Growth hormone deficiency medical therapy: Difference between revisions

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==Overview==
==Overview==
[[Growth hormone|Growth hormone (GH)]] is indicated for children with [[Growth hormone|GH]] deficiency whose [[Epiphysis|epiphyses]] are open. The dose for children is between 0.16 and 0.24 mg/kg/week, divided into once daily injections. Serum levels of [[Insulin-like growth factor 1|insulin-like growth factor I]] (IGF-I) should be measured several weeks after beginning [[Growth hormone|GH]] treatment or making a dose adjustment. GH side effects include [[Headache|headaches]], [[Idiopathic intracranial hypertension]], [[Slipped capital femoral epiphysis]], worsening of existing [[scoliosis]], [[Pancreatitis]], and [[Gynecomastia]]. There is a possible role for [[Growth hormone|GH]] in cancer risk.
Growth hormone (GH) supplementation is indicated for children with GH deficiency whose epiphyses are yet to close. The dose for children is between 0.16 and 0.24 mg/kg/week, divided into once daily injections. Serum levels of insulin-like growth factor I (IGF-I) ought to be measured continuously for several weeks after starting GH treatment or making a dose adjustment. Side effects of GH supplementation include headaches, idiopathic intracranial hypertension, slipped capital femoral epiphysis, worsening of existing scoliosis, pancreatitis, and gynecomastia. There is a likely role for GH in cancer risk.


==Medical Therapy==
==Medical Therapy==


=== Children treatment ===
=== Childhood GH deficiency treatment ===
 
Indications:
==== '''Indications'''<ref name="pmid3481175">{{cite journal| author=Albertsson-Wikland K| title=The effect of human growth hormone injection frequency on linear growth rate. | journal=Acta Paediatr Scand Suppl | year= 1987 | volume= 337 | issue=  | pages= 110-6 | pmid=3481175 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=3481175  }}</ref> ====
* Treatment with [[Growth hormone|Growth hormone (GH)]] is indicated for children with [[Growth hormone|GH]] deficiency whose [[Epiphysis|epiphyses]] are yet to close.  
* Treatment with [[Growth hormone|Growth hormone (GH)]] is indicated for children with [[Growth hormone|GH]] deficiency whose [[Epiphysis|epiphyses]] are open.  
* Treatment should be continued after linear growth ceases until full skeletal development.
* Treatment should be continued until linear growth ceases or even beyond.
Dosing:
 
==== Dosing ====
* The dose for children is between 0.16 and 0.24 mg/kg/week, divided into once daily injections.
* The dose for children is between 0.16 and 0.24 mg/kg/week, divided into once daily injections.
* The dose for patients with severe [[Growth hormone|GH]] deficiency is 20 micrograms/kg/day.
* The dose for patients with severe [[Growth hormone|GH]] deficiency is 20 micrograms/kg/day.
 
Dosing during puberty:
==== '''Dosing during puberty'''<ref name="pmid10506252">{{cite journal| author=Allen DB| title=Issues in the transition from childhood to adult growth hormone therapy. | journal=Pediatrics | year= 1999 | volume= 104 | issue= 4 Pt 2 | pages= 1004-10 | pmid=10506252 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=10506252  }}</ref> ====
* A temporary increase in [[Growth hormone|GH]] dose is preferred if the patient failed to respond to normal doses.  
* A temporary increase in [[Growth hormone|GH]] dose is preferred if the patient failed to respond to normal doses.  
* Although, effective treatment with GH before [[puberty]] is more efficacious than efforts to treat patients during [[puberty]].
* Although, effective treatment with GH before [[puberty]] is more efficacious than efforts to treat patients during [[puberty]].
 
Monitoring:
==== '''Monitoring''' ====
* Serum levels of [[Insulin-like growth factor 1|insulin-like growth factor I]] (IGF-I) should be measured for several weeks after beginning [[Growth hormone|GH]] treatment or making a dose adjustment.
* Serum levels of [[Insulin-like growth factor 1|insulin-like growth factor I]] (IGF-I) should be measured several weeks after beginning [[Growth hormone|GH]] treatment or making a dose adjustment.
* This helps to avoid very high [[Insulin-like growth factor-I|IGF-I]] levels, which are thought to be associated with some of the drug's toxicity as recommended in guidelines from the Pediatric Endocrine Society (PES):<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>
* This helps to avoid very high [[Insulin-like growth factor-I|IGF-I]] levels, which are thought to be associated with some of the drug's toxicity as recommended in guidelines from the Pediatric Endocrine Society (PES):<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>


* If the [[Insulin-like growth factor-I|IGF-I]] level is below this target range, increase the dose of [[Growth hormone|GH]] because [[Growth hormone|GH]] is unlikely to be efficacious if [[Insulin-like growth factor-I|IGF-I]] levels are very low.
* If the [[Insulin-like growth factor-I|IGF-I]] level is below the target range, increasing the dose of [[Growth hormone|GH]] is recommended, as [[Growth hormone|GH]] is unlikely to be efficacious if [[Insulin-like growth factor-I|IGF-I]] levels are very low.
* If the [[Insulin-like growth factor-I|IGF-I]] level is above this target range, we reduce the [[Growth hormone|GH]] dose to prevent [[Growth hormone|GH]] toxicity.
* If the IGF-I level is above this target range, we reduce the GH dose to prevent GH toxicity. For patients with more than one pituitary hormone deficiencies, adrenal and thyroid function need to be reassessed a few months after initiation of GH therapy.<ref name="pmid27884013" />
* For patients with multiple [[pituitary hormone]] deficiencies, [[Adrenal gland|adrenal]] and [[thyroid]] function should be reassessed a few months after initiation of [[Growth hormone|GH]] therapy.<ref name="pmid27884013" />
Duration of therapy :
 
* Treatment is continued at least until linear growth decreases to less than 2.0 to 2.5 cm.
==== '''Duration of therapy''' ====
* More than two-thirds of patients have normal outcomes when retested for GH deficiency as adults.
* Treatment is continued at least until linear growth decreases to less than 2.0 to 2.5 cm.<ref name="pmid27884013" />
* It is vital to repeat the GH stimulation test at some point of the transition period to determine if they will require ongoing therapy.
* More than two-thirds of patients have normal results when retested for [[Growth hormone|GH]] deficiency as adults.  
* Patients can attain normal height if treatment is administered at an early age.
* It is important to repeat the [[Growth hormone|GH]] stimulation test during the transition period to determine if they will require ongoing therapy.
* Patient's height should be reevaluated every 4 to 6 months to determine if the growth response is adequate.
 
