Naykky Singh Ospina

ACTH Stimulation Tests for the Diagnosis of Adrenal Insufficiency: Systematic Review and Meta-Analysis

CONTEXT The diagnosis of adrenal insufficiency is clinically challenging and often requires ACTH stimulation tests. OBJECTIVE To determine the diagnostic accuracy of the high- (250 mcg) and low- (1 mcg) dose ACTH stimulation tests in the diagnosis of adrenal insufficiency. METHODS We searched six databases through February 2014. Pairs of independent reviewers selected studies and appraised the risk of bias. Diagnostic association measures were pooled across studies using a bivariate model. DATA SYNTHESIS For secondary adrenal insufficiency, we included 30 studies enrolling 1209 adults and 228 children. High- and low-dose ACTH stimulation tests had similar diagnostic accuracy in adults and children using different peak serum cortisol cutoffs. In general, both tests had low sensitivity and high specificity resulting in reasonable likelihood ratios for a positive test (adults: high dose, 9.1; low dose, 5.9; children: high dose, 43.5; low dose, 7.7), but a fairly suboptimal likelihood ratio for a negative test (adults: high dose, 0.39; low dose, 0.19; children: high dose, 0.65; low dose, 0.34). For primary adrenal insufficiency, we included five studies enrolling 100 patients. Data were only available to estimate the sensitivity of high dose ACTH stimulation test (92%; 95% confidence interval, 81-97%). CONCLUSION Both high- and low-dose ACTH stimulation tests had similar diagnostic accuracy. Both tests are adequate to rule in, but not rule out, secondary adrenal insufficiency. Our confidence in these estimates is low to moderate because of the likely risk of bias, heterogeneity, and imprecision.

Thyroid hormone treatment among pregnant women with subclinical hypothyroidism: US national assessment

Objective To estimate the effectiveness and safety of thyroid hormone treatment among pregnant women with subclinical hypothyroidism. Design Retrospective cohort study. Setting Large US administrative database between 1 January 2010 and 31 December 2014. Participants 5405 pregnant women with subclinical hypothyroidism, defined as untreated thyroid stimulating hormone (TSH) concentration 2.5-10 mIU/L. Exposure Thyroid hormone therapy. Main outcome measure Pregnancy loss and other pre-specified maternal and fetal pregnancy related adverse outcomes. Results Among 5405 pregnant women with subclinical hypothyroidism, 843 with a mean pre-treatment TSH concentration of 4.8 (SD 1.7) mIU/L were treated with thyroid hormone and 4562 with a mean baseline TSH concentration of 3.3 (SD 0.9) mIU/L were not treated (P<0.01). Pregnancy loss was significantly less common among treated women (n=89; 10.6%) than among untreated women (n=614; 13.5%) (P<0.01). Compared with the untreated group, treated women had lower adjusted odds of pregnancy loss (odds ratio 0.62, 95% confidence interval 0.48 to 0.82) but higher odds of preterm delivery (1.60, 1.14 to 2.24), gestational diabetes (1.37, 1.05 to 1.79), and pre-eclampsia (1.61, 1.10 to 2.37); other pregnancy related adverse outcomes were similar between the two groups. The adjusted odds of pregnancy loss were lower in treated women than in untreated women if their pre-treatment TSH concentration was 4.1-10 mIU/L (odds ratio 0.45, 0.30 to 0.65) but not if it was 2.5-4.0 mIU/L (0.91, 0.65 to 1.23) (P<0.01). Conclusion Thyroid hormone treatment was associated with decreased risk of pregnancy loss among women with subclinical hypothyroidism, especially those with pre-treatment TSH concentrations of 4.1-10 mIU/L. However, the increased risk of other pregnancy related adverse outcomes calls for additional studies evaluating the safety of thyroid hormone treatment in this patient population.

