Shrikant Tamhane

DIAGNOSIS OF ENDOCRINE DISEASE: The diagnostic performance of adrenal biopsy: a systematic review and meta-analysis

OBJECTIVE To perform a systematic review of published literature on adrenal biopsy and to assess its performance in diagnosing adrenal malignancy. METHODS Medline In-Process and Other Non-Indexed Citations, MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trial were searched from inception to February 2016. Reviewers extracted data and assessed methodological quality in duplicate. RESULTS We included 32 observational studies reporting on 2174 patients (39.4% women, mean age 59.8 years) undergoing 2190 adrenal mass biopsy procedures. Pathology was described in 1621/2190 adrenal lesions (689 metastases, 68 adrenocortical carcinomas, 64 other malignancies, 464 adenomas, 226 other benign, 36 pheochromocytomas, and 74 others). The pooled non-diagnostic rate (30 studies, 2013 adrenal biopsies) was 8.7% (95%CI: 6-11%). The pooled complication rate (25 studies, 1339 biopsies) was 2.5% (95%CI: 1.5-3.4%). Studies were at a moderate risk for bias. Most limitations related to patient selection, assessment of outcome, and adequacy of follow-up. Only eight studies (240 patients) could be included in the diagnostic performance analysis with a sensitivity and specificity of 87 and 100% for malignancy, 70 and 98% for adrenocortical carcinoma, and 87 and 96% for metastasis respectively. CONCLUSIONS Evidence based on small sample size and moderate risk of bias suggests that adrenal biopsy appears to be most useful in the diagnosis of adrenal metastasis in patients with a history of extra-adrenal malignancy. Adrenal biopsy should only be performed if the expected findings are likely to alter the management of the individual patient and after biochemical exclusion of catecholamine-producing tumors to help prevent potentially life-threatening complications.

Continuous subcutaneous insulin infusion versus multiple daily injections in individuals with type 1 diabetes: a systematic review and meta-analysis

The relative efficacy of continuous subcutaneous insulin infusion and multiple daily injections in individuals with type 1 diabetes is unclear. We sought to synthesize the existing evidence about the effect of continuous subcutaneous insulin infusion on glycosylated hemoglobin, hypoglycemic events, and time spent in hypoglycemia compared to multiple daily injections. We searched MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials and Database of Systematic Reviews, and Scopus from January 2008 through November 2015 for randomized controlled trials that enrolled children or adults with type 1 diabetes. Trials identified in a previous systematic review and published prior to 2008 were also included. We included 25 randomized controlled trials at moderate risk of bias. Meta-analysis showed a significant reduction in glycosylated hemoglobin in patients treated with continuous subcutaneous insulin infusion compared to multiple daily injections (mean difference 0.37; 95 % confidence interval, 0.24–0.51). This effect was demonstrated in both children and adults. There was no significant difference in minor or severe hypoglycemic events. Continuous subcutaneous insulin infusion was associated with lower incidence of nocturnal hypoglycemia. There was no significant difference in the time spent in hypoglycemia. In children and adults with type 1 diabetes and compared to multiple daily injections, continuous subcutaneous insulin infusion is associated with a modest reduction in glycosylated hemoglobin. There was no difference in severe or minor hypoglycemia, but likely a lower incidence of nocturnal hypoglycemia with continuous subcutaneous insulin infusion.

Shared Decision-Making in Diabetes Care.

Shared decision-making (SDM) is a collaborative process by which patients and clinicians work together in a deliberative dialogue. The purpose of this dialogue is to identify reasonable management options that best fit and addresses the unique situation of the patient. SDM supports the patient-centered translation of research into practice. SDM also helps implement a core principle of evidence-based medicine: evidence is necessary but never sufficient to make a clinical decision, as consideration of patient values and context is also required. SDM conversations build on a partnership between the patient and the clinician, draw on the body of evidence with regard to the different treatment options, and consider options in light of the values, preferences, and context of the patient. SDM is appropriate for diabetes care because diabetes care often requires consideration of management options that differ in ways that matter to patients, such as the way in which they place significant demands on patient’s life and living. In the last decade, SDM has proven feasible and useful for sharing evidence with patients and for involving patients in making decisions with their clinicians. Health care and clinical policies advocate SDM, but these policies have yet to impact diabetes care. In this paper, we describe what SDM is, its known impact on diabetes care, and needed work to implement this patient-centered approach in the care of the millions of patients with diabetes.

