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Control of growth hormone and IGF1 in patients with acromegaly in the UK: responses to medical treatment with somatostatin analogues and dopamine agonists
Objective We investigated the control of GH and IGF1 in acromegaly in routine clinical practice in the UK on and off medical treatment. Design The UK Acromegaly Register collected routine biochemical and clinical data on patients with acromegaly from 31 UK centres with GH data covering >30y. Pati...
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| Published in: | Clinical endocrinology (Oxford) 2013-11, Vol.79 (5), p.689-699 |
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| container_title | Clinical endocrinology (Oxford) |
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| creator | Howlett, Trevor A. Willis, Debbie Walker, Gillian Wass, John A. H. Trainer, Peter J. |
| description | Objective
We investigated the control of GH and IGF1 in acromegaly in routine clinical practice in the UK on and off medical treatment.
Design
The UK Acromegaly Register collected routine biochemical and clinical data on patients with acromegaly from 31 UK centres with GH data covering >30y.
Patients
We identified 2572 patients. Somatostatin analogues (SMS) were used in 40·6% and dopamine agonists (DA) in 41·4%.
Measurements
We identified 29,181 GH records linked to data on IGF1, surgery, radiotherapy and medical treatment and derived data on 9900 distinct Periods of Care including 4206 courses of medical treatment. We considered GH controlled when ≤2 μg/l.
Results
Control of GH and IGF1 improved over time, particularly on medical treatment. Control on medical treatment was better after prior surgery and/or radiotherapy. On long‐term SMS, GH was controlled in 75%, IGF1 in 69% and both in 55%; on long‐term DA, GH control was similar but IGF1 worse (77%/55%/45%). Responses to long‐term treatment with octreotide LAR and lanreotide autogel were broadly similar, but we noted a failure to escalate SMS to maximal effective dose. Increasing precourse GH levels were associated with a decreasing proportion who achieved control, despite greater suppression from baseline.
Conclusions
Control of acromegaly in the UK is improving, but ‘safe’ GH levels are still only achieved in 75% on long‐term medical treatment, with GH and IGF1 both normalized in no more than 55% on SMS and 36% on cabergoline. It remains unclear whether the control of GH, but not IGF1, observed in many patients is sufficient to restore long‐term morbidity and mortality to normal. |
| doi_str_mv | 10.1111/cen.12207 |
| format | article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_proquest_miscellaneous_1443386663</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>1443386663</sourcerecordid><originalsourceid>FETCH-LOGICAL-i3827-fcf8449b88bb9d2612da97f123ccb020e52c515ea71c528ccc0dd806377c8a243</originalsourceid><addsrcrecordid>eNpdkc1uEzEUhS0EoqGw4AWQJYTEZlr_jH_CDo2aUKiKBBQkNpbH40lcZuzBdhTyKjwtThOKhDe2dL9zz_W5ADzH6AyXc26sP8OEIPEAzDDlrCKEs4dghihCFeK8PgFPUrpFCDGJxGNwQigTNRN0Bn43wecYBhh6uIphm9dwHeIYvIXad_ByucDQeTjp7KzPCW5dIbSJYbQrPez2tby28ObDGxhtmoJPNsEc4Gg7Z_QAc7Q6j0V6UKYw6hxSLu18MdBDWG2KYG_VhUmPbu-7Ct6lnJ6CR70ekn12vE_BzeLiS_Ouuvq4vGzeXlWOSiKq3vSyruetlG077wjHpNNz0WNCjWkRQZYRwzCzWmDDiDTGoK6TiFMhjNSkpqfg9aHvFMPPMk1Wo0vGDoP2NmySwnVNqeSc04K-_A-9DZtYvlEoRuZMoDmShXpxpDZtyUFN0Y067tTf1Avw6gjoVELqo_bGpX-cEKKWNSnc-YHbusHu7usYqf3aVVm7ulu7ai6u7x5FUR0UJUD7616h4w_FBRVMfbteqs_NJ774-v67WtI_Nemvfw</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1529570908</pqid></control><display><type>article</type><title>Control of growth hormone and IGF1 in patients with acromegaly in the UK: responses to medical treatment with somatostatin analogues and dopamine agonists</title><source>Wiley-Blackwell Journals</source><creator>Howlett, Trevor A. ; Willis, Debbie ; Walker, Gillian ; Wass, John A. H. ; Trainer, Peter J.</creator><creatorcontrib>Howlett, Trevor A. ; Willis, Debbie ; Walker, Gillian ; Wass, John A. H. ; Trainer, Peter J. ; UK Acromegaly Register Study Group (UKAR-3)</creatorcontrib><description>Objective
We investigated the control of GH and IGF1 in acromegaly in routine clinical practice in the UK on and off medical treatment.
