What is being tested?
Insulin-like growth factor-1 (IGF-1) is a hormone that, along with growth hormone (GH), helps promote normal bone and tissue growth and development. The test measures the amount of IGF-1 in the blood.
IGF-1 is primarily produced in the liver, skeletal muscles, and many other tissues in response to GH stimulation. IGF-1 mediates many of the actions of GH, stimulates the growth of bones and other tissues, and promotes the production of lean muscle mass. IGF-1 also plays a role in non-growth activities, such as glucose and lipid metabolism, and has been implicated in metabolic syndrome.
Since GH is released into the blood in pulses throughout the day, it is difficult to interpret the results from a single GH test. IGF-1 mirrors GH excesses and deficiencies, but unlike GH, its level is stable throughout the day. This makes IGF-1 a useful indicator of average GH levels. The IGF-1 test is therefore often used to help evaluate for GH deficiency or GH excess.
IGF-1 and Growth Deficiency
IGF-1 levels, like GH, are normally low in infancy, increase gradually during childhood, peak during puberty, and then decline in adult life. Deficiencies in GH and IGF-1 may be caused by:
- A dysfunctional pituitary gland with decreased pituitary hormones (hypopituitarism)
- A non-GH-producing pituitary tumor that damages cells that produce hormones
- A lack of responsiveness to GH. This insensitivity may be primary (genetic) or secondary to conditions such as malnutrition, hypothyroidism, sex hormone deficiency, kidney disease, liver disease, and congenital syndromes. Genetic GH insensitivity (GH resistance) is very rare, with about 300 cases reported worldwide.
IGF-1 deficiencies can inhibit bone growth and overall growth development, resulting in a child with a shorter than normal stature. In adults, decreased production can lead to low bone density, less muscle mass, and altered lipid levels. However, testing for IGF-1 deficiency or GH deficiency is not routinely done in adults who have decreased bone density and/or muscle strength or increased lipids. GH deficiency and consequently IGF-1 deficiency is a very rare cause of these disorders.
IGF-1 and Growth Hormone Excess
Excess GH and IGF-1 can cause abnormal growth of the skeleton and other signs and symptoms characteristic of two rare conditions, gigantism and acromegaly, generally due to a pituitary adenoma, a slow-growing, often benign tumor. This causes the pituitary to release excess amounts of GH. Frequently, the tumor can be surgically removed and/or treated with drugs or radiation. In most cases, this will cause GH and IGF-1 levels to return to normal or near-normal levels.
In children, gigantism causes bones to grow longer, resulting in a very tall person with large feet and hands. In adults, acromegaly causes bones to thicken and tissues to soften, as seen with the swelling of the nose. In contrast to giantism, adults with acromegaly do not grow tall. Both conditions can lead to enlarged organs (heart, liver, kidneys, spleen, thyroid/parathyroid glands, pancreas) and other complications such as type 2 diabetes, increased risk of cardiovascular disease, high blood pressure, arthritis, mild increase in cancer (breast, colon, prostate, lung), and a decreased lifespan.
How is the test used?
A test for insulin-like growth factor-1 (IGF-1) may be used along with growth hormone (GH) testing to help:
- Identify GH deficiency; it is not diagnostic of a GH deficiency but may be ordered along with GH stimulation tests
- As follow-up to abnormal results on other hormone tests
- Evaluate pituitary function
- Less commonly, to detect excess growth hormone and to help diagnose and monitor the treatment of two rare conditions, acromegaly and gigantism
IGF-1 testing and a GH suppression test can be used to detect and monitor the treatment of a GH-producing pituitary tumor. An anterior pituitary tumor is typically confirmed with imaging scans (X-rays, CT scan, MRI) that help identify and locate the tumor. If surgery is necessary, GH and IGF-1 levels are measured after the tumor’s removal to determine whether the entire tumor was successfully removed. Drug and/or radiation therapy may be used in addition to, or sometimes instead of, surgery to try to decrease GH production and return IGF-1 to a normal or near-normal concentration. IGF-1 may be ordered to monitor the effectiveness of this therapy at regular intervals for years afterward to monitor GH production and to detect tumor recurrence.
IGF-1 levels and the measurement of GH can also provide information related to GH insensitivity. Before performing definitive GH testing, if the IGF-1 level is found to be normal for age and sex, GH deficiency is excluded and definitive testing is not necessary.
When is it ordered?
IGF-1 testing may be ordered, along with a GH stimulation test, when:
- A child has symptoms of GH deficiency, such as a slowed growth rate and short stature
- Adults have symptoms that a healthcare practitioner suspects may be due to a GH deficiency, such as decreased bone density, fatigue, adverse changes to lipid levels, and reduced exercise tolerance. However, testing for IGF-1 deficiency is not routine in adults who have these symptoms; GH and IGF-1 deficiencies are only very rare causes of these disorders.
An IGF-1 also may be ordered when a healthcare practitioner suspects that you have an underactive pituitary gland and at intervals to monitor those on GH therapy.
Less commonly, IGF-1 testing may be ordered, along with a GH suppression test, when a child has symptoms of gigantism or when an adult shows signs of acromegaly.
When a GH-producing pituitary tumor is found, GH and IGF-1 tests are ordered after the tumor is surgically removed to determine whether all of it has been extracted. IGF-1 also is also ordered at regular intervals during drug and/or radiation therapy that frequently follows tumor surgery. IGF-1 levels may be ordered at regular intervals for many years to monitor your GH production and to watch for pituitary tumor recurrence.
What does the test result mean?
A normal level of IGF-1 must be considered in context. Some people can have a GH deficiency and still have a normal IGF-1 level.
