Changes in membrane lipid composition of human erythrocytes after dietary supplementation of (n-3) polyunsaturated fatty acids. Maintenance of membrane fluidity.

The effect of dietary (n-3) polyunsaturated fatty acids on erythrocyte membrane lipid composition, fluidity, and flexibility was studied in seven healthy subjects. An eight weeks daily supplementation of 3 g of the (n-3) fatty acids eicosapentaenoic and docosahexaenoic acid resulted in an increased unsaturation of erythrocyte phosphatidylcholine (PC) and phosphatidylethanolamine (PE). This change was accompanied by a slight decrease in PC and PE content (P less than 0.05) and an increase in sphingomyelin content (P less than 0.01). The erythrocyte membrane fluidity, measured with electron spin resonance of intact erythrocytes and with fluorescence polarization of erythrocyte ghosts did not change. No change was seen in the viscosity of erythrocyte suspensions of haematocrit = 0.80, measured at various shear rates. The supplementation caused a 42% decrease in plasma triacylglycerol levels. We suggest that the change in the erythrocyte membrane fatty acid composition induced by the dietary supplementation of (n-3) fatty acids might be counteracted by a change in the phospholipid class distribution, resulting in overall maintenance of membrane fluidity.

Carriage of Staphylococcus aureus and inflamed infusion sites with insulin-pump therapy.

The most common complication of continuous subcutaneous insulin infusion (CSII) is inflammation at the infusion site. To determine possible risk factors to these infections, we studied several factors in the management of CSII and compared the pyogenic skin inflammation rate, the carriage rate of Staphylococcus aureus, and the HbA1 level among 50 CSII-treated diabetic patients, 50 diabetic patients on insulin injections, 48 diabetic patients on oral medication, and 40 healthy volunteers. There was no increased carriage rate of S. aureus among CSII-treated patients (42%) as compared with the other groups. An unexpected inverse relationship existed between HbA1 level and carriage rate in the CSII-treated group (HbA1 5-8%, n = 16, 69%; HbA1 8-10% n = 15, 40%; HbA1 greater than 10, n = 19, 21% P = .02). Pyogenic skin inflammations were reported by 24 (48%) CSII-treated patients, of which 18 had infected infusion sites, 6 (12%) insulin injecting patients, 2 (4%) patients on oral medication, and 3 (8%) healthy volunteers (P less than .01). The occurrence of inflamed infusion sites was not associated with carriage of S. aureus, the indwelling time of the needle, or the insulin dosage per day. There was an association, however, with the type of insulin preparation classified according to the added preservative: m-cresol-containing insulin (n = 24, 54%); methyl p-hydroxybenzoate-containing insulin (n = 26, 19%, P = .02). We concluded that the carriage of S. aureus is not increased among diabetic patients on CSII treatment and is not a risk factor in the occurrence of inflammation at the infusion site.(ABSTRACT TRUNCATED AT 250 WORDS)

Preservatives in insulin preparations impair leukocyte function. In vitro study.

m-Cresol and methyl p-hydroxybenzoate are preservatives in insulin preparations. As previously reported, in diabetic patients on continuous subcutaneous insulin infusion, users of insulin-containing m-cresol had significantly more inflamed infusion sites than users of insulin with methyl p-hydroxybenzoate. This study assessed the influence of insulin with and without these preservatives on leukocyte function. Leukocyte function was investigated in a killing experiment, expressed as the percentage of bacteria killed after 60 min incubation of bacteria (Staphylococcus aureus), polymorphonuclear leukocytes, serum, and insulin preparations. Because preservative is retained by the infusion device, insulin with preservative was tested before and after 1 and 4 days perfusion with a PVC pump catheter. After perfusion, the amount of preservative was reduced (percentage of original concentration after 1 and 4 days 8 and 30% m-cresol and 42 and 72% methyl p-hydroxybenzoate, respectively). The killing percentage in insulin with m-cresol reduced compared with insulin without preservative (mean +/- SE 95.4 +/- 0.8%) and the control without insulin (95.8 +/- 0.8%), both before and after 1 and 4 days perfusion (74.8 +/- 0.7, 80.2 +/- 2.8, and 80.6 +/- 1.6%, respectively; P less than 0.01). The same occurred in insulin with methyl p-hydroxybenzoate (85.0 +/- 0.9% before and 88.4 +/- 0.9 and 86.2 +/- 0.8% after 1 and 4 days perfusion; P less than 0.05). All insulin preparations with m-cresol caused lower killing percentages than corresponding insulin preparations with methyl p-hydroxybenzoate (P less than 0.05). These results demonstrate that both preservatives impaired leukocyte function, but m-cresol was the most noxious in this respect.(ABSTRACT TRUNCATED AT 250 WORDS)

Absorption kinetics and action profiles after sequential subcutaneous administration of human soluble and lente insulin through one needle.

