Longitudinal assessment of auxological parameters, adult height outcome and its determinants in leuprolide-treated Indian girls with idiopathic central precocious puberty

Shruti Mondkar; Vaman Khadilkar; Sushil Yewale; Nimisha Dange; Chidvilas More; Anuradha Khadilkar

doi:10.1515/jpem-2023-0353

Article

Longitudinal assessment of auxological parameters, adult height outcome and its determinants in leuprolide-treated Indian girls with idiopathic central precocious puberty

Shruti Mondkar , Vaman Khadilkar , Sushil Yewale , Nimisha Dange , Chidvilas More and Anuradha Khadilkar

Published/Copyright: November 28, 2023

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From the journal Journal of Pediatric Endocrinology and Metabolism Volume 37 Issue 1

Abstract

Objectives

To assess auxological parameters, adult height outcome and its determinants in Indian girls with idiopathic central precocious puberty (iCPP) treated with gonadotropin-releasing hormone analogues (GnRHa).

Methods

Retrospective study. Inclusion: data on girls with iCPP from initiation to stopping GnRHa (n=179). Exclusion: boys, peripheral, organic central precocity.

Results

Mean age of starting GnRHa: 8.2± 1.1 years, duration: 2.8± 1.2 years. 11.7 % had attained menarche at first presentation. The difference between bone (BA) and chronological (CA) ages reduced significantly from 2.6± 0.9 years (onset) to 1.6± 0.8 years (cessation). Weight, BMI Z-scores increased (p<0.01), height Z-scores decreased (0.8 vs. 0.6; p<0.01), predicted adult height (PAH) and Z-scores improved by 3.5 cm, 0.5 SDS following treatment (p<0.01). Overweight/obese girls (vs. normal BMI) were taller, with more advanced BA at starting (height Z-score: 0.7 vs. 1.0, BA-CA: 2.2 vs. 2.9 years), stopping (height Z-score: 0.5 vs. 0.9, BA–CA: 1.4 vs. 1.9 years) treatment, but showed no difference in PAH at starting, stopping treatment. Adult height data (n=58) revealed 1.9 cm gain above target height. Adult height Z-scores significantly exceeded target height Z-scores (p<0.01). Mean adult height (157.1± 5.8 cm) crossed PAH at starting treatment (155.9± 6.4 cm) but remained 1.6 cm lesser than PAH at cessation. Adult weight, BMI Z-scores (−0.2± 1.3, −0.1± 1.2) were significantly lower (p<0.01) than those at stopping GnRHa. Height gain adjusted for age at starting GnRHa correlated negatively with height, weight, BMI, Tanner-staging, BA, FSH, Estradiol at treatment onset, BA at cessation, and correlated positively with treatment duration.

Conclusions

GnRHa treatment in Indian girls with iCPP resulted in improved PAH, decelerated bone age advancement and growth velocity. Most girls achieved adult height within target range, surpassing PAH at treatment initiation. Lesser anthropometric, sexual, skeletal maturity, lower baseline FSH, estradiol, longer treatment duration, less advanced BA at stopping GnRHa may translate into better adult height outcomes.

Keywords: precocious puberty; adult height; obesity; height prediction; leuprolide; GnRH analogue

Corresponding author: Dr. Anuradha Khadilkar, Deputy Director and Consultant Pediatrician, Hirabai Cowasji Jehangir Medical Research Institute, Block V Lower Basement Jehangir Hospital, 32 Sassoon Road, Pune 411001, India; and Interdisciplinary School of Health Sciences, Savitribai Phule University, Pune, India, Phone: +91 0206057004, E-mail: anuradhavkhadilkar@gmail.com

Research ethics: The local Institutional Review Board deemed the study exempt from review owing to retrospective study design and de-identified data (Ethical committee, Jehangir Clinical Development Center Pvt Ltd).
Informed consent: Not applicable owing to retrospective study design and de-identified data.
Author contributions: All authors have accepted responsibility for the entire content of this manuscript and approved its submission.
Competing interests: Authors state no conflict of interest.
Research funding: None declared.
Data availability: The raw data can be obtained on request from the corresponding author.

