The Serum IGF-I Test: Its purpose and its weaknesses, proper use, variation, average responses

Type-IIx

Well-known Member
Author: Type-IIx

The GH serum test is...

Primarily a measure of an individual's GH response
not quality/veracity of a rhGH preparation.

The serum IGF-I test is not advised as a means to determine veracity or quality of an rhGH preparation, as it is not intended for this purpose. Instead, analytical laboratory testing using a GC/MS quantitative method is advised for this purpose.

The effects of rhGH on serum IGF-I are nonlinear, and are affected by the user's GHBP and GH receptor density (in fact, there exist relatively rare genetic conditions that cause extremely low response to GH) -- the principal determinants in { §Interindividual variation }, as well as body composition (fat mass), age, gender, and health status. It is, indeed, possible that a user has no significant change in serum IGF-I levels in response to rhGH treatment even using supraphysiological reference quality rhGH (e.g., Novo Nordisk). This is rare but not unheard of.

Serum IGF-I levels may increase in response to rhGH markedly over several weeks to months, and decrease somewhat, tending to stabilize around a somewhat narrow range. There is a decrement with continuous use, see { §§Practical: Decrement in GH response and cyclical planning }

Long-term rhGH at 2iU daily increased serum IGF-I in adult GHD patients to 351 µ/L [74]
> Subjects: Five male patients (aged 44-56 years, median age 54 years) with postoperative pituitary insufficiency given hGH replacement therapy for 1-2 years (median dose 2.0 U/day; median IGF-I serum concentration 351 microg/l) and 6 months after cessation of hGH treatment (median IGF-I level 77 microg/l - 1 microg/l = 0.131 nmol/l).
[74]
- See also: { §§§Full data (healthy subjects) on serum IGF-I changes with administration, withdrawal }

What is advised, if one does despite consternation, decide to undergo a serum IGF-I test in order to test the legitimacy of a product:

Only take the test:
- 12+ hours post-injection
- 6+ weeks into a course
- If using >2.5iU of rhGH daily (not on a 5/2 schedule)

Interpretation: View the results, first and foremost, as a binary value if and only if you see a significant increase: that is, if your baseline serum IGF-I levels increased by approximately double (or greater) under the testing conditions given, you can be certain that what you are using contains rhGH.
- What you do not know about the contents of your product:
-- % of actual rhGH
-- purity, contaminants
- If your serum IGF-I levels do not meaningfully increase, you still cannot be certain that your product is counterfeit or underdosed due to interindividual variation: you may be a hypo- or non-responder!
- Analytical laboratory testing using a GC/MS method is necessary to determine these values.

GH response: the most important data point in your trial of 1
However, you may view your results if measured under the conditions given, as a measure of your GH response to the product. That is, even if you picked up your 8IU daily dose of Norditropin from the local pharmacy yourself (so you know it's real) and administered it properly (perhaps you have HIV): if your serum IGF-I levels are insignificantly altered, you are unlikely to see significant benefit from the product (or, indeed, any rhGH preparation).
 
So if someone had very poor stimulation of IGF-1 from HGH, what benefits could they expect from exogenous HGH?

As per my understanding not all of HGHs benefits are from IGF-1. For example HGH frag works independant of IGF-1 and is, from what i’ve read, the primary actor of HGHs lipolytic effects.

So could the conclusion be drawn that despite poor IGF-1 response to exogenous HGH a user in that scenario could still benefit from its effects on lipolysis?

Are there other benefits of HGH that are not dependant upon IGF-1 and if so what are they? Collagen synthesis? Inhibition of lipogenesis? Etc.
 
So if someone had very poor stimulation of IGF-1 from HGH, what benefits could they expect from exogenous HGH?

As per my understanding not all of HGHs benefits are from IGF-1. For example HGH frag works independant of IGF-1 and is, from what i’ve read, the primary actor of HGHs lipolytic effects.

So could the conclusion be drawn that despite poor IGF-1 response to exogenous HGH a user in that scenario could still benefit from its effects on lipolysis?

Are there other benefits of HGH that are not dependant upon IGF-1 and if so what are they? Collagen synthesis? Inhibition of lipogenesis? Etc.
If someone has poor GH response (minimal increase in serum IGF-I), they can expect hyperglycemia (as IGF-I is hypoglycemic) and some lipolysis (though limited).

From my hGH + Metformin article:

hGH exerts direct effects on human adipocytes (fat cells) independently of IGF-1. In fact, human fat cells do not contain IGF-1 binding sites but contain specific hGH binding sites that are primary targets of physiological hGH. (DiGirolamo, et. al.). hGH enhances the oxidation of fatty acids relative to glucose (or amino acids). This is achieved by increasing adipose tissue lipolysis and/or reducing triglyceride storage in a nonuniform manner such as to redistribute adipose tissue from intra-abdominal to peripheral depots in addition to decreasing body fat mass. (Shadid, et. al.).

Still, practically IGF-1 is responsible for much of rhGH's downstream effects on fat loss. IGF-1 functions in part by increasing free fatty acid utilization, and enhancing insulin sensitivity upon receptor binding and subsequent intracellular signaling and glucose metabolism

GH has some minor mechanisms in augmenting lipolysis, growth, procollagenous activity directly yes, but with poor GH response (low IGF-I, serum) it'd make more sense to use the Ghrelin mimetics/GHRH-/GHRP- agonists.
 
