ESPE Yearbook of Paediatric Endocrinology

J Pediatr. 2021 Dec 20:S0022-3476(21)01236-1. doi: 10.1016/j.jpeds.2021.12.030. PMID: 34942182https://www.sciencedirect.com/science/article/pii/S0022347621012361

Brief Summary: This study evaluates the efficacy and safety of GnRH analogue treatment with Central Precocious Puberty (CPP) for patients under 2 years of age. The authors conclude that GnRH analogue treatment is safe and effective in this age group.

GnRH analogues (GnRHa) represent the treatment of choice for CPP [1] and have been approved by the Food and Drug Administration for children aged 2 years and above. Although rare, CPP also occurs in children < 2-year-old [2]–[4]. In the absence of any alternative, this situation requires off-label drug use which requires individual allowance and/or lack of coverage by health insurances that both may lead to delaying treatment in some countries. This study evaluated the safety and efficacy of GnRHa treatment in children < 2-year-old.

43 subjects were identified in the literature and 4 of them from a retrospective evaluation at the Riley Hospital for Children. 56.3% were female, while 43.7% were male with an average age at start of GnRHa treatment of 14.5±4.7 months. The cause of the CPP was hypothalamic hamartoma in 24 cases, Rathke cleft cyst in 2 cases, septo-optic dysplasia in 1 case and idiopathic-CPP in 5 cases. Their treatments included depot injections, histrelin implant and rapid-acting formulation. The treatment resulted in suppression of the Hypothalamic-Pituitary-Gonadal axis, with stabilization or regression of pubertal development, growth velocity and hormonal parameters in all cases.

The authors focused mostly on the short-term efficacy of the treatment, which was as effective as in other age groups. No adverse events were reported. Long-term efficacy, including parameters such as age of menarche or final height, was not analyzed. The authors found an equal gender distribution and a preponderance of organic causes [5]–[7], suggesting very different characteristics for CPP in infants and toddlers in comparison to CPP in children between 3-8 years.

In conclusion, age should not be a limiting factor for GnRHa treatment as its efficacy and safety in children aged less than 2 years seems comparable to that in older children.

References: 1. Carel JC, Eugster EA, Rogol A, Ghizzoni L, Palmert MR. (2009) “Consensus statement on the use of gonadotropin-releasing hormone analogs in children.” Pediatrics. 2009 Apr; 123(4):e752–62. 2. Cisternino M, Arrigo T, Pasquino AM, Tinelli C, Antoniazzi F, Beduschi L, Bindi G, Borrelli P, De Sanctis V, Farello G, Galluzzi F, Gargantini L, Lo Presti D, Sposito M, Tatò L. (2000) “Etiology and age incidence of precocious puberty in girls: a multicentric study.” J Pediatr Endocrinol Metab; 13 Suppl 1:695–701. 3. Prété G, Couto-Silva AC, Trivin C, Brauner R. (2008) “Idiopathic central precocious puberty in girls: Presentation factors,” BMC Pediatr.; 8:27. 4. Giabicani E, Allali S, Durand A, Sommet J, Couto-Silva AC, Brauner R. (2013) “Presentation of 493 Consecutive Girls with Idiopathic Central Precocious Puberty: A Single-Center Study,” PLoS ONE; 8(7):e70931. 5. Pedicelli S, Alessio P, Scirè G, Cappa M, Cianfarani S. (2014) “Routine screening by brain magnetic resonance imaging is not indicated in every girl with onset of puberty between the ages of 6 and 8 years.,” J Clin Endocrinol Metab; 99(12): 4455–61. 6. Latronico AC, Brito VN, Carel JC. (2016) “Causes, diagnosis, and treatment of central precocious puberty.,” Lancet Diabetes Endocrinol; 4(3): 265–274. 7. Chemaitilly W, Trivin C, Adan L, Gall V, Sainte-Rose C, Brauner R. (2001) “Central precocious puberty: clinical and laboratory features.,” Clin Endocrinol (Oxf); 54(3): 289–94.