Design
The UK Acromegaly Register collected routine biochemical and clinical data on patients with acromegaly from 31 UK centres with GH data covering >30y.
Patients
We identified 2572 patients. Somatostatin analogues (SMS) were used in 40·6% and dopamine agonists (DA) in 41·4%.
Measurements
We identified 29,181 GH records linked to data on IGF1, surgery, radiotherapy and medical treatment and derived data on 9900 distinct Periods of Care including 4206 courses of medical treatment. We considered GH controlled when ≤2 μg/l.
Results
Control of GH and IGF1 improved over time, particularly on medical treatment. Control on medical treatment was better after prior surgery and/or radiotherapy. On long‐term SMS, GH was controlled in 75%, IGF1 in 69% and both in 55%; on long‐term DA, GH control was similar but IGF1 worse (77%/55%/45%). Responses to long‐term treatment with octreotide LAR and lanreotide autogel were broadly similar, but we noted a failure to escalate SMS to maximal effective dose. Increasing precourse GH levels were associated with a decreasing proportion who achieved control, despite greater suppression from baseline.
Conclusions
Control of acromegaly in the UK is improving, but ‘safe’ GH levels are still only achieved in 75% on long‐term medical treatment, with GH and IGF1 both normalized in no more than 55% on SMS and 36% on cabergoline. It remains unclear whether the control of GH, but not IGF1, observed in many patients is sufficient to restore long‐term morbidity and mortality to normal.</description><identifier>ISSN: 0300-0664</identifier><identifier>EISSN: 1365-2265</identifier><identifier>DOI: 10.1111/cen.12207</identifier><identifier>PMID: 23574573</identifier><identifier>CODEN: CLECAP</identifier><language>eng</language><publisher>Oxford: Blackwell Publishing Ltd</publisher><subject>Acromegaly - blood ; Acromegaly - drug therapy ; Adolescent ; Adult ; Aged ; Aged, 80 and over ; Biological and medical sciences ; Child ; Child, Preschool ; Dopamine ; Dopamine Agonists - therapeutic use ; Endocrinopathies ; Female ; Fundamental and applied biological sciences. Psychology ; Growth Hormone - blood ; Growth hormones ; Humans ; Hypothalamus. Hypophysis. Epiphysis (diseases) ; Insulin-Like Growth Factor I - metabolism ; Male ; Medical sciences ; Medical treatment ; Middle Aged ; Non tumoral diseases. Target tissue resistance. Benign neoplasms ; Pituitary gland ; Radiation therapy ; Somatostatin - analogs & derivatives ; Somatostatin - therapeutic use ; Vertebrates: endocrinology ; Young Adult</subject><ispartof>Clinical endocrinology (Oxford), 2013-11, Vol.79 (5), p.689-699</ispartof><rights>2013 John Wiley & Sons Ltd</rights><rights>2014 INIST-CNRS</rights><rights>2013 John Wiley & Sons Ltd.</rights><rights>Copyright © 2013 John Wiley & Sons Ltd</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1111%2Fcen.12207$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1111%2Fcen.12207$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>315,786,790,27957,27958,50923,51032</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=27774842$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23574573$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Howlett, Trevor A.</creatorcontrib><creatorcontrib>Willis, Debbie</creatorcontrib><creatorcontrib>Walker, Gillian</creatorcontrib><creatorcontrib>Wass, John A. H.</creatorcontrib><creatorcontrib>Trainer, Peter J.</creatorcontrib><creatorcontrib>UK Acromegaly Register Study Group (UKAR-3)</creatorcontrib><title>Control of growth hormone and IGF1 in patients with acromegaly in the UK: responses to medical treatment with somatostatin analogues and dopamine agonists</title><title>Clinical endocrinology (Oxford)</title><addtitle>Clin Endocrinol</addtitle><description>Objective
We investigated the control of GH and IGF1 in acromegaly in routine clinical practice in the UK on and off medical treatment.