Shared decision-making in the care of individuals with diabetes

People with diabetes often live with other chronic conditions and lead complicated lives. Determining what is the best management decision for a patient requires consideration of each individuals personal, social and biomedical context, what he or she values, the reasons he or she has to value the available options, and the relative contribution of each option in terms of benefits, harms, costs and inconveniences. Empathic conversations between patients and clinicians to diagnose the patient situation that necessitates action and the range of evidence‐based actions that best address the situation, so‐called shared decision‐making, are essential to the personalized care of people with diabetes. The aim of the present review was to present key elements of shared decision‐making and propose three different approaches for its application. The first approach focuses on transferring information to patients so that they can make decisions. The second approach, choice, focuses on cultivating the individuals ability to give voice to which choice is best for them. The third approach, conversation, establishes an empathic conversational environment through which the individual with diabetes and their clinician think and talk through how to address the problems of living with diabetes and related illnesses. These approaches are manifest in the design of evidence‐based decision aids created to support shared decision‐making. In randomized trials, decision aids can efficiently improve patients knowledge, satisfaction, risk awareness, decisional conflict and involvement. Further research, however, is needed to better understand when and how to promote the empathic conversations, patient, clinician and service and policy contexts necessary to routinely implement shared decision‐making in different at scale healthcare systems. In the interim, sufficient evidence and tools exist for persons with diabetes and their clinicians to gain expertise in making decisions together.

Malignant Pheochromocytoma and Paraganglioma: 272 Patients Over 55 Years

Context: Malignant pheochromocytoma (PHEO) and paraganglioma (PGL) are rare and knowledge of the natural history is limited. Objective: We aimed to describe baseline characteristics and outcomes of patients with malignant PHEO and PGL (PPGL) and to identify predictors of shorter survival. Design: Retrospective review of patients with malignant PPGL evaluated from 1960 to 2016. Setting: Referral center. Patients: The group comprised 272 patients. Main Outcome Measures: Baseline description, survival outcomes, and predictors of shorter survival were evaluated in patients with rapidly progressive (n = 29) and indolent disease (n = 188). Results: Malignant PPGL was diagnosed at a median age of 39 years (range, 7 to 83 years), with synchronous metastases in 96 (35%) patients. In 176 (65%) patients, metastases developed at a median of 5.5 years (range, 0.3 to 53.4 years) from the initial diagnosis. Median follow‐up was 8.2 years (range, 0.01 to 54.1 years). Median overall and disease‐specific survivals were 24.6 and 33.7 years, respectively. Shorter survival correlated with male sex (P = 0.014), older age at the time of primary tumor (P = 0.0011), synchronous metastases (P < 0.0001), larger primary tumor size (P = 0.0039), elevated dopamine (P = 0.0195), and not undergoing primary tumor resection (P < 0.0001). There was no difference in the type of primary tumor or presence of SDHB mutation. Conclusions: The clinical course of patients with malignant PPGL is remarkably variable. Rapid disease progression is associated with male sex, older age at diagnosis, synchronous metastases, larger tumor size, elevated dopamine, and not undergoing resection of primary tumor. An individualized approach to patients with metastatic PPGL is warranted.

Mortality in adults with hypopituitarism: a systematic review and meta-analysis

PurposeHypopituitarism is a rare disorder with significant morbidity. To study the evidence on the association of premature mortality and hypopituitarism.MethodsA comprehensive search of multiple databases: MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and Scopus was conducted through August, 2015. Eligible studies that evaluated patients with hypopituitarism and reported mortality estimates were selected following a predefined protocol. Reviewers, independently and in duplicate, extracted data and assessed the risk of bias.ResultsWe included 12 studies (published 1996–2015) that reported on 23,515 patients. Compared to the general population, hypopituitarism was associated with an overall excess mortality (weighted SMR of 1.55; 95 % CI 1.14−2.11), I2 = 97.8 %, P = 0.000. Risk factors for increased mortality included younger age at diagnosis, female gender, diagnosis of craniopharyngioma, radiation therapy, transcranial surgery, diabetes insipidus and hypogonadism.ConclusionHypopituitarism may be associated with premature mortality in adults. Risk is particularly higher in women and those diagnosed at a younger age.

Thyroid nodule update on diagnosis and management

Thyroid nodules are common. The clinical importance of thyroid nodules is related to excluding malignancy (4.0 to 6.5% of all thyroid nodules), evaluate their functional status and assess for the presence of pressure symptoms. Incidental thyroid nodules are being diagnosed with increasing frequency in the recent years with the use of newer and highly sensitive imaging techniques. The high prevalence of thyroid nodules necessitates that the clinicians use evidence-based approaches for their assessment and management. New molecular tests have been developed to help with evaluation of malignancy in thyroid nodules. This review addresses advances in thyroid nodule evaluation, and their management considering the current guidelines and supporting evidence.

