Growth hormone deficiency laboratory findings: Difference between revisions
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==Overview== | ==Overview== | ||
==Laboratory Findings== | ==Laboratory Findings== | ||
GH secretion is pulsatile and its secretion is regulated by two hypothalamic factors; growth hormone releasing hormone and somatostatin. | GH secretion is pulsatile and its secretion is regulated by two hypothalamic factors; growth hormone releasing hormone and somatostatin.<ref name="pmid20161791">{{cite journal| author=Osterstock G, Escobar P, Mitutsova V, Gouty-Colomer LA, Fontanaud P, Molino F et al.| title=Ghrelin stimulation of growth hormone-releasing hormone neurons is direct in the arcuate nucleus. | journal=PLoS One | year= 2010 | volume= 5 | issue= 2 | pages= e9159 | pmid=20161791 | doi=10.1371/journal.pone.0009159 | pmc=2820089 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20161791 }}</ref> | ||
So, measurement of a random serum GH level alone is not helpful and usually other tests used with it: | So, measurement of a random serum GH level alone is not helpful and usually other tests used with it: | ||
* Insulin-like growth factor I (IGF-I) | * Insulin-like growth factor I (IGF-I) | ||
* Insulin-like growth factor binding protein-3 (IGFBP-3) levels: it is the major serum carrier protein for IGF-I | * Insulin-like growth factor binding protein-3 (IGFBP-3) levels: it is the major serum carrier protein for IGF-I and the most GH dependent.<ref name="pmid2431001">{{cite journal| author=Baxter RC, Martin JL| title=Radioimmunoassay of growth hormone-dependent insulinlike growth factor binding protein in human plasma. | journal=J Clin Invest | year= 1986 | volume= 78 | issue= 6 | pages= 1504-12 | pmid=2431001 | doi=10.1172/JCI112742 | pmc=423906 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=2431001 }}</ref> | ||
* Their concentrations often reflect the concentration of secreted GH.[35-38].They are better tests than GH level because they are stable during the day and not pulsatile. | * Their concentrations often reflect the concentration of secreted GH.[35-38].They are better tests than GH level because they are stable during the day and not pulsatile.<ref name="pmid2760171">{{cite journal| author=Martha PM, Rogol AD, Veldhuis JD, Kerrigan JR, Goodman DW, Blizzard RM| title=Alterations in the pulsatile properties of circulating growth hormone concentrations during puberty in boys. | journal=J Clin Endocrinol Metab | year= 1989 | volume= 69 | issue= 3 | pages= 563-70 | pmid=2760171 | doi=10.1210/jcem-69-3-563 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=2760171 }}</ref> | ||
Limitations | Limitations | ||
Serum IGF-I levels may be low in conditions other than GHD | Serum IGF-I levels may be low in conditions other than GHD such as growth hormone insensitivity, hypothyroidism, renal failure, diabetes, and cancer.<ref name="pmid3760118">{{cite journal| author=Powell DR, Rosenfeld RG, Baker BK, Liu F, Hintz RL| title=Serum somatomedin levels in adults with chronic renal failure: the importance of measuring insulin-like growth factor I (IGF-I) and IGF-II in acid-chromatographed uremic serum. | journal=J Clin Endocrinol Metab | year= 1986 | volume= 63 | issue= 5 | pages= 1186-92 | pmid=3760118 | doi=10.1210/jcem-63-5-1186 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=3760118 }}</ref> | ||
Interpretation | Interpretation | ||
* Reduced level of IGF-I and IGFBP-3 with delayed bone age: provocative GH testing is needed. | * Reduced level of IGF-I and IGFBP-3 with delayed bone age: provocative GH testing is needed. If the growth failure is severe and IGF-I and IGFBP-3 are severely low, there is no need to perform GH stimulation testing. | ||
* Normal IGF-1 and IGFBP-3: no further testing is required. | |||
'''GH stimulation tests''' | '''GH stimulation tests''' | ||
* It is indicated for most patients suspected to have GHD. | * It is indicated for most patients suspected to have GHD. | ||
| Line 31: | Line 30: | ||
* The stimulation tests are performed after an overnight fast. Serum samples are collected at intervals to capture the peak GH level. | * The stimulation tests are performed after an overnight fast. Serum samples are collected at intervals to capture the peak GH level. | ||
* Two different stimuli should be used for most patients | * Two different stimuli should be used for most patients.<ref name="pmid27884013">{{cite journal| author=Grimberg A, DiVall SA, Polychronakos C, Allen DB, Cohen LE, Quintos JB et al.| title=Guidelines for Growth Hormone and Insulin-Like Growth Factor-I Treatment in Children and Adolescents: Growth Hormone Deficiency, Idiopathic Short Stature, and Primary Insulin-Like Growth Factor-I Deficiency. | journal=Horm Res Paediatr | year= 2016 | volume= 86 | issue= 6 | pages= 361-397 | pmid=27884013 | doi=10.1159/000452150 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=27884013 }}</ref> | ||
