Detailed assessment of hypothalamic damage in craniopharyngioma patients with obesity.

BACKGROUND/OBJECTIVES: Hypothalamic obesity (HO) occurs in 50% of patients with the pituitary tumor craniopharyngioma (CP). Attempts have been made to predict the risk of HO based on hypothalamic (HT) damage on magnetic resonance imaging (MRI), but none have included volumetry. We performed qualitative and quantitative volumetric analyses of HT damage. The results were explored in relation to feeding related peptides and body fat. SUBJECTS/METHODS: A cross-sectional study of childhood onset CPs involving 3 Tesla MRI, was performed at median 22 years after first operation; 41 CPs, median age 35 (range: 17-56), of whom 23 had HT damage, were compared to 32 controls. After exclusions, 35 patients and 31 controls remained in the MRI study. Main outcome measures were the relation of metabolic parameters to HT volume and qualitative analyses of HT damage. RESULTS: Metabolic parameters scored persistently very high in vascular risk particularly among HT damaged patients. Patients had smaller HT volumes compared to controls 769 (35-1168) mm3 vs. 879 (775-1086) mm3; P < 0.001. HT volume correlated negatively with fat mass and leptin among CP patients (rs = -0.67; P < .001; rs = -0.53; P = 0.001), and explained 39% of the variation in fat mass. For every 100 mm3 increase in HT volume fat mass decreased by 2.7 kg (95% CI: 1.5-3.9; P < 0.001). Qualitative assessments revealed HT damage in three out of six patients with normal volumetry, but HT damage according to operation records. CONCLUSIONS: A decrease in HT volume was associated with an increase in fat mass and leptin. We present a method with a high inter-rater reliability (0.94) that can be applied by nonradiologists for the assessment of HT damage. The method may be valuable in the risk assessment of diseases involving the HT.

Moderate dose cranial radiotherapy causes central adrenal insufficiency in long-term survivors of childhood leukaemia.

Acute lymphoblastic leukaemia (ALL) is the most common childhood malignancy. The survival rate in the Scandinavian countries is now around 85 %. ALL patients treated with cranial radiotherapy (CRT) are at risk for growth hormone deficiency (GHD), but little is known about other pituitary insufficiencies, e.g. ACTH. Adult ALL patients (median age at study 25 years), treated with 24 Gy (18-30) of CRT during childhood were investigated. We performed an insulin tolerance test (ITT) to evaluate cortisol secretion. We measured basal serum ACTH and cortisol levels before and after 5 years of GH therapy. 14 out of 37 (38 %) ALL patients had a subnormal cortisol response to an ITT (257-478 nmol/L) while there was no significant difference in basal cortisol levels between 44 patients and controls (P > 0.3). Female, but not male ALL patients had significantly lower ACTH levels compared to controls (P = 0.03). After 5 years of GH therapy only male ALL patients had significantly lowered basal plasma cortisol (P = 0.02). ALL survivors, treated with a moderate dose CRT, have a central adrenal insufficiency 20 years after diagnosis. An increased awareness of the risk for an adrenal insufficiency is of importance and life-long surveillance of the entire hypothalamic-pituitary axis is recommended in these patients.

Microstructural white matter alterations and hippocampal volumes are associated with cognitive deficits in craniopharyngioma.

CONTEXT: Patients with craniopharyngioma (CP) and hypothalamic lesions (HL) have cognitive deficits. Which neural pathways are affected is unknown. OBJECTIVE: To determine whether there is a relationship between microstructural white matter (WM) alterations detected with diffusion tensor imaging (DTI) and cognition in adults with childhood-onset CP. DESIGN: A cross-sectional study with a median follow-up time of 22 (6-49) years after operation. SETTING: The South Medical Region of Sweden (2.5 million inhabitants). PARTICIPANTS: Included were 41 patients (24 women, ≥17 years) surgically treated for childhood-onset CP between 1958-2010 and 32 controls with similar age and gender distributions. HL was found in 23 patients. MAIN OUTCOME MEASURES: Subjects performed cognitive tests and magnetic resonance imaging, and images were analyzed using DTI of uncinate fasciculus, fornix, cingulum, hippocampus and hypothalamus as well as hippocampal volumetry. RESULTS: Right uncinate fasciculus was significantly altered (P ≤ 0.01). Microstructural WM alterations in left ventral cingulum were significantly associated with worse performance in visual episodic memory, explaining approximately 50% of the variation. Alterations in dorsal cingulum were associated with worse performance in immediate, delayed recall and recognition, explaining 26-38% of the variation, and with visuospatial ability and executive function, explaining 19-29%. Patients who had smaller hippocampal volume had worse general knowledge (P = 0.028), and microstructural WM alterations in hippocampus were associated with a decline in general knowledge and episodic visual memory. CONCLUSIONS: A structure to function relationship is suggested between microstructural WM alterations in cingulum and in hippocampus with cognitive deficits in CP.

