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source: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3412109/
There are multiple diagnostic modalities available, but many of them are error-prone and / or inaccurate. One does have to count in factors like age and obesity...
So let's talk about strengths and limitations of available diagnostic tests and their interpretation...
24 Hour GH Secretion / 24-hour serum GH profile
Not very useful, because it shows considerable overlap between healthy and GH deficient subjects. Frequent sampling is highly time and resource consuming. "The test yields a sensitivity of 90% but the specificity ranges from 79% for patients under 40 years to 36% for those over 60 years"
Measurement of Serum Insulin-like Growth Factor-1 (IGF-1) Level
"The value of serum IGF-1 and IGF binding protein-3 (IGFBP-3) in the diagnosis of GH deficiency is a matter of contention among endocrinologists. Various investigators have reported normal IGF-1 values in 37–70% of GH deficient adults [12, 14, 17, 18]. Further studies, however, showed that age, the time of onset of GHD, and the degree of hypopituitarism, all had a significant influence on serum IGF-1 levels—sometimes expressed as standard deviation scores (IGF-1 SDS) or Z scores. In the study by Aimaretti et al., 70% of GHD adults under the age of 40 years had a serum IGF-1 level below the age-related 3rd centile, but the corresponding percentage for those over the age of 40 was only 35% [19]."
In a large retrospective analysis of patients with GHD from the KIMS database, Lissett et al. found that 86% of patients with childhood-onset GHD compared to 52% with adult-onset GHD had serum IGF-1 SDS less than −2 [20]. The latter study also identified gender, BMI, and number of additional pituitary hormone deficiencies as factors which influence serum IGF-1 SDS.
Dynamic Tests of GH Secretion...
Insulin Tolerance Test
Gold-Standard-Test. Insulin is administered, inducing hypoglycemia which is a potent stimulus of GH and ACTH-cortisol secretion. Measurement of GH reserve! GH levels are measured every 15–30 minutes for two hours.
While the insulin tolerance test is considered the “gold-standard,” it is not a perfect test. It can be safely conducted in experienced centres [23] but is contraindicated in patients with a history of seizures or heart disease. Also, it is unpleasant for the patient who requires hospital admission and close medical supervision, and adequate hypoglycaemia is not always achieved [24]. This consumes considerable healthcare resources..."
Glucagon Stimulation Test
reliable and safe alternative to the ITT. Administration of Glucagon (1–1.5 mg) ... serum samples are taken for GH between 90 and 240 minutes. Can also provide co-assessment of ACTH reserve.
The mechanism of glucagon stimulated GH release is not fully understood, although several mechanisms have been proposed. Another possible mechanism is by stimulating noradrenaline release, which may stimulate GH secretion via the α-receptor; a suggestion that is, supported by the finding that the administration of β-blockers enhances glucagon-stimulated GH release [31].
Data comparing the GST with the ITT as GH secretagogues have yielded conflicting results. Cain et al. found the GST to be at least as good as the ITT in provoking GH secretion, based on the comparison of overall responses to the two tests [32]. Although the GST is safe, with almost no contraindications, it causes nausea and sometimes vomiting in 15–20% of subjects. In addition it is resource intensive test lasting for three-four hours due to the delayed action of glucagon.
GHRH + Arginine Test
The co-administration of arginine and GHRH (the combined test) is a powerful stimulus for GH production and has gained increasing acceptance as a useful method of diagnosing GHD [34]. This test has been advocated as a suitable alternative to ITT [6, 35–37]. The GHRH + arginine test allows good separation between healthy subjects and those with GH deficiency [37]. However, the cutoff limit for the diagnosis of severe GHD is controversial, with one study suggesting a cutoff of 9 ng/mL [36], while another reporting an optimal cut-off of 4.1 ng/mL [37]. The latter result is supported by a recent study that reported a cut-point of 3.7 ng/mL with an ultrasensitive chemiluminescence-based immunometric assay which conforms to international GH assay guidelines [38]. The GH response to the combined test seems to be particularly influenced by BMI... This test is safe, and, while half of patients experience flushing, more serious side effects are rare. The GHRH + arginine test may give false normal results in patients with GHD secondary to hypothalamic damage, such as those with radiation induced hypopituitarism [40–43].
There is also an Arginine-standalone-test, but it doesn't seem to be very reliable.