* In a patient with other pituitary hormone defects or a genetic defect, one test is sufficient to establish the diagnosis [32,60]. | * In a patient with other pituitary hormone defects or a genetic defect, one test is sufficient to establish the diagnosis [32,60]. | ||
* Pharmacologic stimuli include | * Pharmacologic stimuli include clonidine, glucagon, arginine, and insulin-induced hypoglycemia:<ref name="pmid169508">{{cite journal| author=| title=Stimulation of growth hormone secretion by levodopa-propranolol in children and adolescents. | journal=Pediatrics | year= 1975 | volume= 56 | issue= 2 | pages= 262-6 | pmid=169508 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=169508 }}</ref> | ||
* Clonidine stimulates GH by several mechanisms, including the stimulation of GHRH via alpha-adrenergic pathways. Side effects of clonidine are hypotension and hypoglycemia. So, blood pressure and blood glucose level need to be measured during the test. | * Clonidine stimulates GH by several mechanisms, including the stimulation of GHRH via alpha-adrenergic pathways. Side effects of clonidine are hypotension and hypoglycemia. So, blood pressure and blood glucose level need to be measured during the test.<ref name="pmid18717243">{{cite journal| author=Obara-Moszyńska M, Kedzia A, Korman E, Niedziela M| title=Usefulness of growth hormone (GH) stimulation tests and IGF-I concentration measurement in GH deficiency diagnosis. | journal=J Pediatr Endocrinol Metab | year= 2008 | volume= 21 | issue= 6 | pages= 569-79 | pmid=18717243 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18717243 }}</ref> | ||
* Arginine: | * Arginine: There are no side effects from this test. | ||
* Glucagon: side effects of glucagon are transient hyperglycemia. | * Glucagon: side effects of glucagon are transient hyperglycemia.<ref name="pmid11318781">{{cite journal| author=Leong KS, Walker AB, Martin I, Wile D, Wilding J, MacFarlane IA| title=An audit of 500 subcutaneous glucagon stimulation tests to assess growth hormone and ACTH secretion in patients with hypothalamic-pituitary disease. | journal=Clin Endocrinol (Oxf) | year= 2001 | volume= 54 | issue= 4 | pages= 463-8 | pmid=11318781 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11318781 }}</ref>It is a good choice for infants and young children. Side effects include nausea, vomiting, sweating, or headaches. | ||
* Insulin-induced hypoglycemia is a potent stimulant of GH release this test is less commonly used in children because of safety concerns. | * Insulin-induced hypoglycemia is a potent stimulant of GH release this test is less commonly used in children because of safety concerns.<ref name="pmid110954192">{{cite journal| author=Growth Hormone Research Society| title=Consensus guidelines for the diagnosis and treatment of growth hormone (GH) deficiency in childhood and adolescence: summary statement of the GH Research Society. GH Research Society. | journal=J Clin Endocrinol Metab | year= 2000 | volume= 85 | issue= 11 | pages= 3990-3 | pmid=11095419 | doi=10.1210/jcem.85.11.6984 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11095419 }}</ref> | ||
The interpretation of the test results depends upon age and sex hormone concentrations | The interpretation of the test results depends upon age and sex hormone concentrations.Children with constitutional delay of growth and puberty may have low GH results on provocative testing in the absence of true GHD (ie, false-positive results). Administration of sex steroids for a few days prior to the provocative GH testing reduces the chance of a false-positive result, as discussed below. | ||
==References== | ==References== | ||
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
Overview
Laboratory Findings
GH secretion is pulsatile and its secretion is regulated by two hypothalamic factors; growth hormone releasing hormone and somatostatin.[1]
So, measurement of a random serum GH level alone is not helpful and usually other tests used with it:
- Insulin-like growth factor I (IGF-I)
- Insulin-like growth factor binding protein-3 (IGFBP-3) levels: it is the major serum carrier protein for IGF-I and the most GH dependent.[2]
- Their concentrations often reflect the concentration of secreted GH.[35-38].They are better tests than GH level because they are stable during the day and not pulsatile.[3]
Limitations
Serum IGF-I levels may be low in conditions other than GHD such as growth hormone insensitivity, hypothyroidism, renal failure, diabetes, and cancer.[4]
Interpretation
- Reduced level of IGF-I and IGFBP-3 with delayed bone age: provocative GH testing is needed. If the growth failure is severe and IGF-I and IGFBP-3 are severely low, there is no need to perform GH stimulation testing.
- Normal IGF-1 and IGFBP-3: no further testing is required.
