Calciotropic Effects After hCG Stimulation Test
Condition: Hypogonadism, Male
MeSH terms: Hypogonadism; Eunuchism
Study type: Observational

Summary: 
      We have in a pilot study found that serum calcium levels change in response to hCG
      stimulation test. We observed that serum calcium level measured at baseline and 72 hours
      after hCG stimulation were different in men with gonadal insufficiency referred for this
      stimulation test. Now we want to investigate a large cohort of men referred for hCG
      stimulation test due to suspected impaired gonadal function.
    

Detailed description: 
      Introduction:

      hCG signals through the LHCGR receptor and is know to stimulate testosterone production. hCG
      stimulation tests are therefore used to evaulate the capacity of the testis to respond to
      LH/hCG and thereby determine the degree og gonadal insufficiency and need for testosterone
      supplementation. Some groups have found LHCRG in extragondal tissues indicating a direct
      effect of hCG/LH outside the gonads. We noticed that some men with gonadal insuffciency had a
      low calcium level after hCG stimulation test. Now we would like to investigate whether this
      putative effect on calcium homeostasis of hCG is due to a direct effect or an indirect effect
      through testosterone or other sex steroids that also change in response to hCG stimulation.
      Moreover, we would like to clarify whether the chnage in calcium is compensated by classical
      regulators such as PTH, 1,25OH2D3, calcitonin, phosphate, CTX, alkaline phosphatase or other
      factors.

      Aim of study:

      The purpose of this study is to describe changes in calcium and calciotropic hormones after
      hCG stimulation test

      DESIGN This is a prospective observational study

      Patients and methods 100 men referred for hCG stimulation test due to suspected gonadal
      insuffciency age 18-60 years at Department of growth and reproduction, Rigshospitalet

      Exclusion criteria are

      intake of high dose calcium (above 1 mg daily) Known Disorders related to calcium metabolism,
      hypercalcemia, Granulomatous disease such as Wegener, tuberculosis, etc,

      SAMPLE SIZE CALCULATION AND STATISTICS By using a test level of 5% (level of significance),
      power of 80% and at least 100 men completing the trial will enable us to detect a change in
      calcium of 10%, and a change in serum PTH of 30%.

      SCREENING AND TIME COURSE Men referred for hCG stimulation test at ourDepartment will be
      screened for eligibility to the study. Those who meet the criteria for participation will be
      informed, and if they consent allocated to the study.

      Each person will have one blood sampling performed prior to the test and 72 and 96 hours
      after the test.

      Blood samples Venus blood is drawn preoperatively before hCG administration, 72 and 96 hours
      after. Serum will be send for analysis within 45 minutes and the rest frozen within 1 hour
      and will be stored at minus 20 degrees celsius until analysis.

      OUTCOME MEASUREMENTS

      Primary endpoints

      •Changes in total, albumin corrected and ionized calcium

      Main Secondary endpoints

        -  Changes in PTH

        -  Changes in 1,25OH2D3

        -  Changes in Phosphate

        -  Changes in FGF23

        -  Changes in Calcitonin

        -  Changes in LHCGR in serum

        -  Changes in Cortisol

        -  Changes in total and free testosterone

        -  Changes in total and free estradiol

        -  Changes in kidney function (GFR/creatinin)

        -  Changes in gonadotropins

        -  Changes in 25OHD, 24,25OH2D3

        -  Changes in serum concentrations of putative regulators and downstream signals
           osteocalcin, osteopontin, RANKL, osteoprotegerin (OPG), alpha Klotho, Sclerostin and
           IGF-1.

      Temporal changes in serum level of binding proteins. differences for vitamin D binding
      protein, albumin and sex hormone binding globulin.

      Predefined subgroups orchiectomized men/ bilaterally irradiated testis High versus low
      baseline estradiol/testosterone Low/high calcium/PTH baseline

      ANALYSIS AND INTERVENTION

      Reproductive hormones and growth factors will be analysed at dept. of GR, Rigshospitalet.
      Other serum analyses will be analysed at Department of clinical biochemistry, and Aarhus
      Kommune Hospital

      ETHICS AND SIDE EFFECTS All the patients will have full-filled their investigation, before
      they are invited to the study. They will be informed of potential adverse effects, and they
      can leave the trial at any point without any consequences. This study poses no additional
      risk to the patients except for the blood samples as everything else is according to standard
      clinical practice.

      PUBLICATION OF RESULTS All results, positive or negative will be submitted to peer reviewed
      scientific journals. Data will successively be obtained and transferred to a statistical
      database.
    

Intervention name(s): human chorionic gonadotropin
Intervention type(s): Drug
Intervention description(s): 5000 IE times one
Other intervention name(s): hCG
Intervention MeSH terms: Chorionic Gonadotropin
Observational model: Case-Only
Time perspective: Prospective
Sampling method: Probability Sample
Study population: 
        men with suspected gonadal i suffciency ofter after orchiectomy or bilateral irradiation
        due to testis cancer
      
Biospecimen description: 
      serum