Reproductive · Year 2 · from Reproductive
Case 2: Hypogonadotropic Hypogonadism (Kallmann Syndrome)
Clinical Image
Source: Radiopaedia - Kallmann syndrome - CC BY-NC-SA 3.0
Case Presentation
An 18-year-old male is referred to endocrinology for delayed puberty. He has not yet developed facial hair, his voice has not deepened, and he has noticed minimal genital development compared to peers. He also reports that he has never been able to smell, even as a child. Physical examination reveals Tanner stage I genital development with prepubertal testes measuring 3 mL bilaterally (normal adult 15-25 mL). There is no facial or axillary hair, and the arm span exceeds height by 6 cm (eunuchoid proportions). Laboratory studies show: testosterone 45 ng/dL (severely low), FSH 1.2 mIU/mL (inappropriately low/normal), LH 0.8 mIU/mL (inappropriately low/normal). Formal olfactory testing confirms anosmia. MRI of the brain reveals absent olfactory bulbs and sulci. The diagnosis is Kallmann syndrome, a form of congenital hypogonadotropic hypogonadism with anosmia due to failure of GnRH neuron migration during embryonic development. Treatment is initiated with testosterone replacement for virilization. The patient is counseled that if he desires fertility in the future, pulsatile GnRH or gonadotropin therapy (hCG + FSH) can induce spermatogenesis.
Key Learning Points
- Kallmann syndrome is caused by failure of GnRH neurons to migrate from the olfactory placode to the hypothalamus during embryonic development
- The combination of hypogonadotropic hypogonadism and anosmia is pathognomonic for Kallmann syndrome
- Low/normal gonadotropins in the setting of low testosterone indicates secondary (central) hypogonadism
- Testosterone replacement achieves virilization but suppresses spermatogenesis; gonadotropin therapy is required for fertility