Testotoxicosis without Testicular Mass: Revealed by Peripheral Precocious Puberty and Confirmed by Somatic LHCGR Gene Mutation.
Endocrine Research. 2019-08-08; 45(1): 32-40
DOI: 10.1080/07435800.2019.1645163
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1. Endocr Res. 2020 Feb;45(1):32-40. doi: 10.1080/07435800.2019.1645163. Epub 2019
Aug 8.
Testotoxicosis without Testicular Mass: Revealed by Peripheral Precocious Puberty
and Confirmed by Somatic LHCGR Gene Mutation.
Daussac A(1), Barat P(1)(2), Servant N(3), Yacoub M(4), Missonier S(5), Lavran
F(6), Gaspari L(7), Sultan C(3)(7), Paris F(3)(7).
Author information:
(1)Département de Pédiatrie, Endocrinologie Pédiatrique, CHU de Bordeaux,
Bordeaux, France.
(2)Département de Pédiatrie, Centre d’Investigation Clinique (CIC 0005), CHU de
Bordeaux, Bordeaux, France.
(3)Département d’Hormonologie (Développement et Reproduction), CHU de
Montpellier, Hôpital Lapeyronie, Université de Montpellier, Montpellier, France.
(4)Unité d’Anatomo cytopathologie, CHU de Bordeaux, Bordeaux, France.
(5)Unité de Radiologie pédiatrique, CHU de Bordeaux, Bordeaux, France.
(6)Unité de Chirurgie viscérale pédiatrique, CHU de Bordeaux, Bordeaux, France.
(7)Unité d’Endocrinologie-Gynécologie Pédiatriques, Département de Pédiatrie, CHU
de Montpellier, Hôpital Arnaud de Villeneuve, Université Montpellier 1,
Montpellier, France.
Purpose: Testotoxicosis is an autosomal dominant form of limited
gonadotropin-independent precocious puberty in boys. It is caused by a
heterozygous constitutively activating mutation of the LHCGR gene encoding the
luteinizing/hormone receptor (LHR). Some twenty mutations of the LHCGR gene have
been reported. Most of them are constitutive mutations isolated from blood
leukocyte DNA, although others are somatic, found only in testicular tumoural
tissue. In all the previously reported cases of these somatic mutations, the
tumour, whether a nodular Leydig cell adenoma or hyperplasia, was easily visible
on testicular ultrasonography. The aim of this study was to describe an unusual
presentation of a patient with the clinical and hormonal characteristics of
testotoxicosis but no well-circumscribed lesion at testicular
ultrasonography.Materials and Methods: Molecular analysis of the LHCGR gene was
performed by direct sequencing of DNA extracted from peripheral leucocytes and
testicular biopsy.Results: Molecular analysis didn’t find any LHR mutation in
blood, whereas it revealed for the first time a somatic D578H mutation in
testicular tissue despite no evidence of a nodular aspect at testis
ultrasonography.Conclusions: This observation underlines the need to look for a
somatic LHCGR gene mutation from the testicular biopsies of all boys with
testotoxicosis with no constitutive LHCGR gene mutation identified from blood
DNA, even in the absence of circumscribed testicular lesion at ultrasonography.
In addition, based on the known link between LHR mutations and testicular
tumourigenesis, yearly ultrasound monitoring of the testes should be considered
for these patients.
DOI: 10.1080/07435800.2019.1645163
PMID: 31394950 [Indexed for MEDLINE]