A 14-year-old boy is brought to the physician by his mother. She is concerned because although tall, her son looks much younger than his peers and shows no signs of "masculinity." On physical examination, the boy has poorly developed secondary sexual characteristics. He is unable to distinguish smells but has good visual acuity. Which of the following pathways is most likely defective in this patient?

Question

A 14-year-old boy is brought to the physician by his mother.  She is concerned because although tall, her son looks much younger than his peers and shows no signs of "masculinity."  On physical examination, the boy has poorly developed secondary sexual characteristics.  He is unable to distinguish smells but has good visual acuity.  Which of the following pathways is most likely defective in this patient?

Quizplus · Accepted Answer

This patient has delayed puberty plus anosmia, consistent with a diagnosis of Kallmann syndrome. Kallmann syndrome results from a failure of GnRH-secreting neurons to migrate from their origin in the olfactory placode (situated outside the central nervous system) to their normal anatomic location in the hypothalamus. Most often, the cause is a mutation in the KAL-1 gene or the fibroblast growth factor receptor-1 gene, which code for proteins required in this migration. Patients with Kallmann syndrome classically have central hypogonadism and anosmia, although there may be other midline defects as well (eg, cleft lip or cleft palate). Most often, these patients present with delayed puberty. On physical examination, the testes are often just 1-2 mL in volume. There is usually some pubic hair because adrenarche occurs normally. In the United States, delayed puberty is defined as the absence or incomplete development of secondary sexual characteristics by age 14 in boys and by age 12 in girls. Testicular enlargement is the first sign of puberty in boys, and breast enlargement is the first sign in girls. The initiation of puberty and the maintenance of secondary sexual characteristics and fertility require the coordinated efforts of the hypothalamus, pituitary, and gonads. Delayed puberty can result from a derangement anywhere in this axis. (Choices B, C, D, and E) These pathways represent normal feedback loops between the testes and the hypothalamus and pituitary. Pituitary follicle-stimulating hormone (FSH) stimulates proliferation of the seminiferous tubules and spermatogenesis. The seminiferous tubules produce inhibin, which feeds back to inhibit pituitary FSH secretion. Luteinizing hormone from the pituitary stimulates the interstitial Leydig cells to produce testosterone, which also participates in feedback inhibition. Educational objective: In Kallmann syndrome, there is an absence of GnRH secretory neurons in the hypothalamus due to defective migration from the olfactory placode. These patients have central hypogonadism and anosmia, and often present with delayed puberty.

A 14-Year-Old Boy Is Brought to the Physician by His