The effects of sequential administration through one needle of human soluble and human lente insulin on plasma insulin levels and action profiles, assessed with glucose clamping, were studied in six healthy volunteers. Insulin kinetics after administration of human soluble insulin (0.22 IU/kg) alone were compared with those after sequential administration of 1) human soluble insulin followed by human lente insulin and 2) human lente insulin followed by human soluble insulin. Total insulin dose in both sequences was 0.55 IU/kg, 40% of which was short-acting insulin. Plasma insulin levels were not significantly different at any time point between 0 and 240 min after soluble insulin compared with either combination. Although insulin levels were slightly but significantly lower at 30 and 105 min after lente followed by soluble insulin compared with soluble followed by lente insulin, these differences probably reflect chance occurrences. Glucose requirements were not significantly different after either of the three administrations. We therefore conclude that the unwanted retarding effect after mixing of human soluble insulin with human lente insulin in the syringe on the onset of action of the soluble insulin can be prevented by sequential subcutaneous injection of these insulins with two syringes through one needle.

Consequences of childhood-onset growth hormone deficiency for adult bone mass.

To assess the implications of prolonged growth hormone deficiency (GHD) for the acquisition and maintenance of bone mass, bone mineral density (BMD) was measured in 70 adult males (mean age 26.7 +/- 4.5 years) with childhood-onset GHD, 7.4 +/- 4.2 years after discontinuation of previous GH therapy. Because most of these patients were short (mean height 165.8 +/- 6.6 cm), the influence of body height on standard BMD measurements, conventionally reported as the areal density (BMDarea, expressed in g/cm2), was analyzed in a group of age-matched healthy males. In GHD patients, BMDarea was significantly reduced at the lumbar spine (Z score -1.59 +/- 1.08, p < 0.001) as well as at the nondominant hip (Z score -1.18 +/- 0.95, p < 0.001). The reduction in BMDarea was similar for patients with isolated GHD (N = 25) and those with combined deficiencies of GH and luteinizing hormone (N = 40). In patients and controls, BMDarea was positively correlated with body height, a relation that was attributed to skeletal size. Bone dimensions were significantly smaller in patients than in controls, and therefore it was hypothesized that the difference in areal density between patients and controls might be confounded by differences in bone size. Measured bone mineral content corrected for the estimated bone volume (BMDvolume, expressed in g/cm3) remained significantly reduced (Z score: lumbar spine, -0.90 +/- 1.08, p < 0.001; femoral neck, -0.74 +/- 1.00, p < 0.001), but the differences between GHD patients and controls were less than indicated by BMDarea (p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Dose-response characteristics for arginine-stimulated insulin secretion in man and influence of hyperglycemia.

To test the hypothesis that glucose only affects the responsiveness (maximum velocity) of the beta-cell to arginine without changing the sensitivity (ED50) of the beta-cell to arginine, we investigated the influence of hyperglycemia on the responsiveness and sensitivity of arginine-induced insulin secretion in eight healthy male volunteers. Plasma C-peptide and insulin levels achieved during infusions of five doses of arginine (30 min) with and without a 60-min hyperglycemic clamp (17 mmol/L) were analyzed using a modified Michaelis-Menten equation. At euglycemia, the ED50 (half-maximally stimulating serum arginine concentration) was significantly less for first phase than for second phase plasma C-peptide secretion (0.7 +/- 0.1 vs. 2.7 +/- 0.4 mmol/L; P less than 0.002). Hyperglycemia significantly increased arginine-induced insulin secretion at all arginine infusion rates (P less than 0.01) without significantly altering the ED50 for either phase. We conclude 1) that the regulation of arginine-induced insulin secretion differs between both phases of insulin secretion, and 2) that a 1-h infusion with glucose significantly potentiates arginine-induced insulin secretion without influencing the difference in regulation of both phases of arginine-induced insulin secretion, supporting the validity of the use of arginine as a secretagogue in studies involving hyperglycemia.

