How to prepare for the ‘IGF-1’ test: rules for taking it

Insulin-like growth factor-1 (IGF-1) is the main mediator of the action of growth hormone and the primary laboratory marker for assessing it. Unlike growth hormone itself, IGF-1 is relatively stable over the course of the day, so it is convenient to measure it once. But the result depends on age, nutrition, the state of the liver and thyroid, and even on the laboratory's test system. The editorial team explains how to prepare for the test and how to read it correctly.

What IGF-1 is and why it is measured

IGF-1 is a peptide hormone synthesised mainly in the liver in response to growth hormone (somatotropin). It is through IGF-1 that most of the growth-promoting and anabolic effects of growth hormone are realised: the lengthwise growth of bones in childhood, the maintenance of muscle and bone mass in adults, the effect on metabolism.

Growth hormone is released in pulses, mainly at night, and in the intervals between them its concentration can be almost undetectable. IGF-1 in the blood is bound to proteins, primarily IGFBP-3 and the acid-labile subunit, so its level changes much less over the course of the day. This makes IGF-1 a convenient ‘integral’ indicator of growth hormone secretion.

The Endocrine Society clinical guideline on acromegaly (Katznelson et al., 2014) recommends measuring IGF-1 as the first step in diagnosing an excess of growth hormone and for monitoring treatment. The guideline on growth hormone deficiency in adults (Molitch et al., 2011) considers IGF-1 an auxiliary indicator, keeping in mind that a normal level does not rule out a deficiency.

The test is also ordered for children with growth retardation, patients with pituitary diseases and when monitoring growth hormone therapy.

Rules for preparing for the test

Since the daily fluctuations of IGF-1 are small, there is no strict requirement regarding the hour of the draw, as there is for testosterone. However, laboratories and doctors recommend unified conditions so that results can be compared over time.

• have it done in the morning, fasting or after an overnight fast of 8–12 hours, if the laboratory requires it;
• the day before, avoid intense training and alcohol;
• do not take it during an acute illness, after surgery or trauma;
• do not do the test at the peak of a strict diet or prolonged fasting, if a ‘baseline’ assessment is needed;
• inform the doctor about hormonal agents, oral estrogens, growth hormone drugs and biotin.

The most important thing is the stability of the state. IGF-1 responds sensitively to a prolonged energy and protein deficit, so a person who has been on a very low-calorie diet for several weeks will get a lower result than with normal nutrition.

Biotin in high doses can affect some immunoassays; the FDA has published a separate warning about this. Check with the laboratory whether their IGF-1 test uses a ‘streptavidin–biotin’ system and whether a break is needed.

For monitoring over time it is worth taking the test in one laboratory: different test systems give different results, as discussed below.

Factors that alter IGF-1

The IGF-1 level is determined not only by growth hormone. A number of conditions and drugs can alter it independently of somatotropin secretion, and this must be taken into account when interpreting.

Oral estrogens, in particular as part of combined contraceptives and hormone replacement therapy, lower IGF-1 through their effect on the liver. Transdermal forms of estrogens have a much smaller effect. The guideline on growth hormone deficiency in adults takes this circumstance into account when interpreting.

The kidneys, liver, thyroid and nutritional state — all of these affect IGF-1. Therefore, with an unexpected result, the doctor usually assesses liver panels, TSH, glycemia and nutritional status.

A reduced IGF-1 in a person with a pronounced weight deficit or anorexia is an expected adaptation to fasting, rather than an independent growth hormone deficiency.

Age reference, SDS and differences between test systems

IGF-1 changes so strongly with age that a ‘single norm’ does not exist. The level is low in early childhood, reaches a maximum in puberty and gradually decreases throughout adult life.

Therefore the result is assessed only relative to the age (and in puberty — also the sex and pubertal) interval. Many laboratories additionally provide the SDS (standard deviation score) — the number of standard deviations from the mean for age. SDS values make it easier to compare results over time and between people of different ages.

A significant problem is the differences between test systems. Results obtained by different methods can differ noticeably, so each test system requires its own age reference ranges. It was precisely such intervals from birth to old age for one of the automated test systems that were established by the multicentre study of Bidlingmaier and colleagues (2014). The consensus statement on the standardisation of growth hormone and IGF-1 assays (Clemmons, 2011) called for calibration against an international standard and validation of age reference ranges.

The practical conclusion: do not compare results from different laboratories and rely on the reference given on your form. The units of measurement — ng/mL or nmol/L — must also be taken into account.

IGF-1 in sport: what is important to know

In the sports community, IGF-1 is often perceived as a ‘marker of anabolism’. It is indeed linked to protein metabolism, but its level in a healthy person largely reflects age, nutrition and the state of the liver, rather than the ‘quality of training’. Short-term fluctuations after training have no practical significance for assessing progress.

Growth hormone, IGF-1 and their analogues, as well as substances that stimulate growth hormone secretion, are on the WADA Prohibited List (section S2) and are banned both in and out of competition. For athletes subject to doping control, this is important to take into account during any treatment.

An excess of growth hormone and IGF-1 has real health consequences: in acromegaly, insulin resistance and diabetes mellitus, cardiomyopathy, arterial hypertension, arthropathy, carpal tunnel syndrome develop. The guideline by Katznelson and colleagues (2014) describes these complications as the basis for active treatment.

If an athlete has taken any drugs that affect the growth hormone axis, the doctor must know about this, because otherwise the test result will be interpreted incorrectly.

Editorial conclusions

IGF-1 is a stable and convenient marker of growth hormone activity, but its interpretation is possible only taking into account age, sex, nutrition, the state of the liver and thyroid, and the intake of estrogens.

For a correct result, take the test in the morning, in a stable state, without a strict diet or acute illnesses, in one and the same laboratory, with the doctor informed about all drugs and biotin.

Diagnosis of a deficiency or excess of growth hormone is carried out by an endocrinologist, often using stimulation or suppression tests.

The editorial team advises also reading our articles on preparing for the prolactin, total testosterone and LH tests.

References

1. Katznelson L, Laws ER Jr, Melmed S, et al. Acromegaly: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2014;99(11):3933–3951.
2. Molitch ME, Clemmons DR, Malozowski S, et al. Evaluation and treatment of adult growth hormone deficiency: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2011;96(6):1587–1609.
3. Clemmons DR. Consensus statement on the standardization and evaluation of growth hormone and insulin-like growth factor assays. Clin Chem. 2011;57(4):555–559.
4. Bidlingmaier M, Friedrich N, Emeny RT, et al. Reference intervals for insulin-like growth factor-1 (IGF-I) from birth to senescence: results from a multicenter study using a new automated chemiluminescence IGF-I immunoassay conforming to recent international recommendations. J Clin Endocrinol Metab. 2014;99(5):1712–1721.
5. World Anti-Doping Agency. World Anti-Doping Code: International Standard — Prohibited List. Montreal: WADA; current edition.
6. U.S. Food and Drug Administration. The FDA warns that biotin may interfere with lab tests: FDA safety communication. 2017.