Endocrine Abstracts

Objective: To assess olfactory bulbs sizes and define the most common molecular defects in adolescents with congenital isolated hypogonadotropic hypogonadism.

Materials and Methods: Single-centre comparative study. 36 patients were included. The main group consisted of 21 patients with mean age of 15.9 years (17 boys, 4 girls) with congenital isolated hypogonadotropic hypogonadism (IHH): 13 - with Kallmann syndrome (KS), 8 – with normosmic isolated hypogonadotropic hypogonadism (nIHH). Kallmann syndrome was diagnosed due to complaints of hypo/anosmia. Olfactory bulbs width and height were assessed via MRI. Molecular-genetic studies were provided in all patients from main group. 15 patients were enrolled as controls (6 girls, 9 boys). Groups were matched for age, height and weight.

Results: Olfactory bulb malforrmations were founded in 20 out of 21 patients: bilateral olfactory bulb hypoplasia was diagnosed in 7, bilateral aplasia – in 4, unilateral hypoplasia – in 6, unilateral aplasia -2, aplasia of the one bulb and hypoplasia of another - 1. Olfactory bulb defects were found in 7 out of 8 nIHH children with no complains of hypo/anosmia. Height and width of olfactory bulbs were significantly smaller in main group in comparison with controls (P< 0.05 via Mann–Whitney U test). Median of right bulb height was 1.0 mm [0.2;1.2] in patients from the main group vs. 3.0 [2.5;3.2] in control group. Median of right bulb width was 1,0 mm [0.2;1.7] in patients from the main group vs. 2.5 [2.0;3.0] in control. Median of left olfactory bulb height was 0.8 mm [0.0;1.1] in main group vs. 3.0 [2.7;3.2] in controls. Median of left olfactory bulb width was 0.4 mm [0.0;1.1] in main group vs. 2.5 [2.0;3.0] in comparison with control group. There were no statistically significant differences in olfactory bulb sizes between patients with KS and nIHH (P> 0.05). Molecular defects were identified in 9 patients: defects in FGFR1 were found in 4 out of 9 patients, СHD7 - 3, KAL1-1, FGF17 - 1. 5 defects were identified as variants of uncertain significance, 2 as likely pathogenic and 2 as pathogenic.

Conclusion: Bilateral olfactory bulb hypoplasia is a reliable sign of hypogonadotropic hypogonadism: it was identified in every third adolescent with congenital IHH. All pathogenic genetic variants were in FGFR1 and were associated with uni/bilateral olfactory bulbs hypoplasia. Normal sense of smell doesn’t rule out olfactory bulbs defects.