Biomedical subjects

M Thorén

Publications and source records attributed to M Thorén.

At least 19 recordsLinked to original sources

PubMed2005

An 88-year-old woman diagnosed with adrenal tumor and congenital adrenal hyperplasia: connection or coincidence?

An 88-yr-old woman presented with a 3x4x5 cm adrenal incidentaloma. Apart from partial cortisol deficiency there were no clinical or laboratory signs of abnormal hormone production. Because of suspicion of carcinoma, a urinary steroid profile was carried out which indicated 21-hydroxylase deficiency with elevated pregnantriol. Biopsy of the tumor showed benign adenoma tissue. The genetic analysis showed two mutations in the CYP21-gene, V281L and 1172N consistent with mild non-classic congenital adrenal hyperplasia (CAH). The patient showed a general improvement with a low prednisolone dose. Previous reports have shown increased prevalence of CAH in patients with adrenal tumors although, to our knowledge, no one has reported the combination in a patient as old as in ours. Thus, clinical signs and symptoms of CAH should be looked for in patients with adrenal incidentalomas, even in the very old ones, and if suspicion further diagnostic work-up should be carried out to provide adequate treatment and follow-up.

Adenoma↗

PubMed2005

Cognitive, emotional, physical and social effects of growth hormone treatment in adults with Prader-Willi syndrome.

BACKGROUND: Prader-Willi syndrome (PWS) is a multisystem genetic disorder characterized by short stature, muscular hypotonia, hyperphagia, obesity, maladaptive behaviour, hypogonadism and partial growth hormone (GH) deficiency (GHD). Severe GHD of other aetiologies has been shown to affect mood and quality of life negatively, and there are reports of improvements with GH replacement. We have studied cognitive, emotional, physical and social parameters in PWS adults at baseline, during and after GH treatment. PATIENTS AND METHODS: Nineteen patients, 9 females and 10 males, median age 25 years, mean BMI 35 kg/m2 participated in this study. Approximately half of the group had GHD. All patients fulfilled the clinical criteria for PWS and 13 had a positive genotype. The patients were randomized to 6 months of treatment with either GH [1.6 IU/day (0.53 mg/day)] or placebo, followed by 12 months of active GH treatment. Treatment was then stopped, and the patients were followed for an additional period of 6 months. A test battery for general cognitive evaluation and a computer-based measurement of reaction time, motor speed and fluency were employed at baseline, after 6 months and at the end of GH treatment. At the same time intervals, a self-evaluation questionnaire was answered at the end of each test session. Other questionnaires reflecting the patients' cognitive, emotional, physical and social status were answered by relatives/caretakers at baseline and at 3 and 6 months following cessation of GH treatment. RESULTS: Baseline cognitive level was estimated to be moderately to mildly impaired; IQ range was 40-90. The results from some of the cognitive and the motor performance tests improved significantly after 6 and 18 months of GH treatment. According to the questionnaires, both the patients and the relatives/caretakers evaluated physical status rather negatively at baseline, but still, impairments in both physical and social status and overall functioning were observed when GH treatment was discontinued. The self-evaluation did not change in any aspect during GH treatment. CONCLUSIONS: In this pilot study of an adult PWS cohort, we were able to document beneficial effects in mental speed and flexibility and in motor performance during GH treatment. Impairment was seen in physical and social status as well as overall functioning, when GH treatment stopped. Studies of larger cohorts are needed to further elucidate the role of GH treatment in this group of patients.

Adult↗

PubMed2003

The hypothalamus-pituitary function after pituitary stereotactic radiosurgery: evaluation of growth hormone deficiency.

