Bulimia nervosa--a primary defect in the hypothalamic-pituitary-adrenal axis?

Bulimia nervosa has been associated with impaired satiety, decreased resting metabolic rate and abnormal neuroendocrine regulation. The aim of this study was to investigate the diurnal cortisol secretion and the pituitary-adrenal response to corticotropin-releasing hormone (CRH) in subjects suffering from bulimia nervosa. Eight female subjects with remitted bulimia nervosa, ages 24-56, and 8 sex- and weight-matched controls volunteered to participate. After an overnight fast they were admitted to the Clinical Research Center for 24 hour recording of plasma cortisol secretion. Blood were drawn every 2nd hour from 8 AM. After another overnight fast, the subjects performed a 120-min CRH test (100 microg i.v.), drawn for measurements of adrenocorticotropin releasing hormone (ACTH) and cortisol. Compared to the control group (CG), the diurnal cortisol secretions in the bulimic group (BG) decreased at time points 6 AM to 2 PM. In the CRH test, the ACTH response was significantly stronger in the BG than in the CG. Similar observations were found for cortisol, although not at significant levels. Remitted bulimic patients exhibit a neuroendocrine pattern of decreased HPA axis activity with a hyperreactivity to CRH. This may indicate a complex and so far poorly understood neuroendocrine dysregulation of HPA axis associated with the disease.

Left ventricular dysfunction in subjects with mild secondary hyperparathyroidism detected with pulsed wave tissue Doppler echocardiography.

AIMS: To assess left ventricular function by conventional and pulsed wave tissue Doppler (PWTD) echocardiography in subjects with mild secondary hyperparathyroidism, and to evaluate whether PWTD would be more sensitive than conventional echocardiography in detecting subtle changes in LV systolic and diastolic function. METHODS: In the fifth Tromsø study (2001) serum PTH and calcium were measured in 7,954 subjects. One hundred subjects with secondary hyperparathyroidism (SHPT; serum PTH >6.40 pmol/l and serum calcium <2.40 mmol/l) and 106 control subjects with normal PTH and calcium levels and with no history of cardiovascular disease were examined at the follow-up 6-12 months later. RESULTS: Conventional transthoracic echocardiography and PWTD of mitral annulus were successfully performed in 83 cases and 88 controls. At follow-up mean serum PTH values were 6.0 +/- 2.2 versus 3.2 +/- 1.3 pmol/l (p < 0.05) and mean calcium 2.28 +/- 0.10 versus 2.33 +/- 0.08 mmol/l (p < 0.05) in cases and controls, respectively. Unpaired t test and multiple linear regression analyses were used. No significant differences in conventional echocardiographic parameters were found. However, PWTD showed reduced systolic velocity in septal, lateral and anterior mitral annulus (p < 0.05) and also reduced early diastolic velocity in septal and anterior mitral annulus (p < 0.05). CONCLUSION: Subjects with mild SHPT have impaired left ventricular long axis function as evaluated by PWTD compared to conventional echocardiography. PWTD seems to be a more sensitive tool in detecting minor changes in left ventricular function and the new modality should routinely be included in studies evaluating left ventricular function, especially the long axis function.

Causes of secondary hyperparathyroidism in a healthy population: the Tromsø study.

Secondary hyperparathyroidism (SHPT) develops as a compensatory mechanism when the body is in calcium deficit. SHPT may be harmful and has been associated with elevated blood pressure. The cause of SHPT could be low calcium intake, reduced intestinal calcium absorption, or increased excretion. However, the relative importance of these factors for the development of SHPT is not known. During the 5th Tromsø study, serum PTH and calcium were measured in 7954 subjects. Then 96 subjects with SHPT (defined as serum PTH above 6.4 pmol/l together with serum calcium below 2.40 mmol/l) and 106 control subjects were examined at follow-up with a food frequency questionnaire, calcium absorption test, measurement of 24-h urinary calcium excretion, and serum vitamin D status. The statistical analyses showed several interactions necessitating subgroup analysis. It was found that the calcium intake was significantly lower in the SHPT group, but only in nonsmoking males; the calcium absorption was nonsignificantly higher in the SHPT group; the serum 25-hydroxyvitamin D levels were significantly lower in the SHPT group but only in nonsmokers; and the 24-h urinary calcium excretion was significantly lower in the SHPT group but only in those not on blood pressure medication. The most frequent cause of SHPT appeared to be low calcium intake (18%) and a low serum 25-hydroxyvitamin D level (18%). However, in most subjects with SHPT all tests were within the normal range, and the cause is therefore probably a combination of several factors.

