Alev ÖZÖN, Doğuş VURALLI, Ayfer ALİKAŞİFOĞLU, E. Nazlı GÖNÇ, Nurgün KANDEMİR, Kader K. OĞUZ

Gender-related differences in etiology of organic central precocious puberty

Background. Central precocious puberty (CPP) is idiopathic in 90% of girls and 60% of boys, while some cases are caused by lesions of central nervous system (CNS), a condition often referred to as organic CPP. We aimed to analyze the etiology of organic CPP in a large cohort of girls and boys and determine gender-related differences. Methods. Medical files of 256 girls and 120 boys diagnosed and treated for CPP in a single center in the last two decades were reviewed. Patients were classified into four groups with respect to previous history and MRI findings: (1) previously established CNS pathology at the time of diagnosis, (2) novel CNS pathology previously asymptomatic, (3) incidentalomas considered to be unrelated to CPP, and (4) completely normal MRI. Group 1 and 2 were considered as organic CPP whereas group 3 and 4 were considered as idiopathic CPP.Results. Prevalence of CNS pathology was significantly higher in boys than girls (21.7% vs 6.2%). Previous CNS pathologies such as developmental anomaly of CNS, parenchymal injury, necrotic lesions and hydrocephalus were present in 3.5% of girls and 8.3% of boys. Prevalence of novel CNS pathology as determined by imaging among neurologically asymptomatic patients was 2.8% in girls and 14.5% in boys. The most common novel CNS pathologies in boys were hamartomas (5%) and suprasellar arachnoid cysts (3.3%); which were significantly lower in girls (0.8 and 0.8% respectively). Onset of organic CPP was before six years in girls, and seven years in boys.Conclusions. Organic CPP was 3.5 times more common in boys compared to girls. It is possible to detect an underlying CNS pathology in one out of every five boys with CPP. Frequency and distribution of organic etiology also differ between girls and boys, hypothalamic hamartomas and suprasellar arachnoid cysts being more common in boys than girls. The likelihood of novel intracranial pathology associated with CPP is quite low in girls with an onset after six years of age and in boys with an onset after seven years of age.

