| 1. |
- Holmer, Helene
(författare)
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Bone health and cardiovascular risk in hypopituitary patients on complete hormone replacement, including GH
- 2007
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Growth hormone deficiency (GHD) is associated with decreased bone mineral density (BMD). Low BMD is correlated to increased fracture risk. There are no studies on fracture risk in GHD patients on GH therapy and no studies on BMD in adults with childhood onset (CO) craniopharyngioma (CP) on GH therapy. We have shown a doubled fracture incidence in CO GHD women and decreased incidence of fractures in adult onset (AO) GHD men. We have also shown decreased BMD in adult women with CO CP on GH therapy, in comparison to matched controls, but not in CO CP men. The cause is not known but insufficient sex steroid and GH replacements, particularly during adolescence, in CO GHD and CP women, and an adequate substitution rate of testosterone and GH in AO GHD and CO CP men are possible explanations. GHD is also associated with increased cardiovascular mortality and morbidity. The impact of long-term GH replacement on cerebral- and cardiovascular diseases and diabetes mellitus (DM) in hypopituitary patients and the prevalence of cardiovascular morbidity and risk factors in adults with childhood onset (CO) craniopharyngioma (CP) are unknown. We have shown that the life-long incidence of non-fatal stroke was tripled in GHD women and doubled in men, but a decline was seen among both genders during the periods where most patients had GH replacement. Life-long incidence of non-fatal cardiac events was similar in the patient and control cohorts, but declined in GHD men during the periods where most patients had GH replacement. GHD women had higher prevalence of type 2 DM and lipid-lowering medication, whereas GHD men had higher prevalence of antihypertensive medication. This cardio-protective medication, together with the GH therapy may have resulted in the decline in non-fatal stroke risk, particularly noted in GHD women, and in significantly lower non-fatal cardiac risk that was seen in GHD men. We have also shown that patients with a CO CP, on GH therapy, had increased cardiovascular morbidity and particularly women were at risk. Of CP women 60% had increased risk for cardiovascular disease. Insulin tolerance test (ITT) is the recommended test for diagnosing GHD. We have shown that GHD patients during an ITT had very low nadir blood glucose levels and few symptoms of hypoglycemia and in 31% unawareness was seen. If the ITT is still going to be recommended, we ask for more uniform recommendations.
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| 2. |
- Holmer, Helene, et al.
(författare)
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Fracture incidence in GH-deficient patients on complete hormone replacement including GH
- 2007
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Ingår i: Journal of Bone and Mineral Research. - : Wiley. - 0884-0431 .- 1523-4681. ; 22:12, s. 1842-1850
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Tidskriftsartikel (refereegranskat)abstract
- Fracture risk in GHD patients is not definitely established. Studying fracture incidence in 832 patients on GH therapy and 2581 matched population controls, we recorded a doubled fracture risk in CO GHD women, but a significantly lower fracture risk in AO GHD men. Introduction: The objective of this study was to evaluate fracture incidence in patients wilh confirmed growth hormone deficiency (GHD) on replacement therapy (including growth hormone [GH]) compared with population controls, while also taking potential confounders and effect modifiers into account. Materials and Methods: Eight hundred thirty-two patients with GHD and 2581 matched population controls answered a questionnaire about fractures and other background information. Incidence rate ratio (IRR) and 95% CI for first fracture were estimated. The median time on GH therapy for childhood onset (CO) GHD men and women was 15 and 12 yr, respectively, and 6 and 5 yr for adult onset (AO) GHD men and women, respectively. Results: A more than doubled risk (IRR, 2.29; 95% CI, 1.23-4.28) for nonosteoporotic fractures was recorded in women with CO GHD, whereas no risk increase was observed among CO GHD men (IRR. 0.61) and AO GHD women (IRR, 1.08). A significantly decreased incidence of fractures (IRR, 0.54; 95% CI 0.34-0.86) was recorded in AO GHD men. Conclusions: Increased fracture risk in CO GHD women can most likely be explained by interaction between oral estrogen and the GH-IGF-I axis. The adequate substitution rate of testosterone (90%) and GH (94%) may have resulted in significantly lower fracture risk in AO GHD men.
