Ann Pediatr Endocrinol Metab.  2020 Sep;25(3):152-155. 10.6065/apem.2040004.002.

Gonadotropin-releasing hormone stimulation test and diagnostic cutoff in precocious puberty: a mini review

• Ab Rahim SN
• Omar J
• Tuan Ismail TS

• KMID: 2507556
• DOI: http://doi.org/10.6065/apem.2040004.002

Abstract

The gonadotropin-releasing hormone (GnRH) stimulation test is a valuable tool in diagnosing and differentiating causes of early pubertal occurrences. Utility of the test can be limited in some instances, however, including the early phases of pubertal hypothalamic-pituitary-gonadal axis activation, in girls showing commonly overlapping pictures, and in obese children due to excess circulating estrogen that suppresses luteinizing hormone (LH). A lack of consistent baseline and stimulated gonadotropin cutoffs observed in different studies also contributes to limitations in testing. Nevertheless, early detection of true pathological causes for pubertal disorders is needed to allow prompt treatment and better prognosis. While basal LH can be beneficial as a good screening tool for detecting pubertal disorder, it does not preclude the need for GnRH testing. The aim of this review was to highlight the role of GnRH stimulation tests and varying testing cutoffs in diagnosis of precocious puberty and its classification.

Keyword

Gonadotropin-releasing hormone; Precocious puberty; GnRH analogues; Premature thelarche

Reference

References

1. Kumar M, Muk hopadhyay S, Dutta D. Challenges and controversies in diagnosis and management of gonadotropin dependent precocious puberty: an Indian perspective. Indian J Endocrinol Metab. 2015; 19:228–35.

2. Mogensen SS, Aksglaede L, Mouritsen A, Sørensen K, Main KM, Gideon P, et al. Diagnostic work-up of 449 consecutive girls who were referred to be evaluated for precocious puberty. J Clin Endocrinol Metab. 2011; 96:1393–401.

3. Prasad HK, Khaldikar VV, Jahagirdar R, Khaldikar AV, Lalwani SK. Evaluation of GnRH analogue testing in diagnosis and management of children with pubertal disorders. Indian J Endocrinol Metab. 2012; 16:400–5.

4. Binay C, Simsek E, Bal C. The correlation between GnRH stimulation testing and obstetric ultrasonographic parameters in precocious puberty. J Pediatr Endocrinol Metab. 2014; 27:1193–9.

5. Nam HK, Rhie YJ, Son CS, Park SH, Lee KH. Factors to predict positive results of gonadotropin releasing hormone stimulation test in girls with suspected precocious puberty. J Korean Med Sci. 2012; 27:194–9.

6. Wei C, Davis N, Honour J, Crowne E. The investigation of children and adolescents with abnormalities of pubertal timing. Ann Clin Biochem. 2016; 54:20–32.

7. Menon PS. Precocious puberty, GnRH stimulation test and monitoring GnRH analog therapy. Indian J Pediatr. 2015; 82:980–2.

8. Kandemir N, Demirbilek H, Özön ZA, Gönç N, Alikaşifoğlu A. GnRH stimulation test in precocious puberty: single sample is adequate for diagnosis and dose adjustment. J Clin Res Pediatr Endocrinol. 2011; 3:12–7.

9. Kim HK, Kee SJ, Seo JY, Yang EM, Chae HJ, Kim CJ. Gonadotropin-releasing hormone stimulation test for precocious puberty. Korean J Lab Med. 2011; 31:244–9.

10. Yazdani P, Lin Y, Raman V, Haymond M. A single sample GnRHa stimulation test in the diagnosis of precocious puberty. Int J Pediatr Endocrinol. 2012; 2012:23.

11. Fuqua JS. Treatment and outcomes of precocious puberty: an update. J Clin Endocrinol Metab. 2013; 98:2198–207.

12. Lee HS, Park HK, Ko JH, Kim YJ, Hwang JS. Utility of basal luteinizing hormone levels for detecting central precocious puberty in girls. Horm Metabolic Res. 2012; 44:851–4.

13. Pasternak Y, Friger M, Loewenthal N, Haim A, Hershkovitz E. The utility of basal serum LH in prediction of central precocious puberty in girls. Eur J Endocrinol. 2012; 166:295–9.

14. Carel JC, Eugster E, Rogol A, Ghizzoni L, Palmert MR. Consensus statement on the use of gonadotropin-releasing hormone analogs in children. Pediatrics. 2009; 123:e752–62.

15. Kang YS, Yoo DY, Chung IH, Yoo EG. Diurnal variation of gonadotropin levels in girls with early stages of puberty. Ann Pediatr Endocrinol Metab. 2017; 22:183–8.

16. Bordini B, Littlejohn E, Rosenfield RL. LH dynamics in overweight girls with premature adrenarche and slowly progressive sexual precocity. Int J Pediatr Endocrinol. 2010; 2010:724696.

17. Lee HS, Park HK, Ko JH, Kim YJ, Hwang JS. Impact of body mass index on luteinizing hormone secretion in gonadotropin-releasing hormone stimulation tests of boys experiencing precocious puberty. Neuroendocrinology. 2013; 97:225–31.

18. Fu JF, Liang JF, Zhou XL, Prasad HC, Jin JH, Dong GP, et al. Impact of BMI on gonadorelin-stimulated LH peak in premenarcheal girls with idiopathic central precocious puberty. Obesity. 2015; 23:637–43.

19. Heo S, Lee YS, Yu J. Basal serum luteinizing hormone value as the screening biomarker in female central precocious puberty. Ann Pediatr Endocrinol Metab. 2019; 24:164–71.

20. Lee HS, Yoon JS, Hwang JS. Luteinizing hormone secretion during gonadotropin-releasing hormone stimulation tests in obese girls with central precocious puberty. J Clin Res Pediatr Endocrinol. 2016; 8:392–8.

21. Kılıç A, Durmuş MS, Ünüvar E, Yıldız İ, Aydın BK, Uçar A, et al. Clinical and laboratory characteristics of children referred for early puberty: preponderance in 7-8 years of age. J Clin Res Pediatr Endocrinol. 2012; 4:208–12.

22. Karaoglan M, Keskin M, Kul S, Ozkur A. A diagnostic scoring system to distinguish precocious puberty from premature thelarche based on clinical and laboratory findings. Iran J Pediatr. 2018; 28:e64118.

23. Menon PS, Vijayakumar M. Precocious puberty-perspectives on diagnosis and management. Indian J Pediatr. 2014; 81:76–83.

24. Klein DA, Emerick JE, Sylvester JE, Vogt KS. Disorders of puberty: an approach to diagnosis and management. Am Fam Physician. 2017; 96:590–9.

25. Harrington J, Palmert MR. Distinguishing constitutional delay of growth and puberty from isolated hypogonadotropic hypogonadism: critical appraisal of available diagnostic tests. J Clin Endocrinol Metab. 2012; 97:3056–67.

26. Wheeler MJ. The measurement of LH, FSH, and prolactin. In : Wheeler MJ, editor. Hormone assays in biological fluids. methods in molecular biology (methods and protocols). Totowa (NJ): Humana Press;2013. p. 1065. PalmertMR.