* During the preliminary growth period, the 75th percentile curve for height pace is the proper target as an adequate growth response to GH..
* If GH is administered at an early age, patients can achieve [[adult]] height.<ref name="pmid16537676">{{cite journal| author=Reiter EO, Price DA, Wilton P, Albertsson-Wikland K, Ranke MB| title=Effect of growth hormone (GH) treatment on the near-final height of 1258 patients with idiopathic GH deficiency: analysis of a large international database. | journal=J Clin Endocrinol Metab | year= 2006 | volume= 91 | issue= 6 | pages= 2047-54 | pmid=16537676 | doi=10.1210/jc.2005-2284 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16537676  }}</ref>
* Patients heights should be rechecked every four to six months to determine if the growth response is adequate.
* During the initial growth period, the 75<sup>th</sup> percentile curve for height velocity is an appropriate target to define an adequate growth response to [[Growth hormone|GH]].  
 
==== Effect of treatment ====


===== '''Growth''' =====
=== Effect of treatment ===
* Results usually better if [[Growth hormone|GH]] therapy is started in early childhood.<ref name="pmid12114235">{{cite journal| author=Carel JC, Ecosse E, Nicolino M, Tauber M, Leger J, Cabrol S et al.| title=Adult height after long term treatment with recombinant growth hormone for idiopathic isolated growth hormone deficiency: observational follow up study of the French population based registry. | journal=BMJ | year= 2002 | volume= 325 | issue= 7355 | pages= 70 | pmid=12114235 | doi= | pmc=117125 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12114235  }}</ref>
Growth :
* [[Growth hormone|GH]] therapy started early in childhood have better prognosis.<ref name="pmid12114235">{{cite journal| author=Carel JC, Ecosse E, Nicolino M, Tauber M, Leger J, Cabrol S et al.| title=Adult height after long term treatment with recombinant growth hormone for idiopathic isolated growth hormone deficiency: observational follow up study of the French population based registry. | journal=BMJ | year= 2002 | volume= 325 | issue= 7355 | pages= 70 | pmid=12114235 | doi= | pmc=117125 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12114235  }}</ref>
* Increase in height continues for more than 2 years even after cessation of treatment.<ref>{{Cite journal


===== '''Bone mass''' =====
| author = [[Z. Laron]], [[B. Klinger]], [[S. Anin]], [[A. Pertzelan]] & [[P. Lilos]]
* Children with [[Growth hormone|GH]] deficiency have low bone mass compared with control children.  
| title = Growth during and 2 years after stopping GH treatment in prepubertal children with idiopathic short stature
* To maximize bone mass, it is important to consider the continuation of GH treatment even after linear growth has ceased until full skeletal.<ref name="pmid19324976">{{cite journal| author=Conway GS, Szarras-Czapnik M, Racz K, Keller A, Chanson P, Tauber M et al.| title=Treatment for 24 months with recombinant human GH has a beneficial effect on bone mineral density in young adults with childhood-onset GH deficiency. | journal=Eur J Endocrinol | year= 2009 | volume= 160 | issue= 6 | pages= 899-907 | pmid=19324976 | doi=10.1530/EJE-08-0436 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19324976  }}</ref>  
| journal = [[Journal of pediatric endocrinology & metabolism : JPEM]]
* GH therapy increases bone mass.<ref name="pmid1874933">{{cite journal| author=Bonjour JP, Theintz G, Buchs B, Slosman D, Rizzoli R| title=Critical years and stages of puberty for spinal and femoral bone mass accumulation during adolescence. | journal=J Clin Endocrinol Metab | year= 1991 | volume= 73 | issue= 3 | pages= 555-63 | pmid=1874933 | doi=10.1210/jcem-73-3-555 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=1874933  }}</ref>Without adequate GH replacement, GH deficiency can be associated with low bone mass during adulthood.<ref name="pmid8126140">{{cite journal| author=Holmes SJ, Economou G, Whitehouse RW, Adams JE, Shalet SM| title=Reduced bone mineral density in patients with adult onset growth hormone deficiency. | journal=J Clin Endocrinol Metab | year= 1994 | volume= 78 | issue= 3 | pages= 669-74 | pmid=8126140 | doi=10.1210/jcem.78.3.8126140 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8126140  }}</ref>
| volume = 10
| issue = 2
| pages = 191–196
| year = 1997
| month = March-April
| pmid = 9364352
}}</ref>
Bone mass :
* Children with [[Growth hormone|GH]] deficiency have low [[bone mass]] compared with normal children.  
* To maximize [[bone mass]], it is important to consider the continuation of treatment even after linear growth has ceased until full skeletal development.<ref name="pmid19324976">{{cite journal| author=Conway GS, Szarras-Czapnik M, Racz K, Keller A, Chanson P, Tauber M et al.| title=Treatment for 24 months with recombinant human GH has a beneficial effect on bone mineral density in young adults with childhood-onset GH deficiency. | journal=Eur J Endocrinol | year= 2009 | volume= 160 | issue= 6 | pages= 899-907 | pmid=19324976 | doi=10.1530/EJE-08-0436 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19324976  }}</ref>  
* [[Growth hormone|GH]] therapy increases bone mass.<ref name="pmid1874933">{{cite journal| author=Bonjour JP, Theintz G, Buchs B, Slosman D, Rizzoli R| title=Critical years and stages of puberty for spinal and femoral bone mass accumulation during adolescence. | journal=J Clin Endocrinol Metab | year= 1991 | volume= 73 | issue= 3 | pages= 555-63 | pmid=1874933 | doi=10.1210/jcem-73-3-555 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=1874933  }}</ref>
* Without adequate GH replacement, [[Growth hormone|GH]] deficiency can be associated with low [[bone mass]] during adulthood.<ref name="pmid8126140">{{cite journal| author=Holmes SJ, Economou G, Whitehouse RW, Adams JE, Shalet SM| title=Reduced bone mineral density in patients with adult onset growth hormone deficiency. | journal=J Clin Endocrinol Metab | year= 1994 | volume= 78 | issue= 3 | pages= 669-74 | pmid=8126140 | doi=10.1210/jcem.78.3.8126140 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8126140  }}</ref>


