PubMed Health⌕ Search

Biomedical subjects

E R Christ

Publications and source records attributed to E R Christ.

At least 19 recordsLinked to original sources
PubMed2006

[Simultaneous defect of visual fields and loss of libido--a coincidence?].

We present the case of a 60 year old male patient with incidentally detected visual abnormalities. Detailed personal history revealed a hypogonadism that had been present for several years. Further investigations established the diagnosis of an infiltrative macroadenoma. Medical treatment with cabergoline led to a rapid regression of ophthalmologic symptoms and, subsequently, of tumor size. In male subjects symptoms of hypogonadism are often reported only late in the course of the disease, thereby leading to a generally larger tumor size at the point of diagnosis. In contrast to other pituitary tumors that are mainly treated by surgery, medical treatment with dopamine agonists is the principal therapeutic option in prolactinomas.

Cabergoline↗
PubMed2006

QTc interval and resting heart rate as long-term predictors of mortality in type 1 and type 2 diabetes mellitus: a 23-year follow-up.

AIMS/HYPOTHESIS: We evaluated the association of QT interval corrected for heart rate (QT(c)) and resting heart rate (rHR) with mortality (all-causes, cardiovascular, cardiac, and ischaemic heart disease) in subjects with type 1 and type 2 diabetes. METHODS: We followed 523 diabetic patients (221 with type 1 diabetes, 302 with type 2 diabetes) who were recruited between 1974 and 1977 in Switzerland for the WHO Multinational Study of Vascular Disease in Diabetes. Duration of follow-up was 22.6 +/- 0.6 years. Causes of death were obtained from death certificates, hospital records, post-mortem reports, and additional information given by treating physicians. RESULTS: In subjects with type 1 diabetes QT(c), but not rHR, was associated with an increased risk of: (1) all-cause mortality (hazard ratio [HR] 1.10 per 10 ms increase in QT(c), 95% CI 1.02-1.20, p = 0.011); (2) mortality due to cardiovascular (HR 1.15, 1.02-1.31, p = 0.024); and (3) mortality due to cardiac disease (HR 1.19, 1.03-1.36, p = 0.016). Findings for subjects with type 2 diabetes were different: rHR, but not QT(c) was associated with mortality due to: (1) all causes (HR 1.31 per 10 beats per min, 95% CI 1.15-1.50, p < 0.001); (2) cardiovascular disease (HR 1.43, 1.18-1.73, p < 0.001); (3) cardiac disease (HR 1.45, 1.19-1.76, p < 0.001); and (4) ischaemic heart disease (HR 1.52, 1.21-1.90, p < 0.001). Effect modification of QT(c) by type 1 and rHR by type 2 diabetes was statistically significant (p < 0.05 for all terms of interaction). CONCLUSIONS/INTERPRETATION: QT(c) is associated with long-term mortality in subjects with type 1 diabetes, whereas rHR is related to increased mortality risk in subjects with type 2 diabetes.

Adult↗
PubMed2006

Transient MR changes and symptomatic epilepsy following gamma knife treatment of a residual GH-secreting pituitary adenoma in the cavernous sinus.

OBJECTIVE: To report a rare side effect of gamma knife treatment of pituitary macroadenoma. CASE REPORT: In a forty-one-year old female patient acromegaly was diagnosed due to a growth hormone secreting pituitary macroadenoma. Following transsphenoidal surgery the patient underwent gamma knife treatment for persistent uncontrolled acromegaly activity of residual tumor, infiltrating the left cavernous sinus. 15 months later, complex partial seizures were diagnosed and 17 months after gamma knife treatment a gadolinium enhancing lesion was detected in her left medial temporal lobe. Radiation induced changes, radiation necrosis or a glioma were considered. Neuropsychological testing indicated potentially significant post-surgical deficits. Therefore, surgical action was postponed and anti-epileptic treatment was started. Four months later she was free of seizures and an MR scan showed an almost complete regression of the gadolinium enhancing lesion, indicating that it had been due to radiation induced changes. CONCLUSION: Gamma knife surgery of a pituitary adenoma may cause radiation induced MR changes of the mesial temporal lobe mimicking glioma or radionecrosis and cause symptomatic epileptic seizures. The awareness of this rare complication is important to avoid unnecessary and potentially harmful diagnostic or therapeutic interventions.

