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Vol. 64, No. 1, 2005
Issue release date: September 2005
Horm Res 2005;64:3–8

Macroorchidism in Two Unrelated Prepubertal Boys with a Normal FSH Receptor

Velaga M.R. · Wright C. · Crofton P.M. · Allen L. · Jennings C.E. · Cheetham T.D.
aInstitute of Human Genetics, School of Clinical Medical Sciences, University of Newcastle, Newcastle upon Tyne; cDepartment of Paediatric Biochemistry, Royal Hospital for Sick Children, Edinburgh, and Departments of bPathology and dPaediatrics, Royal Victoria Infirmary, Newcastle upon Tyne, UK

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Background: Macroorchidism in prepuberty is an uncommon condition which we hypothesised might reflect constitutive activation of the FSH receptor (FSHR). Patients and Methods: Patient 1 was found to have macroorchidism (15 ml testicular volume) at the time of orchidopexy when 3.7 years of age. A gonadal biopsy was obtained at the time of surgery. Patient 2 developed macroorchidism (5 ml) when 8.8 years old. Despite a testicular volume >4 ml, morning testosterone levels were unrecordable with no measurable gonadotrophin production in either patient. Patient 2 had prepubertal gonadotrophin levels 3 years later despite a testicular volume that was 8 ml bilaterally. Inhibin B was measured and the FSHR sequenced in both patients. Results: Inhibin B levels were age and pubertal stage appropriate. Gonadal biopsy (patient 1) demonstrated areas of Sertoli cell hyperplasia. Sequence analysis of all 10 exons of the FSHR was normal. There was significant, presumed gonadotrophin-dependent testosterone production in both boys by 15 years of age. Conclusions: The cause of prepubertal macroorchidism in our patients is unclear but the pronounced difference in phenotype suggests that there may be more than one underlying mechanism. This mechanism was not constitutive activation of a mutated FSHR.

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