==== '''ADVERSE EFFECTS OF GROWTH HORMONE THERAPY''' ====
=== Adverse effects of growth hormone therapy===
Treatment of children with [[Recombinant DNA|recombinant]] human [[Growth hormone|GH]] has generally been safe.<ref name="pmid9745413">{{cite journal| author=Saenger P, Attie KM, DiMartino-Nardi J, Hintz R, Frahm L, Frane JW| title=Metabolic consequences of 5-year growth hormone (GH) therapy in children treated with GH for idiopathic short stature. Genentech Collaborative Study Group. | journal=J Clin Endocrinol Metab | year= 1998 | volume= 83 | issue= 9 | pages= 3115-20 | pmid=9745413 | doi=10.1210/jcem.83.9.5089 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9745413  }}</ref><ref name="pmid20523016">{{cite journal| author=Carel JC, Butler G| title=Safety of recombinant human growth hormone. | journal=Endocr Dev | year= 2010 | volume= 18 | issue=  | pages= 40-54 | pmid=20523016 | doi=10.1159/000316126 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20523016  }}</ref>
Treatment of children with [[Recombinant DNA|recombinant]] human [[Growth hormone|GH]] has generally been safe.<ref name="pmid9745413">{{cite journal| author=Saenger P, Attie KM, DiMartino-Nardi J, Hintz R, Frahm L, Frane JW| title=Metabolic consequences of 5-year growth hormone (GH) therapy in children treated with GH for idiopathic short stature. Genentech Collaborative Study Group. | journal=J Clin Endocrinol Metab | year= 1998 | volume= 83 | issue= 9 | pages= 3115-20 | pmid=9745413 | doi=10.1210/jcem.83.9.5089 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9745413  }}</ref><ref name="pmid20523016">{{cite journal| author=Carel JC, Butler G| title=Safety of recombinant human growth hormone. | journal=Endocr Dev | year= 2010 | volume= 18 | issue=  | pages= 40-54 | pmid=20523016 | doi=10.1159/000316126 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20523016  }}</ref>


