Poster Presentation The Annual Scientific Meeting of the Endocrine Society of Australia and the Society for Reproductive Biology 2014

Two cases of congenital hypogonadotropic hypogonadism: similar but different (#269)

Natalie Marijanovic 1 , Jui Ho 1
  1. Southern Adelaide Diabetes and Endocrine Service, Flinders Medical Centre, Bedford Park, South Australia, Australia

We present two cases of Congenital Hypogonadotropic Hypogonadism (CHH) who
both presented with absence of menses by the age of 16. On specific questioning, Case 1 reported anosmia.

On examination, Case 1 was of normal weight and height. She had Tanner stage 4 development of secondary sexual characteristics, microdontia of the incisor teeth and brachydactyly of the hands and feet. Case 2 was overweight (BMI 26 kg/m2) and had underdeveloped, rudimentary breasts (Tanner stage 2), sparse pubic hair (Tanner stage 1), and absent axillary hair. Case 2 also had acanthosis nigricans.

Investigations of both cases showed hypogonadotropic hypogonadism with no other pituitary hormone abnormalities. Further, there was no evidence of calcium homeostasis abnormalities. The karyotype of both cases was 46, XX. Insulin resistance was confirmed for Case 2 (HbA1c 6.0 %).
Pelvic ultrasound of both cases identified a prepubertal-sized small uterus and small ovaries, but no urogenital tract anomalies. Pituitary MRI was normal in both cases. Plain radiographs of the hands and feet of Case 1 showed bilaterally short fourth metacarpals with Madelung deformities of the wrists and bilaterally short metacarpal bones, respectively.


CHH is rare and is usually due to an isolated deficiency or lack of efficacy of gonadotropin-releasing hormone (1). The prototype of CHH, where there is associated anosmia/hyposmia, is termed Kallmann Syndrome. In females, CHH presents with delayed or absent puberty with primary amenorrhoea. The main differential diagnosis of CHH is constitutional delay of puberty. Our cases highlight the variable phenotype of CHH. This variability can be attributed to the over twenty genes in which defects have been identified in patients with CHH and the complex heritability of these genes (2). These genes are also associated with other features such as bony and dental anomalies and renal agenesis. The identification of these genes in individuals has reproductive implications.

  1. Seminara et al. Gonadotropin-releasing hormone deficiency in the human (idiopathic hypogonadotropic hypogonadism and Kallmann's syndrome): pathophysiological and genetic considerations. Endocr Rev, 1998; 19.
  2. Miraoui et al. Mutations in FGF17, IL17RD, DUSP6, SPRY4, and FLRT3 are identified in individuals with congenital hypogonadotropic hypogonadism. Am J Hum Genet, 2013; 92.