title: Testotoxicosis: Report of Two Cases, One with a Novel Mutation in LHCGR Gene.
abstract: Testotoxicosis is a rare disorder which presents as isosexual peripheral precocious puberty in males. Despite the pattern of autosomal dominant inheritance, sporadic cases also may occur. Due to activating mutation in luteinizing hormone (LH))/choriogonadotropin receptor (LHCGR) gene, early virilization and advancement in bone age are common with increased serum testosterone levels above adult ranges, despite low LH and follicular-stimulating hormone (FSH) levels. There are different treatment regimens, such as combination of bicalutamide (antiandrogen agent) and a third-generation aromatase inhibitor, that are reported to be well-tolerated and successful in slowing bone age advancement and preventing progression of virilization. We report here two patients who presented with peripheral precocious puberty and an activating mutation in the LHCGR gene: one with a family history and previously determined mutation and the other without family history and with a novel mutation (c.830G>T). Combination of bicalutamide+anastrozole was ineffective in slowing pubertal progression and bone age. Short-term results were better with ketoconazole.
authors.forename: Bahar
authors.initials: B
authors.lastname: Özcabı
authors.forename: Feride
authors.initials: F
authors.lastname: Tahmiscioğlu Bucak
authors.forename: Serdar
authors.initials: S
authors.lastname: Ceylaner
authors.forename: Rahşan
authors.initials: R
authors.lastname: Özcan
authors.forename: Cenk
authors.initials: C
authors.lastname: Büyükünal
authors.forename: Oya
authors.initials: O
authors.lastname: Ercan
authors.forename: Beyhan
authors.initials: B
authors.lastname: Tüysüz
authors.affiliation: İstanbul University Cerrahpaşa Faculty of Medicine, Department of Pediatric Endocrinology, İstanbul, Turkey Phone: +90 212 414 30 00 E-mail: olcayevliyaoglu@hotmail.com.
authors.forename: Olcay
authors.initials: O
authors.lastname: Evliyaoğlu
mesh_terms: D000077384:Anastrozole; D000726:Androgen Antagonists / Q000627:therapeutic use; D000813:Anilides / Q000627:therapeutic use; D047072:Aromatase Inhibitors / Q000627:therapeutic use; D065692:Cytochrome P-450 CYP3A Inhibitors / Q000627:therapeutic use; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D007223:Infant; D007654:Ketoconazole / Q000627:therapeutic use; D008297:Male; D009154:Mutation; D009570:Nitriles / Q000627:therapeutic use; D011629:Puberty, Precocious / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics*; D011974:Receptors, LH / Q000235:genetics*; D017422:Sequence Analysis, DNA / Q000379:methods; D013739:Testosterone / Q000097:blood; D014105:Tosyl Compounds / Q000627:therapeutic use; D014230:Triazoles / Q000627:therapeutic use
chemical_list: D000726:Androgen Antagonists; D000813:Anilides; D047072:Aromatase Inhibitors; D065692:Cytochrome P-450 CYP3A Inhibitors; D009570:Nitriles; D011974:Receptors, LH; D014105:Tosyl Compounds; D014230:Triazoles; D000077384:Anastrozole; D013739:Testosterone; C053541:bicalutamide; D007654:Ketoconazole
references.citation: Nature. 1993 Oct 14;365(6447):652-4
references.pmid: 7692306
references.citation: Urol Int. 1996;57(3):199-202
references.pmid: 8912454
references.citation: J Pediatr. 2001 Jun;138(6):949-51
references.pmid: 11391350
references.citation: J Gastroenterol Hepatol. 2003 Dec;18(12):1426-9
references.pmid: 14675275
references.citation: J Clin Endocrinol Metab. 1981 Feb;52(2):271-8
references.pmid: 6780588
references.citation: J Clin Endocrinol Metab. 1983 Sep;57(3):571-9
references.pmid: 6223935
references.citation: Acta Paediatr. 1994 Sep;83(9):994-7
references.pmid: 7819701
references.citation: Proc Natl Acad Sci U S A. 1995 Mar 14;92(6):1906-10
references.pmid: 7892197
references.citation: Hepatology. 1997 Jan;25(1):103-7
references.pmid: 8985273
references.citation: Horm Res. 1997;48(5):235-9
references.pmid: 9362394
references.citation: J Clin Endocrinol Metab. 1998 Feb;83(2):476-80
references.pmid: 9467560
references.citation: Eur J Endocrinol. 1998 Jul;139(1):101-6
references.pmid: 9703386
references.citation: J Clin Endocrinol Metab. 2005 Jan;90(1):147-51
references.pmid: 15522928
references.citation: J Pediatr Endocrinol Metab. 2006 Apr;19(4):541-4
references.pmid: 16759041
references.citation: Pediatr Radiol. 2008 Jun;38(6):688-90
references.pmid: 18246339
references.citation: Clin Endocrinol (Oxf). 2008 Jul;69(1):93-8
references.pmid: 18088394
references.citation: J Pediatr Endocrinol Metab. 2008 Oct;21(10):995-1002
references.pmid: 19209621
references.citation: J Pediatr Endocrinol Metab. 2009 Dec;22(12):1163-7
references.pmid: 20333877
references.citation: Pediatrics. 2010 Sep;126(3):e728-33
references.pmid: 20713483
references.citation: J Pediatr Endocrinol Metab. 2010 Oct;23(10):999-1009
references.pmid: 21158211
references.citation: Endocr J. 2010;57(12):1055-60
references.pmid: 21060208
references.citation: Acta Cir Bras. 2011 Oct;26(5):387-90
references.pmid: 21952663
references.citation: Nat Rev Endocrinol. 2012 Mar;8(3):135-47
references.pmid: 22024975
references.citation: Pediatr Med Chir. 2012 Jul-Aug;34(4):192-7
references.pmid: 23173412
references.citation: Urology. 1999 Jan;53(1):209-13
references.pmid: 9886614
references.citation: Arch Pathol Lab Med. 1985 Nov;109(11):990-5
references.pmid: 3901957
references.citation: J Clin Endocrinol Metab. 1987 Feb;64(2):328-33
references.pmid: 3539979
references.citation: J Clin Endocrinol Metab. 2000 Dec;85(12):4799-805
references.pmid: 11134146
references.citation: Biochem Mol Med. 1996 Aug;58(2):192-8
references.pmid: 8812739