Somatotropin: growth hormone in analysis

Somatotropic hormone, or growth hormone, is produced by the pituitary gland and is involved not only in children's linear growth but also in protein, fat, and carbohydrate metabolism, maintaining muscle mass, bone tissue, and metabolic balance in adults. Its action is largely mediated by insulin-like growth factor 1, which is synthesized primarily in the liver and reflects the holistic effect of growth hormone on tissue. [1]

The key feature of growth hormone is that it is not released continuously, but in pulses. During the day, its levels can be very low, then briefly rise, and at night, especially during deep sleep, more powerful surges occur. Because of this, a single, "random" blood test for growth hormone can easily hit either a peak or a trough, failing to reflect the true state of the system.

This is why, in modern diagnostics, the primary laboratory benchmark is often insulin-like growth factor 1, rather than random growth hormone levels. Unlike growth hormone, it is more stable throughout the day and is therefore better suited for initial screening for excess or deficiency of this axis activity. MedlinePlus explicitly states that it is more reliable to monitor growth hormone through insulin-like growth factor 1 levels rather than through a single growth hormone measurement. [2]

However, insulin-like growth factor 1 is not a perfect "test for everything." It must be interpreted taking into account age, gender, puberty, nutrition, liver function, concomitant diseases, and medications. Therefore, modern assessment of growth hormone axis function is almost always based on a combination of clinical presentation, insulin-like growth factor 1, and dynamic tests, rather than simply reading a single number from a form. [3]

For growth hormone excess, such as acromegaly in adults and gigantism in children, the initial biochemical test is usually insulin-like growth factor 1. For growth hormone deficiency, a random growth hormone level is also inappropriate, and provocative testing is required in most cases. The Endocrine Society and the Pediatric Endocrine Society emphasize that diagnosis cannot be based on a random growth hormone measurement. [4]

Table 1 summarizes what studies are actually used to evaluate this system.[5]

Study	What does it show?	When is it especially useful?	The main drawback
Random somatotropic hormone	Instantaneous growth hormone level	Of limited use in routine diagnostics	Strong pulsation of secretion
Insulin-like growth factor 1	The integrative effect of growth hormone	First screening for acromegaly, gigantism, suspected deficiency	Depends on age, nutrition, liver, estrogen
Provocative test	The ability of the pituitary gland to secrete growth hormone in response to a stimulus	Diagnosis of growth hormone deficiency	There is no single perfect test
Glucose suppression test	Ability to suppress growth hormone	Confirmation of acromegaly	Requires proper preparation
Insulin-like growth factor-binding protein 3	Additional growth axis marker	Sometimes useful in young children	Does not replace the main tests

When is a growth hormone test really necessary?

In adults, tests of this axis are most often ordered in two situations. The first is when acromegaly is suspected, when there is enlargement of the hands and feet, changes in facial features, sweating, headaches, carpal tunnel syndrome, arthralgia, sleep apnea, type 2 diabetes, or a pituitary tumor has been detected. The Endocrine Society recommends measuring insulin-like growth factor 1 in patients with typical manifestations of acromegaly and in patients with a pituitary tumor. [6]

The second major situation is suspected growth hormone deficiency in adults. However, testing is not prescribed for everyone with fatigue or fat gain. The Endocrine Society emphasizes that confirming deficiency in adults usually requires stimulation testing and that testing is most warranted in patients with hypothalamic-pituitary disease, after surgery, radiation therapy, or other pituitary hormone deficiencies. [7]

In children, the logic is different. The main reason for examination is not a "bad test result," but rather the clinical picture: low growth rate, growth retardation relative to age norms, deviations from the growth curve, low growth compared to the family's genetic potential, as well as data from an examination and, if necessary, pituitary imaging. The Pediatric Endocrine Society recommends not relying solely on the stimulation test, but taking into account height, growth rate, physical examination, insulin-like growth factor 1, and other indicators. [8]

