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Biomedical subjects

Johan Svensson

Publications and source records attributed to Johan Svensson.

At least 19 recordsLinked to original sources

Growth hormone (GH) replacement therapy in GH deficient adults: predictors of one-year metabolic and clinical response.

OBJECTIVE: This study investigated whether baseline status could predict the responsiveness to one-year growth hormone (GH) replacement therapy in adult GH deficient (GHD) patients. DESIGN: A total of 380 European patients with adult onset GHD due to non-functioning pituitary adenoma that had been enrolled in Pfizer International Metabolic Database (KIMS), and that had completed one year of GH replacement therapy within KIMS, were studied. RESULTS: The mean initial dose of GH was 0.22 (SEM 0.01) mg/day and after one year, the mean dose was 0.36 (0.01) mg/day. The mean insulin-like growth factor-I (IGF-I) SD score increased from -1.75 (0.08) at baseline to 0.47 (0.05) after one year. Quality of life (QoL)-Assessment of GHD in Adults (QoL-AGHDA), waist circumference, waist:hip ratio, and serum lipid pattern improved. Women received a higher dose of GH than men after one year, and demonstrated similar treatment response. In multiple stepwise forward regression analyses, the one-year changes in QoL-AGHDA score, waist:hip ratio, and serum low density lipoprotein-cholesterol (LDL-C) level correlated inversely with the baseline values of the same variable. In addition, the change after one year in QoL-AGHDA score correlated inversely with duration of hypopituitarism and baseline serum high density lipoprotein-cholesterol (HDL-C) level, and the change in waist:hip ratio correlated inversely, although more weakly, with baseline serum HDL-C level and UK citizenship and positively with baseline waist circumference and the initial GH dose. The change in serum LDL-C level additionally correlated inversely with the mean GH dose and duration of hypopituitarism and positively with UK citizenship. CONCLUSIONS: Baseline status could, with moderate strength, predict the responsiveness in the same variable whereas it could not, or only weakly, predict the response in other variables. Therefore, when the decision to start GH replacement is undertaken, as many outcome variables as possible should be evaluated in order to adequately evaluate the likelihood of clinical benefit. Finally, women have a similar response to GH replacement as men when individualised GH dosing schedules are employed and should therefore be selected for GH therapy to a similar extent.

Cohort Studies↗

Baseline characteristics and effects of growth hormone therapy over two years in younger and elderly adults with adult onset GH deficiency.

CONTEXT: The effects of GH replacement in elderly GH-deficient (GHD) adults are not well known. OBJECTIVE/DESIGN/PATIENTS: In this prospective, single-center, open-label study, baseline characteristics and the effects of 2-yr GH replacement were determined in 24 GHD adults above 65 yr of age and in 24 younger GHD patients (mean age, 37 yr; range, 27-46 yr). All patients had adult onset disease, and both groups were comparable in terms of the number of pituitary hormonal deficiencies, gender, body mass index, and waist/hip ratio. Duration of hypopituitarism was, however, longer in the elderly patients. RESULTS: The mean maintenance dose of GH was 0.31 (sem, 0.03) mg/d in the elderly GHD patients and 0.44 (0.04) mg/d in the younger patients. The less marked response in IGF-I sd score, total body fat, and extracellular water in the elderly patients lost significance when the dose of GH was accounted for in the statistical analyses. Despite the lower dose in the elderly GHD group, these patients had a more marked reduction in waist/hip ratio and serum low-density lipoprotein-cholesterol level, and these differences remained also after correction for duration of hypopituitarism. There was no difference at baseline or in responsiveness in lean mass, bone mineral density, and glucose homeostasis. CONCLUSIONS: This study identifies elderly GHD adults as a GH-sensitive group in whom a low dose of GH can improve body composition and serum lipid profile without any significant impairment of glucose metabolism. GH replacement should therefore be considered in elderly GHD adults.

Adult↗

Levothyroxine treatment reduces thyroid size in children and adolescents with chronic autoimmune thyroiditis.