OBJECTIVES: Radiation therapy to the pituitary gland means a considerable risk of developing hypopituitarism. The aim of the study was to investigate the growth hormone releasing hormone (GHRH)-growth hormone (GH)-insulin-like growth factor-I (IGF-I) axis after treatment with stereotactic radiosurgery to the pituitary because of Cushing's disease. SETTING: Inpatient ward in university clinic. SUBJECTS: Eleven adult patients (eight women, three men), 20-65 years of age were studied 2.5-11.3 years after stereotactic radiosurgery (isocentre dose 50-100 Gy lesion-1) and compared with healthy controls. MAIN OUTCOME MEASURES: Spontaneous GH secretion was evaluated as 12-h night GH profiles. Stimulated GH responses were evaluated in seven of 11 patients using arginine-insulin and GHRH tests. Serum IGF-I levels were measured in fasting serum morning samples. RESULTS: All patients except one displayed blunted nocturnal GH profiles. After arginine-insulin challenge, six of seven patients displayed low GH release. GH response was higher after GHRH injection compared with both the response to arginine-insulin and to the maximum GH levels in the nocturnal profiles. Seven patients had an IGF-I standard deviation score (SDS) within the normal range for age. Serum IGF-I values were correlated to mean GH values in the 12-h night profile (r = 0.67, P < 0.05) and both these variables were negatively correlated to time elapse since last radiation treatment (r = -0.64, P < 0.05 and r = -0.78, P < 0.05, respectively). CONCLUSIONS: Our patients with Cushing's disease evaluated several years after stereotactic radiosurgery as the primary and only treatment, demonstrated severely blunted spontaneous GH secretion and GH response to arginine-insulin. A disturbed regulation at the hypothalamic level was suggested as mechanism for this. Noteworthy is that serum IGF-I values correlated to the mean values of the 12-h GH profile.

Adult↗

PubMed2001

In vitro release of aldosterone and cortisol in human adrenal adenomas correlates to mRNA expression of steroidogenic enzymes for genes CYP11B2 and CYP17.

Adenomas of the adrenal cortex cause different disorders depending on the main steroid synthesized and released. The aim of this research is to increase our understanding of the pathophysiology of steroidogenesis in adrenocortical disorders by comparing the release of steroids from adrenocortical adenomas in vitro with the messenger RNA (mRNA) expression of steroid synthesizing enzymes. Fourteen patients with adrenal tumors were included in the present study; nine were diagnosed with primary aldosteronism and three with Cushing's syndrome. Two patients had an adrenal tumor discovered on computed tomography (CT) during workup for an unrelated disease. Serum cortisol, plasma aldosterone, and urinary catecholamines were normal. Tissue was taken for in vitro steroid release, and aldosterone and cortisol in the medium after a 1-hour incubation were determined. Oligonucleotide probes with sequences complementary to mRNAs encoding for the steroid synthesizing enzymes 11 beta-hydroxylase (CYP11B1), 18-hydroxylase (CYP11B2), 17 alpha-hydroxylase (CYP17), and 21-hydroxylase (CYP21) were synthesized (Genset, Paris, France) and in situ hybridization was performed. Moderate expression of CYP11B2 and low expression of CYP11B1 were seen in the zona glomerulosa. The zona fasciculata of the control adrenals expressed a high signal of CYP11B1, whereas the expression of CYP11B2 was very low. There was considerable variation in aldosterone release from the aldosteronomas, whereas the tumors from the Cushing patients showed no detectable release of aldosterone. In contrast, tumors from patients with primary aldosteronism, Cushing's syndrome, and no hyperfunction all had the ability to synthesize and release cortisol in vitro. The highest cortisol release was found in tumors from patients with Cushing's syndrome, but also the nonhyperfunctioning tumors and some of the aldosteronomas released significant amounts of cortisol. The two patients with highest release of aldosterone in vitro showed the highest expression of CYP11B2 and the lowest expression of CYP11B1 and CYP17. The remaining aldosteronomas had low expression of CYP11B2, similar to the two other groups. Expression of CYP11B1 was high as expected in the Cushing adenomas, but also the two nonhyperfunctioning tumors and some of the aldosteronomas showed a moderate expression. Adenomas from Cushing's syndrome, nonhyperfunctioning adenomas, and some of the aldosterone-producing adenomas had moderate to high expression of CYP17. This paper presents new means for functional characterization of adrenocortical tumors. Diagnosis of an aldosteronoma is often difficult, and with the advent of these methods it is possible to determine the functional capacity of a tumor, once it is removed. This is of special interest if the patient remains hypertensive postoperatively, and it is not clear whether the patient indeed had a functioning tumor.

Adrenal Cortex Neoplasms↗

PubMed2001

The role of gamma knife radiosurgery in the management of pituitary adenomas.

