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Biomedical subjects

Leif Mosekilde

Publications and source records attributed to Leif Mosekilde.

At least 73 records · Page 4Linked to original sources
PubMed2003

Hyperthyroidism, bone mineral, and fracture risk--a meta-analysis.

This study examined changes in bone mineral and fracture risk after treatment for hyperthyroidism in a meta-analysis. The PubMed and EMBASE were searched using the MESH terms "hyperthyroidism," "bone mineral density" (BMD), and "fracture," resulting in retrieval of 289 references. Twenty references describing BMD and five describing fracture risk were included in the meta-analysis. BMD was significantly decreased in patients with untreated hyperthyroidism. Upon treatment BMD increased significantly and reversed to normal levels with a temporary increase above normal levels 1-4 years after diagnosis. The risk of hip fractures increased significantly with age at diagnosis of hyperthyroidism. The hip fracture risk after diagnosis predicted from studies on BMD was close to that observed in clinical studies comparing fracture risk in hyperthyroid patients with normal controls. Thus BMD is significantly decreased and fracture risk increased in untreated hyperthyroidism. Upon normalization of the hyperthyroid state BMD return to normal even though no specific antiosteoporotic measures are taken other than normalizing the hyperthyroid state.

Age Factors↗
PubMed2003

Age-related changes in cortical bone content of insulin-like growth factor binding protein (IGFBP)-3, IGFBP-5, osteoprotegerin, and calcium in postmenopausal osteoporosis: a cross-sectional study.

Serum GH and IGF-I levels decline with increasing age, whereas osteoprotegerin (OPG) increases. IGFs as well as OPG are present in bone matrix and mediate the effects of many upstream hormones (e.g. estrogen). To evaluate whether changes in these proteins may to some extent explain the decrease in bone mass in postmenopausal or senile osteoporosis, we measured bone contents of IGF-I, IGF-II, IGF binding protein (IGFBP)-3, IGFBP-5, and OPG in combined extracts obtained after EDTA and guanidine hydrochloride extraction in 60 postmenopausal women aged 47-74 (mean, 63) yr with a previous distal forearm fracture and a hip or spine Z-score less than 0. We found age-related increases in IGFBP-3 (r = 0.35; P < 0.01), IGFBP-5 (r = 0.59; P < 0.001), and OPG (r = 0.36; P < 0.01) in cortical bone, significantly inversely correlated with femoral neck and lumbar spine BMD. A correlation between age and OPG was also detected in trabecular bone (r = 0.27; P < 0.05). A pronounced age-related decrease in cortical calcium contents (r = -0.60; P < 0.001), positively correlated with femoral neck and lumbar spine BMD, was also found. No age-related changes were detected for IGF-I or IGF-II. The present study demonstrates age-related changes in cortical bone contents of IGFBPs, calcium, and OPG, possibly related to the pathophysiology of postmenopausal osteoporosis. As for OPG, our findings probably represent compensatory responses to increased osteoclastic resorption.

Age Factors↗
PubMed2003

A common methylenetetrahydrofolate reductase (C677T) polymorphism is associated with low bone mineral density and increased fracture incidence after menopause: longitudinal data from the Danish osteoporosis prevention study.

A polymorphism in the gene encoding methylenetetrahydrofolate reductase (MTHFR) has recently been associated with bone mineral density (BMD) in postmenopausal Japanese women. It is not known whether this effect is also present in European populations and whether it is caused by lower peak bone mass or accelerated postmenopausal bone loss. MTHFR genotyping was done in 1748 healthy postmenopausal Danish women participating in a prospective study of risk factors for osteoporosis. At the time of enrollment, 3-24 months after last menstrual period, the less prevalent genotype (TT, 8.7% of the population) was associated with significantly lower BMD at the femoral neck (ANOVA, p < 0.05), total hip (p < 0.01), and spine (p < 0.05 adjusted for lifestyle covariates, p = 0.06 without adjustment). The mean difference was between 0.1 and 0.3 SD, depending on measurement site. MTHFR genotype added significantly to prediction of BMD by weight and age. Fracture incidence was increased more than 2-fold in subjects with the TT genotype (risk ratio [RR], 2.6; 95% CI 1.2-5.6). This remained significant when the Cox analysis was controlled for BMD (RR, 2.4; 95% CI 1.1-5.2). No differences in serum osteocalcin, bone-specific alkaline phosphatase, and 25-OH-vitamin D were found between genotypes. The response to hormone replacement therapy (HRT) did not differ, but the association of the TT genotype with reduced BMD was maintained at the total hip after 5 years of HRT. The MTHFR TT genotype is associated with low BMD and increased fracture incidence in early postmenopausal women.

