Hexarelin as a test of pituitary reserve in patients with pituitary disease
BACKGROUND The insulin tolerance test (ITT) is the reference standard for the diagnosis of cortisol and growth hormone (GH) deficiency, but problems have occurred in small children in inexperienced hands and it is contraindicated in patients with cardiac disease and epilepsy. Hexarelin is a growth h...
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| Veröffentlicht in: | Clinical endocrinology (Oxford) 1999-09, Vol.51 (3), p.369-375 |
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| creator | Korbonits, Márta Kaltsas, Gregory Perry, Leslie A. Grossman, Ashley B. Monson, John P. Besser, G. Michael Trainer, Peter J. |
| description | BACKGROUND
The insulin tolerance test (ITT) is the reference standard for the diagnosis of cortisol and growth hormone (GH) deficiency, but problems have occurred in small children in inexperienced hands and it is contraindicated in patients with cardiac disease and epilepsy. Hexarelin is a growth hormone‐releasing peptide with GH‐, ACTH/cortisol‐ and prolactin‐releasing effects which involve both hypothalamic and direct pituitary mechanisms. We therefore investigated whether it could be used to test GH and ACTH/cortisol reserve in patients with pituitary disease.
METHODS AND SUBJECTS
The changes in GH and cortisol in response to insulin‐induced hypoglycaemia (intravenous human Actrapid 0.15 IU/kg) and hexarelin (2 μg/kg) in 19 patients with possible pituitary disease (5 males, mean age 39 years, range 21–70) were compared. The patients' responses during the hexarelin test were also compared to normal ranges of GH and cortisol responses established in healthy volunteers following hexarelin administration.
RESULTS AND DISCUSSION
GH peak levels were significantly higher after hexarelin than after hypoglycaemia (mean ± SEM; 67.1 ± 16 vs. 26.9 ± 6.8 mU/l respectively; P |
| doi_str_mv | 10.1046/j.1365-2265.1999.00828.x |
| format | Article |
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The insulin tolerance test (ITT) is the reference standard for the diagnosis of cortisol and growth hormone (GH) deficiency, but problems have occurred in small children in inexperienced hands and it is contraindicated in patients with cardiac disease and epilepsy. Hexarelin is a growth hormone‐releasing peptide with GH‐, ACTH/cortisol‐ and prolactin‐releasing effects which involve both hypothalamic and direct pituitary mechanisms. We therefore investigated whether it could be used to test GH and ACTH/cortisol reserve in patients with pituitary disease.
METHODS AND SUBJECTS
The changes in GH and cortisol in response to insulin‐induced hypoglycaemia (intravenous human Actrapid 0.15 IU/kg) and hexarelin (2 μg/kg) in 19 patients with possible pituitary disease (5 males, mean age 39 years, range 21–70) were compared. The patients' responses during the hexarelin test were also compared to normal ranges of GH and cortisol responses established in healthy volunteers following hexarelin administration.
RESULTS AND DISCUSSION
GH peak levels were significantly higher after hexarelin than after hypoglycaemia (mean ± SEM; 67.1 ± 16 vs. 26.9 ± 6.8 mU/l respectively; P < 0.001), while cortisol levels were significantly lower (420 ± 34 vs. 605 ± 50 nmol/l; P < 0.001). The peak responses of both hormones correlated significantly between the hexarelin and insulin‐induced hypoglycaemia tests (r = 0.80, P < 0.001 for cortisol). Peak GH levels after hexarelin and ITT showed a significant positive correlation with IGF‐I levels (r = 0.84 and r = 0.77, P < 0.001 for both). All patients with a subnormal GH response to hexarelin (<41.4 mU/l) had a peak GH response to ITT of <9 mU/l, and only one patient had a normal (although borderline) response to hexarelin with a subnormal GH response to the ITT. Although 17 of the 19 patients had corresponding cortisol responses to hexarelin and the ITT test (either failing or passing both), two patients had normal cortisol responses to hexarelin but subnormal responses to the ITT. A peak serum cortisol level following hypoglycaemia of >580 nmol/l is indicative of normal cortisol reserve, as established in patients undergoing surgery; only five of the normal volunteers and one of the thirteen patients with a normal ACTH/cortisol reserve on ITT had a peak cortisol >580 nmol/l in response to hexarelin.