GH safety workshop position paper: a critical appraisal of recombinant human GH therapy in children and adults.

Recombinant human GH (rhGH) has been in use for 30 years, and over that time its safety and efficacy in children and adults has been subject to considerable scrutiny. In 2001, a statement from the GH Research Society (GRS) concluded that 'for approved indications, GH is safe'; however, the statement highlighted a number of areas for on-going surveillance of long-term safety, including cancer risk, impact on glucose homeostasis, and use of high dose pharmacological rhGH treatment. Over the intervening years, there have been a number of publications addressing the safety of rhGH with regard to mortality, cancer and cardiovascular risk, and the need for long-term surveillance of the increasing number of adults who were treated with rhGH in childhood. Against this backdrop of interest in safety, the European Society of Paediatric Endocrinology (ESPE), the GRS, and the Pediatric Endocrine Society (PES) convened a meeting to reappraise the safety of rhGH. The ouput of the meeting is a concise position statement.

Increased plasma gonadotropin levels in spontaneous hyperthyroidism reproduced by thyroxine but not by triiodothyronine administration to normal subjects.

In nine hyperthyroid women studied in the follicular phase of the menstrual cycle basal plasma LH concentrations and LH and FSH responses to GnRH were increased compared to those in nine normal women. The increased gonadotropin levels could not be related to changes in body weight or plasma estradiol or serum sex hormone-binding globulin levels, and they approached normal levels during or after treatment of hyperthyroidism. When normal women were treated with T4 (0.5 mg daily for 6-10 days), their mean serum free T4 level increased to about 60% of that in the hyperthyroid patients, while their serum T3 levels increased to a lesser degree. During T4 administration these women had gonadotropin changes similar to those of the hyperthyroid patients. When the normal women took T3 (60-120 micrograms for 6-8 days), their serum T3 level rose almost to the level in the hyperthyroid patients, but basal and GnRH-stimulated LH and FSH remained close to control levels. Dopaminergic blockade with metoclopramide did not alter the gonadotropin response to GnRH in any subject group. We conclude that serum T4 is of greater importance than serum T3 for at least short term gonadotropin regulation.

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.

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.

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.

Quality of life in adults with growth hormone (GH) deficiency: response to treatment with recombinant human GH in a placebo-controlled 21-month trial.

We examined the effect of GH supplementation on the psychological capacity and sense of well-being in 36 patients with adult-onset GH deficiency (GHD). Recombinant human GH was given in a 21-month cross-over, double blind trial, and quality of life was assessed by using three self-rating questionnaires: the Hopkins Symptom Check List (HSCL), the Nottingham Health Profile (NHP), and the Psychological General Well-Being index. In addition, at the final examination the spouses completed a short questionnaire concerning their partner. Before treatment, the patients had lowered quality of life as determined by the HSCL and NHP inventories, and a correlation between the duration of GHD and the reported symptoms was observed. Upon treatment, the HSCL score was lower (better) after placebo administration (mean +/- SD, 84 +/- 21.3) than at baseline (89 +/- 18.9; P = NS) and fell to 80.2 +/- 18.5 (P < 0.001) when active drug was given. The subscales regarding anxiety, fearfulness, and cognition were the most sensitive. It was apparent that the effect determined after GH therapy in part was due to a placebo effect. With NHP, the dimensions of energy and emotions responded most to treatment. Further, the spouses observed their partners to be improved in several aspects of mood and behavior (P < 0.05 to P < 0.0001) when active drug was given. The data thus demonstrate that GH, which is known to have multiple somatic effects, produces an improvement in the quality of life of adults with GHD.

Decreased serum testosterone and free triiodothyronine levels in healthy middle-aged men indicate an age effect at the pituitary level.