GH stimulation tests
- It is indicated for most patients suspected to have GHD.
- The results should be interpreted in the context of auxological findings, bone age, and IGF-1 and IGFBP-3 concentrations.
- If the clinical and other laboratory criteria are sufficient to make the diagnosis of GHD, there is no need to perform the test.
- A serum GH concentration of >10 mcg/L, but a cutoff of 7.5 mcg/L is often used for modern assays.
- The stimulation tests are performed after an overnight fast. Serum samples are collected at intervals to capture the peak GH level.
- Two different stimuli should be used for most patients.[5]
- In a patient with other pituitary hormone defects or a genetic defect, one test is sufficient to establish the diagnosis [32,60].
- Pharmacologic stimuli include clonidine, glucagon, arginine, and insulin-induced hypoglycemia:[6]
- Clonidine stimulates GH by several mechanisms, including the stimulation of GHRH via alpha-adrenergic pathways. Side effects of clonidine are hypotension and hypoglycemia. So, blood pressure and blood glucose level need to be measured during the test.[7]
- Arginine: There are no side effects from this test.
- Glucagon: side effects of glucagon are transient hyperglycemia.[8]It is a good choice for infants and young children. Side effects include nausea, vomiting, sweating, or headaches.
- Insulin-induced hypoglycemia is a potent stimulant of GH release this test is less commonly used in children because of safety concerns.[9]
The interpretation of the test results depends upon age and sex hormone concentrations.Children with constitutional delay of growth and puberty may have low GH results on provocative testing in the absence of true GHD (ie, false-positive results). Administration of sex steroids for a few days prior to the provocative GH testing reduces the chance of a false-positive result, as discussed below.
References
- ↑ Osterstock G, Escobar P, Mitutsova V, Gouty-Colomer LA, Fontanaud P, Molino F; et al. (2010). "Ghrelin stimulation of growth hormone-releasing hormone neurons is direct in the arcuate nucleus". PLoS One. 5 (2): e9159. doi:10.1371/journal.pone.0009159. PMC 2820089. PMID 20161791.
- ↑ Baxter RC, Martin JL (1986). "Radioimmunoassay of growth hormone-dependent insulinlike growth factor binding protein in human plasma". J Clin Invest. 78 (6): 1504–12. doi:10.1172/JCI112742. PMC 423906. PMID 2431001.
- ↑ Martha PM, Rogol AD, Veldhuis JD, Kerrigan JR, Goodman DW, Blizzard RM (1989). "Alterations in the pulsatile properties of circulating growth hormone concentrations during puberty in boys". J Clin Endocrinol Metab. 69 (3): 563–70. doi:10.1210/jcem-69-3-563. PMID 2760171.
- ↑ Powell DR, Rosenfeld RG, Baker BK, Liu F, Hintz RL (1986). "Serum somatomedin levels in adults with chronic renal failure: the importance of measuring insulin-like growth factor I (IGF-I) and IGF-II in acid-chromatographed uremic serum". J Clin Endocrinol Metab. 63 (5): 1186–92. doi:10.1210/jcem-63-5-1186. PMID 3760118.
- ↑ Grimberg A, DiVall SA, Polychronakos C, Allen DB, Cohen LE, Quintos JB; et al. (2016). "Guidelines for Growth Hormone and Insulin-Like Growth Factor-I Treatment in Children and Adolescents: Growth Hormone Deficiency, Idiopathic Short Stature, and Primary Insulin-Like Growth Factor-I Deficiency". Horm Res Paediatr. 86 (6): 361–397. doi:10.1159/000452150. PMID 27884013.
- ↑ "Stimulation of growth hormone secretion by levodopa-propranolol in children and adolescents". Pediatrics. 56 (2): 262–6. 1975. PMID 169508.
- ↑ Obara-Moszyńska M, Kedzia A, Korman E, Niedziela M (2008). "Usefulness of growth hormone (GH) stimulation tests and IGF-I concentration measurement in GH deficiency diagnosis". J Pediatr Endocrinol Metab. 21 (6): 569–79. PMID 18717243.
- ↑ Leong KS, Walker AB, Martin I, Wile D, Wilding J, MacFarlane IA (2001). "An audit of 500 subcutaneous glucagon stimulation tests to assess growth hormone and ACTH secretion in patients with hypothalamic-pituitary disease". Clin Endocrinol (Oxf). 54 (4): 463–8. PMID 11318781.
- ↑ Growth Hormone Research Society (2000). "Consensus guidelines for the diagnosis and treatment of growth hormone (GH) deficiency in childhood and adolescence: summary statement of the GH Research Society. GH Research Society". J Clin Endocrinol Metab. 85 (11): 3990–3. doi:10.1210/jcem.85.11.6984. PMID 11095419.