A separate group are newborns with hypoglycemia and signs of hypopituitarism. At this age, a random growth hormone level may be more useful than in adults, but even here it cannot be interpreted in isolation. The pediatric guideline emphasizes that a low growth hormone concentration during spontaneous hypoglycemia is not sufficient for diagnosis in itself, although in a newborn in the first week of life, a value of about 5 micrograms per liter or lower, combined with other pituitary deficiencies and hypoglycemia, makes deficiency more likely. [9]

There are also situations when testing is not recommended. If an adult has no history of pituitary disease, surgery, radiation therapy, or other compelling signs, and the complaints are nonspecific, testing for growth hormone deficiency is generally not recommended. For adults with low clinical probability, testing may yield more false positives than benefits. [10]

Table 2 shows which route is most often chosen in different clinical scenarios. [11]

Situation	First test	What do they do next?
Suspicion of acromegaly	Insulin-like growth factor 1	If the result is elevated or questionable, a glucose suppression test is performed.
Pituitary tumor	Insulin-like growth factor 1	If there is a deviation, the growth hormone is clarified and a profile assessment is performed.
Suspected deficiency in an adult	Insulin-like growth factor 1 and clinical evaluation	More often than not, one stimulation test is needed.
Suspected deficiency in a child	Height, growth velocity, insulin-like growth factor 1	A more extensive clinical examination and dynamic testing are usually required.
Newborn with hypoglycemia and signs of hypopituitarism	Growth hormone in the context of other hormones	The diagnosis is based on a combination of data
Nonspecific fatigue without signs of pituitary disease	Usually they don't start with these tests.	First, they look for more probable causes

How to properly prepare for tests

Preparation depends on the specific test being ordered. The insulin-like growth factor 1 test typically requires no special preparation. MedlinePlus notes that this test requires no special preparation, making it a convenient initial screening tool. [12]

Dynamic tests are designed entirely differently. A growth hormone stimulation test typically requires a 10-12 hour fast, and certain medications can interfere with the results, so discussing their use with your doctor beforehand. MedlinePlus also notes that eating before the test can affect the results. [13]

The glucose suppression test, which is used when acromegaly is suspected, also requires preparation. According to MedlinePlus, the patient provides a baseline blood sample on an empty stomach, then drinks a glucose solution, after which several repeat samples are taken over a period of two hours. The idea behind the test is that in a healthy person, glucose should suppress growth hormone secretion, but this does not occur in acromegaly. [14]

There are also less obvious factors that distort the interpretation. Insulin-like growth factor 1 levels are affected by diet, liver disease, severe infections, poorly controlled diabetes, hypothyroidism, and oral estrogen use. Therefore, a low or borderline normal insulin-like growth factor 1 level does not always indicate growth hormone deficiency, and an unexpectedly "calm" result in suspected acromegaly does not always rule out the disease without further contextual assessment. [15]

For children, puberty is an additional factor. The Pediatric Endocrine Society recommends considering sex steroid priming before stimulation tests in prepubertal boys over 11 years of age and girls over 10 years of age in certain clinical groups to reduce the risk of a false diagnosis of growth hormone deficiency due to constitutional growth retardation and puberty. [16]

Table 3 is a brief reminder on how to prepare for various studies. [17]

Test	Preparation	What is especially important
Insulin-like growth factor 1	Usually without special training	The clinical context is more important than fasting.
Stimulation test	Usually 10-12 hours on an empty stomach	Medications and physical activity may affect the results.
Glucose suppression test	On an empty stomach, then take a glucose solution	A series of blood draws is required over a 2-hour period.
Repeated tests	Preferably in the same laboratory	Methods and thresholds may vary.
Pediatric testing	According to the center protocol	During peripuberty, priming with sex steroids is sometimes necessary.

Standards and how to read the results

For growth hormone, a routine random test has virtually no useful universal "normal" value that can be safely used for diagnostic purposes. This is due to pulsatile secretion: even in a healthy person, a single level can be very low and then quickly become high. Therefore, a normal random result does not rule out either excess or deficiency of growth hormone, and an elevated result does not confirm a diagnosis without context.