No treatment modality has been entirely successful in the management of pituitary adenomas. Although most patients with pituitary microadenomas can be cured by transsphenoidal surgery, the results are less satisfactory in macroadenomas in particular with suprasellar and/or parasellar extension. Additional treatment is then called for. Conventional fractional radiotherapy can often control tumour growth but is limited to 45-50 Gy with a very slow reduction in elevated pituitary hormones and a high incidence of pituitary insufficiency. Stereotactic radiosurgery allows the delivery of radiation with high precision to the target with low doses to the surrounding tissues permitting higher radiation doses. Gamma knife radiosurgery using photon energy with gamma beams from multiple cobalt 60 radiation sources is now used in many centers. It can be carried out in an outpatient setting with one single treatment. A more rapid normalization of pituitary hormone hypersecretion than with conventional radiation can be achieved as well as arrest of tumour growth and reduction of tumour mass. We therefore consider gamma knife radiosurgery as a valuable compliment to pituitary surgery. Long-term prospective studies are needed to evaluate the frequency of pituitary insufficiency in patients where the target area is determined with stereotactic magnetic resonance imaging (MRI).

Adenoma↗

PubMed2001

Commencing growth hormone replacement in adults with a fixed low dose. Effects on serum lipoproteins, glucose metabolism, body composition, and cardiovascular function.

The safety and effects of a fixed low dose of growth hormone (GH), 0.17 mg/day was evaluated for 3 months, on glucose metabolism, serum lipids, body composition and cardiac function in 53 GH deficient adults aged 18-78 years. Body composition was determined by dual energy X-ray absorptiometry and total body water was determined by bioelectrical impedance. Echocardiography was used to assess cardiac function and bicycle ergonometry was used to determine exercise capacity. All investigations were performed at baseline and after 3 months. At 3 months, serum levels of insulin-like growth factor (IGF)-I, IGF binding protein (IGFBP)-3 and lipoprotein (a) and lean body mass were increased (P<0.05). Total and low density lipoprotein cholesterol levels and fat mass were reduced (P<0.05). There was an increase in the serum glucose value at 120 min after an oral glucose tolerance test performed at 3 months (P<0.05), no other changes in glucose metabolism or in cardiac function were noted. Side-effects were few and mild. This fixed low-dose regime resulted in improvements in body composition and lipid profile, without causing serious side effects. This is therefore a valid method to institute GH replacement in adults.

Adult↗

PubMed2001

Adrenocorticotropic hormone-producing pituitary tumors: 12- to 22-year follow-up after treatment with stereotactic radiosurgery.

OBJECTIVE: To study retrospectively long-term outcomes of patients with adrenocorticotropic hormone-producing pituitary tumors that were treated with stereotactic Leksell gamma knife unit radiosurgery. METHODS: Eighty-nine patients aged 5 to 67 years were treated between 1976 and 1985. Eighteen patients aged 18 to 68 years (mean age, 41 yr) were followed in detail. Fifteen patients were women. None had previously received conventional radiotherapy, but pituitary microsurgery had been performed in two patients, and one patient had had an adrenalectomy. In the remaining 15 patients, radiosurgery was the primary therapy. RESULTS: Sixty-four patients had one stereotactic treatment, and 25 patients had two or more treatments. No complications were observed during treatment and the immediate follow-up period. At follow-up, 17 patients had died 1 to 20 years after the first treatment. No deaths were related to the treatment. In our 18 patients, the follow-up time after the first radiosurgical treatment was 12 to 22 years (mean follow-up period, 17 yr). Urinary cortisol levels gradually normalized in 83% of the patients. No recurrences were observed. Pituitary hormone insufficiencies developed in about two of every three patients and occurred even more than 10 years after treatment. Eight patients had transient hyperprolactinemia. The patients' vision and visual fields were unaffected, and none of them had signs of radiation-induced side effects such as brain tumors or brain necrosis. CONCLUSION: Stereotactic radiosurgery is a safe and effective method in the treatment of patients with adrenocorticotropic hormone-producing pituitary tumors, and the effect of treatment is long-lasting. Stereotactic radiosurgery is mainly a complement to microsurgery because of its gradually appearing effect and the occurrence of pituitary insufficiency. New pituitary deficiencies may be found more than 10 years after treatment.

Adolescent↗

PubMed2000

Growth hormone deficiency and replacement in elderly hypopituitary adults. KIMS Study Group and the KIMS International Board. Pharmacia and Upjohn International Metabolic Database.