Design
The UK Acromegaly Register collected routine biochemical and clinical data on patients with acromegaly from 31 UK centres with GH data covering >30y.
Patients
We identified 2572 patients. Somatostatin analogues (SMS) were used in 40·6% and dopamine agonists (DA) in 41·4%.
Measurements
We identified 29,181 GH records linked to data on IGF1, surgery, radiotherapy and medical treatment and derived data on 9900 distinct Periods of Care including 4206 courses of medical treatment. We considered GH controlled when ≤2 μg/l.
Results
Control of GH and IGF1 improved over time, particularly on medical treatment. Control on medical treatment was better after prior surgery and/or radiotherapy. On long‐term SMS, GH was controlled in 75%, IGF1 in 69% and both in 55%; on long‐term DA, GH control was similar but IGF1 worse (77%/55%/45%). Responses to long‐term treatment with octreotide LAR and lanreotide autogel were broadly similar, but we noted a failure to escalate SMS to maximal effective dose. Increasing precourse GH levels were associated with a decreasing proportion who achieved control, despite greater suppression from baseline.
Conclusions
Control of acromegaly in the UK is improving, but ‘safe’ GH levels are still only achieved in 75% on long‐term medical treatment, with GH and IGF1 both normalized in no more than 55% on SMS and 36% on cabergoline. It remains unclear whether the control of GH, but not IGF1, observed in many patients is sufficient to restore long‐term morbidity and mortality to normal.</description><subject>Acromegaly - blood</subject><subject>Acromegaly - drug therapy</subject><subject>Adolescent</subject><subject>Adult</subject><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Biological and medical sciences</subject><subject>Child</subject><subject>Child, Preschool</subject><subject>Dopamine</subject><subject>Dopamine Agonists - therapeutic use</subject><subject>Endocrinopathies</subject><subject>Female</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Growth Hormone - blood</subject><subject>Growth hormones</subject><subject>Humans</subject><subject>Hypothalamus. Hypophysis. Epiphysis (diseases)</subject><subject>Insulin-Like Growth Factor I - metabolism</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Medical treatment</subject><subject>Middle Aged</subject><subject>Non tumoral diseases. Target tissue resistance. Benign neoplasms</subject><subject>Pituitary gland</subject><subject>Radiation therapy</subject><subject>Somatostatin - analogs & derivatives</subject><subject>Somatostatin - therapeutic use</subject><subject>Vertebrates: endocrinology</subject><subject>Young Adult</subject><issn>0300-0664</issn><issn>1365-2265</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><recordid>eNpdkc1uEzEUhS0EoqGw4AWQJYTEZlr_jH_CDo2aUKiKBBQkNpbH40lcZuzBdhTyKjwtThOKhDe2dL9zz_W5ADzH6AyXc26sP8OEIPEAzDDlrCKEs4dghihCFeK8PgFPUrpFCDGJxGNwQigTNRN0Bn43wecYBhh6uIphm9dwHeIYvIXad_ByucDQeTjp7KzPCW5dIbSJYbQrPez2tby28ObDGxhtmoJPNsEc4Gg7Z_QAc7Q6j0V6UKYw6hxSLu18MdBDWG2KYG_VhUmPbu-7Ct6lnJ6CR70ekn12vE_BzeLiS_Ouuvq4vGzeXlWOSiKq3vSyruetlG077wjHpNNz0WNCjWkRQZYRwzCzWmDDiDTGoK6TiFMhjNSkpqfg9aHvFMPPMk1Wo0vGDoP2NmySwnVNqeSc04K-_A-9DZtYvlEoRuZMoDmShXpxpDZtyUFN0Y067tTf1Avw6gjoVELqo_bGpX-cEKKWNSnc-YHbusHu7usYqf3aVVm7ulu7ai6u7x5FUR0UJUD7616h4w_FBRVMfbteqs_NJ774-v67WtI_Nemvfw</recordid><startdate>201311</startdate><enddate>201311</enddate><creator>Howlett, Trevor A.</creator><creator>Willis, Debbie</creator><creator>Walker, Gillian</creator><creator>Wass, John A. H.</creator><creator>Trainer, Peter J.</creator><general>Blackwell Publishing Ltd</general><general>Blackwell</general><general>Wiley Subscription Services, Inc</general><scope>BSCLL</scope><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>7QP</scope><scope>K9.