Alleles↗
PubMed2003

Standardization of BMD T-Scores in the first five years after the menopause: do femoral neck-equivalent and older normative range T-Scores improve diagnostic agreement?

Calculating T-scores using an older reference population reduces inconsistency between measurement sites when osteoporosis is diagnosed in the elderly. The present analysis in a younger, early postmenopausal cohort examined 5-yr consistency of normalization by local and femoral neck-equivalent T-scores. NHANES (femur) and Hologic (spine and forearm) references were applied to baseline, 1-, 2-, 3-, and 5-yr scans in 925 untreated women in a national cohort study, and alternative local and neck-equivalent scores calculated. The baseline prevalence of osteopenia/osteoporosis was 35.5%/4.1% (spine), 31.0%/1.2% (neck), 31.3%/1.2% (total hip), and 37.2%/2.5% (forearm). It increased to 54.6%/7% by combining sites. The prevalences at 5-yr were 57.2%/12.4% (spine), 51.9%/5.0% (neck), 46.6%/3.7% (total hip), 52.5%/7.4% (forearm), and 77.3%/17.8% (any). A T-score cut-off at the lowest of four sites of -1.65 for osteopenia and -3.37 for osteoporosis was equivalent in patient numbers to T<-1 and T<-2.5 at the femoral neck. The proportion of inconsistently classified subjects decreased from 48% to 42% (p<0.05) with neck-equivalent scores. No improvement remained after 5 yr. Kappa scores did not improve by the use of local or femoral neck scores. In conclusion, adjusted thresholds cannot remove the anatomic discrepancy between T-scores. To overcome this problem, risk-based diagnostic cut-offs must therefore be calculated separately for each measurement site and fracture localization.

Absorptiometry, Photon↗
PubMed2002

Risk of renal stone events in primary hyperparathyroidism before and after parathyroid surgery: controlled retrospective follow up study.

AIM: To study the risk of renal stone episodes and risk factors for renal stones in primary hyperparathyroidism before and after surgery. DESIGN: Register based, controlled retrospective follow up study. SETTING: Tertiary hospitals in Denmark. PARTICIPANTS: 674 consecutive patients with surgically verified primary hyperparathyroidism. Each patient was compared with three age- and sex-matched controls randomly drawn from the background population. Hospital admissions for renal stone disease were compared between patients and controls. Risk factors for renal stones among patients were assessed. MAIN OUTCOME MEASURES: Number of renal stone episodes; comparison of hospital admissions for renal stones in patients and controls; assessment of risk factors for renal stones. RESULTS: Relative risk of a stone episode was 40 (95% confidence interval 31 to 53) before surgery and 16 (12 to 23) after surgery. Risk was increased 10 years before surgery, and became normal more than 10 years after surgery. Stone-free survival 20 years after surgery was 90.4% in patients and 98.7% in controls (risk difference 8.3%, 4.8% to 11.7%). Patients with preoperative stones had 27 times the risk of postoperative stone incidents than controls. Before surgery, males had more stone episodes than females and younger patients had more stone episodes than older patients. Neither parathyroid pathology, weight of removed tissue, plasma calcium levels, nor skeletal pathology (fractures) influenced the risk of renal stones. After surgery, younger age, preoperative stones and ureteral strictures were significant risk factors for stones. CONCLUSIONS: The risk of renal stones is increased in primary hyperparathyroidism and decreases after surgery. The risk profile is normal 10 years after surgery. Preoperative stone events increase the risk of postoperative stones. Stone formers and non-stone formers had the same risk of skeletal complications.

Cohort Studies↗
PubMed2002

Fracture risk in patients with celiac Disease, Crohn's disease, and ulcerative colitis: a nationwide follow-up study of 16,416 patients in Denmark.

