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ABSTRACT: Context:Hypothalamic damage caused by craniopharyngioma (CP) is associated with poor functional outcome.Objective:To assess cognitive function and quality of life (QoL) in childhood onset CP on hormonal replacement, including GH treatment.Design:A cross sectional study with a median follow-up time of 20 years (1-40).Setting:Patients were recruited from the South Medical Region of Sweden.Participants:The study included 42 patients (20 women), surgically treated for a childhood onset CP between 1958 and 2000. Patients were aged ≥17 years. Equally many controls, matched for age, sex, residence and smoking habits, were included. Tumor growth into the third ventricle (TGTV) was found in 25 patients.Main Outcome Measures:All subjects were examined with a battery of cognitive tests and the questionnaires: Symptom Checklist-90 (SCL-90), the Interview Schedule for Social Interaction and the Social Network concept.Results:The CP patients had lower cognitive performance, reaching statistical significance in 12 of 20 test variables, including executive function and memory. Comparison of patients with TGTV to controls revealed, a significant lower mean total score (P = 0.006). A significant negative correlation was recorded between mean z-score of cognitive performance and years since operation (r= -0.407; P = 0.014). No statistically significant group differences were observed across any of the nine SCL-90 subscales.Conclusions:Adults with childhood onset CP, on hormone replacement, including GH treatment, have memory defects, disturbed attention and impaired processing speed. Patients with hypothalamic involvement are more affected. Patients rated their QoL as good as their matched controls.
The Journal of clinical endocrinology and metabolism 06/2013; · 6.50 Impact Factor
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ABSTRACT: BACKGROUND: Acute lymphoblastic leukaemia (ALL) patients treated with cranial radiotherapy (CRT) have an increased risk of GH deficiency (GHD). Little is known about insufficiencies of prolactin (PRL) and TSH, but also lactation failure has been reported in this population. OBJECTIVE: To study the long-term outcome of CRT on PRL and thyroid hormone levels in GHD ALL patients, and the prevalence of lactation failure. DESIGN: CASE-CONTROL STUDY: PATIENTS: We examined 40 GHD and 4 GH insufficient ALL patients, in median 20 years (range 8-27) after ALL diagnosis and 44 matched population controls. MEASUREMENTS: PRL secretion (area under the curve; AUC) after GHRH-arginine test in all patients and matched controls, and PRL and TSH AUC after a TRH test in 13 patients and 13 controls. And basal PRL and thyroid hormone levels after 5 years with GH therapy and 8 years without GH therapy. RESULTS: Compared to controls ALL patients had significantly lower basal and AUC PRL after GHRH-Arginine (P = 0.03, P = 0.02), and AUC PRL after TRH (P = 0.001). After 5 and 8 years, PRL levels decreased further (P = 0.01, P = 0.03), but thyroid hormones remained normal at baseline and at follow up. PRL insufficiency was significantly associated with increased levels of BMI and insulin. Six out of seven pregnant ALL women reported lactation failure. CONCLUSIONS: Long-term ALL survivors treated with CRT have GHD and PRL insufficiency, and a high prevalence of lactation failure, but thyroid hormones remained normal. PRL insufficiency was associated with cardiovascular risk. © 2012 Blackwell Publishing Ltd.
Clinical Endocrinology 11/2012; · 3.17 Impact Factor
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Helene Holmer,
Johan Svensson,
Lars Rylander,
Gudmundur Johannsson,
Thord Rosén,
Bengt-Åke Bengtsson,
Marja Thorén,
Charlotte Höybye,
Marie Degerblad,
Margareta Bramnert,
Erik Hägg,
Britt Edén Engström,
Bertil Ekman, Eva-Marie Erfurth
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ABSTRACT: CONTEXT: The psychosocial health and working capacity in hypopituitary patients receiving long-term growth hormone (GH) therapy are unknown. OBJECTIVE: Psychosocial health and levels of employment were compared between GH deficient (GHD) patients on long-term replacement and the general population. DESIGN AND PARTICIPANTS: In a Swedish nationwide study, 851 GHD patients [101 childhood onset (CO) and 750 adult onset (AO)] and 2622 population controls answered a questionnaire regarding current living, employment and educational level, alcohol consumption and smoking habits. The median time on GH therapy for both men and women with CO GHD was 9 years and for AO GHD 6 years, respectively. RESULTS: As compared to the controls, the GHD patients were less often working full time, more often on sick leave/disability pension, and to a larger extent alcohol abstainers and never smokers (all; P<0.05). Predominantly CO GHD women and men, but to some extent also AO GHD women and men, lived less frequently with a partner and more often with their parents. Particularly AO GHD craniopharyngioma women used more antidepressants, while AO GHD men with a craniopharyngioma used more analgesics. CONCLUSIONS: A working capacity to the level of the general population was not achieved among hypopituitary patients, although receiving long-term GH therapy. Patients were less likely to use alcohol and tobacco. The CO GHD population lived a less independent life.
