Search PubMed⌕ Search

Biomedical subjects

B Bülow

Publications and source records attributed to B Bülow.

At least 19 recordsLinked to original sources
PubMed2002

Adrenal incidentaloma--experience of a standardized diagnostic programme in the Swedish prospective study.

OBJECTIVE: To report the 5-year experience of a diagnostic programme for adrenal incidentaloma with special emphasis to diagnose hormonally active and malignant lesions. DESIGN: A prospective study in which new cases of adrenal incidentalomas in Sweden have been evaluated by a standardized diagnostic protocol between January 1996 and July 2001. SETTING: Thirty-three different Swedish hospitals have contributed with cases. SUBJECTS: A total of 381 patients (217 females, 164 males) with adrenal incidentalomas were studied. INTERVENTIONS: Diagnostic procedures were undertaken according to a standardized programme. Operation was recommended if the incidentaloma had a size of more than 3-4 cm or if there was a suspicion of a hypersecreting tumour. MAIN OUTCOME MEASURES: The size of the incidentaloma, clinical characteristics of the patients and results of biochemical diagnostic tests were registered. RESULTS: The median age of the patients was 64 years (18-84 years), and the median size of the incidentalomas was 3 cm (1-20 cm). A total of 85(22%) patients were operated. Twenty of these patients were diagnosed with a benign hypersecreting tumour and 14 with a malignant tumour. Fourteen of 15 operated patients with diagnosed pheochromocytoma had elevated 24-h urinary noradrenaline and all of the patients operated because of a biochemical suspicion of aldosterone or cortisol hypersecretion (n = 6) were found to have adrenal adenomas. Of the 14 operated patients with malignant diseases, 10 were adrenal carcinomas (median size 10 cm; range 4-16 cm). In a multiple logistic regression model, incidentaloma size was significantly associated with the risk of a malignant tumour (P = 0.009), and there was a tendency of an association between age/male sex and the risk of a malignancy (both, P = 0.07). CONCLUSION: In this Swedish multicentre study of 381 cases with adrenal incidentalomas, 5% had benign hypersecreting tumours and nearly 4% had malignant tumours. The results of the biochemical diagnostic tests used had a high compatibility with the histological diagnosis found at operation in the patients with hypersecreting tumours. Tumour size, male gender and high age were predictive for the risk of a malignant tumour. A follow-up of the patients is warranted in order to establish whether there are undiscovered cases of malignant or hypersecreting tumours amongst the nonoperated patients.

Adenoma↗
PubMed2001

Is there an increase in second brain tumours after surgery and irradiation for a pituitary tumour?

OBJECTIVE: To assess the incidence of second brain tumours in patients operated and irradiated for pituitary tumours. DESIGN AND PATIENTS: The study base consisted of a consecutive series of 325 patients operated and irradiated for pituitary tumours, excluding patients with acromegaly and Cushing's disease. Comparison was made with the general population from the same catchment area as the patients. The follow-up period started in 1958 and on an individual basis patients were followed from the onset of postoperative irradiation until December 1995, or until date of death, emigration or a second brain tumour diagnosis, whichever occurred first. RESULTS: Three brain tumours (two astrocytomas and one meningioma) were observed, compared with 1-13 expected (standardized incidence ratios (SIR) 2.7; 95% confidence interval (CI) 0.6-7.8). CONCLUSION: The present study gives no firm support for an increased incidence of a second brain tumour in patients operated and irradiated for pituitary tumours. A crude meta-analysis of the present and previously published cohort studies of patients with irradiated pituitary tumours gives an SIR of 6.1 (95% CI 3.16-10.69). Thus, the results of the meta-analysis are in favour of an increased risk for second brain tumours. A genetic trait that predisposes to both pituitary tumours and brain tumours is an alternative causal factor. There is no definite proof that cranial irradiation per se is the causal factor. This question cannot be fully answered until sufficient cohort studies of nonirradiated pituitary tumour patients have been carried out.

Adult↗
PubMed2001

Low individualized growth hormone (GH) dose increased renal and cardiac growth in young adults with childhood onset GH deficiency.