Neuropsychological function and symptoms in subjects with subclinical hypothyroidism and the effect of thyroxine treatment.

OBJECTIVE: Our objective was to examine the relation between neuropsychological function and subclinical hypothyroidism (SHT), defined as serum TSH of 3.5-10.0 mIU/liter and normal serum free T4 and free T3 levels, and to study the effect of T4 supplementation. SUBJECTS: A total of 89 subjects (45 males) with SHT and 154 control subjects (72 males) were recruited from a general health survey (the fifth Tromsø study). Sixty-nine of those with SHT were included in a placebo-controlled, double-blind intervention study with T4 medication for 1 yr. MAIN OUTCOME MEASURES: We used fourteen tests of cognitive function, Beck Depression Inventory, General Health Questionnaire, and a questionnaire on hypothyroid symptoms. RESULTS: The mean +/- sd serum TSH in the SHT and control group were 5.57 +/- 1.68 and 1.79 +/- 0.69 mIU/liter, respectively. There were no significant differences in cognitive function and hypothyroid symptoms between the two groups, but those with SHT scored significantly better than the controls on the GHQ-30. At the end of the intervention study, serum TSH in the T4 group (n = 36) and the placebo group (n = 33) were 1.52 +/- 1.51 and 5.42 +/- 1.96 mIU/liter, respectively. T4 substitution had no effect on any of the parameters measured. CONCLUSION: In subjects with SHT where the serum TSH level is in the 3.5-10.0 mIU/liter range, there is no neuropsychological dysfunction, and compared with healthy controls, there is no difference in symptoms related to hypothyroidism.

Serum parathyroid hormone as a predictor of increase in systolic blood pressure in men.

BACKGROUND: In cross-sectional studies there appears to be a link between calcium metabolism and blood pressure, and most studies have found a positive association between serum parathyroid hormone (PTH) and hypertension. OBJECTIVE: To determine the prognostic value of serum PTH regarding a future increase in blood pressure. DESIGN: A prospective cohort study. SUBJECTS: A total of 1784 individuals who had measurements of PTH in serum samples from both the fourth (1994) and fifth (2001) Tromsø studies, who did not use blood pressure medication during the observation period, and had serum calcium less than 2.61 mmol/l, were included. MAIN OUTCOME MEASURE: Delta blood pressure (blood pressure from 2001 minus blood pressure from 1994). RESULTS: The mean delta systolic blood pressure in the men and women during these 7 years was 5.8 and 8.1 mmHg, respectively. In a sex-specific linear regression model correcting for age, body mass index (BMI), and smoking status, serum PTH from 1994 was a significant predictor of delta systolic blood pressure in men (P < 0.01), but not in women. The difference in delta systolic blood pressure between those in the highest and those in the lowest PTH quartile was 3.5 mmHg. Similarly, delta serum PTH (serum PTH from 2001 minus serum PTH from 1994) was a significant predictor of delta systolic blood pressure in men (P < 0.05). CONCLUSIONS: Although these findings do not prove a causal relationship between PTH and blood pressure, it adds to the growing number of indications that PTH is involved in the development of hypertension.

Fatigue in patients with lupus is not associated with disturbances in cerebral blood flow as detected by SPECT.

OBJECTIVES: Fatigue is a common complaint in patients with systemic lupus erythematosus (SLE). We investigated whether focal or general disturbances of cerebral blood flow (CBF), as assessed by SPECT, were associated with the presence of fatigue in an unselected group of SLE patients. METHODS: Fifty-six patients were included. Mean age was 47.5 years (+/-12.7), mean disease duration 14.7 years (+/-8.9), and disease activity measured by SLE disease activity index (SLEDAI) was 5.7 (+/-5.4). Fatigue was assessed by the Fatigue Severity Scale (FSS) and CBF by Tc-99m-hexamethyl propylamine oxime (HMPAO)-SPECT. The images were read and processed quantitatively by a computer program using the primary visual cortex as reference region and > 15% CBF deviation as definition of abnormality. RESULTS: The mean FSS score was 4.6 (+/-1.8). SPECT revealed focal CBF disturbances in 17 patients (30.4 %). Generalized symmetrical CBF reductions were present in 32 patients (57.1 %). There were no significant associations between CBF disturbances in any region of the brain and the degree of fatigue. CONCLUSIONS: Fatigue in SLE patients is not related to focal or general CBF disturbances. Therefore, factors that do not influence blood flow seem responsible for the fatigue phenomenon.

