Clinical guidelines «Precocious puberty»

The precocious puberty is an urgent problem of pediatric endocrinology characterized by clinical and pathogenetic heterogeneity. The appearance of secondary sex characteristics before the age of 8 years in girls and 9 years in boys requires timely diagnosis and the appointment of pathogenetically justified treatment in order to achieve the target indicators of final growth and prevent social deprivation. The developed clinical guidelines are the main working tool of the practitioner. They briefly and structurally present the main information about the epidemiology and modern classification of рrecocious puberty, methods of its diagnosis and treatment based on the principles of evidence-based medicine.

1. Dedov II, Semicheva TV, Peterkova VA. Polovoe razvitie: norma i patologiya. Moscow: Kolor It Studio; 2002. P. 67-69. (In Russ.).

2. Dedov II, Peterkova VA. Rukovodstvo po detskoi endokrinologii. Moscow: Universum pablishing; 2006. (In Russ.).

3. Carel J-C, Eugster EA, Rogol A, et al. Consensus Statement on the Use of Gonadotropin-Releasing Hormone Analogs in Children. Pediatrics. 2009;123(4):e752-e762. doi: https://doi.org/10.1542/peds.2008-1783

4. Marshall WA, Tanner JM. Variations in the Pattern of Pubertal Changes in Boys. Arch Dis Child. 1970;45(239):13-23. doi: https://doi.org/10.1136/adc.45.239.13

5. Chen M, Eugster EA. Central Precocious Puberty: Update on Diagnosis and Treatment. Pediatr Drugs. 2015;17(4):273-281. doi: https://doi.org/10.1007/s40272-015-0130-8

6. Partsch C-J, Japing I, Siebert R, et al. Central precocious puberty in girls with Williams syndrome. J Pediatr. 2002;141(3):441-444. doi: https://doi.org/10.1067/mpd.2002.127280

7. Temple IK, Cockwell A, Hassold T, et al. Maternal uniparental disomy for chromosome 14. J Med Genet. 1991;28(8):511-514. doi: https://doi.org/10.1136/jmg.28.8.511

8. Ioannides Y, Lokulo-Sodipe K, Mackay DJ, et al. Temple syndrome: improving the recognition of an underdiagnosed chromosome 14 imprinting disorder: an analysis of 51 published cases. J Med Genet. 2014;51(8):495-501. doi: https://doi.org/10.1136/jmedgenet-2014-102396

9. Wakeling EL, Brioude F, Lokulo-Sodipe O, et al. Diagnosis and management of Silver-Russell syndrome: first international consensus statement. Nat Rev Endocrinol. 2017;13(2):105-124. doi: https://doi.org/10.1038/nrendo.2016.138

10. Berberoğlu M. Precocious puberty and normal variant puberty: definition, etiology, diagnosis and current management. J Clin Res Pediatr Endocrinol. 2009;1(4):164-174. doi: https://doi.org/10.4274/jcrpe.v1i4.3

11. Haddad NG, Eugster EA. Peripheral precocious puberty including congenital adrenal hyperplasia: causes, consequences, management and outcomes. Best Pract Res Clin Endocrinol Metab. 2019;33(3):101273. doi: https://doi.org/10.1016/j.beem.2019.04.007

12. Rousseau-Merck MF, Misrahi M, Atger M, et al. Localization of the human luteinizing hormone/choriogonadotropin receptor gene (LHCGR) to chromosome 2p21. Cytogenet Genome Res. 1990;54(1-2):77-79. doi: https://doi.org/10.1159/000132962

13. Shenker A, Laue L, Kosugi S, et al. A constitutively activating mutation of the luteinizing hormone receptor in familial male precocious puberty. Nature. 1993;365(6447):652-654. doi: https://doi.org/10.1038/365652a0

14. Weinstein LS, Shenker A, Gejman PV., et al. Activating Mutations of the Stimulatory G Protein in the McCune–Albright Syndrome. N Engl J Med. 1991;325(24):1688-1695. doi: https://doi.org/10.1056/NEJM199112123252403

15. Svoboda P, et al. Biochemistry of transmembrane signaling mediated by trimeric G proteins. Physiol. Res. 2004;53(1):141-152.

16. Dumitrescu CE, Collins MT. McCune-Albright syndrome. Orphanet J Rare Dis. 2008;3(1):12. doi: https://doi.org/10.1186/1750-1172-3-12

17. Collins MT, Singer FR, Eugster E. McCune-Albright syndrome and the extraskeletal manifestations of fibrous dysplasia. Orphanet J Rare Dis. 2012;7(S1):S4. doi: https://doi.org/10.1186/1750-1172-7-S1-S4

18. Coutant R, Lumbroso S, Rey R, et al. Macroorchidism due to Autonomous Hyperfunction of Sertoli Cells and G s α Gene Mutation: An Unusual Expression of McCune-Albright Syndrome in a Prepubertal Boy. J Clin Endocrinol Metab. 2001;86(4):1778-1781. doi: https://doi.org/10.1210/jcem.86.4.7391

19. Sinnecker G, Willig RP, Stahnke N, Braendle W. Precocious pseudopuberty associated with multiple ovarian follicular cysts and low plasma oestradiol concentrations. Eur J Pediatr. 1989;148(7):600-602. doi: https://doi.org/10.1007/BF00441508