Acromegaly↗
PubMed2006

Apolipoprotein B as a long-term predictor of mortality in type 1 diabetes mellitus: a 15-year follow up.

OBJECTIVES: To evaluate the association of apolipoprotein B (apo B) with mortality due to all causes, to cardiac disease and to ischaemic heart disease (IHD) in subjects with type 1 diabetes mellitus. SUBJECTS: 165 subjects with type 1 diabetes included in the Swiss Cohort of the WHO Multinational Study of Vascular Disease in Diabetes were followed for 14.7+/-0.45 years. METHODS: Causes of death were obtained from death certificates, hospital records and postmortem reports. Using a parametric proportional hazards model the association of apo B with mortality rates was assessed by time-to-event analysis, including the absolute cumulative mortality risk over time for various apo B levels at baseline. RESULTS: Apo B was positively associated with all-cause mortality [hazard ratio (HR) 2.65 per g L-1 increase of apo B, 95% CI: 1.11-6.36, P=0.029], cardiac mortality (HR 11.64, 1.03-131.11, P=0.047) and IHD mortality (HR 9.36, 1.26-69.66, P=0.029). An apo B>or=0.96 g L-1 translated into a duplication of overall mortality hazard (HR 1.93, 1.00-3.72, P=0.050), and a sevenfold increase of mortality because of cardiac disease or IHD (HR 7.44, 1.44-38.42, P=0.017 and HR 7.38, 0.78-69.82, P=0.081). A baseline apo B of 1.5 g L-1 predicted an absolute cumulative risk to die over the next 10 years of 12.1% (5.2-31.7) for male and of 10.4% (4.7-26.1) for female subjects whereas risks were 6.3% (1.8-21.4) and 5.4% (0.8-15.8) for an apo B of 0.8 g L-1. CONCLUSION: Apo B is consistently associated with an increased mortality in type 1 diabetes.

Apolipoproteins B↗
PubMed2005

[Endogenous hypercortisolism and immunologically-mediated disease: three cases].

HISTORY AND CLINICAL FINDINGS: We report three women with hypercortisolism presenting with symptoms and signs of Cushing's syndrome. In two of the patients, initial symptoms of hypercortisolism were associated with spontaneous amelioration of previously known atopic dermatitis and psoriasis, respectively. DIAGNOSTIC PROCEDURES: Diagnosis was established by demonstrating both lack of responsiveness to dexamethasone (1mg) suppression test and increased 24-hour urine cortisol secretion. One patient had a low serum ACTH level indicating Cushing's syndrome of adrenal origin. In the other two patients hypercortisolism proved to be ACTH-dependent, the source being the pituitary, as demonstrated by CRH stimulation test (elevation of ACTH and cortisol by 35 % and 20 %, respectively) and sampling of the petrosus sinus. In both patients imaging confirmed the presence of a pituitary adenoma. TREATMENT AND COURSE: All three patients underwent successful surgery: the first patient had an adrenalectomy, the other two transseptal transsphenoidal hypophysectomy. As symptoms and signs of hypercortisolism improved, the previously quiescent signs of atopic dermatitis and psoriasis recurred and one patient developed Graves' disease. CONCLUSIONS: Following successful treatment of endogenous hypercortisolism, symptoms of unrelated immunologically mediated conditions, especially autoimmune thyroiditis, may occasionally appear. Furthermore, the clinical course of coexisting immunologically mediated diseases may help to diagnose Cushing's syndrome and to monitor the patients after surgical treatment.

Adult↗
PubMed2005

Treatment outcomes and mortality of 94 patients with acromegaly.

