Endocrine Abstracts

Introduction: Kallmann syndrome (KS) is a developmental disorder characterised by hypogonadotropic hypogonadism and anosmia. 30% of cases are related with genetic causes, with FGFR1 mutations being identified in 10%. There are more than 140 FGFR1 gene mutations identified. We present a female patient with KS due to a FGFR1 mutation, where the presenting features included primary amenorrhoea and anosmia.

Case description: A 16 year old female presented with primary amenorrhoea, anosmia and severe acne. She firstly noticed axillary hair at the age of 9 years, subsequently pubic hair at 13 years old but this was sparse and covering a small area. Her weight was 62.4 kg (following 75th centile) and a static height of 158.2 (between 9th and 25th centiles; MPH 50thcentile). She had an uneventful antenatal and perinatal history. Family history of maternal ovarian cancer. Maternal menarche at 13 years of age. She has a 14 year old brother with anosmia showing pubertal development. Physical exam: sturdy build, Tanner III, one café aux lait spot in abdomen, otherwise unremarkable.

Investigations: Blood tests: ACTH, cortisol, thyroid profile, liver and renal function and growth factors all within reference ranges. LH 3.1 IU/L, FSH 6.6 IU/L, testosterone 1.2 nmol/L, progesterone <1 nmol/L. Renal and pelvic USS: normal renal and bladder findings. No structural abnormality of uterus or adnexa. Bone age (TW 2 score 988): 14.3 years at a chronological age of 16.75 years. MRI pituitary gland: no abnormality detected. Molecular genetics: heterozygous for the pathogenic variant c.1118delT p. (Leu373A rgfsTer27) in the FGFR1 gene. This result confirms a diagnosis of hypogonadotropic hypogonadism 2 with anosmia.

Management and discussion: Started on combined pill. Menstrual spotting started after 2 months. On retinoic acid for acne as per Dermatology. Sibling is under investigation, awaiting molecular genetics to rule out KS. Hormone replacement therapies are used to stimulate the development of secondary sexual characteristics at the time of puberty, and later to induce fertility. There is currently no treatment for olfactory deficit.