A 16-year-old girl has primary amenorrhea with no breast development. Height is appropriate for her family. Serum LH is 1.2 IU/L, FSH 1.8 IU/L, and estradiol 12 pg/mL. MRI shows a normal pituitary fossa. She reports she has never been able to smell coffee or perfumes since childhood. Which defect best explains her condition?

• A Autoimmune destruction of GnRH-secreting hypothalamic neurons
• B Failure of migration of GnRH neurons from the olfactory placode to the hypothalamus ✓
• C Gonadal resistance to FSH receptor signaling
• D Defect in aromatase enzyme activity in the ovary

Explanation

Anosmia with isolated hypogonadotropic hypogonadism defines Kallmann syndrome, caused by failed embryonic migration of GnRH neurons from the olfactory placode along olfactory axons into the hypothalamus; mutations involve KAL1, FGFR1, and related genes. Gonadotropins are low because the pulsatile GnRH signal never reaches the pituitary. The absence of smell is the discriminator from constitutional delay and isolated GnRH deficiency, both of which have intact olfaction.

Reference: Speroff's Clinical Gynecologic Endocrinology and Infertility, 9th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.