BACKGROUND: Due to new therapeutic modalities and modified therapeutic goals outcome of patients with acromegaly may change over time and differ by centre. We analysed treatment outcomes and mortality of our patients with acromegaly seen between 1971 and 2003. METHOD: The cohort consisted of 94 patients who had been followed for 0.3-31 years (mean 10.6 years). Remission criteria were a normalized IGF-I concentration, a nadir GH level during oral glucose load of <1.0 microg/l and a random GH value of <2.5 microg/l. FINDINGS: Transsphenoidal surgery achieved remission in 80% of patients with micro-adenomas (<1 cm), 65% with meso-adenomas (> or = 1 cm to <2 cm) and 27% with macro-adenomas (> or = 2 cm). Patients with meso-adenomas operated on after 1995 tended to have a better outcome compared to those operated on before 1995 (Remission in 83% vs. 38%). Radiotherapy resulted in disease control in 22 of 47 patients (47%). Intramuscular depot formulation of octreotide (Sandostatin LAR) led to disease control in 17 of 26 patients (65%). After multimodal therapy persistent acromegalic activity remained in 18% of the patients; only one of them had an adenoma of <2 cm. The standardized mortality ratio was 1.30 (95% CI 0.52-2.67) for patients in remission and 1.38 (95% CI 0.51-3.00) for patients with persistent acromegalic activity. CONCLUSIONS. Most patients with adenomas of <2 cm can be expected to achieve remission by transsphenoidal surgery alone. Furthermore, virtually all patients with adenomas of <2 cm and more than 80% of patients with adenomas of > or = 2 cm can be expected to achieve remission by adjuvant treatment. Aggressive multimodal therapy is critical in the management of acromegaly reducing mortality risk close to that of the general population.

Acromegaly↗
PubMed2004

Effects of growth hormone (GH) replacement therapy on low-density lipoprotein apolipoprotein B100 kinetics in adult patients with GH deficiency: a stable isotope study.

GH replacement therapy has been shown to improve the dyslipidemic condition in a substantial proportion of patients with adult GH deficiency. The mechanisms are not yet fully elucidated. Low-density lipoprotein (LDL) apolipoprotein B100 (apoB) formation and catabolism are important determinants of plasma cholesterol concentrations. This study examined the effect of GH replacement therapy on LDL apoB metabolism using a stable isotope turnover technique. LDL apoB kinetics was determined in 13 adult patients with GH deficiency before and after 3 months GH/placebo treatment in a randomized, double-blind, placebo-controlled study. LDL apoB (13)C-leucine enrichment was determined by isotope-ratio mass spectrometry. Plasma volume was assessed by standardized radionuclide dilution technique. GH replacement therapy significantly decreased LDL cholesterol, LDL apoB concentrations, and LDL apoB pool size compared with placebo. Compared with baseline, GH replacement therapy resulted in a significant increase in plasma volume and fractional catabolic rate, whereas LDL formation rate remained unchanged. LDL lipid content did not significantly change after GH and placebo. This study suggests that short-term GH replacement therapy decreases the LDL apoB pool by increasing removal of LDL particles without changing LDL composition or LDL apoB production rate. In addition, it is possible that the beneficial effects of GH on the cardiovascular system contribute to these findings.

Apolipoprotein B-100↗
PubMed2003

Effects of alcohol consumption on mortality in patients with Type 2 diabetes mellitus.

AIMS/HYPOTHESIS: Moderate alcohol intake has been associated with increased life expectancy due to reduced mortality from cardiovascular disease. We prospectively examined the effects of alcohol consumption on mortality in Type 2 diabetic patients in Switzerland. METHODS: A total of 287 patients with Type 2 diabetes mellitus (125 women, 162 men), recruited in Switzerland for the WHO Multinational Study of Vascular Disease in Diabetes, were included in this study. After a follow-up period of 12.6+/-0.6 years (means +/- SD), mortality from CHD and from all causes was assessed. RESULTS: During the follow-up, 70 deaths occurred (21 from CHD, 49 from other causes). Compared with non-drinkers, alcohol consumers who drank alcohol 1 to 15 g, 16 to 30 g and 30 g or more per day had the following risk rates of death from CHD: 0.87 (95% CI: 0.25 to 2.51, NS), 0.00 (95% CI: 0.00 to 0.92, p less than 0.05) and 0.37 (95% CI, 0.01 to 2.42, NS), respectively. The corresponding risk rates of death from all causes were 1.27 (95% CI: 0.68 to 2.28, NS), 0.36 (95% CI: 0.09 to 0.99, p less than 0.05) and 1.66 (95% CI: 0.76 to 3.33, NS). CONCLUSIONS/INTERPRETATION: In Swiss Type 2 diabetic patients moderate alcohol consumption of 16 to 30 g per day was associated with reduced mortality from CHD and from all causes. Alcohol intake above 30 g per day was associated with a tendency towards increased all-cause mortality.

Adult↗
PubMed2003

The effect of growth hormone (GH) replacement therapy in adult patients with type 1 diabetes mellitus and GH deficiency.