===== '''Acute effects''' =====
Acute effects :
* [[Headache|Headaches]] which usually are benign.
* [[Headache|Headaches]] which usually are benign.
* [[Idiopathic intracranial hypertension]] (formerly known as [[Idiopathic intracranial hypertension|pseudotumor cerebri]]), increased [[Intraocular pressure (IOP)|intraocular pressure]] usually resolves with discontinuation of [[Growth hormone|GH]] therapy. Treatment can often be resumed at a lower dose without the return of symptoms back up to standard doses.<ref name="pmid22727870">{{cite journal| author=Youngster I, Rachmiel R, Pinhas-Hamiel O, Bistritzer T, Zuckerman-Levin N, de Vries L et al.| title=Treatment with recombinant human growth hormone during childhood is associated with increased intraocular pressure. | journal=J Pediatr | year= 2012 | volume= 161 | issue= 6 | pages= 1116-9 | pmid=22727870 | doi=10.1016/j.jpeds.2012.05.024 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22727870  }}</ref>  
* [[Idiopathic intracranial hypertension]] (known as [[Idiopathic intracranial hypertension|pseudotumor cerebri]]), increased [[Intraocular pressure (IOP)|intraocular pressure]] usually resolves with discontinuation of [[Growth hormone|GH]] therapy. Treatment can often be resumed at a lower dose without the return of symptoms back up to standard doses.<ref name="pmid22727870">{{cite journal| author=Youngster I, Rachmiel R, Pinhas-Hamiel O, Bistritzer T, Zuckerman-Levin N, de Vries L et al.| title=Treatment with recombinant human growth hormone during childhood is associated with increased intraocular pressure. | journal=J Pediatr | year= 2012 | volume= 161 | issue= 6 | pages= 1116-9 | pmid=22727870 | doi=10.1016/j.jpeds.2012.05.024 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22727870  }}</ref>  
* [[Slipped capital femoral epiphysis]]: routine monitoring is recommended for suggestive symptoms such as hip and/or [[knee pain]], and changes in [[gait]]. This condition usually requires surgical pinning of the [[Epiphysis|capital femoral epiphysis]].<ref name="pmid18174706">{{cite journal| author=Darendeliler F, Karagiannis G, Wilton P| title=Headache, idiopathic intracranial hypertension and slipped capital femoral epiphysis during growth hormone treatment: a safety update from the KIGS database. | journal=Horm Res | year= 2007 | volume= 68 Suppl 5 | issue=  | pages= 41-7 | pmid=18174706 | doi=10.1159/000110474 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18174706  }}</ref>  
* [[Slipped capital femoral epiphysis]]: routine monitoring is recommended for suggestive symptoms such as hip and/or [[knee pain]], and changes in [[gait]]. This condition requires surgical pinning of the [[Epiphysis|capital femoral epiphysis]].<ref name="pmid18174706">{{cite journal| author=Darendeliler F, Karagiannis G, Wilton P| title=Headache, idiopathic intracranial hypertension and slipped capital femoral epiphysis during growth hormone treatment: a safety update from the KIGS database. | journal=Horm Res | year= 2007 | volume= 68 Suppl 5 | issue=  | pages= 41-7 | pmid=18174706 | doi=10.1159/000110474 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18174706  }}</ref>  
* Worsening of existing [[scoliosis]].<ref name="pmid8626820">{{cite journal| author=Blethen SL, Allen DB, Graves D, August G, Moshang T, Rosenfeld R| title=Safety of recombinant deoxyribonucleic acid-derived growth hormone: The National Cooperative Growth Study experience. | journal=J Clin Endocrinol Metab | year= 1996 | volume= 81 | issue= 5 | pages= 1704-10 | pmid=8626820 | doi=10.1210/jcem.81.5.8626820 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8626820  }}</ref>  
* Worsening of existing [[scoliosis]].<ref name="pmid8626820">{{cite journal| author=Blethen SL, Allen DB, Graves D, August G, Moshang T, Rosenfeld R| title=Safety of recombinant deoxyribonucleic acid-derived growth hormone: The National Cooperative Growth Study experience. | journal=J Clin Endocrinol Metab | year= 1996 | volume= 81 | issue= 5 | pages= 1704-10 | pmid=8626820 | doi=10.1210/jcem.81.5.8626820 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8626820  }}</ref>  
* [[Pancreatitis]]
* [[Pancreatitis]]
* [[Gynecomastia]]
* [[Gynecomastia]]
* Increase in the growth and pigmentation of [[Nevus|nevi,]] without [[malignant]] degeneration.<ref name="pmid8099381">{{cite journal| author=Bourguignon JP, Piérard GE, Ernould C, Heinrichs C, Craen M, Rochiccioli P et al.| title=Effects of human growth hormone therapy on melanocytic naevi. | journal=Lancet | year= 1993 | volume= 341 | issue= 8859 | pages= 1505-6 | pmid=8099381 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8099381  }}</ref>
* Increase in the growth and [[pigmentation]] of [[Nevus|nevi]].<ref name="pmid8099381">{{cite journal| author=Bourguignon JP, Piérard GE, Ernould C, Heinrichs C, Craen M, Rochiccioli P et al.| title=Effects of human growth hormone therapy on melanocytic naevi. | journal=Lancet | year= 1993 | volume= 341 | issue= 8859 | pages= 1505-6 | pmid=8099381 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8099381  }}</ref>
* [[Carpal tunnel syndrome]], [[edema]], and [[arthralgia]] are more common in adults undergoing [[Growth hormone|GH]] treatment but are unusual in children.
* [[Carpal tunnel syndrome]], [[edema]], and [[arthralgia]] are more common in adults than in children.
* Most usually occur soon after therapy is initiated, and some of these effects are probably caused by sodium and water retention.  
* [[Antibodies|Neutralizing antibodies]] against [[Growth hormone|GH]] may be formed resulting in loss of [[efficacy]].<ref name="pmid12014526">{{cite journal| author=Pitukcheewanont P, Schwarzbach L, Kaufman FR| title=Resumption of growth after methionyl-free human growth hormone therapy in a patient with neutralizing antibodies to methionyl human growth hormone. | journal=J Pediatr Endocrinol Metab | year= 2002 | volume= 15 | issue= 5 | pages= 653-7 | pmid=12014526 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12014526  }}</ref>
* [[Antibodies|Neutralizing antibodies]] against [[Growth hormone|GH]] may be formed resulting in loss of efficacy.<ref name="pmid12014526">{{cite journal| author=Pitukcheewanont P, Schwarzbach L, Kaufman FR| title=Resumption of growth after methionyl-free human growth hormone therapy in a patient with neutralizing antibodies to methionyl human growth hormone. | journal=J Pediatr Endocrinol Metab | year= 2002 | volume= 15 | issue= 5 | pages= 653-7 | pmid=12014526 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12014526  }}</ref>
* Development of [[insulin resistance]] and [[glucose intolerance]] may occur in children receiving [[Growth hormone|GH]] therapy.<ref name="pmid10696981">{{cite journal| author=Cutfield WS, Wilton P, Bennmarker H, Albertsson-Wikland K, Chatelain P, Ranke MB et al.| title=Incidence of diabetes mellitus and impaired glucose tolerance in children and adolescents receiving growth-hormone treatment. | journal=Lancet | year= 2000 | volume= 355 | issue= 9204 | pages= 610-3 | pmid=10696981 | doi=10.1016/S0140-6736(99)04055-6 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=10696981  }}</ref>
* Development of [[insulin resistance]] and disorders of [[glucose intolerance]] may occur in children receiving [[Growth hormone|GH]] therapy.<ref name="pmid10696981">{{cite journal| author=Cutfield WS, Wilton P, Bennmarker H, Albertsson-Wikland K, Chatelain P, Ranke MB et al.| title=Incidence of diabetes mellitus and impaired glucose tolerance in children and adolescents receiving growth-hormone treatment. | journal=Lancet | year= 2000 | volume= 355 | issue= 9204 | pages= 610-3 | pmid=10696981 | doi=10.1016/S0140-6736(99)04055-6 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=10696981  }}</ref>
Chronic effects:
 