PDF

___

1.Cisternino M, Arrigo T, Pasquino AM, et al. Etiology and age incidence of precocious puberty in girls: a multicentric study. J Pediatr Endocrinol Metab 2000; 13(Suppl 1): 695-701.
2.Chemaitilly W, Trivin C, Adan L, Gall V, Sainte-Rose C, Brauner R. Central precocious puberty: clinical and laboratory features. Clin Endocrinol (Oxf) 2001; 54: 289-294.
3.Chalumeau M, Hadjiathanasiou CG, Ng SM, et al. Selecting girls with precocious puberty for brain imaging: validation of European evidence-based diagnosis rule. J Pediatr 2003; 143: 445-450.
4.Pescovitz OH, Comite F, Hench K, et al. The NIH experience with precocious puberty: diagnostic subgroups and response to short-term luteinizing hormone releasing hormone analogue therapy. J Pediatr 1986; 108: 47-54.
5.Desai M, Colaco MP, Choksi CS, Ambadkar MC, Vaz FE, Gupte C. Isosexual precocity: the clinical and etiologic profile. Indian Pediatr 1993; 30: 607-623.
6.Alikasifoglu A, Vuralli D, Gonc EN, Ozon A, Kandemir N. Changing etiological trends in male precocious puberty: evaluation of 100 cases with central precocious puberty over the last decade. Horm Res Paediatr 2015; 83: 340-344.
7.Neely EK, Hintz RL, Wilson DM, et al. Normal ranges for immunochemiluminometric gonadotropin assays. J Pediatr 1995; 127: 40-46.
8.Neely EK, Wilson DM, Lee PA, Stene M, Hintz RL. Spontaneous serum gonadotropin concentrations in the evaluation of precocious puberty. J Pediatr 1995; 127: 47-52.
9.Carel JC, Lahlou N, Roger M, Chaussain JL. Precocious puberty and statural growth. Hum Reprod Update 2004; 10: 135-147.
10.Rosenfield RL, Cooke DW, Radovick S. Puberty and its disorders in a female. In: Sperling MA (ed). Pediatric Endocrinology (3rd ed). Philadelphia: WB Saunders 2008: 573-590.
11.Marshall WA, Tanner JM. Variations in pattern of pubertal changes in girls. Arch Dis Child 1969; 44: 291-303.
12.Brito VN, Spinola-Castro AM, Kochi C, Kopacek C, Silva PC, Guerra-Junior G. Central precocious puberty: revisiting the diagnosis and therapeutic management. Arch Endocrinol Metab 2016; 60: 163-172.
13.Milner GR, Levick RK, Kay R. Assessment of bone age: a comparison of the greulich and pyle, and the tanner and whitehouse methods. Clin Radiol 1986; 37: 119-121.
14.De Sanctis V, Corrias A, Rizzo V, et al. Etiology of central precocious puberty in males: the results of the Italian Study Group for Physiopathology of Puberty. J Pediatr Endocrinol Metab 2000; 13(Suppl 1): 687-693.
15.Topor LS, Bowerman K, Machan JT, Gilbert CL, Kangarloo T, Shaw ND. Central precocious puberty in Boston boys: a 10-year single center experience. PLoS One 2018; 13: e0199019.
16.Chalumeau M, Chemaitilly W, Trivin C, Adan L, Breart G, Brauner R. Central precocious puberty in girls: an evidence-based diagnosis tree to predict central nervous system abnormalities. Pediatrics 2002; 109: 61-67.
17.Ng SM, Kumar Y, Cody D, Smith CS, Didi M. Cranial MRI scans are indicated in all girls with central precocious puberty. Arch Dis Child 2003; 88: 414-418.
18.Mogensen SS, Aksglaede L, Mouritsen A, et al. Pathological and incidental findings on brain MRI in a single-center study of 229 consecutive girls with early or precocious puberty. PLoS One 2012; 7: e29829.
19.Mogensen SS, Aksglaede L, Mouritsen A, et al. Diagnostic work-up of 449 consecutive girls who were referred to be evaluated for precocious puberty. J Clin Endocrinol Metab 2011; 96: 1393-1401.
20.Cacciari E, Zucchini S, Carla G, et al. Endocrine function and morphological findings in patients with disorders of the hypothalamo-pituitary area: a study with magnetic resonance. Arch Dis Child 1990; 65: 1199-1202.
21.Argyropoulou MI, Kiortsis DN. MRI of the hypothalamic-pituitary axis in children. Pediatr Radiol 2005; 35: 1045-1055.
22.Arita K, Kurisu K, Kiura Y, Iida K, Otsubo H. Hypothalamic hamartoma. Neurol Med Chir (Tokyo) 2005; 45: 221-231.
23.Chan YM, Fenoglio-Simeone KA, Paraschos S, et al. Central precocious puberty due to hypothalamic hamartomas correlates with anatomic features but not with expression of GnRH, TGFalpha, or KISS1. Horm Res Paediatr 2010; 73: 312-319.
24.Molitch ME, Russell EJ. The pituitary “incidentaloma”. Ann Intern Med 1990; 112: 925-931.
25.Pedicelli S, Alessio P, Scire G, Cappa M, Cianfarani S. 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 2014; 99: 4455-4461.
26.Adan L, Bussieres L, Dinand V, Zerah M, Pierre-Kahn A, Brauner R. Growth, puberty and hypothalamic-pituitary function in children with suprasellar arachnoid cyst. Eur J Pediatr 2000; 159: 348-355.
27.Kornreich L, Horev G, Blaser S, Daneman D, Kauli R, Grunebaum M. Central precocious puberty: evaluation by neuroimaging. Pediatr Radiol 1995; 25: 7-11.
28.Cassio A, Cacciari E, Zucchini S, Balsamo A, Diegoli M, Orsini F. Central precocious puberty: clinical and imaging aspects. J Pediatr Endocrinol Metab 2000; 13(Suppl 1): 703-708.
29.Lebrethon MC, Bourguignon JP. Management of central isosexual precocity: diagnosis, treatment, outcome. Curr Opin Pediatr 2000; 12: 394-399.
30.Cacciari E, Frejaville E, Cicognani A, et al. How many cases of true precocious puberty in girls are idiopathic? J Pediatr 1983; 102: 357-360.
31.Lyon AJ, De Bruyn R, Grant DB. Isosexual precocious puberty in girls. Acta Paediatr Scand 1985; 74: 950-955.
32.Ng SM, Kumar Y, Cody D, Smith C, Didi M. The gonadotrophins response to GnRH test is not a predictor of neurological lesion in girls with central precocious puberty. J Pediatr Endocrinol Metab 2005; 18: 849-852.
33.Kaplowitz PB. Do 6-8 year old girls with central precocious puberty need routine brain imaging? Int J Pediatr Endocrinol 2016; 2016: 9.