OBJECTIVES: Specific problems in patients with insulin-dependent diabetes mellitus (IDDM) and GH deficiency are hypoglycaemic attacks, increased insulin sensitivity and loss of energy. These problems may be related to GH deficiency. PATIENTS: GH replacement was initiated in five patients with type 1 diabetes mellitus and GH deficiency for 6 months [four males and one female, mean age 41.6 +/- 3.8 years, mean +/- standard error of the mean (SEM); body mass index (BMI) 22.3 +/- 1.2 kg/m2]. METHODS: Body composition (bioimpedance), metabolic control [haemoglobin A1C (HbA1C)], insulin requirement and frequency of hypoglycaemia were measured, and quality of life was assessed using validated questionnaires. Monthly eye photographs were taken. RESULTS: IGF-I concentrations were below the age-adjusted range at baseline and increased significantly following GH replacement therapy [analysis of variance (ANOVA), P < 0.05]. Diabetes control as assessed by HbA1C remained stable (8.2 +/- 0.2 vs. 8.0 +/- 0.4), but needed a 1.75-fold increase in insulin dose/day. Lean body mass tended to increase (P = 0.07) and body fat mass decreased significantly (P > 0.01). Number of severe hypoglycaemic (< 3 mmol/l) attacks decreased significantly (P < 0.04) and quality of life assessed by validated questionnaires improved significantly in all patients [Psychological and General Well-Being Schedule (PGWBS), P < 0.04; Nottingham Health Profile (NHP), P < 0.05]. Monthly eye photographs revealed no changes in the retina in any patients. CONCLUSION: GH replacement therapy has a beneficial effect at the dose used. It restores body composition and decreases frequency and severity of hypoglycaemic episodes, thus improving quality of life. Long-term trials are needed to determine the safety of GH replacement therapy in these patients.

Adult↗
PubMed2001

Normal VLDL metabolism despite altered lipoprotein composition in type 1 diabetes mellitus.

OBJECTIVES: Patients with type 1 diabetes are at increased risk of cardiovascular disease, which may be related to abnormal lipid metabolism. Secretion and clearance of VLDL apolipoprotein B100 (apoB) are important determinants of plasma lipid concentrations and are known to be influenced by hormones, including insulin and growth hormone. PATIENTS: This study examined overnight VLDL apoB metabolism and VLDL composition in six lean patients with type 1 diabetes during euglycaemia (controlled by a varying insulin infusion) and in six age-, sex- and BMI-matched control subjects. METHODS: VLDL apoB kinetics were determined using a primed constant 1-13C leucine infusion, and VLDL apoB enrichment was measured by gas-chromatography mass-spectrometry. Fasting lipid profile, IGF-I, IGFBP-3, overnight GH profiles and free insulin concentrations were also assessed. RESULTS: Fasting concentrations of triglycerides (TG), total cholesterol (TC), HDL-cholesterol (HDL-C) and LDL-cholesterol (LDL-C) were similar in both groups. The VLDL apoB secretion and metabolic clearance rates were not significantly different between the two groups, but the VLDL-TGNLDL apoB and the VLDL-CNLDL apoB ratios were significantly increased in those with diabetes (P < 0.02 and P < 0.03, respectively). Total IGF-I concentrations were similar between the two groups; however, the GH area under the curve and free insulin concentrations were increased in patients with type 1 diabetes (GH: diabetes: 94.8 +/- 15.1 vs. controls: 45.6 +/- 10-6, mU/L/h, P < 0.04; free insulin: diabetes: 78.4 +/- 5.0 vs. controls: 28.3 +/- 3.26, pmol/l, P < 0.001). IGFBP-3 concentrations were lower in diabetic patients (diabetes: 2,454.2 +/- 68.7 vs. controls: 3,219.4 +/- 76.4, ng/ml, P < 0.001). In the control group overnight GH secretion correlated negatively with fasting TC (P < 0.01) and LDL-C (P < 0.03) concentrations, whereas free insulin concentrations correlated positively with fasting TG concentrations (P < 0.009). No significant correlations were found in the patients with diabetes. CONCLUSION: This study suggests that in euglycaemic conditions patients with type 1 diabetes mellitus have normal VLDL apoB kinetics but altered VLDL composition. The altered VLDL composition may be associated with accelerated atherogenesis. We speculate that the disrupted hormonal balance and, in particular, the increased GH secretion might be responsible for the compositional changes of VLDL particles in type 1 diabetes mellitus.

