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  • Author: Niels Birkebæk x
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Jelena Stankovic Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Aarhus, Denmark

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Kurt Kristensen Steno Diabetes Center Aarhus (SDCA), Aarhus University Hospital, Aarhus, Denmark
Department of Pediatrics, Aarhus University Hospital, Aarhus, Denmark

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Niels Birkebæk Department of Pediatrics, Aarhus University Hospital, Aarhus, Denmark

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Jens Otto Lunde Jørgensen Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Aarhus, Denmark

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Esben Søndergaard Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Aarhus, Denmark
Steno Diabetes Center Aarhus (SDCA), Aarhus University Hospital, Aarhus, Denmark

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Background

The diagnosis of the polyuria–polydipsia syndrome is challenging. Copeptin is a robust biomarker of arginine vasopressin (AVP) secretion. Arginine, which stimulates growth hormone (GH), has been shown also to stimulate copeptin secretion via unknown mechanisms.

Aim

The aim was to investigate copeptin levels in response to three different GH stimulation tests in patients suspected of GH deficiency.

Methods

In this cross-sectional study, we measured plasma copeptin levels at baseline and at 60, 105, and 150 min in patients undergoing a stimulation test for growth hormone deficiency with either arginine (n = 16), clonidine (n = 8) or the insulin tolerance test (ITT) (n = 10).

Results

In patients undergoing the arginine test, the mean age was 9 years, and 10 years for clonidine. The ITT was only performed in adult patients (>18 years) with a mean age of 49 years. Copeptin level increased significantly from baseline to 60 min after arginine (P <0.01) and ITT (P < 0.01). By contrast, copeptin level tended to decrease after clonidine stimulation (P = 0.14).

Conclusion

These data support that infusion of arginine increases plasma copeptin levels and reveal a comparable response after an ITT. We hypothesize that the underlying mechanism is abrogation of somatostatin-induced AVP suppression.

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Mette Marie Baunsgaard Department of Clinical Medicine, Aarhus University, Aarhus, Denmark
Department of Pediatrics and Adolescent Medicine, Aarhus University Hospital, Aarhus, Denmark

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Anne Sophie Lind Helligsoe Department of Clinical Medicine, Aarhus University, Aarhus, Denmark
Department of Pediatrics and Adolescent Medicine, Aarhus University Hospital, Aarhus, Denmark

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Louise Tram Henriksen Department of Clinical Medicine, Aarhus University, Aarhus, Denmark
Department of Pediatrics and Adolescent Medicine, Aarhus University Hospital, Aarhus, Denmark

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Torben Stamm Mikkelsen Department of Clinical Medicine, Aarhus University, Aarhus, Denmark
Department of Pediatrics and Adolescent Medicine, Aarhus University Hospital, Aarhus, Denmark

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Michael Callesen Department of Paediatrics, Odense University Hospital, Odense, Funen, Denmark

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Britta Weber The Danish Center for Particle Therapy, Aarhus University Hospital, Aarhus, Denmark

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Henrik Hasle Department of Clinical Medicine, Aarhus University, Aarhus, Denmark
Department of Pediatrics and Adolescent Medicine, Aarhus University Hospital, Aarhus, Denmark

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Niels Birkebæk Department of Clinical Medicine, Aarhus University, Aarhus, Denmark
Department of Pediatrics and Adolescent Medicine, Aarhus University Hospital, Aarhus, Denmark
Steno Diabetes Center Aarhus, Aarhus University Hospital, Aarhus, Denmark

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Objective

Growth hormone deficiency (GHD) is the most common endocrine late effect in irradiated survivors of childhood brain tumors. This study aimed to determine the prevalence of GHD in adults treated with proton or photon irradiation for a brain tumor in childhood and to detect undiagnosed GHD.

Design

This study is a cross-sectional study.

Methods

We investigated GHD in 5-year survivors from two health regions in Denmark treated for childhood brain tumors with cranial or craniospinal irradiation in the period 1997–2015. Medical charts were reviewed for endocrinological and other health data. Survivors without a growth hormone (GH) test at final height were invited to a GH stimulation test.

Results

Totally 41 (22 females) survivors with a median age of 21.7 years (range: 15.1–33.8 years) at follow-up and 14.8 years (range: 5.1–23.4 years) since diagnosis were included; 11 were treated with proton and 30 with photon irradiation; 18 of 21 survivors were previously found to have GHD; 16 of 20 survivors with no GH test at final height were tested, 8 (50 %) had GHD. In total, 26 of 41 patients (63%) had GHD. Insulin-like growth factor-1 (IGF-1) is associated poorly with the insulin tolerance test (ITT).

Conclusion

This study identified a high prevalence of undiagnosed GHD in survivors with no GH test at final height. The results stress the importance of screening for GHD at final height in survivors of childhood brain tumors with prior exposure to cranial irradiation, irrespective of radiation modality and IGF-1.

Significance statement

This cross-sectional study reports a prevalence of 63% of GHD in irradiated childhood brain tumor survivors. Furthermore, the study identified a considerable number of long-term survivors without a GH test at final height, of whom, 50% subsequently were shown to have undiagnosed GHD. Additionally, this study confirmed that a normal serum IGF-1 measurement cannot exclude the diagnosis of GHD in irradiated survivors. This illustrates the need for improvements in the diagnostic approach to GHD after reaching final height in childhood brain tumor survivors at risk of GHD. In summary, our study stresses the need for GHD testing in all adult survivors treated with cranial irradiation for a brain tumor in childhood irrespective of radiation modality.

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