Growth hormone deficiency laboratory findings: Difference between revisions
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==Overview== | ==Overview== | ||
An immediate investigation should be started in severe [[short stature]] defined as a short child more than 3 sd below the mean of children at the same age. Measurement of a random serum [[Growth hormone|GH]] level alone is not helpful. Measurement of [[Insulin-like growth factor 1|Insulin-like growth factor I]] (IGF-I) and [[Insulin-like growth factor binding protein 3|Insulin-like growth factor binding protein-3]] ([[IGFBP3|IGFBP-3]]) is more helpful than GH level alone. | |||
GH stimulation tests is indicated for most patients suspected to have GHD. If the clinical and other laboratory criteria are sufficient to make the diagnosis of GHD, there is no need to perform the test. Pharmacologic stimuli include [[clonidine]], [[glucagon]], [[arginine]], and [[insulin]]-induced [[hypoglycemia]]. Administration of [[sex steroids]] for a few days prior to the provocative [[Growth hormone|GH]] testing reduces the chance of a false-positive result. | |||
==Laboratory Findings== | ==Laboratory Findings== | ||
=== ''Neonatal evaluation'' === | === ''Neonatal evaluation'' === | ||
* A GH level should always be measured: | * A [[Growth hormone|GH level]] should always be measured: | ||
** | **In the presence of [[Hypoglycemia|neonatal hypoglycemia]] | ||
** | **In the absence of a metabolic disorder. | ||
**A random GH measurement in a polyclonal RIA of less than 20 mg/L would suggest GHD in the newborn. | **A random [[Growth hormone|GH]] measurement in a [[polyclonal]] RIA of less than 20 mg/L would suggest GHD in the newborn. | ||
**An IGFBP-3 measurement is of value for the diagnosis of GHD in infancy. | **An [[IGFBP3|IGFBP-3]] measurement is of value for the diagnosis of GHD in infancy. | ||
=== Children evaluation === | === Children evaluation === | ||
Criteria to initiate immediate investigation include: | Criteria to initiate immediate investigation include: | ||
* | * Severe [[short stature]], defined as a short child more than 3 sd below the mean of children at the same age | ||
* | * Height more than 1.5 sd below the mid-parental height; | ||
* | * Height more than 2 sd below the mean and a height velocity over 1 yr more than 1 sd below the mean for chronological age, or a decrease in height sd of more than 0.5 over 1 yr in children over 2 yr of age; | ||
* | * In the absence of [[short stature]], a height velocity more than 2 sd below the mean over 1 yr or more than 1.5 sd sustained over 2 yr; this may occur in GHD, presenting in infancy, or in organic GHD. | ||
* Signs indicative of an [[Intracranial mass|intracranial lesion]] | |||
* | The evaluation for GHD in a short child should not be initiated until other causes of [[growth failure]], such as [[hypothyroidism]], chronic systemic disease, [[Turner syndrome]] have been considered excluded. | ||
The evaluation for GHD in a short child | |||
=== '''Adults evaluation''' === | === '''Adults evaluation''' === | ||
* Adults with known hypothalamic or pituitary disease | Criteria to initiate immediate investigation include: | ||
* Panhypopituitarism is documented deficiencies of thyroid-stimulating hormone (TSH), corticotropin (ACTH), and gonadotropins. | * Adults with known [[hypothalamic]] or [[pituitary disease]] | ||
* | * [[Panhypopituitarism]] is documented deficiencies of [[thyroid-stimulating hormone]] (TSH), [[corticotropin]] (ACTH), and [[Gonadotropins|gonadotropins.]] | ||
* | * Multiple deficiencies of other pituitary hormones correlated highly with a subnormal GH response to a stimulation test [25] | ||
* Adults with a history of GH deficiency in childhood. Some will be found to have normal GH secretion as adults, although this is not likely in those with GH deficiency due to an organic | * A low serum [[Insulin-like growth factor-I|IGF-1]] concentration confirms the diagnosis of GH deficiency in these patients; provocative testing is not required [26] | ||
* Adults with a history of GH deficiency in childhood. Some will be found to have normal GH secretion as adults, although this is not likely in those with GH deficiency due to an organic such as [[pituitary adenoma]] | |||
=== What to measure? === | === What to measure? === | ||
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> | GH secretion is pulsatile and its secretion is regulated by two [[Hypothalamus|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 [[Growth hormone|GH]] level alone is not helpful and usually other tests used with it: | ||
