Preclinical diagnosis of testotoxicosis in a boy with an activating mutation of the luteinizing hormone receptor.
BACKGROUND
Testotoxicosis is an autosomal dominant disorder usually recognized by progressive virilization, linear growth acceleration, skeletal maturation and pubertal testosterone levels in boys before 4 years of age.


OBJECTIVE
To describe the clinical and hormonal follow-up of a male infant with testotoxicosis who was initially diagnosed by molecular analysis.


METHODS
A healthy asymptomatic 10 month-old boy was referred to the endocrinologist because his older brother had diagnosis of familial testotoxicosis due to the activating mutation Thr577Ile of the luteinizing hormone (LH) receptor.


RESULTS
Automatic sequencing of exon 11 of the LH receptor gene revealed the same heterozygous Thr577Ile mutation in the asymptomatic boy. He had no signs of virilization or accelerated growth. His bone age was delayed. Serum LH and follicle stimulating hormone (FSH) concentrations were in the prepubertal range, testosterone levels were slightly elevated (31 ng/dl [1.07 nmol/l]). In the following 6 months, his testosterone levels progressively increased, achieving higher levels (146 ng/dl [5 nmol/l]) without testicular enlargement or pubic hair development. Despite the lack of virilization signs, an anti-androgen was started due to the increase in testosterone levels and growth velocity at the age of 1.3 years.


CONCLUSIONS
We describe the preclinical diagnosis of testotoxicosis in a boy by DNA analysis. Very early diagnosis in affected families can result in prompt treatment, and reduce the deleterious consequences of premature puberty in boys with this rare monogenic disorder.
Teles
Milena
M
Unidade de Endocrinologia do Desenvolvimento, Laboratório de Hormônios e Genética Molecular, Hospital das Clínicas, Universidade de São Paulo, Brasil.
Brito
Vinicius Nahime
VN
Arnhold
Ivo Jorge Prado
IJ
Mendonca
Berenice Bilharinho
BB
Latronico
Ana Claudia
AC
D000726:Androgen Antagonists / Q000627:therapeutic use; D006801:Humans; D007223:Infant; D008297:Male; D017354:Point Mutation; D011629:Puberty, Precocious / Q000175:diagnosis* / Q000188:drug therapy / Q000235:genetics*; D011974:Receptors, LH / Q000235:genetics*; D017422:Sequence Analysis, DNA
D000726:Androgen Antagonists; D011974:Receptors, LH