References

1. Howard, S, De Roux, N, Leger, J, Carel, JC, Dunkel, L. Puberty and its disorders. In: Dattani, M, Brook, C, editors. Brook’s clinical pediatric endocrinology, 7th ed. UK: Wiley; 2020:235–83 pp.10.1002/9781119152712.ch7Search in Google Scholar

2. Verzani, M, Bizzarri, C, Chioma, L, Bottaro, G, Pedicelli, S, Cappa, M. Impact of COVID-19 pandemic lockdown on early onset of puberty: experience of an Italian tertiary center. Ital J Pediatr 2021;47:52, https://doi.org/10.1186/s13052-021-01015-6.Search in Google Scholar PubMed PubMed Central

3. Stagi, S, De Masi, S, Bencini, E, Losi, S, Paci, S, Parpagnoli, M, et al.. Increased incidence of precocious and accelerated puberty in females during and after the Italian lockdown for the coronavirus 2019 (COVID-19) pandemic. Ital J Pediatr 2020;46:165, https://doi.org/10.1186/s13052-020-00931-3.Search in Google Scholar PubMed PubMed Central

4. Acar, S, Özkan, B. Increased frequency of idiopathic central precocious puberty in girls during the COVID-19 pandemic: preliminary results of a tertiary center study. J Pediatr Endocrinol Metab 2021;35:249–51, https://doi.org/10.1515/jpem-2021-0565.Search in Google Scholar PubMed

5. Knific, T, Lazarevič, M, Žibert, J, Obolnar, N, Aleksovska, N, Šuput Omladič, J, et al.. Final adult height in children with central precocious puberty – a retrospective study. Front Endocrinol 2022;13:1008474, https://doi.org/10.3389/fendo.2022.1008474.Search in Google Scholar PubMed PubMed Central

6. Mondkar, SA, Oza, C, Khadilkar, V, Shah, N, Gondhalekar, K, Kajale, N, et al.. Impact of COVID-19 lockdown on idiopathic central precocious puberty – experience from an Indian centre. J Pediatr Endocrinol Metab 2022;35:895–900, https://doi.org/10.1515/jpem-2022-0157.Search in Google Scholar PubMed

7. Carel, JC, Eugster, EA, Rogol, A, Ghizzoni, L, Palmert, MR, Antoniazzi, F, et al.. Consensus statement on the use of gonadotropin-releasing hormone analogs in children. Pediatrics 2009;123:e752–62, https://doi.org/10.1542/peds.2008-1783.Search in Google Scholar PubMed

8. Oostdijk, W, Rikken, B, Schreuder, S, Otten, B, Odink, R, Rouwe, C, et al.. Final height in central precocious puberty after long term treatment with a slow release GnRH agonist. Arch Dis Child 1996;75:292–7, https://doi.org/10.1136/adc.75.4.292.Search in Google Scholar PubMed PubMed Central

9. Khadilkar, VV, Khadilkar, AV. Revised Indian Academy of Pediatrics 2015 growth charts for height, weight and body mass index for 5–18-year-old Indian children. Indian J Endocrinol Metab 2015;19:470–6, https://doi.org/10.4103/2230-8210.159028.Search in Google Scholar PubMed PubMed Central

10. Maheshwari, A. Growth retardation. In: Khadilkar, V, Bajpai, A, Prasad, H, editors. IAP textbook on pediatric endocrinology, 1st ed. India: Jaypee; 2019:55–67 pp.Search in Google Scholar

11. Marshall, WA, Tanner, JM. Variations in pattern of pubertal changes in girls. Arch Dis Child 1969;44:291–303, https://doi.org/10.1136/adc.44.235.291.Search in Google Scholar PubMed PubMed Central

12. Tanner, JM, Healy, MJ, Goldstein, H, Cameron, N, editors. The method in practice: reference values for skeletal maturity and TW3 bone age. In: Assessment of skeletal maturity and prediction of adult height (TW 3 method), 3rd ed. London: WB Saunder; 2001:9–21 pp.Search in Google Scholar

13. Tanner, JM, Healy, MJ, Goldstein, H, Cameron, N, editors. Prediction of adult height: TW3 equations. In: Assessment of skeletal maturity and prediction of adult height (TW 3 method), 3rd ed. London: WB Saunder; 2001:26–42 pp.Search in Google Scholar