The authors studied fracture risk among 16,416 Danish patients with bowel disease. All patients diagnosed with celiac disease (n = 1,021), Crohn's disease (n = 7,072), or ulcerative colitis (n = 8,323) in Denmark between January 1, 1983, and December 31, 1996, were included. Each patient was compared with three age- and gender-matched controls randomly drawn from the background population. No increase in fracture risk could be demonstrated for celiac disease before or after diagnosis. In patients with Crohn's disease, overall fracture risk was increased both before diagnosis (incidence rate ratio = 1.15, 95% confidence interval (CI): 1.00, 1.32) and after diagnosis (incidence rate ratio = 1.19, 95% CI: 1.06, 1.33). Bowel surgery was associated with a decreased risk of sustaining a fracture before diagnosis (odds ratio = 0.70, 95% CI: 0.54, 0.90) and after diagnosis (hazard ratio = 0.81, 95% CI: 0.67, 0.99). Overall fracture risk was not increased in patients with ulcerative colitis, except for a small increase around the time of diagnosis. Increasing age and having a fracture before diagnosis increased the risk of sustaining a new fracture after diagnosis. Crohn's disease was associated with a minor increase in overall fracture risk in contrast to ulcerative colitis and celiac disease. The severity of the inflammatory process and the amount of corticosteroids given may explain the difference in fracture risk.

Adult↗
PubMed2002

[Osteoclast function is regulated by neighbouring osteoblasts. Osteoprotegerin, RAND and RANK ligand constitute a unique regulatory system for bone resorption with important pathophysiological and therapeutic aspects].

Maturation of macrophages to osteoclasts requires the presence of marrow stromal cells or osteoblasts. Most calcitropic hormones act indirectly on osteoclasts through receptors on neighbouring osteoblasts. The discovery of osteoprotegerin (OPG), the receptor activator of nuclear factor-kappa b ligand (RANKL), and its receptor (RANK) has elucidated these phenomena. It appears that osteoclast differentiation, activity, and survival are regulated by the proportion of inhibiting OPG to stimulating RANKL. OPG and RANKL are produced by osteoblasts, whereas RANK is located to the osteoclasts. Treatment with OPG inhibits bone resorption in postmenopausal women. Mutations in the system may be responsible for focal skeletal disorders. The discovery opens up for new treatment opportunities in postmenopausal and steroid-induced osteoporosis, Paget's disease, hypercalcaemia, and rheumatoid arthritis.

Bone Remodeling↗
PubMed2002

Fractures in patients with anorexia nervosa, bulimia nervosa, and other eating disorders--a nationwide register study.

OBJECTIVE: To study fracture risk in patients with anorexia nervosa (AN), bulimia nervosa (BN), or eating disorders not otherwise specified (EDNOS). METHOD: Cohort study including all Danes diagnosed with AN (n = 2,149), BN (n = 1,294), or EDNOS (n = 942) between 1977 and 1998. Each patient was compared with three randomly drawn age- and gender-matched control subjects. RESULTS: Fracture risk was increased in AN after diagnosis compared to controls (incidence rate ratio: 1.98, 95% CI: 1.60-2.44), but not before. The increased fracture risk persisted more than 10 years after diagnosis. A significant increase in fracture risk was found before diagnosis in BN (1.31, 95% CI: 1.04-1.64), with a trend towards an increase after diagnosis (1.44, 95% CI: 0.93-2.22). EDNOS patients had a significant increase in fracture risk before (1.39, 95% CI: 1.06-1.81) and after diagnosis (1.77, 95% CI: 1.25-2.51). DISCUSSION: The increased fracture risk many years after diagnosis indicates permanent skeletal damage.

Adult↗
PubMed2002

Improved physical performance and increased lean tissue and fat mass in patients with ulcerative colitis four to six years after ileoanal anastomosis with a J-pouch.