Psychoneuroendocrinology 10/2012; · 5.81 Impact Factor
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ABSTRACT: A craniopharyngioma (CP) is an embryonic malformation of the sellar and parasellar region. The annual incidence is 0.5-2.0 cases/million/year and approximately 60 % of CP are seen in adulthood. Craniopharyngiomas have the highest mortality of all pituitary tumors. Typical initial manifestations at diagnosis in adults are visual disturbances, hypopituitarism and symptoms of elevated intracranial pressure. The long-term morbidity is substantial with hypopituitarism, increased cardiovascular risk, hypothalamic damage, visual and neurological deficits, reduced bone health, and reduction in quality of life and cognitive function. Therapy of choice is surgery, followed by cranial radiotherapy in about half of the patients. The standardised overall mortality rate varies 2.88-9.28 in cohort studies. Patients with CP have a 3-19 fold higher cardiovascular mortality in comparison to the general population. Women with CP have an even higher risk.
Pituitary 09/2012; · 1.83 Impact Factor
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ABSTRACT: Data on bone mineral density (BMD) are lacking in adults with childhood onset (CO)-craniopharyngioma (CP) with hypothalamic damage from the tumor. In patients with CO GH deficiency, BMD increases during GH treatment.
The aims were to evaluate BMD in adults with CO-CPs on complete hormone replacement, including long-term GH and to evaluate the impact of hypothalamic damage on these measures.
BMD (dual-energy X-ray absorptiometry), markers of bone turn over, physical activity and calcium intake were assessed in 39 CO-CP adults (20 women), with a median age of 28 (17-57) years, in comparison with matched population controls.
Late puberty induction was recorded in both genders, but reduced androgen levels in females only. Only CP women had lower BMD (P=0.03) at L2-L4, and reduced Z-scores at femoral neck (P=0.004) and L2-L4 (P=0.004). Both genders had increased serum leptin levels (P=0.001), which significantly correlated negatively with BMD at L2-L4 (P=0.003; r=-0.5) and 45% of CP women had Z-score levels ≤-2.0 s.d. Furthermore, 75% of those with a Z-score ≤-2.0 s.d. had hypothalamic involvement by the tumor. Calcium intake (P=0.008) and physical activity (P=0.007) levels were reduced in CP men only. Levels of ostecalcin and crossLaps were increased in CP men only.
Despite continuous GH therapy, low BMD was recorded in CO-CP females. Insufficient estrogen and androgen supplementation during adolescence was the main cause, but hypothalamic involvement with consequent leptin resistance was also strongly associated with low BMD in both genders.
European Journal of Endocrinology 07/2011; 165(1):25-31. · 3.42 Impact Factor
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ABSTRACT: Bone mineral density (BMD) in survivors of acute lymphoblastic leukaemia (ALL) seems to vary with time, type of treatments and GH status. We aimed to evaluate BMD in ALL patients with GH deficiency (GHD), with and without GH therapy.
Case-control study.
We examined 44 (21 women) GHD patients (median 25 years) treated with cranial radiotherapy (18-24 Gy) and chemotherapy and matched population controls for BMD with dual-energy X-ray absorptiometry. For 5 and 8 years, two subgroups with (0.5 mg/day) (n=16) and without GH therapy (n=13) and matched controls were followed respectively.