20. Pienkowski C, Cartault A, Carfagna L, et al. Ovarian cysts in prepubertal girls. Endocr Dev. 2012;22:101-111. doi: https://doi.org/10.1159/000326627

21. Dehner LP. Gonadal and extragonadal germ cell neoplasia of childhood. Hum Pathol. 1983;14(6):493-511. doi: https://doi.org/10.1016/S0046-8177(83)80004-5

22. McLachlan RI, O’Donnell L, Meachem SJ, et al. Identification of specific sites of hormonal regulation in spermatogenesis in rats, monkeys, and man. Recent Prog Horm Res. 2002;57:149-179. doi: https://doi.org/10.1210/rp.57.1.149

23. Kubo O, Yamasaki N, Kamijo Y, et al. Human chorionic gonadotropin produced by ectopic pinealoma in a girl with precocious puberty. J Neurosurg. 1977;47(1):101-105. doi: https://doi.org/10.3171/jns.1977.47.1.0101

24. Kitanaka C, Matsutani M, Sora S, et al. Precocious puberty in a girl with an hCG-secreting suprasellar immature teratoma. J Neurosurg. 1994;81(4):601-604. doi: https://doi.org/10.3171/jns.1994.81.4.0601

25. Anasti JN, Flack MR, Froehlich J, et al. A potential novel mechanism for precocious puberty in juvenile hypothyroidism. J Clin Endocrinol Metab. 1995;80(1):276-279. doi: https://doi.org/10.1210/jcem.80.1.7829625

26. Bezlepkina OB, Semicheva TV, Yarovaya IS. Van Wyk-Grumbach syndrome in children (Review of literature with descriptions of clinical cases). Problems of Endocrinology. 1994;40(4):35-38. (In Russ.). doi: https://doi.org/10.14341/probl12143

27. Wyk JJ Van, Grumbach MM. Syndrome of precocious menstruation and galactorrhea in juvenile hypothyroidism: an example of hormonal overlap in pituitary feedback. J Pediatr. 1960;57(3):416-435. doi: https://doi.org/10.1016/S0022-3476(60)80250-8

28. Fuqua JS. Treatment and outcomes of precocious puberty: an update. J Clin Endocrinol Metab. 2013;98(6):2198-2207. doi: https://doi.org/10.1210/jc.2013-1024

29. de Vries L, Guz-Mark A, Lazar L, et al. Premature thelarche: age at presentation affects clinical course but not clinical characteristics or risk to progress to precocious puberty. J Pediatr. 2010;156(3):466-471. doi: https://doi.org/10.1016/j.jpeds.2009.09.071

30. Novello L, Speiser PW. Premature Adrenarche. Pediatr Ann. 2018;47(1):e7-e11. doi: https://doi.org/10.3928/19382359-20171214-04

31. Teilmann G. Prevalence and Incidence of Precocious Pubertal Development in Denmark: An Epidemiologic Study Based on National Registries. Pediatrics. 2005;116(6):1323-1328. doi: https://doi.org/10.1542/peds.2005-0012

32. Jung H, Ojeda SR. Pathogenesis of precocious puberty in hypothalamic hamartoma. Hormone Research. 2002;57(2):31-34. doi: https://doi.org/10.1159/000058097

33. Valdueza JM, Cristante L, Dammann O, et al. Hypothalamic Hamartomas. Neurosurgery. 1994;34(6):949-958. doi: https://doi.org/10.1227/00006123-199406000-00001

34. Gjikopulli A, Kollcaku L, Grimci L, et al. P32 – 2702: Hypothalamic hamartoma, gelastic epilepsy and precocious puberty. Eur J Paediatr Neurol. 2015;19:S103. doi: https://doi.org/10.1016/S1090-3798(15)30345-7

35. Stephen M, Zage P, Waguespack S. Gonadotropin-Dependent Precocious Puberty: Neoplastic Causes and Endocrine Considerations. Int J Pediatr Endocrinol. 2011;2011(1):184502. doi: https://doi.org/10.1155/2011/184502

36. Wood LD, Noë M, Hackeng W, et al. Patients with McCune-Albright syndrome have a broad spectrum of abnormalities in the gastrointestinal tract and pancreas. Virchows Arch. 2017;470(4):391-400. doi: https://doi.org/10.1007/s00428-017-2086-2

37. Imel EA, Econs MJ. Fibrous dysplasia, phosphate wasting and fibroblast growth factor 23. Pediatr Endocrinol Rev PER. 2007;4(4):434-439.

38. Foster CM, Ross JL, Shawker T, et al. Absence of Pubertal Gonadotropin Secretion in Girls with McCune-Albright Syndrome. J Clin Endocrinol Metab. 1984;58(6):1161-1165. doi: https://doi.org/10.1210/jcem-58-6-1161

39. Rivarola M, Belgorosky A, Mendilaharzu H, Vidal G. Precocious puberty in children with tumours of the suprasellar and pineal areas: Organic central precocious puberty. Acta Paediatr. 2007;90(7):751-756. doi: https://doi.org/10.1111/j.1651-2227.2001.tb02800.x

40. Mills JL. Premature Thelarche. Am J Dis Child. 1981;135(8):743. doi: https://doi.org/10.1001/archpedi.1981.02130320057019