If someone has poor GH response (minimal increase in serum IGF-I), they can expect hyperglycemia (as IGF-I is hypoglycemic) and some lipolysis (though limited).

From my hGH + Metformin article:



GH has some minor mechanisms in augmenting lipolysis, growth, procollagenous activity directly yes, but with poor GH response (low IGF-I, serum) it'd make more sense to use the Ghrelin mimetics/GHRH-/GHRP- agonists.

Why would it make more sense to use secretagogues verse rHGH in such circumstances?

In relying on secretagogues one is opening themselves up to the possibility of poor response to secretagogues, by which i mean low endogenous GH release in the presence of secretagogues. Assuming thats not the case, what advantage does a secretagogue offer over exogenous rHGH?

The advantage of rHGH would be a guaranteed level of GH. The disadvantage of a secretagogue would be potentially poor response.

So unless you are inferring that ghrelin, or GHRH receptor action has benefits beyond just GH release (if so, what?) i dont see why you would conclude secretagogues would be better? Unless you are suggesting greater overall daily GH levels in secretagogue use due to somatostatin related negative feedback mechanisms being more triggered by exogenous rHGH verse secretagogues? But if thats the case wouldnt secretagogues be superior even in a person with optimal IGF-1 response to GH?

Whilst im unsure on GHRH, i do know Ghrelin receptor agonism has effects beyond just GH release. So perhaps your implying those GH-independant effects would be superior, but if so that brings me back to my question why secretagogues wouldnt be superior even in someone with optimal IGF-1 response to GH?
 
Why would it make more sense to use secretagogues verse rHGH in such circumstances?

In relying on secretagogues one is opening themselves up to the possibility of poor response to secretagogues, by which i mean low endogenous GH release in the presence of secretagogues. Assuming thats not the case, what advantage does a secretagogue offer over exogenous rHGH?

The advantage of rHGH would be a guaranteed level of GH. The disadvantage of a secretagogue would be potentially poor response.

So unless you are inferring that ghrelin, or GHRH receptor action has benefits beyond just GH release (if so, what?) i dont see why you would conclude secretagogues would be better? Unless you are suggesting greater overall daily GH levels in secretagogue use due to somatostatin related negative feedback mechanisms being more triggered by exogenous rHGH verse secretagogues? But if thats the case wouldnt secretagogues be superior even in a person with optimal IGF-1 response to GH?

Whilst im unsure on GHRH, i do know Ghrelin receptor agonism has effects beyond just GH release. So perhaps your implying those GH-independant effects would be superior, but if so that brings me back to my question why secretagogues wouldnt be superior even in someone with optimal IGF-1 response to GH?
Good question. My rationale for supposing the secretagogues may be superior for persons with reduced GH response (i.e., low serum IGF-I) is due primarily to the pivotal role of estrogens in diminished GH response. Though this ignores the hepatic and reduced somatotrophs reflecting GH receptor in some persons with diminished GH response, it at least saves them money and may augment the lipolytic, cardiometabolic, bone, lean mass, et cetera benefits of GH when it is estrogens (a la increased IGFBP-1) that are modulating (suppressing) the GH response more economically, and with some benefit (primarily for women, MAYBE the obese - though they may not respond well to these either, those with high serum estradiol, etc.) The secretagogues vs. say the classical subcutaneous GH bolus would have a lower GH AUC so as to reduce the hyperglycemic effects (I believe).
 
Say if someone was already running exogenous rHGH and wanted to get a baseline IGF-1 number for a reference, how long after withdrawing from the rHGH would it take for the IGF-1 level to drop back to baseline?
 
Only take the test:
- 12+ hours post-injection
- 6+ weeks into a course
- If using >2.5iU of rhGH daily (not on a 5/2 schedule)
Hmmm, so what would you say to someone doing 4iu 6/1 or very occasionally 5/2 (usually 6/1)? Would the test not be worth it? I just find that day or two off elevates the slight sides I get (numb hands) but if it’s significantly denting the impact of the treatment bumping my igf I’ll just suck it up.

Also, entirely off topic for the thread, but I just wanted to thank you for discussing elsewhere (can’t remember where) the igf-1 down regulation at 6 months inspiring me to do 4 or 5 month cycles gh followed by a washout period. Your information is invaluable.
 
Hmmm, so what would you say to someone doing 4iu 6/1 or very occasionally 5/2 (usually 6/1)? Would the test not be worth it? I just find that day or two off elevates the slight sides I get (numb hands) but if it’s significantly denting the impact of the treatment bumping my igf I’ll just suck it up.
It's still worth taking the test for 4 IU 6.i.w.
Also, entirely off topic for the thread, but I just wanted to thank you for discussing elsewhere (can’t remember where) the igf-1 down regulation at 6 months inspiring me to do 4 or 5 month cycles gh followed by a washout period. Your information is invaluable.
Great. I will be hashing out the full principles of rational rhGH use in Bolus, that is one aspect.
 
Back
Top