At baseline, no significant differences in BMD or Z-scores at femoral neck and L2-L4 were recorded (all P>0.3). After another 8 years with GHD, the Z-scores at femoral neck had significantly decreased compared with baseline (0.0 to -0.5; P<0.03) and became lower at the femoral neck (P=0.05), and at L2-L4 (P<0.03), compared with controls. After 5 years of GH therapy, only female ALL patients had a significantly lower femoral neck Z-scores (P=0.03). The female ALL patients reached an IGF1 level of -0.7 s.d. and male patients reached the level of +0.05 s.d.
On average, 25 years after diagnosis, GH-deficient ALL patients experienced a significant decrease in Z-scores at femoral neck, and if Z-scores continue to decrease, there could be a premature risk for osteoporosis. GH therapy was not shown to have a clear beneficial effect on BMD. Whether higher GH doses, particularly in women, will improve Z-scores needs further investigation.
European Journal of Endocrinology 03/2011; 164(5):695-703. · 3.42 Impact Factor
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ABSTRACT: This 15-year-old girl was operated due to an ectopic recurrence of a craniopharyngioma along the previous surgical route. She presented with a sellar craniopharyngioma at the age of 4 years and underwent a right subfrontal craniotomy. Two and a half years later she had a local recurrence in the sella that was resected along the same surgical route. Postoperative cranial radiotherapy was administered with 50 Gy divided into 28 fractions. Nine years later, magnetic resonance imaging (MRI) revealed a local recurrence within the sella together with a supraorbital cystic mass. Both tumors were surgically removed. Microscopic examination revealed recurrence of an adamantinous craniopharyngioma at both localisations. Histopathological preparations showed a higher MIB-1 index at the simultaneous recurrences in the sella and in the frontal lobe and also an elevated focal p53 expression, compared to previous operations, suggesting a transformation to a more aggressive tumor. This is the first case report of ectopic recurrence in a child that had received conventional radiotherapy of 50 Gy to the sella. Careful intra-operative procedure is probably crucial for preventing ectopic recurrences. The future will reveal if the transsphenoidal surgical route will put an end to ectopic tumor recurrence in patients with a craniopharyngioma.
Child s Nervous System 01/2011; 27(5):845-51. · 1.54 Impact Factor
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ABSTRACT: Obesity is a frequent manifestation of hypothalamic damage from a craniopharyngioma (CP). It is not yet clarified whether the obesity is due to alterations in energy expenditure, i.e. basal metabolic rate (BMR) and physical activity, or to increased energy intake (EI).
The aim was to investigate whether energy expenditure and EI differed between childhood onset CP patients and matched population controls and whether these measures were related to hypothalamic damage, as tumor growth into the third ventricle (TGTV).
Forty-two CP patients (20 women) aged 28 yr (range, 17-57 yr) operated between 1958 and 2000 in the South Medical Region of Sweden (population, 2.5 million) were studied. Body composition, satiety hormones, BMR (indirect calorimetry), physical activity, EI, and attitudes toward eating were assessed. Comparisons were made with matched controls and between patients with (n=25) and without (n=17) TGTV.
After adjustment, patients had lower BMR compared to controls (-90 kcal/24 h; P=0.02) and also had lower EI (1778 vs. 2094 kcal/24 h; P=0.008), and the EI/BMR ratio was significantly lower in TGTV patients. Similar dietary macronutrient composition was found, and only significantly higher scales in restricting food intake were recorded in patients. Ghrelin levels were significantly lower in patients, whereas serum insulin and leptin levels were higher (P<0.001), and both ghrelin and insulin correlated significantly to tumor growth. Lower levels of physical activity (P<0.01) were recorded in patients.
The major mechanisms that reinforced obesity were hypothalamic damage causing disrupted or impaired sensitivity to feeding-related signals for leptin, insulin, and ghrelin, and reductions in both BMR and physical activity.
The Journal of clinical endocrinology and metabolism 12/2010; 95(12):5395-402. · 6.50 Impact Factor
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ABSTRACT: Long-term data are missing in GH-treated acute lymphoblastic leukemia (ALL) patients. GH therapy may result in poorer outcome regarding cardiovascular (CV) and particularly cardiac effects than in patients with hypothalamic-pituitary disease.
Our objective was to evaluate GH therapy on CV risk, cardiac function, physical activity, and quality of life in ALL patients treated with cranial radiotherapy (18-24 Gy) and chemotherapy (anthracycline dose 120 mg/m2).