Long-term effects of growth hormone (GH) replacement in men with childhood-onset GH deficiency.

Short term GH replacement therapy has been shown to improve body composition and exercise capacity. It is not yet known whether GH replacement remains beneficial over the long term. We assessed the effects of long term GH replacement on body composition, bone mineral density, and cardiac function. Thirty-eight men with childhood-onset GH deficiency were studied for a period of 3-5 yr. Measurements included anthropometry, computed tomographic scanning of abdomen and upper leg, bone densitometry, echo cardiography, and bicycle ergometry. The initial GH dose of 1-3 IU/m2 x day (9-27 microg/kg) was gradually tapered to 1.30+/-0.38 IU/m2 x day (11 g/kg), aiming at physiological insulin-like growth factor I levels. During the study, leg muscle mass progressively increased by 28.7% (P<0.001). Subcutaneous and intraabdominal fat decreased by 30.9% and 46.0%, respectively, after 1 yr (both P<0.001), but demonstrated a partial regain thereafter. Bone mineral density at the lumbar spine, femoral neck, and trochanter gradually increased by 9.6%, 11.1%, and 16.2%, respectively (all P<0.001). Left ventricular mass exceeded baseline values by 14.1% after 1 yr (P<0.001), but returned to pretreatment values thereafter. Stroke volume and cardiac output increased by 16.3% (P = 0.002) and 33.4% (P<0.001), respectively. Maximal work load increased from 189+/-30 to 232+/-41 watts (P<0.001). Thus, long term GH replacement is safe and beneficial. It improves cardiac performance without inducing left ventricular hypertrophy and progressively increases bone mineral density.

Growth hormone (GH) substitution in hypogonadotropic, GH-deficient women decreases the follicle-stimulating hormone threshold for monofollicular growth.

The FSH threshold concept for monofollicular growth (which means that at the time the largest follicle reaches 18 mm there are no other follicles with a diameter of 13-18 mm also present) was used during ovulation induction in hypogonadotropic women, who appeared to be GH deficient. This concept was used to investigate whether 1) GH influences the FSH threshold for monofollicular growth and 2) whether such an influence would depend upon the endogenous GH/insulin-like growth factor I (IGF-I)/IGF-binding protein-3 (IGFBP-3) levels. In six hypogonadotropic women the GH response after an insulin challenge did not exceed 6 microg/L. Patients underwent ovulation induction according to a low dose step-up protocol by hMG during two consecutive cycles. GH substitution was provided only during the second cycle. Except for one GH treated cycle, all cycles were ovulatory. IGF-I levels as well as IGFBP-3 levels significantly increased (P < 0.01) during GH substitution. Monofollicular growth was not achieved in the first cycles. In five of six GH-substituted cycles, monofollicular growth was obtained. FSH threshold levels decreased in all patients during GH substitution. The FSH area under the curve was negatively correlated to IGF-I (r = -0.6; P < 0.05) and IGFBP-3 (r = -0.6; P < 0.05). The results of this study indicate that GH may play a role in the physiological growth of the follicle; most likely this occurs by influencing the IGF-I or IGFBP-3 levels. GH appears to selectively increase the sensitivity of the dominant follicle to FSH, facilitating monofollicular growth.

Direct measurement of human plasma corticotropin-releasing hormone by "two-site" immunoradiometric assay.