Endogenous sex hormones in relation to age, sex, lifestyle factors, and chronic diseases in a general population: the Tromsø Study.

The role played by endogenous hormones in many diseases makes it important to understand factors influencing their levels. This study examined the distribution of total and free estradiol, FSH, and dehydroepiandrosterone sulfate (DHEAS) by age and sex and associations of these hormones with body mass index (BMI), lifestyle factors, and chronic diseases. Plasma samples taken from 1555 men and 1952 women 25-84 yr of age in 1994-1995 Tromsø Study were analyzed in 2001. Total estradiol increased with age among men (P < 0.001), with or without adjustment for BMI and lifestyle factors. FSH increased with age both in men (P < 0.001) as well as pre- (P < 0.001) and postmenopausal women (P = 0.01) after similar adjustment, and DHEAS decreased with age in both sexes (P < 0.001). With increasing BMI, free estradiol increased in men (P = 0.004), total and free estradiol increased in postmenopausal women (P < 0.001), and FSH decreased in men (P = 0.03) and postmenopausal women (P < 0.001). Men with chronic diseases had lower levels of DHEAS, compared with healthy men (P < 0.001). Smokers had higher DHEAS levels than nonsmokers. Further studies are needed to confirm these hormonal changes with age and disease.

Waist circumference and testosterone levels in community dwelling men. The Tromsø study.

To examine the relationship of total and free testosterone and sex hormone-binding globulin (SHBG) with central obesity in men, we studied 1548 men aged 25-84 years that took part in the 1994--1995 survey of the Tromsø study. Total testosterone and SHBG were measured by immuno-assay and the free testosterone fraction was calculated. These measurements were analyzed in relation to anthropometric data and lifestyle factors. The age-adjusted correlation between waist circumference (WC) and total testosterone was -0.34 (p < 0.001), between WC and free testosterone -0.09 (p < 0.001) and, between WC and SHBG -0.44 (p < 0.001). Adjusting for BMI and lifestyle factors weakened, but did not eliminate these associations. All hormone and SHBG associations were stronger for WC than for waist-hip ratio or BMI. In age- and BMI-adjusted analyses men with a WC > or = 102 cm had significantly lower levels of total testosterone and SHBG compared to men with an optimal WC, defined as < 94 cm (12.3 vs. 13.9 nmol/l; p < 0.01 and 48.5 vs. 55.1 nmol/l; p < 0.001, respectively). The lowest levels of total and free testosterone were observed in men with relatively high WC despite relatively low overall obesity (BMI), suggesting that WC should be the preferred anthropometric measurement in predicting endogenous testosterone levels.

Serum parathyroid hormone level is associated with body mass index. The 5th Tromsø study.

OBJECTIVE: To study whether serum parathyroid hormone (PTH) and serum calcium are associated with body mass index (BMI), and their predicting role in obesity. DESIGN: Population based, cross-sectional study. METHODS: In 2001 a population-based health survey was held in Tromsø, North Norway. Questionnaires on medical history and life-style factors were completed and anthropometric data were collected. Calcium and vitamin D intakes and a physical activity score were calculated. Serum calcium and PTH were measured in a subset of 3447 men and 4507 women. Pearson correlation and linear regression were used to evaluate associations between BMI, PTH and serum calcium, and logistic regression was used to test PTH and serum calcium as predictors of obesity and to calculate odds ratio. Relative risk was calculated using frequency tables. RESULTS: For serum calcium and PTH there was a significant positive relation to BMI in both genders (P<0.001), which to our knowledge has not previously been reported on the basis of a large epidemiological study. Age, low calcium and vitamin D intakes were explanatory variables for serum PTH. The highest quartile of serum PTH (>4.20 pmol/l) was a significant predictor for obesity (P<0.001) in both genders, adjusted for age, physical activity and serum calcium. Obesity rates were higher in those with PTH levels in the highest quartile compared with those in the lower quartiles, which resulted in a relative risk of 1.40 (95% confidence interval (C.I.) 1.20-1.60) for men and 1.48 (95% C.I. 1.31-1.67) for women. CONCLUSIONS: Serum PTH, adjusted for age, physical activity and serum calcium, is positively associated with BMI in both sexes, and serum PTH is an independent predictor of obesity in our statistical model.

Serum parathyroid hormone levels predict coronary heart disease: the Tromsø Study.

