| 1. |
- Nordenström, Anna, et al.
(författare)
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Are carriers of CYP21A2 mutations less vulnerable to psychological stress? A population-based national cohort study
- 2016
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Ingår i: Clinical Endocrinology. - Stockholm : Karolinska Institutet, Dept of Medical Epidemiology and Biostatistics. - 0300-0664 .- 1365-2265.
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Tidskriftsartikel (refereegranskat)abstract
- Background: Congenital adrenal hyperplasia (CAH) is one of the most common monogenic autosomal recessive disorders with an incidence of one in 15 000. About one in 70 individuals in the general population are carriers of a severe CYP21A2 mutation. It has been suggested that this confers a survival advantage, perhaps as a result of increased activity in the hypothalamic–pituitary–adrenal axis. We investigated vulnerability to psychological stress in obligate carriers. Method: The Swedish CAH Registry encompasses more than 600 patients. Parents, that is obligate carriers of the CYP21A2 mutation, were identified through the Multigeneration Register. The diagnosis of the child was used as the psychological stressor. Psychiatric diagnoses before and after the birth of a child with CAH were compared to those of controls derived from (i) the general population, (ii) parents of children with hypospadias and (iii) parents of children with diabetes mellitus type 1 (T1DM). Results: Parents of children with CAH had less risk of being diagnosed with any psychiatric disorder (OR, 0 6), an affective disorder (OR, 0 5) or substance misuse (OR, 0 5) after the diagnosis of the child, compared to the general population. Their risk was also decreased compared to parents of a child with hypospadias (OR, 0 6, 0 4 and 0 2, respectively) and parents of a child with T1DM (OR 0 7, 0 6 and 0 2, respectively). The CYP21A2 carriers had a lower risk of developing mood and stress-related disorders after the diagnosis of the child. Conclusion: Obligate CYP21A2 carriers had a reduced risk of a psychiatric diagnosis and were less vulnerable to a psychologically stressful situation, at least with respect to receiving a psychiatric diagnosis. This indicates a better ability to cope with psychological stress among heterozygous carriers of severe CYP21A2 mutations, which may contribute to the apparent survival advantage
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| 2. |
- Almqvist, Erik, et al.
(författare)
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Increase of bioavailable testosterone is associated with gain in bone mineral density after cure of primary hyperparathyroidism in postmenopausal women
- 2006
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Ingår i: Clinical Endocrinology. - : Wiley. - 1365-2265 .- 0300-0664. ; 64:1, s. 58-62
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Tidskriftsartikel (refereegranskat)abstract
- Objective The recovery of bone mineral density (BMD) after surgical cure of primary hyperparathyroidism (PHPT) seems to be multifactorial and not just dependent on declining PTH. The aim of the present study was to evaluate the role of sex steroids in this context. Design and patients Thirty-six postmenopausal women with PHPT were examined before and 1 year after curative parathyroidectomy. Their mean age at inclusion in the study was 71.7 +/- 1.1 years (range 54-83). BMD was measured in hip and lumbar spine using dual energy X-ray absorptiometry. No patient received any replacement therapy with sex hormones or treatment with corticosteroids, oestrogen receptor modulators or bisphosphonates. Measurements Serum concentrations of oestradiol, testosterone, androstenedione, dehydroepiandrosterone sulphate, SHBG, PTH and calcium. Results Postoperative increase of free (bioavailable) testosterone was positively correlated to the change of BMD in the hip (P < 0.01), whereas the change of PTH in serum correlated to the change of BMD in the lumbar spine (P < 0.05). Multiple regression analysis showed that bioavailable testosterone was the most important determinant of change in BMD in both spine and hip (femoral neck: P < 0.05; Ward's triangle: P < 0.001; trochanter: P < 0.01; lumbar spine: P < 0.05). The increase of bioavailable testosterone after curative parathyroidectomy was related to declining SHBG. Conclusions An increase of bioavailable testosterone following surgical cure of PHPT is related to improvement of hip and lumbar spine BMD in postmenopausal women. This previously unknown hormonal interaction may also be important to other aspects of hyperparathyroidism.
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| 3. |
- Almqvist, Erik, et al.
(författare)
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Increased plasma concentrations of N-terminal pro-B-type natriuretic peptide in patients with mild primary hyperparathyroidism.