OBJECTIVE: Although elderly hypopituitary adults demonstrate an increase in total and central fat compared with age-matched controls and are distinguishable from control subjects in terms of growth hormone (GH) responsiveness on dynamic testing, there are few data available on response to GH replacement. The objective of this study was to compare the baseline characteristics and longitudinal response to GH replacement in patients aged > 65 years with that observed in younger patients enrolled in KIMS (Pharmacia and Upjohn International Metabolic Database). KIMS is a physician-managed, open, long-term surveillance study of adult GH-deficient patients receiving GH replacement. Patients were entered and data provided by interested physicians. PATIENTS: Baseline characteristics were studied in 109 patients (66 males) aged > 65 years commencing GH replacement at time of entry into KIMS and the effects of GH replacement on blood pressure, lipids and quality of life in 64 patients who had completed at least 6 months of GH replacement. Data were compared with baseline data on 863 patients aged < 65 years with adult onset GH deficiency, who had not received GH for at least 6 months prior to entry into KIMS, 220 of whom went on to complete > 6 months GH therapy in KIMS. RESULTS: Blood pressure, cholesterol and LDL cholesterol were positively correlated with age, particularly in females, and older patients had a predictably higher prevalence of diabetes mellitus and history of hypertension. The frequency of previous fractures was increased in females but not in males aged > 65 years. Body mass index, waist/hip ratio and quality of life (AGHDA score) was similar in both groups prior to commencement of GH therapy. GH replacement doses were similar in younger and older patients and the percentage of patients with serum IGF-I of > 2SD above the age-related normal mean was not significantly different between the groups (< 65 years, 20%; > 65 years, 11%). After 6 months of GH replacement significant improvements were evident in waist circumference, waist/hip ratio, diastolic blood pressure, total and LDL cholesterol and AGHDA score in patients aged < 65 years. Similar significant reductions in total and LDL cholesterol were evident in patients > 65 years. In addition, male patients aged > 65 years demonstrated significant reductions in diastolic blood pressure and AGHDA score but no change in waist circumference whereas females aged > 65 years demonstrated a trend to reduction in waist circumference and AGHDA score. CONCLUSIONS: These data, derived from the largest series of GH-treated hypopituitary patients published to date, confirm similar baseline characteristics and positive benefit from GH replacement in older compared with younger hypopituitary patients particularly in relation to quality of life.

Aged↗

PubMed2000

Growth hormone replacement therapy improves body composition and increases bone metabolism in elderly patients with pituitary disease.

Although a specific GH deficiency (GHD) syndrome in the adult and the response to GH replacement therapy are well recognized, there are few data available on the effect of GH replacement therapy in elderly GH-deficient patients. We studied the effect of GH therapy on body composition and bone mineral density measured by dual energy x-ray absorptiometry, markers for bone metabolism, insulin-like growth factors (IGFs), and IGF-binding proteins (IGFBPs) in 31 patients (6 women and 25 men; aged 60-79 yr; mean, 68 yr) with multiple pituitary hormone deficiencies. The GH response to arginine or insulin was below 3 microg/L (9 mU/L) in all subjects. They were randomized to GH (Humatrope, Eli Lilly & Co.) or placebo for 6 months, followed by 12 months of open treatment. The dose was 0.05 IU/kg x week for 1 month, and after that it was 0.1 IU/kg x week divided into daily sc injections (0.75-1.25 IU/day). There were no changes in any of the measured variables during placebo treatment. GH treatment normalized serum IGF-I in a majority of the patients and increased IGFBP-3 and -5 as well as IGFBP-4 and IGF-II to values within normal range. Lean body mass was increased, and the increase at 6 and 12 months correlated with the increase in IGF-I (r = 0.46; P = 0.010 and r = 0.54, respectively; P = 0.003). GH treatment caused a modest, but highly significant, reduction of total body fat. Mean bone mineral density was not different from that in healthy subjects of the same age and did not change during the observation period. Markers for bone formation (bone-specific alkaline phosphatase activity, osteocalcin, and procollagen I carboxyl-terminal peptide in serum) increased within the normal range, and levels were sustained throughout the study. The bone resorption marker (pyridinoline in urine) was significantly elevated for 12 months. Side-effects were mild, mostly attributed to fluid retention. In two patients with normal glucose tolerance at the start of the study, pathological glucose tolerance occurred in one patient and was impaired in one. In conclusion, elderly patients with GHD respond to replacement therapy in a similar manner as younger subjects, with an improvement in body composition and an increase in markers for bone metabolism. Side-effects are few, and elderly GHD patients can be offered treatment. As long-term risks are unknown, GH doses should be titrated to keep IGF-I within the age-related physiological range.

