New-onset primary adrenal insufficiency in pregnancy associated with a unilateral adrenal infarction: a case report.

Summary: New-onset primary adrenal insufficiency is rare in pregnancy. The symptoms of adrenal insufficiency such as nausea, vomiting and dizziness may be attributed to the pregnancy itself, which can lead to a delay in the diagnosis. The presence of hypotension, hypoglycemia or hyperkalemia should raise the suspicion for adrenal insufficiency. We report the case of a 25-year-old woman who presented with tachycardia, left flank pain and vomiting at 36 weeks' gestation. She was found to have primary adrenal insufficiency and started on hydrocortisone and fludrocortisone with resolution of the vomiting and tachycardia. MRI of the abdomen revealed an acute nonhemorrhagic infarct of the left adrenal gland. The contralateral adrenal gland was normal. Autoimmune and infectious etiologies of primary adrenal insufficiency were ruled out and the adrenal insufficiency was attributed to the unilateral adrenal infarction. Adrenal insufficiency persisted after delivery and then resolved at approximately 16 months post partum. This case highlights the need to test women with unilateral adrenal infarction in pregnancy for the presence of primary adrenal insufficiency. Learning points: Adrenal insufficiency should be considered when a pregnant woman develops nausea, vomiting and dizziness in association with hypotension or hypoglycemia. Hypovolemic hyponatremia related to vomiting can occur in pregnancy, but the failure to correct hyponatremia despite adequate IV hydration should raise the suspicion for adrenal insufficiency. Adrenal infarction should be in the differential diagnosis for unilateral flank pain in pregnancy. Other common etiologies for flank pain in pregnancy include nephrolithiasis, pyelonephritis and acute cholecystitis. Unilateral adrenal infarction in pregnancy can lead to the development of primary adrenal insufficiency. Following delivery, these patients need to be monitored for the resolution of the adrenal insufficiency.

Ectopic Adrenocorticotropic Hormone-Producing Metastatic Gastrinoma: A Case Report.

Pancreatic neuroendocrine tumors secreting gastrin and adrenocorticotropic hormone (ACTH) are rare. The presentation of the cases can be varied, making the diagnosis challenging and often delayed. Here, we present a patient who presented with severe hypokalemia and was found to have ectopic Cushing's syndrome. An abdominal CT scan showed a pancreatic lesion with metastatic liver disease. A biopsy of the liver lesion confirmed a metastatic neuroendocrine tumor. The final diagnosis was ectopic ACTH-producing metastatic gastrinoma. Twenty-four-hour urinary cortisol was significantly elevated at 9,790 mcg/24 hours. The excess hormonal secretion was successfully treated with ketoconazole and somatostatin analogs. She was further started on chemotherapy with capecitabine plus temozolomide, which has become the preferred chemotherapy treatment after the results of the recently completed trial. She also received Y90 therapy for metastatic liver disease. The prognosis of metastatic pancreatic neuroendocrine tumors is poor. Multidisciplinary combined therapies can help control disease and improve prognosis. We present an 18-month-long patient follow-up and a literature review of ectopic ACTH-producing metastatic gastrinomas.

Bilateral pheochromocytoma: Clinical characteristics, treatment and longitudinal follow-up.

OBJECTIVE: Comprehensive data about patients with bilateral pheochromocytoma are limited. We aimed to describe the clinical presentation, genetic analysis, treatment and outcomes of patients with bilateral pheochromocytoma. DESIGN: A retrospective study at a tertiary care centre. PATIENTS: All patients with bilateral pheochromocytoma evaluated at Mayo Clinic in Rochester, Minnesota between January 1951 and December 2015. MEASUREMENTS: Tumour size, genetic testing, plasma/urine metanephrines and catecholamines. RESULTS: A total of 94 patients (51% women) were diagnosed with bilateral pheochromocytoma at a median age at first presentation of 31 years (range, 4-70). Bilateral disease was noted in 8.0% of pheochromocytoma patient overall and 37.5% of patients 18 years of younger. Most patients presented with synchronous tumours (80%). Median time to metachronous tumours was 4.5 years (range, 1-38). Genetic disease was identified in 75 (80%) patients, including MEN 2A (42.6%), VHL (19.1%), MEN 2B (9.6%) and NF1 (8.5%). Excess catecholamines were present in 97% of patients. Patients with synchronous pheochromocytoma commonly underwent simultaneous bilateral adrenalectomy (99%), and 18 (24%) had cortical-sparing surgery. Multicentric tumours were reported in 23 of 77 (30%) patients with available data. Recurrent disease was found in 9.6% of patients, and 8.5% developed metastatic disease. Median follow-up was 8.5 years. At the study conclusion, 4 patients had died due to pheochromocytoma or adrenalectomy. CONCLUSIONS: Bilateral pheochromocytoma occurred in 7.0% of adults with pheochromocytoma and 37.5% of paediatric patients. Genetic disease was identified in 80% of patients, predominantly MEN2A. Multicentric tumours were common, but most were still cured following adrenalectomy.