CONTEXT: The use of levothyroxine to reduce thyroid size in pediatric patients with goiter due to chronic autoimmune thyroiditis (AIT) remains controversial. In overtly hypothyroid patients, reductions in thyroid volume have been reported, whereas the effect in subclinically hypothyroid and euthyroid patients is less clear. OBJECTIVE: The objective of the study was to evaluate the effect of levothyroxine treatment on thyroid size (determined with thyroid ultrasonography) in children and adolescents with AIT. DESIGN AND SETTING: This study included patients with AIT treated at a university hospital outpatient clinic between 1987 and 2004. PATIENTS: Ninety children with AIT (73 girls and 17 boys, aged 6.1-17.7 yr) were included in the study. INTERVENTION: Intervention was treatment with levothyroxine for a median 2.8 yr (range 0.5-10.2). MAIN OUTCOME MEASURE: Change in thyroid volume sd score (SDS) during the study period was measured. RESULTS: Median thyroid volume SDS was reduced in patients euthyroid (-0.4 SDS, P < 0.001), subclinically hypothyroid (-1.4 SDS, P < 0.001), and overtly hypothyroid (-1.8 SDS, P < 0.002) at diagnosis of AIT. Both hypothyroid and euthyroid patients with goiter (thyroid volume > 2.0 SDS) at baseline reduced their median thyroid volume SDS (-1.6 and -0.9, respectively, P < 0.001). Hypothyroid patients without goiter also reduced median thyroid volume SDS (-1.2, P < 0.004), whereas no change was noticed in euthyroid children without goiter. CONCLUSIONS: Levothyroxine treatment is effective in reducing thyroid volume in pediatric patients and is suggested in treatment of goiter caused by AIT, especially in cases of hypothyroid, but also in euthyroid children.

Adolescent↗

Histidine tag fusion increases expression levels of active recombinant amelogenin in Escherichia coli.

Amelogenin is a dental enamel matrix protein involved in formation of dental enamel. In this study, we have expressed two different recombinant murine amelogenins in Escherichia coli: the untagged rM179, and the histidine tagged rp(H)M180, identical to rM179 except that it carries the additional N-terminal sequence MRGSHHHHHHGS. The effects of the histidine tag on expression levels, and on growth properties of the amelogenin expressing cells were studied. Purification of a crude protein extract containing rp(H)M180 was also carried out using IMAC and reverse-phase HPLC. The results of this study showed clearly that both growth properties and amelogenin expression levels were improved for E. coli cells expressing the histidine tagged amelogenin rp(H)M180, compared to cells expressing the untagged amelogenin rM179. The positive effect of the histidine tag on amelogenin expression is proposed to be due to the hydrophilic nature of the histidine tag, generating a more hydrophilic amelogenin, which is more compatible with the host cell. Human osteoblasts treated with the purified rp(H)M180 showed increased levels of secreted osteocalcin, compared to untreated cells. This response was similar to cells treated with enamel matrix derivate, mainly composed by amelogenin, suggesting that the recombinant protein is biologically active. Thus, the histidine tag favors expression and purification of biologically active recombinant amelogenin.

Amelogenin↗

Dihydrotestosterone treatment results in obesity and altered lipid metabolism in orchidectomized mice.

OBJECTIVE: To determine the role of androgen receptor (AR) activation for adipose tissue metabolism. Sex steroids are important regulators of adipose tissue metabolism in men. Androgens may regulate the adipose tissue metabolism in men either directly by stimulation of the AR or indirectly by aromatization of androgens into estrogens and, thereafter, by stimulation of the estrogen receptors. Previous studies have shown that estrogen receptor alpha stimulation results in reduced fat mass in men. RESEARCH METHODS AND PROCEDURES: Orchidectomized mice were treated with the non-aromatizable androgen 5alpha-dihydrotestosterone (DHT), 17beta-estradiol, or vehicle. Vo(2), Vco(2), resting metabolic rate, locomotor activity, and food consumption were measured. Furthermore, changes in hepatic gene expression were analyzed. RESULTS: DHT treatment resulted in obesity, associated with reduced energy expenditure and fat oxidation. In contrast, DHT did not affect food consumption or locomotor activity. Furthermore, DHT treatment resulted in increased high-density lipoprotein-cholesterol and triglyceride levels associated with markedly decreased 7alpha-hydroxylase gene expression, indicating decreased bile acid production. DISCUSSION: We showed that AR activation results in obesity and altered lipid metabolism in orchidectomized mice. One may speculate that AR antagonists might be useful in the treatment of obesity in men.