* Insulin-like growth factor I (IGF-I) | * [[Insulin-like growth factor 1|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.<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> | * [[Insulin-like growth factor binding protein 3|Insulin-like growth factor binding protein-3]] ([[IGFBP3|IGFBP-3]]) levels: it is the major serum carrier protein for [[Insulin-like growth factor-I|IGF-I]] and the most [[Growth hormone|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.<ref name="pmid8626859">{{cite journal| author=Nunez SB, Municchi G, Barnes KM, Rose SR| title=Insulin-like growth factor I (IGF-I) and IGF-binding protein-3 concentrations compared to stimulated and night growth hormone in the evaluation of short children--a clinical research center study. | journal=J Clin Endocrinol Metab | year= 1996 | volume= 81 | issue= 5 | pages= 1927-32 | pmid=8626859 | doi=10.1210/jcem.81.5.8626859 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8626859 }}</ref>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> | * Their concentrations often reflect the concentration of secreted [[Growth hormone|GH]].<ref name="pmid8626859">{{cite journal| author=Nunez SB, Municchi G, Barnes KM, Rose SR| title=Insulin-like growth factor I (IGF-I) and IGF-binding protein-3 concentrations compared to stimulated and night growth hormone in the evaluation of short children--a clinical research center study. | journal=J Clin Endocrinol Metab | year= 1996 | volume= 81 | issue= 5 | pages= 1927-32 | pmid=8626859 | doi=10.1210/jcem.81.5.8626859 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8626859 }}</ref>They are better tests than [[Growth hormone|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 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> | Serum [[Insulin-like growth factor-I|IGF-I]] levels may be low in conditions other than GHD such as [[Growth hormone insensitivity syndrome|growth hormone insensitivity]], [[hypothyroidism]], [[renal failure]], [[Diabetes mellitus|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- | * Reduced level of [[Insulin-like growth factor-I|IGF-I]] and [[IGFBP3|IGFBP-3]] with [[Bone age|delayed bone age]]: provocative [[Growth hormone|GH]] testing is needed. If the growth failure is severe and [[Insulin-like growth factor-I|IGF-I]] and [[IGFBP3|IGFBP-3]] are severely low, there is no need to perform [[Growth hormone|GH]] stimulation testing. | ||
* Normal IGF-1 and IGFBP-3: no further testing is required. | * Normal [[Insulin-like growth factor-I|IGF-1]] and [[IGFBP3|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. | ||
* The results should be interpreted in the context of | * The results should be interpreted in the context of [[bone age]], and [[Insulin-like growth factor-I|IGF-1]] and [[IGFBP3|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. | * If the clinical and other laboratory criteria are sufficient to make the diagnosis of GHD, there is no need to perform the test. | ||
| Line 55: | Line 59: | ||
* A serum GH concentration of >10 mcg/L, but a cutoff of 7.5 mcg/L is often used for modern assays. | * 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. | * The stimulation tests are performed after an overnight fast. Serum samples are collected at intervals to capture the peak [[Growth hormone|GH]] level. | ||
* 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> | * 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.<ref name="pmid18425584">{{cite journal| author=Richmond EJ, Rogol AD| title=Growth hormone deficiency in children. | journal=Pituitary | year= 2008 | volume= 11 | issue= 2 | pages= 115-20 | pmid=18425584 | doi=10.1007/s11102-008-0105-7 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18425584 }}</ref> | * In a patient with other [[pituitary hormone]] defects or a [[Genetics|genetic]] defect, one test is sufficient to establish the diagnosis.<ref name="pmid18425584">{{cite journal| author=Richmond EJ, Rogol AD| title=Growth hormone deficiency in children. | journal=Pituitary | year= 2008 | volume= 11 | issue= 2 | pages= 115-20 | pmid=18425584 | doi=10.1007/s11102-008-0105-7 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18425584 }}</ref> | ||
* Pharmacologic stimuli include clonidine, | * 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> | ||
==== Interpretation ==== | ==== Interpretation ==== | ||
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 | * The interpretation of the test results depends upon age and [[Sex hormones|sex hormone]] concentrations. | ||
* Children with [[Constitutional growth delay|constitutional delay]] of growth and puberty may have low [[Growth hormone|GH]] results on provocative testing in the absence of true GHD. | |||
* Administration of [[sex steroids]] for a few days prior to the provocative GH testing reduces the chance of a false-positive result. | |||
==References== | ==References== | ||
{{Reflist|2}} | {{Reflist|2}} | ||
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Mohammed Abdelwahed M.D[2]
Overview
An immediate investigation should be started in severe short stature defined as a short child more than 3 sd below the mean of children at the same age. Measurement of a random serum GH level alone is not helpful. Measurement of Insulin-like growth factor I (IGF-I) and Insulin-like growth factor binding protein-3 (IGFBP-3) is more helpful than GH level alone.
