Journal of Clinical Endocrinology & Metabolism, Vol 64, 283-291, Copyright © 1987 by Endocrine Society

ARTICLES

The spectrum of abnormal patterns of gonadotropin-releasing hormone secretion in men with idiopathic hypogonadotropic hypogonadism: clinical and laboratory correlations

DI Spratt, DB Carr, GR Merriam, RE Scully, PN Rao and WF Crowley Jr

Several lines of evidence indicate that hypothalamic-pituitary-gonadal activity varies among men with idiopathic hypogonadotropic hypogonadism (IHH). To test the hypothesis that a spectrum of abnormalities of GnRH secretion underlies the syndrome of IHH, we characterized the patterns of GnRH-induced gonadotropin secretion during periods of frequent sampling in 50 consecutive men with IHH and contrasted them with those in 20 normal men. The largest group of IHH patients (n = 42) had no detectable LH or FSH pulsations and could be categorized into 2 subsets according to the presence or absence of evidence of spontaneous puberty. The most severely affected subset (n = 32), who recalled no history of puberty, had testes with a mean volume of 3.3 +/- 0.5 (+/- SEM) ml, with a prepubertal appearance on biopsy, and often were anosmic (n = 17). The second subset of apulsatile IHH men (n = 10) had histories of partial or complete spontaneous sexual development with subsequent isolated loss of sexual function, testes with a mean volume of 13.3 +/- 1.9 ml (P less than 0.01 compared to the first subset), a pubertal or adult appearance of the testes on biopsy, and an intact sense of smell. In a second group of IHH patients (n = 3), LH was secreted predominantly in a nighttime pattern similar to that of normal children during early puberty. These men were aged 18-24 yr, had a mean testicular volume of 10.5 +/- 2.3 ml, pubertal changes on testicular biopsy, and an intact sense of smell. A third group of IHH men (n = 4) had LH pulses of abnormally low amplitude. Only one patient in this group had a history of spontaneous sexual development. The mean testicular volume of these patients was 5.6 +/- 1.9 ml, and the testes appeared prepubertal (n = 3) or pubertal (n = 1) on biopsy. In addition to these groups, another patient had apparent LH pulsations and nearly normal amplitude, but the LH was bioinactive and appeared to consist chiefly of alpha-subunit. Testing of other anterior pituitary hormone functions did not distinguish IHH men from normal men. However, those IHH patients with some evidence of endogenous GnRH secretion had higher basal and stimulated serum PRL levels than IHH men without such evidence (P less than 0.05), suggesting an influence of GnRH on PRL secretion.

This article has been cited by other articles:

				P. A. Kumar, N. Pitteloud, P. A.M. Andrews, A. Dwyer, F. Hayes, W. F. Crowley Jr, and M. Dym Testis morphology in patients with idiopathic hypogonadotropic hypogonadism Hum. Reprod., April 1, 2006; 21(4): 1033 - 1040. [Abstract] [Full Text] [PDF]

				J. S. Jorgensen, C. C. Quirk, and J. H. Nilson Multiple and Overlapping Combinatorial Codes Orchestrate Hormonal Responsiveness and Dictate Cell-Specific Expression of the Genes Encoding Luteinizing Hormone Endocr. Rev., August 1, 2004; 25(4): 521 - 542. [Abstract] [Full Text] [PDF]

				A. Ulloa-Aguirre, J. A. Janovick, A. Leanos-Miranda, and P. M. Conn Misrouted cell surface GnRH receptors as a disease aetiology for congenital isolated hypogonadotrophic hypogonadism Hum. Reprod. Update, March 1, 2004; 10(2): 177 - 192. [Abstract] [Full Text] [PDF]

				S. B. Seminara, S. Messager, E. E. Chatzidaki, R. R. Thresher, J. S. Acierno Jr., J. K. Shagoury, Y. Bo-Abbas, W. Kuohung, K. M. Schwinof, A. G. Hendrick, et al. The GPR54 Gene as a Regulator of Puberty N. Engl. J. Med., October 23, 2003; 349(17): 1614 - 1627. [Abstract] [Full Text] [PDF]

				N. Pitteloud, F. J. Hayes, A. Dwyer, P. A. Boepple, H. Lee, and W. F. Crowley Jr. Predictors of Outcome of Long-Term GnRH Therapy in Men with Idiopathic Hypogonadotropic Hypogonadism J. Clin. Endocrinol. Metab., September 1, 2002; 87(9): 4128 - 4136. [Abstract] [Full Text] [PDF]

