• Liaqat Ali
  • Afrose Adeel


Background: The prevalence of Idiopathic Hypogonadotropic Hypogonadism (IHH) is approximately1 in 10,000 men. Objectives of this study were to evaluate the role of basal and stimulated serumprolactin in differentiating Constitutional Delayed Puberty (CDP) from IHH. Methods: This crosssectional study was carried out at the Department of Diabetes and Endocrinology, Military Hospital,Rawalpindi. A total of 20 male patients presenting with provisional diagnosis of IHH/CDP wereenrolled in the study. Patients with known diseases were excluded from the study. Baseline FSH, LH,testosterone, and prolactin were estimated and the patients were subjected to provocative prolactinstimulation by Thyrotropin releasing hormone stimulation (TRH) test and chlorpromazine challenge.At each 6 monthly follow-up visit for 4 years, the patients were evaluated for adrenarche, pubarche andother secondary sexual characters. Tanner scale was taken as standards for comparing stage of pubertyat a particular age. No treatment was given to both groups for 2 years. At the end of 2 years IHHpatients with failed puberty or progression of puberty and CDP who lagged behind by more than 2years by Tanner scale or 4 years per bone age with compelling psychosocial or psychosexual reasons atschool or at home were given short courses of 50 mg injection testosterone in an attempt to expedite theonset or progression of puberty. Patients from either group with failed puberty after low dosetestosterone were managed with high dose testosterone therapy to induce secondary sexual characters.Results: Twenty patients enrolled in the study were provisionally divided into 2 groups called IHH(n=9), and CDP (n=11) based on high basal and provocative serum prolactin levels in CDP group. Twopatients from CDP group were lost in the follow-up leaving 9 patients in each group. A total of 10 (56%)patients, 3 (17%) from IHH group and 7 (39%) from CDP group achieved grade 4 puberty without anytreatment. Remaining 8 (44%) patients, 6 (67%) from IHH group and 2 (22%) from CDP group wereinduced secondary sexual characters with full dose of 100 mg testosterone given parenterally at 4 weeksintervals. Conclusion: Differentiation between IHH and CDP on the basis of basal and post-TRH andChorpromazine challenge reported earlier could not be substantiated by our study.Keywords: Hypogonadotropic hypogonadism, Constitutional delayed puberty, prolactin, FSH, LH


Fromantin M, Gineste J, Didier A, Rouvier J. Impuberism and

hypogonadism at induction into military service. Statistical study.

Probl Actuels Endocrinol Nutr 1973;16:179–99.

Filippi G. Klinefelter's syndrome in Sardinia. Clinical report of

hypogonadic males detected at the time of check-up. Clin

Genet 1986;30(4):276–84.

Dode C, Levilliers J, Dupont M, De Paepe A, Le Dû N, SoussiYanicostas N, et al. Loss-of-function mutations in FGFR1 cause

autosomal dominant Kallmann syndrome. Nat Genet


Pitteloud N, Durrani S, Raivio T, Sykiotis P. Complex genetics in

idiopathic hypogonadotropic hypogonadism. Front Horm Res


Pitteloud N, Zhang C, Pignatelli D, Li JD, Raivio T, Cole W,

Plummer L, et al. Loss-of-function mutation in the prokineticin 2

gene causes Kallmann syndrome and normosmic idiopathic

hypogonadotropic hypogonadism. Proc Natl Acad Sci USA


Dode C, Teixeira L, Levilliers J, Fouveaut C, Bouchard P,

Kottler ML, et al. Kallmann syndrome: mutations in the genes

encoding prokineticin-2 and prokineticin receptor-2. PLoS Genet


Skinningsrud B, Husebye ES, Gilfillan GD, Frengen E, Erichsen A,

Gervin K, et al. X-linked congenital adrenal hypoplasia with

hypogonadotropic hypogonadism caused by an inversion disrupting

a conserved noncoding element upstream of the NR0B1 (DAX1)

gene. J Clin Endocrinol Metab 2009;94:4086–93.

A case of adult-onset idiopathic hypogonadotropic

hypogonadism presenting with infertility. Hinyokika Kiyo


Canto P, Munguía P, Söderlund D, Castro JJ, Méndez JP.