</scope><scope>NAPCQ</scope><scope>7X8</scope></search><sort><creationdate>201311</creationdate><title>Control of growth hormone and IGF1 in patients with acromegaly in the UK: responses to medical treatment with somatostatin analogues and dopamine agonists</title><author>Howlett, Trevor A. ; Willis, Debbie ; Walker, Gillian ; Wass, John A. H. ; Trainer, Peter J.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-i3827-fcf8449b88bb9d2612da97f123ccb020e52c515ea71c528ccc0dd806377c8a243</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>Acromegaly - blood</topic><topic>Acromegaly - drug therapy</topic><topic>Adolescent</topic><topic>Adult</topic><topic>Aged</topic><topic>Aged, 80 and over</topic><topic>Biological and medical sciences</topic><topic>Child</topic><topic>Child, Preschool</topic><topic>Dopamine</topic><topic>Dopamine Agonists - therapeutic use</topic><topic>Endocrinopathies</topic><topic>Female</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Growth Hormone - blood</topic><topic>Growth hormones</topic><topic>Humans</topic><topic>Hypothalamus. Hypophysis. Epiphysis (diseases)</topic><topic>Insulin-Like Growth Factor I - metabolism</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Medical treatment</topic><topic>Middle Aged</topic><topic>Non tumoral diseases. Target tissue resistance. Benign neoplasms</topic><topic>Pituitary gland</topic><topic>Radiation therapy</topic><topic>Somatostatin - analogs & derivatives</topic><topic>Somatostatin - therapeutic use</topic><topic>Vertebrates: endocrinology</topic><topic>Young Adult</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Howlett, Trevor A.</creatorcontrib><creatorcontrib>Willis, Debbie</creatorcontrib><creatorcontrib>Walker, Gillian</creatorcontrib><creatorcontrib>Wass, John A. H.</creatorcontrib><creatorcontrib>Trainer, Peter J.</creatorcontrib><creatorcontrib>UK Acromegaly Register Study Group (UKAR-3)</creatorcontrib><collection>Istex</collection><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Premium</collection><collection>MEDLINE - Academic</collection><jtitle>Clinical endocrinology (Oxford)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Howlett, Trevor A.</au><au>Willis, Debbie</au><au>Walker, Gillian</au><au>Wass, John A. H.</au><au>Trainer, Peter J.</au><aucorp>UK Acromegaly Register Study Group (UKAR-3)</aucorp><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Control of growth hormone and IGF1 in patients with acromegaly in the UK: responses to medical treatment with somatostatin analogues and dopamine agonists</atitle><jtitle>Clinical endocrinology (Oxford)</jtitle><addtitle>Clin Endocrinol</addtitle><date>2013-11</date><risdate>2013</risdate><volume>79</volume><issue>5</issue><spage>689</spage><epage>699</epage><pages>689-699</pages><issn>0300-0664</issn><eissn>1365-2265</eissn><coden>CLECAP</coden><notes>Novartis Ltd</notes><notes>Appendix S1. Further details of the Register Database and Data-Processing Algorithms. Table S1. Discrepancies in on-treatment flags in the GH export table. Table S2. Summary of GH levels and control of GH and IGF1 in Periods of Care, stratified by Treatment Status and Era. Table S3. Responses of GH and IGF1 to treatment with SMS and DA in treatment courses during the 2000s: (a) Percentages achieving biochemical control. (b) Distribution of GH levels. Table S4. Responses of GH and IGF1 during treatment courses with different types of somatostatin analogue in the 1990s and 2000s: (a) Percentages achieving biochemical control, (b) Distribution of GH levels. Table S5. Patient characteristics and pre-treatment GH levels in courses of lanreotide autogel compared to octreotide LAR. Table S6. (a) Summary Dose Information for Lanreotide Autogel courses in the 2000s. Table S7. Responses of GH and IGF1 during treatment courses with bromocriptine and cabergoline: (a) Percentages achieving biochemical