Adenoma↗

PubMed1999

Serum levels of insulin-like growth factor I in 152 patients with growth hormone deficiency, aged 19-82 years, in relation to those in healthy subjects.

Serum insulin-like growth factor I (IGF-I) levels within normal range for age have been reported to be common in adults with GH deficiency (GHD). Therefore, serum IGF-I levels were determined in 152 consecutive patients (71 women and 81 men) with evidence of hypothalamic-pituitary disorders or previous cranial radiation, who fulfilled the presently used criteria for GHD i.e. peak GH response below 3 microg/L at stimulation test. Patients treated for acromegaly were excluded. Forty-three patients, aged 19-63 yr, had childhood onset GHD, and 109, aged 23-82 yr, had adult-onset GHD. Their IGF-I levels were expressed in SD scores in relation to normal reference values based on 448 healthy subjects, aged 20-96 yr (247 women and 201 men). In healthy subjects a linear inverse correlation, without gender difference, was found between logarithmic transformed IGF-I levels and age (r = -0.774; P < 0.001). In contrast, no age dependency was found in GHD patients. All patients with childhood-onset GHD had IGF-I values below -2 SD, significantly lower than those in adult-onset GHD patients (-6.2 +/- 0.3 vs. -3.2 +/- 0.2 SD score; P < 0.001). In patients with adult-onset GHD, 34% of the IGF-I levels were within normal range, increasing to 40% in the subgroup above 60 yr of age, in whom 86% were diagnosed with hypothalamic-pituitary tumors. Normal IGF-I was more common in men than in women, but no difference was observed between patients with panhypopituitarism and those with partial pituitary insufficiency. High frequencies of IGF-I levels within the normal range were found in GHD patients with pituitary tumors (20 of 57 nonsecreting pituitary adenomas, 5 of 15 prolactinomas, 6 of 12 Cushing's disease, and 4 of 25 craniopharyngiomas), but in only 2 of 43 patients with GHD due to other causes. In conclusion, an IGF-I level below -2 SD seems to be of diagnostic value in GHD with onset in childhood or early adulthood, whereas values within normal range are common in patients over 60 yr of age, especially those with pituitary tumors. The outcome of GH replacement therapy may reveal whether the addition of IGF-I as a diagnostic criterion is of predictive value in older patients.

Adult↗

PubMed1999

Determinants of circulating insulin-like growth factor-I.

Total IGF-I level in serum is a sensitive index during growth hormone (GH) replacement therapy of adults, since GH stimulates the hepatic expressions of both insulin-like growth factor (IGF-I) and acid-labile subunit (ALS) and the major part of IGF-I in the circulation is found in a ternary complex together with ALS and IGFBP-3. However, other regulators of the proteins constituting the ternary complex may influence IGF-I levels. In healthy subjects the serum IGF-I levels are low at birth, rise during childhood, with peak levels during puberty, and decline with increasing age. This pattern has been attributed to the age-dependent GH production, but it is unknown whether the wide range of IGF-I levels within each age interval is due to GH production or GH sensitivity. In elderly twins approximately 60% of IGF-I levels are genetically determined. The remaining environmental dependency of IGF-I is partly due to nutrition. Both caloric and protein content of the diet is of importance. Thus, low IGF-I levels are found in GH deficient patients as well as in patients with GH resistance due to malnutrition or GH receptor defects. It is essential that IGF-I determination is performed by assays in which IGFBPs do not interfere, and that IGF-I concentration is evaluated in relation to age, i.e. expressed in SD score, and the number of individuals constituting the reference intervals improves the sensitivity and specificity. Although determination of IGF-I is recommended in assessing GH deficiency in children, its diagnostic value in patients with adult onset of GH deficiency is not agreed upon. In the age group above 40-80 years many patients with pituitary/hypothalamic disorders and GH peaks below 3 microg/l during provocation tests have normal IGF-I levels. It is not clarified, whether the IGF-I levels within normal range for age is due to endogenous basal GH production being sufficient or other factors stimulating IGF-I, IGFBP-3 or ALS expressions.