===== Chronic effects =====
* There is a possible role for [[Growth hormone|GH]] in cancer risk especially [[prostate cancer]].<ref name="pmid12147365">{{cite journal| author=Giovannucci E, Pollak M| title=Risk of cancer after growth-hormone treatment. | journal=Lancet | year= 2002 | volume= 360 | issue= 9329 | pages= 268-9 | pmid=12147365 | doi=10.1016/S0140-6736(02)09561-2 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12147365  }}</ref><ref name="pmid26227295">{{cite journal| author=Swerdlow AJ, Cooke R, Albertsson-Wikland K, Borgström B, Butler G, Cianfarani S et al.| title=Description of the SAGhE Cohort: A Large European Study of Mortality and Cancer Incidence Risks after Childhood Treatment with Recombinant Growth Hormone. | journal=Horm Res Paediatr | year= 2015 | volume= 84 | issue= 3 | pages= 172-83 | pmid=26227295 | doi=10.1159/000435856 | pmc=4611066 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=26227295  }}</ref>
* There is a possible role for [[Growth hormone|GH]] in cancer risk especially [[prostate cancer]].<ref name="pmid12147365">{{cite journal| author=Giovannucci E, Pollak M| title=Risk of cancer after growth-hormone treatment. | journal=Lancet | year= 2002 | volume= 360 | issue= 9329 | pages= 268-9 | pmid=12147365 | doi=10.1016/S0140-6736(02)09561-2 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12147365  }}</ref><ref name="pmid26227295">{{cite journal| author=Swerdlow AJ, Cooke R, Albertsson-Wikland K, Borgström B, Butler G, Cianfarani S et al.| title=Description of the SAGhE Cohort: A Large European Study of Mortality and Cancer Incidence Risks after Childhood Treatment with Recombinant Growth Hormone. | journal=Horm Res Paediatr | year= 2015 | volume= 84 | issue= 3 | pages= 172-83 | pmid=26227295 | doi=10.1159/000435856 | pmc=4611066 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=26227295  }}</ref>
* [[Growth hormone|GH]] therapy does not increase the risk of leukemia or other cancers compared with the general population.<ref name="pmid281872252">{{cite journal| author=Swerdlow AJ, Cooke R, Beckers D, Borgström B, Butler G, Carel JC et al.| title=Cancer Risks in Patients Treated With Growth Hormone in Childhood: The SAGhE European Cohort Study. | journal=J Clin Endocrinol Metab | year= 2017 | volume= 102 | issue= 5 | pages= 1661-1672 | pmid=28187225 | doi=10.1210/jc.2016-2046 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=28187225 }}</ref>
* [[Growth hormone|GH]] therapy does not increase the risk of [[leukemia]] or other cancers compared with the general population.<ref name="pmid281872252">{{cite journal| author=Swerdlow AJ, Cooke R, Beckers D, Borgström B, Butler G, Carel JC et al.| title=Cancer Risks in Patients Treated With Growth Hormone in Childhood: The SAGhE European Cohort Study. | journal=J Clin Endocrinol Metab | year= 2017 | volume= 102 | issue= 5 | pages= 1661-1672 | pmid=28187225 | doi=10.1210/jc.2016-2046 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=28187225  }}</ref>
* However, a lack of association with cancer was also found in other studies.<ref name="pmid25839904">{{cite journal| author=Raman S, Grimberg A, Waguespack SG, Miller BS, Sklar CA, Meacham LR et al.| title=Risk of Neoplasia in Pediatric Patients Receiving Growth Hormone Therapy--A Report From the Pediatric Endocrine Society Drug and Therapeutics Committee. | journal=J Clin Endocrinol Metab | year= 2015 | volume= 100 | issue= 6 | pages= 2192-203 | pmid=25839904 | doi=10.1210/jc.2015-1002 | pmc=5393518 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=25839904 }}</ref>
* For patients with a primary cancer diagnosis that led to the [[Growth hormone|GH]] treatment, [[recombinant]] [[GH]] was associated with an increase in risk for [[cancer]].<ref name="pmid281872252" />
* For patients with a primary cancer diagnosis that led to the [[Growth hormone|GH]] treatment, recombinant GH was associated with a modest increase in risk for secondary cancer.<ref name="pmid281872252" />
* The increased risk was significant for a variety of secondary cancers including [[Bone|bone,]] [[melanoma]], [[kidney]], [[brain]], [[thyroid]] cancer and [[leukemia]].  
* The increased risk was significant for a variety of secondary cancers including [[Bone|bone,]] [[melanoma]], [[kidney]], [[brain]], [[thyroid]] cancer and [[leukemia]].  
* Cancer mortality increased with [[Growth hormone|GH]] dose and duration of treatment.
* For children with [[cancer]], guidelines suggest a 12-month period after completion of cancer-directed therapy to confirm that the [[cancer]] was eradicated before initiating [[Growth hormone|GH therapy]].
* For children with cancer, guidelines suggest a 12-month period after completion of cancer-directed therapy to confirm that the cancer was eradicated before initiating GH therapy.


==== Transition of GH treatment from childhood to adults<ref name="pmid21270511">{{cite journal| author=Molitch ME| title=Growth hormone treatment in adults with growth hormone deficiency: the transition. | journal=J Endocrinol Invest | year= 2011 | volume= 34 | issue= 2 | pages= 150-4 | pmid=21270511 | doi=10.3275/7483 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21270511  }}</ref> ====
=== Transition of GH treatment from childhood to adults ===
* The transition period between childhood treatment and adults treatment begins in late [[puberty]] and ends with full adult maturation.
* The transition period between childhood treatment and adults treatment begins in late [[puberty]] and ends with full adult maturation.
* Children treated with [[Growth hormone|GH]] should be retested near the time of reaching the adult height to determine if they have persistence of GHD.
* Children treated with [[Growth hormone|GH]] should be retested if they have persistence of GHD near the time of reaching adulthood.
* Patients with idiopathic GHD usually do not need [[Growth hormone|GH]] treatment anymore, children with organic causes of GHD usually are found to have GHD on retesting.  
* Patients with idiopathic GHD usually do not need [[Growth hormone|GH]] treatment anymore, children with organic causes of GHD usually are found to have GHD on retesting.  
* Retesting involves measurement of [[Insulin-like growth factor-I|IGF-I]] and stimulation with [[insulin]]-induced [[hypoglycemia]] or [[arginine]].
* Retesting involves measurement of [[Insulin-like growth factor-I|IGF-I]] and stimulation with [[insulin]]-induced [[hypoglycemia]] or [[arginine]].
* Most studies have shown the benefit of [[Growth hormone|GH]] treatment in young adults with GHD in body composition, especially the achievement of peak [[bone mass]].  
* Most studies have shown benefit of [[Growth hormone|GH]] treatment in young adults with GHD in [[body composition]], especially the achievement of peak [[bone mass]].  


=== Adult-type GH deficiency treatment ===
=== Adult-type GH deficiency treatment ===
 
Treatment protocol:
==== '''Treatment protocol''' ====
* [[Growth hormone|GH]] is administered by subcutaneous injection once a day, usually in the evening.
* [[Growth hormone|GH]] is administered by subcutaneous injection once a day, usually in the evening.
* The goal should be to start with low doses and increase gradually until the serum [[Insulin-like growth factor-I|IGF-1]] concentration is normal.
* The goal should be to start with low doses and increase gradually until the serum [[Insulin-like growth factor-I|IGF-1]] concentration is normal.
* The eventual goal is to find the [[Growth hormone|GH]] dose that maintains the serum [[Insulin-like growth factor-I|IGF-1]] concentration within the middle of the age-adjusted normal range.<ref name="pmid27736313">{{cite journal| author=Fleseriu M, Hashim IA, Karavitaki N, Melmed S, Murad MH, Salvatori R et al.| title=Hormonal Replacement in Hypopituitarism in Adults: An Endocrine Society Clinical Practice Guideline. | journal=J Clin Endocrinol Metab | year= 2016 | volume= 101 | issue= 11 | pages= 3888-3921 | pmid=27736313 | doi=10.1210/jc.2016-2118 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=27736313  }}</ref>
* The eventual goal is to find the [[Growth hormone|GH]] dose that maintains the serum [[Insulin-like growth factor-I|IGF-1]] concentration within the middle of the age-adjusted normal range.<ref name="pmid27736313">{{cite journal| author=Fleseriu M, Hashim IA, Karavitaki N, Melmed S, Murad MH, Salvatori R et al.| title=Hormonal Replacement in Hypopituitarism in Adults: An Endocrine Society Clinical Practice Guideline. | journal=J Clin Endocrinol Metab | year= 2016 | volume= 101 | issue= 11 | pages= 3888-3921 | pmid=27736313 | doi=10.1210/jc.2016-2118 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=27736313  }}</ref>
* If side effects occur or the serum [[Insulin-like growth factor-I|IGF-1]] concentration increases to above normal at any dose, the dose should be decreased.
* If side effects occur or the serum [[Insulin-like growth factor-I|IGF-1]] concentration increases to above normal at any dose, the dose should be decreased.
 
