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The accuracy of diagnostic tests for GH deficiency in adults: a systematic review and meta-analysis

Ahmad Hazem, Mohamed B Elamin, German Malaga, Irina Bancos, Yolanda Prevost, Claudia Zeballos-Palacios, Edgar R Velasquez, Patricia J Erwin, Neena Natt, Victor M Montori, and Mohammad Hassan Murad

Context

The diagnostic accuracy of tests used to diagnose GH deficiency (GHD) in adults is unclear.

Objective

We conducted a systematic review and meta-analysis of studies that provided data on the available diagnostic tests.

Data sources

We searched electronic databases (MEDLINE, EMBASE, Cochrane CENTRAL, Web of Sciences, and Scopus) through April 2011.

Study selection

Review of reference lists and contact with experts identified additional candidate studies. Reviewers, working independently and in duplicate, determined study eligibility.

Data extraction

Reviewers, working independently and in duplicate, determined the methodological quality of studies and collected descriptive, quality, and outcome data.

Data synthesis

Twenty-three studies provided diagnostic accuracy data; none provided patient outcome data. Studies had fair methodological quality, used several reference standards, and included over 1100 patients. Several tests based on direct or indirect stimulation of GH release were associated with good diagnostic accuracy, although most were assessed in one or two studies decreasing the strength of inference due to small sample size. Serum levels of GH or IGF1 had low diagnostic accuracy. Pooled sensitivity and specificity of the two most commonly used stimulation tests were found to be 95 and 89% for the insulin tolerance test and 73 and 81% for the GHRH+arginine test respectively. Meta-analytic estimates for accuracy were associated with substantial heterogeneity.

Conclusion

Several tests with reasonable diagnostic accuracy are available for the diagnosis of GHD in adults. The supporting evidence, however, is at high risk of bias (due to heterogeneity, methodological limitations, and imprecision).

Free access

THERAPY OF ENDOCRINE DISEASE: Improvement of cardiovascular risk factors after adrenalectomy in patients with adrenal tumors and subclinical Cushing’s syndrome: a systematic review and meta-analysis

Irina Bancos, Fares Alahdab, Rachel K Crowley, Vasileios Chortis, Danae A Delivanis, Dana Erickson, Neena Natt, Massimo Terzolo, Wiebke Arlt, William F Young Jr, and M Hassan Murad

Objective

Beneficial effects of adrenalectomy on cardiovascular risk factors in patients with subclinical Cushing’s syndrome (SCS) are uncertain. We sought to conduct a systematic review and meta-analysis with the following objectives: (i) determine the effect of adrenalectomy compared with conservative management on cardiovascular risk factors in patients with SCS and (ii) compare the effect of adrenalectomy on cardiovascular risk factors in patients with SCS vs those with a nonfunctioning (NF) adrenal tumor.

Methods

MEDLINE In-Process & Other Non-Indexed Citations, MEDLINE, EMBASE and Cochrane Central Register of Controlled Trial were searched on 17 November 2015. Reviewers extracted data and assessed methodological quality in duplicate.

Results

We included 26 studies reporting on 584 patients with SCS and 457 patients with NF adrenal tumors. Studies used different definitions of SCS. Patients with SCS undergoing adrenalectomy demonstrated an overall improvement in cardiovascular risk factors (61% for hypertension, 52% for diabetes mellitus, 45% for obesity and 24% for dyslipidemia). When compared with conservative management, patients with SCS undergoing adrenalectomy experienced improvement in hypertension (RR 11, 95% CI: 4.3–27.8) and diabetes mellitus (RR 3.9, 95% CI: 1.5–9.9), but not dyslipidemia (RR 2.6, 95% CI: 0.97–7.2) or obesity (RR 3.4, 95% CI: 0.95–12). Patients with NF adrenal tumors experienced improvement in hypertension (21/54 patients); however, insufficient data exist for comparison to patients with SCS.

Conclusions

Available low-to-moderate-quality evidence from heterogeneous studies suggests a beneficial effect of adrenalectomy on cardiovascular risk factors in patients with SCS overall and compared with conservative management.

Free access

THERAPY IN ENDOCRINE DISEASE: Body composition and quality of life in adults treated with GH therapy: a systematic review and meta-analysis

Ahmad Hazem, Mohamed B Elamin, Irina Bancos, German Malaga, Gabriela Prutsky, Juan Pablo Domecq, Tarig A Elraiyah, Nisrin O Abu Elnour, Yolanda Prevost, Jaime P Almandoz, Claudia Zeballos-Palacios, Edgar R Velasquez, Patricia J Erwin, Neena Natt, Victor M Montori, and Mohammad Hassan Murad

Objective

To summarise the evidence about the efficacy and safety of using GH in adults with GH deficiency focusing on quality of life and body composition.

Data sources

We searched MEDLINE, EMBASE, Cochrane CENTRAL, Web of Science and Scopus through April 2011. We also reviewed reference lists and contacted experts to identify candidate studies.

Study selection

Reviewers, working independently and in duplicate, selected randomised controlled trials (RCTs) that compared GH to placebo.

Data synthesis

We pooled the relative risk (RR) and weighted mean difference (WMD) by the random effects model and assessed heterogeneity using the I 2 statistic.

Results

Fifty-four RCTs were included enrolling over 3400 patients. The quality of the included trials was fair. GH use was associated with statistically significant reduction in weight (WMD, 95% confidence interval (95% CI): −2.31 kg, −2.66 and −1.96) and body fat content (WMD, 95% CI: −2.56 kg, −2.97 and −2.16); increase in lean body mass (WMD, 95% CI: 1.38, 1.10 and 1.65), the risk of oedema (RR, 95% CI: 6.07, 4.34 and 8.48) and joint stiffness (RR, 95% CI: 4.17, 1.4 and 12.38); without significant changes in body mass index, bone mineral density or other adverse effects. Quality of life measures improved in 11 of the 16 trials although meta-analysis was not feasible.

Results

GH therapy in adults with confirmed GH deficiency reduces weight and body fat, increases lean body mass and increases oedema and joint stiffness. Most trials demonstrated improvement in quality of life measures.