The effect of growth hormone replacement in patients with hypopituitarism on pituitary tumor recurrence, secondary cancer, and stroke

Growth hormone replacement therapy has benefits for patients with hypopituitarism. The safety profile in regard to tumor recurrence or progression, development of secondary malignancies, or cerebrovascular stroke is still an area of debate. A comprehensive search of multiple databases—MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and Scopus was conducted through August 2015. Eligible studies that evaluated long-term adverse events in adult patients with hypopituitarism treated with growth hormone replacement therapy and reported development of pituitary tumor recurrence or progression, secondary malignancies, or cerebrovascular stroke were selected following a predefined protocol. Reviewers, independently and in duplicate, extracted data and assessed the risk of bias. Random-effects meta-analysis was used to pool relative risks and 95 % confidence intervals. We included 15 studies (published 1995–2015) that reported on 46,148 patients. Compared to non-replacement, growth hormone replacement therapy in adults with hypopituitarism was not associated with statistically significant change in pituitary tumor progression or recurrence (relative risk, 0.77; 95 % confidence interval, 0.53–1.13) or development of secondary malignancy (relative risk, 0.99; 95 % confidence interval, 0.70–1.39). In two retrospective studies, there was higher risk of stroke in patients who did not receive replacement (relative risk, 2.07; 95 % confidence interval, 1.51–2.83). The quality of evidence is low due to study limitations and imprecision. This systematic review and meta-analysis supports the overall safety of growth hormone therapeutic use in adults with hypopituitarism with no clear evidence of increased risk of pituitary tumor recurrence, malignancy, or stroke.

GH Therapy in Childhood Cancer Survivors: A Systematic Review and Meta-Analysis

Background GH deficiency (GHD) is common among childhood cancer survivors (CCSs) with history of tumors, surgery, and/or radiotherapy involving the hypothalamus-pituitary region. We aimed to evaluate the effects of GH therapy (GHT) in CCSs on adult height, risk of diabetes mellitus, abnormal lipids, metabolic syndrome, quality of life, secondary tumors, and disease recurrence. Methods We searched multiple databases for randomized and observational studies. Pairs of reviewers independently selected studies and collected data. Random effects meta-analysis was used to pool outcomes across the studies. Results We included 29 observational studies at moderate to high risk of bias. Sixteen studies compared CCSs on GHT with those not on GHT (512 patients, GH dose: 0.3 to 0.9 IU/kg/week). GHT was significantly associated with height gain [standard deviation score, 0.61; 95% CI, 0.08 to 1.13] and was not significantly associated with the occurrence of secondary tumors [odds ratio (OR), 1.10; 95% CI, 0.72 to 1.67] or tumor recurrence (OR, 0.57; 95% CI, 0.31 to 1.02). Thirteen studies compared CCSs on GHT with normal age- or sex-matched controls or controls with idiopathic GHD or short stature. GHT was associated with either improved or unchanged risk of diabetes, lipid profiles, and metabolic syndrome. GHT was associated with improvements in quality of life. Conclusion CCSs treated with GHT gain height compared with the untreated controls. GHT may improve lipid profiles and quality of life and does not appear to increase the risk of diabetes or the development of secondary tumors, although close monitoring for such complications remains warranted due to uncertainty in the current evidence.

Systematic reviews of diagnostic tests in endocrinology: an audit of methods, reporting, and performance

BackgroundSystematic reviews provide clinicians and policymakers estimates of diagnostic test accuracy and their usefulness in clinical practice. We identified all available systematic reviews of diagnosis in endocrinology, summarized the diagnostic accuracy of the tests included, and assessed the credibility and clinical usefulness of the methods and reporting.MethodsWe searched Ovid MEDLINE, EMBASE, and Cochrane CENTRAL from inception to December 2015 for systematic reviews and meta-analyses reporting accuracy measures of diagnostic tests in endocrinology. Experienced reviewers independently screened for eligible studies and collected data. We summarized the results, methods, and reporting of the reviews. We performed subgroup analyses to categorize diagnostic tests as most useful based on their accuracy.ResultsWe identified 84 systematic reviews; half of the tests included were classified as helpful when positive, one-fourth as helpful when negative. Most authors adequately reported how studies were identified and selected and how their trustworthiness (risk of bias) was judged. Only one in three reviews, however, reported an overall judgment about trustworthiness and one in five reported using adequate meta-analytic methods. One in four reported contacting authors for further information and about half included only patients with diagnostic uncertainty.ConclusionUp to half of the diagnostic endocrine tests in which the likelihood ratio was calculated or provided are likely to be helpful in practice when positive as are one-quarter when negative. Most diagnostic systematic reviews in endocrine lack methodological rigor, protection against bias, and offer limited credibility. Substantial efforts, therefore, seem necessary to improve the quality of diagnostic systematic reviews in endocrinology.