Adiposity↗

Thyroid autoantibodies in cord blood sera from children and adolescents with autoimmune thyroiditis.

Autoimmune thyroid disease is common among women of childbearing age. Thyroid autoantibodies are predominantly of the immunoglobulin G (IgG)-type and pass the placental barrier from mother to child. Recent studies have suggested a pathogenetic role for transplacentally transmitted autoantibodies in the development of autoimmune disease. The aim of the present study was to investigate if children and adolescents with autoimmune thyroiditis (AIT) have been exposed to thyroid autoantibodies already in utero. Cord blood sera taken at delivery from 34 newborns who had developed AIT during childhood and adolescence, and sera from 31 of their mothers, were analyzed for the presence of autoantibodies against thyroid peroxidase (TPOAb) and thyroglobulin (TgAb), and compared to 233 randomly selected control children and their mothers. The prevalence of TPOAb in cord blood sera was elevated among the children and adolescents with AIT compared to controls (38% versus 14%; odds ratio [OR] 4.12, p < 0.001). An increased prevalence of TPOAb was also found among their mothers (29% versus 15%; OR 2.17, p < 0.048). No significant difference in the prevalence of TgAb was found either between children with AIT and the control children (18% versus 9%; OR 2.16, p < 0.15), or between their mothers and the control mothers (23% versus 12%; OR 2.17, p < 0.16). Most of the TPOAb-positive children had TPOAb-positive mothers, indicating the maternal origin of their TPOAb. In conclusion, a large proportion of children who later developed AIT had already been exposed to transplacentally transmitted TPOAb in utero. Whether these autoantibodies have any pathogenetic role in the development of AIT in offspring or if they simply mirror the inheritance of AIT, remains to be investigated.

Adolescent↗

Increase of bioavailable testosterone is associated with gain in bone mineral density after cure of primary hyperparathyroidism in postmenopausal women.

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.

Aged↗

Increased plasma concentrations of N-terminal pro-B-type natriuretic peptide in patients with mild primary hyperparathyroidism.

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.

Aged↗

Healthcare utilization, quality of life and patient-reported outcomes during two years of GH replacement therapy in GH-deficient adults--comparison between Sweden, The Netherlands and Germany.

OBJECTIVE: This study set out to determine the change in quality of life (QoL) and healthcare utilization during 2 years of growth hormone (GH) replacement therapy in adults with GH deficiency. Data were compared from three European countries. DESIGN: Analysis was made from KIMS, the Pfizer International Metabolic Database on adult GH deficiency. METHODS: QoL and healthcare utilization were measured at baseline and after 1 and 2 years of GH replacement in patient cohorts from Sweden (n = 302), The Netherlands (n = 103) and Germany (n = 98). QoL was assessed by the QoL-Assessment in Growth Hormone Deficient Adults (QoL-AGHDA) questionnaire, and the KIMS Patient Life Situation Form was used to evaluate healthcare utilization. RESULTS: QoL improved significantly (P < 0.0001) and comparably in all three cohorts. The improvement was seen during the first year of treatment and QoL remained improved during the second year. The number of days in hospital was reduced by 83% (P < 0.0001) during GH replacement. There were no country-specific differences either at baseline or during follow-up. The same was true for the number of days of sick leave (reduction of 63%; P = 0.0004). Significant reductions were recorded in the number of doctor visits in each of the three cohorts after 2 years of GH replacement (P < 0.05). CONCLUSIONS: This study provides a detailed comparative analysis of GH replacement therapy in GHD patients in three European countries. Despite some differences in treatment strategies, the beneficial effects on QoL, patient-reported outcomes and healthcare utilization are essentially similar in the healthcare environment of Western European countries.

Adult↗

GH secretory pattern in young adults who discontinued GH treatment for GH deficiency and decreased longitudinal growth in childhood.