We conducted a 5- and 8-yr open nonrandomized prospective study in a university hospital clinic.
Two groups of GH-deficient ALL patients (aged 25 yr; range 19-32 yr) and matched population controls participated.
One ALL group (n=16) received GH for 5 yr, and the other ALL group (n=13) did not receive GH therapy.
We evaluated the prevalence of CV risk factors and metabolic syndrome (International Diabetes Federation consensus), cardiac function (echocardiography), and quality of life and physical activity questionnaires.
In comparison with 8 yr without, 5 yr with GH therapy resulted in significant positive changes in plasma glucose (-0.5 vs. 0.6 mmol/liter, P=0.002), apolipoprotein B/apolipoprotein A1 ratio (-0.1 vs. 0.0, P=0.03), and high-density lipoprotein-cholesterol (0.20 vs.-0.01 mmol/liter, P=0.008) and a significant reduction in the prevalence of metabolic syndrome (P=0.008). No significant difference in the left-ventricular systolic function or in physical activity and quality of life was recorded before and after 5 or 8 yr, respectively (all P>0.3).
GH therapy reduced the CV risk in this young ALL population but resulted in no clear benefit or deterioration in cardiac function.
The Journal of clinical endocrinology and metabolism 08/2010; 95(8):3726-35. · 6.50 Impact Factor
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ABSTRACT: Metabolic and body compositional consequences of GH deficiency (GHD) in adults are associated with a phenotype similar to the metabolic syndrome (MetS).
We assessed MetS prevalence in adult GHD patients (n = 2531) enrolled in the Hypopituitary Control and Complications Study. Prevalence was assessed at baseline and after 3 yr of GH replacement in a subset of 346 adult-onset patients.
Baseline MetS crude prevalence was 42.3%; age-adjusted prevalence in the United States and Europe was 51.8 and 28.6% (P < 0.001), respectively. In the United States, age-adjusted prevalence was significantly higher (P < 0.001) than in a general population survey. Increased MetS risk at baseline was observed for age 40 yr or older (adjusted relative risk 1.34, 95% confidence interval 1.17-1.53, P < 0.001), females (1.15, 1.05-1.25, P = 0.002), and adult onset (1.77, 1.44-2.18, P < 0.001). In GH-treated adult-onset patients, MetS prevalence was not changed after 3 yr (42.5-45.7%, P = 0.172), but significant changes were seen for waist circumference (62.1-56.9%, P = 0.008), fasting glucose (26.0-32.4%, P < 0.001), and blood pressure (59.8-69.7%, P < 0.001). Significantly increased risk of MetS at yr 3 was associated with baseline MetS (adjusted relative risk 4.09, 95% confidence interval 3.02-5.53, P < 0.001) and body mass index 30 kg/m(2) or greater (1.53, 1.17-1.99, P = 0.002) and increased risk (with a P value < 0.1) for GH dose 600 microg/d or greater (1.18, 95% confidence interval 0.98-1.44, P = 0.088).
MetS prevalence in GHD patients was higher than in the general population in the United States and higher in the United States than Europe. Prevalence was unaffected by GH replacement, but baseline MetS status and obesity were strong predictors of MetS after GH treatment.
The Journal of clinical endocrinology and metabolism 11/2009; 95(1):74-81. · 6.50 Impact Factor
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ABSTRACT: Craniopharyngioma patients without GH therapy are at an increased cardiovascular disease (CVD) risk and particularly concerning women. No previous study on long-term GH therapy in adults with childhood onset (CO) craniopharyngioma was identified.
To investigate CVD risk in adults with CO craniopharyngioma on complete hormone replacement, including long-term GH therapy, and to investigate the impact of disease-related factors on CVD risk.
In a cross-sectional study of operated CO craniopharyngiomas (1958-2000) from a defined area of Sweden (2.5 million), we enrolled 42 patients (20 women) with a median age of 28 years (range 17-57) and assessed CVD risk of 20 (4-40) years after first operation. Comparisons were made with matched controls and between patients with tumor growth into the third ventricle (TGTV) versus non-TGTV. GH therapy was 10-12 years in women and men. Results In comparison with controls, both male and female patients had increased body mass index, fat mass, insulin, and leptin levels. Overall, while not significantly increased in male patients, 55-60% of female patients had a medium-high CVD risk, compared with 10-20% in controls. An increased CVD risk (all P<0.05) and higher levels of fat mass and insulin were recorded in the TGTV group versus the non-TGTV group. Late puberty induction and lack of androgens were shown in female patients.