GH stimulation tests is indicated for most patients suspected to have GHD. If the clinical and other laboratory criteria are sufficient to make the diagnosis of GHD, there is no need to perform the test. Pharmacologic stimuli include clonidine, glucagon, arginine, and insulin-induced hypoglycemia. Administration of sex steroids for a few days prior to the provocative GH testing reduces the chance of a false-positive result.
Laboratory Findings
Neonatal evaluation
- A GH level should always be measured:
- In the presence of neonatal hypoglycemia
- In the absence of a metabolic disorder.
- A random GH measurement in a polyclonal RIA of less than 20 mg/L would suggest GHD in the newborn.
- An IGFBP-3 measurement is of value for the diagnosis of GHD in infancy.
Children evaluation
Criteria to initiate immediate investigation include:
- Severe short stature, defined as a short child more than 3 sd below the mean of children at the same age
- Height more than 1.5 sd below the mid-parental height;
- Height more than 2 sd below the mean and a height velocity over 1 yr more than 1 sd below the mean for chronological age, or a decrease in height sd of more than 0.5 over 1 yr in children over 2 yr of age;
- In the absence of short stature, a height velocity more than 2 sd below the mean over 1 yr or more than 1.5 sd sustained over 2 yr; this may occur in GHD, presenting in infancy, or in organic GHD.
- Signs indicative of an intracranial lesion
The evaluation for GHD in a short child should not be initiated until other causes of growth failure, such as hypothyroidism, chronic systemic disease, Turner syndrome have been considered excluded.
Adults evaluation
Criteria to initiate immediate investigation include:
- Adults with known hypothalamic or pituitary disease
- Panhypopituitarism is documented deficiencies of thyroid-stimulating hormone (TSH), corticotropin (ACTH), and gonadotropins.
- Multiple deficiencies of other pituitary hormones correlated highly with a subnormal GH response to a stimulation test [25]
- A low serum IGF-1 concentration confirms the diagnosis of GH deficiency in these patients; provocative testing is not required [26]
- Adults with a history of GH deficiency in childhood. Some will be found to have normal GH secretion as adults, although this is not likely in those with GH deficiency due to an organic such as pituitary adenoma
What to measure?
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.[3]They are better tests than GH level because they are stable during the day and not pulsatile.[4]
Limitations
Serum IGF-I levels may be low in conditions other than GHD such as growth hormone insensitivity, hypothyroidism, renal failure, diabetes, and cancer.[5]
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.
GH stimulation tests
- It is indicated for most patients suspected to have GHD.
- The results should be interpreted in the context of 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.[6]
- In a patient with other pituitary hormone defects or a genetic defect, one test is sufficient to establish the diagnosis.[7]
- Pharmacologic stimuli include clonidine, glucagon, arginine, and insulin-induced hypoglycemia:[8]
Interpretation
- 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.
- Administration of sex steroids for a few days prior to the provocative GH testing reduces the chance of a false-positive result.
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.
- ↑ Nunez SB, Municchi G, Barnes KM, Rose SR (1996). "Insulin-like growth factor I (IGF-I) and IGF-binding protein-3 concentrations compared to stimulated and night growth hormone in the evaluation of short children--a clinical research center study". J Clin Endocrinol Metab. 81 (5): 1927–32. doi:10.1210/jcem.81.5.8626859. PMID 8626859.
- ↑ 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.
- ↑ Richmond EJ, Rogol AD (2008). "Growth hormone deficiency in children". Pituitary. 11 (2): 115–20. doi:10.1007/s11102-008-0105-7. PMID 18425584.
- ↑ "Stimulation of growth hormone secretion by levodopa-propranolol in children and adolescents". Pediatrics. 56 (2): 262–6. 1975. PMID 169508.