				R. Vazquez-Martinez, G. M. Leclerc, M. E. Wierman, and F. R. Boockfor Episodic Activation of the Rat GnRH Promoter: Role of the Homeoprotein Oct-1 Mol. Endocrinol., September 1, 2002; 16(9): 2093 - 2100. [Abstract] [Full Text] [PDF]

				N. Pitteloud, F. J. Hayes, P. A. Boepple, S. DeCruz, S. B. Seminara, D. T. MacLaughlin, and W. F. Crowley Jr. The Role of Prior Pubertal Development, Biochemical Markers of Testicular Maturation, and Genetics in Elucidating the Phenotypic Heterogeneity of Idiopathic Hypogonadotropic Hypogonadism J. Clin. Endocrinol. Metab., January 1, 2002; 87(1): 152 - 160. [Abstract] [Full Text] [PDF]

				H. Krishnamurthy, P. Suresh Babu, C. R. Morales, and M. R. Sairam Delay in Sexual Maturity of the Follicle-Stimulating Hormone Receptor Knockout Male Mouse Biol Reprod, August 1, 2001; 65(2): 522 - 531. [Abstract] [Full Text] [PDF]

				N. Pitteloud, P. A. Boepple, S. DeCruz, S. B. Valkenburgh, W. F. Crowley Jr., and F. J. Hayes The Fertile Eunuch Variant of Idiopathic Hypogonadotropic Hypogonadism: Spontaneous Reversal Associated with a Homozygous Mutation in the Gonadotropin-Releasing Hormone Receptor J. Clin. Endocrinol. Metab., June 1, 2001; 86(6): 2470 - 2475. [Abstract] [Full Text] [PDF]

				L. M. B. Oliveira, S. B. Seminara, M. Beranova, F. J. Hayes, S. B. Valkenburgh, E. Schipani, E. M. F. Costa, A. C. Latronico, W. F. Crowley Jr., and M. Vallejo The Importance of Autosomal Genes in Kallmann Syndrome: Genotype-Phenotype Correlations and Neuroendocrine Characteristics J. Clin. Endocrinol. Metab., April 1, 2001; 86(4): 1532 - 1538. [Abstract] [Full Text]

				S. B. Seminara, J. E. Hall, A. E. Taylor, W. F. Crowley Jr., and K. A. Martin The Reproductive Endocrine Associates of the Massachusetts General Hospital: Fifteen Years of Integrated Clinical Practice and Investigation J. Clin. Endocrinol. Metab., June 1, 1999; 84(6): 1912 - 1918. [Full Text]

				F. J. Hayes, D. J. McNicholl, D. Schoenfeld, E. E. Marsh, and J. E. Hall Free {alpha}-Subunit Is Superior to Luteinizing Hormone as a Marker of Gonadotropin-Releasing Hormone Despite Desensitization at Fast Pulse Frequencies J. Clin. Endocrinol. Metab., March 1, 1999; 84(3): 1028 - 1036. [Abstract] [Full Text]

				S. B. Seminara, F. J. Hayes, and W. F. Crowley Jr. Gonadotropin-Releasing Hormone Deficiency in the Human (Idiopathic Hypogonadotropic Hypogonadism and Kallmann's Syndrome): Pathophysiological and Genetic Considerations Endocr. Rev., October 1, 1998; 19(5): 521 - 539. [Abstract] [Full Text]

				L. B. Nachtigall, P. A. Boepple, F. P. Pralong, and W. F. Crowley Adult-Onset Idiopathic Hypogonadotropic Hypogonadism -- A Treatable Form of Male Infertility N. Engl. J. Med., February 6, 1997; 336(6): 410 - 415. [Abstract] [Full Text] [PDF]

				N. A. Georgopoulos, F. P. Pralong, C. E. Seidman, J. G. Seidman, W. F. Crowley Jr., and M. Vallejo Genetic Heterogeneity Evidenced by Low Incidence of KAL-1 Gene Mutations in Sporadic Cases of Gonadotropin-Releasing Hormone Deficiency J. Clin. Endocrinol. Metab., January 1, 1997; 82(1): 213 - 217. [Abstract] [Full Text] [PDF]