Aging↗

PubMed1998

Serum levels of insulin-like growth factor binding proteins (IGFBP)-4 and -5 correlate with bone mineral density in growth hormone (GH)-deficient adults and increase with GH replacement therapy.

Adults with growth hormone deficiency (GHD) exhibit low bone mineral density (BMD) which improves by growth hormone (GH) replacement therapy. The insulin-like growth factor (IGF) system has an established role in mediating the effects of GH on bone and IGF binding proteins (IGFBP)-4 and IGFBP-5 have been shown to modulate the effects of IGFs in bone. Therefore, we studied serum levels of IGFBP-4 and IGFBP-5 and their relationship to serum levels of bone biochemical markers and BMD in adults with GH deficiency (GHD) before and during GH therapy. Serum levels of IGFBP-5 and IGFBP-4 were measured on samples from 20 patients (11 males) 22-57 years of age. All had IGF-I serum values below -2 standard deviation score. The first 6 months were placebo controlled and all received 3 years of active treatment with the mean dose 0.23 +/- 0.01 IU/kg/week divided into daily subcutaneous injections. Serum IGFBP-5 levels in GHD adults were low at baseline and positively related to total body, femoral neck, trochanter, and Ward's triangle BMD (r = 0.471, 0.549, 0.462, and 0.470, respectively, p < 0.05). The mean serum IGFBP-5 level increased by about 2-fold within 3 months after the initiation of GH therapy and was correlated with serum IGF-I (r = 0.719, 0.801, and 0.722 before and after 18 and 36 months, respectively,p < 0.001). A positive correlation between serum IGFBP-5 levels and lumbar spine BMD was found during GH treatment but not before. The percentage increase of serum IGFBP-5 after GH therapy showed a positive correlation with the percentage increase of total alkaline phosphate activity (r = 0.347 p < 0.05). In contrast to IGFBP-5, serum IGFBP-4 levels were positively related to body mass index (r = 0.607, p < 0.01). Baseline serum IGFBP-4 levels also correlated with total body, femoral neck, trochanter, and Ward's triangle BMD (r = 0.502, 0.590, 0.612, and 0.471, respectively,p < 0.05). The mean serum IGFBP-4 level was increased by 25% within 3 months after initiation of GH therapy and did not correlate with serum IGF-I levels. Although the above findings are consistent with the idea that GH-induced changes in serum IGFBP-5 and IGFBP-4 levels may in part mediate the anabolic effects of GH on bone tissue in adults with GHD, further studies are needed to establish the cause and effect relationship.

Adult↗

PubMed1997

Serum insulin-like growth factor I (IGF-I), IGF-binding protein-1 and -3, and the acid-labile subunit as serum markers of body composition during growth hormone (GH) therapy in adults with GH deficiency.

Serum levels of insulin-like growth factor I (IGF-I), IGF-binding protein-3 (IGFBP-3), the acid-labile subunit (ALS), insulin, and IGFBP-1 were evaluated as indicators of body composition during GH replacement therapy in 20 GH-deficient patients (9 women and 11 men), aged 22-57 yr, with IGF-I levels below -2 SD. The mean GH dose was 0.128 +/- 0.003 IU/kg.week during the first month and thereafter 0.23 +/- 0.01 IU/kg.week, divided into daily doses (0.7-4.3 IU/day). Serum levels of IGF-I, ALS, and IGFBP-3 above the normal range were reached in seven, five, and three subjects, respectively, after 12 months of GH therapy. IGF-I and ALS levels, but not IGFBP-3 levels, correlated with the total daily GH dose (r = 0.676; P = 0.001 and r = 0.631; P = 0.003). The mean increase in lean body mass (LBM) measured by dual energy x-ray absorptiometry was 3.0 +/- 0.5 kg (P < 0.001). At 12 months, the LBM values were significantly correlated to the IGF-I levels (r = 0.718; P < 0.001), but not to ALS or IGFBP-3 levels. No correlation was found before therapy, and the increase in LBM at 12 months correlated with the IGF-I increase (r = 0.514; P = 0.029) only after exclusion of two nonresponders. Both before and during therapy, LBM was inversely related to IGFBP-1 (r = -0.715; P < 0.004 at 12 months). None of the GH-induced proteins could be used as indicators of body fat changes. In conclusion, both IGF-I and ALS can be used as indicators to avoid GH excess during replacement therapy, but only IGF-I relates to changes in LBM.

