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follow-up of acromegaly and gigantism, IGFBP-3 measurement adds little if anything to IGF-1 testing.
The combination of IGF-1 and IGFBP-3 measurements appears superior to determining either analyte
alone in the diagnosis of GH deficiency and resistance, and in the monitoring of recombinant human GH
(rhGH) therapy. IGF-1 and IGFBP-3 levels below the 2.5th percentile for age are consistent with GH
deficiency or severe GH resistance, but patients with incomplete GH deficiency or mild-to-moderate GH
resistance may have levels within the reference range. In GH deficiency, GH levels may also be low and
can show suboptimal responses in stimulation tests (eg, exercise, clonidine, arginine, ghrelin, growth
hormone-releasing hormone [GHRH], insulin-induced hypoglycemia), while in severe GH resistance, GH
levels are substantially elevated. However, dynamic GH testing is not always necessary for diagnosis. If it
is undertaken, it should be performed and interpreted in endocrine testing centers under the supervision of
a pediatric or adult endocrinologist. The aim of both pediatric and adult GH replacement therapy is to
achieve IGF-1 and IGFBP-3 levels within the reference range, ideally within the middle-to-upper third.
Higher levels are rarely associated with any further therapeutic gains, but could potentially lead to
long-term problems of GH excess. Elevated IGF-1 and IGFBP-3 levels support the diagnosis of
acromegaly or gigantism in individuals with appropriate symptoms or signs. In successfully treated
patients, both levels should be within the normal range, ideally within the lower third. In both diagnosis
and follow-up, IGF-1 levels correlate better with clinical disease activity than IGFBP-3 levels. Increased
concentrations of IGF-1 are normal during pregnancy however reference ranges on this population have
not been formally established in our institution. After transsphenoidal removal of pituitary tumors in
patients with acromegaly, IGF-I concentration starts to decrease and returns to normal levels in most
patients postoperatively by the fourth day.(1) Persons with anorexia or malnutrition have low values of
IGF-1. IGF-1 is a more sensitive indicator than prealbumin, retinol-binding protein, or transferrin for
monitoring nutritional repletion. Puberty onset, ie the transition from Tanner stage 1 (prepubertal) to
Tanner stage 2 (early pubertal), occurs for girls at a median age of 10.5 (+/- 2) years and for boys at a
median age of 11.5 (+/-2) years. There is evidence that it may occur up to 1 year earlier in obese girls and
in African-American girls. By contrast, for boys there is no definite proven relationship between puberty
onset and body weight or ethnic origin. Progression through Tanner stages is variable. Tanner stage 5
(young adult) should be reached by age 18. IGF-1 reference values according to Tanner stages I–V(2)
-Males - Stage I: 63-279 ng/mL - Stage II: 75-420 ng/mL - Stage III: 94-765 ng/mL - Stage IV: 192-861
ng/mL - Stage V: 171-814 ng/mL -Females - Stage I: 49-342 ng/mL - Stage II: 115-428 ng/mL - Stage
III: 145-760 ng/mL - Stage IV: 244-787 ng/mL - Stage V: 143-859 ng/mL
Reference Values:
Age ng/mL 0.1 Percentile (ng/mL)
15 days-5 months 48-313 39
6-11 months 57-344 34
1 year 55-327 33
2 years 51-303 31
3 years 49-289 30
4 years 49-283 29
5 years 50-286 30
6 years 52-297 31
7 years 52-300 31
8 years 58-329 35
9 years 67-373 41
10 years 80-438 49
11 years 101-538 62
12 years 131-690 82
13 years 172-872 108
14 years 215-1,026 137
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