41. DeSalvo DJ, Mehra R, Vaidyanathan P, Kaplowitz PB. In children with premature adrenarche, bone age advancement by 2 or more years is common and generally benign. J Pediatr Endocrinol Metab. 2013;26(3-4):215-221. doi: https://doi.org/10.1515/jpem-2012-0283

42. Van Winter JT, Noller KL, Zimmerman D, Melton LJ. Natural history of premature thelarche in Olmsted County, Minnesota, 1940 to 1984. J Pediatr. 1990;116(2):278-280. doi: https://doi.org/10.1016/S0022-3476(05)82891-4

43. de Vries L, Horev G, Schwartz M, Phillip M. Ultrasonographic and clinical parameters for early differentiation between precocious puberty and premature thelarche. Eur J Endocrinol. 2006;154(6):891-898. doi: https://doi.org/10.1530/eje.1.02151

44. Millar DM, Blake JM, Stringer DA, et al. Prepubertal Ovarian Cyst Formation: 5 Years’ Experience. J Diagnostic Med Sonogr. 1993;9(3):168-168. doi: https://doi.org/10.1177/875647939300900331

45. de Sousa G, Wunsch R, Andler W. Precocious pseudopuberty due to autonomous ovarian cysts: A report of ten cases and long-term follow-up. Hormones. 2008;7(2):170-174. doi: https://doi.org/10.1007/BF03401509

46. Papanikolaou A, Michala L. Autonomous Ovarian Cysts in Prepubertal Girls. How Aggressive Should We Be? A Review of the Literature. J Pediatr Adolesc Gynecol. 2015;28(5):292-296. doi: https://doi.org/10.1016/j.jpag.2015.05.004

47. Papadimitriou A, Beri D, Tsialla A, et al. Early growth acceleration in girls with idiopathic precocious puberty. J Pediatr. 2006;149(1):43-46. doi: https://doi.org/10.1016/j.jpeds.2006.02.005

48. Fontoura M, Brauner R, Prevot C, Rappaport R. Precocious puberty in girls: early diagnosis of a slowly progressing variant. Arch Dis Child. 1989;64(8):1170-1176. doi: https://doi.org/10.1136/adc.64.8.1170

49. Ladjouze A, Soskin S, Garel C, et al. GH deficiency with central precocious puberty: A new rare disorder associated with a developmental defect of the hypothalamic-pituitary area. Eur J Endocrinol. 2007;156(4):463-469. doi: https://doi.org/10.1530/EJE-06-0688

50. Burke AB, Collins MT, Boyce AM. Fibrous dysplasia of bone: craniofacial and dental implications. Oral Dis. 2017;23(6):697-708. doi: https://doi.org/10.1111/odi.12563

51. Robinson C, Collins MT, Boyce AM. Fibrous Dysplasia/McCune-Albright Syndrome: Clinical and Translational Perspectives. Curr Osteoporos Rep. 2016;14(5):178-186. doi: https://doi.org/10.1007/s11914-016-0317-0

52. Kim I-S, Kim ER, Nam HJ, et al. Activating Mutation of GSα in McCune-Albright Syndrome Causes Skin Pigmentation by Tyrosinase Gene Activation on Affected Melanocytes. Horm Res Paediatr. 1999;52(5):235-240. doi: https://doi.org/10.1159/000023467

53. 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(1):695-701. doi: https://doi.org/10.1515/JPEM.2000.13.S1.695

54. Marshall WA, Tanner JM. Variations in the Pattern of Pubertal Changes in Boys. Arch Dis Child. 1970;45(239):13-23. doi: https://doi.org/10.1136/adc.45.239.13

55. Marshall WA, Tanner JM. Variations in pattern of pubertal changes in girls. Arch Dis Child. 1969;44(235):291-303. doi: https://doi.org/10.1136/adc.44.235.291

56. Neely EK, Hintz RL, Wilson DM, et al. Normal ranges for immunochemiluminometric gonadotropin assays. J Pediatr. 1995;127(1):40-46. doi: https://doi.org/10.1016/S0022-3476(95)70254-7

57. Neely EK, Wilson DM, Lee PA, et al. Spontaneous serum gonadotropin concentrations in the evaluation of precocious puberty. J Pediatr. 1995;127(1):47-52. doi: https://doi.org/10.1016/S0022-3476(95)70255-5

58. Houk CP, Kunselman AR, Lee PA. Adequacy of a Single Unstimulated Luteinizing Hormone Level to Diagnose Central Precocious Puberty in Girls. Pediatrics. 2009;123(6):e1059-e1063. doi: https://doi.org/10.1542/peds.2008-1180

59. Resende EAMR, Lara BHJ, Reis JD, et al. Assessment of Basal and Gonadotropin-Releasing Hormone-Stimulated Gonadotropins by Immunochemiluminometric and Immunofluorometric Assays in Normal Children. J Clin Endocrinol Metab. 2007;92(4):1424-1429. doi: https://doi.org/10.1210/jc.2006-1569

60. Bay K, Andersson A-M, Skakkebaek NE. Estradiol levels in prepubertal boys and girls - analytical challenges. Int J Androl. 2004;27(5):266-273. doi: https://doi.org/10.1111/j.1365-2605.2004.00487.x

