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- Bülow, Birgitta, et al.
(författare)
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Adrenal incidentaloma - follow-up results from a Swedish prospective study
- 2006
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Ingår i: European journal of endocrinology / European Federation of Endocrine Societies. - : Oxford University Press (OUP). - 0804-4643 .- 1479-683X. ; 154:3, s. 419-23
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: To examine the risk of developing adrenal carcinomas and clinically overt hypersecreting tumours during short-term follow-up in patients with adrenal incidentalomas. DESIGN: 229 (98 males and 131 females) patients with adrenal incidentalomas were investigated in a prospective follow-up study (median time 25 months; range 3-108 months). The patients were registered between January 1996 and July 2001 and followed until December 2004. Twenty-seven Swedish hospitals contributed with follow-up results. METHODS: Diagnostic procedures were undertaken according to a protocol including reinvestigation with computed tomography scans after 3-6 months, 15-18 months and 27-30 months, as well as hormonal evaluation at baseline and after 27-30 months of follow-up. Operation was recommended when the incidentaloma size increased or if there was a suspicion of a hypersecreting tumour. RESULTS: The median age at diagnosis of the 229 patients included in the follow-up study was 64 years (range 28-84 years) and the median size of the adrenal incidentalomas when discovered was 2.5 cm (range 1-8 cm). During the follow-up period, an increase in incidentaloma size of > or =0.5 cm was reported in 17 (7.4%) and of > or =1.0 cm was reported in 12 (5.2%) of the 229 patients. A decrease in size was seen in 12 patients (5.2%). A hypersecreting tumour was found in 2% of the hormonally investigated patients: Cushing's syndrome (n = 2) and phaeochromocytoma (n = 1). Eleven patients underwent adrenalectomy, but no cases of primary adrenal malignancy were observed. CONCLUSIONS: Patients with adrenal incidentaloma had a low risk of developing malignancy or hormonal hypersecretion during a short-term follow-up period.
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| 2. |
- Bulow, Birgitta
(författare)
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Cardiovascular mortality and morbidity in hypopituitary patients and metabolic effects of growth hormone treatment
- 1999
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Premature atherosclerosis, cardiovascular risk factors and increased cardiovascular mortality have been shown in patients with hypopituitarism on conventional hormone treatment, but without growth hormone (GH) replacement. The aims of paper I-III were to investigate separately the risks for cerebrovascular and cardiac mortality as well as the incidence of cardiovascular disease in patients with hypopituitarism and to assess the long-term prognosis for patients with craniopharyngioma. GH replacement has been associated with an impairment of glucose tolerance and the objectives of paper IV-V were to investigate whether individualized GH replacement therapy could avoid such a deterioration. There was a 1.75-fold increased cardiovascular mortality in 344 hypopituitary patients operated for a pituitary tumour compared to the general population. The risk for death in cerebrovascular disease was higher than for cardiac disease and females had a higher risk increase than males. A survival analysis of 60 patients operated for craniopharyngioma showed a more than 3-fold increase in cardiovascular mortality compared to the general population. There were no protective effects of radicality at surgery or radiotherapy on survival in patients with craniopharyngioma. Increased incidence of cardiovascular disease and increased prevalence of cardiovascular risk factors, such as lower degree of physical exercise, higher WHR, lower HDL-cholesterol and higher LDL:HDL ratio were observed in 33 hypopituitary females compared to a control group matched for sex, age, smoking habits, educational level and residence location. The increased cardiovascular mortality and morbidity could not be explained by inadequate treatment with corticosteroids, thyroid hormones or sex hormones alone. Unsubstituted GH deficiency (GHD) is likely to be a more important contributing factor. Individualized GH treatment to ten patients with childhood onset GHD caused a significant decrease in fat mass, but no impairment was observed in glucose tolerance during euglycemic conditions. The GH dose was adjusted after serum insulin-like growth facor-I (IGF-I) levels, which could be a useful method for monitoring GH treatment in adults with childhood onset GHD. During hypoglycemia, GH therapy caused an increase in insulin resistance, which could not be explained by changes in the counterregulatory hormones or serum IGF-binding protein-1.
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| 3. |
- Bülow, Birgitta, et al.
