The robustness of diagnostic tests for GH deficiency in adults

Andersen, Marianne

doi:10.1016/j.ghir.2015.03.001

Cited by 14 publications

(11 citation statements)

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“…The variation in reported prevalence of hypopituitarism and GHD in the literature is most likely reflective of the heterogeneous endocrine tests used to diagnose hormonal deficiency, different time points of endocrine assessment and varying thresholds for defining GHD [ 23 , 31 , 32 ]. Indeed, several of previous studies relied solely on low serum IGF-1 concentrations to diagnose GHD [ 13 , 15 , 33 , 34 ], in spite of its limited diagnostic accuracy [ 35 – 37 ]. Additionally, even though isolated GHD is consistently reported as the most common deficiency post SAH, few studies confirm this with a second dynamic test [ 19 – 21 ].…”

Section: Discussionmentioning

confidence: 99%

“…Even other stimulatory tests, such as the insulin tolerance test (ITT) and growth hormone releasing hormone (GHRH)-arginine stimulation test, show that GH response is BMI dependent [ 44 , 45 ]. It has even been suggested that waist circumference corrected cut-offs for GH peaks should be established [ 37 ] given that serum GH levels correlate inversely with WHR and abdominal fat in adults with no pituitary disease [ 46 ]. Diagnosing GHD in the presence of obesity can therefore be very challenging, and an appreciation of this is vital to ensure that results are interpreted with caution.…”

Section: Discussionmentioning

confidence: 99%

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The prevalence of growth hormone deficiency in survivors of subarachnoid haemorrhage: results from a large single centre study

et al. 2017

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ObjectiveThe variation in reported prevalence of growth hormone deficiency (GHD) post subarachnoid haemorrhage (SAH) is mainly due to methodological heterogeneity. We report on the prevalence of GHD in a large cohort of patients following SAH, when dynamic and confirmatory pituitary hormone testing methods are systematically employed.DesignIn this cross-sectional study, pituitary function was assessed in 100 patients following SAH. Baseline pituitary hormonal profile measurement and glucagon stimulation testing (GST) was carried out in all patients. Isolated GHD was confirmed with an Arginine stimulation test and ACTH deficiency was confirmed with a short synacthen test.ResultsThe prevalence of hypopituitarism in our cohort was 19% and the prevalence of GHD was 14%. There was no association between GHD and the clinical or radiological severity of SAH at presentation, treatment modality, age, or occurrence of vasospasm. There were statistically significant differences in terms of Glasgow Outcome Scale (GOS; p = 0.03) between patients diagnosed with GHD and those without. Significant inverse correlations between GH peak on GST with body mass index (BMI) and waist hip ratio (WHR) was also noted (p < 0.0001 and p < 0.0001 respectively).ConclusionUsing the current testing protocol, the prevalence of GHD detected in our cohort was 14%. It is unclear if the BMI and WHR difference observed is truly due to GHD or confounded by the endocrine tests used in this protocol. There is possibly an association between the development of GHD and worse GOS score. Routine endocrine screening of all SAH survivors with dynamic tests is time consuming and may subject many patients to unnecessary side-effects. Furthermore the degree of clinical benefit derived from growth hormone replacement in this patient group, remains unclear. Increased understanding of the most appropriate testing methodology in this patient group and more importantly which SAH survivors would derive most benefit from GHD screening is required.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

The prevalence of growth hormone deficiency in survivors of subarachnoid haemorrhage: results from a large single centre study

et al. 2017

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“…In patients with suspicion for GHD, current guidelines regard testing with well-established dynamic endocrine procedures as mandatory (1,2,7). Over the last years, the GARG test has repeatedly been described as a reliable alternative to the traditional gold standard ITT, which is nowadays regarded as unpleasant, cumbersome and potentially life-threatening (1,2,5,7,17,18,19).…”

Section: Discussionmentioning

confidence: 99%

“…Some of these tests have severe limitations (e.g. impaired sensitivity, high costs); however, the GHRH plus arginine (GARG) test has repeatedly been described as a good alternative to the ITT (1,2,5,7,17,18,19). Of note, as GH responses during the GARG test decline by increasing body mass index (BMI) and age, adjusted cutoffs have been proposed (13,14).…”