Documentation of hypoglycemia assessment among adults with diabetes during clinical encounters in primary care and endocrinology practices.

PURPOSE: To examine the proportion of diabetes-focused clinical encounters in primary care and endocrinology practices where the evaluation for hypoglycemia is documented; and when it is, identify clinicians' stated actions in response to patient-reported events. METHODS: A total of 470 diabetes-focused encounters among 283 patients nonpregnant adults (≥18 years) with type 1 or type 2 diabetes mellitus in this retrospective cohort study. Participants were randomly identified in blocks of treatment strategy and care location (95 and 52 primary care encounters among hypoglycemia-prone medications (i.e. insulin, sulfonylurea) and others patients, respectively; 94 and 42 endocrinology encounters among hypo-treated and others, respectively). Documentation of hypoglycemia and subsequent management plan in the electronic health record were evaluated. RESULTS: Overall, 132 (46.6%) patients had documentation of hypoglycemia assessment, significantly more prevalent among hypo-treated patients seen in endocrinology than in primary care (72.3% vs. 47.4%; P = 0.001). Hypoglycemia was identified by patient in 38.2% of encounters. Odds of hypoglycemia assessment documentation was highest among the hypo-treated (OR 13.6; 95% CI 5.5-33.74, vs. others) and patients seen in endocrine clinic (OR 4.48; 95% CI 2.3-8.6, vs. primary care). After documentation of hypoglycemia, treatment was modified in 30% primary care and 46% endocrine clinic encounters; P = 0.31. Few patients were referred to diabetes self-management education and support (DSMES). CONCLUSIONS: Continued efforts to improve hypoglycemia evaluation, documentation, and management are needed, particularly in primary care. This includes not only screening at-risk patients for hypoglycemia, but also modifying their treatment regimens and/or leveraging DSMES.

Assessment of The Bethesda System for Reporting Thyroid Cytopathology.

OBJECTIVES: Long-term follow-up is important for determining performance characteristics of thyroid fine-needle aspiration (FNA). METHODS: Histologic or 3 or more years of clinical follow-up was used to calculate performance characteristics of thyroid FNA before and after implementation of The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC). The impact of noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) classification was also investigated. RESULTS: Follow-up was obtained for 1,277/1,134 and 1,616/1,393 aspirates/patients (median clinical follow-up, 9.9 and 4.4 years, pre- and post-TBSRTC, respectively). Nondiagnostic, suspicious for follicular neoplasm, and suspicious for malignancy (SFM) diagnoses decreased and benign diagnoses increased post-TBSRTC, while atypical rate remained less than 1%. Negative predictive value for benign nodules and positive predictive value (PPV) for SFM increased significantly. Eleven nodules were reclassified as NIFTP, slightly decreasing PPV/risk of malignancy (ROM). CONCLUSIONS: Appropriate ROM for thyroid FNA can be achieved through application of TBSRTC terminology with minimal use of atypical category.

Cardiovascular and Metabolic Outcomes in Congenital Adrenal Hyperplasia: A Systematic Review and Meta-Analysis.

Background: Individuals with congenital adrenal hyperplasia (CAH) require glucocorticoid therapy to replace cortisol and to control androgen excess. We sought to evaluate the effects of glucocorticoid therapy on cardiovascular and metabolic outcomes in individuals with CAH. Methods: We searched bibliographical databases through January 2016 for studies evaluating cardiovascular risk factors in individuals with CAH treated with glucocorticoids compared with controls without CAH. We used a random-effects model to synthesize quantitative data. Results: We included 20 observational studies (14 longitudinal, six cross-sectional) with a moderate to high risk of bias. The average dose of glucocorticoids (in hydrocortisone equivalents) was 9 to 26.5 mg/m2/d. In the meta-analysis (416 patients), compared with controls without CAH, individuals with CAH had increased systolic blood pressure [weighted mean difference (WMD), 4.44 mm Hg; 95% CI, 3.26 to 5.63 mm Hg], diastolic blood pressure (WMD, 2.35 mm Hg; 95% CI, 0.49 to 4.20 mm Hg), homeostatic model assessment of insulin resistance (WMD, 0.49; 95% CI, 0.02 to 0.96), and carotid intima thickness (WMD, 0.08 mm; 95% CI, 0.01 to 0.15 mm). No statistically significant differences were noted in fasting blood glucose, insulin level, glucose, or insulin level after 2-hour glucose load or serum lipids. Data on cardiac events were sparse, and most of the literature focused on surrogate outcomes. Conclusion: Individuals with CAH demonstrate a high prevalence of cardiovascular and metabolic risk factors. The current evidence relies on surrogate outcomes. Long-term prospective studies are warranted to assess strategies for reducing cardiovascular risk in individuals with CAH.

