IGF-1: When More is Less

While some colleagues believe in a more traditional laboratory definition of some conditions, I try to treat the patient but without going overboard.  For a number of issues, more is better.  More home runs hit, more bases stolen, more free throws sunk, more goals scored.  However, when it comes to medicine, I think the Goldilocks theory applies.

On the other hand, some of my former colleagues believe in the more is more strategy, especially when it comes to treating growth hormone deficiency.  When treating their patients, they believe that everyone should have and be treated to an IGF-1 of 300ng/mL or even higher, based upon reference ranges from older equipment that is not currently being used.  This is despite current use of equipment that has a significantly lower upper limit of normal.

Well, in a study released early just 2 days ago (to be published in September), the authors noted a U-shaped curve when comparing all-cause, cancer & cardiovascular mortality to IGF-1 levels.  In other words, those participants who had IGF-1 outside the mid-centile reference range, whether high or low, had a greater risk of death, even though their IGF-1 was still within the normal reference range.  Of course, this begs the question, what is considered normal?

Well, the normal reference range is that range which includes approximately 95-96% of the "normal" population.  Of course, one could always argue whether having two-thirds of our population overweight or obese is really & truly "normal".  Nevertheless, we take a bunch of "normal" participants and throw out the lowest 2-2.5% and the highest 2-2.5%, even though they must be "normal" by definition in order to included.

But that still doesn't make us feel any more comfortable about aiming for high (or low) IGF-1 levels.  The authors analyzed data from 12 population-based cohort & (nested) case-control studies including 14,906 participants who were deemed normal.  For instance, studies of patients w/acromegaly, acute renal failure or liver cirrhosis where excluded.  Children & patients in intensive care units were also excluded.

As noted above, different assays (lab equipment) were used over time and by different laboratories, each with their own specific reference ranges, precluding direct comparison of IGF-1 levels.  Therefore, the authors compared percentiles of IGF-1, since the distribution of results should be same, regardless of the test used.  Yet, time & again, those in the 10th percentile (lowest grouping) had 56% greater risk of mortality than those in the 50th percentile (mid-range).  And those in the 90th percentile (highest grouping) had 29% greater risk compared to those in the 50th percentile.

Granted, this is observational data.  So one shouldn't necessarily jump to the conclusion that treating to lower (which begs the question, why treat at all) and higher levels is worse or more dangerous/deadly than treating to the mid-range of your lab's reference range.  But until proven otherwise, I think the Goldilocks theory of medicine applies here.  To wit, give the right amount, not too little, and not too much.