OBJECTIVE: In childhood onset GH deficiency (GHD) a reduction in left ventricular mass (LV-mass) and impairment of systolic function as well an impairment in glomerular filtration rate (GFR) has been shown. The aim of the present study was to assess if a low GH dose resulted in an improvement in morphological and functional parameters of these organs. DESIGN AND PATIENTS: Eleven patients with childhood onset GHD were investigated before and after 10 months of GH treatment at a dose of 1.5 IU/day (range 1-2), corresponding to 0.02 IU/kg/day or 7 microg/ kg/day. The GH dose resulted in a serum IGF-I level in the normal range in all but one patient. MEASUREMENTS: Doppler echocardiography of the heart and ultrasound examination of the kidneys was performed. Glomerular filtration rate (GFR) was estimated with iohexol clearance and urinary proteinuria was measured with 24-h urinary samples collected for analyses of albumin, alpha-1-microglobulin, IgG and albumin/creatinine clearance ratio. Body composition was measured by bioelectric impedance analysis. RESULTS: L V-mass index increased significantly after GH treatment (P = 0.04), and there was a clear trend for a positive correlation between the increase in serum IGF-I and the increase in LV-mass index, although it did not reach significance (r= 0.57, P = 0.07). GH treatment did not increase cardiac fractional shortening. Kidney length increased significantly (P = 0.02) with an average increase of 1 cm (range - 0.5-1.5 cm). No significant changes in median GFR or serum creatinine were recorded. Three patients with subnormal GFR before GH treatment normalized after 10 months of treatment. Urine analysis showed no abnormalities before or after GH treatment. A significant decrease in percentage fat mass was recorded (P = 0.03). CONCLUSION: A low individualized GH dose to adults with childhood onset GHD resulted in an increase in LV-mass index and kidney length. Re-establishing GH treatment with a low dose in this patient group can lead to a further somatic maturation of these organs, probably not accomplished previously.

Adolescent↗
PubMed2001

Incidence of a second tumor in hypopituitary patients operated for pituitary tumors.

Recently, an association between increased blood levels of insulin-like growth factor I (IGF-I) and increased risks of prostate, breast, lung, and colorectal cancers has been suggested. As today adults with GH deficiency are subjected to GH substitution, there is a pressing need for baseline tumor incidence data. The aim of the study was to assess the risk for a second tumor in a cohort of 328 patients with hypopituitarism treated for a pituitary tumor from 1958--1992. The patients were receiving conventional hormone treatment, but without GH substitution. The overall tumor incidence [standardized incidence ratio (SIR)] was lower than expected (0.85), but the 95% confidence interval (CI) did not exclude unity (0.59--1.21). Only two prostate cancers occurred (SIR, 0.34; 95% CI, 0.04--1.24). Two brain tumors (SIR, 1.96; 95% CI, 0.24--7.08) and two endocrine tumors (part of multiple endocrine neoplasm syndromes; SIR, 4.00; 95% CI, 0.48--14.5) had occurred. When excluding brain and endocrine tumors, the overall SIR decreased to 0.77, but did still not differ significantly from unity (0.52--1.13). Thus, a tendency for a decreased overall tumor risk, although not statistically significant, was noted, especially when excluding brain and endocrine tumors. This tendency was more emphasized for prostate cancer, but low numbers hamper a firm conclusion. These results may serve as a baseline for tumor risk among adult patients with pituitary insufficiency supplemented with GH.

Adolescent↗
PubMed2001

Increased leptin and tumour necrosis factor alpha per unit fat mass in hypopituitary women without growth hormone treatment.

BACKGROUND: The adipocyte products, leptin and tumour necrosis factor (TNF)alpha, are associated with atherosclerotic diseases and may be factors contributing to the enhanced cardiovascular risk in hypopituitary patients with growth hormone (GH) deficiency. OBJECTIVE: To investigate whether leptin and TNFalpha are increased in a group of hypopituitary women previously found to have increased cardiovascular morbidity, and to compare them with matched individuals of the same sex and age and with similar body composition. DESIGN AND PATIENTS: Thirty-three GH-deficient women with a median age of 64 years (range 39-77 years) were investigated cross-sectionally. The patients were compared with 33 controls matched for sex, age, smoking habits, educational level and residence. METHODS: Body composition was measured by bioimpedance analysis. Fasting concentrations of leptin, TNFalpha and insulin were analysed in patients and controls. RESULTS: There was no significant difference in body mass index or fat mass between patients and controls (both P > or =0.4). Serum leptin did not differ significantly between patients and controls. However, when serum leptin concentrations were expressed per kilogram fat mass, the patients had significantly greater concentrations (P=0.01). Serum TNFalpha and TNFalpha per kilogram fat mass were also significantly greater in the patients (both P=0.001). In contrast, serum insulin did not differ significantly between patients and controls. In the patients, serum leptin concentrations correlated positively with kilogram fat mass (r=0.54, P=0.002). Leptin concentration per kilogram fat mass was positively correlated with insulin (r=0.40, P=0.03). CONCLUSIONS: In contrast to serum concentrations of TNFalpha, serum leptin did not differ from that in controls, implying that leptin is not a major contributor to the previously found increase in cardiovascular morbidity in the hypopituitary women investigated. However, the patients had increased leptin concentrations per unit fat mass, indicating an altered adipocyte secretory function in this group.

