A 14-year-old girl has no breast development, primary amenorrhea, anosmia, and normal karyotype 46,XX. LH and FSH are very low. Which diagnosis and underlying physiological mechanism is MOST appropriate?
- A Kallmann syndrome — failure of GnRH neuron migration from olfactory placode to hypothalamus causing hypogonadotropic hypogonadism ✓
- B Turner syndrome — gonadal dysgenesis from 45,X karyotype
- C Constitutional delayed puberty — transient GnRH pulse generator immaturity
- D Pituitary microadenoma — compression of gonadotrophs reducing FSH and LH
Explanation
The combination of hypogonadotropic hypogonadism (absent puberty, very low LH/FSH) with anosmia (absent/reduced sense of smell) in a 46,XX female is diagnostic of Kallmann syndrome. Physiologically, GnRH neurons normally originate from the olfactory placode and migrate along olfactory nerves to the hypothalamus during fetal development (regulated by KAL1/FGFR1 genes). In Kallmann syndrome, this migration fails — GnRH neurons do not reach the hypothalamus, and the olfactory bulbs are hypoplastic (causing anosmia). Turner syndrome has 45,X karyotype (excluded here); constitutional delay has no anosmia and is self-resolving; microadenoma presents differently.
Reference: Guyton & Hall, Textbook of Medical Physiology, 14th ed.
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Written and medically reviewed by the StethoPrep medical team.