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| 3. |
- Holmer, Helene, et al.
(författare)
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Hypothalamic involvement predicts cardiovascular risk in adults with childhood onset craniopharyngioma on long-term GH therapy.
- 2009
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Ingår i: European Journal of Endocrinology. - 0804-4643 .- 1479-683X. ; 16, s. 671-679
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Tidskriftsartikel (refereegranskat)abstract
- Context: Craniopharyngioma patients without GH therapy are at an increased cardiovascular disease (CVD) risk and particularly concerning women. No previous study on long-term GH therapy in adults with childhood onset (CO) craniopharyngioma was identified. Objective: To investigate CVD risk in adults with CO craniopharyngioma on complete hormone replacement, including long-term GH therapy, and to investigate the impact of disease-related factors on CVD risk. Design and participants: In a cross-sectional study of operated CO craniopharyngiomas (1958–2000) from a defined area of Sweden (2.5 million), we enrolled 42 patients (20 women) with a median age of 28 years (range 17–57) and assessed CVD risk of 20 (4–40) years after first operation. Comparisons were made with matched controls and between patients with tumor growth into the third ventricle (TGTV) versus non-TGTV. GH therapy was 10–12 years in women and men. Results: In comparison with controls, both male and female patients had increased body mass index, fat mass, insulin, and leptin levels. Overall, while not significantly increased in male patients, 55–60% of female patients had a medium–high CVD risk, compared with 10–20% in controls. An increased CVD risk (all P<0.05) and higher levels of fat mass and insulin were recorded in the TGTV group versus the non-TGTV group. Late puberty induction and lack of androgens were shown in female patients. Conclusions: Adult patients with CO craniopharyngioma, especially those with TGTV, have persistently increased CVD risk. Conventional hormone substitution, including GH, is insufficient to normalize CVD risk, suggesting an important role for irreversible hypothalamic dysfunction.
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| 4. |
- Holmer, Helene, et al.
(författare)
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Nonfatal stroke, cardiac disease, and diabetes mellitus in hypopituitary patients on hormone replacement including growth hormone
- 2007
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Ingår i: Journal of Clinical Endocrinology and Metabolism. - : The Endocrine Society. - 1945-7197 .- 0021-972X. ; 92:9, s. 3560-3567
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Tidskriftsartikel (refereegranskat)abstract
- Context: The impact of long-term GH replacement on cerebrovascular and cardiovascular diseases and diabetes mellitus in hypopituitary patients is unknown. Objective: The incidence of nonfatal stroke and cardiac events, and prevalence of type 2 diabetes mellitus ( T2D) and cardioprotective medication were compared between cohorts of GH-deficient (GHD) patients and population controls. Design and Participants: The incidence of nonfatal stroke and cardiac events was estimated retrospectively from questionnaires in 750 GHD patients and 2314 matched population controls. A prevalence of T2D and cardioprotective medication was recorded at the distribution of questionnaires. Time since first pituitary deficiency to start of GH therapy was 4 and 2 yr, and time on GH therapy was 6 yr for GHD women and men, respectively. Results: Lifelong incidence of nonfatal stroke was tripled in GHD women and doubled in GHD men, but a decline was seen in both genders during periods after first pituitary hormone deficiency and GHD, during which most patients had GH therapy. The lifelong incidence of nonfatal cardiac events declined in GHD men during first pituitary hormone deficiency and GHD periods. GHD women had a higher prevalence of T2D and lipid-lowering medication, whereas GHD men had a higher prevalence of antihypertensive medication. Conclusions: The declined risks of nonfatal stroke in both genders and of nonfatal cardiac events in GHD men during periods on GH replacement may be caused by prescription of cardioprotective drugs and 6-yr GH replacement. GHD women had an increased prevalence of T2D, partly attributed to higher body mass index and lower physical activity.
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