OBJECTIVE: Some adolescents who discontinue GH treatment due to GH deficiency (GHD) and short stature in childhood do not have classical GHD at retesting in adult life. It is unknown whether there is a neuroendocrine disturbance in the spontaneous pattern of GH release in these patients. DESIGN/PATIENTS/METHODS: Thirty-seven adolescents, who had received treatment with GH due to impaired longitudinal growth, were included. The adolescents were divided into two groups; one (GHD; n = 19) with classical GHD in adult life and another (GH sufficient (GHS); n = 18) without classical adult GHD. One year after GH discontinuation, 24-h GH profiles were performed with blood sampling every 30 min. Sixteen matched healthy controls were also studied. All blood samples were analysed using an ultrasensitive GH assay and then, approximate entropy (ApEn) and deconvolution analysis were performed. RESULTS: The GHD group had higher mean ApEn level than the healthy controls (P < 0.05). As measured by deconvolution analysis, they had lower basal GH secretion (P < 0.01), increased number of GH peaks (P < 0.001), but lower burst mass (P < 0.001), lower percentage pulsatile GH secretion (P < 0.001) and lower total GH secretion (P < 0.001), compared with control subjects. Adolescents in the GHS group had a pattern of 24-h GH release similar to that in healthy controls. CONCLUSION: Young adults with childhood-onset severe GHD have a high-frequency, low-amplitude GH secretion with decreased orderliness. The adolescents without classical GHD in adult life maintain a pattern of spontaneous GH release that is not statistically different from that in the healthy controls.

Adolescent↗

Thigh intermuscular fat is inversely associated with spontaneous GH release in post-menopausal women with abdominal obesity.

CONTEXT: The metabolic syndrome is characterized by an increased accumulation of visceral adipose tissue (VAT) and blunted GH secretion. There are, however, no data on the association between GH secretion and other fat depots (in liver and muscle). OBJECTIVE/DESIGN: The aim of this cross-sectional study, which included 20 post-menopausal women with abdominal obesity, was to determine the association between GH secretion and regional adipose tissue (AT) distribution. Twelve-hour GH profiles (2000-0800 h) were performed by blood sampling every 20 min. GH was analyzed using an ultra-sensitive assay followed by approximate entropy (ApEn) and deconvolution analysis. RESULTS: In simple regression analyses, both basal and pulsatile GH secretions correlated negatively with VAT and thigh intermuscular adipose tissue (IMAT), but not with hepatic fat content. There was no correlation between ApEn and the AT depots studied. In multiple regression analysis, pulsatile GH secretion correlated inversely with thigh IMAT (B-coefficient=-0.67; P<0.01), whereas the correlation with VAT became non-significant. Furthermore, in multiple regression analysis, basal GH secretion correlated negatively with VAT (B-coefficient=-0.77; P=0.001), but not significantly with thigh IMAT. CONCLUSION: In post-menopausal women with abdominal obesity, pulsatile GH secretion demonstrated an independent, negative association with thigh IMAT, whereas basal GH secretion showed an independent, negative association with VAT. These findings suggest that the neuroendocrine association between fat mass and somatotropic axis is depot-dependent. We have identified thigh IMAT to be important in this interplay.

Abdominal Fat↗

Liver-derived IGF-I regulates exploratory activity in old mice.

Growth hormone (GH) replacement in hypopituitary patients improves well-being and initiative. Experimental studies indicate that these psychic effects may be reflected in enhanced locomotor activity in mice. It is unknown whether these phenomena are mediated directly by GH or by circulating IGF-I. IGF-I production in the liver was inactivated at 6-10 wk of age (LI-IGF-I-/- mice), resulting in an 80-85% reduction of circulating IGF-I, and, secondary to this, increased GH secretion. Using activity boxes on three different occasions during 1 wk, 6-mo-old LI-IGF-I-/- mice had similar activity levels, and 14-mo-old mice had a moderate but significant decrease in activity level, compared with control mice. At 20 mo of age, the LI-IGF-I-/- mice displayed a more prominent decrease in activity level with decreased horizontal activity throughout the test period, and at day 1, there were several signs of an altered habituation process with different time patterns of locomotor activity and horizontal activity compared with the control mice. At days 3 and 5, rearing activity was lower in the 20-mo-old LI-IGF-I-/- mice. Anxiety level was unaffected in all age groups, as measured using the Montgomery's elevated plus-maze. In conclusion, old LI-IGF-I-/- mice displayed a decrease in both horizontal and rearing (exploratory) activity level and an altered habituation process. These results indicate that liver-derived IGF-I mediates at least part of the effects of GH on exploratory activity in mice.