PURPOSE: This study was designed to examine the long-term changes in physical performance, body composition, and bone mineral density in patients with ulcerative colitis undergoing ileoanal anastomosis with J-pouch. Patients were also screened for abnormalities in blood biochemistry. METHODS: Maximal isometric strength (sum of pinching, hand grip, arm flexion, and knee extension), work capacity (ergometer test at 1.5 W/kg), pulmonary function, body composition (dual-energy x-ray absorptiometry scan), and fatigue level were assessed before surgery and four to six years later. RESULTS: Of 24 patients examined preoperatively, 12 females and 8 males were retested. At follow-up, their mean age +/- standard deviation was 38 +/- 9 years, weight was 76 +/- 14 kg, and height was 173 +/- 7 cm. Compared with preoperative assessments, muscular strength had increased 10.6 +/- 17.2 percent (P = 0.015), work capacity 10.4 +/- 13.3 percent (P = 0.003), total tissue mass 4.6 +/- 5.4 kg (P = 0.001), lean tissue mass 2.3 +/- 2.2 kg (P < 0.001), fat mass 2.2 +/- 3.7 kg (P = 0.014), and bone mineral density 1.6 +/- 2.4 percent (P = 0.008). Seventeen of 20 patients had biochemical abnormalities. CONCLUSIONS: After ileoanal anastomosis with J-pouch, muscular strength and work capacity improved concomitant with an increase in total tissue mass, lean tissue mass, fat mass, and bone mineral density. Biochemical abnormalities were common.

Adult↗
PubMed2002

Fracture risk is increased in patients with GH deficiency or untreated prolactinomas--a case-control study.

OBJECTIVE: The pituitary secretes many hormones of significance to bone turnover and thus skeletal integrity. The aim of this study was to examine fracture risk in patients with pituitary disorders with special reference to GH deficiency and hyperprolactinaemia. DESIGN: Case-control study. MEASUREMENTS: Fracture occurrence. PATIENTS: A self-administered questionnaire was issued to 537 consecutive patients with pituitary disorders excluding Cushing's disease. A total of 426 (79%) returned the questionnaire and 422 of these could be analysed. Each respondent was compared to three age- and gender-matched control respondents to the same questionnaire drawn randomly from the background population. RESULTS: The patients had a mean age of 51.4 +/- 14.8 years. One hundred and eight patients had acromegaly, 86 had prolactinomas, 136 had non-functioning pituitary adenomas (NFPA), 23 had craniopharyngiomas, and 73 had other types of pituitary disorders. For the total group the fracture risk was not elevated either before or after confirmed diagnosis compared to controls. However, among the patients with prolactinomas, the fracture risk was significantly increased before (relative risk, RR = 1.6, 95% CI: 1.1--2.3) but not after diagnosis. In patients with NFPA, fracture risk was borderline significantly elevated following diagnosis (RR = 1.6, 95% CI: 1.0--2.6). Patients with subnormal stimulated peak GH values suggestive of GH deficiency had a significantly higher risk of fractures after diagnosis than patients who had normal stimulated peak GH values (odds ratio, OR = 4.90, 95% CI: 1.10--21.88). CONCLUSIONS: Untreated prolactinomas were associated with a significant increase in fracture risk. Growth hormone deficiency was also associated with a higher fracture risk.

Adenoma↗
PubMed2002

Smoking as a risk factor for Graves' disease, toxic nodular goiter, and autoimmune hypothyroidism.

To study the association between smoking and thyroid disease (Graves' disease [E05.0], nodular toxic goiter [E05.2], and autoimmune hypothyroidism [E03.9]) in a low-iodine intake area a case-control study was undertaken. A self-administered questionnaire was issued to 864 consecutive patients with hyperthyroidism and 628 patients with autoimmune hypothyroidism treated at five university or regional endocrinologic clinics in Denmark between January 1, 1990 and December 31, 1998. Each respondent was compared to an age- (+/- 5 years) and gender-matched normal control person randomly drawn from the background population. A total of 621 patients with hyperthyroidism (72%) and 411 patients with autoimmune hypothyroidism (66%) responded. Of these, 617 (542 females) and 408 (364 females) could be analyzed, respectively. There was an increased risk of both Graves' disease (odds ratio [OR] = 2.5, 95% confidence interval [CI]: 1.8-3.5), toxic nodular goiter (OR = 1.7, 95% CI: 1.1-2.5), and autoimmune hypothyroidism (OR = 1.5, 95% CI: 1.1-2.1) with ever smoking compared to never smoking in women, but not in men. With the high proportion of ever-smokers among women (56%), the attributable risk of smoking in women was 45% in Graves' disease, 28% in toxic nodular goiter, and 23% in autoimmune hypothyroidism. Ever use of oral contraceptives was associated with a slightly lower risk of Graves' disease in women, but not of toxic nodular goiter or autoimmune hypothyroidism. In conclusion, smoking is a powerful risk factor for thyroid disease, especially in populations with a high smoking frequency. Oral contraceptive use is associated with a slightly lower frequency of Graves' disease.

