Gonadotropin-Releasing Hormone Deficiency in Adults Workup

Updated: Feb 17, 2022
  • Author: Vaishali Popat, MD, MPH; Chief Editor: Richard Scott Lucidi, MD, FACOG  more...
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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. [47, 48] 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.