Age Factors↗

Adiponectin, leptin, and erythrocyte sodium/lithium countertransport activity, but not resistin, are related to glucose metabolism in growth hormone-deficient adults.

In a randomized, placebo-controlled, crossover study under metabolic ward conditions, 10 GH-deficient adults received 1-wk GH replacement therapy (9.5 microg/kg.d). The effect of this treatment on the erythrocyte sodium/lithium countertransport (SLC) activity and on serum levels of adiponectin, resistin, leptin, IGF binding protein-1 (IGFBP-1) and IL-6 was determined. The 1-wk GH replacement impaired glucose homeostasis determined from an oral glucose tolerance test. The other measured variables in serum were unchanged by GH replacement. At baseline, serum adiponectin level was inversely correlated and serum leptin level was positively correlated with measures of glucose tolerance and insulin sensitivity. The changes in serum leptin level and erythrocyte SLC activity were positively correlated, and the change in serum IGFBP-1 level was negatively correlated, correlated with changes in measures of glucose metabolism. In conclusion, short-term GH treatment induced glucose intolerance but did not significantly change the erythrocyte SLC activity and the serum levels of adipokines, arguing against direct effects of GH on these measures. However, baseline values or changes in erythrocyte SLC activity, adiponectin, leptin, and IGFBP-1 correlated with glucose metabolism. This suggests that these factors are of importance for glucose homeostasis in GH-deficient adults, most likely through GH-independent mechanisms.

Adiponectin↗

The effects of five-year growth hormone replacement therapy on muscle strength in elderly hypopituitary patients.

OBJECTIVE: Little is known of the long-term effects of GH replacement therapy on muscle strength in elderly adults with adult onset GH deficiency (GHD). In this study, the effects of 5 years of GH replacement therapy on muscle function were determined in adults over 60 years of age with adult onset GHD. DESIGN: A prospective, open-label, single-centre study. Patients Twenty-six (12 male and 14 female) consecutive hypopituitary adults with adult onset GHD, mean age 65.0 (range 61-74) years. MEASUREMENTS: Upper leg muscle strength was measured using a Kin-Com dynamometer. Right and left handgrip strength were measured using an electronic grip force instrument. RESULTS: The mean insulin-like growth factor-I (IGF-I) SD score increased from -1.10 at baseline to 1.21 at end of the study. Body weight was unchanged during the 5-year study. A sustained increase in lean body mass and a sustained reduction of body fat was observed as measured using dual-energy X-ray absorptiometry (DEXA). The GH replacement therapy induced a sustained increase in isometric (60 degrees ) knee flexor strength. After statistical correction for age and sex variables using observed/predicted value ratios, a sustained increase was also observed in concentric knee flexor strength at an angular velocity of 60 degrees /s, concentric knee extensor strength at 60 degrees /s and 180 degrees /s, and peak right handgrip strength. At baseline, knee flexor strength was 90-96% of predicted, knee extensor strength was 85-87% of predicted, and hand-grip strength was 74-80% of predicted values. At study end, knee flexor strength was 98-106% of predicted, knee extensor strength was 90-100% of predicted, and hand-grip strength was 80-87% of predicted values. CONCLUSION: Elderly patients with adult onset GH deficiency had decreased baseline muscle strength also after correction for age and sex. The 5-year GH replacement therapy normalized knee flexor strength and improved, but did not fully normalize, knee extensor strength and handgrip strength.

Absorptiometry, Photon↗

Three-years of growth hormone (GH) replacement therapy in GH-deficient adults: effects on quality of life, patient-reported outcomes and healthcare consumption.