Genetic analysis in patients with Kallmann syndrome:

coexistence of mutations in prokineticin receptor 2 and KAL1. J

Androl 2009;30(1):41–5.

Oliveira LM, Seminara SB, Beranova M, Hayes FJ, Valkenburgh

SB, Schipani E, et al. The importance of autosomal genes in

Kallmann syndrome: genotype-phenotype correlations and

neuroendocrine characteristics.J Clin Endocrinol Metab


Edouard T, Tauber M. Delayed puberty. Arch Pediatr


Marshall WA, Tanner JM. Variations in the pattern of pubertal

changes in boys. Arch Dis Child 1970;45(239):13–23.

Marshall WA, Tanner JM. Variations in pattern of pubertal

changes in girls. Arch Dis Child 1969;44(235):291–303.

Harrington J, Palmert MR. Distinguishing constitutional delay of

growth and puberty from isolated hypogonadotropic

hypogonadism: critical appraisal of available diagnostic tests. J

Clin Endocrinol Metab 2012;97:3056–67.

Spitz IM, Hirsch HJ, Trestian S. The prolactin response to

thyrotrophic releasing hormone differentiates isolated

hypogonadotropin deficiency from delayed puberty. N Engl J

Med 1983;308:575–9.

Delemarre-van de Waal HA. Application of gonadotropin

releasing hormone in hypogonadotropic hypogonadismdiagnostic and therapeutic aspects. Eur J Endocrinol

;151(Suppl 3):U89–94.

Shargil AA. Treatment of idiopathic hypogonadotropic

hypogonadism in men with luteinizing hormone-releasing

hormone: a comparison of treatment with daily injections and

with the pulsatile infusion pump. Fertil Steril 1987;47:492–501.

Kim SO, Ryu KH, Hwang IS, Jung SI, Oh KJ, Park K. Penile

Growth in Response to Human Chorionic Gonadotropin (hCG)

Treatment in Patients with Idiopathic Hypogonadotrophic

Hypogonadism. Chonnam Med J 2011;47(1):39–42.

Nieschlag E, Behre M, Bouchard P, Corrales J, Jones H, Stalla G,

et al. Testosterone replacement therapy: current trends and future

directions. Human Reprod Update 2004;10:409–19.

Quinton R, Duke VM, de Zoysa PA, Platts AD, Valentine A,

Kendall B, et al. The neuroradiology of Kallmann’s syndrome: a

genotypic and phenotypic analysis. J Clin Endocrinol Metab


Callewaert F, Morreels M, Kumar N, Sitruk-Ware R, Van K,

Hespel P, et al. 7α-methyl-19-nortestosterone vs. testosterone

implants for hypogonadal osteoporosis: a preclinical study in the

aged male orchidectomized rat model. Int J Androl 2011;34(6 Pt


Raivio T, Falardeau J, Dwyer A, Quinton R, Hayes FJ, Hughes

VA, et al. Reversal of idiopathic hypogonadotropic

hypogonadism. N Engl J Med 2007;30:357:863–73.

Liu L, Banks SM, Barnes KM, Sherins RJ. Two-year comparison

of testicular responses to pulsatile gonadotropin-releasing

hormone and exogenous gonadotropins from the inception of

therapy in men with isolated hypogonadotropic hypogonadism J

Clin Endocrinol Metab 1988;67:1140–5.

Barkan AL, Reame NE, Kelch RP, Marshall JC. Idiopathic

hypogonadotropic hypogonadism in men: dependence of the

hormone responses to gonadotropin-releasing hormone (GnRH)

on the magnitude of the endogenous GnRH secretary defect. J

Clin Endocrinol Metab 1985;61:1118–22.

Finkelstein JS, Badger TM, O'Dea LS, Spratt DI, Crowley WF.

Effects of decreasing the frequency of gonadotropin-releasing

hormone stimulation on gonadotropin secretion in gonadotropinreleasing hormone-deficient men and perfused rat pituitary cells.

J Clin Invest 1988;81:1725–33.

Pitteloud N, Hayes J, Dwyer A, Boepple A, Lee H, Crowley F.

Predictors of outcome of long-term GnRH therapy in men with

idiopathic hypogonadotropic hypogonadism. J Clin Endocrinol

Metab 2002;87:4128–36.