Accuracy of various tests alone and in combination to differentiate IHH from CDGP

Abstract

Context: Constitutional delay in growth and puberty (CDGP) is a normal physiological variant of delayed puberty in both sexes and is the most common cause of delayed puberty. Idiopathic hypogonadotropic hypogonadism (IHH) is due to deficiency in or insensitivity to gonadotropin-releasing hormone (GnRH) with normal structure and function of the anterior pituitary after exclusion of secondary causes of hypogonadotropic hypogonadism. To differentiate CDGP from IHH is crucial because it not only helps in decision making in management but also lessen anxiety of the parents. Aim: In this study we aimed to find out the accuracy of hormonal tests used individually as well as in various combinations to distinguish cases of IHH from CDGP. Methods: A cohort of 34 boys with delayed puberty were recruited in this study. Detailed history, clinical examination, hormonal analysis including basal serum testosterone, inhibin-B, LH, FSH as well as GnRH analogue stimulated gonadotrophins and testosterone along with hCG stimulated testosterone was done. At 6 monthly follow-up, detailed clinical examination was repeated and the cohort was followed until 2 years. Results: Out of the 29 boys taken for final analysis, CDGP was diagnosed in 23 boys and IHH in 6 boys. Basal LH, basal inhibin-B, 3 hours post leuprolide LH and 72 hours post hCG testosterone were significantly higher in CDGP than IHH. However, no statistically significant difference was observed between basal FSH, basal testosterone and 3 hours post leuprolide FSH between these two groups. When basal LH (cut-off <0.565 IU/L) and basal inhibin-B (cut-off <105 pg/ml) were taken together the sensitivity and specificity were increased to 100% as was for the combination of basal LH (cutoff <0.565 IU/L) and 3 hours post leuprolide LH (cutoff <6.16 IU/L) for diagnosis of IHH. Both combinations have PPV of 100% and NPV of 100%. A combination of 3 hours post leuprolide LH with 72 hours post hCG testosterone also has good sensitivity (100%), specificity (96%), PPV (90%) and NPV (100%). Conclusion: Differentiating IHH from CDGP is a challenging task due to considerable overlap in their clinical as well as hormonal profiles. Therefore we suggest that a combination of basal LH and basal inhibin-B may be considered as a useful screening tool to differentiate IHH from CDGP rather than the cumbersome and invasive stimulation tests.

Role of Inhibin B, AMH, GnRHa Test and HCG Stimulation Test to Distinguish Isolated Hypogonadotropic Hypogonadism (IHH) from Constitutional Delay in Growth and Puberty (CDGP)

“…The results on post-HCG-stimulated testosterone varied across studies. The present study found that post-HCG day 4 testosterone at a cut-off of 99.7 ng/dl had a sensitivity of 85.7% and specificity of 93.3%, which was similar to the study by Mishra et al ,[ 20 ] which had 100% sensitivity and 91% specificity at a cut-off of 110 ng/dl.…”

“…Others have studies on leuprolide or GnRH as a stimulatory agent for distinguishing both. [ 9 , 19 , 20 ] The present study also found that basal testosterone had good sensitivity (100%) and poor specificity (53.3%) at a cut-off of 20.8 ng/dl. The study by Coutant et al .…”

“…A similar study by Mishra et al . [ 20 ] found that inhibin B at a cut-off of 105 pg/ml had 100% sensitivity and 83% specificity. These results show that inhibin B had good sensitivity and specificity to distinguish IHH from CDGP.…”

“…[ 6 ] found that basal testosterone at a cut-off of 9 ng/dl had 100% sensitivity and specificity, whereas the study by Mishra et al . [ 20 ] at a cut-off of 19.71 ng/dl found sensitivity and specificity of 67% and 78%, respectively. These test results show that basal testosterone is not a specific test to distinguish IHH from CDGP in boys.…”