For acromegaly, the primary test is insulin-like growth factor 1, but only within the age-specific reference ranges of a specific laboratory. The Endocrine Society recommends using it as the first test, and the 2023 consensus states that in a patient with typical features of acromegaly, a value above 1.3 times the upper limit of normal for age confirms the diagnosis. In ambiguous cases, it is useful to repeat the test using the same validated method and, if necessary, perform a glucose suppression test. [18]

According to the Endocrine Society guidelines, the classic criterion for confirming acromegaly with a glucose suppression test is the absence of growth hormone suppression below 1 microgram per liter after a standard glucose load. Newer, ultra-sensitive methods in some centers use more stringent thresholds, around 0.4 micrograms per liter, but this depends on the assay platform and local protocol. [19]

For growth hormone deficiency in adults, the underlying principle is different: low insulin-like growth factor 1 alone is usually insufficient. In most adults, the diagnosis is confirmed with a stimulation test. A review of growth hormone diagnostics emphasizes that there is no ideal test, that thresholds depend on the method and body mass index, and that obesity itself reduces growth hormone secretion and may require different interpretive thresholds. [20]

In children, the interpretation is even more complex. The Pediatric Endocrine Society recommends against making a diagnosis based solely on the results of a provocative test. Very low peaks do indeed support severe deficiency, but the boundary between normal, partial deficiency, and false-positive results depends on the test, the kit used, the pubertal status, and the overall clinical picture. [21]

Table 4 shows not so much “norms from the Internet” as the modern logic of interpreting the results. [22]

Result	What does it most often mean?	Important disclaimer
Normal random somatotropic hormone	Nothing excludes itself	Due to pulsation it is uninformative
Age-related insulin-like growth factor 1 in the reference	Usually against acromegaly	But it does not cancel out a re-evaluation in case of strong clinical suspicion
Insulin-like growth factor 1 above the upper limit of normal	Suspected excess growth hormone	Requires confirmation or clinical correlation
Insulin-like growth factor 1 above 1.3 upper limit of normal in typical clinical setting	A strong argument for acromegaly	In doubtful cases, a repeat and sometimes suppression test is needed.
No growth hormone suppression after glucose	Supports acromegaly	The threshold depends on the method
Low insulin-like growth factor 1	Growth hormone deficiency is possible	Malnutrition, liver disease, diabetes, and estrogen are also possible.

Special situations in children and adults

In adults with a high clinical probability of growth hormone deficiency, testing may be shorter. A recent review indicates that in patients with three or more pituitary hormone deficiencies, low insulin-like growth factor 1, and a history of a pituitary tumor, surgery, or radiation therapy, the likelihood of growth hormone deficiency is very high, and in such cases, stimulation testing may sometimes be omitted. However, this applies to a highly selected group, not all patients. [23]

If the risk of disease is lower, a stimulation test is usually necessary. The insulin tolerance test remains the classic standard in adults, but it requires careful monitoring because it causes hypoglycemia and is contraindicated in some patients. Alternatives include the glucagon test and the oral macimorelin test. Neither option is ideal in all clinical situations. [24]

In children, the basis for diagnosis is not biochemistry per se, but growth dynamics. Even a good laboratory test is no substitute for height measurement, growth velocity assessment, comparison with family genetic potential, bone age, and examination for syndromes or other endocrine disorders. This is why the Pediatric Endocrine Society emphasizes that provocative testing should not be the sole diagnostic criterion. [25]

Puberty creates a separate diagnostic pitfall. In children with constitutional growth and pubertal delay, growth hormone peaks on provocative tests may be artificially low, even though there is no true severe deficiency. Therefore, short-term priming with sex steroids before testing in some children increases diagnostic specificity and helps reduce the incidence of unnecessary treatment. [26]

For acromegaly, on the contrary, the particular problem is not low sensitivity, but rather late diagnosis and analytical discrepancies. The consensus on acromegaly emphasizes that insulin-like growth factor 1 results should be assessed on the same validated platform, as interlaboratory variability remains significant. This is especially important when the result is only slightly above the normal range or when the assay is used for monitoring after surgery and during treatment. [27]

Table 5 summarizes the most important special situations that most often become sources of errors. [28]