Adult↗
PubMed2000

Growth hormone replacement in adults with growth hormone deficiency: assessment of current knowledge.

The recent availability of recombinant human growth hormone (GH) has led to intense investigation of the consequences of adult GH deficiency (GHD) and the effects of GH replacement. These studies have led to the identification of a characteristic syndrome of GHD consisting of decreased mood and well-being, with alterations in body composition and substrate metabolism. In both placebo-controlled and open studies, GH replacement therapy has consistently been shown to reverse or correct these features. Whether long-term GH replacement will result in a reduction of osteoporotic fractures, cardiovascular morbidity and mortality is not yet known. To date, no permanent serious adverse effects have been associated with GH replacement in GHD, and although currently expensive, it is anticipated that GH replacement will become routine in the treatment of the severely hypopituitary adult.

Adult↗
PubMed2000

IGF-I treatment in adults with type 1 diabetes: effects on glucose and protein metabolism in the fasting state and during a hyperinsulinemic-euglycemic amino acid clamp.

Type 1 diabetes is associated with abnormalities of the growth hormone (GH)-IGF-I axis. Such abnormalities include decreased circulating levels of IGF-I. We studied the effects of IGF-I therapy (40 microg x kg(-1) x day(-1)) on protein and glucose metabolism in adults with type 1 diabetes in a randomized placebo-controlled trial. A total of 12 subjects participated, and each subject was studied at baseline and after 7 days of treatment, both in the fasting state and during a hyperinsulinemic-euglycemic amino acid clamp. Protein and glucose metabolism were assessed using infusions of [1-13C]leucine and [6-6-2H2]glucose. IGF-I administration resulted in a 51% rise in circulating IGF-I levels (P < 0.005) and a 56% decrease in the mean overnight GH concentration (P < 0.05). After IGF-I treatment, a decrease in the overnight insulin requirement (0.26+/-0.07 vs. 0.17+/-0.06 U/kg, P < 0.05) and an increase in the glucose infusion requirement were observed during the hyperinsulinemic clamp (approximately 67%, P < 0.05). Basal glucose kinetics were unchanged, but an increase in insulin-stimulated peripheral glucose disposal was observed after IGF-I therapy (37+/-6 vs. 52+/-10 micromol x kg(-1) x min(-1), P < 0.05). IGF-I administration increased the basal metabolic clearance rate for leucine (approximately 28%, P < 0.05) and resulted in a net increase in leucine balance, both in the basal state and during the hyperinsulinemic amino acid clamp (-0.17+/-0.03 vs. -0.10+/-0.02, P < 0.01, and 0.25+/-0.08 vs. 0.40+/-0.06, P < 0.05, respectively). No changes in these variables were recorded in the subjects after administration of placebo. These findings demonstrated that IGF-I replacement resulted in significant alterations in glucose and protein metabolism in the basal and insulin-stimulated states. These effects were associated with increased insulin sensitivity, and they underline the major role of IGF-I in protein and glucose metabolism in type 1 diabetes.

Adult↗
PubMed1999

Growth hormone (GH) replacement therapy reduces serum sialic acid concentrations in adults with GH-deficiency: a double-blind placebo-controlled study.

