title: Long-term treatment of familial male-limited precocious puberty (testotoxicosis) with cyproterone acetate or ketoconazole.
abstract: BACKGROUND
  Familial male-limited precocious puberty (FMPP) or testotoxicosis is a rare gonadotrophin-independent form of sexual precocity caused by constitutively activating mutations of the LH receptor. Several clinical therapeutic approaches have been reported for this disorder, but with a paucity of long-term outcome data.
  
  
  OBJECTIVE
  To evaluate the long-term treatment of testotoxicosis with cyproterone acetate or ketoconazole.
  
  
  METHODS
  A multicentric retrospective clinical study.
  
  
  METHODS
  Ten boys from eight unrelated Brazilian families who carried known LH-receptor activating mutations were treated with 70 mg/m(2) cyproterone acetate (n = 5) or 10 mg/kg ketoconazole (n = 5) for a mean period of 5 and 8 years, respectively.
  
  
  METHODS
  Chronological and bone ages, bone age/chronological age ratio, target height (TH) range, adult height, basal and GnRH-stimulated gonadotrophin levels and basal testosterone levels were assessed.
  
  
  RESULTS
  Growth velocity decreased significantly during treatment with cyproterone acetate or ketoconazole when compared to pretreatment value in each group (P < 0.05). Bone age/chronological age ratio decreased significantly after cyproterone acetate or ketoconazole therapy. Basal testosterone levels were significantly lower in patients undergoing ketoconazole compared to cyproterone acetate treatment [0.6 +/- 0.3 nmol/l (42 +/- 21 ng/dl) vs. 5.6 +/- 4.0 nmol/l (392 +/- 280 ng/dl); P < 0.05], as expected. Secondary gonadotrophin-dependent precocious puberty occurred at a similar frequency (40%) in both groups. Five patients have attained adult height and two patients have already reached 90% of their adult height. Two of them achieved their TH range and one patient, for whom TH was not available, had an adult height of 0.3 SDS. Four boys (two in each group) did not attain their TH range.
  
  
  CONCLUSIONS
  Long-term treatment with cyproterone acetate or ketoconazole resulted in similar outcomes without important side-effects in boys with testotoxicosis. However, both therapies showed limited efficacy in attaining normal adult height.
authors: Unidade de Endocrinologia do Desenvolvimento, Laboratório de Hormônios e Genética Molecular/LIM42 da Disciplina de Endocrinologia do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil. madsonalmeida@gmail.com
authors: Madson Queiroz
authors: MQ
authors: Almeida
authors: Vinicius Nahime
authors: VN
authors: Brito
authors: Thereza Selma S
authors: TS
authors: Lins
authors: Gil
authors: G
authors: Guerra-Junior
authors: Margaret
authors: M
authors: de Castro
authors: Sonir Roberto
authors: SR
authors: Antonini
authors: Ivo Jorge Prado
authors: IJ
authors: Arnhold
authors: Berenice Bilharinho
authors: BB
authors: Mendonca
authors: Ana Claudia
authors: AC
authors: Latronico
mesh_terms: D000293:Adolescent; D000726:Androgen Antagonists / Q000627:therapeutic use; D001827:Body Height / Q000187:drug effects; D002648:Child; D002675:Child, Preschool; D017373:Cyproterone Acetate / Q000627:therapeutic use*; D005500:Follow-Up Studies; D006801:Humans; D007223:Infant; D007654:Ketoconazole / Q000627:therapeutic use*; D008297:Male; D011629:Puberty, Precocious / Q000188:drug therapy* / Q000235:genetics; D011974:Receptors, LH / Q000235:genetics; D012189:Retrospective Studies; D012737:Sex Factors; D013997:Time Factors
chemical_list: D000726:Androgen Antagonists; D011974:Receptors, LH; D017373:Cyproterone Acetate; D007654:Ketoconazole