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Endocrine Abstracts (2024) 99 P551 | DOI: 10.1530/endoabs.99.P551

1Section of Investigative Medicine, Department of Metabolism, Digestion and Reproduction, Imperial College School of Medicine, Imperial College London, London, United Kingdom; 2Department of Diabetes and Endocrinology, Imperial College Healthcare NHS trust, London, United Kingdom; 3Department of Paediatric Endocrinology, Queen Mary University of London, London, United Kingdom


Introduction: Kallmann syndrome (KS) is a rare condition characterised by congenital hypogonadotropic hypogonadism (CHH), usually due to defective migration of olfactory axons and GnRH-neurons. KS is typically associated with absent (anosmia) or reduced (microsmia) sense of smell. Unilaterally hypoplastic or absent olfactory bulbs on MRI are reported, although disturbance in smell is usually bilateral. Kisspeptin is a potent stimulator of hypothalamic GnRH-neurons, and endocrine responses to kisspeptin boluses are usually minimal in CHH. We present an unusual case of KS with unilateral anosmia and her responses to kisspeptin.

Case Presentation: An 18yr old woman presented to the endocrine clinic for management of KS. Her mother and sister were known to have KS (heterozygous for FGFR1-mutation) having previously presented with primary amenorrhea and anosmia. Her mother required ovulation induction to conceive. She had spontaneous albeit borderline late menarche aged 16yrs, but only five menstrual periods over the subsequent two years, followed by secondary amenorrhea. She didn’t have any other medical history, psychological stress, undertake excessive exercise and took no regular medications. At presentation, her BMI was 22 kg/m2 and she had normal secondary sexual characteristics. Unusually, she reported a normal sense of smell via the right nostril, but anosmia via the left nostril. Unilateral anosmia was confirmed with an UPSIT smell test (right nostril 32/40 (normosmia); left nostril 12/40 (anosmia)). MRI-brain revealed unilaterally absent left olfactory nerve, bulb, and sulcus. She had undetectable serum estradiol (<100 pmol/l), low LH (0.2 IU/l) and low FSH (0.4IU/L). Pelvic ultrasound demonstrated a thin endometrium (3mm), consistent with hypoestrogenism. Whole-exome sequencing confirmed a heterozygous FGFR1 variant. An intravenous GnRH-test (100 mg) induced an LH rise of 24.8IU/L indicating a functional pituitary gland. An intravenous bolus of kisspeptin-54 (9.8 nmol/kg) induced a subnormal early rise in LH (3.4IU/L), which is greater than typically seen in CHH. On separate occasions, intranasal (12.8nmol/kg) KP54 delivered only to the right nostril, led to a small rise in LH of 0.5IU/L, whereas KP54 delivered only to the left nostril did not induce any LH rise.

Discussion: This lady had spontaneous puberty and menarche indicating some residual GnRH-neuronal function, despite inheriting an FGFR1 variant. Further, she had a small early subnormal gonadotropin response to kisspeptin, rather than the absent response typically observed in complete KS. This, and in view of her unilateral anosmia, unilateral olfactory bulb on MRI, a unilateral albeit small response to intranasal kisspeptin-54, suggest that she has an unusual partial/unilateral form of KS.

Volume 99

26th European Congress of Endocrinology

Stockholm, Sweden
11 May 2024 - 14 May 2024

European Society of Endocrinology 

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