61. Harrington J, Palmert MR, Hamilton J. Use of local data to enhance uptake of published recommendations: an example from the diagnostic evaluation of precocious puberty. Arch Dis Child. 2014;99(1):15-20. doi: https://doi.org/10.1136/archdischild-2013-304414

62. Lee D-M, Chung I-H. Morning basal luteinizing hormone, a good screening tool for diagnosing central precocious puberty. Ann Pediatr Endocrinol Metab. 2019;24(1):27-33. doi: https://doi.org/10.6065/apem.2019.24.1.27

63. Bangalore Krishna K, Fuqua JS, Rogol AD, et al. Use of Gonadotropin-Releasing Hormone Analogs in Children: Update by an International Consortium. Horm Res Paediatr. 2019;91(6):357-372. doi: https://doi.org/10.1159/000501336

64. Kuiri-Hänninen T, Sankilampi U, Dunkel L. Activation of the Hypothalamic-Pituitary-Gonadal Axis in Infancy: Minipuberty. Horm Res Paediatr. 2014;82(2):73-80. doi: https://doi.org/10.1159/000362414

65. Bizzarri C, Spadoni GL, Bottaro G, et al. The Response to Gonadotropin Releasing Hormone (GnRH) Stimulation Test Does Not Predict the Progression to True Precocious Puberty in Girls With Onset of Premature Thelarche in the First Three Years of Life. J Clin Endocrinol Metab. 2014;99(2):433-439. doi: https://doi.org/10.1210/jc.2013-3292

66. Pescovitz OH, Hench KD, Barnes KM, et al. Premature Thelarche and Central Precocious Puberty: The Relationship Between Clinical Presentation and the Gonadotropin Response to Luteinizing Hormone-Releasing Hormone. J Clin Endocrinol Metab. 1988;67(3):474-479. doi: https://doi.org/10.1210/jcem-67-3-474

67. Oerter KE, Uriarte MM, Rose SR, et al. Gonadotropin Secretory Dynamics During Puberty in Normal Girls and Boys. J Clin Endocrinol Metab. 1990;71(5):1251-1258. doi: https://doi.org/10.1210/jcem-71-5-1251

68. Neely EK, Hintz RL, Wilson DM, et al. Normal ranges for immunochemiluminometric gonadotropin assays. J Pediatr. 1995;127(1):40-46. doi: https://doi.org/10.1016/S0022-3476(95)70254-7

69. Brito VN. Diagnostic Value of Fluorometric Assays in the Evaluation of Precocious Puberty. J Clin Endocrinol Metab. 1999;84(10):3539-3544. doi: https://doi.org/10.1210/jc.84.10.3539

70. Brito VN, Latronico AC, Arnhold IJP, Mendonca BB. A Single Luteinizing Hormone Determination 2 Hours after Depot Leuprolide Is Useful for Therapy Monitoring of Gonadotropin-Dependent Precocious Puberty in Girls. J Clin Endocrinol Metab. 2004;89(9):4338-4342. doi: https://doi.org/10.1210/jc.2003-031537

71. Pasternak Y, Friger M, Loewenthal N, et al. The utility of basal serum LH in prediction of central precocious puberty in girls. Eur J Endocrinol. 2012;166(2):295-299. doi: https://doi.org/10.1530/EJE-11-0720

72. Sathasivam A, Garibaldi L, Shapiro S, et al. Original article: Leuprolide stimulation testing for the evaluation of early female sexual maturation. Clin Endocrinol (Oxf). 2010;73(3):375-381. doi: https://doi.org/10.1111/j.1365-2265.2010.03796.x

73. Lee DS, Ryoo NY, Lee SH, et al. Basal luteinizing hormone and follicular stimulating hormone: is it sufficient for the diagnosis of precocious puberty in girls? Ann Pediatr Endocrinol Metab. 2013;18(4):196. doi: https://doi.org/10.6065/apem.2013.18.4.196

74. Freire AV, Escobar ME, Gryngarten MG, et al. High diagnostic accuracy of subcutaneous Triptorelin test compared with GnRH test for diagnosing central precocious puberty in girls. Clin Endocrinol (Oxf). 2013;78(3):398-404. doi: https://doi.org/10.1111/j.1365-2265.2012.04517.x

75. Eckert KL, Wilson DM, Bachrach LK, et al. A single-sample, subcutaneous gonadotropin-releasing hormone test for central precocious puberty. Pediatrics. 1996;97:517-519.

76. Roger M, Lahlou N, Chaussain JL. Gonadotropin-releasing hormone testing in pediatrics. In: Ranke MB, ed. Diagnostics of Endocrine Function in Children and Adolescents. Heidelberg, Germany: Johann Ambrosius Barth; 1996. P. 346-369.

77. Wilson DA, Hofman PL, Miles HL, et al. Evaluation of the buserelin stimulation test in diagnosing gonadotropin deficiency in males with delayed puberty. J Pediatr. 2006;148(1):89-94. doi: https://doi.org/10.1016/j.jpeds.2005.08.045

78. Khadilkar V, Khadilkar A, Prasad H, et al. Evaluation of GnRH analogue testing in diagnosis and management of children with pubertal disorders. Indian J Endocrinol Metab. 2012;16(3):400. doi: https://doi.org/10.4103/2230-8210.95682

79. Bolmasova AV. Optimizatsiya rostovogo prognoza u detei s gonadotropinzavisimymi formami prezhdevremennogo polovogo razvitiya opukholevogo i neopukholevogo geneza. [dissertation] Moscow; 2012. (In Russ.).