Genital Reconstructive Surgery in Females With Congenital Adrenal Hyperplasia: A Systematic Review and Meta-Analysis.

Background: Females with congenital adrenal hyperplasia (CAH) and atypical genitalia often undergo complex surgeries; however, their outcomes remain largely uncertain. Methods: We searched several databases through 8 March 2016 for studies evaluating genital reconstructive surgery in females with CAH. Reviewers working independently and in duplicate selected and appraised the studies. Results: We included 29 observational studies (1178 patients, mean age at surgery, 2.7 ± 4.7 years; mostly classic CAH). After an average follow-up of 10.3 years, most patients who had undergone surgery had a female gender identity (88.7%) and were heterosexual (76.2%). Females who underwent surgery reported a sexual function score of 25.13 using the Female Sexual Function Index (maximum score, 36). Many patients continued to complain of substantial impairment of sensitivity in the clitoris, vaginal penetration difficulties, and low intercourse frequency. Most patients were sexually active, although only 48% reported comfortable intercourse. Most patients (79.4%) and treating health care professionals (71.8%) were satisfied with the surgical outcomes. Vaginal stenosis was common (27%), and other surgical complications, such as fistulas, urinary incontinence, and urinary tract infections, were less common. Data on quality of life were sparse and inconclusive. Conclusion: The long-term follow-up of females with CAH who had undergone urogenital reconstructive surgery shows variable sexual function. Most patients were sexually active and satisfied with the surgical outcomes; however, some patients still complained of impairment in sexual experience and satisfaction. The certainty in the available evidence is very low.

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.

Diagnosis of GH Deficiency as a Late Effect of Radiotherapy in Survivors of Childhood Cancers.

Background: Limited guidance exists for selecting a laboratory method for diagnosing GH deficiency (GHD) when it occurs as a late effect of radiotherapy in childhood cancer survivors (CCSs). Methods: We searched Medline, Embase, Cochrane Central Register of Controlled Trials and Database of Systematic Reviews, and Scopus for studies evaluating GHD that used IGF-1 or IGF-binding protein 3 (IGFBP-3) measurements compared with GH dynamic testing. Results: We included 15 studies [IGF-1 (8 studies) and IGFBP-3 (7 studies)] enrolling 477 patients. Comparator tests varied widely. Overall, both IGF-1 and IGFBP-3 had suboptimal diagnostic accuracy but were strongly correlated. The use of both tests simultaneously in the same cohort did not improve the diagnostic accuracy. Despite high variability in the testing protocols, dynamic tests remained the most accurate for appropriately identifying patients with GHD. The insulin tolerance test (ITT) appears to be the most accepted reference test when used alone or in combination with arginine; however, standardized testing strategies among practice groups are absent. GHRH and arginine stimulation performed almost similarly to the ITT; however, in one study GHRH with arginine stimulation had 66% sensitivity and 88% specificity compared with the ITT. Insufficient data were available to assess the accuracy of serial GH testing (nocturnal or over 24 hours). Conclusion: The diagnostic accuracy of various dynamic tests for GHD in CCSs appears to follow the same patterns as those in non-CCSs. Interpreting GHRH stimulation is a challenge given the primarily hypothalamic dysfunction in CCSs. IGF-1 and IGFBP-3 perform poorly in this population.

High Glucose Variability in Hospitalized Patients with Type 1 Diabetes Mellitus.

BACKGROUND: Glucose variability (GV) has been increasingly (or more extensively) studied in patients with type 1 diabetes (T1D) in the ambulatory setting; limited data exist on GV in hospitalized patients with T1D. MATERIALS AND METHODS: Retrospective single center cohort study, we analyzed in-hospital glucose measurements to assess GV in 736 hospitalized patients in different units over a consecutive 5-year period of time. GV was assessed by mean blood glucose (BG), Average daily risk range (ADRR), high BG index, and low BG index. To place our findings in context, we conducted a systematic review using Cochrane collaboration methodology to critically analyze current published literature on GV in hospitalized T1D patients. RESULTS: Overall, glycemic control was suboptimal with mean BG 183 ± 51.5 mg/dL and mean ADRR 35 with only 16% patients being categorized as low risk (ADRR <20) for hypo or hyperglycemia. Patients admitted in medical units had mean BG of 194.4 ± 42.8 mg/dL (95% CI = 101.2-346.6) and ADRR of 39.4 ± 16 (95% CI = 1.3-118.7), which were higher than the patients admitted in the surgical units (mean BG 168.1 ± 35.7 (95% CI = 74.8-301.8) and mean ADRR (28.8 ± 13.1 [95% CI = 0.3-93.1]). For the systematic review, initial search yielded 2336 studies for screening, however, none of them had data specific for T1D. CONCLUSION: GV is high in hospitalized T1D patients admitted at our tertiary care center. Review of the literature shows paucity of data regarding GV in hospitalized patients with T1D.