CONCLUSION
Adult patients who have a subnormal peak GH response to hexarelin are likely to be GH deficient on an insulin tolerance test. However, our data suggest that the hexarelin test is not a useful test of ACTH/cortisol reserve. The hexarelin test could be a useful first/screening test to diagnose adult GH deficiency, particularly in patients in whom an insulin tolerance test is contraindicated or who are already ACTH deficient and in whom the GH reserve alone is of interest.]]></description><identifier>ISSN: 0300-0664</identifier><identifier>EISSN: 1365-2265</identifier><identifier>DOI: 10.1046/j.1365-2265.1999.00828.x</identifier><identifier>PMID: 10469018</identifier><identifier>CODEN: CLECAP</identifier><language>eng</language><publisher>Oxford BSL: Blackwell Science Ltd</publisher><subject>Adrenocorticotropic Hormone - blood ; Adult ; Aged ; Biological and medical sciences ; Female ; Functional investigation of endocrine glands and genital system ; Growth Hormone - blood ; Humans ; Hydrocortisone - blood ; Insulin ; Investigative techniques, diagnostic techniques (general aspects) ; Male ; Medical sciences ; Middle Aged ; Oligopeptides ; Pituitary Diseases - physiopathology ; Pituitary Gland - physiopathology ; Predictive Value of Tests</subject><ispartof>Clinical endocrinology (Oxford), 1999-09, Vol.51 (3), p.369-375</ispartof><rights>1999 INIST-CNRS</rights><rights>Copyright Blackwell Scientific Publications Ltd. Sep 1999</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4588-c64f8c27e6f80c6a46b0ecb41da8935eb14c6e1fe8c9915928cd8eb9c56d01103</citedby><cites>FETCH-LOGICAL-c4588-c64f8c27e6f80c6a46b0ecb41da8935eb14c6e1fe8c9915928cd8eb9c56d01103</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1046%2Fj.1365-2265.1999.00828.x$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1046%2Fj.1365-2265.1999.00828.x$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,776,780,1411,27901,27902,45550,45551</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=1947298$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/10469018$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Korbonits, Márta</creatorcontrib><creatorcontrib>Kaltsas, Gregory</creatorcontrib><creatorcontrib>Perry, Leslie A.</creatorcontrib><creatorcontrib>Grossman, Ashley B.</creatorcontrib><creatorcontrib>Monson, John P.</creatorcontrib><creatorcontrib>Besser, G. Michael</creatorcontrib><creatorcontrib>Trainer, Peter J.</creatorcontrib><title>Hexarelin as a test of pituitary reserve in patients with pituitary disease</title><title>Clinical endocrinology (Oxford)</title><addtitle>Clinical Endocrinology</addtitle><description><![CDATA[BACKGROUND
The insulin tolerance test (ITT) is the reference standard for the diagnosis of cortisol and growth hormone (GH) deficiency, but problems have occurred in small children in inexperienced hands and it is contraindicated in patients with cardiac disease and epilepsy. Hexarelin is a growth hormone‐releasing peptide with GH‐, ACTH/cortisol‐ and prolactin‐releasing effects which involve both hypothalamic and direct pituitary mechanisms. We therefore investigated whether it could be used to test GH and ACTH/cortisol reserve in patients with pituitary disease.
METHODS AND SUBJECTS
The changes in GH and cortisol in response to insulin‐induced hypoglycaemia (intravenous human Actrapid 0.15 IU/kg) and hexarelin (2 μg/kg) in 19 patients with possible pituitary disease (5 males, mean age 39 years, range 21–70) were compared. The patients' responses during the hexarelin test were also compared to normal ranges of GH and cortisol responses established in healthy volunteers following hexarelin administration.
RESULTS AND DISCUSSION
GH peak levels were significantly higher after hexarelin than after hypoglycaemia (mean ± SEM; 67.1 ± 16 vs. 26.9 ± 6.8 mU/l respectively; P < 0.001), while cortisol levels were significantly lower (420 ± 34 vs. 605 ± 50 nmol/l; P < 0.001). The peak responses of both hormones correlated significantly between the hexarelin and insulin‐induced hypoglycaemia tests (r = 0.80, P < 0.001 for cortisol). Peak GH levels after hexarelin and ITT showed a significant positive correlation with IGF‐I levels (r = 0.84 and r = 0.77, P < 0.001 for both). All patients with a subnormal GH response to hexarelin (<41.4 mU/l) had a peak GH response to ITT of <9 mU/l, and only one patient had a normal (although borderline) response to hexarelin with a subnormal GH response to the ITT. Although 17 of the 19 patients had corresponding cortisol responses to hexarelin and the ITT test (either failing or passing both), two patients had normal cortisol responses to hexarelin but subnormal responses to the ITT. A peak serum cortisol level following hypoglycaemia of >580 nmol/l is indicative of normal cortisol reserve, as established in patients undergoing surgery; only five of the normal volunteers and one of the thirteen patients with a normal ACTH/cortisol reserve on ITT had a peak cortisol >580 nmol/l in response to hexarelin.