Adipose Tissue↗

PubMed1997

Different responses of bone alkaline phosphatase isoforms during recombinant insulin-like growth factor-I (IGF-I) and during growth hormone therapy in adults with growth hormone deficiency.

We studied serum bone alkaline phosphatase (ALP) isoforms and other markers of bone turnover in growth hormone-deficient (GHD) adults (n = 22). The patients were followed during 1 week of insulin-like growth factor-I (IGF-I) administration, 40 micrograms/kg of body weight/day (n = 6), and during 24 months of growth hormone (GH) therapy, 0.125 IU/kg of body weight/week for the first month, and then 0.250 IU/kg of body weight/week (n = 20). Six ALP isoforms were separated and quantified by high-performance liquid chromatography: one bone/intestinal, two bone (B1, B22), and three liver ALP isoforms. At baseline, the mean levels of B1, B22, and osteocalcin were higher in GHD adults than in healthy adults. After 2 week of IGF-I administration and 1 month of GH therapy, only B1 was decreased. We suggest that the initial decrease of B1 during GH therapy could be an effect of endocrine IGF-I action mediated by GH. After 3 months of GH therapy, both B1 and B2 increased as compared with placebo. Osteocalcin, carboxy-terminal propeptide of type I procollagen (PICP), cross-linked carboxy-terminal telopeptide of type I collagen (ICTP), and urinary pyridinoline cross-links/creatinine ratio increased during GH therapy. PICP increased significantly before bone ALP and osteocalcin, indicating early stimulation of type I collagen synthesis as previously demonstrated by in vitro models. Different responses of the bone ALP isoforms during IGF-I and during GH therapy suggest different regulations in vivo.

Adult↗

PubMed1996

Long-term treatment of Swiss 3T3 fibroblasts with dexamethasone attenuates MAP kinase activation induced by insulin-like growth factor-I (IGF-I).

Bone formation is reduced in hyperglucocorticoid states, e.g. Cushing's syndrome or long-term treatment with synthetic glucocorticoids during rheumatic diseases. possibly related to decreased sensitivity of the target to insulin-like growth factor-I (IGF-I). In this study, we have sought to identify postreceptor-mechanisms for glucocorticoid-induced resistance to insulin-like peptides in a model system. Treatment of Swiss 3T3 fibroblasts with 100 nM dexamethasone for 48h reduced IGF-I-induced activation of mitogen-activated protein kinase (MAP kinase). The level of insulin receptor substrate-1 (IRS-1) was reduced in dexamethasone-treated cells, as measured by Western blot; however, the pattern of tyrosine-phosphorylated protein subsequent to stimulation with IGF-I (1 min) was not altered. No inhibitory effect of dexamethasone was observed on the level of phosphotyrosine in IRS-1 in extracts from IGF-I-treated cells. The amount of IGF-I-induced association of insulin receptor substrate-1 and phosphatidylinositol 3-kinase was increased in steroid treated cells. Addition of IGF-I increased the synthesis of lipid, glycogen and protein, and the reduction of a tetrazolium dye, MTS, in untreated cells. The response to IGF-I in terms of glycogen synthesis was blunted, whereas the effect of IGF-I was unaffected for the other three parameters in cells pretreated with dexamethasone. These findings indicate that the activation of MAP kinase may be dissociated from IGF-I-induced anabolic pathways and tyrosine phosphorylation of IRS-1. The results agree with the previously proposed role for the activation of MAP kinase in the regulation of glycogen synthesis. Furthermore, they suggest that dexamethasone-induced reduction of IRS-1 expression may be important for the impaired activation of MAP kinase by insulin-like peptides in steroid-treated cells.

3T3 Cells↗

PubMed1996

Systems approach to clothing for disabled users. Why is it difficult for disabled users to find suitable clothing.

