Pitteloud et al. (2002) examined historical, clinical, biochemical, histologic, and genetic features in 78 men with IHH to gain further insight into the phenotypic heterogeneity of the syndrome. They hypothesized that at least some of the spectrum of phenotypes could be explained by placing the disorder into a developmental and genetic context. Thirty-eight percent of the population had Kallmann syndrome, 54% had normosmic IHH, and 8% had acquired IHH after completion of puberty. Phenotypically, Kallmann syndrome represented the most severe subtype (87% with complete absence of any history or signs of spontaneous pubertal development), normosmic IHH displayed the most heterogeneity (41% with some evidence of spontaneous puberty), and acquired IHH after completion of puberty clustered at the mildest end (all had complete puberty). Classification based on historical or clinical evidence of prior pubertal development, rather than the presence or absence of sense of smell, served to distinguish the population more clearly with respect to other clinical and biochemical features. Mean gonadotropin levels and the finding of apulsatile LH secretion based on frequent sampling (80% vs 55%; p less than ) were statistically different between patients lacking and those exhibiting partial pubertal development, but the overlap was extensive. The authors concluded that use of clinical parameters (presence or absence of some evidence of prior pubertal development, cryptorchidism ( 219050 ), and microphallus), biochemical markers of testicular growth and differentiation (inhibin B, mullerian inhibitory substance), and genetic evidence provides insight into the time of onset and the severity of GnRH deficiency. The authors further concluded viewing IHH in the full context of its developmental, genetic, and biochemical complexity permits greatest insight into its phenotypic variability.
Hormonal therapy using gonadotropins to stimulate the production of more testosterone is effective in some children in causing the testes to descend into the scrotum without surgery. This approach, however, is usually successful only with undescended testes that are already close to the scrotum; its rate of success ranges from 10–50%. Undescended testes that are located higher almost never respond to hormonal therapy. In addition, treatment with hormones has several undesirable side effects, including aggressive behavior.