Dosing:
==== Dosing ====
* The starting dose should be 2 to 5 mcg/kg body weight once daily.
The starting dose should be 2 to 5 mcg/kg body weight once daily.
Duration of therapy:
 
==== '''Duration of therapy''' ====
* Treatment should be continued indefinitely.<ref name="pmid23572082">{{cite journal| author=Appelman-Dijkstra NM, Claessen KM, Roelfsema F, Pereira AM, Biermasz NR| title=Long-term effects of recombinant human GH replacement in adults with GH deficiency: a systematic review. | journal=Eur J Endocrinol | year= 2013 | volume= 169 | issue= 1 | pages= R1-14 | pmid=23572082 | doi=10.1530/EJE-12-1088 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23572082  }}</ref>
* Treatment should be continued indefinitely.<ref name="pmid23572082">{{cite journal| author=Appelman-Dijkstra NM, Claessen KM, Roelfsema F, Pereira AM, Biermasz NR| title=Long-term effects of recombinant human GH replacement in adults with GH deficiency: a systematic review. | journal=Eur J Endocrinol | year= 2013 | volume= 169 | issue= 1 | pages= R1-14 | pmid=23572082 | doi=10.1530/EJE-12-1088 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23572082  }}</ref>
* Stopping the treatment causes an increase in [[C-reactive protein (CRP)|C-reactive protein]] and increases in both [[LDL Cholesterol|LDL]] and [[HDL Cholesterol|HDL]] cholesterol but improved insulin sensitivity and decreased glycated hemoglobin [[Hemoglobin A1c|(A1C]]).<ref name="pmid22791760">{{cite journal| author=Filipsson Nyström H, Barbosa EJ, Nilsson AG, Norrman LL, Ragnarsson O, Johannsson G| title=Discontinuing long-term GH replacement therapy--a randomized, placebo-controlled crossover trial in adult GH deficiency. | journal=J Clin Endocrinol Metab | year= 2012 | volume= 97 | issue= 9 | pages= 3185-95 | pmid=22791760 | doi=10.1210/jc.2012-2006 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22791760  }}</ref>
* Stopping the treatment causes an increase in [[C-reactive protein (CRP)|C-reactive protein]] and increases in both [[LDL Cholesterol|LDL]] and [[HDL Cholesterol|HDL]] cholesterol but improved [[insulin]] [[sensitivity]] and decreased glycated [[hemoglobin]] [[Hemoglobin A1c|(A1C]]).<ref name="pmid22791760">{{cite journal| author=Filipsson Nyström H, Barbosa EJ, Nilsson AG, Norrman LL, Ragnarsson O, Johannsson G| title=Discontinuing long-term GH replacement therapy--a randomized, placebo-controlled crossover trial in adult GH deficiency. | journal=J Clin Endocrinol Metab | year= 2012 | volume= 97 | issue= 9 | pages= 3185-95 | pmid=22791760 | doi=10.1210/jc.2012-2006 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22791760  }}</ref>
 
Monitoring:
==== '''Monitoring''' ====
* Measurement of serum [[Insulin-like growth factor-I|IGF-1]] is probably the best single test of the adequacy of [[Growth hormone|GH]] treatment.<ref name="pmid8636336">{{cite journal| author=de Boer H, Blok GJ, Popp-Snijders C, Stuurman L, Baxter RC, van der Veen E| title=Monitoring of growth hormone replacement therapy in adults, based on measurement of serum markers. | journal=J Clin Endocrinol Metab | year= 1996 | volume= 81 | issue= 4 | pages= 1371-7 | pmid=8636336 | doi=10.1210/jcem.81.4.8636336 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8636336  }}</ref>
* Measurement of serum [[Insulin-like growth factor-I|IGF-1]] is probably the best single test of the adequacy of [[Growth hormone|GH]] treatment.<ref name="pmid8636336">{{cite journal| author=de Boer H, Blok GJ, Popp-Snijders C, Stuurman L, Baxter RC, van der Veen E| title=Monitoring of growth hormone replacement therapy in adults, based on measurement of serum markers. | journal=J Clin Endocrinol Metab | year= 1996 | volume= 81 | issue= 4 | pages= 1371-7 | pmid=8636336 | doi=10.1210/jcem.81.4.8636336 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8636336  }}</ref>
* We suggest measuring a serum [[Insulin-like growth factor-I|IGF-1]] two months after starting therapy.
* Measurment of  serum [[Insulin-like growth factor-I|IGF-1]] two months after starting therapy is recommended.
* GH treatment should increase the serum [[Insulin-like growth factor-I|IGF-1]] concentration to within, but not higher than, the age-specific range of normal to avoid over replacement.
* GH treatment should increase the serum [[Insulin-like growth factor-I|IGF-1]] concentration to within, but not higher than, the age-specific range of normal to avoid over replacement.
* Once serum [[Insulin-like growth factor-I|IGF-1]] is in the normal range, we suggest repeating it every 6 to 12 months.  
* Once serum [[Insulin-like growth factor-I|IGF-1]] is in the normal range, repeat measurements every 6 to 12 months is recommended.  
* If [[Insulin-like growth factor-I|IGF-1]] is ever above normal, the [[Growth hormone|GH]] dose should be decreased by 1 to 2 mcg/kg increments and serum [[Insulin-like growth factor-I|IGF-1]] should be repeated every two months until it returns to the normal range.
* If [[Insulin-like growth factor-I|IGF-1]] is ever above normal, the [[Growth hormone|GH]] dose should be decreased by 1 to 2 mcg/kg increments and serum [[Insulin-like growth factor-I|IGF-1]] should be repeated every 2 months until it returns to the normal range.