- 2006
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Ingår i: Clinical endocrinology. - : Wiley. - 0300-0664 .- 1365-2265. ; 65:6, s. 760-6
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Primary hyperparathyroidism (PHPT) is associated with heart disease. The aims of the present study were to evaluate how cardiac function and secretion of N-terminal pro-B-type natriuretic peptide (NT-proBNP) correlate in patients with mild PHPT, and how the plasma level of NT-proBNP is influenced by cure of the parathyroid disease. DESIGN AND PATIENTS: Forty-two patients with PHPT without symptoms of heart disease were examined before and 1 year after curative parathyroidectomy. MEASUREMENTS: Plasma or serum concentrations of NT-proBNP, calcium, PTH, creatinine, oestradiol, testosterone and SHBG were measured. Cardiac function was evaluated by equilibrium radionuclide angiography (ERNA). RESULTS: At baseline, NT-proBNP levels correlated negatively with systolic function [left ventricular ejection fraction (LVEF), P < 0.001]. Twelve per cent of the patients had NT-proBNP levels above normal reference values preoperatively. One year postoperatively, the corresponding proportion was 21%. The mean plasma concentration of NT-proBNP increased after parathyroidectomy (P < 0.01) in parallel with a dip in diastolic function (peak filling rate, P < 0.05) and a falling trend in systolic function (LVEF, P = 0.08). The postoperative percentage changes in circulating NT-proBNP and total oestradiol correlated positively (P < 0.05). CONCLUSIONS: Patients with mild PHPT and normal renal function may have high levels of circulating NT-proBNP despite the absence of symptomatic heart disease. Cure of the parathyroid disease is followed by a further increase in NT-proBNP secretion in parallel with ERNA measures, indicating subclinical changes in heart function. These results are in line with data indicating an association between PHPT and increased risk of premature death.
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| 4. |
- Birgander, Mats, et al.
(författare)
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Adrenergic and cardiac dysfunction in primary hyperparathyroidism.
- 2012
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Ingår i: Clinical Endocrinology. - : Wiley. - 1365-2265 .- 0300-0664. ; 76, s. 189-195
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Primary hyperparathyroidism (PHPT) is associated with cardiovascular morbidity and premature death but the underlying mechanisms are incompletely understood. The aim of this study was to investigate if adrenergic dysfunction may be a contributing factor. Patients and methods: Forty-nine patients with mild PHPT (serum calcium 2.7 ± 0.1 mmol/L) and 48 control subjects, matched for age and sex, were examined; patients within 1 month before parathyroidectomy (PTX) and 6 months postoperatively; control subjects at inclusion. Heart rate variability (HRV) was analyzed in 24-hour electrocardiograms, and plasma concentrations of epinephrine and norepinephrine were measured at rest and immediately after standardized physical tests. Results: At baseline, the patients showed, compared to the controls, reduced stress-related increase of circulating epinephrine (P < 0.05) and norepinephrine (P < 0.05). No significant change was observed 6 months after PTX. At baseline, there were no significant differences between patients and controls in HRV or heart rate but 6 months after curative PTX, the patients showed significantly reduced HRV in both frequency and time domain, and their maximum and average heart rate had decreased (P = 0.011 and P = 0.018, respectively). The patients with the highest preoperative levels of circulating parathyroid hormone showed the greatest changes in heart rate and HRV postoperatively. Conclusions: This study demonstrates a previously unknown impairment of catecholamine response to physical stress in PHPT along with changes of HRV, also indicating adrenergic dysfunction. These factors should be considered in the ongoing controversy regarding the management of patients with mild "asymptomatic" PHPT.
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| 5. |
- Bülow, Birgitta, et al.
(författare)
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High incidence of mental disorders, reduced mental well-being and cognitive function in hypopituitary women with GH deficiency treated for pituitary disease
- 2002
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Ingår i: Clinical Endocrinology. - : Wiley. - 1365-2265 .- 0300-0664. ; 56:2, s. 183-193
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Previous studies have shown possible neuroendocrine effects of GH. In the present study we investigated the incidence of mental disorders and the prevalence of mental distress and cognitive dysfunction in hypopituitary women with untreated GH deficiency compared to population-based controls.DESIGN AND PATIENTS: Thirty-three hypopituitary women with a median age of 64 years (range 39--77 years) were investigated cross-sectionally, without any change in hormone substitutions. Twenty-nine of the patients had been operated for a pituitary tumour, 25 had received radiotherapy and 15 had visual dysfunction. The patients were with a very high probability GH deficient, as 29 had subnormal IGF-I levels and the other four were GH deficient as assessed by an insulin tolerance test. The patients were compared with 33 controls matched for sex, age, smoking habits, educational level and residence.MEASUREMENTS: The incidence of mental disorders was calculated from the date of diagnosed hypopituitarism to the time of the present investigation. Mental well-being was assessed by three self-rating questionnaires: the Symptom Checklist-90 (SCL-90), the Interview Schedule for Social Interaction (ISSI) and the social network concept. The subjects were examined with neuropsychological tests of vocabulary (SRB:1 vocabulary test), perceptual speed (WAIS-R Digit Symbol), spatial ability (WAIS-R Block Design), verbal memory (Cronholm--Molander verbal memory test), spatial learning (Austin Maze Test) and reaction time (APT Two-way Reaction Time and APT Inhibition).RESULTS: The hypopituitary women had a higher incidence of mental disorders than the controls; Incidence Rate Ratio 4.5 (95% CI 1.0--21). The Global Severity Index, i.e. the average score of all 90 questions of the SCL-90, was higher in patients (P = 0.001), and the patients had significantly more symptoms of somatization, anxiety, depression, obsession--compulsion, hostility--irritability, phobic and psychotic symptoms (all P less-than-or-equal 0.04). Moreover, 14 patients compared to four controls were classified as possible cases of mental distress according to the SCL-90 (P = 0.006). The patients experienced lower availability of both social attachment (P = 0.02) and integration (P = 0.001), but there were no group differences in the adequacy of these dimensions or in emotional support. The patients had lower scores in four of seven neuropsychological tests (all P less-than-or-equal 0.04).CONCLUSIONS: The hypopituitary women had a higher incidence of mental disorders, more symptoms of mental distress and increased prevalence of cognitive dysfunction. The impaired results in the patients could possibly be explained by several factors, such as transfrontal surgery, radiotherapy, visual dysfunction and unphysiological hormone substitution. Moreover, it is probable that GH deficiency contributed, but placebo-controlled double-blind studies are warranted to investigate whether the psychological dysfunction is reversible on GH substitution.