There are multiple diagnostic modalities available, but many of them are error-prone and / or inaccurate. One does have to count in factors like age and obesity...
So let's talk about strengths and limitations of available diagnostic tests and their interpretation...
24 Hour GH Secretion / 24-hour serum GH profile
Not very useful, because it shows considerable overlap between healthy and GH deficient subjects. Frequent sampling is highly time and resource consuming. "The test yields a sensitivity of 90% but the specificity ranges from 79% for patients under 40 years to 36% for those over 60 years"
Measurement of Serum Insulin-like Growth Factor-1 (IGF-1) Level
"The value of serum IGF-1 and IGF binding protein-3 (IGFBP-3) in the diagnosis of GH deficiency is a matter of contention among endocrinologists. Various investigators have reported normal IGF-1 values in 37–70% of GH deficient adults [12, 14, 17, 18]. Further studies, however, showed that age, the time of onset of GHD, and the degree of hypopituitarism, all had a significant influence on serum IGF-1 levels—sometimes expressed as standard deviation scores (IGF-1 SDS) or Z scores. In the study by Aimaretti et al., 70% of GHD adults under the age of 40 years had a serum IGF-1 level below the age-related 3rd centile, but the corresponding percentage for those over the age of 40 was only 35% [19]."
In a large retrospective analysis of patients with GHD from the KIMS database, Lissett et al. found that 86% of patients with childhood-onset GHD compared to 52% with adult-onset GHD had serum IGF-1 SDS less than −2 [20]. The latter study also identified gender, BMI, and number of additional pituitary hormone deficiencies as factors which influence serum IGF-1 SDS.
Dynamic Tests of GH Secretion...
Insulin Tolerance Test
Gold-Standard-Test. Insulin is administered, inducing hypoglycemia which is a potent stimulus of GH and ACTH-cortisol secretion. Measurement of GH reserve! GH levels are measured every 15–30 minutes for two hours.
While the insulin tolerance test is considered the “gold-standard,” it is not a perfect test. It can be safely conducted in experienced centres [23] but is contraindicated in patients with a history of seizures or heart disease. Also, it is unpleasant for the patient who requires hospital admission and close medical supervision, and adequate hypoglycaemia is not always achieved [24]. This consumes considerable healthcare resources..."
Glucagon Stimulation Test
reliable and safe alternative to the ITT. Administration of Glucagon (1–1.5 mg) ... serum samples are taken for GH between 90 and 240 minutes. Can also provide co-assessment of ACTH reserve.
The mechanism of glucagon stimulated GH release is not fully understood, although several mechanisms have been proposed. Another possible mechanism is by stimulating noradrenaline release, which may stimulate GH secretion via the α-receptor; a suggestion that is, supported by the finding that the administration of β-blockers enhances glucagon-stimulated GH release [31].
Data comparing the GST with the ITT as GH secretagogues have yielded conflicting results. Cain et al. found the GST to be at least as good as the ITT in provoking GH secretion, based on the comparison of overall responses to the two tests [32]. Although the GST is safe, with almost no contraindications, it causes nausea and sometimes vomiting in 15–20% of subjects. In addition it is resource intensive test lasting for three-four hours due to the delayed action of glucagon.
GHRH + Arginine Test
The co-administration of arginine and GHRH (the combined test) is a powerful stimulus for GH production and has gained increasing acceptance as a useful method of diagnosing GHD [34]. This test has been advocated as a suitable alternative to ITT [6, 35–37]. The GHRH + arginine test allows good separation between healthy subjects and those with GH deficiency [37]. However, the cutoff limit for the diagnosis of severe GHD is controversial, with one study suggesting a cutoff of 9 ng/mL [36], while another reporting an optimal cut-off of 4.1 ng/mL [37]. The latter result is supported by a recent study that reported a cut-point of 3.7 ng/mL with an ultrasensitive chemiluminescence-based immunometric assay which conforms to international GH assay guidelines [38]. The GH response to the combined test seems to be particularly influenced by BMI... This test is safe, and, while half of patients experience flushing, more serious side effects are rare. The GHRH + arginine test may give false normal results in patients with GHD secondary to hypothalamic damage, such as those with radiation induced hypopituitarism [40–43].
There is also an Arginine-standalone-test, but it doesn't seem to be very reliable.
