Frans Brandt, Anders Green, Laszlo Hegedüs and Thomas H Brix
The authors and the journal apologise for an error in Figure 2 of this article published in European Journal of Endocrinology (2011) 165 491–497.
Frans Brandt, Anders Green, Laszlo Hegedüs and Thomas H Brix
Overt hyperthyroidism has been associated with cardiac arrhythmias, hypercoagulopathy, stroke, and pulmonary embolism, all of which may increase mortality. Some, but not all, studies show an increased mortality in patients with hyperthyroidism. This inconsistency may be due to differences in study design, characteristics of participants, or confounders. In order to test whether hyperthyroidism influences mortality, we performed a critical review and statistical meta-analysis.
Based on an electronic PubMed search, using the Medical Subject Heading words such as hyperthyroidism, thyrotoxicosis, and mortality or survival, case–control and cohort studies were selected and reviewed. Using meta-analysis, an overall relative risk (RR) of mortality was calculated.
Eight studies fulfilled the inclusion criteria, six of which showed an increased all-cause mortality; seven studies, including 31 138 patients and 4 00 000 person years at risk, allowed calculation of mortality in a meta-analysis. Based on this, the RR of overall mortality was 1.21 (95% confidence interval: 1.05–1.38). Analyses including studies considering setting, treatment, and control for co-morbidity did not significantly alter this finding. As the measured heterogeneity (I2) ranges from 89.1 to 98.3%, which is much higher than the 50% generally viewed on as a threshold, the statistical heterogeneity is very pronounced in the included studies.
In patients diagnosed with hyperthyroidism, mortality is increased by ∼20%. Future studies need to address the cause of hyperthyroidism, impact of type of therapy, time dependency, as well as the potential influence of confounding or genetic susceptibility before the question of causality can be answered.
Frans Brandt, Marianne Thvilum, Dorthe Almind, Kaare Christensen, Anders Green, Laszlo Hegedüs and Thomas Heiberg Brix
Thyroid hormones are essential for the normal development of the fetal brain, while hyperthyroidism in adults is associated with mood symptoms and reduced quality of life. In this study, we aimed to investigate the association and temporal relationship between hyperthyroidism and psychiatric morbidity.
Register-based nationwide cohort study.
Data on hyperthyroidism and psychiatric morbidity were obtained by record linkage of the Danish National Patient Registry and the Danish National Prescription Registry. A total of 2631 hyperthyroid individuals were identified and matched 1:4 with non-hyperthyroid controls and followed for a mean duration of 6 years (range 0–13). Logistic and Cox regression models were used to assess the risk of psychiatric morbidity before and after the diagnosis of hyperthyroidism respectively.
Before the diagnosis of hyperthyroidism, such individuals had an increased risk of being hospitalized with psychiatric diagnoses (odds ratio (OR): 1.33; 95% CI: 0.98–1.80) and an increased risk of being treated with antipsychotics (OR: 1.17; 95% CI: 1.00–1.38), antidepressants (OR: 1.13; 95% CI: 1.01–1.27), or anxiolytics (OR: 1.28; 95% CI: 1.16–1.42). After the diagnosis of hyperthyroidism, there was a higher risk of being hospitalized with psychiatric diagnoses (hazard ratio (HR): 1.51; 95% CI: 1.11–2.05) and an increased risk of being treated with antipsychotics (HR: 1.46; 95% CI: 1.20–1.79), antidepressants (HR: 1.54; 95% CI: 1.36–1.74), or anxiolytics (HR: 1.47; 95% CI: 1.27–1.69).
Hyperthyroid individuals have an increased risk of being hospitalized with psychiatric diagnoses and being treated with antipsychotics, antidepressants, and anxiolytics, both before and after the diagnosis of hyperthyroidism.
Vagn Haas, Margaret Marley, Anders Green, John Date, Mogens Blichert-Toft and Erik F. Mogensen
Abstract. The excretion of urinary iodine was studied in a representative population sample from the county of Funen, Denmark, comprising 505 persons between 25–44 years of age, stratified according to geography, age, and sex. Urine samples were collected for 5 h during late afternoon and early evening. The 24-h iodine excretion was estimated on the basis of iodine and creatinine determinations using correlation equations determined in a pilot study of 50 men and women. The iodine excretion was significantly higher in men: 89 μg/24 h (median) than in women: 76 μg/24 h; the whole population: 85 μg/24 h. No significant differences were observed among the age groups studied. The iodine excretion was significantly higher in people living on small islands: 98 μg/24 h (median) compared with 84 μg/24 h in urban regions and 78 μg/24 h in rural districts. Median iodine excretion per gram of creatinine was 58.8 μg for the whole sample. The iodine excretion for men was 77% higher than reported in an earlier investigation performed in Funen, 1969, but still lower than internationally recommended (WHO).