80. Chudecka-Głaz A, Rzepka-Górska I, Kosmowska B, Głaz C. The levels of selected hormones in serum and ovarian cyst fluid in girls and young women. Ginekol Pol. 1999;70(5):236-241.

81. Padilla SL. Androgen-producing tumors in children and adolescents. Adolesc Pediatr Gynecol. 1989;2(3):135-142. doi: https://doi.org/10.1016/S0932-8610(89)80003-9

82. Englund AT. Pediatric Germ Cell and Human Chorionic Gonadotropin — Producing Tumors. Am J Dis Child. 1991;145(11):1294. doi: https://doi.org/10.1001/archpedi.1991.02160110086026

83. Livadas S, Dracopoulou M, Dastamani A, et al. The spectrum of clinical, hormonal and molecular findings in 280 individuals with nonclassical congenital adrenal hyperplasia caused by mutations of the CYP21A2 gene. Clin Endocrinol (Oxf). 2015;82(4):543-549. doi: https://doi.org/10.1111/cen.12543

84. Razavi Z., RastgooHaghi A. Precocious Puberty Associated with an Adrenal Tumor: A case report. Iran J Ped Hematol Oncol. 2016;l6(2):136-141

85. Goyal A, Malhotra R, Khadgawat R. Precocious pseudopuberty due to virilising adrenocortical carcinoma progressing to central precocious puberty after surgery. BMJ Case Rep. 2019;12(3):e229476. doi: https://doi.org/10.1136/bcr-2019-229476

86. Kafi SE, Alagha E, Shazly MA, Al-Agha A. Pseudo-precocious Puberty Associated with an Adrenocortical Tumor in a Young Child. Cureus. 2019;11(12):e6440. doi: https://doi.org/10.7759/cureus.6440

87. Armengaud J-B, Charkaluk M-L, Trivin C, et al. Precocious Pubarche: Distinguishing Late-Onset Congenital Adrenal Hyperplasia from Premature Adrenarche. J Clin Endocrinol Metab. 2009;94(8):2835-2840. doi: https://doi.org/10.1210/jc.2009-0314

88. Comite F, Schiebinger RJ, Albertson BD, et al. Isosexual Precocious Pseudopuberty Secondary to a Feminizing Adrenal Tumor. J Clin Endocrinol Metab. 1984;58(3):435-440. doi: https://doi.org/10.1210/jcem-58-3-435

89. Tanner JM, Whitehouse RH, Marshall WA, et al. Assessment of Skeletal Maturity and Prediction of Adult Height (TW2 Method). New York: Academic Press$ 1975.

90. Vejvoda M, Grant DB. Discordant bone maturation of the hand in children with precocious puberty and congenital adrenal hyperplasia. Acta Paediatr. 1981;70(6):903-905. doi: https://doi.org/10.1111/j.1651-2227.1981.tb06248.x

91. Zhukovskii MA, Bukhman AI. Sroki okosteneniya skeleta kisti i distal’nogo otdela predplech’ya u detei i podrostkov g. Moskvy In: Detskaya endokrinologiya: Rukovodstvo dlya vrachei. Moscow: Meditsina; 1995. P. 40. (In Russ.).

92. Greulich W, Pyle S. Radiographic Atlas of Skeletal Development of the Hand and Wrist. Stanford, Calif: Stanford University Press; 1999.

93. Bull RK, Edwards PD, Kemp PM, et al. Bone age assessment: a large scale comparison of the Greulich and Pyle, and Tanner and Whitehouse (TW2) methods. Arch Dis Child. 1999;81(2):172-173. doi: https://doi.org/10.1136/adc.81.2.172

94. Fahmy JL, Kaminsky CK, Kaufman F, et al. The radiological approach to precocious puberty. Br J Radiol. 2000;73(869):560-567. doi: https://doi.org/10.1259/bjr.73.869.10884758

95. Martin DD, Stahl K, Schweizer R, et al. Validation of BoneXpert in children with precocious puberty. Horm Res 2008;70(1):73.

96. Breen MA, Tsai A, Stamm A, Kleinman PK. Bone age assessment practices in infants and older children among Society for Pediatric Radiology members. Pediatr Radiol. 2016;46(9):1269-1274. doi: https://doi.org/10.1007/s00247-016-3618-7

97. Xu Y-Q, Li G-M, Li Y. Advanced bone age as an indicator facilitates the diagnosis of precocious puberty. J Pediatr (Rio J). 2018;94(1):69-75. doi: https://doi.org/10.1016/j.jped.2017.03.010

98. Martin DD, Wit JM, Hochberg Z, et al. The Use of Bone Age in Clinical Practice – Part 2. Horm Res Paediatr. 2011;76(1):10-16. doi: https://doi.org/10.1159/000329374

99. 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(1):e29829. doi: https://doi.org/10.1371/journal.pone.0029829

100. Lee J, Kim J, Yang A, et al. Etiological trends in male central precocious puberty. Ann Pediatr Endocrinol Metab. 2018;23(2):75-80. doi: https://doi.org/10.6065/apem.2018.23.2.75