OBJECTIVES: Patients with adult GH-deficiency are thought to have an increased risk of cardiovascular disease. Sialic acid (SA) concentrations have been proposed as a marker of atherosclerotic disease probably related to an inflammatory response of the arterial wall. SA as a marker of cardiovascular disease in adult GH-deficiency and its relation to changes in fasting lipid profile and hormone concentrations have not yet been investigated. PATIENTS: We performed a randomised, double-blind placebo-controlled study in 18 patients with adult GH-deficiency before and after 3 months GH replacement therapy (0.036 U/kg/d; GH-treated group: 6 females, 3 males; age: 47.3 +/- 5.4 years., mean +/- SEM; placebo-group: 5 females, 4 males; mean age 50.2 +/- 4.7). In addition, SA concentrations were measured in 18 sex and age matched healthy control subjects. METHODS: Blood samples were obtained after an overnight fast. Serum SA, triglycerides and cholesterol were measured using enzymatic methods. Lipoprotein classes were separated by ultracentrifugation. Insulin and IGF-I were determined by radioimmunoassay, HbA1C was measured by anion exchange liquid chromatography. RESULTS: SA concentrations of the patients with adult GH-deficiency were not significantly different compared to the control group (GH-deficient group: 2.29 +/- 0.02 mmol/l, mean +/- SEM vs. control group: 2.09 +/- 0.13 mmol/l, P = 0.25). Before GH replacement therapy SA concentrations correlated positively with the patients age (r = 0.45; P < 0.04) and fasting insulin concentrations (r = 0.5; P < 0.03) but not with fasting lipid profile. GH replacement therapy significantly increased IGF-I (GH: + 27 +/- 2.6 vs. placebo: + 1.0 +/- 0.8 nmol/l, P < 0.001) and fasting insulin concentrations (GH: + 71.9 +/- 8.0 vs. placebo: + 19.6 +/- 22.6 pmol/l, P < 0.04) compared to placebo therapy. SA concentrations (GH: - 0.41 +/- 0.15 vs. placebo: - 0.01 +/- 0.12 mmol/l, P < 0.05), total cholesterol (GH: - 0.71 +/- 0.16 vs. placebo: 0.23 +/- 0.21 mmol/l, P < 0.003) and LDL-cholesterol (- 0.71 +/- 0.14 vs. placebo: - 0.12 +/- 0.21 mmol/l P < 0.04) significantly decreased after GH replacement therapy compared to placebo therapy. No significant correlation between changes in SA concentrations and changes in lipid profile were observed following GH replacement therapy. CONCLUSION: These results suggest that, firstly, GH replacement therapy may have a beneficial effect on the pathogenesis of atherosclerosis despite the increase in insulin concentrations, a surrogate marker of insulin resistance, secondly, the proposed beneficial effect of GH on the atherosclerotic process is likely to be multifactorial and cannot only be explained by changes in lipid profile and finally, SA might be a useful marker for the process of atherosclerotic disease in interventional studies.

Adult↗
PubMed1999

Growth hormone replacement therapy in adults with growth hormone deficiency improves vascular reactivity.

OBJECTIVE: Patients with adult growth hormone (GH) deficiency are thought to be of increased risk of cardiovascular disease. Impaired vascular reactivity to endothelium derived nitric oxid (NO) is an early event in the development of atherosclerosis. In order to detect a possible effect of GH on vascular endothelium we examined forearm vasodilator responses in 8 patients with adult GH-deficiency before and after 3 months GH replacement therapy. METHODS: Forearm blood flow studies were performed using venous occlusion plethysmography. Blood flow was measured at baseline and during intra-arterial infusions of 3 cumulative doses (7.5, 15 and 30 microg/minutes) of acetylcholine chloride and of sodium nitroprusside (1, 3 and 10 microg/minutes). Fasting blood samples were collected for measurement of lipid profile, Haemoglobin A1C (HbA1C), glucose, IGF-I and insulin. RESULTS: GH replacement therapy significantly increased IGF-I concentrations and tended to increase fasting insulin concentrations (IGF-I: 72.7 +/- 12.4 vs. 130.8 +/- 18.5 microg/l, P < 0.001; fasting insulin: 14.3 +/- 3.4 vs. 32.9 +/- 18.6, mU/l, P = 0.06). Fasting lipid profile, glucose and HbA1C did not significantly change. Blood flow responses to acetylcholine were significantly greater after GH replacement therapy (10.3 +/- 1.0 vs. 17.6 +/- 2.5 ml/minutes/100 ml for the highest dose, P < 0.03). There was a strong tendency to increased blood flow response to nitroprusside after GH therapy (10.7 +/- 1.2 vs. 17.5 +/- 1.7 ml/minutes/100 ml for the highest dose, P = 0.06). CONCLUSION: These findings suggest that GH replacement therapy may have a beneficial effect on endothelium function which is independent of quantitative changes in fasting lipid profile.

Acetylcholine↗
PubMed1999

Atorvastatin compared with simvastatin-based therapies in the management of severe familial hyperlipidaemias.