==References==
==References==

Latest revision as of 19:41, 27 October 2017

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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

Growth hormone (GH) supplementation is indicated for children with GH deficiency whose epiphyses are yet to close. The dose for children is between 0.16 and 0.24 mg/kg/week, divided into once daily injections. Serum levels of insulin-like growth factor I (IGF-I) ought to be measured continuously for several weeks after starting GH treatment or making a dose adjustment. Side effects of GH supplementation include headaches, idiopathic intracranial hypertension, slipped capital femoral epiphysis, worsening of existing scoliosis, pancreatitis, and gynecomastia. There is a likely role for GH in cancer risk.

Medical Therapy

Childhood GH deficiency treatment

Indications:

  • Treatment with Growth hormone (GH) is indicated for children with GH deficiency whose epiphyses are yet to close.
  • Treatment should be continued after linear growth ceases until full skeletal development.

Dosing:

  • The dose for children is between 0.16 and 0.24 mg/kg/week, divided into once daily injections.
  • The dose for patients with severe GH deficiency is 20 micrograms/kg/day.

Dosing during puberty:

  • A temporary increase in GH dose is preferred if the patient failed to respond to normal doses.
  • Although, effective treatment with GH before puberty is more efficacious than efforts to treat patients during puberty.

Monitoring:

  • Serum levels of insulin-like growth factor I (IGF-I) should be measured for several weeks after beginning GH treatment or making a dose adjustment.
  • This helps to avoid very high IGF-I levels, which are thought to be associated with some of the drug's toxicity as recommended in guidelines from the Pediatric Endocrine Society (PES):[1]
  • If the IGF-I level is below the target range, increasing the dose of GH is recommended, as GH is unlikely to be efficacious if IGF-I levels are very low.
  • If the IGF-I level is above this target range, we reduce the GH dose to prevent GH toxicity. For patients with more than one pituitary hormone deficiencies, adrenal and thyroid function need to be reassessed a few months after initiation of GH therapy.[1]

Duration of therapy :

  • Treatment is continued at least until linear growth decreases to less than 2.0 to 2.5 cm.
  • More than two-thirds of patients have normal outcomes when retested for GH deficiency as adults.
  • It is vital to repeat the GH stimulation test at some point of the transition period to determine if they will require ongoing therapy.
  • Patients can attain normal height if treatment is administered at an early age.
  • Patient's height should be reevaluated every 4 to 6 months to determine if the growth response is adequate.
  • During the preliminary growth period, the 75th percentile curve for height pace is the proper target as an adequate growth response to GH..

Effect of treatment

Growth :

  • GH therapy started early in childhood have better prognosis.[2]
  • Increase in height continues for more than 2 years even after cessation of treatment.[3]

Bone mass :

  • Children with GH deficiency have low bone mass compared with normal children.
  • To maximize bone mass, it is important to consider the continuation of treatment even after linear growth has ceased until full skeletal development.[4]
  • GH therapy increases bone mass.[5]
  • Without adequate GH replacement, GH deficiency can be associated with low bone mass during adulthood.[6]

Adverse effects of growth hormone therapy

Treatment of children with recombinant human GH has generally been safe.[7][8]

Acute effects :

Chronic effects:

  • There is a possible role for GH in cancer risk especially prostate cancer.[15][16]
  • GH therapy does not increase the risk of leukemia or other cancers compared with the general population.[17]
  • For patients with a primary cancer diagnosis that led to the GH treatment, recombinant GH was associated with an increase in risk for cancer.[17]
  • The increased risk was significant for a variety of secondary cancers including bone, melanoma, kidney, brain, thyroid cancer and leukemia.
  • For children with cancer, guidelines suggest a 12-month period after completion of cancer-directed therapy to confirm that the cancer was eradicated before initiating GH therapy.

Transition of GH treatment from childhood to adults

  • The transition period between childhood treatment and adults treatment begins in late puberty and ends with full adult maturation.
  • Children treated with GH should be retested if they have persistence of GHD near the time of reaching adulthood.
  • Patients with idiopathic GHD usually do not need GH treatment anymore, children with organic causes of GHD usually are found to have GHD on retesting.
  • Retesting involves measurement of IGF-I and stimulation with insulin-induced hypoglycemia or arginine.
  • Most studies have shown benefit of GH treatment in young adults with GHD in body composition, especially the achievement of peak bone mass.

Adult-type GH deficiency treatment

Treatment protocol:

  • GH is administered by subcutaneous injection once a day, usually in the evening.
  • The goal should be to start with low doses and increase gradually until the serum IGF-1 concentration is normal.
  • The eventual goal is to find the GH dose that maintains the serum IGF-1 concentration within the middle of the age-adjusted normal range.[18]
  • If side effects occur or the serum IGF-1 concentration increases to above normal at any dose, the dose should be decreased.

Dosing:

  • The starting dose should be 2 to 5 mcg/kg body weight once daily.

Duration of therapy:

Monitoring:

  • Measurement of serum IGF-1 is probably the best single test of the adequacy of GH treatment.[21]
  • Measurment of serum IGF-1 two months after starting therapy is recommended.
  • GH treatment should increase the serum IGF-1 concentration to within, but not higher than, the age-specific range of normal to avoid over replacement.
  • Once serum IGF-1 is in the normal range, repeat measurements every 6 to 12 months is recommended.
  • If IGF-1 is ever above normal, the GH dose should be decreased by 1 to 2 mcg/kg increments and serum IGF-1 should be repeated every 2 months until it returns to the normal range.