101. Kaplowitz PB. Do 6-8 year old girls with central precocious puberty need routine brain imaging? Int J Pediatr Endocrinol. 2016;2016(1):9. doi: https://doi.org/10.1186/s13633-016-0027-5

102. Kim I, Young RH, Scully RE. Leydig cell tumors of the testis. Am J Surg Pathol. 1985;9(3):177-192. doi: https://doi.org/10.1097/00000478-198503000-00002

103. Cecchetto G, Alaggio R, Bisogno G, et al. Sex cord-stromal tumors of the testis in children. A clinicopathologic report from the Italian TREP project. J Pediatr Surg. 2010;45(9):1868-1873. doi: https://doi.org/10.1016/j.jpedsurg.2010.02.120

104. Wendt S, Shelso J, Wright K, Furman W. Neoplastic causes of abnormal puberty. Pediatr Blood Cancer. 2014;61(4):664-671. doi: https://doi.org/10.1002/pbc.24825

105. Alagha E, Kafi SE, Shazly MA, Al-Agha A. Precocious Puberty Associated with Testicular Hormone-secreting Leydig Cell Tumor. Cureus. December 2019;11(12):e6441. doi: https://doi.org/10.7759/cureus.6441

106. Haber HP, Wollmann HA, Ranke MB. Pelvic ultrasonography: Early differentiation between isolated premature thelarche and central precocious puberty. Eur J Pediatr. 1995;154(3):182-186. doi: https://doi.org/10.1007/BF01954267

107. Sathasivam A, Rosenberg HK, Shapiro S, et al. Pelvic Ultrasonography in the Evaluation of Central Precocious Puberty: Comparison with Leuprolide Stimulation Test. J Pediatr. 2011;159(3):490-495. doi: https://doi.org/10.1016/j.jpeds.2011.02.032

108. Badouraki M, Christoforidis A, Economou I, et al. Evaluation of pelvic ultrasonography in the diagnosis and differentiation of various forms of sexual precocity in girls. Ultrasound Obstet Gynecol. 2008;32(6):819-827. doi: https://doi.org/10.1002/uog.6148

109. Kang E, Cho JH, Choi J-H, Yoo H-W. Etiology and therapeutic outcomes of children with gonadotropin-independent precocious puberty. Ann Pediatr Endocrinol Metab. 2016;21(3):136. doi: https://doi.org/10.6065/apem.2016.21.3.136

110. Schneider DT, Terenziani M, Cecchetto G. et al., editors. Gonadal and extragonadal germ cell tumors, sex cord stromal and rare gonadal tumors. In: Rare Tumors in Children and Adolescents. Germany: Springer Berlin Heidelberg; 2102. P. 327-402.

111. Parida L. Nonurological malignancies in children. J Indian Assoc Pediatr Surg. 2014;19:31-37. doi: https://doi.org/10.4103/0971-9261.125960

112. Lin X, Wu D, Zheng N, et al. Gonadal germ cell tumors in children. Medicine (Baltimore). 2017;96(26):e7386. doi: https://doi.org/10.1097/MD.0000000000007386

113. Javaid MK, Boyce A, Appelman-Dijkstra N, et al. Best practice management guidelines for fibrous dysplasia/McCune-Albright syndrome: a consensus statement from the FD/MAS international consortium. Orphanet J Rare Dis. 2019;14(1):139. doi: https://doi.org/10.1186/s13023-019-1102-9

114. Mulder RL, Kremer LCM, Santen HM van, et al. Prevalence and risk factors of radiation-induced growth hormone deficiency in childhood cancer survivors: A systematic review. Cancer Treat Rev. 2009;35(7):616-632. doi: https://doi.org/10.1016/j.ctrv.2009.06.004

115. van Iersel L, Li Z, Srivastava DK, et al. Hypothalamic-Pituitary Disorders in Childhood Cancer Survivors: Prevalence, Risk Factors and Long-Term Health Outcomes. J Clin Endocrinol Metab. 2019;104(12):6101-6115. doi: https://doi.org/10.1210/jc.2019-00834

116. Costin G, Kaufman F. Hypopituitarism and precocious puberty (pp). Pediatr Res. 1984;18(1):166A-166A. doi: https://doi.org/10.1203/00006450-198404001-00437

117. Darzy KH, Shalet SM. Hypopituitarism following radiotherapy. Pituitary. 2009;12(1):40-50. doi: https://doi.org/10.1007/s11102-008-0088-4

118. Darzy KH. Radiation-induced hypopituitarism after cancer therapy: who, how and when to test. Nat Clin Pract Endocrinol Metab. 2009;5(2):88-99. doi: https://doi.org/10.1038/ncpendmet1051

119. Bangalore Krishna K, Fuqua JS, Rogol AD, et al. Use of Gonadotropin-Releasing Hormone Analogs in Children: Update by an International Consortium. Horm Res Paediatr. 2019;91(6):357-372. doi: https://doi.org/10.1159/000501336

120. Federal Law of Russian Federation №403 оf 26.04.2012 (Ed. 20.11.2018) «O poryadke vedeniya Federal’nogo registra lits, stradayushchikh zhizneugrozhayushchimi i khronicheskimi progressiruyushchimi redkimi (orfannymi) zabolevaniyami, privodyashchimi k sokrashcheniyu prodolzhitel’nosti zhizni grazhdan ili ikh invalidnosti, i ego regional’nogo segmenta». (In Russ.).