Kirstine Stochholm, Torben Laursen, Anders Green, Peter Laurberg, Marianne Andersen, Lars Østergaard Kristensen, Ulla Feldt-Rasmussen, Jens Sandahl Christiansen, Morten Frydenberg and Claus Højbjerg Gravholt
To estimate morbidity in Denmark in all patients with GH deficiency (GHD).
Morbidity was analyzed in 1794 GHD patients and 8014 controls matched on age and gender. All records in the GHD patients were studied and additional morbidity noted. Diagnoses and dates of admissions were identified in the National Patient Registry. Lag time until first admission was used as a measure of morbidity. Patients were divided into childhood onset (CO) and adult onset (AO), discriminated by an age cut-off of 18 years at onset of GHD.
Sex- and cause-specific hazard ratios (HRs) in CO and AO GHD compared with controls.
Total morbidity was significantly increased in the GHD patients. HR for CO males: 3.1 (95% confidence interval (CI): 2.7–3.7), CO females: 3.2 (95% CI: 2.6–3.9), AO males: 2.9 (95% CI: 2.6–3.2), and AO females: 3.2 (95% CI: 2.8–3.6). In 18 out of 20 chapters from the International Classification of Diseases-10, a significantly increased morbidity was identified for at least one of the four subgroups of patients. Morbidity was significantly increased in all the four subgroups due to infectious, endocrine, pulmonary, urogenital, and neurological diseases; cancer; diseases of the eye, ear, and circulatory diseases; and traumas. Fractures were significantly increased in AO females, not in males.
Morbidity was significantly increased in the GHD patients. The increased morbidity was due to a variety of disorders, some of which can readily be explained by GHD and other pituitary deficiencies, while others cannot be easily explained.
Kirstine Stochholm, Claus H Gravholt, Torben Laursen, Jens O Jørgensen, Peter Laurberg, Marianne Andersen, Lars Ø Kristensen, Ulla Feldt-Rasmussen, Jens S Christiansen, Morten Frydenberg and Anders Green
Objective: Data on incidence rates are scarce in GH deficiency (GHD). Here, we estimate the incidence rate in childhood onset (CO) and adult onset (AO) GHD in Denmark.
Design: We used three national registries to identify 9131 cases with an increased risk of GHD. Date of entry was defined using the date when a registration had taken place and when a date of sufficient information could be defined from a thorough examination of a record of a GHD patient, which ever came last. We considered date of entry as the incident date.
Methods: Sex-specific incidence rates of GHD in children and adults using the background population as reference.
Results: During 1980–1999, 1823 patients were incident. Three-hundred and three males and 191 females had CO, 744 males and 585 females had AO GHD. The incidence rate over time was stable for females with AO GHD and increasing for the other three subgroups. Average incidence rate for CO males, 2.58 (95% confidence interval (CI), 2.30–2.88), CO females, 1.70 (95% CI, 1.48–1.96), AO males, 1.90 (95% CI, 1.77–2.04), and AO females, 1.42 (95% CI, 1.31–1.54) all per 100 000. The incidence rate was significantly higher in males compared to females in the CO GHD group (P < 0.001) and in the AO GHD group in the age ranges of 45–64 and 65+years (P < 0.001). There was no significant difference in the 18–44 years age group.
Conclusions: In conclusion, we have identified the incidence rates of GHD in a nationwide study of Denmark. In this population-based study, we have identified in CO GHD and in the two oldest age groups of AO GHD, a statistically significant higher incidence rate in males when compared with females.
Kirstine Stochholm, Claus Højbjerg Gravholt, Torben Laursen, Peter Laurberg, Marianne Andersen, Lars Østergaard Kristensen, Ulla Feldt-Rasmussen, Jens Sandahl Christiansen, Morten Frydenberg and Anders Green
Objective: To estimate the mortality in Denmark in patients suffering from GH deficiency (GHD).
Design: Mortality was analyzed in 1794 GHD patients and 8014 controls matched on age and gender. All records in GHD patients were studied and additional morbidity noted. Patients were divided into childhood onset (CO) and adult onset (AO), discriminated by an age cutoff below or above 18 years at onset of GHD.
Method: Data on death were identified in national registries. Sex- and cause-specific mortalities were identified in CO and AO GHD when compared with controls.
Results: Mortality was increased in CO and AO GHD in both genders, when compared with controls. The hazard ratio (HR) for CO males was 8.3 (95% confidence interval (CI) 4.5–15.1) and for females 9.4 (CI 4.6–19.4). For AO males, HR was 1.9 (CI 1.7–2.2) and for females 3.4 (CI 2.9–4.0). We found a significantly higher HR in AO females versus AO males, both compared with controls (P < 0.001). In AO, mortality was increased due to cancer in all subgroups, due to circulatory diseases in all age groups for females and for males in the oldest age group. For CO, the increased mortality was due to cancer.
Conclusions: We found a significantly increased mortality in GHD patients when compared with controls, possibly due to their hypopituitary status. Mortality was increased in AO female patients when compared with males. For CO and AO GHD, different causes of significantly increased mortality were identified.