Section: Introductionmentioning

confidence: 99%

Anthropometric factors have significant influence on the outcome of the GHRH–arginine test: establishment of normative data for an automated immunoassay specifically measuring 22 kDa human growth hormone

Deutschbein

Bidlingmaier

Schopohl

et al. 2017

European Journal of Endocrinology

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“…Additional weaknesses include the lack of a control population inherent to the retrospective nature of the study, and the absence of a gold standard test to confirm or refute the diagnosis of GH deficiency. Some recommend use of the insulin tolerance test as a gold standard, however, others argue that no “gold standard test” for the diagnosis of GHD exists and that results from each must be interpreted within the clinical context [1]. Finally, the standardization for the GH assay on the Immulite 2000 platform changed during the course of this study.…”

Section: Discussionmentioning

confidence: 99%

Effects of gender, body weight, and blood glucose dynamics on the growth hormone response to the glucagon stimulation test in patients with pituitary disease

Wilson

Utz

Devin

2016

Growth Hormone & IGF Research

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Objective Body weight blunts the growth hormone (GH) response to provocative stimuli. The appropriate GH cut-off to confirm GH deficiency in obese and overweight patients undergoing the glucagon stimulation test (GST) has recently been questioned. We hypothesized that the peak GH would be inversely related to the nadir blood glucose (BG) after glucagon and that this may be a mechanism influencing peak GH in overweight patients. This retrospective study examined effects of gender, body weight, and BG dynamics on GH response to GST in patients evaluated in our Pituitary Center. Design Adult patients who underwent GST from September 2009–2014 were included. Continuous variable comparisons were analyzed using the Mann-Whitney U-test and categorical data by Fisher’s Exact Test. Spearman correlation was used to determine associations between continuous variables. Results 42 patients (N=28, 66.7% female) had sufficient data for analysis. Obese patients (N=26) had a reduced GH response, summarized as GH area under the curve (AUC) (p=0.03 vs. non-obese patients) and higher BG during GST, summarized as AUC (p<0.01 vs. non-obese patients). Obese women (N=19), in particular, stimulated lower (p=0.03 vs. non-obese women) and had a higher nadir BG (p=0.03 vs. non-obese women). While weight correlated with extent (rs=0.35; p=0.02) and timing (rs=0.31; p=0.05) of nadir BG reached, there was no significant correlation between BG dynamics and the GH response in the total population (N=42). Ten patients (7 with pan anterior hypopituitarism, defined as 3 anterior pituitary deficiencies) had a peak GH ≤ 0.1 ng/mL during GST. When these subjects with a negligible peak GH response were excluded from the analysis, weight was associated with GH AUC (rs= −0.45; p=0.01), peak GH response (rs= −0.42; p=0.02) and nadir BG (rs= 0.48; p<0.01). Furthermore, the nadir BG achieved during GST was inversely related to GH AUC (rs= −0.38; p=0.03) and peak GH (rs= −0.37; p=0.04) such that patients (N=32) with higher nadir BG had lower peak GH in response to glucagon. Conclusions Obese patients, particularly women, do not respond as robustly to glucagon stimulation. These data suggest that there exists an altered BG profile during GST in obese individuals, and that a less robust hypoglycemic stimulus may contribute to an impaired GH response. We suggest measuring BG levels during glucagon stimulation testing to assist with clinical interpretation of GH dynamics. The diagnostic accuracy of the GST in patients with known disorders in glucose metabolism and those taking anti-diabetic medications deserves further study.

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The robustness of diagnostic tests for GH deficiency in adults

Cited by 14 publications

References 90 publications

The prevalence of growth hormone deficiency in survivors of subarachnoid haemorrhage: results from a large single centre study

The prevalence of growth hormone deficiency in survivors of subarachnoid haemorrhage: results from a large single centre study

Anthropometric factors have significant influence on the outcome of the GHRH–arginine test: establishment of normative data for an automated immunoassay specifically measuring 22 kDa human growth hormone

Effects of gender, body weight, and blood glucose dynamics on the growth hormone response to the glucagon stimulation test in patients with pituitary disease

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