OBJECTIVE: The objective was to investigate the effects of 3 years of growth hormone (GH) replacement therapy in GH deficient (GHD) patients in Sweden. DESIGN AND PATIENTS: An open label study in 237 adults with GHD (116 men and 121 women), consecutively enrolled in KIMS (Pfizer's international metabolic database) in Sweden. MEASUREMENTS: QoL and healthcare consumption were determined using questionnaires [QoL-assessment of GHD in Adults (QoL-AGHDA), the psychological general well-being (PGWB) index and the patient life situation form (PLSF)]. RESULTS: The mean starting dose of GH was 0.13 mg/day and the mean maintenance dose was 0.37 mg/day. The mean insulin-like growth factor I (IGF-I) SD score increased from -1.92 at baseline to 0.38 after 3 years. There was a sustained increase in QoL as measured by the QoL-AGHDA and PGWB questionnaires. The number of doctor visits and the number of days in hospital were reduced after 3 years of GH replacement. The number of days of sickleave decreased during the first 2 years of treatment, but returned towards baseline values after 3 years. Leisure-time physical activity and satisfaction with physical activity increased. CONCLUSION: Three years of GH replacement therapy induced a sustained improvement in QoL. Healthcare consumption was reduced, although the reduction in the number of days of sickleave was not statistically significant after 3 years of treatment.

Adult↗

Early parathyroidectomy increases bone mineral density in patients with mild primary hyperparathyroidism: a prospective and randomized study.

BACKGROUND: There is an ongoing controversy regarding how to take care of patients with mild primary hyperparathyroidism (PHPT) and how to grade their disease activity in terms of bone parameters. This prospective and randomized study was undertaken to evaluate skeletal effects of delayed surgical treatment in such patients. METHODS: Fifty patients with mild PHPT (serum calcium, 2.55 to 2.95 mmol/L; 10.2 to 11.8 mg/dL) were randomized to parathyroidectomy either at diagnosis or 1 year later. Hip and spine bone mineral density (BMD, determined by dual energy x-ray absorptiometry), bone alkaline phosphatase in serum, osteocalcin and beta-CrossLaps in plasma, and calcium in urine were measured in all patients at inclusion in the study and 1 and 2 years later. RESULTS: The skeletal effects of mild PHPT varied with anatomy and time of exposure. Parathyroidectomy decreased all biochemical bone markers ( P < .0001) and increased lumbar spine BMD ( P < .05) equally in both groups, even in patients without overt osteoporosis, whereas hip BMD was increased ( P < .05) in the early intervention group only. CONCLUSION: Prolonged exposure to mild and seemingly stable PHPT is a risk factor for hip fractures, which adds to other reasons for surgical treatment of this condition without delay regardless of serum calcium levels.

Aged↗

Interpretation of normative thyroid volumes in children and adolescents: is there a need for a multivariate model?

The use of thyroid ultrasonography for determination of thyroid volume requires reliable reference criteria. The current World Health Organization/International Council for the Control of Iodine Deficiency Disorders (WHO/ICCIDD) reference has been questioned since iodine-sufficient children have been found throughout the world with distinctly smaller thyroid volumes. A difference in part explained by a systematic bias when generating the WHO/ICCIDD reference data. The objective with this study was to evaluate normative thyroid volumes in our region and, if possible, develop a multivariate model for their interpretation. Thyroid ultrasonography was performed and anthropometrical measurements were taken in 561 children and adolescents. The best predictor for thyroid volume in both girls and boys was body surface area (BSA), followed by age, weight, and height. References for normative thyroid volumes were calculated for each of the predictors. When these references were compared with other references throughout the world, the age-specific references were in good accord, but distinct differences were found between our BSA-specific references and other references based on a majority of children younger than ours. Using multivariate analyses, BSA and age were found to significantly influence thyroid volume, independently of each other. Multiple regression models by gender using BSA and age as predictors for thyroid volume were constructed. Using these models the difference between the BSA-specific references could be markedly reduced. To interpret thyroid volume accurately we propose the use of a multivariate model using age and BSA as predictors of thyroid volume.

Adolescent↗