121. Lazar L, Padoa A, Phillip M. Growth Pattern and Final Height after Cessation of Gonadotropin-Suppressive Therapy in Girls with Central Sexual Precocity. J Clin Endocrinol Metab. 2007;92(9):3483-3489. doi: https://doi.org/10.1210/jc.2007-0321

122. Parker KL, Baens-Bailon RG, Lee PA. Depot Leuprolide Acetate Dosage for Sexual Precocity*. J Clin Endocrinol Metab. 1991;73(1):50-52. doi: https://doi.org/10.1210/jcem-73-1-50

123. Partsch, E von Büren, M Bra C-J. Efficacy of the subcutaneous reformulated triptorelin depot in children with central precocious puberty. Acta Paediatr. 1998;87(12):1240-1244. doi: https://doi.org/10.1080/080352598750030906

124. Tatò L, Savage MO, Antoniazzi F, et al. Optimal Therapy of Pubertal Disorders in Precocious/Early Puberty. J Pediatr Endocrinol Metab. 2001;14(2):985-995. doi: https://doi.org/10.1515/jpem-2001-s211

125. Antoniazzi F, Zamboni G. Central Precocious Puberty. Pediatr Drugs. 2004;6(4):211-231. doi: https://doi.org/10.2165/00148581-200406040-00002

126. Yilmaz GC, Kara C, Bitkin EC, Aydin HM. Comparison of Triptorelin Versus Leuprolide in Treatment of Girls with Central Precocious Puberty. In European Society for Paediatric Endocrinology; [Internet] 2016 [cited 2019 Dec 9]. Available from: http://abstracts.eurospe.org/hrp/0086/hrp0086p2-p778.

127. Lahlou N, Carel J-C, Chaussain J-L, Roger M. Pharmacokinetics and Pharmacodynamics of GnRH Agonists: Clinical Implications in Pediatrics. J Pediatr Endocrinol Metab. 2000;13(1):723-737. doi: https://doi.org/10.1515/JPEM.2000.13.S1.723

128. Boepple PA, Mansfield MJ, Wierman ME, et al. Use of a Potent, Long Acting Agonist of Gonadotropin-Releasing Hormone in the Treatment of Precocious Puberty*. Endocr Rev. 1986;7(1):24-33. doi: https://doi.org/10.1210/edrv-7-1-24

129. Cook JS, Doty KL, Conn PM, Hansen JR. Assessment of depot leuprolide acetate dose-adequacy for central precocious puberty. J Clin Endocrinol Metab. 1992;74(5):1206-1209. doi: https://doi.org/10.1210/jcem.74.5.1569169

130. Carel J-C, Lahlou N, Guazzarotti L, et al. Treatment of central precocious puberty with depot leuprorelin. Eur J Endocrinol. 1995;132(6):699-704. doi: https://doi.org/10.1530/eje.0.1320699

131. Lawson ML, Cohen N. A Single Sample Subcutaneous Luteinizing Hormone (LH)-Releasing Hormone (LHRH) Stimulation Test for Monitoring LH Suppression in Children with Central Precocious Puberty Receiving LHRH Agonists 1. J Clin Endocrinol Metab. 1999;84(12):4536-4540. doi: https://doi.org/10.1210/jcem.84.12.6181

132. Brito VN, Latronico AC, Arnhold IJP, Mendonca BB. A Single Luteinizing Hormone Determination 2 Hours after Depot Leuprolide Is Useful for Therapy Monitoring of Gonadotropin-Dependent Precocious Puberty in Girls. J Clin Endocrinol Metab. 2004;89(9):4338-4342. doi: https://doi.org/10.1210/jc.2003-031537

133. Carel J-C, Blumberg J, Seymour C, et al. Three-month sustained-release triptorelin (11.25 mg) in the treatment of central precocious puberty. Eur J Endocrinol. 2006;154(1):119-124. doi: https://doi.org/10.1530/eje.1.02056

134. Badaru A, Wilson DM, Bachrach LK, et al. Sequential Comparisons of One-Month and Three-Month Depot Leuprolide Regimens in Central Precocious Puberty. J Clin Endocrinol Metab. 2006;91(5):1862-1867. doi: https://doi.org/10.1210/jc.2005-1500

135. Latronico AC, Brito VN, Carel J-C. Causes, diagnosis, and treatment of central precocious puberty. Lancet Diabetes Endocrinol. 2016;4(3):265-274. doi: https://doi.org/10.1016/S2213-8587(15)00380-0

136. Bangalore Krishna K, Fuqua JS, Rogol AD, et al. Use of Gonadotropin-Releasing Hormone Analogs in Children: Update by an International Consortium. Horm Res Paediatr. 2019;91:1-16. doi: https://doi.org/10.1159/000501336

137. Federal’nye klinicheskie rekomendatsii (protokoly) po vedeniyu detei F32 s endokrinnymi zabolevaniyami. Ed by Dedova II, Peterkovoi VA. Moscow: Praktika; 2014. P. 277–294. (In Russ.).

138. Prikaz Ministerstva zdravookhraneniya i sotsial’nogo razvitiya Rossiiskoi Federatsii ot 5.05.2012. №502n «Ob utverzhdenii poryadka sozdaniya i deyatel’nosti vrachebnoi komissii meditsinskoi organizatsii». (In Russ.).