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

BACKGROUND: Systematic 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. METHODS: We 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. RESULTS: We 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. CONCLUSION: Up 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.

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.

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.

Real-time continuous glucose monitoring in type 1 diabetes: a systematic review and individual patient data meta-analysis.

BACKGROUND: Real-time continuous glucose monitoring (RTCGM) may help in the management of individuals with type 1 diabetes mellitus (T1DM); however, the evidence supporting its use is unclear. The available meta-analyses on this topic use aggregate data which weaken inference. OBJECTIVE: Individual patient data were obtained from randomized controlled trials (RCTs) to conduct a meta-analysis and synthesize evidence about the effect of RTCGM on glycosylated haemoglobin (HbA1c), hypoglycaemic events and time spent in hypoglycaemia in T1DM. METHODS: We searched MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials and Database of Systematic Reviews, and Scopus through January 2015. We included RCTs that enrolled individuals with T1DM and compared RTCGM vs control group. A two-step regression model was used to pool individual patient data. RESULTS: We included 11 RCTs at moderate risk of bias. Meta-analysis suggests that the use of RTCGM is associated with a statistically significant but modest reduction in HbA1c (-0·276; 95% confidence interval -0·465 to -0·087). The improvements in HbA1c were primarily seen in individuals over age 15 years. We were unable to identify a statistically significant difference in time spent in hypoglycaemia or the number of hypoglycaemic episodes although these analyses were imprecise and warrant lower confidence. There was no difference between males and females. CONCLUSION: RTCGM in T1DM is associated with a reduction in HbA1c primarily in individuals over 15 years of age. We were unable to identify a statistically significant difference in the time spent in hypoglycaemia or the incidence of hypoglycaemic episodes.

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

PURPOSE: Hypopituitarism is a rare disorder with significant morbidity. To study the evidence on the association of premature mortality and hypopituitarism. METHODS: 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 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. RESULTS: We 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), I 2 = 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. CONCLUSION: Hypopituitarism may be associated with premature mortality in adults. Risk is particularly higher in women and those diagnosed at a younger age.

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.

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.

Shared decision making in endocrinology: present and future directions.

In medicine and endocrinology, there are few clinical circumstances in which clinicians can accurately predict what is best for their patients. As a result, patients and clinicians frequently have to make decisions about which there is uncertainty. Uncertainty results from limitations in the research evidence, unclear patient preferences, or an inability to predict how treatments will fit into patients' daily lives. The work that patients and clinicians do together to address the patient's situation and engage in a deliberative dialogue about reasonable treatment options is often called shared decision making. Decision aids are evidence-based tools that facilitate this process. Shared decision making is a patient-centred approach in which clinicians share information about the benefits, harms, and burden of different reasonable diagnostic and treatment options, and patients explain what matters to them in view of their particular values, preferences, and personal context. Beyond the ethical argument in support of this approach, decision aids have been shown to improve patients' knowledge about the available options, accuracy of risk estimates, and decisional comfort. Decision aids also promote patient participation in the decision-making process. Despite accumulating evidence from clinical trials, policy support, and expert recommendations in endocrinology practice guidelines, shared decision making is still not routinely implemented in endocrine practice. Additional work is needed to enrich the number of available tools and to implement them in practice workflows. Also, although the evidence from randomised controlled trials favours the use of this shared decision making in other settings, populations, and illnesses, the effect of this approach has been studied in a few endocrine disorders. Future pragmatic trials are needed to explore the effect and feasibility of shared decision making implementation into routine endocrinology and primary care practice. With the available evidence, however, endocrinologists can now start to practice shared decision making, partner with their patients, and use their expertise to formulate treatment plans that reflect patient preferences and are more likely to fit into the context of patients' lives. In this Personal View, we describe shared decision making, the evidence behind the approach, and why and how both endocrinologists and their patients could benefit from this approach.

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.

Retraction Note: Thyroid nodules update in diagnosis and management.

[This retracts the article DOI: 10.1186/s40842-015-0011-7.].