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| 6. |
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| 7. |
- Bülow, B, et al.
(författare)
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The gender differences in growth hormone-binding protein and leptin persist in 80-year-old men and women and is not caused by sex hormones.
- 2003
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Ingår i: Clinical Endocrinology. - : Wiley. - 1365-2265 .- 0300-0664. ; 59:4, s. 6-482
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Tidskriftsartikel (refereegranskat)abstract
- objective Leptin and growth hormone-binding protein (GHBP) both show gender differences that might be explained by sex hormones. To study the potential relevance of oestradiol and testosterone, we have examined 80-year-old subjects in whom oestradiol is higher in men than in women. The interrelationships between leptin, insulin, GHBP and fat mass in this age group were also investigated. design and subjects Ninety-four subjects (55 females and 39 males), all 80 years old, were investigated in a community-based study. None of the investigated subjects was being treated for diabetes mellitus and none of the women had oestrogen replacement. methods Levels of testosterone, oestradiol, SHBG, IGF-I, GHBP, glucose, insulin and leptin were analysed. Body composition was measured with bioimpedance analysis (BIA). results As in younger age groups, serum leptin, the ratio leptin/kilogram fat mass and serum GHBP were higher in the women (all, P <= 0·007), although serum oestradiol was higher in the men (P < 0·001). There were no significant associations between sex hormones and leptin or GHBP either in women or in men (all, r < 0·13, P > 0·1). Leptin correlated to kilogram fat mass in both women (r = 0·55, P < 0·001) and men (r = 0·47, P = 0·003), but in contrast, there were no significant correlations between GHBP and fat mass and GHBP and IGF-I, either in women or in men (all, r < 0·24, P > 0·2). Insulin and leptin were significantly associated with GHBP, both in women (r = 0·48, P < 0·001 and r = 0·43, P = 0·001, respectively) and in men (r = 0·40, P = 0·01 and r = 0·34, P = 0·03, respectively). conclusions Although the 80-year-old men had higher oestradiol levels than the women, the women had higher levels of leptin and GHBP. There were no correlations between sex hormones and leptin and GHBP, which indicates that the gender differences are not caused by sex hormones in old age. In contrast to studies in younger subjects, GHBP did not correlate to fat mass in the investigated 80-year-old men and women. In the older subjects investigated, as in younger subjects, GHBP was significantly correlated with leptin and insulin.
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| 8. |
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| 9. |
- Crump, Casey, et al.
(författare)
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PRETERM BIRTH AND RISK OF MEDICALLY TREATED HYPOTHYROIDISM IN YOUNG ADULTHOOD.
- 2011
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Ingår i: Clinical Endocrinology. - : Wiley. - 1365-2265 .- 0300-0664. ; 75, s. 255-260
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Previous studies suggest that low birth weight is associated with thyroid autoimmunity and hypothyroidism in later life, but the potential effect of preterm birth, independent of fetal growth, is unknown. Our objective was to determine whether preterm birth is independently associated with medically treated hypothyroidism in young adulthood. Design/Participants: National cohort study of 629,806 individuals born in Sweden from 1973 through 1979, including 27,935 born preterm (<37 weeks). Measurements: Thyroid hormone prescription during 2005-2009 (ages 25.5-37.0 years), obtained from all outpatient and inpatient pharmacies throughout Sweden. Results: Preterm birth was associated with increased relative odds of thyroid hormone prescription in young adulthood, after adjusting for fetal growth and other potential confounders. This association appeared stronger among twins than singletons (P=0.04 for the interaction). Twins had increased relative odds across the full range of preterm gestational ages, whereas singletons had increased relative odds only if born very preterm (23-31 weeks). Among twins and singletons, respectively, adjusted odds ratios for individuals born preterm (<37 weeks) were 1.54 (95% CI, 1.11-2.14) and 1.08 (95% CI, 0.98-1.19), and for individuals born very preterm (23-31 weeks) were 2.62 (95% CI, 1.30-5.27) and 1.59 (95% CI, 1.18-2.14), relative to full-term births. Conclusions: This national cohort study suggests that preterm birth is associated with an increased risk of medically treated hypothyroidism in young adulthood. This association was independent of fetal growth and appeared stronger among twins than singletons. Additional studies are needed to confirm these new findings in other populations and to elucidate the mechanisms.
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