Adipose Tissue↗
PubMed2000

Is vascular mortality increased in hypopituitarism?

Hitherto four relevant cohort studies have been published on the life expectancy of patients with hypopituitarism, two from the UK and two from Sweden. In all four studies patients with acromegaly or Cushing's disease were excluded, and patients with GH replacement were not included. A crude meta-analysis, not considering differences in validity of the study designs, gives an overall Relative Risk (RR) of 1.47, with a relatively small 95% confidence interval of 1.27-1.70. The aim of this critical review was to assess whether lacking validity in the design of one or several of these studies indicates that the true RR might be higher or lower than indicated by meta-analyses. A high frequency of cranial irradiation in one of the Swedish cohorts may explain part of the very high observed RR for cerebrovascular mortality, but there remained a 40% risk increase for cardiac diseases that cannot be explained by irradiation. Some other validity problems, especially seen in the UK studies, will result in under-estimation of the true RR, but for others the direction of bias is uncertain due to lacking information in the original publications. According to our view, it is more probable that the observed overall 50% risk increase for vascular mortality is an under-estimation than an over-estimation of the true RR. This analysis is of a qualitative nature, and it is not possible to quantify to what extent the lacking validity may have affected the RR.

Aged↗
PubMed2000

Hypopituitary females have a high incidence of cardiovascular morbidity and an increased prevalence of cardiovascular risk factors.

We recently reported that female patients with hypopituitarism receiving controlled thyroid and steroid hormone substitution, but without GH replacement, had a more than 2-fold increase in cardiovascular mortality compared to the general population. In the present study we investigated the incidence of cardiovascular disease as well as the prevalence of cardiovascular risk factors in 33 females with hypopituitarism for 6-46 yr (median, 18) compared to those in 33 control subjects recruited from the general population in the same geographical area and matched for sex, age, smoking habits, educational level, and residence location. The patients were with a very high probability GH deficient, as 29 had subnormal serum insulin-like growth factor I levels, and the other 4 were GH deficient, as assessed by an insulin tolerance test. The incidence of cardiovascular disease was significantly higher among the hypopituitary patients (incidence ratio, 3.7; 95% confidence interval, 1.2-11.3), and the consumption of cardioactive drugs was also significantly higher (P = 0.002). Hypopituitary patients had a lower degree of physical exercise during their spare time (P = 0.02), a higher waist/hip ratio (P = 0.01), lower high density lipoprotein cholesterol (P = 0.002), and higher low density/high density lipoprotein ratio (P = 0.009). Furthermore, the patients had a significantly increased left atrium size (P = 0.05), but no difference was observed for other cardiac measures. In the patients, serum insulin-like growth factor I levels significantly correlated with left ventricular mass index (r = 0.48; P = 0.006), suggesting that GH has a strong impact on cardiac size. More episodes of bradycardia (P = 0.05), but no increased occurrence of extrasystolies, were encountered in the patients during 24-h continuous electrocardiogram monitoring. Carotid artery intima-media thickness and plaque numbers did not differ between patients and controls. In conclusion, hypopituitary females exhibit an increased incidence of cardiovascular disease, higher cardioactive drug consumption, and an increased prevalence of cardiovascular risk factors. The increased cardiovascular morbidity could not be ascribed to inadequate estrogen or thyroid hormone treatment, and unsubstituted GH deficiency is probably an important contributing factor.

Adult↗
PubMed1999

Individualized low-dose growth hormone (GH) treatment in GH-deficient adults with childhood-onset disease: metabolic effects during fasting and hypoglycemia.