A "two-site" immunoradiometric assay (IRMA) which allows the direct estimation of human CRH (hCRH) in plasma is described. Using this IRMA, basal levels of CRH in normal subjects ranged from 2-28 pg/mL [mean, 15 +/- 7 (+/- SD) pg/mL; n = 58]. Values in men and women were similar. Plasma CRH values within this range were also found in patients with Cushing's syndrome, Addison's disease, and Nelson's syndrome, with no correlation between plasma CRH and ACTH levels in these patients. Elevated plasma CRH levels were found in pregnant women near term [1462 +/- 752 (+/- SD) pg/mL; n = 55], and the dilution curve of this CRH-like immunoreactivity paralleled the IRMA standard curve. After its immunoadsorption from maternal plasma, this CRH-like material eluted on reverse phase high performance liquid chromatography with a retention time identical to that of synthetic CRH and had equipotent bioactivity with the synthetic peptide in the perfused anterior pituitary cell bioassay. Circulating CRH was not detected in Wistar rats, even after adrenalectomy and subsequent ether stress. Synthetic hCRH was degraded by fresh human plasma relatively slowly; 65% of added CRH remained after 1 h of incubation at 37 C. Degradation was inhibited by heat treatment (54 C; 1 h), cold treatment (4 C; 4 h), or freezing and thawing. Loss of synthetic rat CRH occurred more rapidly when fresh rat plasma was used; only 20% of added CRH remained under the same conditions. The inability to measure CRH in peripheral rat plasma may be due to the presence of active CRH-degrading enzymes which fragment the CRH molecule into forms not recognized by the CRH IRMA.

Body composition in adult growth hormone-deficient men, assessed by anthropometry and bioimpedance analysis.

Anthropometry and bioimpedance analysis (BIA) were used to assess body composition in 42 GH-deficient (GHD) adult males (mean age, 27.2 +/- 4.7 yr). During childhood, all patients had received GH treatment for a mean period of 8.4 +/- 3.8 yr. At the start of this study, GH therapy had been discontinued for a mean period of 7.5 +/- 4.5 yr. Eighteen patients had isolated GH deficiency (I-GHD). Twenty-four patients had multiple pituitary hormone deficiencies (M-PHD), substituted adequately. Compared to age- and sex-matched controls, the sum of skinfolds measured at 7 different sites was significantly higher in I-GHD and M-PHD patients [controls, 73.1 +/- 25.4 mm; I-GHD patients, 102.1 +/- 37.7 mm (P less than 0.001); M-PHD patients, 126.8 +/- 35.4 mm (P less than 0.001)]. The increase in sc fat deposition was most pronounced on the trunk, particularly in the breast and abdominal area. Total body muscle mass was significantly lower in GHD patients (P less than 0.001). In patients, body muscle mass and plasma somatomedin-C level were positively correlated (r = 0.43; P less than 0.005). Total body resistance measured by whole body BIA was significantly higher in the patient group and was negatively correlated with plasma somatomedin-C (r = -0.53; P less than 0.001). The high resistance values observed in GHD patients could only in part be explained by their lower lean body mass. The most important cause, however, was an increase in specific electrical resistance of the lean body mass (LBM), reflecting relative dehydration. We conclude that GH deficiency in adult males is associated with an increase in sc fat and a decrease in body muscle mass. In addition, there is a qualitative change in LBM. The BIA data indicate that in these patients, the hydration state of the LBM is lower than normal, due to a decrease in extracellular water.

The effect of growth hormone (GH) on histomorphometric indices of bone structure and bone turnover in GH-deficient men.

We investigated the effects of GH on bone structure and turnover by histomorphometry in GH-deficient adults. Therefore, transiliac bone biopsies were obtained before and after 1 yr of treatment in 36 GH-deficient men (mean age, 28 +/- 4 yr). Thirteen patients had isolated GH deficiency and 23 patients had multiple pituitary hormone deficiencies. Patients were randomly assigned to four treatment groups. Groups 1, 2, and 3 received 1, 2, and 3 IU/m2/day (0.35, 0.69, and 1.3 mg/m2/day) [corrected] GH, respectively, and the fourth group received placebo for the first 6 months and 2 IU/m2/day (5.8 mg/m2/day) GH for the subsequent 6 months. GH treatment resulted in an increase of cortical thickness from 0.98 +/- 0.27 to 1.20 +/- 0.35 mm (P = 0.005), but trabecular bone volume did not change. Bone formation variables increased significantly: osteoid surface increased from 8.5 +/- 5.3 to 15.5 +/- 6.1% (P = 0.0002), mineralizing surface increased from 6.7 +/- 2.5 to 10.8 +/- 4.4% (P = 0.0002), and bone formation rate increased from 0.04 +/- 0.02 to 0.08 +/- 0.04 mm3/mm2/day (P = 0.0001). Eroded surface did not change, but osteoclast number increased from 0.6 +/- 0.5 to 1.25 +/- 0.5 Oc/mm2 (P = 0.0001). The relative formation period increased significantly (P = 0.001), whereas the resorption period, including reversal phase, decreased from 65 to 40 days (P = 0.02). Activation frequency increased from 0.39 +/- 0.17 to 0.74 +/- 0.34 y(-1) (P = 0.0001). These data indicate a stimulated bone turnover as a result of GH treatment and a shorter resorption and reversal time. The increased turnover did not result in an increased trabecular bone volume, but the cortical thickness increased significantly.

