I would like to perform serum testosterone, dihydrotestosterone,17, hydroxyprogestrone, LH and FSH levels in children with 46, XY DSD. Should I take the basal levels of testosterone & dihydrotestosterone or the children should first be given an injection of HCG and then the levels of these hormones?
Pre- and post should both be helpful, especially since I do not know the age of the child with reference to the mini-puberty of infancy. ADR
That has always been a quagmire--one or a few injections over a week or so up to perhaps 1,500 U (very supraphysiological). There is no single standard. We have been discussing this same question for the 40 years that I have been in practice! Please note this is for diagnosis and not therapy. There is just as much controversy about that subject as well.
there is several protocol for HCG stimulation in children either single dose of 5000 then estimation of testosterone and its precursors or stimulation with a total dose of 7500 over 4 days , a long stimulation over 6 weeks can be done in case of equivocal response
I concur with Dr. Rogol that the age of the children is key -- the mini-puberty of infancy is a brief window of time during which these hormones are often elevated to pubertal levels (starting within a couple weeks after birth and usually over after a few months), but after this time baseline values are often undetectable. Thus, hCG can be helpful to induce T and DHT for detecting functional testicular tissue, and also thought to help in testicular descent (though I have rarely hear do this being effective). Anti-mullerian hormone may also be helpful and there are several papers on this topic in series of 46 XY DSD patients. You may have to do several hCG injections and the timing of blood drawing is important.
Thank you all for the comments. We have 56 children who presented with DSD and their chromosome analysis revealed 46, XY. Their age range from 06 days to 18 years (majority of them are below 5 years of age). We would like to catagories them into types of DSD according to their hormone profile (Gonadal dysgenesis, androgen synthetic defect, 5 alpha reductase deficiency, androgen insensitivity syndrome etc).
Hello Saqib
As Alan said the doses of hCG for testing or even treatment are so controversial and supraphysiological like synacthen and other endocrine tests in children
If you have this big number of cases, may I suggest that you standardize the test and make it simple, just one big dose for all cases, then test and compare outcome with the more complex dosing regimes that you might have used already on some cases.
I am sure you will get the same outcome from the diagnostic point of view.
If that comes true, publish it and let us know; it is a step forward.
What do you think Alan of this pragmatic simplification?
Many thanks everyone for sharing.
Dear Dr Mahmood,
as seen from the answers above, there is no single pathway and we desperately need a consensus on the exact protocols. However, also the methods of measurement play a very important role. So my advice is:
To distinguish generalised gonadal dysorders (gonadal dysgenesis) from specific disorders of sexual differentiation (androgen biosynthesis and action) determine AMH or Inhibin B, which will be low in the first, but within the normal reference intervals for age in males within the second (or even elevated)
For distinguishing androgen biosynthesis defects, you should take into account urinary steroid profiling. It is very sensitive in all DSD forms with adrenal dysfunction and also in 5alpha-reductase deficiency. Measurement of DHT is a major problem for most labs and only valid if done with LCMSMS.
If this is ruled out I would recommend an hCG-Test in prepubertal children and determine testosterone and androstenedione. 17beta HSD deficiency can be distinguished both in urinary and serum steroid analysis.
Last then, you get to the clinical and biochemical diagnosis of androgen insensitivity, which needs to be (as the others also) by molecular genetic analysis.
Best wishes, Olaf
Please see Olaf's answer and note that there is a large series. As Dr. Ainine suggests a "standard" protocol would be terrific. Olaf and I were at a conference on this subject and the December, 2012 issue of Pediatric Urology speaks to this point. The specific article that may inform you about a "protocol" is Hughes IA, Morel Y, McElreavey K, Rogol A. Biological assessment of abnormal genitalia. J Pediatr Urol, 2012; 8(6):592-596. Please note that the algorithm follows that of Prof Morel (one of the three authors) and the rationale can be obtained from some of his refs in the Hughes article. I am certain that one or another of the research labs will evaluate your samples so that assay issues will not cloud your results. You have quite an opportunity. Best wishes. ADR
I think that one should divide the tests into 2 categories: (i0 initial tests, and (ii) additional tests depending on initial findings; I assume that a full karyotype, FISH with X- and Y-specific probe detection, and imaging of the abdomen and pelvis have already been done by you. Thus, I would do a basal testosterone, FSH, LH and 17(OH)progesterone, and antiMullerian hormone first. Thereafter, if the diagnosis is still in doubt, one can go on to hCG and synacthen stimulation tests to assess testicular and adrenal steroid biosynthesis. Remember that even with the best and all available testing, only 50% of 46,XY DSD will receive a definite diagnosis..Could you perhaps send me your email address as I would like to discuss this with you in depth. Many thanks. Prof Ismail Haffejee: [email protected]
I'm not a clinical endocrinologist, but in order to have proper control of the effects of hCG, I think the best way is to measure the basal levels of hormones of these boys and then compare it to the the hCG treatment.
Hello there, the first question is how old are yours patients ? Below age 6 monthes kids have high testosterone levels so you need not perform HCG, after this age you will definitely need HCG injections prior to testosterone and DHT assay. There are several protocols depending on patients' age, etc. I can help if you tell us how old patients are by sending a protocol (will need your email address then). Best wishes.
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