14. Bajpai, A, Sharma, J, Kabra, M, Gupta, AK, Menon, PSN. Long-acting GnRH analogue triptorelin therapy in central isosexual precocious puberty. Indian Pediatr 2002;39:633–9.Search in Google Scholar

15. Selvaraj, M, Prasad, HK, Ramji, B, Thiagarajan, A, Narayanasamy, K, Krishnamoorthy, N. Response of South Indian girls with central precocious puberty to gonadotrophin analogue (GnRHa) therapy – a single center experience. Pediatr Endocrinol Diabetes Metab 2021;27:253–7, https://doi.org/10.5114/pedm.2021.109125.Search in Google Scholar PubMed PubMed Central

16. Phadte, A, Sarathi, V, Budyal, S, Lila, A, Memon, SS, Karlekar, M, et al.. Gonadotropin-dependent precocious puberty: single-center experience from Western India. Indian Pediatr 2023;60:463–6, https://doi.org/10.1007/s13312-023-2909-y.Search in Google Scholar

17. Bereket, A. A critical appraisal of the effect of gonadotropin-releasing hormon analog treatment on adult height of girls with central precocious puberty. J Clin Res Pediatr Endocrinol 2017;9:33–48, https://doi.org/10.4274/jcrpe.2017.s004.Search in Google Scholar

18. Vuralli, D, Gonc, NE, Ozon, ZA, Kandemir, N, Alikasifoglu, A. Which parameters predict the beneficial effect of GnRHa treatment on height in girls with central precocious puberty? Clin Endocrinol 2021;94:804–10, https://doi.org/10.1111/cen.14420.Search in Google Scholar PubMed

19. Park, J, Hwang, TH, Kim, YD, Han, HS. Longitudinal follow-up to near final height of auxological changes in girls with idiopathic central precocious puberty treated with gonadotropin-releasing hormone analog and grouped by pretreatment body mass index level. Ann Pediatr Endocrinol Metab 2018;23:14–20, https://doi.org/10.6065/apem.2018.23.1.14.Search in Google Scholar PubMed PubMed Central

20. Sinthuprasith, P, Dejkhamron, P, Wejaphikul, K, Unachak, K. Near final adult height, and body mass index in overweight/obese and normal-weight children with idiopathic central precocious puberty and treated with gonadotropin-releasing hormone analogs. J Pediatr Endocrinol Metab 2019;32:1369–75, https://doi.org/10.1515/jpem-2019-0136.Search in Google Scholar PubMed

21. Dayal, D, Yadav, J, Seetharaman, K, Aggarwal, A, Kumar, R. Etiological spectrum of precocious puberty: data from Northwest India. Indian Pediatr 2020;57:63–4, https://doi.org/10.1007/s13312-020-1705-1.Search in Google Scholar

22. Arrigo, T, Cisternino, M, Galluzzi, F, Bertelloni, S, Pasquino, AM, Antoniazzi, F, et al.. Analysis of the factors affecting auxological response to GnRH agonist treatment and final height outcome in girls with idiopathic central precocious puberty. Eur J Endocrinol 1999;141:140–4, https://doi.org/10.1530/eje.0.1410140.Search in Google Scholar PubMed

23. Prader, A, Largo, RH, Molinari, L, Issler, C. Physical growth of Swiss children from birth to 20 years of age. First Zurich longitudinal study of growth and development. Helv Paediatr Acta Suppl 1989;52:1–125.Search in Google Scholar

24. Savaş-Erdeve Ş, Şıklar, Z, Hacıhamdioğlu, B, Kocaay, P, Çamtosun, E, Öcal, G, et al.. Gonadotropin-releasing hormone analogue treatment in females with moderately early puberty: no effect on final height. J Clin Res Pediatr Endocrinol 2016;8:211–7, https://doi.org/10.4274/jcrpe.2356.Search in Google Scholar PubMed PubMed Central

Received: 2023-07-28

Accepted: 2023-10-28

Published Online: 2023-11-28

Published in Print: 2024-01-29

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Articles in the same Issue

https://doi.org/10.1515/jpem-2023-0353

Keywords for this article

precocious puberty; adult height; obesity; height prediction; leuprolide; GnRH analogue