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From mini-puberty to pre-puberty: early impairment of the hypothalamus–pituitary–gonadal axis with normal testicular function in children with non-mosaic Klinefelter syndrome

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Abstract

Purpose

Klinefelter syndrome (KS) is a genetic disorder caused by the presence of an extra X chromosome in males. The aim of this study was to evaluate the hypothalamic–pituitary–gonadal (HPG) axis and the clinical profile of KS boys from mini-puberty to early childhood.

Patients and methods

In this retrospective, cross-sectional, population study, 145 KS boys and 97 controls aged 0–11.9 years were recruited. Serum FSH, LH, testosterone (T), Inhibin B (INHB), sex hormone binding globulin (SHBG) and anti-Müllerian hormone (AMH) were determined. Auxological parameters were assessed. To better represent the hormonal and clinical changes that appear in childhood, the entire population was divided into 3 groups: ≤ 6 months (group 1; mini-puberty); > 6 months and ≤ 8 years (group 2; early childhood); > 8 and ≤ 12 years (group 3; mid childhood).

Results

During mini-puberty (group 1), FSH and LH were significantly higher in KS infants than controls (p < 0.05), as were INHB and T (respectively p < 0.0001 and p < 0.005). INHB was also significantly higher in KS than controls in group 2 (p < 0.05). AMH appeared higher in KS than in controls in all groups, but the difference was only statistically significant in group 2 (p < 0.05). No significant differences were found in height, weight, testicular volume, and penile length.

Conclusions

No hormonal signs of tubular or interstitial damage were found in KS infants. The presence of higher levels of gonadotropins, INHB and testosterone during mini-puberty and pre-puberty may be interpreted as an alteration of the HPG axis in KS infants.

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Acknowledgements

The authors would like to thank Marie-Hélène Hayles MITI for the language revision.

Funding

This study was supported by the Italian Ministry of Health and the Italian Medicines Agency (AIFA): research project MRAR08Q009 on rare diseases.

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Authors and Affiliations

  1. Department of Experimental Medicine, Section of Medical Pathophysiology, Food Science and Endocrinology, Sapienza University of Rome, Level-1, Room 33, Policlinico Umberto I, 00161, Rome, Italy

    M. Spaziani, S. Granato, F. M. Rossi, N. Tahani, C. Pozza, D. Gianfrilli, G. Papi, A. Anzuini, A. Lenzi & A. F. Radicioni

  2. Department of Pediatrics, Sapienza University of Rome, 00161, Rome, Italy

    N. Liberati & L. Tarani

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  1. M. Spaziani
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Correspondence to M. Spaziani.

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Spaziani, M., Granato, S., Liberati, N. et al. From mini-puberty to pre-puberty: early impairment of the hypothalamus–pituitary–gonadal axis with normal testicular function in children with non-mosaic Klinefelter syndrome. J Endocrinol Invest 44, 127–138 (2021). https://doi.org/10.1007/s40618-020-01281-x

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