Insulin-like growth factor-I and cognitive function in healthy older men.

The GH/insulin-like growth factor-I (GH/IGF-I) axis is known to be involved in aging of physiological functions. Recent studies indicate that the GH/IGF-I axis may be associated with cognitive functioning. The aim of the present study was to determine whether the age-related decline in circulating levels of IGF-I, as an index of anabolic status, is associated with cognitive functions that are known to decline with aging, but not with cognitive functions not sensitive to aging. Twenty five healthy older men with well-preserved functional ability participated in the study. We also administered neuropsychological tests of general knowledge, vocabulary, basic visual perception, reading ability, visuoconstructive ability, perceptual-motor speed, mental tracking, and verbal long-term memory. Performance on the last four tests decline with aging, whereas the first four of these tests have been shown not to be sensitive to cognitive aging. Mean age of the subjects was 69.1 +/- 3.4 (SD) yr (range 65-76 yr), their mean body mass index was 27.0 +/- 2.4 kg/m2, and their mean IGF-I level was 122 ng/mL (range: 50-220). We found IGF-I levels to be significantly associated with the performances (controlled for education) on the Digit Symbol Substitution test (r = 0.52, P = 0.009) and the Concept Shifting Task (r = -0.55, P = 0.005), which measure perceptual-motor and mental processing speed. Subjects with higher IGF-I levels performed better on these tests, performance on which is known to decline with aging. In conclusion, the results of this study support the hypothesis that circulating IGF-I may play a role in the age-related reduction of certain cognitive functions, specifically speed of information processing.

Linoleic-acid-enriched diet: long-term effects on serum lipoprotein and apolipoprotein concentrations and insulin sensitivity in noninsulin-dependent diabetic patients.

Long-term (30 wk) effects on serum lipoproteins and insulin sensitivity of two diets, one with a low polyunsaturated to saturated fat ratio (P:S 0.3) and one with a P:S of 1.0, were compared in 14 patients with noninsulin-dependent diabetes mellitus (NIDDM) in a crossover study. Total and LDL-cholesterol levels declined by 7.6% (p less than 0.01) and 9.8% (p less than 0.01), respectively, during the high P:S diet. VLDL-, HDL2-, and HDL3-cholesterol; triacylglycerol; and apolipoprotein A1, A2, and B levels were not affected by the change in P:S. Despite a modest increase of insulin-mediated glucose disposal at physiologic insulinemia during the high P:S diet, no influence was seen on glycemic control, and on blood glucose, plasma insulin, and C peptide responses to mixed meals. In conclusion, a linoleic-enriched diet in patients with NIDD causes a less atherogenic lipoprotein profile but does not influence glycemic control and carbohydrate tolerance.

Hypocholesterolemic effect of dietary soy protein versus casein in rhesus monkeys (Macaca mulatta).

Ten mature female rhesus monkeys were alternately fed semipurified diets containing casein or soy protein for periods of 13 to 17 wk. Each diet was fed for two periods. When the animals were changed from the commercial diet to the semipurified diet containing soy protein, a significant elevation in serum cholesterol occurred. The serum cholesterol levels gradually increased further, when the soy protein in the diet was replaced by casein. However, when subsequently the casein in the diet was replaced by soy protein, a significant decrease in serum cholesterol levels was observed. Finally, when the animals were changed back to the casein diet, a significant increase in serum cholesterol again occurred. Changes in serum cholesterol due to modulations in the type of protein in the diet were reflected mainly by changes in low-density lipoprotein cholesterol. Thus, the results of this study clearly show that the type of protein in the diet markedly affects serum cholesterol levels not only in experimental animals such as the rabbit, as is well known, but also in the rhesus monkey, which is more akin to man.