Hypoglycemia as an indicator of good diabetes care

Rene Rodriguez-Gutierrez and colleagues argue that more attention should be paid to hypoglycemia when assessing management of diabetes

Safety and Efficacy of Percutaneous Parathyroid Ethanol Ablation in Patients with Recurrent Primary Hyperparathyroidism and Multiple Endocrine Neoplasia Type 1

CONTEXT The most common feature of multiple endocrine neoplasia type 1 (MEN1) is primary hyperparathyroidism (PHP), which occurs in approximately 95% of MEN1 patients. Approximately 40-60% of patients with MEN1 develop recurrent hypercalcemia within 10-12 years after their initial parathyroid surgery and the successful management of recurrent PHP is challenging. OBJECTIVE This study sought to evaluate the safety and efficacy of percutaneous ethanol ablation (PEA) for the treatment of recurrent PHP in patients with MEN1. DESIGN, SETTING, PATIENTS, INTERVENTION, OUTCOME MEASURED: We performed an electronic search to identify patients with a billing code for MEN1 who were seen at Mayo Clinic between 1977 and 2013. Patients with recurrent PHP who underwent PEA were identified and their clinical information was collected. We performed t test analyses to compare mean values. RESULTS Thirty-seven patients underwent 80 PEA treatments that included 123 sessions of ethanol administration. Twenty-one patients were women (56.8%) and the mean age at diagnosis of PHP was 33.8 years. The mean preprocedure calcium level was 10.7 mg/dl ± 0.57 (SD) and the mean postprocedure calcium level was 9.6 mg/dl ± 0.76 (P < .01). In 14 treatments (18.9%) the postprocedure calcium was greater than 10.1 mg/dl. Postprocedure hypocalcemia occurred in six treatments (8.1%). Normocalcemia was achieved in 54 of the treatment episodes (73%) and the mean duration of normocalcemia was 24.8 months. PEA was safe with transient hoarseness occurring in four of the treatments (5%). CONCLUSION The treatment of recurrent PHP in patients with MEN1 represents a challenge that is associated with increased morbidity. PEA is an effective treatment option for achieving normocalcemia in the majority of the patients with MEN1. PEA is associated with low rates of hypocalcemia and no permanent complications.

Prevalence of parathyroid carcinoma in 348 patients with multiple endocrine neoplasia type 1 - case report and review of the literature.

To report the prevalence of parathyroid carcinoma (PC) in patients with multiple endocrine neoplasia type 1 (MEN1) and review of the literature.

Sex Steroids and Cardiovascular Outcomes in Transgender Individuals: A Systematic Review and Meta-Analysis

Background: Transgender individuals receive cross‐sex hormonal therapy to induce desired secondary sexual characteristics despite limited data regarding its effects on cardiovascular health. Methods: A comprehensive search of several databases up to 7 April 2015 was conducted for studies evaluating the effect of sex steroid use on lipids, myocardial infarction, stroke, venous thromboembolism (VTE), and mortality in transgender individuals. Pairs of reviewers selected and appraised the studies. A random‐effects model was used to pool weighted mean differences and 95% confidence intervals (CIs). Results: We found 29 eligible studies with moderate risk of bias. In female‐to‐male (FTM) individuals, sex steroid therapy was associated with statistically significant increases in serum triglyceride (TG) levels at 3 to 6 months and at ≥24 months (21.4 mg/dL; 95% CI: 0.14 to 42.6) and in low‐density lipoprotein cholesterol (LDL‐C) levels at 12 months and ≥24 months (17.8 mg/dL; 95% CI: 3.5 to 32.1). High‐density lipoprotein cholesterol (HDL‐C) levels decreased significantly across all follow‐up periods (highest at ≥24 months, −8.5 mg/dL; 95% CI: −13.0 to −3.9). In male‐to‐female (MTF) individuals, serum TG levels were significantly higher at ≥24 months (31.9 mg/dL; 95% CI: 3.9 to 59.9) without any changes in other parameters. Few myocardial infarction, stroke, VTE, and death events were reported (more frequently in MTF individuals). Conclusions: Low‐quality evidence suggests that sex steroid therapy may increase LDL‐C and TG levels and decrease HDL‐C level in FTM individuals, whereas oral estrogens may increase TG levels in MTF individuals. Data about important patient outcomes remain sparse.

Inclusion of Hypoglycemia in Clinical Practice Guidelines and Performance Measures in the Care of Patients With Diabetes

HEALTH CARE POLICY AND LAW Inclusion of Hypoglycemia in Clinical Practice Guidelines and Performance Measures in the Care of Patients With Diabetes Health care organizations use publicly reported performance measures for quality measurement and improvement and payfor-performance initiatives.1 These measures should ideally promote high-quality care that is evidence based and congruent with clinical practice guidelines. However, they should also reward patient-centered care that yields optimal outcomes with the lowest risk of harm.2 For patients with both type 1 and type 2 diabetes, high-quality care should therefore minimize the risk of hypoglycemia.2 The degree to which existing performance measures are aligned with guidelines, particularly in regard to hypoglycemia avoidance, is uncertain. We therefore conducted an environmental scan to assess the inclusion and prioritization of hypoglycemia in contemporary clinical guidelines and performance measures for patients with diabetes.

