Hypogonadotropic hypogonadism, phenotype genotype correlation

Hana Charfi; Hamdi Frikha; Wajdi Safi; Mouna Elleuch; Nesrine Dhieb; Salah Dhoha Ben; Fatma Mnif; Nadia Charfi; Kacem Akid Faten Haj; Mouna Mnif; Mohamed Abid; Majdoub Nabila Rekik

doi:10.1530/endoabs.99.EP347

Introduction: Congenital hypogonadotropic hypogonadism (CHH) of hypothalamic or pituitary origin is a rare condition (1 in 5000 births). Clinical manifestations var, depending on the patient’s age and the severity, of the deficiency. CHH is often diagnosed in the context of delayed puberty, without impaired stature, typically, associated with tall stature.

Patients and Methods: This is a bicentric study conducted at the Endocrinology Department of Hedi Chaker University Hospital in Sfax and Fattouma Bourguiba University Hospital in Monastir. It is a retrospective descriptive and analytical study involving 29 cases of CHH, followed between 1991 and 2019. Patients with chronic conditions potentially, affecting pituitary function, those with acquired organic causes of pituitary dysfunction leading to significant hormonal deficiency and those with somatotropic axis deficiency, were excluded.

Results: A clear male predominance was noted with a sex ratio of 2M/1F. The average age at diagnosis was 18.5 years [2-32]. Family, consanguinity, was reported in 62.7% of cases. The most common reason for consultation was delayed puberty, in 73% of cases. The average height of patients was 165.85 cm [123-193]. Sixty, percent of patients had above-average stature at the time of diagnosis, and 16% had a stature delay, between -2 SD and -4 SD, related to molecular abnormalities of sex chromosomes or associated congenital bone anomalies. Ninety, percent of our population reached pubertal bone age at the time of diagnosis. Extra-pituitary involvement was present in 50% of patients: anosmia (30%) and neurosensory impairment (20%). Anterior pituitary exploration revealed corticotrope and lactotrope insufficiency in 5 and 3 patients, respectively. Hypothalamic-pituitary MRI was abnormal in 30% of cases, with pituitary hypoplasia in 6 cases (20%), one of which was associated with corpus callosum atrophy. The posterior pituitary was found in a normal position in all patients. Genetic testing was performed in 9 patients, including 4 relatives, revealing a missense mutation (c.386C>A, p.T129K) in the homozygous state of the KISS1-R gene in 3 relatives.

Conclusion: Although genetic analysis could only, be performed in 9 patients, we attempted to correlate phenotypic aspects with the various biomolecular abnormalities found. The genotype-phenotype correlation for this type of mutation remains challenging due to its modulation by, the cellular and molecular environment.

Endocrine Abstracts

EP347