Characteristics of insulin binding to H35 hepatoma cells.

Well differentiated hepatoma cells in culture exhibit insulin binding and insulin effects. We have studied insulin binding in control and in H35 hepatoma cells down-regulated with insulin. H35 cells were grown in monolayers in alpha MEM. Insulin binding was measured with A14 mono 125I labelled insulin 72 h after seeding. Binding was time, temperature and pH-dependent. Receptor down-regulation was studied by exposing cells to increasing concentrations of unlabelled insulin. Monolayers preincubated with 10 micrograms/ml unlabelled insulin for 24 h showed a decrease of 65% in the number of insulin binding sites. There was no change in affinity.

Growth hormone administration in addition to a very low calorie diet and an exercise program in obese subjects.

A major problem of weight reduction in obesity is the undesirable loss of lean body mass that accompanies fat loss, particularly in severe calorie restriction. In order to achieve maximal fat loss, but without great loss of lean tissue, growth hormone (GH) in a dose of 6 U/day subcutaneously was added to a very low calorie diet and an exercise program for moderately obese subjects. Body weight, body composition and hormonal status were studied during an eight-week period. The results of seven patients using GH (seven females; mean age 39.1 +/- 7.9 years; mean body weight 94.2 +/- 10.7 kg; mean body mass index 35.1 +/- 2.3 kg/m2) were compared to the results of eight patients using placebo (two males, six females; mean age 38.9 +/- 10.4 years; 100.0 +/- 11.0 kg; mean body mass index 32.9 +/- 1.9 kg/m2). The groups were comparable for demographic data. Both serum insulin-like growth factor I (IGF-I) and IGF binding protein 3 (IGFBP-3) levels became significantly higher in the GH group (p = 0.001 and p = 0.014, respectively). Mean serum IGF-I levels increased from 29.0 +/- 8.19 nmol/l at randomization to 50.14 +/- 14.66 nmol/l after 2 weeks in the GH group, whereas the levels decreased from 34.25 +/- 10.26 nmol/l to 27.63 +/- 8.14 nmol/l in the placebo group. After two weeks, IGF-I and IGFBP-3 levels stabilized. In the first half of the study serum free triiodothyronine (T3) levels remained stable in the GH group, whereas a decrease was found in the placebo group.(ABSTRACT TRUNCATED AT 250 WORDS)

A five day treatment with daily subcutaneous injections of growth hormone-releasing peptide-2 causes response attenuation and does not stimulate insulin-like growth factor-I secretion in healthy young men.

The synthetic hexapeptide growth hormone-releasing peptide (GHRP)-2 specifically stimulates GH release in man. To determine the effects of prolonged treatment and whether response attenuation occurs in man, we administered to nine healthy subjects a daily s.c. injection of 100 microg GHRP-2 over 5 days. Every day blood samples were taken to determine GH, IGF-I, IGF-binding protein (IGFBP)-3 and osteocalcin levels. On days 1,3 and 5, GH was measured at -20,0,20,40,60,90,120 and 180 min using an immunometric and an immunofunctional assay. Mean-/+S.D). peak GH concentrations were 83+/-31, 59+/-22 and 51+/-13 microg/l on days 1, 3 and 5 respectively. Mean+/-S.D. areas under the curve for days 1, 3 and 5 were 6366+/-2514, 3987 +/- 1418 and 3392+/-1215 mU/l per min. Despite the maintained GH release, analysis of variance revealed that significant response attenuation occurred (P < 0.01). Mean serum IGF-I concentration did not increase after a 5 day treatment with GHRP-2. Mean basal levels were 22, 25,23,25,23,24 nmol/l measured on days 1 to 6. However, osteocalcin, another serum marker of GH activity in tissue, increased significantly from 3.2+/-1.0 to 4.2+/-0.4 microg/l (mean+S.D.) (P< 0.01).

Long-term residual complaints and psychosocial sequelae after remission of hyperthyroidism.