BACKGROUND: Primary hyperparathyroidism (PHPT) is associated with hypertension, coronary atherosclerosis and other cardiovascular diseases. We aimed to evaluate serum parathyroid hormone (PTH) levels as an independent risk factor for coronary heart disease (CHD) in subjects with serum calcium within the reference range. DESIGN: Population-based cross-sectional study. METHODS: The Tromsø Study was attended by 27159 subjects aged 25-79 years. Serum PTH was measured in 3570 subjects. They all completed a questionnaire on medical history, including questions on angina pectoris and myocardial infarction along with a food-frequency questionnaire. A total of 1459 men and 1753 women with serum calcium 2.20-2.60 mmol/l, serum creatinine<121 micromol/l and who did not use diuretics were included in the present study. Linear regression was used to reveal associations between PTH, age, body mass index, serum calcium, calcium intake, cholesterol, blood pressure, glycosylated haemoglobin (HbA1c) and smoking status. A logistic regression model was used to find the independent predictors of CHD. RESULTS: When stratified for age the rate of CHD was higher in the subjects with serum PTH > 6.8 pmol/l than in those with normal or low serum PTH levels [relative risk 1.67, 95% confidence interval (CI) 1.26-2.23 in men and 1.78, 95% CI 1.22-2.57 in women]. The highest PTH quartile (> 3.50 pmol/l in men and > 3.30 pmol/l in women) predicted CHD, with odds ratios of 1.70 (95% CI 1.08-2.70) for men and 1.73 (95% CI 1.04-2.88) for women, versus the lowest PTH quartile (< 1.90 pmol/l for men and <1.80 pmol/l for women). CONCLUSIONS: Serum PTH predicts CHD in subjects with calcium levels within the reference range. This may indicate a role for PTH in the development of CHD.

123I-beta-CIT SPECT demonstrates increased presynaptic dopamine transporter binding sites in basal ganglia in vivo in schizophrenia.

RATIONALE: The dopamine hypothesis for schizophrenia postulates overactivity of dopamine transmission in the basal ganglia. Most effective antipsychotic drugs block postsynaptic dopamine receptors, but in-vivo imaging studies have not been able to show changes in these receptors in drug-naive schizophrenics. OBJECTIVES: The presynaptic dopamine transporter (DAT) is thought to be an important regulator of synaptic dopamine concentration. We have used SPECT with (123)I-beta-CIT, which has a high affinity for DAT, in order to further examine the dopamine hypothesis for schizophrenia. METHODS: Six patients with chronic schizophrenia treated with classic dopamine D(2)-receptor blocking neuroleptics were investigated. The number of DAT binding sites in the basal ganglia was calculated and compared with five healthy volunteers and ten parkinsonian patients. RESULTS: The schizophrenic patients showed a 36-63% increase in DAT binding sites compared with the volunteers, whereas the parkinsonian patients showed a 57-96% decrease. The differences between the groups were highly significant (even after correction for different age composition within the groups). CONCLUSIONS: There was an increased number of DAT binding sites in the schizophrenic patients treated with dopamine D(2)-receptor blocking neuroleptics. This fits well with several recent reports that have shown increased volumes of basal ganglia in this patient category. It thus appears that there is an increased number of presynaptic dopamine releasing nerve terminals in the basal ganglia, possibly as a biological adaptation to counteract the postsynaptic dopamine D(2)-receptor blockade.

Seasonal variation of testosterone and waist to hip ratio in men: the Tromsø study.

Studies of seasonal variation in male testosterone levels show contradictory results. We report here a cross-sectional study of the seasonal variation in total and free testosterone, LH, and SHBG levels in 1548 men living in north Norway, a population exposed to a wide seasonal variation in temperature and daylight. Total testosterone showed a bimodal seasonal variation (P < 0.001) with a small peak in February, the nadir in June, and a more prominent peak in October and November. Free testosterone also showed a significant seasonal pattern (P < 0.001), with the peak in December and the nadir in August. These patterns persisted after adjusting for age and waist to hip ratio (P < 0.001). Lowest testosterone levels occurred in months with the highest temperatures and longest hours of daylight. Waist to hip ratio paralleled the change in daylight and temperature, with the highest values during the summer and was thus inversely related to the seasonal testosterone variation. The variations in hormone levels were large, with a 31% difference between the lowest and highest monthly mean level of free testosterone. Prospective studies are needed to establish the direction of the association and its etiology.

The associations of age, lifestyle factors and chronic disease with testosterone in men: the Tromsø Study.