In an attempt to study further the age-specific influence on the hypothalamo-pituitary-gonadal axis as well as the hypothalamo-pituitary-thyroid axis, we have now investigated young and middle-aged men, considering possible confounding factors. Both serum total testosterone, free testosterone and the total ratio of testosterone to sex-hormone binding globulin were significantly lower among middle-aged men as compared with young men (p = 0.02, p = 0.002 and p = 0.0003, respectively). In accordance with these findings there was also a decrease in the luteinizing hormone response to gonadotrophin-releasing hormone in the middle-aged men (p = 0.02). Free testosterone was correlated significantly with the luteinizing hormone response (r = 0.32, p = 0.02). Serum free triiodothyronine was significantly higher among young men as compared with middle-aged men (p = 0.002) and the thyrotrophin-releasing hormone-stimulated thyrotrophin response was also higher in the young group compared with the middle-aged group. The present results may indicate that the age effect on serum levels of testosterone and free triiodothyronine is mediated at the pituitary level.

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.

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.

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.

Plasma homocysteine in 80-year-olds: relationships to medical, psychological and social variables.

Plasma homocysteine concentrations in a group of 80-year-old persons were related to symptoms and signs. Plasma homocysteine concentrations higher than 15 micromol/l were associated with lower total life satisfaction (P<0.01), mood (P<0.05), zest for life (P<0.05), lower scores for reasoning (P<0.05), spatial ability (P<0.05), memory recognition (P<0.05), and subjective health (P<0.01). In an instrument comprising of 30 symptoms, plasma homocysteine concentrations higher than 15 micromol/l were associated with impaired concentration (P<0.05), restlessness (P<0.05), feeling cold (P<0.05), loss of weight (P<0.05), and feeling depressed (P<0.01). The above data indicate that plasma homocysteine values over 15 micromol/l could be relevant markers for clinical intervention.

Plasma levels of persistent organohalogens and hormone levels in adult male humans.

In this study the authors assessed the possible relationship between high dietary exposure to persistent organohalogens (OHS) through fatty fish from the Baltic Sea and hormone levels in adult men. Blood samples were drawn from 110 men who consumed varying amounts of fish (i.e., 0-32 meals per month) for analysis of plasma levels of 18 polychlorinated biphenyl (PCB) congeners, 5 hydroxy-PCBs, 1,1,1-trichloro-2,2-bis(4-chlorophenyl)-ethane (p,p'-DDT), 1,1-dichloro-2,2-bis(4-chlorophenyl)-ethene (p,p'-DDE), hexachlorobenzene, and 2,2',4,4'-tetrabromodiphenyl ether. In addition, plasma levels of follicle-stimulating hormone, luteinizing hormone, prolactin, plasma thyrotropin, free and total T3, free and total T4, and free testosterone were analyzed. The authors adjusted for age, and the only significant associations that remained were negative correlations between 2,2',4,4'-tetrabromodiphenyl ether and plasma thyrotropin (p < .001), and between pentachlorophenol and follicle-stimulating hormone (p = .04). The authors expected that there would be some significant correlations that resulted from pure chance. High consumption of organohalogen-polluted fish did not appear to affect plasma concentrations of pituitary, thyroid, or testosterone hormone levels in male adults.

Effects of lead on the endocrine system in lead smelter workers.

In this study of the effects of lead on the endocrine system, 77 secondary lead-smelter workers (i.e., 62 active and 15 retired) were compared with 26 referents. Lead concentrations were determined in plasma with inductively coupled plasma mass spectrometry (i.e., index of recent exposure), in blood with atomic absorption spectrophotometry, and in fingerbone with K x-ray fluorescence technique (i.e., index of long-term exposure). In addition, pituitary hormones were determined in serum by fluoroimmunoassay, and thyroid hormones and testosterone in serum were determined with radioimmunoassay. Nine lead workers and 11 referents were challenged with gonadotrophin-releasing hormone and thyrotrophin-releasing hormone, followed by measurements of stimulated pituitary hormone levels in serum. Median levels of lead in plasma were 0.14 microg/dl (range = 0.04-3.7 microg/dl) in active lead workers, 0.08 microg/dl (range = 0.05-0.4 microg/dl) in retired lead workers, and 0.03 microg/dl (range = 0.02-0.04 microg/dl) in referents (1 microg/dl = 48.3 nmol/l). Corresponding blood lead concentrations were 33.2 microg/dl (range = 8.3-93.2 microg/dl), 18.6 microg/dl (range = 10.4-49.7 microg/dl), and 4.1 microg/dl (range 0.8-6.2 microg/dl), respectively. Respective bone lead levels were 21 microg/gm (range = -13 to 99 microg/gm), 55 microg/gm (range = 3-88 microg/gm), and 2 microg/gm (range = -21 to 14 microg/gm). Concentrations of basal serum hormone (i.e., free thyroid hormones, thyrotrophin, sex hormone binding globulin, and testosterone) were similar in the 3 groups. There were no significant associations between the hormones mentioned herein and blood plasma, blood lead, and bone lead levels. In the challenge test, stimulated follicle-stimulating hormone levels were significantly lower in lead workers (p = .014) than in referents, indicating an effect of lead at the pituitary level. Also, there was a tendency toward lower basal stimulated follicle-stimulating hormone concentrations in lead workers (p = .08). This effect, however, was not associated with blood plasma level, blood lead level, or bone lead level. In conclusion, a moderate exposure to lead was associated with only minor changes in the male endocrine function, particularly affecting the hypothalamic-pituitary axis. Given that sperm parameters were not studied, the authors could not draw conclusions about fertility consequences.