(författare)
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High incidence of mental disorders, reduced mental well-being and cognitive function in hypopituitary women with GH deficiency treated for pituitary disease
- 2002
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Ingår i: Clinical Endocrinology. - : Wiley. - 1365-2265 .- 0300-0664. ; 56:2, s. 183-193
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Previous studies have shown possible neuroendocrine effects of GH. In the present study we investigated the incidence of mental disorders and the prevalence of mental distress and cognitive dysfunction in hypopituitary women with untreated GH deficiency compared to population-based controls.DESIGN AND PATIENTS: Thirty-three hypopituitary women with a median age of 64 years (range 39--77 years) were investigated cross-sectionally, without any change in hormone substitutions. Twenty-nine of the patients had been operated for a pituitary tumour, 25 had received radiotherapy and 15 had visual dysfunction. The patients were with a very high probability GH deficient, as 29 had subnormal IGF-I levels and the other four were GH deficient as assessed by an insulin tolerance test. The patients were compared with 33 controls matched for sex, age, smoking habits, educational level and residence.MEASUREMENTS: The incidence of mental disorders was calculated from the date of diagnosed hypopituitarism to the time of the present investigation. Mental well-being was assessed by three self-rating questionnaires: the Symptom Checklist-90 (SCL-90), the Interview Schedule for Social Interaction (ISSI) and the social network concept. The subjects were examined with neuropsychological tests of vocabulary (SRB:1 vocabulary test), perceptual speed (WAIS-R Digit Symbol), spatial ability (WAIS-R Block Design), verbal memory (Cronholm--Molander verbal memory test), spatial learning (Austin Maze Test) and reaction time (APT Two-way Reaction Time and APT Inhibition).RESULTS: The hypopituitary women had a higher incidence of mental disorders than the controls; Incidence Rate Ratio 4.5 (95% CI 1.0--21). The Global Severity Index, i.e. the average score of all 90 questions of the SCL-90, was higher in patients (P = 0.001), and the patients had significantly more symptoms of somatization, anxiety, depression, obsession--compulsion, hostility--irritability, phobic and psychotic symptoms (all P less-than-or-equal 0.04). Moreover, 14 patients compared to four controls were classified as possible cases of mental distress according to the SCL-90 (P = 0.006). The patients experienced lower availability of both social attachment (P = 0.02) and integration (P = 0.001), but there were no group differences in the adequacy of these dimensions or in emotional support. The patients had lower scores in four of seven neuropsychological tests (all P less-than-or-equal 0.04).CONCLUSIONS: The hypopituitary women had a higher incidence of mental disorders, more symptoms of mental distress and increased prevalence of cognitive dysfunction. The impaired results in the patients could possibly be explained by several factors, such as transfrontal surgery, radiotherapy, visual dysfunction and unphysiological hormone substitution. Moreover, it is probable that GH deficiency contributed, but placebo-controlled double-blind studies are warranted to investigate whether the psychological dysfunction is reversible on GH substitution.
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| 4. |
- Bülow, Birgitta, et al.
(författare)
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Individualized low-dose growth hormone (GH) treatment in GH-deficient adults with childhood-onset disease: metabolic effects during fasting and hypoglycemia
- 1999
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Ingår i: Metabolism, Clinical and Experimental. - 1532-8600. ; 48:8, s. 10-1003
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 7. |
- Erfurth, Eva Marie, et al.
(författare)
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Incidence of a second tumor in hypopituitary patients operated for pituitary tumors
- 2001
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Ingår i: Journal of Clinical Endocrinology and Metabolism. - 1945-7197. ; 86:2, s. 659-662
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 8. |
- Erfurth, Eva Marie, et al.
(författare)
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Is there an increase in second brain tumours after surgery and irradiation for a pituitary tumour?
- 2001
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Ingår i: Clinical Endocrinology. - : Wiley. - 1365-2265 .- 0300-0664. ; 55:5, s. 613-616
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Tidskriftsartikel (refereegranskat)abstract
- 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% Cl 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.
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| 9. |
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| 10. |
- Link, Katarina, et al.
(författare)
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Low individualized growth hormone (GH) dose increased renal and cardiac growth in young adults with childhood onset GH deficiency
- 2001
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Ingår i: Clinical Endocrinology. - : Wiley. - 1365-2265 .- 0300-0664. ; 55:6, s. 741-748
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Tidskriftsartikel (refereegranskat)abstract
- 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 mug/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.
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