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      Diagnostic value of a ghrelin test for the diagnosis of GH deficiency after subarachnoid hemorrhage

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          Abstract

          Objective

          To determine the diagnostic value of a ghrelin test in the diagnosis of GH deficiency (GHD) shortly after aneurysmal subarachnoid hemorrhage (SAH).

          Design

          Prospective single-center observational cohort study.

          Methods

          A ghrelin test was assessed after the acute phase of SAH and a GH-releasing hormone (GHRH)–arginine test 6 months post SAH. Primary outcome was the diagnostic value of a ghrelin test compared with the GHRH–arginine test in the diagnosis of GHD. The secondary outcome was to assess the safety of the ghrelin test, including patients' comfort, adverse events, and idiosyncratic reactions.

          Results

          Forty-three survivors of SAH were included (15 males, 35%, mean age 56.6±11.7). Six out of 43 (14%) SAH survivors were diagnosed with GHD by GHRH–arginine test. In GHD subjects, median GH peak during ghrelin test was significantly lower than that of non-GHD subjects (5.4 vs 16.6, P=0.002). Receiver operating characteristics analysis showed an area under the curve of 0.869. A cutoff limit of a GH peak of 15 μg/l corresponded with a sensitivity of 100% and a false-positive rate of 40%. No adverse events or idiosyncratic reactions were observed in subjects undergoing a ghrelin test, except for one subject who reported flushing shortly after ghrelin infusion.

          Conclusion

          Owing to its convenience, validity, and safety, the ghrelin test might be a valuable GH provocative test, especially in the early phase of SAH.

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          Most cited references24

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          Consensus guidelines for the diagnosis and treatment of adults with GH deficiency II: a statement of the GH Research Society in association with the European Society for Pediatric Endocrinology, Lawson Wilkins Society, European Society of Endocrinology, Japan Endocrine Society, and Endocrine Society of Australia.

          Ken Ho (2007)
          The GH Research Society held a Consensus Workshop in Sydney, Australia, 2007 to incorporate the important advances in the management of GH deficiency (GHD) in adults, which have taken place since the inaugural 1997 Consensus Workshop. Two commissioned review papers, previously published Consensus Statements of the Society and key questions were circulated before the Workshop, which comprised a rigorous structure of review with breakout discussion groups. A writing group transcribed the summary group reports for drafting in a plenary forum on the last day. All participants were sent a polished draft for additional comments and gave signed approval to the final revision. Testing for GHD should be extended from hypothalamic-pituitary disease and cranial irradiation to include traumatic brain injury. Testing may indicate isolated GHD; however, idiopathic isolated GHD occurring de novo in the adult is not a recognized entity. The insulin tolerance test, combined administration of GHRH with arginine or growth hormone-releasing peptide, and glucagon are validated GH stimulation tests in the adult. A low IGF-I is a reliable diagnostic indicator of GHD in the presence of hypopituitarism, but a normal IGF-I does not rule out GHD. GH status should be reevaluated in the transition age for continued treatment to complete somatic development. Interaction of GH with other axes may influence thyroid, glucocorticoid, and sex hormone requirements. Response should be assessed clinically by monitoring biochemistry, body composition, and quality of life. There is no evidence that GH replacement increases the risk of tumor recurrence or de novo malignancy.
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            Long-term outcomes of patients with aneurysmal subarachnoid haemorrhage.

            More and more patients survive aneurysmal subarachnoid haemorrhage (aSAH), with case fatality decreasing by 17% in absolute terms over the past three decades and incidence remaining relatively stable at nine per 100,000 patient-years. The mean age at which aSAH occurs is reasonably young at 55 years, and people of this age in the general population have a good life expectancy. However, there are few data for life expectancy after aSAH, and the risks of late recurrent aSAH and other vascular diseases are unclear. The course of associated long-term physical and cognitive deficits after aSAH is not well established, leading to questions about potential outcomes to quality of life and working capacity, as well as best clinical practices. Copyright © 2011 Elsevier Ltd. All rights reserved.
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              Reference ranges for two automated chemiluminescent assays for serum insulin-like growth factor I (IGF-I) and IGF-binding protein 3 (IGFBP-3).

              Assays for insulin-like growth factor I (IGF-I) and IGF-binding protein 3 (IGFBP-3) have become essential tools in the diagnostic work-up of disorders of the somatotropic axis in children and adults. The aim of this study was to evaluate the automated IMMULITE IGF-I and IGFBP-3 assays and to establish reference limits--central 95% intervals, median, 0.1 and other centiles as clinically relevant--as a function of age from 797 females and 787 males, from the first week of life through the ninth decade. Pubertal children were classified by sex and by sexual maturation (Tanner stage). IGF-I and IGFBP-3 levels were also assayed in 20 pediatric patients each with growth hormone deficiency (GHD) and Turner syndrome (UTS), before and during 12 months of recombinant growth hormone (rhGH) therapy, as well as in 11 adult patients with GHD and seven with acromegaly before therapy. Both the IGF-I and IGFBP-3 assays were accurate, specific and sufficiently sensitive to measure IGF-I and IGFBP-3 in serum with good linearity and recovery. In the IGF-I assay, potential interference from IGFBPs was eliminated by blocking with excess IGF-II. Circulating IGF-I and IGFBP-3 concentrations, and their ratio IGF-I/IGFBP-3, were age-dependent, showing low levels immediately after birth, a typical pubertal peak for girls and boys, and a pronounced decline after puberty, reaching a plateau in early adulthood. In adults IGF-I and IGFBP-3 levels decreased smoothly but steadily with age. Children with GHD and UTS had low circulating IGF-I and IGFBP-3 levels which increased to normal reference limits under therapy with rhGH. Adult GHD patients showed IGF-I levels below the age-related median; untreated acromegalic patients mostly had IGF-I and IGFBP-3 levels above the age-related 97.5th centile. In conclusion, the automated IMMULITE IGF-I and IGFBP-3 assays are reliable tools in the diagnosis of pathologies of the GH/IGF axis and in the follow-up of their therapies.

                Author and article information

                Journal
                Eur J Endocrinol
                Eur. J. Endocrinol
                EJE
                European Journal of Endocrinology
                BioScientifica (Bristol )
                0804-4643
                1479-683X
                October 2013
                17 July 2013
                : 169
                : 4
                : 497-502
                Affiliations
                [1]Department of Medicine – Endocrinology Erasmus University Medical Center Rotterdam PO Box 20403000 CA, RotterdamThe Netherlands
                [2]Department of Neurology Erasmus University Medical Center Rotterdam PO Box 20403000 CA, RotterdamThe Netherlands
                [3]Department of Rehabilitation Medicine Erasmus University Medical Center Rotterdam PO Box 20403000 CA, RotterdamThe Netherlands
                [4]Rijndam Rehabilitation Center RotterdamThe Netherlands
                Author notes
                (Correspondence should be addressed to L Khajeh; Email: l.khajeh@ 123456erasmusmc.nl )
                Article
                EJE130436
                10.1530/EJE-13-0436
                3776685
                24037787
                55fe96b5-32cd-42ef-a502-288674585a96
                © 2013 European Society of Endocrinology

                This work is licensed under a Creative Commons Attribution 3.0 Unported License

                History
                : 22 May 2013
                : 31 July 2013
                Categories
                Clinical Study

                Endocrinology & Diabetes
                Endocrinology & Diabetes

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