open access

Vol 62, No 3 (2011)
Case report
Published online: 2011-06-29
Submitted: 2013-02-15
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Hypogonadotropic hypogonadism due to GnRH receptor mutation in a sibling

Piotr Fichna, Marta Fichna, Magdalena Żurawek, Jerzy Nowak
Endokrynologia Polska 2011;62(3):264-267.

open access

Vol 62, No 3 (2011)
Case report
Published online: 2011-06-29
Submitted: 2013-02-15

Abstract

Hypogonadotropic hypogonadism (HH) is characterised by delayed puberty and infertility. Congenital HH comprises Kallmann syndrome with hypo-/anosmia and idiopathic HH (IHH). The genetic origin remains unknown in most cases, but the defective GnRH receptor gene (GNRHR) accounts for a considerable proportion of IHH.
Here we describe a pair of siblings diagnosed with IHH. Aged 17 years, the boy was referred because of short stature (162 cm) and overweight (62.5 kg). He presented no signs of puberty, bone age of 14.5 years and insulin resistance. His sister, aged 16 years, also displayed delayed puberty. She was 166 cm tall and weighed 52 kg; her bone age was 12.5 years. Pelvic ultrasonography showed an infantile uterus and fibrous ovaries. In both siblings, serum gonadotropins were extremely low, and non-responsive to GnRH. Testosterone (1.38 nmol/l) and IGF1 (273 ng/ml) were decreased in the boy, although the girl did not present IFG1 deficiency. Her serum oestradiol was 10 pg/ml. MRIs of the hypothalamo-pituitary region and olfactory bulbs revealed them to be normal. The patients’ sense of smell was unaltered. Their parents appeared to be first degree cousins. Considering the clinical data and potentially autosomal recessive HH transmission, the GNRHR gene was screened. The siblings turned out to be homozygous for the G416A transition, which had previously been identified in other HH individuals. The parents were heterozygous mutation carriers. The proband, moderately responding to LH, was started on low dose testosterone replacement, and his sister on transdermal oestradiol. Molecular data indicative of GnRH resistance could guide their future therapy should they desire fertility restoration. Further observations of the male patient may provide insights into androgen’s influence on body mass, growth and insulin sensitivity. (Pol J Endocrinol 2011; 62 (3): 264–267)

Abstract

Hypogonadotropic hypogonadism (HH) is characterised by delayed puberty and infertility. Congenital HH comprises Kallmann syndrome with hypo-/anosmia and idiopathic HH (IHH). The genetic origin remains unknown in most cases, but the defective GnRH receptor gene (GNRHR) accounts for a considerable proportion of IHH.
Here we describe a pair of siblings diagnosed with IHH. Aged 17 years, the boy was referred because of short stature (162 cm) and overweight (62.5 kg). He presented no signs of puberty, bone age of 14.5 years and insulin resistance. His sister, aged 16 years, also displayed delayed puberty. She was 166 cm tall and weighed 52 kg; her bone age was 12.5 years. Pelvic ultrasonography showed an infantile uterus and fibrous ovaries. In both siblings, serum gonadotropins were extremely low, and non-responsive to GnRH. Testosterone (1.38 nmol/l) and IGF1 (273 ng/ml) were decreased in the boy, although the girl did not present IFG1 deficiency. Her serum oestradiol was 10 pg/ml. MRIs of the hypothalamo-pituitary region and olfactory bulbs revealed them to be normal. The patients’ sense of smell was unaltered. Their parents appeared to be first degree cousins. Considering the clinical data and potentially autosomal recessive HH transmission, the GNRHR gene was screened. The siblings turned out to be homozygous for the G416A transition, which had previously been identified in other HH individuals. The parents were heterozygous mutation carriers. The proband, moderately responding to LH, was started on low dose testosterone replacement, and his sister on transdermal oestradiol. Molecular data indicative of GnRH resistance could guide their future therapy should they desire fertility restoration. Further observations of the male patient may provide insights into androgen’s influence on body mass, growth and insulin sensitivity. (Pol J Endocrinol 2011; 62 (3): 264–267)
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Keywords

GnRH receptor gene mutation; idiopathic hypogonadotropic hypogonadism; gender impact on IHH clinical features

About this article
Title

Hypogonadotropic hypogonadism due to GnRH receptor mutation in a sibling

Journal

Endokrynologia Polska

Issue

Vol 62, No 3 (2011)

Pages

264-267

Published online

2011-06-29

Bibliographic record

Endokrynologia Polska 2011;62(3):264-267.

Keywords

GnRH receptor gene mutation
idiopathic hypogonadotropic hypogonadism
gender impact on IHH clinical features

Authors

Piotr Fichna
Marta Fichna
Magdalena Żurawek
Jerzy Nowak

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