Situation	Why is it important?	Practical conclusion
Obesity in adults	Reduces the secretion of growth hormone	Caution and other stimulation test thresholds needed
Puberty in a child	Changes the answer to tests	Sometimes priming with sex steroids is necessary
Malnutrition or liver disease	Reduce insulin-like growth factor 1	A low level does not always equal growth hormone deficiency.
Oral estrogens	May reduce insulin-like growth factor 1	The result is interpreted with reservations
Severe concomitant disease	Distorts the growth hormone and insulin-like growth factor 1 axis	First, the general clinical background is taken into account
High probability of hypopituitarism	It may allow some adults to do without testing.	The decision is made by a specialized endocrinologist

What to do after receiving the results

If the result suggests acromegaly, the next step is usually biochemical confirmation and then pituitary imaging. With a typical clinical picture and markedly elevated insulin-like growth factor-1, the diagnosis is highly probable. If elevated or questionable values are present, a glucose suppression test is performed. Following biochemical confirmation, magnetic resonance imaging of the pituitary gland is performed. [29]

If growth hormone deficiency is suspected, the next step depends on age and clinical probability. In adults, a single, carefully selected stimulation test is usually needed, while in children, the decision is based on a combination of height, growth velocity, insulin-like growth factor 1, test results, and imaging data. A simple rule here is: treat the confirmed disease, not the test. [30]

The most practical conclusion on this topic is this: a random growth hormone test rarely answers a clinical question. Modern diagnostics are built around insulin-like growth factor 1, dynamic testing, and a competent assessment of the context. Therefore, a good result is not just a number on a form, but the right test chosen in the right situation. [31]

FAQ

Can a single random blood test for growth hormone determine whether a disease is present?
Usually, no. Growth hormone secretion is pulsatile, so a random blood test often doesn't reflect the actual condition of the axis and is not suitable as a standalone diagnostic test.

What test is considered the primary one when acromegaly is suspected?
The primary starting test is insulin-like growth factor 1. The Endocrine Society recommends measuring it specifically for typical signs of acromegaly and for pituitary tumors. [32]

Is a glucose test required for acromegaly?
Not always, but very often. If insulin-like growth factor 1 is elevated or questionable, the diagnosis is confirmed by the absence of growth hormone suppression after a glucose load; in very typical clinical presentations and a significant increase in insulin-like growth factor 1, current consensus suggests that this may be sufficient to confirm the diagnosis. [33]

Can a normal insulin-like growth factor 1 rule out acromegaly?
In most cases, a normal age-appropriate value makes acromegaly unlikely. However, in cases of strong clinical suspicion, analytical doubts, or special conditions, a repeat measurement using the same method and further evaluation may be necessary. [34]

Does all adults with fatigue need insulin-like growth factor 1?
Generally, no. In adults without evidence of pituitary disease, surgery, radiation therapy, or other compelling reasons, testing for growth hormone deficiency is not considered a rational first step. [35]

Why doesn't low insulin-like growth factor 1 always indicate growth hormone deficiency?
Because it's also reduced by other conditions, including malnutrition, liver disease, severe infections, poorly controlled diabetes, hypothyroidism, and oral estrogens. Therefore, the results should always be interpreted in a clinical context. [36]

What test is considered the standard for suspected growth hormone deficiency in adults?
The insulin tolerance test remains the classic standard, but it is not suitable for everyone. Alternatives include the glucagon test and the macimorelin test, and the choice depends on contraindications, availability, and the clinical situation. [37]

Can a child be diagnosed based solely on a provocative test?
No, this is not considered the correct approach. The Pediatric Endocrine Society explicitly recommends not relying solely on the provocative test result and taking into account height, growth velocity, insulin-like growth factor 1, physical examination, and other factors. [38]

Do I need to fast?
No special preparation is usually required for insulin-like growth factor-1 testing. For stimulation and suppression tests, fasting is generally required, typically for 10-12 hours. [39]

Why can results vary between laboratories?
Because for insulin-like growth factor 1 and growth hormone, the specifics of the method and platform are important. This is especially critical for borderline results and when monitoring acromegaly after treatment, so it is best to monitor the dynamics in a single laboratory. [40]