Adult↗
PubMed2002

Fractures in patients with hyperthyroidism and hypothyroidism: a nationwide follow-up study in 16,249 patients.

AIM: To study fracture risk in patients with hyperthyroidism and hypothyroidism. SUBJECTS AND METHODS: All patients with hyperthyroidism or autoimmune hypothyroidism diagnosed for the first time between 1983 and 1996 in Denmark were identified through the National Patient Discharge Register. Each patient was compared with three age- and gender-matched controls randomly selected from the general population. Fracture occurrence before and after diagnosis was compared between patients and controls. RESULTS: 11,776 patients with hyperthyroidism (6301 patients with diffuse toxic goiter, mean age, 52.1 +/- 18.6 years, and 5475 with nodular toxic goiter, mean age, 60.4 +/- 15.9 years), and 4473 patients with hypothyroidism (mean age, 66.1 +/- 17.3) were identified. In patients with hyperthyroidism, fracture risk was only significantly increased around the time of diagnosis (incidence rate ratio [IRR] between 1.26 and 2.29), but decreased to normal levels after diagnosis. Surgical treatment of hyperthyroidism was associated with a decreased fracture risk after diagnosis (RR = 0.66, 95% confidence interval [CI]: 0.55-0.78). In hypothyroidism, fracture risk was significantly increased both before and after diagnosis with a peak around the time of diagnosis (IRR between 2.17 and 2.35). CONCLUSIONS: Fracture risk is increased in hyperthyroidism and hypothyroidism. Thyroid surgery seems associated with a decreased fracture risk in hyperthyroid patients.

Absorptiometry, Photon↗
PubMed2002

Marked disproportionality in bone size and mineral, and distinct abnormalities in bone markers and calcitropic hormones in adult turner syndrome: a cross-sectional study.

Most women with Turner syndrome (TS) have no gonadal activity and thus lack estrogen. Bone mineral density (BMD) is often reduced, leading to an increased risk of osteoporosis and fractures. However, growth retardation with reduced final height and other endocrine disturbances may compromise interpretation of skeletal measurements. The aim of the present study was to explore skeletal findings, bone metabolism, and calcium homeostasis in TS. Sixty women with TS (age, 37 +/- 9 yr) and 181 normal age-matched female controls were studied. Bone area (A; square centimeters), bone mineral content (BMC; grams), area-adjusted BMD (aBMD; grams/square centimeter), and volumetric BMD (vBMD; grams/cubic centimeter) were measured at lumbar spine, femoral neck, and forearm using dual energy x-ray absorptiometry. Twenty-eight percent had osteopenia, and 23% had osteoporosis, according to World Health Organization criteria. At the lumbar spine, A, BMC, aBMD, and vBMD were reduced by 18, 27, 11, and 6%, respectively; at the femoral neck, A, BMC, and aBMD were reduced by 2, 10, and 8%, respectively, whereas the 9% reduction in vBMD was insignificant (P = 0.07); and in the forearm, A, BMC, and aBMD were reduced by 53, 55, and 9%, respectively. Bone markers indicated an enhanced bone resorption (21 and 23% increase in C-terminal and N-terminal cross-linking telopeptides of type I collagen/creatinine, respectively) with unchanged (osteocalcin, procollagen I N-terminal propeptide) or reduced (54% reduction in bone alkaline phosphatase) bone formation. Plasma levels of calcium and 25-hydroxyvitamin D (26%) were reduced, and PTH levels increased (74%) in TS. IGF-I (30%), IGF binding protein 3 (18%), testosterone (50%), and SHBG (40%) were reduced in TS. In summary, A, BMC, and aBMD were found to be universally reduced in TS, whereas vBMD was slightly reduced in the spine. Increased resorption of bone was present, with normal or blunted bone formation, suggesting uncoupling or imbalance in bone remodeling. Skeletal changes may be induced by chromosome abnormalities or by secondary endocrine or metabolic changes related to a relative estrogen deficiency, testosterone deficiency, reduced IGF-I, low vitamin D status, and secondary hyperparathyroidism.

