronary heart disease, and improve neuropsychiatric and musculoskeletal symptoms associated with hypothyroidism. These benefits are counteracted by cardiovascular, neuropsychiatric and musculoskeletal side effects. SCH is associated with adverse maternal and fetal outcomes that may improve with treatment. Treating SCH in children is safe and may improve growth. Importantly, the evidence in this field is largely from retrospective and prospective studies with design limitations, which precludes a conclusive recommendation for the treatment of SCH.

Kisspeptin signalling and its roles in humans.

Kisspeptins are a group of peptide fragments encoded by the KISS1 gene in humans. They bind to kisspeptin receptors with equal efficacy. Kisspeptins and their receptors are expressed by neurons in the arcuate and anteroventral periventricular nuclei of the hypothalamus. Oestrogen mediates negative feedback of gonadotrophin-releasing hormone secretion via the arcuate nucleus. Conversely, it exerts positive feedback via the anteroventral periventricular nucleus. The sexual dimorphism of these nuclei accounts for the differential behaviour of the hypothalamic-pituitary-gonadal axis between genders. Kisspeptins are essential for reproductive function. Puberty is regulated by the maturation of kisspeptin neurons and by interactions between kisspeptins and leptin. Hence, kisspeptins have potential diagnostic and therapeutic applications. Kisspeptin agonists may be used to localise lesions in cases of hypothalamic-pituitary-gonadal axis dysfunction and evaluate the gonadotrophic potential of subfertile individuals. Kisspeptin antagonists may be useful as contraceptives in women, through the prevention of premature luteinisation during in vitro fertilisation, and in the treatment of sex steroid-dependent diseases and metastatic cancers.