139. Mieszczak J, Lowe ES, Plourde P, Eugster EA. The Aromatase Inhibitor Anastrozole Is Ineffective in the Treatment of Precocious Puberty in Girls with McCune-Albright Syndrome. J Clin Endocrinol Metab. 2008;93(7):2751-2754. doi: https://doi.org/10.1210/jc.2007-2090

140. Estrada A, Boyce AM, Brillante BA, et al. Long-term outcomes of letrozole treatment for precocious puberty in girls with McCune–Albright syndrome. Eur J Endocrinol. 2016;175(5):477-483. doi: https://doi.org/10.1530/EJE-16-0526

141. Feuillan P, Calis K, Hill S, et al. Letrozole Treatment of Precocious Puberty in Girls with the McCune-Albright Syndrome: A Pilot Study. J Clin Endocrinol Metab. 2007;92(6):2100-2106. doi: https://doi.org/10.1210/jc.2006-2350

142. Eugster EA, Rubin SD, Reiter EO, et al. Tamoxifen treatment for precocious puberty in McCune-Albright syndrome: a multicenter trial. J Pediatr. 2003;143(1):60-66. doi: https://doi.org/10.1016/S0022-3476(03)00128-8

143. de G. Buff Passone C, Kuperman H, Cabral de Menezes-Filho H, et al. Tamoxifen Improves Final Height Prediction in Girls with McCune-Albright Syndrome: A Long Follow-Up. Horm Res Paediatr. 2015;84(3):184-189. doi: https://doi.org/10.1159/000435881

144. Sims EK, Garnett S, Guzman F, et al. Fulvestrant treatment of precocious puberty in girls with McCune-Albright syndrome. Int J Pediatr Endocrinol. 2012;2012(1):26. doi: https://doi.org/10.1186/1687-9856-2012-26

145. Kreher NC, Pescovitz OH, Delameter P, et al. Treatment of familial male-limited precocious puberty with bicalutamide and anastrozole. J Pediatr. 2006;149(3):416-420. doi: https://doi.org/10.1016/j.jpeds.2006.04.027

146. Reiter EO, Mauras N, McCormick K, et al. Bicalutamide plus Anastrozole for the Treatment of Gonadotropin-Independent Precocious Puberty in Boys with Testotoxicosis: A Phase II, Open-Label Pilot Study (BATT). J Pediatr Endocrinol Metab. 2010;23(10). doi: https://doi.org/10.1515/jpem.2010.161

147. Tessaris D, Matarazzo P, Mussa A, et al. Combined treatment with bicalutamide and anastrozole in a young boy with peripheral precocious puberty due to McCune-Albright Syndrome. Endocr J. 2012;59(2):111-117. doi: https://doi.org/10.1507/endocrj.EJ11-0214

148. Güven A, Nurcan Cebeci A, Hancili S. Gonadotropin releasing hormone analog treatment in children with congenital adrenal hyperplasia complicated by central precocious puberty. Hormones. 2015;14(2):265. doi: https://doi.org/10.14310/horm.2002.1555

149. Pescovitz OH, Comite F, Cassorla F, et al. True Precocious Puberty Complicating Congenital Adrenal Hyperplasia: Treatment with a Luteinizing Hormone-Releasing Hormone Analog*. J Clin Endocrinol Metab. 1984;58(5):857-861. doi: https://doi.org/10.1210/jcem-58-5-857

150. Brito VN, Spinola-Castro AM, Kochi C, et al. Central precocious puberty: Revisiting the diagnosis and therapeutic management. Arch Endocrinol Metab. 2016;60(2):163-172. doi: https://doi.org/10.1590/2359-3997000000144

151. Breen JL, Maxson WS. Ovarian tumors in children and adolescents. Clinical Obstetrics Gynecol. 1977;20(3):607e23.

152. Mayer SK, Oligny LL, Deal C, et al. Childhood adrenocortical tumors: Case series and reevaluation of prognosis - A 24-year experience. J Pediatr Surg. 1997;32(6):911. doi: https://doi.org/10.1016/S0022-3468(97)90649-7

153. Cheville JC, Sebo TJ, Lager DJ, et al. Leydig cell tumor of the testis: A clinicopathologic, DNA content, and MIB-1 comparison of nonmetastasizing and metastasizing tumors. Am J Surg Pathol. 1998;22(11):1361. doi: https://doi.org/10.1097/00000478-199811000-00006

154. Michalkiewicz E, Sandrini R, Figueiredo B, et al. Clinical and Outcome Characteristics of Children With Adrenocortical Tumors: A Report From the International Pediatric Adrenocortical Tumor Registry. J Clin Oncol. 2004;22(5):838-845. doi: https://doi.org/10.1200/JCO.2004.08.085

155. Murray MJ, Bartels U, Nishikawa R, et al. Consensus on the management of intracranial germ-cell tumours. Lancet Oncol. 2015;16(9):e470-e477. doi: https://doi.org/10.1016/S1470-2045(15)00244-2

156. Klinicheskie rekomendatsii «Ekstrakranial’nye germinogenno-kletochnye opukholi u detei» razrabotannye Natsional’nym obshchestvom detskikh gematologov, onkologov. 2020. (In Russ.). Доступно по ссылке: https://cr.minzdrav.gov.ru/schema/69_1#doc_b