CONCLUSION
Adult patients who have a subnormal peak GH response to hexarelin are likely to be GH deficient on an insulin tolerance test. However, our data suggest that the hexarelin test is not a useful test of ACTH/cortisol reserve. The hexarelin test could be a useful first/screening test to diagnose adult GH deficiency, particularly in patients in whom an insulin tolerance test is contraindicated or who are already ACTH deficient and in whom the GH reserve alone is of interest.]]></description><subject>Adrenocorticotropic Hormone - blood</subject><subject>Adult</subject><subject>Aged</subject><subject>Biological and medical sciences</subject><subject>Female</subject><subject>Functional investigation of endocrine glands and genital system</subject><subject>Growth Hormone - blood</subject><subject>Humans</subject><subject>Hydrocortisone - blood</subject><subject>Insulin</subject><subject>Investigative techniques, diagnostic techniques (general aspects)</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Middle Aged</subject><subject>Oligopeptides</subject><subject>Pituitary Diseases - physiopathology</subject><subject>Pituitary Gland - physiopathology</subject><subject>Predictive Value of Tests</subject><issn>0300-0664</issn><issn>1365-2265</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1999</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNkNGK1DAUhoMo7rj6ChJEvGs9aZM0AW9kWHfUZUVZEbwJaXqKGTvtbNK6s29vaod18cqrBPL9f875CKEMcgZcvt7mrJQiKwopcqa1zgFUofLDA7K6e3hIVlACZCAlPyFPYtwCgFBQPSYnc4kGplbk4wYPNmDne2ojtXTEONKhpXs_Tn604ZYGjBh-IU3E3o4e-zHSGz_-uIc0PqKN-JQ8am0X8dnxPCVf351drTfZxafz9-u3F5njQqnMSd4qV1QoWwVOWi5rQFdz1lilS4E1404ia1E5rZnQhXKNwlo7IRtgDMpT8mrp3YfhekoDm52PDrvO9jhM0UhdgOJSJPDFP-B2mEKfZjNMqyopUDJBaoFcGGIM2Jp98Lu0lmFgZlFma2apZpZqZtvmj21zSNHnx_6p3mFzL7joTcDLI2Cjs10bbO98_MtpXhV6xt4s2I3v8Pa__zfrs8t0SfFsifs44uEubsNPI6uyEubb5bn5IL7ozefvzFyVvwExh6lm</recordid><startdate>199909</startdate><enddate>199909</enddate><creator>Korbonits, Márta</creator><creator>Kaltsas, Gregory</creator><creator>Perry, Leslie A.</creator><creator>Grossman, Ashley B.</creator><creator>Monson, John P.</creator><creator>Besser, G. Michael</creator><creator>Trainer, Peter J.</creator><general>Blackwell Science 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>AAYXX</scope><scope>CITATION</scope><scope>7QP</scope><scope>K9.</scope><scope>NAPCQ</scope><scope>7X8</scope></search><sort><creationdate>199909</creationdate><title>Hexarelin as a test of pituitary reserve in patients with pituitary disease</title><author>Korbonits, Márta ; Kaltsas, Gregory ; Perry, Leslie A. ; Grossman, Ashley B. ; Monson, John P. ; Besser, G. Michael ; Trainer, Peter J.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4588-c64f8c27e6f80c6a46b0ecb41da8935eb14c6e1fe8c9915928cd8eb9c56d01103</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1999</creationdate><topic>Adrenocorticotropic Hormone - blood</topic><topic>Adult</topic><topic>Aged</topic><topic>Biological and medical sciences</topic><topic>Female</topic><topic>Functional investigation of endocrine glands and genital system</topic><topic>Growth Hormone - blood</topic><topic>Humans</topic><topic>Hydrocortisone - blood</topic><topic>Insulin</topic><topic>Investigative techniques, diagnostic techniques (general aspects)</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Middle Aged</topic><topic>Oligopeptides</topic><topic>Pituitary Diseases - physiopathology</topic><topic>Pituitary Gland - physiopathology</topic><topic>Predictive Value of Tests</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Korbonits, Márta</creatorcontrib><creatorcontrib>Kaltsas, Gregory</creatorcontrib><creatorcontrib>Perry, Leslie A.</creatorcontrib><creatorcontrib>Grossman, Ashley B.</creatorcontrib><creatorcontrib>Monson, John P.</creatorcontrib><creatorcontrib>Besser, G. Michael</creatorcontrib><creatorcontrib>Trainer, Peter J.</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>CrossRef</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>Korbonits, Márta</au><au>Kaltsas, Gregory</au><au>Perry, Leslie A.</au><au>Grossman, Ashley B.</au><au>Monson, John P.</au><au>Besser, G. Michael</au><au>Trainer, Peter J.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Hexarelin as a test of pituitary reserve in patients with pituitary disease</atitle><jtitle>Clinical endocrinology (Oxford)</jtitle><addtitle>Clinical Endocrinology</addtitle><date>1999-09</date><risdate>1999</risdate><volume>51</volume><issue>3</issue><spage>369</spage><epage>375</epage><pages>369-375</pages><issn>0300-0664</issn><eissn>1365-2265</eissn><coden>CLECAP</coden><abstract><![CDATA[BACKGROUND
The insulin tolerance test (ITT) is the reference standard for the diagnosis of cortisol and growth hormone (GH) deficiency, but problems have occurred in small children in inexperienced hands and it is contraindicated in patients with cardiac disease and epilepsy. Hexarelin is a growth hormone‐releasing peptide with GH‐, ACTH/cortisol‐ and prolactin‐releasing effects which involve both hypothalamic and direct pituitary mechanisms. We therefore investigated whether it could be used to test GH and ACTH/cortisol reserve in patients with pituitary disease.
