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Gonadotropin-Releasing Hormone Deficiency in Adults Workup

  • Author: Vaishali Popat, MD, MPH; Chief Editor: Richard Scott Lucidi, MD, FACOG  more...
Updated: Nov 11, 2013

Laboratory Studies

Along with the above-described clinical manifestations, most patients have low serum levels of basal gonadotropins, estrogen/testosterone, and poor response to gonadotropin-releasing hormone (GnRH) stimulation. The difficulty arises when trying to differentiate between healthy prepubertal males and those with idiopathic hypogonadotropic hypogonadism (IHH) or Kallmann syndrome (KS).

Patients with KS can be distinguished from prepubertal males aged 12.5 years or older by determining the level of luteinizing hormone (LH) in pooled serum samples collected every 20 minutes for 6 hours commencing 1 hour after sleep onset.

The GnRH stimulation test using a synthetic GnRH analog, such as buserelin, has been used to differentiate males with gonadotropin deficiency from those with delayed puberty. In a study by Wilson et al, a total 31 prepubertal males were given 100 µcg of buserelin subcutaneously, and blood samples for LH and follicle-stimulating hormone (FSH) were obtained at 0 and 4 hours after treatment.[43] Participants were then followed for a mean duration of 4.2 years to determine if they progressed through puberty. Twenty-six percent of individuals failed to undergo puberty and were diagnosed with gonadotropin deficiency. None of these men had had a buserelin-stimulated serum LH level higher than 5 U/L. In fact, the LH response was significantly lower when compared with those males who ultimately developed puberty. The stimulated FSH levels were comparable in both groups, and thus are not useful when distinguishing delayed puberty from IHH or KS.


Imaging Studies

MRI appears to be the single best study for the diagnosis of KS and exclusion of other CNS disorders associated with hypogonadotropic hypogonadism.

T1-weighted MRI of the inferior frontal region in the coronal plane appears most helpful in examining the olfactory sulci, bulbs, and rhinencephalon.

Because of the lack of production of sex steroids, men and women with KS and IHH can experience abnormal bone development. The prudent use of a dual-energy x-ray absorptiometry (DEXA) scan to monitor bone mineral density in these individuals is appropriate.


Other Tests

Many affected individuals are unaware of their loss of olfaction, especially those with partial defects. Testing with graded dilutions of pure scents is often necessary to identify the impaired olfaction. The magnitude of GnRH deficiency appears to correlate with the severity of anosmia.

Along with the anosmia, another interesting neurological finding is that of mirror movements related to the cerebellar defects. Mirroring, involuntary movements of a limb that mirror voluntary movements of the contralateral limb, is present in as many as 85% of patients.

Contributor Information and Disclosures

Vaishali Popat, MD, MPH Clinical Investigator, Intramural Research Program in Reproductive and Adult Endocrinology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health

Vaishali Popat, MD, MPH is a member of the following medical societies: American College of Physicians, Endocrine Society

Disclosure: Nothing to disclose.


Karim Anton Calis, PharmD, MPH FASHP, FCCP, Clinical Professor, Medical College of Virginia, Virginia Commonwealth University; Clinical Professor, University of Maryland; Clinical Investigator, Office of the Clinical Director, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health

Karim Anton Calis, PharmD, MPH is a member of the following medical societies: American College of Clinical Pharmacy, American Society of Health-System Pharmacists, Endocrine Society

Disclosure: Nothing to disclose.

Ziad Rafic Hubayter, MD, MPH Fellow, The Howard and Georgeanna Jones Division of Reproductive Endocrinology and Infertility, Department of Gynecology and Obstetrics, Johns Hopkins University, National Institute of Health, National Institute of Child Health and Human Development

Ziad Rafic Hubayter, MD, MPH is a member of the following medical societies: American College of Obstetricians and Gynecologists, American Medical Association, American Society for Reproductive Medicine

Disclosure: Nothing to disclose.

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Chief Editor

Richard Scott Lucidi, MD, FACOG Associate Professor of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, Virginia Commonwealth University School of Medicine

Richard Scott Lucidi, MD, FACOG is a member of the following medical societies: American College of Obstetricians and Gynecologists, American Society for Reproductive Medicine

Disclosure: Nothing to disclose.

Additional Contributors

Bruce A Meyer, MD, MBA Executive Vice President for Health System Affairs, Executive Director, Faculty Practice Plan, Professor, Department of Obstetrics and Gynecology, University of Texas Southwestern Medical School

Bruce A Meyer, MD, MBA is a member of the following medical societies: Medical Group Management Association, American College of Obstetricians and Gynecologists, American Association for Physician Leadership, American Institute of Ultrasound in Medicine, Association of Professors of Gynecology and Obstetrics, Massachusetts Medical Society, Society for Maternal-Fetal Medicine

Disclosure: Nothing to disclose.


The authors and editors of Medscape Reference gratefully acknowledge the contributions of previous authors James N Anasti, MD and Michael Cackovic, MD to the development and writing of this article.

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Human GPR54 receptor model. Mutations identified in patients with idiopathic hypogonadotropic hypogonadism are indicated.
KiSS-1 protein product model. Amino acids 1-19 are predicted to form a signal peptide. Proteolytic processing is predicted to produce kisspeptin-54, corresponding to amino acids 68-121. Shown is the C-terminal amidated decapeptide sequence, wherein biologic actively resides.
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