Adult↗
PubMed2002

Increased risk of osteoporotic fractures in patients with Cushing's syndrome.

OBJECTIVE: To evaluate if fracture risk was increased in patients with Cushing's syndrome due to the increased endogenous cortisol production. DESIGN: Cohort. METHODS: A self-administered questionnaire was mailed to 125 patients with Cushing's syndrome diagnosed between 1985 and 1999 in Denmark. The response of each patient was compared with that of three age- and gender-matched control subjects randomly drawn among respondents to the same questionnaire from the background population. RESULTS: One hundred and four patients (83%) responded. The median age of the patients was 48 years (range 19-85 years). Sixty-eight had pituitary disease, 28 had adrenal disease, four had had both pituitary and adrenal surgery while four had not undergone surgery at the time of the study. The median time from diagnosis to surgery was 0.2 (range 0-3) years. Eighty-six percent were cured following surgery. There was an increased fracture risk within the last 2 years prior to diagnosis (incidence rate ratio 6.0, 95% confidence intervals (CI): 2.1-17.2). More than 2 years prior to diagnosis and following diagnosis there was no difference in fracture risk between patients and controls. The patients had more low-energy fractures than the controls (relative risk 5.4, 95% CI: 1.4-20.1). There was no difference in fracture risk between patients with adrenal or pituitary disease. CONCLUSIONS: Patients with Cushing's syndrome had an increased fracture risk in a narrow time interval before diagnosis, while no increase in fracture risk could be demonstrated after diagnosis and treatment.

Adrenal Glands↗
PubMed2002

Diurnal rhythm of plasma 1,25-dihydroxyvitamin D and vitamin D-binding protein in postmenopausal women: relationship to plasma parathyroid hormone and calcium and phosphate metabolism.

OBJECTIVE: Diurnal variations in plasma levels of 1,25-dihydroxyvitamin D (1,25(OH)(2)D) have previously only been investigated in young individuals, and these studies have failed to demonstrate a diurnal rhythm. We have studied whether plasma levels of 1,25(OH)(2)D and vitamin D-binding protein (DBP) vary in a diurnal rhythm in postmenopausal women. METHODS: Blood and urine were sampled with 2- and 4-h intervals in order to assess diurnal variations in plasma levels of 1,25(OH)(2)D, DBP and parathyroid hormone (PTH), as well as in plasma levels and urinary excretion rates of calcium and phosphate. Additionally, the free 1,25(OH)(2)D index was calculated (the molar ratio of 1,25(OH)(2)D to DBP). RESULTS: Plasma 1,25(OH)(2)D exhibited a diurnal rhythm (P<0.01) with a nadir in the morning (99+/-12 pmol/l), followed by a rapid increase to a plateau during the day (113+/-13 pmol/l, i.e. 14% above nadir level; P=0.005). A similar pattern of variation was found in plasma levels of DBP with peak levels 15% above nadir levels (P<0.01). The free 1,25(OH)(2)D index did not vary in a diurnal rhythm. PTH and plasma levels and urinary excretions of calcium and phosphate exhibited a diurnal pattern of variation. The diurnal rhythm of DBP was correlated with the rhythm of 1,25(OH)(2)D (r=0.47, P<0.01) and plasma albumin (r=0.76, P<0.01). Moreover, the rhythm of plasma calcium and PTH varied inversely (r=-0.36, P=0.02). CONCLUSIONS: With the disclosure of a diurnal rhythm of total plasma 1,25(OH)(2)D, all major hormones and minerals related to calcium homeostasis have now been shown to exhibit diurnal variations. In clinical studies, the diurnal variations of 1,25(OH)(2)D and DBP must be considered, i.e. blood sampling must be standardised according to the time of day.

Aged↗
PubMed2002

Short-term growth hormone treatment in girls with Turner syndrome decreases fat mass and insulin sensitivity: a randomized, double-blind, placebo-controlled, crossover study.