OBJECTIVE: To study whether lifestyle factors and/or chronic disease are associated with the age-related decline of total and free testosterone in men, or if these factors might be associated with the variation of total and free testosterone but not with their age-related decline. DESIGN: A population-based, cross-sectional study was used. METHODS: Total testosterone and sex hormone binding globulin (SHBG) levels were analyzed and free testosterone levels were calculated in 1563 men participating in the Tromsø study in 1994/1995. Anthropometric characteristics were also measured and two standardized questionnaires completed, including lifestyle factors and medical history. The data were analyzed with multiple linear regression analysis of covariance, and logistic regression. RESULTS: Total and free testosterone were inversely associated (P=0.001 and P<0.001), while SHBG was positively associated (P<0.001) with age. Body mass index (BMI) was inversely associated with total (P<0.001) and free (P=0.016) testosterone and SHBG (P<0.001). Both total and free testosterone were positively associated with tobacco consumption (P<0.001 and P=0.004) and total testosterone was positively associated with coffee consumption (P<0.001). SHBG was positively associated with smoking (P=0.004) and coffee consumption (P<0.001). Men who reported having had a stroke or having a cancer diagnosis had lower levels of total testosterone (P<0.001 and P<0.01) and free testosterone (P<0.01). CONCLUSIONS: BMI and smoking are independent contributors to the variation of total and free testosterone and SHBG levels, and coffee consumption to the variation of total testosterone and SHBG. Thus, lifestyle factors can have a direct effect on circulating levels of free endogenous sex hormones and to total levels due to the effect on SHBG levels.

The effects of calcium supplementation to patients with primary hyperparathyroidism and a low calcium intake.

BACKGROUND: In patients with primary hyperparathyroidism (PHPT) a low calcium intake might cause increased bone loss and thus aggravate osteoporosis, and a high intake might increase serum calcium level and the risk of nephrolithiasis. AIM OF THE STUDY: Generally, guidelines recommend a normal calcium intake, and accordingly, those with a low intake might benefit from a modest calcium supplementation. This hypothesis was tested in the present study. METHODS: Thirty-one patients with asymptomatic PHPT were recruited from an epidemiological study (The Tromsø study 1994/95). Those with a daily calcium intake below 450 mg were given calcium supplementation (500 mg Ca(2+)), and those with an intake above 450 mg were followed without supplementation. The study was open and lasted 1 year. Serum levels of calcium, PTH, 25-hydroxyvitamin D3 and 1,25-dihydroxyvitamin D, urinary calcium excretion, blood pressure, and bone mineral density (BMD) were measured. RESULTS: Three subjects dropped out without reason, 1 developed abdominal discomfort from the calcium supplementation, and 3 had an increase in serum calcium of more than 0.2 mmol/L and were therefore excluded. The latter three did not differ from the rest of the group at baseline. Of the remaining 24 that completed the study, 17 were given calcium. In this group there was a non-significant increase in serum calcium and urinary calcium excretion, a significant decrease in PTH after 4 weeks (13.2 (6.0) vs 9.4 (3.0) pmol/L, P < 0.05), and a significant increase in BMD at the femoral neck at the end of the study (0.849 (0.139) vs 0.870 (0.153) g/cm(2), P < 0.05). The blood pressure was not significantly affected. CONCLUSIONS: Most patients with mild PHPT and a low calcium intake tolerate a moderate calcium supplement. This may have beneficial effects on the bones, but the patients must be followed carefully.

Hypothalamic-pituitary-adrenal axis in the night eating syndrome.

The typical neuroendocrine characteristics of the night eating syndrome have previously been described as changes in the circadian rhythm by an attenuation in the nocturnal rise of the plasma concentrations of melatonin and leptin and an increased circadian secretion of cortisol. The aim of this study was to test the hypothesis that night eaters have an overexpressed hypothalamic-pituitary-adrenal axis with an attenuated response to stress. Five female subjects with the night-eating syndrome and five sex-, age-, and weight-matched controls performed a 120-min corticotropin-releasing hormone (CRH) test (100 microg iv). Blood samples were drawn intravenously for measurements of the plasma concentrations of ACTH and cortisol. The results showed that, in night eaters compared with controls, the CRH-induced ACTH and cortisol response was significantly decreased to 47 and 71%, respectively. In conclusion, disturbances in the hypothalamic-pituitary-adrenal axis with an attenuated ACTH and cortisol response to CRH were found in subjects with night-eating syndrome.