control. (b) Distribution of GH levels. Table S8. Sequence of use of different classes of GH-lowering drugs in individual patients analysed at the point of last period of care on medical treatment, and stratified by the era of that treatment course. Table S9. Control of GH and IGF1 by DA and SMS in 1990s and 2000s, stratified by the mean GH level in the period of care off treatment prior to the current treatment course. Table S10. Control of GH and IGF1 by DA and SMS in 1990s and 2000s, stratified by the mean GH level in the period of care before any medical, surgical or radiotherapy treatment.</notes><notes>ark:/67375/WNG-SCR6FVJZ-G</notes><notes>ArticleID:CEN12207</notes><notes>istex:C9943720A7C805BB36531D84E55AF70A9AAEFD33</notes><notes>ObjectType-Article-1</notes><notes>SourceType-Scholarly Journals-1</notes><notes>ObjectType-Feature-2</notes><notes>content type line 23</notes><abstract>Objective
We investigated the control of GH and IGF1 in acromegaly in routine clinical practice in the UK on and off medical treatment.
Design
The UK Acromegaly Register collected routine biochemical and clinical data on patients with acromegaly from 31 UK centres with GH data covering >30y.
Patients
We identified 2572 patients. Somatostatin analogues (SMS) were used in 40·6% and dopamine agonists (DA) in 41·4%.
Measurements
We identified 29,181 GH records linked to data on IGF1, surgery, radiotherapy and medical treatment and derived data on 9900 distinct Periods of Care including 4206 courses of medical treatment. We considered GH controlled when ≤2 μg/l.
Results
Control of GH and IGF1 improved over time, particularly on medical treatment. Control on medical treatment was better after prior surgery and/or radiotherapy. On long‐term SMS, GH was controlled in 75%, IGF1 in 69% and both in 55%; on long‐term DA, GH control was similar but IGF1 worse (77%/55%/45%). Responses to long‐term treatment with octreotide LAR and lanreotide autogel were broadly similar, but we noted a failure to escalate SMS to maximal effective dose. Increasing precourse GH levels were associated with a decreasing proportion who achieved control, despite greater suppression from baseline.
Conclusions
Control of acromegaly in the UK is improving, but ‘safe’ GH levels are still only achieved in 75% on long‐term medical treatment, with GH and IGF1 both normalized in no more than 55% on SMS and 36% on cabergoline. It remains unclear whether the control of GH, but not IGF1, observed in many patients is sufficient to restore long‐term morbidity and mortality to normal.</abstract><cop>Oxford</cop><pub>Blackwell Publishing Ltd</pub><pmid>23574573</pmid><doi>10.1111/cen.12207</doi><tpages>11</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Clinical endocrinology (Oxford), 2013-11, Vol.79 (5), p.689-699 |
| issn | 0300-0664 1365-2265 |
| language | eng |
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| source | Wiley-Blackwell Journals |
| subjects | Acromegaly - blood Acromegaly - drug therapy Adolescent Adult Aged Aged, 80 and over Biological and medical sciences Child Child, Preschool Dopamine Dopamine Agonists - therapeutic use Endocrinopathies Female Fundamental and applied biological sciences. Psychology Growth Hormone - blood Growth hormones Humans Hypothalamus. Hypophysis. Epiphysis (diseases) Insulin-Like Growth Factor I - metabolism Male Medical sciences Medical treatment Middle Aged Non tumoral diseases. Target tissue resistance. Benign neoplasms Pituitary gland Radiation therapy Somatostatin - analogs & derivatives Somatostatin - therapeutic use Vertebrates: endocrinology Young Adult |
| title | Control of growth hormone and IGF1 in patients with acromegaly in the UK: responses to medical treatment with somatostatin analogues and dopamine agonists |
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