The issue of residual complaints after treatment for hyperthyroidism in current euthyroid patients was investigated by means of a survey. Patients treated for hyperthyroidism were selected from medical records of the previous 6 years in two Dutch University Clinics. After the exclusion of patients with comorbidity, 303 one-time hyperthyroid respondents were included in the analysis. A total of 77% of these patients had been diagnosed with Graves' Disease. The newly developed Hyperthyroidism Complaint Questionnaire (HCQ), was used to quantify problems of somatic and mental functioning. The SymptomsCheckList-90 (SCL-90) was used to assess self-reported psychopathological symptoms, the Nottingham Health Profile was used to measure perceived health/quality of life. Dysthyroid patients (n = 20) had a mean HCQ-score of 14.5 (+/- 8.1) complaints; patients who reported euthyroidism for less than 12 months (n = 171) had a mean of 9.3 (+/- 7.6) residual complaints; patients who reported euthyroidism for more than 12 months (n = 54) a mean of 6.6 (+/- 6.8) residual complaints. On each dimension of psychopathology covered by the SCL-90, including depression and anxiety, approximately one third of the total sample had a score exceeding 80% of adult females. According to the NHP lack of energy was evident in 53% of all respondents. Over one third of patients with a full-time job were unable to resume the same work after treatment. It appears that many of these patients are in need of psychological support.

Cognitive changes during growth hormone replacement in adult men.

The present study evaluates the effects of 2 years of growth hormone (GH) replacement therapy on psychological well-being and cognitive performance in adults with childhood-onset growth hormone deficiency (CO-GHD). A total of 48 GHD adult men (mean age: 27 years) were randomly assigned to one of four treatment groups: placebo treatment, or GH replacement in a dose of 1, 2, or 3 IU/m2, respectively. Placebo treatment was given for 6 months. Psychological assessments were made every 6 months. Assessments included somatic and psychological complaints, depression, fatigue, vigor, tension, state/trait anxiety, iconic memory, short-term memory, long-term memory and perceptual-motor skill. GH treatment was considered physiological if the observed insulin-like growth factor-I (IGF-I) levels were within the normal range. It was considered supraphysiological if serum IGF-I rose to a value exceeding the upper normal limit. During the placebo-controlled phase of the study the changes in memory performance were positively correlated to the GH induced changes in serum IGF-I concentration and, more weakly, to the daily GH substitution dose. At 6 months memory only had improved in the group receiving supraphysiological GH treatment, but not in the group of patients who had a normalization of serum IGF-I. However, after 1 year of treatment a normalization of memory functioning was found in both groups of patients and this was preserved during the 2nd year of treatment. No changes were observed in psychological well-being and perceptual-motor skill. We conclude that GH replacement improves memory function in adults with CO-GHD. It has no effect on psychological well-being or perceptual-motor skill. Supraphysiological treatment accelerates the recovery of memory performance. However, the long-term effects are not different from those achieved with physiological GH replacement.

Cognitive impairments and mood disturbances in growth hormone deficient men.

In order to establish whether reported psychological complaints in hypopituitary adults are related to growth hormone (GH) deficiency or other pituitary hormone deficiencies, emotional well-being and cognitive performance were evaluated in 31 men with multiple pituitary hormone deficiencies (MPHD) and in 17 men with isolated growth hormone deficiency (IGHD). Assessments included evaluation of somatic and psychological complaints, depression, fatigue, vigor, tension, state and trait anxiety, iconic memory, short-term memory, long-term memory and perceptual-motor skill. The control group consisted of 41 healthy men, matched for age. Growth hormone secretion was more severely impaired in MPHD than in IGHD patients. Despite oral replacement therapy, MPHD patients also had lower serum testosterone levels than IGHD subjects. The MPHD patients were found to have lower vigor scores, higher state anxiety scores, worse perceptual-motor skill and worse memory performance than controls. In contrast, IGHD patients only showed subnormal memory performance. It was concluded, therefore, that the cognitive impairment in both MPHD and IGHD was related to GH deficiency. The subnormal vigor scores in MPHD patients were attributed to the reduced testosterone levels. The worse perceptual-motor skill in MPHD patients might be related specifically to ACTH deficiency. Finally, the higher state anxiety in MPHD was attributed to a low self-esteem, which may be the psychological consequence of the hypogonadal appearance these patients have. We conclude that, from a psychological point of view, MPHD and IGHD adult patients are quite distinct groups.