Today's clothing market is not adapted for people with unusual body dimensions and/or different kinds of functional impairments. They will be referred to as disabled users. The method of user-oriented product development combined with the soft systems methodology has been applied in order to understand and possibly solve their problem. Sixty five disabled users were interviewed. The results show that the disabled users must be divided into subgroups. Their requirements are very much dependent on their impairment not only regarding the fit and function of the clothing, but also regarding shopping and service in the stores. The symbolic values of clothing are just as important as the functional values. However, it is essential not to focus on the end product only, but to look at the problem as a system consisting of: manufacturing, marketing and end use. A new method of taking three dimensional measurements from range images of the human body has been developed. In combination with other developments in information technology it will be possible to synthesise a new system where the manufacturers and retailers of clothing can co-operate in order to give service to disabled users.

Journal Article↗

PubMed1996

The individual responsiveness to growth hormone (GH) treatment in GH-deficient adults is dependent on the level of GH-binding protein, body mass index, age, and gender.

The aim of the present trial was to study the individual responsiveness to GH treatment in terms of body composition and to search for possible predictors of the response in GH-deficient adults. Sixty-eight patients (44 men and 24 women) with a mean age of 44.3 (1.2) yr and verified GH deficiency participated in a 2-phase treatment trial with an initial randomized, double blind, placebo-controlled, 6-month period, followed by an open treatment period, thereby ensuring all patients 12 months of GH treatment. Recombinant human GH was administered sc daily at bedtime, with a target dose of 12 micrograms/kg x day. GHBP was measured by ligand-mediated immunofunctional assay, and serum insulin-like growth factor I (IGF-I) was determined by RIA after acid-ethanol extraction, using a truncated IGF-I analog as the radioligand. Lean body mass (LBM) and body fat (BF) were determined by dual energy x-ray absorptiometry, and total body water (TBW) was determined by bioelectrical impedance. During the placebo control period, serum IGF-I,LBM, and TBW increased (P < 0.001), whereas BF decreased (P < 0.001) and serum GHBP was unchanged in the group treated with GH compared with the patients treated with placebo. After 12 months of GH treatment, the individual changes in BF ranged from -12.5 to 4.3 kg and from -4.5 to 10.1 kg in LBM. Age (P < 0.05) and baseline GHBP level (P < 0.01) were inversely correlated with the increase in LBM. The GH-induced increment in IGF-I and TBW was greater in men than in women (P < 0.01), whereas the decreases in BF were similar in men and women. This trial demonstrates the variability in responsiveness to GH administration in GH-deficient adults. The best response to GH was obtained in younger patients with low GHBP levels. Furthermore, men responded better than women.

Absorptiometry, Photon↗

PubMed1995

Patient evaluation of a new injection pen for growth hormone treatment in children and adults.

The aim of this study was to evaluate patients' perception and acceptance of a new multi-dose injection device (Genotropin Pen) for recombinant growth hormone (GH) supplied in a two-chamber cartridge. The pen is combined with a very thin needle (B-D Microfine + (29 G) and meets future demands when dosing of GH will be changed from International Units (IU) to milligrams (mg). A total of 39 children receiving GH treatment (East Hospital, Gothenburg and St Bartholomew's Hospital, London), aged between 7 and 17 years, and 39 GH-treated adults (Sahlgrenska Hospital, Gothenburg and Karolinska Hospital, Stockholm), aged between 20 and 68 years, participated in the study. The daily dose ranged from 0.3 mg to 2.6 mg. The injections were given subcutaneously, once daily, and most of the patients used the thigh as an injection site. After a trial period of 2 weeks, injection technique, pain, fear of injection and convenience of the Genotropin Pen were compared with the experience with the prestudy device (Genotropin KabiPen 16, 16(8) or 36) by questionnaire. A total of 95% of the patients preferred the Genotropin Pen to the prestudy device for the following reasons: a greater certainty of correct dosing with the digital display; the possibility of correcting the set dose; the lock function of the injection button when injection is complete; more comfortable to hold due to the design and the plastic material; and reduced pain when injecting due to the thinner needles. Four patients (5%) preferred the prestudy device KabiPen as they considered this to be 'good enough'. Thus, the Genotropin Pen is a convenient injection device and most patients prefer it to the KabiPen.

Adolescent↗