References

  1. ↑ 1.0 1.1 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.
  2. ↑ Carel JC, Ecosse E, Nicolino M, Tauber M, Leger J, Cabrol S; et al. (2002). "Adult height after long term treatment with recombinant growth hormone for idiopathic isolated growth hormone deficiency: observational follow up study of the French population based registry". BMJ. 325 (7355): 70. PMC 117125. PMID 12114235.
  3. ↑ Z. Laron, B. Klinger, S. Anin, A. Pertzelan & P. Lilos (1997). "Growth during and 2 years after stopping GH treatment in prepubertal children with idiopathic short stature". Journal of pediatric endocrinology & metabolism : JPEM. 10 (2): 191–196. PMID 9364352. Unknown parameter |month= ignored (help)
  4. ↑ Conway GS, Szarras-Czapnik M, Racz K, Keller A, Chanson P, Tauber M; et al. (2009). "Treatment for 24 months with recombinant human GH has a beneficial effect on bone mineral density in young adults with childhood-onset GH deficiency". Eur J Endocrinol. 160 (6): 899–907. doi:10.1530/EJE-08-0436. PMID 19324976.
  5. ↑ Bonjour JP, Theintz G, Buchs B, Slosman D, Rizzoli R (1991). "Critical years and stages of puberty for spinal and femoral bone mass accumulation during adolescence". J Clin Endocrinol Metab. 73 (3): 555–63. doi:10.1210/jcem-73-3-555. PMID 1874933.
  6. ↑ Holmes SJ, Economou G, Whitehouse RW, Adams JE, Shalet SM (1994). "Reduced bone mineral density in patients with adult onset growth hormone deficiency". J Clin Endocrinol Metab. 78 (3): 669–74. doi:10.1210/jcem.78.3.8126140. PMID 8126140.
  7. ↑ Saenger P, Attie KM, DiMartino-Nardi J, Hintz R, Frahm L, Frane JW (1998). "Metabolic consequences of 5-year growth hormone (GH) therapy in children treated with GH for idiopathic short stature. Genentech Collaborative Study Group". J Clin Endocrinol Metab. 83 (9): 3115–20. doi:10.1210/jcem.83.9.5089. PMID 9745413.
  8. ↑ Carel JC, Butler G (2010). "Safety of recombinant human growth hormone". Endocr Dev. 18: 40–54. doi:10.1159/000316126. PMID 20523016.
  9. ↑ Youngster I, Rachmiel R, Pinhas-Hamiel O, Bistritzer T, Zuckerman-Levin N, de Vries L; et al. (2012). "Treatment with recombinant human growth hormone during childhood is associated with increased intraocular pressure". J Pediatr. 161 (6): 1116–9. doi:10.1016/j.jpeds.2012.05.024. PMID 22727870.
  10. ↑ Darendeliler F, Karagiannis G, Wilton P (2007). "Headache, idiopathic intracranial hypertension and slipped capital femoral epiphysis during growth hormone treatment: a safety update from the KIGS database". Horm Res. 68 Suppl 5: 41–7. doi:10.1159/000110474. PMID 18174706.
  11. ↑ Blethen SL, Allen DB, Graves D, August G, Moshang T, Rosenfeld R (1996). "Safety of recombinant deoxyribonucleic acid-derived growth hormone: The National Cooperative Growth Study experience". J Clin Endocrinol Metab. 81 (5): 1704–10. doi:10.1210/jcem.81.5.8626820. PMID 8626820.
  12. ↑ Bourguignon JP, Piérard GE, Ernould C, Heinrichs C, Craen M, Rochiccioli P; et al. (1993). "Effects of human growth hormone therapy on melanocytic naevi". Lancet. 341 (8859): 1505–6. PMID 8099381.
  13. ↑ Pitukcheewanont P, Schwarzbach L, Kaufman FR (2002). "Resumption of growth after methionyl-free human growth hormone therapy in a patient with neutralizing antibodies to methionyl human growth hormone". J Pediatr Endocrinol Metab. 15 (5): 653–7. PMID 12014526.
  14. ↑ Cutfield WS, Wilton P, Bennmarker H, Albertsson-Wikland K, Chatelain P, Ranke MB; et al. (2000). "Incidence of diabetes mellitus and impaired glucose tolerance in children and adolescents receiving growth-hormone treatment". Lancet. 355 (9204): 610–3. doi:10.1016/S0140-6736(99)04055-6. PMID 10696981.
  15. ↑ Giovannucci E, Pollak M (2002). "Risk of cancer after growth-hormone treatment". Lancet. 360 (9329): 268–9. doi:10.1016/S0140-6736(02)09561-2. PMID 12147365.
  16. ↑ Swerdlow AJ, Cooke R, Albertsson-Wikland K, Borgström B, Butler G, Cianfarani S; et al. (2015). "Description of the SAGhE Cohort: A Large European Study of Mortality and Cancer Incidence Risks after Childhood Treatment with Recombinant Growth Hormone". Horm Res Paediatr. 84 (3): 172–83. doi:10.1159/000435856. PMC 4611066. PMID 26227295.
  17. ↑ 17.0 17.1 Swerdlow AJ, Cooke R, Beckers D, Borgström B, Butler G, Carel JC; et al. (2017). "Cancer Risks in Patients Treated With Growth Hormone in Childhood: The SAGhE European Cohort Study". J Clin Endocrinol Metab. 102 (5): 1661–1672. doi:10.1210/jc.2016-2046. PMID 28187225.
  18. ↑ Fleseriu M, Hashim IA, Karavitaki N, Melmed S, Murad MH, Salvatori R; et al. (2016). "Hormonal Replacement in Hypopituitarism in Adults: An Endocrine Society Clinical Practice Guideline". J Clin Endocrinol Metab. 101 (11): 3888–3921. doi:10.1210/jc.2016-2118. PMID 27736313.
  19. ↑ Appelman-Dijkstra NM, Claessen KM, Roelfsema F, Pereira AM, Biermasz NR (2013). "Long-term effects of recombinant human GH replacement in adults with GH deficiency: a systematic review". Eur J Endocrinol. 169 (1): R1–14. doi:10.1530/EJE-12-1088. PMID 23572082.
  20. ↑ Filipsson Nyström H, Barbosa EJ, Nilsson AG, Norrman LL, Ragnarsson O, Johannsson G (2012). "Discontinuing long-term GH replacement therapy--a randomized, placebo-controlled crossover trial in adult GH deficiency". J Clin Endocrinol Metab. 97 (9): 3185–95. doi:10.1210/jc.2012-2006. PMID 22791760.
  21. ↑ de Boer H, Blok GJ, Popp-Snijders C, Stuurman L, Baxter RC, van der Veen E (1996). "Monitoring of growth hormone replacement therapy in adults, based on measurement of serum markers". J Clin Endocrinol Metab. 81 (4): 1371–7. doi:10.1210/jcem.81.4.8636336. PMID 8636336.

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