Deaths among adult patients with hypopituitarism: hypocortisolism during acute stress, and de novo malignant brain tumors contribute to an increased mortality.

CONTEXT: Patients with hypopituitarism have an increased standardized mortality rate. The basis for this has not been fully clarified. OBJECTIVE: To investigate in detail the cause of death in a large cohort of patients with hypopituitarism subjected to long-term follow-up. DESIGN AND METHODS: All-cause and cause-specific mortality in 1286 Swedish patients with hypopituitarism prospectively monitored in KIMS (Pfizer International Metabolic Database) 1995-2009 were compared to general population data in the Swedish National Cause of Death Registry. In addition, events reported in KIMS, medical records, and postmortem reports were reviewed. MAIN OUTCOME MEASURES: Standardized mortality ratios (SMR) were calculated, with stratification for gender, attained age, and calendar year during follow-up. RESULTS: An excess mortality was found, 120 deaths vs 84.3 expected, SMR 1.42 (95% confidence interval: 1.18-1.70). Infections, brain cancer, and sudden death were associated with significantly increased SMRs (6.32, 9.40, and 4.10, respectively). Fifteen patients, all ACTH-deficient, died from infections. Eight of these patients were considered to be in a state of adrenal crisis in connection with death (medical reports and post-mortem examinations). Another 8 patients died from de novo malignant brain tumors, 6 of which had had a benign pituitary lesion at baseline. Six of these 8 subjects had received prior radiation therapy. CONCLUSION: Two important causes of excess mortality were identified: first, adrenal crisis in response to acute stress and intercurrent illness; second, increased risk of a late appearance of de novo malignant brain tumors in patients who previously received radiotherapy. Both of these causes may be in part preventable by changes in the management of pituitary disease.

Bone loss after childhood acute lymphoblastic leukaemia: an observational study with and without GH therapy.

OBJECTIVE: 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. DESIGN: Case-control study. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Physiological restitution after night-call duty in anaesthesiologists: impact on metabolic factors.

BACKGROUND: Several studies have shown impaired mental well-being and performance in physicians work on call, but knowledge of the physiological effects is scarce. The aims of the present study were to investigate if there was a metabolic stress response in the restitutional phase after night-call duty, indicating potential negative health effects, and determine whether there were differences between physician specialities. METHODS: Anaesthesiologists (n = 19) were compared with paediatricians/ear, nose and throat (ENT) surgeons (n = 18). On an ordinary workday, 1 and 3 days after work on night call, blood samples were taken for analysis of glucose, thyroid-stimulating hormone (TSH), free thyroxine, testosterone, insulin growth factor-1 (IGF-1), high- and low-density lipoprotein cholesterol (HDL and LDL), triglycerids (TG) and insulin. Saliva cortisol was sampled on an ordinary working day, a day including 16-h night call, the third day following, and for anaesthesiologists also on a day off work. RESULTS: TSH differed significantly between days in both groups, with a 26% lower level 1 day after on-call duty (P < 0.001). A 48% cortisol rise in the morning preceding night duty was found for paediatricians/ENT surgeons (P < 0.01). CONCLUSION: The significant dip in TSH level 24 h after night-call duty indicates a metabolic effect of working on night call and should be studied further. However, the levels were within the normal range and the overall results do not imply any serious metabolic changes and only minor differences were seen between specialist groups.