We compared atorvastatin with simvastatin-based therapies in a prospective observational study of 201 patients with severe hyperlipidaemia. Atorvastatin 10 mg therapy was substituted for simvastatin 20 mg, 20 mg for 40 mg, 40 mg for simvastatin 40 mg plus resin, and 80 mg for simvastatin-fibrate-resin therapy. Lipid and safety profiles were assessed. Atorvastatin reduced total cholesterol by 31 +/- 11-40 +/- 14% vs. 25 +/- 12-31 +/- 11%; LDL by 38 +/- 16-45 +/- 18% vs. 31 +/- 18-39 +/- 18% and geometric mean triglycerides by 29.3-37.3% vs. 16.6-24.8%, but reduced HDL 11% +/- 47% at 80 mg compared with a 16% +/- 34% increase with simvastatin-based therapy. Target LDL < 3.5 mmol/l was achieved more often with atorvastatin (63% vs. 50%; p < 0.001). Atorvastatin increased geometric mean fibrinogen by 12-20% vs. a 0-6% fall with simvastatin (p << 0.001). Side effects were noted in 10-36% of patients, including one case of rhabdomyolysis, and 36% discontinued therapy. These data suggest that atorvastatin is more effective than current simvastatin-based therapies in achieving treatment targets in patients with familial hypercholesterolaemia but at the expense of a possible increase in side-effects. This issue needs further study in randomized controlled trials.

Anticholesteremic Agents↗
PubMed1999

Effects of growth hormone (GH) replacement therapy on very low density lipoprotein apolipoprotein B100 kinetics in patients with adult GH deficiency: a stable isotope study.

Patients with adult GH deficiency are often dyslipidemic and may have an increased risk of cardiovascular disease. The secretion and clearance of very low density lipoprotein apolipoprotein B 100 (VLDL apoB) are important determinants of plasma lipid concentrations. This study examined the effect of GH replacement therapy on VLDL apoB metabolism using a stable isotope turnover technique. VLDL apoB kinetics were determined in 14 adult patients with GH deficiency before and after 3 months GH or placebo treatment in a randomized double blind, placebo-controlled study using a primed constant [1-(13)C]leucine infusion. VLDL apoB enrichment was determined by gas chromatography-mass spectrometry. GH replacement therapy increased plasma insulin-like growth factor I concentrations 2.9 +/- 0.5-fold (P < 0.001), fasting insulin concentrations 1.8 +/- 0.6-fold (P < 0.04), and hemoglobin A1C from 5.0 +/- 0.2% to 5.3 +/- 0.2% (mean +/- SEM; P < 0.001). It decreased fat mass by 3.4 +/- 1.3 kg (P < 0.05) and increased lean body mass by 3.5 +/- 0.8 kg (P < 0.01). The total cholesterol concentration (P < 0.02), the low density lipoprotein cholesterol concentration (P < 0.02), and the VLDL cholesterol/VLDL apoB ratio (P < 0.005) decreased. GH therapy did not significantly change the VLDL apoB pool size, but increased the VLDL apoB secretion rate from 9.2 +/- 2.0 to 25.9 +/- 10.3 mg/kg x day (P < 0.01) and the MCR from 11.5 +/- 2.7 to 20.3 +/- 3.2 mL/min (P < 0.03). No significant changes were observed in the placebo group. This study suggests that GH replacement therapy improves lipid profile by increasing the removal of VLDL apoB. Although GH therapy stimulates VLDL apoB secretion, this is offset by the increase in the VLDL apoB clearance rate, which we postulate is due to its effects in up-regulating low density lipoprotein receptors and modifying VLDL composition.

Adult↗
PubMed1999

Dynamics of lipoprotein metabolism in adult growth hormone deficiency.

Dyslipidaemia is often associated with adult growth hormone (GH) deficiency. Reduced removal of very-low-density lipoprotein (VLDL) apolipoprotein B-100 (apo B-100) can, in part, explain the "unfavourable" lipid profile of these patients. By modifying VLDL composition and through its action on low-density lipoprotein (LDL) receptors, GH may improve the lipid profile by increasing direct hepatic uptake of VLDL apo B-100, thereby decreasing conversion to LDL. Although GH stimulates VLDL apo B-100 secretion, this is exceeded by its effects in upregulating LDL receptors and modifying VLDL composition. We hypothesize that the improved lipid profile, in particular the decrease in cholesterol-rich VLDL particles, may contribute to a possible antiatherogenic action of GH. GH appears to have an important role in hepatic apo B-100 metabolism. However, we are just at the beginning of understanding the underlying mechanism. Further studies are required to investigate the effect of GH on other lipoprotein classes, in particular VLDL subfractions, intermediate-density lipoprotein, LDL and high-density lipoprotein. The key question, however, remains as to whether GH replacement therapy can reduce cardiovascular mortality. Long-term studies with sufficient numbers of patients are required to answer this question.

Animals↗