Growth hormone (GH) has insulin-antagonistic effects, and GH secretion is augmented during fasting and hypoglycemia. In the present study, 10 patients aged 21 to 28 years with childhood-onset GH deficiency (GHD) were studied during a 24-hour fast and a hypoglycemic glucose clamp before and after 9 months of GH replacement. During the 24-hour fast, blood glucose, serum insulin, and serum free fatty acid (FFA) levels were measured. In the hypoglycemic clamp, the counterregulatory hormones (plasma catecholamines, serum glucagon, and serum cortisol), serum insulin-like growth factor (IGF) binding protein-1 (IGFBP-1), serum FFA, and glucose uptake were measured. The GH dose was adjusted to the response of serum IGF-I, and the median GH dose was 0.14 IU/kg/wk (range, 0.08 to 0.19). At the end of the study, serum IGF-I levels were normalized in all but one patient, in whom serum IGF-I was above the normal range. Nine months of GH treatment did not cause any significant changes in the blood glucose level, insulin to glucose ratio, or serum FFA level during the 24-hour fast, and none of the patients experienced hypoglycemia either before or after GH treatment. However, GH therapy resulted in increased insulin resistance during hypoglycemia, without changes in the counterregulatory hormonal responses, serum IGFBP-1, or serum FFA.

Adult↗
PubMed1999

High incidence of cardiovascular disease and increased prevalence of cardiovascular risk factors in women with hypopituitarism not receiving growth hormone treatment: preliminary results.

Recently, epidemiological evidence has suggested that hypopituitarism with untreated growth hormone deficiency (GHD) is associated with a high incidence of cardiovascular mortality and that women are particularly at risk. In the present study, the incidence of cardiovascular disease and prevalence of cardiovascular risk factors in 33 such women was assessed and compared with matched controls. A significantly higher number of diagnosed circulatory disorders occurred in the women with hypopituitarism compared with controls, and drug consumption for cardiovascular disorders was also significantly higher in this group. Furthermore, patients with hypopituitarism had a significantly higher waist:hip ratio and a higher ratio of low-density lipoprotein to high-density lipoprotein than controls. Electrocardiogram data showed that hypopituitarism was associated with more episodes of bradycardia. In summary, women with hypopituitarism had an increased incidence of cardiovascular disease and a less favourable risk factor profile compared with matched controls. The data add support to previous studies that have shown increased risks of cardiovascular mortality associated with hypopituitarism with untreated GHD. We conclude that adequate cardiovascular surveillance programmes are required for patients with pituitary insufficiency.

Adult↗
PubMed1999

A low individualized GH dose in young patients with childhood onset GH deficiency normalized serum IGF-I without significant deterioration in glucose tolerance.

OBJECTIVE: Many GH deficient (GHD) patients have impaired glucose tolerance and GH substitution in these patients has caused deleterious effects on glucose tolerance with hyperinsulinaemia. This further impairment of glucose tolerance might be due to an unphysiologically high dose of GH. Whether such a deterioration can be avoided by an optimal GH replacement dose is not known. In most previous studies, the GH dose was calculated according to body weight or body surface area and not adjusted according to the serum IGF-I response. DESIGN: The study was of open design and investigations were performed before the start of GH substitution and after nine months of treatment. The GH dose was adjusted according to the response in serum IGF-I, and in patients with sub-normal serum IGF-I levels (all but two) we aimed for a serum IGF-I level in the middle of the normal range. The median GH dose at the end of the study was 0.14 IU/kg/week. PATIENTS: Ten patients, eight males and two females, with childhood onset GHD were examined. Their median age was 27 years (range 21-28). MEASUREMENTS: Overnight and 24-h fasting levels of glucose, insulin and IGFBP-1 were measured. Directly after the 24-h fast an oral glucose tolerance test (OGTT), with measurements of glucose, insulin and IGFBP-1 was performed. An intravenous glucose tolerance test (IVGTT) was performed after overnight fasting. Body composition was measured with bio-impedance analysis (BIA) and quality of life was assessed using a self-rating questionnaire, Qol-AGHDA. RESULTS: After GH treatment, there were no significant changes in glucose tolerance, measured by overnight and 24-h fasting levels of glucose, insulin and IGFBP-1, an oral glucose tolerance test (after 24-h fasting) and an intravenous glucose tolerance test (after overnight fasting). Percentage fat mass and BMI correlated negatively with both the 24 h fasting IGFBP-1 levels and the IGFBP-1 responses after the OGTT. All patients decreased their percentage of fat mass measured by BIA [median -2.9%; range -1.0-(-6.6); P = 0.005]. The administered GH dose correlated negatively with the relative change in whole body resistance (r = -0.66; P = 0.04). All, but one of the patients improved their quality of life score after GH therapy. CONCLUSIONS: In a group of young patients with childhood onset GH deficiency, 9 months of treatment with a low GH dose (median 0.14 IU/kg/week) caused no significant deterioration of glucose tolerance. The strong negative associations between BMI or percentage fat mass and IGFBP-1 suggest that serum IGFBP-1 is more closely related than insulin to body composition in GH deficient patients. It is important to consider which critical endpoints should determine the GH dose. We would suggest that, apart for normalizing the serum IGF-I level, another main endpoint should be normalization of, or at least avoidance of any deterioration in glucose tolerance.