Adult patients with CO craniopharyngioma, especially those with TGTV, have persistently increased CVD risk. Conventional hormone substitution, including GH, is insufficient to normalize CVD risk, suggesting an important role for irreversible hypothalamic dysfunction.
European Journal of Endocrinology 09/2009; 161(5):671-9. · 3.42 Impact Factor
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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% 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.
Clinical Endocrinology 12/2008; 55(5):613 - 616. · 3.17 Impact Factor
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Helene Holmer,
Johan Svensson,
Lars Rylander,
Gudmundur Johannsson,
Thord Rosén,
Bengt-Ake Bengtsson,
Marja Thorén,
Charlotte Höybye,
Marie Degerblad,
Margareta Bramnert,
Erik Hägg,
Britt Edén Engström,
Bertil Ekman,
Karl-Göran Thorngren,
Lars Hagmar, Eva-Marie Erfurth
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ABSTRACT: Fracture risk in GHD patients is not definitely established. Studying fracture incidence in 832 patients on GH therapy and 2581 matched population controls, we recorded a doubled fracture risk in CO GHD women, but a significantly lower fracture risk in AO GHD men.
The objective of this study was to evaluate fracture incidence in patients with confirmed growth hormone deficiency (GHD) on replacement therapy (including growth hormone [GH]) compared with population controls, while also taking potential confounders and effect modifiers into account.
Eight hundred thirty-two patients with GHD and 2581 matched population controls answered a questionnaire about fractures and other background information. Incidence rate ratio (IRR) and 95% CI for first fracture were estimated. The median time on GH therapy for childhood onset (CO) GHD men and women was 15 and 12 yr, respectively, and 6 and 5 yr for adult onset (AO) GHD men and women, respectively.
A more than doubled risk (IRR, 2.29; 95% CI, 1.23-4.28) for nonosteoporotic fractures was recorded in women with CO GHD, whereas no risk increase was observed among CO GHD men (IRR, 0.61) and AO GHD women (IRR, 1.08). A significantly decreased incidence of fractures (IRR, 0.54; 95% CI, 0.34-0.86) was recorded in AO GHD men.
Increased fracture risk in CO GHD women can most likely be explained by interaction between oral estrogen and the GH-IGF-I axis. The adequate substitution rate of testosterone (90%) and GH (94%) may have resulted in significantly lower fracture risk in AO GHD men.
Journal of Bone and Mineral Research 01/2008; 22(12):1842-50. · 6.37 Impact Factor
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Helene Holmer,
Johan Svensson,
Lars Rylander,
Gudmundur Johannsson,
Thord Rosén,
Bengt-Ake Bengtsson,
Marja Thorén,
Charlotte Höybye,
Marie Degerblad,
Margareta Bramnert,
Erik Hägg,
Britt Edén Engström,
Bertil Ekman,
Bo Norrving,
Lars Hagmar, Eva-Marie Erfurth
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ABSTRACT: The impact of long-term GH replacement on cerebrovascular and cardiovascular diseases and diabetes mellitus in hypopituitary patients is unknown.
The incidence of nonfatal stroke and cardiac events, and prevalence of type 2 diabetes mellitus (T2D) and cardioprotective medication were compared between cohorts of GH-deficient (GHD) patients and population controls.
The incidence of nonfatal stroke and cardiac events was estimated retrospectively from questionnaires in 750 GHD patients and 2314 matched population controls. A prevalence of T2D and cardioprotective medication was recorded at the distribution of questionnaires. Time since first pituitary deficiency to start of GH therapy was 4 and 2 yr, and time on GH therapy was 6 yr for GHD women and men, respectively.
Lifelong incidence of nonfatal stroke was tripled in GHD women and doubled in GHD men, but a decline was seen in both genders during periods after first pituitary hormone deficiency and GHD, during which most patients had GH therapy. The lifelong incidence of nonfatal cardiac events declined in GHD men during first pituitary hormone deficiency and GHD periods. GHD women had a higher prevalence of T2D and lipid-lowering medication, whereas GHD men had a higher prevalence of antihypertensive medication.