BACKGROUND: Most girls with Turner syndrome (TS) receive growth hormone (GH) treatment during childhood and adolescence, but controlled data on the effects on body composition and glucose metabolism are lacking. OBJECTIVE: To study the effects of GH treatment on insulin sensitivity, glucose metabolism, bone turnover, and body composition. METHODS: A randomized, placebo-controlled, crossover study was conducted with girls with TS. All girls with TS were treated with GH 0.1 IU/kg/d subcutaneously at bedtime or with placebo for 2 months and studied at the end of each period. Control subjects were studied once without treatment. Twelve girls with TS, aged 9.5 to 14.8 years (median: 12.9 years) and 16 age-matched control subjects (10.3-16.0 years; median: 12.1 years) were studied. Twenty-four-hour sampling of blood was performed; GH, insulin-like growth factor I (IGF-I), IGF binding proteins (IGFBPs), insulin, glucose, and lipolytic and gluconeogenic precursors were assayed, followed by an oral glucose tolerance test. Body composition was evaluated by dual-energy x-ray absorptiometry scanning and body mass index (BMI). Fasting bone markers were measured. RESULTS: Height was reduced in TS as compared with control subjects. In the placebo situation, 24-hour integrated GH as well as IGF-I was significantly reduced in girls with TS compared with control subjects. Controlling for differences in lean body mass (LBM; or fat mass [FM]) and sexual development did not explain the difference in 24-hour integrated GH. Differences in sexual development, BMI, FM, insulin sensitivity, and IGFBP-3 could explain the difference in IGF-I between TS and control subjects. Carbohydrate metabolism in TS was comparable with control subjects. GH treatment induced insulin resistance, with increments in fasting glucose and insulin, as well as 24-hour insulin. Circulating levels of lipid and gluconeogenic substrates were comparable in TS and control subjects and unchanged in response to treatment. Bone markers increased in response to GH. Total FM was increased in girls with TS, accounted for by an increased FM in the arms and trunk, whereas LBM was decreased. Especially LBM in the legs was decreased. Overall, bone mineral content was diminished. Treatment with GH reduced FM in TS, especially in the arms and legs, and likewise increased total LBM, primarily in the trunk. CONCLUSION: This study documented evidence of impaired GH secretion and action, disproportionate body composition, but a normal carbohydrate metabolism in girls with TS. Short-term GH administration was associated with favorable changes in body composition but also with relative impairment of glucose tolerance and insulin sensitivity. We recommend that glucose metabolism be monitored carefully during long-term GH treatment in these patients.

Adipose Tissue↗
PubMedDate not supplied

Hyperthyroidism and risk of atrial fibrillation or flutter: a population-based study.

BACKGROUND: Atrial fibrillation is a common cardiac manifestation of hyperthyroidism. The relation between hyperthyroidism and atrial fibrillation has so far been analyzed in a limited number of selected patients, and the strength of the association has not been estimated. We examined the risk of atrial fibrillation among patients aged 20 to 89 years with hyperthyroidism diagnosed in hospitals in Denmark during a 20-year period. METHODS: We identified all patients with an incident hospital diagnosis of hyperthyroidism during the study period in the Danish National Registry of Patients, and among those we identified patients with a diagnosis of atrial fibrillation or flutter that occurred +/-30 days from the date of the hospital diagnosis of hyperthyroidism. We used logistic regression analysis to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for the association between sex, 10-year age group, cardiovascular diseases, and risk of atrial fibrillation or flutter. RESULTS: Among 40 628 patients diagnosed as having hyperthyroidism, 3362 (8.3%) were diagnosed as having atrial fibrillation or flutter within +/-30 days from the date of the diagnosis of hyperthyroidism. The following factors were associated with risk of atrial fibrillation or flutter: male sex (OR, 1.8; 95% CI, 1.6-1.9), age (OR, 1.7; 95% CI, 1.7-1.8) per 10-year increment, ischemic heart disease (OR, 1.8; 95% CI, 1.6-2.0), congestive heart failure (OR, 3.9; 95% CI, 3.5-4.4), and heart valve disease (OR, 2.6; 95% CI, 1.9-3.4). CONCLUSION: Male sex, increasing age, ischemic heart disease, congestive heart failure, and heart valve disease are associated with an increased risk of atrial fibrillation or flutter in patients with hyperthyroidism.

Adult↗