If the IGF-1 level is decreased, then it is likely that there is a GH deficiency or an insensitivity to GH. If this is in a child, the GH deficiency may have already caused short stature and delayed development and may be treated with GH supplementation. GH deficiency seen at birth is due to a genetic mutation or may be due to a brain defect/trauma. Adults will have an age-related decrease in production, but lower than expected levels may reflect a GH deficiency or insensitivity.
If a decrease in IGF-1 is suspected to be due to a more general decrease in pituitary function (hypopituitarism), then several other endocrine glands and their pituitary regulating hormones will need to be evaluated to decide on appropriate treatment. Reduced pituitary function may be due to inherited defects or can develop as a result of pituitary damage following conditions such as trauma, infections, and inflammation.
Decreased levels of IGF-1 also may be seen with nutritional deficiencies (including anorexia nervosa), chronic kidney or liver diseases, inactive/ineffective forms of GH, and with high doses of estrogen.
Elevated levels of IGF-1 usually indicate increased production of GH. Since GH levels vary throughout the day, IGF-1 levels are a reflection of average GH production, not of the actual amount of GH in the blood at the time that the sample for the IGF-1 measurement was taken. This is accurate up to the point at which the liver’s capacity to produce IGF-1 is reached. With severely increased GH production, the IGF-1 level will stabilize at an elevated maximum level. Elevated IGF-1 and GH may indicate acromegaly in adults.
Increased levels of GH and IGF-1 are normal during puberty and pregnancy; during the latter, serum IGF-1 increases on average almost 2-fold. Otherwise, increased levels are most frequently due to pituitary tumors (usually benign). Excess GH can lead to gigantism in children and acromegaly in adults.
If IGF-1 is being monitored after the surgery to remove a pituitary tumor and the level is still elevated, then the surgery may not have been fully effective. Decreasing IGF-1 levels during subsequent drug and/or radiation therapies indicate that the treatment is lowering GH production. However, normal GH levels may take several years to achieve. If levels of IGF-1 become “normalized,” then you are no longer producing excess amounts of GH. When you are undergoing long-term monitoring, an increase in IGF-1 levels may indicate that the pituitary tumor has returned.
What is a GH stimulation test?
GH stimulation tests help to diagnose GH deficiency and hypopituitarism. For a stimulation test, a sample of blood is drawn after 10-12 hours of fasting. Then, under close medical supervision, you are given an intravenous solution of a substance that normally stimulates the release of GH from the pituitary. Blood samples are then drawn at timed intervals and GH levels are tested in each to see if the pituitary gland was stimulated to produce the expected levels of GH. Since exercise normally causes an increase in GH, vigorous exercise may also be used as the stimulant for GH release.
What is a GH suppression test?
GH suppression tests help to diagnose GH excess by determining if GH production is being suppressed by high blood sugar. For a suppression test, a sample of blood is drawn after 10-12 hours of fasting. You are then given a standard glucose solution (either weight-based in children or a standard 100 grams of glucose in adults) to drink. Blood samples are drawn at timed intervals and tested for GH to see if the pituitary gland is sufficiently suppressed by the dose of glucose.
What signs and symptoms are seen with deficient GH and IGF-1?
In children, the following may indicate GH and/or IGF-1 deficiency:
- Slowed growth rate in early childhood relative to group norms
- Shorter stature, arm and leg lengths, and lower weight than other children of the same age
- Delayed puberty
- X-rays showing delayed bone development
- Thin hair
- Poor nail growth
- Delayed closure of the sutures of the skull
In adults, abnormally low levels of GH and/or IGF-1 may cause subtle, nonspecific symptoms such as:
- Decreased bone density
- Adverse lipid changes
- Reduced exercise tolerance
- Thinning, dry skin
What signs and symptoms are seen with excess GH and IGF-1 production?
In a child, the main sign is unusually tall stature. Other signs and symptoms of gigantism in children include:
- Mild to moderate obesity
- Overly large head
- Exaggerated growth of hands and feet
With an adult, it may be more subtle: a larger nose, thicker lips, a more prominent jaw, or thickening of fingers (rings and shoes that no longer fit). Other signs and symptoms may include:
- Deepened, husky voice
- Enlarged organs (liver, heart, kidneys, spleen, thyroid/parathyroid glands, pancreas)
- Enlarged tongue
- Erectile dysfunction
- Headaches and visual disturbances
- Joint pain and swelling
- Menstrual cycle irregularities
- Muscle weakness
- Increased size/function of sebaceous and sweat glands, resulting in excessive sweating and body odor
- Thickening of the skin, skin tags, increased coarse body hair
- Peripheral neuropathy (e.g., carpal tunnel syndrome)
Can this test be done in my doctor's office?
No. In fact, this test is not available in every laboratory. Your blood may be sent to a reference laboratory.
How long do I have to be monitored?
As long as you are considered to have abnormal (low or high) GH production or are receiving GH replacement therapy, your IGF-1 will need to be monitored. However, IGF-1 is not routinely measured to monitor GH treatment of GH-deficient children. The best way to determine whether GH treatment is working in children who are GH-deficient is noting that they are growing faster and taller.
Is there anything else I should know?
If an IGF-1 level is normal and a healthcare practitioner still strongly suspects a GH deficiency, then the healthcare provider may order another test, an IGFBP-3 (insulin-like growth factor binding protein 3), to help confirm the GH deficiency. Almost all IGF-1 in the blood is bound and then transported by binding proteins, primarily IGFBP-3. IGFBP-3 is stimulated by GH and is also produced in the liver. It plays a role in the regulation of IGF-1 signaling and may be useful in monitoring recombinant human GH therapy.