METHODS AND SUBJECTS
The changes in GH and cortisol in response to insulin‐induced hypoglycaemia (intravenous human Actrapid 0.15 IU/kg) and hexarelin (2 μg/kg) in 19 patients with possible pituitary disease (5 males, mean age 39 years, range 21–70) were compared. The patients' responses during the hexarelin test were also compared to normal ranges of GH and cortisol responses established in healthy volunteers following hexarelin administration.
RESULTS AND DISCUSSION
GH peak levels were significantly higher after hexarelin than after hypoglycaemia (mean ± SEM; 67.1 ± 16 vs. 26.9 ± 6.8 mU/l respectively; P < 0.001), while cortisol levels were significantly lower (420 ± 34 vs. 605 ± 50 nmol/l; P < 0.001). The peak responses of both hormones correlated significantly between the hexarelin and insulin‐induced hypoglycaemia tests (r = 0.80, P < 0.001 for cortisol). Peak GH levels after hexarelin and ITT showed a significant positive correlation with IGF‐I levels (r = 0.84 and r = 0.77, P < 0.001 for both). All patients with a subnormal GH response to hexarelin (<41.4 mU/l) had a peak GH response to ITT of <9 mU/l, and only one patient had a normal (although borderline) response to hexarelin with a subnormal GH response to the ITT. Although 17 of the 19 patients had corresponding cortisol responses to hexarelin and the ITT test (either failing or passing both), two patients had normal cortisol responses to hexarelin but subnormal responses to the ITT. A peak serum cortisol level following hypoglycaemia of >580 nmol/l is indicative of normal cortisol reserve, as established in patients undergoing surgery; only five of the normal volunteers and one of the thirteen patients with a normal ACTH/cortisol reserve on ITT had a peak cortisol >580 nmol/l in response to hexarelin.
CONCLUSION
Adult patients who have a subnormal peak GH response to hexarelin are likely to be GH deficient on an insulin tolerance test. However, our data suggest that the hexarelin test is not a useful test of ACTH/cortisol reserve. The hexarelin test could be a useful first/screening test to diagnose adult GH deficiency, particularly in patients in whom an insulin tolerance test is contraindicated or who are already ACTH deficient and in whom the GH reserve alone is of interest.]]></abstract><cop>Oxford BSL</cop><pub>Blackwell Science Ltd</pub><pmid>10469018</pmid><doi>10.1046/j.1365-2265.1999.00828.x</doi><tpages>7</tpages></addata></record> |
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| ispartof | Clinical endocrinology (Oxford), 1999-09, Vol.51 (3), p.369-375 |
| issn | 0300-0664 1365-2265 |
| language | eng |
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| source | Wiley Online Library - AutoHoldings Journals; MEDLINE |
| subjects | Adrenocorticotropic Hormone - blood Adult Aged Biological and medical sciences Female Functional investigation of endocrine glands and genital system Growth Hormone - blood Humans Hydrocortisone - blood Insulin Investigative techniques, diagnostic techniques (general aspects) Male Medical sciences Middle Aged Oligopeptides Pituitary Diseases - physiopathology Pituitary Gland - physiopathology Predictive Value of Tests |
| title | Hexarelin as a test of pituitary reserve in patients with pituitary disease |
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