The declined risks of nonfatal stroke in both genders and of nonfatal cardiac events in GHD men during periods on GH replacement may be caused by prescription of cardioprotective drugs and 6-yr GH replacement. GHD women had an increased prevalence of T2D, partly attributed to higher body mass index and lower physical activity.
Journal of Clinical Endocrinology & Metabolism 10/2007; 92(9):3560-7. · 6.50 Impact Factor
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ABSTRACT: Cranial radiotherapy (CRT) was, until recently, important for achieving long-term survival in acute lymphoblastic leukaemia (ALL). Because survival rates have improved markedly, the long-term complications, such as GH deficiency (GHD) and neuropsychological impairment, have become increasingly important.
The level of self-reported quality of life and neuropsychological functioning was investigated in 44 adults (21 women) with a median age of 25 years who had been treated for childhood onset (CO) ALL with CRT (median 24 Gy). Comparison was made with matched population controls. A subset of patients with GHD was evaluated for neuropsychological functioning after 1 year of GH treatment.
Compared to controls, the patients had significantly lower performance in neuropsychological tests. Early age at treatment had a significant negative impact on neuropsychological performance in adulthood. No relationship was found between dose of CRT, time since treatment of ALL or gender and neuropsychological performance. Compared to controls, the patients did not show a poor quality of life or a lowered availability of social interactions or social networks; however, significantly more patients were living alone or with their parents. After GH testing, the patients were all considered GH deficient or insufficient, but no relationship was observed between stimulated peak GH secretion and neuropsychological performance. Treatment with GH for 1 year in a subgroup of the patients did not improve their neuropsychological performance.
This study showed that adults treated with CRT for CO ALL had GHD and significantly impaired neuropsychological performance, although self-reported quality of life was not affected. The effect of GH treatment in this patient group has to be further elucidated.
Clinical Endocrinology 12/2006; 65(5):617-25. · 3.17 Impact Factor
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ABSTRACT: Animal and epidemiologic data indicate that exposure to persistent organochlorine pollutants (POPs) may disrupt the hypothalamus-pituitary-thyroid (HPT) and the hypothalamus-pituitary-gonadal (HPG) axes. We have assessed whether the POP-biomarkers 2,2'4,4',5,5'-hexachlorobiphenyl (CB-153) and 1,1-dichloro-2,2-bis(4-chlorophenyl)-ethene (p,p'-DDE) affect thyrotropin (TSH), thyroid hormones, gonadotropins or sex hormone concentrations in men.
Lipid adjusted serum concentrations of CB-153, and p,p'-DDE, were determined in 196 men (median age 59 years, range 48-82). Hormone analyses in serum were performed with immunoassays. The effect of CB-153 and p,p'-DDE (as continuous or categorized variables) were evaluated by linear regression models, adjusting for potential confounders.
There was a significant positive association between p,p'-DDE and TSH. An increase of 100 ng/g lipid of p,p'-DDE corresponded to an increase of 0.03 mU/l (95% Confidence Interval (CI) 0.01, 0.05) in TSH level. The explanatory value (R(2)) of the multivariate model was only 7%. Moreover, there was a significant negative association between p,p'-DDE and estradiol. An increase of 100 ng/g lipid of p,p'-DDE corresponded to a decrease of 0.57 pmol/l (95% CI -1.0, -0.12) in estradiol level. The R(2)-value was only 4%. No associations were observed between any of the POP biomarkers and the other hormones.
The positive association between p,p'-DDE and TSH and the negative association between p,p'-DDE and estradiol, among middle-aged and elderly men, were not accompanied by associations between the POP-markers and thyroxin, testosterone, and gonadotropins, respectively. The results gives some additional support for that POP exposure may affect HPT- and HPG-axes also in humans, but the overall epidemiological data are still not coherent enough to allow any firm conclusions.
Chemosphere 11/2006; 65(3):375-81. · 3.21 Impact Factor
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ABSTRACT: Survivors of childhood-onset (CO) acute lymphoblastic leukemia (ALL) treated with prophylactic cranial radiotherapy often exhibit GH deficiency (GHD), which is associated with increased prevalence of cardiovascular risk factors and cardiac dysfunction.
