The Relevance of Insulin-like Growth Factor-1 Concentration as a Screening Test for Diagnosis of Growth Hormone Deficiency

Abstract

Objective: Growth hormone deficiency (GHD) is one of the most important endocrine and treatable causes of short stature. Insulin-like growth factor 1 (IGF-1) concentration is not recommended to establish the diagnosis of GHD. The aim of our study was to analyze the relevance of IGF-1 concentration as a screening test for the diagnosis of GHD. Materials and Methods: We retrospectively studied patients who were evaluated for short stature at the Endocrinology Department of King Fahad Armed Forces Hospital, Jeddah, Saudi Arabia from January 2015 to December 2018. For IGF-1, laboratory reference ranges were based on age and sex. For all eligible patients, IGF-1 concentration was determined and an ITT was performed. Patients with a peak GH of ≤ 5.0 ng/ml were considered to be GHD and patients with a peak GH of ≥ 5.1 ng/ml were considered non-GHD (nGHD). Results: We retrospectively included 47 patients for analysis. Mean age was 14.7 ± 1.7 years. There were 38 males (80.9%) and 9 females (19.1%) and mean IGF-1 concentration was 146.4 ± 69.4 ng/dl. Results from the ITT indicated that 27 (57.4%) had GHD. Age was not significantly different between GHD and non-GHD (14.7 ± 1.8 vs. 14.8 ± 1.6 years, P = 0.9). There were non-significantly more males than females in GHD patients (59% vs. 50%, P = 0.7). Mean IGF-1 concentration was not significantly different (146.9 ± 70.4 ng/dl vs. 145.7 ± 69.8 ng/dl, P = 0.9). IGF-1 concentration below the reference ranges for age and gender was non-significantly higher in patients with GHD compared to non-GHD (53.8% vs. 46.2%, P = 0.8). The mean peak for GH concentration was significantly lower in patients with GHD (2.2 ± 1.3 ng/ml vs. 9.9 ± 5.6 ng/ml, P < 0.0001). Peak GH concentration was not significantly correlated with IGF-1 concentration (r = 0.213, P = 0.2). We plotted a ROC curve of IGF-1 concentration according to the diagnosis of GHD as established using ITT. The AUC was 49%. An IGF-1 threshold of 154 ng/dl was selected to emphasize sensitivity rather than specificity. With a threshold of 154 ng/dl, sensitivity was 52% (95% confidence interval (95% CI); 32%, 71%), specificity was 40% (95% CI; 19%, 64%) and the negative predictive value for the diagnosis of GHD was 38% (95% CI; 24%, 54%). With a threshold of 105 ng/dl, the sensitivity was 41% and the specificity was 70%. A threshold of 74 ng/dl, gave a positive predictive value of 60% but a negative predictive value of 43%. 7 of the patients with IGF-1 concentration above the threshold of 154 ng/dl (N = 20) were normal and 13 had GH deficiency. These 13 GHD patients had IGF-1 concentration that differs significantly from those of their GH-sufficient counterparts (105 ± 35 vs. 222 ± 49 ng/dl, P < 0.0001). If IGF-1 was used as a screening test (with a concentration threshold of 154 ng/dl) and ITT as a confirmatory test, 20 (43%) out of 47 ITT would not have been performed, leading to the misdiagnosis of 13 GH-deficient adults. Thus, in our study population, such a procedure would misdiagnose 13 out of 27 GHD patients (48%) and yield a sensitivity of 52%. Conclusion: Many reports have already reported that IGF-1 concentration is lower in patients with GHD than in the general population, our study demonstrated the poor negative predictive value of IGF-1 concentration for the diagnosis of GHD, making it the need of the use of the “gold standard” method ITT. This observation remains to be validated by population-based studies.