FSH-stimulated Inhibin B (FSH-iB): A Novel Marker for the Accurate Prediction of Pubertal Outcome in Delayed Puberty

Chaudhary, Shakun; Walia, Rama; Bhansali, Anil; Dayal, Devi; Sachdeva, Naresh; Singh, Tulika; Bhadada, Sanjay Kumar

doi:10.1210/clinem/dgab357

Cited by 22 publications

(13 citation statements)

References 25 publications

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“…Recently, new developments raise the availability of differentiate CDGP from CHH in the clinical setting [9]. The FSH-stimulated inhibin B has been shown to correctly differentiate pubertal delay from a hypogonadoptrophic hypogonadism; however further studies are need to confirm this interesting point [10]. A family history of DP strongly suggests a condition of CDGP (observed in 50-75%).…”

Section: Diagnostic Approachmentioning

confidence: 99%

Current clinical management of constitutional delay of growth and puberty

et al. 2022

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Background Constitutional delay of growth and puberty (CDGP) is classified as the most frequent cause of delayed puberty (DP). Finding out the etiology of DP during first evaluation may be a challenge. In details, pediatricians often cannot differentiate CDGP from permanent hypogonadotropic hypogonadism (PHH), with definitive diagnosis of PHH awaiting lack of puberty by age 18 yr. Neverthless, the ability in providing a precise and tempestive diagnosis has important clinical consequences. Main text A growth failure in adolescents with CDGP may occur until the onset of puberty; after that the growth rate increases with rapidity. Bone age is typically delayed. CDGP is generally a diagnosis of exclusion. Nevertheless, other causes of DP must be evaluated. A family history including timing of puberty in the mother and in the father as well as physical examination may givee information on the cause of DP. Patients with transient delay in hypothalamic-pituitary-gonadal axis maturation due to associated conditions, such as celiac disease, inflammatory bowel diseases, kidney insufficiency and anorexia nervosa, may experience a functional hypogonadotropic hypogonadism. PHH revealing testosterone or estradiol low serum values and reduced FSH and LH levels may be connected to abnormalities in the central nervous system. So, magnetic resonance imaging is required in order to exclude either morphological alterations or neoplasia. If the adolescent with CDGP meets psychological difficulties, treatment is recommended. Conclusion Even if CDGP is considered a variant of normal growth rather than a disease, short stature and retarded sexual development may led to psychological problems, sometimes associated to a poor academic performance. A prompt and precise diagnosis has an important clinical outcome. Aim of this mini-review is throwing light on management of patients with CDGP, emphasizing the adolescent diagnosis and trying to answer all questions from paediatricians.

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Section: Diagnostic Approachmentioning

confidence: 99%

Current clinical management of constitutional delay of growth and puberty

et al. 2022

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“…have also reported the accuracy of a composite outcome based on both the LH response to GnRHa and INB in prepubertal males aged 13.7-17.5 years ( 27 ), which provided 100% sensitivity and 98.1% specificity when LH <0.3 IU/L and INB <111 pg/ml cut-offs were applied ( 27 ). More recently in addition to kisspeptin-stimulated-LH ( 30 ) (discussed above), FSH-stimulated-INB ( 38 ) and GnRHa-stimulated INB ( 39 ) have been proposed as potential diagnostic tests to predict outcomes in delayed puberty.…”

Section: Discussionmentioning

confidence: 99%

Insulin-like peptide 3 (INSL3) in congenital hypogonadotrophic hypogonadism (CHH) in boys with delayed puberty and adult men

et al. 2022

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BackgroundDelayed puberty in males is almost invariably associated with constitutional delay of growth and puberty (CDGP) or congenital hypogonadotrophic hypogonadism (CHH). Establishing the cause at presentation is challenging, with “red flag” features of CHH commonly overlooked. Thus, several markers have been evaluated in both the basal state or after stimulation e.g. with gonadotrophin releasing hormone agonist (GnRHa).Insulin-like peptide 3 (INSL3) is a constitutive secretory product of Leydig cells and thus a possible candidate marker, but there have been limited data examining its role in distinguishing CDGP from CHH. In this manuscript, we assess INSL3 and inhibin B (INB) in two cohorts: 1. Adolescent boys with delayed puberty due to CDGP or CHH and 2. Adult men, both eugonadal and having CHH.Materials and methodsRetrospective cohort studies of 60 boys with CDGP or CHH, as well as 44 adult men who were either eugonadal or had CHH, in whom INSL3, INB, testosterone and gonadotrophins were measured.Cohort 1: Boys with delayed puberty aged 13-17 years (51 with CDGP and 9 with CHH) who had GnRHa stimulation (subcutaneous triptorelin 100mcg), previously reported with respect to INB.Cohort 2: Adult cohort of 44 men (22 eugonadal men and 22 men with CHH), previously reported with respect to gonadotrophin responses to kisspeptin-54.ResultsMedian INSL3 was higher in boys with CDGP than CHH (0.35 vs 0.15 ng/ml; p=0.0002). Similarly, in adult men, median INSL3 was higher in eugonadal men than CHH (1.08 vs 0.05 ng/ml; p<0.0001). However, INSL3 more accurately differentiated CHH in adult men than in boys with delayed puberty (auROC with 95% CI in adult men: 100%, 100-100%; boys with delayed puberty: 86.7%, 77.7-95.7%).Median INB was higher in boys with CDGP than CHH (182 vs 59 pg/ml; p<0.0001). Likewise, in adult men, median INB was higher in eugonadal men than CHH (170 vs 36.5 pg/ml; p<0.0001). INB performed better than INSL3 in differentiating CHH in boys with delayed puberty (auROC 98.5%, 95.9-100%), than in adult men (auROC 93.9%, 87.2-100%).ConclusionINSL3 better identifies CHH in adult men, whereas INB better identifies CHH in boys with delayed puberty.

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“…Recently, Chaudhary et al . [ 14 ] demonstrated that FSH stimulated inhibin B at a cut off of 116.14 pg/ml in males has very good sensitivity and specificity for labeling entry into puberty.…”

Section: Discussionmentioning

confidence: 99%

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

Mishra¹,

Mishra²,

Choudhury³

et al. 2022

Indian Journal of Endocrinology and Metabolism

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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.

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FSH-stimulated Inhibin B (FSH-iB): A Novel Marker for the Accurate Prediction of Pubertal Outcome in Delayed Puberty

Cited by 22 publications

References 25 publications

Current clinical management of constitutional delay of growth and puberty

Current clinical management of constitutional delay of growth and puberty

Insulin-like peptide 3 (INSL3) in congenital hypogonadotrophic hypogonadism (CHH) in boys with delayed puberty and adult men

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

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