The objective of the study was to evaluate the effect of GH replacement on cardiovascular risk factors and cardiac function in former CO ALL patients.
Eighteen former CO ALL patients (aged 19-32 yr) treated with cranial radiotherapy (18-24 Gy) and chemotherapy and with confirmed GHD were studied at baseline and after 12 (n = 18) and 24 months (n = 13) of GH treatment (median 0.5 mg/d). A group of 18 age- and sex-matched subjects served as controls.
After 12 months of GH treatment, a significant decrease in serum leptin (P = 0.002), leptin per kilogram fat mass (FM) (P = 0.01), plasma glucose (P = 0.004), FM (P = 0.002), and hip (P = 0.04) and waist (P = 0.02) circumference and increased muscle mass (P = 0.004) were recorded in the patients. Before GH treatment six patients had a metabolic syndrome, but after 12 months only one had it and after 24 months none. After 24 months of GH treatment, an increase in left ventricular mass index (P = 0.06) and significant improvements in cardiac systolic function, measured as fractional shortening (P = 0.03) and ejection fraction (P = 0.03), were recorded.
Improvement in cardiac systolic function and reduced prevalence of metabolic syndrome were recorded after 2 yr of GH replacement in former CO ALL patients with GHD. Long-term follow-up is highly warranted.
Journal of Clinical Endocrinology & Metabolism 06/2006; 91(5):1872-5. · 6.50 Impact Factor
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ABSTRACT: Background
Animal and epidemiologic data indicate that exposure to persistent organochlorine pollutants (POPs) may disrupt the hypothalamus–pituitary–thyroid (HPT) and the hypothalamus–pituitary–gonadal (HPG) axes. We have assessed whether the POP-biomarkers 2,2′4,4′,5,5′-hexachlorobiphenyl (CB-153) and 1,1-dichloro-2,2-bis(4-chlorophenyl)-ethene (p,p′-DDE) affect thyrotropin (TSH), thyroid hormones, gonadotropins or sex hormone concentrations in men.
Chemosphere 01/2006; 65(3):375-381. · 3.21 Impact Factor
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ABSTRACT: The insulin tolerance test (ITT) is the current standard diagnostic test for the diagnosis of adult GH deficiency (GHD), but alternative tests, such as the GHRH-arginine test, have been proposed.
We investigated the sensitivity and specificity of the GHRH-arginine test using ITT as the gold standard in diagnosing GHD in a group of young adults treated with cranial irradiation (CRT) for childhood acute lymphoblastic leukemia (ALL). We estimated the positive and negative predictive values of the GHRH-arginine test among patients as well as a number of individual characteristics and therapy-related factors during both the GHRH-arginine test and ITT.
Forty-three young adults, treated for childhood ALL with 18-30 Gy CRT and chemotherapy, were studied, and comparison was made with matched controls.
We evaluated four different cutoff levels for GHD in the GHRH-arginine test: 5, 7.5, 9, and 16.5 microg/liter. Using 7.5 microg/liter as the cutoff yielded high specificity (94%), but at the same time the sensitivity was only 66%, which leads to a low negative predictive value (27%). In contrast, a failed GH response to the GHRH-arginine test accurately reflects the presence of radiation-induced GHD, illustrated by a high positive predictive value (95% at 7.5 microg/liter). Only age at CRT and body mass index remained significant predictors of the peak GH during the GHRH-arginine test. Because a high proportion of GHD patients show a normal response to the GHRH-arginine test, it cannot be used reliably to exclude GHD in these patients. Complementary ITT is also warranted to confirm GHD in obese patients.
Journal of Clinical Endocrinology & Metabolism 12/2005; 90(11):6048-54. · 6.50 Impact Factor
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ABSTRACT: Several studies have shown that patients with acromegaly have increased mortality rates for cardiovascular disease and cerebrovascular disease (CVD). Similar associations have also been seen for patients with hypopituitarism or with non-functional pituitary adenomas. This review summarizes these data and discusses the relative importance of different risk factors for cardiovascular, especially CVD, mortality among patients with acromegaly or non-functional pituitary adenomas, and for those with hypopituitarism as a result of other causes.
Trends in Endocrinology and Metabolism 10/2005; 16(7):334-42. · 8.11 Impact Factor