Adult↗
PubMed1998

Postoperative prognosis in craniopharyngioma with respect to cardiovascular mortality, survival, and tumor recurrence.

Specific causes of death, survival, and recurrence rates were assessed in a cohort of 60 patients who had undergone surgery for craniopharyngioma between 1951 and 1988. Compared to the general population, the standardized mortality ratio (SMR) was increased [5.55; 95% confidence interval (CI), 3.68-8.22], and it was higher among females (SMR, 11.4) than males (SMR, 4.79). The risk of cardio- and cerebrovascular mortality (SMR, 3.21; 95% CI, 1.29-6.61) was also enhanced. The cumulative survival rates 10 and 15 yr after the initial operation were 68% (95% CI 54-78) and 59% (95% CI 30-63), respectively. A multivariate survival analysis adjusting for age showed a protective effect of radiotherapy (hazard ratio, 0.3; 95% CI, 0.1-0.8) and an increased risk of death after recurrence (hazard ratio, 4.4; 95% CI, 1.4-14), but no obvious effect of radicality at surgery. However, when patients who had died within 6 months after surgery were excluded, no significant protective effect of radiotherapy remained. The cumulative frequency of recurrence after 10 yr was 33% (95% CI, 22-48%), and that after 15 yr was 40% (95% CI, 28-56%). The incidence of recurrence did not differ significantly with respect to age, radicality at surgery, or postoperative radiotherapy. The determinants for long term outcome in patients with craniopharyngioma are interrelated in a complex way, which calls for strict selection criteria in follow-up studies and the use of multivariate statistical models.

Cardiovascular Diseases↗
PubMed1997

Increased cerebrovascular mortality in patients with hypopituitarism.

OBJECTIVE: An increased prevalence of atherosclerosis has been shown among patients with hypopituitarism. The aim of the present study was to assess whether patients with hypopituitarism experience increased cardiovascular, in particular cerebrovascular, mortality. DESIGN AND PATIENTS: Retrospective cohort study of mortality, 1952-1992, in 344 patients, of whom 130 were female, receiving conventional hormone replacement for hypopituitarism following neurosurgery for pituitary tumours. The general population in the catchment area of southern Sweden from which the patients were recruited constituted the reference population. Expected mortality was obtained from cause, sex, calendar year, and 5-year age-specific death raise for the area. RESULTS: Increased mortality from cerebrovascular disease (standardized mortality ratio (SMR) 3.39; 95% CI 2.27-4.99) was the main contributor to the increased overall cardiovascular mortality (SMR 1.75; 95% CI 1.40-2.19). The increase in mortality from cardiac diseases was much smaller (SMR 1.41; 95% CI 1.04-1.88). The risk for cerebrovascular death was higher in women (SMR 4.91) than in men (SMR 2.64). The relative risk for cerebrovascular death was independent of the time interval since diagnosis of pituitary insufficiency, but was greater in subjects diagnosed at an earlier age (< 55 years). No increased mortality in malignant tumours was observed (SMR 0.95; 95% CI 0.60-1.48). CONCLUSION: The increased cerebrovascular mortality may be due to GH deficiency, or to long-term lack or inadequacy of substitution for other pituitary hormones. The observations that an early onset of pituitary insufficiency and female sex are predictors for a high risk for cerebrovascular mortality merit particular attention when treating this group of patients.

Adult↗