PREDICTORS OF BIOCHEMICAL REMISSION AND RECURRENCE AFTER SURGICAL AND RADIATION TREATMENTS OF CUSHING DISEASE: A SYSTEMATIC REVIEW AND META-ANALYSIS.

OBJECTIVE We conducted a systematic review and meta-analysis to synthesize the evidence about predictors that may affect biochemical remission and recurrence after transsphenoidal surgery (TSS), radiosurgery (RS), and radiotherapy (RT) in Cushing disease. METHODS We searched multiple databases through December 2014 including original controlled and uncontrolled studies that enrolled patients with Cushing disease who received TSS (first-line), RS, or RT. We extracted data independently, in duplicates. Outcomes of interest were biochemical remission and recurrence. A meta-analysis was conducted using the random-effects model to estimate event rates with 95% confidence intervals (CIs). RESULTS First-line TSS was associated with high remission (76% [95% CI, 72 to 79%]) and low recurrence rates (10% [95% CI, 6 to 16%]). Remission after TSS was higher in patients with microadenomas or positive-adrenocorticotropic hormone tumor histology. RT was associated with a high remission rate (RS, 68% [95% CI, 61 to 77%]; RT, 66% [95% CI, 58 to 75%]) but also with a high recurrence rate (RS, 32% [95% CI, 16 to 60%]; RT, 26% [95% CI, 14 to 48%]). Remission after RS was higher at short-term follow-up (≤2 years) and with high-dose radiation, while recurrence was higher in women and with lower-dose radiation. Remission was after RT in adults who received TSS prior to RT, and with lower radiation doses. There was heterogeneity (nonstandardization) in the criteria and cutoff points used to define biochemical remission and recurrence. CONCLUSION First-line TSS is associated with high remission and low recurrence, while RS and RT are associated with reasonable remission rates but important recurrence rates. The current evidence warrants low confidence due to the noncomparative nature of the studies, high heterogeneity, and imprecision.

Diagnostic accuracy of thyroid nodule growth to predict malignancy in thyroid nodules with benign cytology: Systematic review and meta-analysis

Thyroid ultrasound to assess for nodular growth is commonly performed during the follow‐up of patients with benign thyroid nodules, with the goal of identifying patients with a missed diagnosis of thyroid cancer. The objective of this study was to summarize the evidence regarding the diagnostic accuracy of growth during follow‐up of benign thyroid nodules for thyroid cancer.

Is the endocrine research pipeline broken? A systematic evaluation of the Endocrine Society clinical practice guidelines and trial registration

BackgroundVery low quality (VLQ) evidence translates into very low confidence in the balance of risk and benefits based on the estimates drawn from the body of evidence. Consequently, this assessment highlights gaps in the research evidence, i.e. knowledge gaps, for important clinical questions. In this way, expert guideline panels identify priority knowledge gaps that, arguably, should inform the research agenda and prioritize scarce research economical resources. The extent to which the research agenda reflects the knowledge gaps identified in clinical practice guidelines is unknown.MethodsA systematic evaluation of the Endocrine Society (ES) clinical practice guidelines portfolio from 2008 to 2014 was conducted with the objectives to identify (1) recommendations in the ES clinical practice guidelines based on VLQ evidence reflecting knowledge gaps in endocrinology, and (2) active research designed to address these gaps by searching the clinical trial registry, clinicaltrials.gov, using terms describing patients (diseases), interventions, comparison, and outcomes.ResultsIn 25 ES guidelines, we found 660 recommendations, of which 131 (20 %) were supported by VLQ evidence. Clinical trialists are attempting to answer 28 (21 %) of these knowledge gaps by performing 69 clinical trials.ConclusionThe research enterprise is addressing one in five knowledge gaps identified in clinical practice recommendations in endocrinology. These findings suggest an inefficiency in the allocation of very scarce research economical resources. Linking the research agenda to evidence gaps in clinical practice guidelines may improve both the efficiency of the research enterprise and the translation of evidence into more confident clinical practice.