PubMed Health⌕ Search

Biomedical subjects

Juan J Díez

Publications and source records attributed to Juan J Díez.

At least 19 recordsLinked to original sources
PubMed2006

Serum ghrelin concentrations in patients with chronic renal failure undergoing dialysis.

BACKGROUND: Ghrelin is a recently discovered protein hormone mainly synthesized in the gastric endocrine cells. This hormone not only is a potent growth hormone secretagogue but also is involved in the regulation of food ingestion and energy metabolism. Derangements in ghrelin secretion in patients with chronic renal failure (CRF) have not been fully evaluated. OBJECTIVE: Our aim has been to quantify serum concentrations of total ghrelin in a group of patients with CRF on chronic therapy with both haemodialysis (HD) and peritoneal dialysis (PD) in comparison with a group of patients on conservative management (predialysis). PATIENTS AND MEASUREMENTS: We studied 68 CRF patients treated by HD (n = 30, 16 men, age 61.2 +/- 1.8 years) and PD groups (n = 38, 21 men, age 54.4 +/- 1.7 years). A group of 19 uraemic patients on conservative management served as the control. Serum concentrations of ghrelin, leptin, insulin, IGF I and GH were measured in all subjects. RESULTS: Patients undergoing HD showed similar concentrations of ghrelin in comparison with the control group (9491 +/- 787 vs 9280 +/- 918 pg/ml, NS). However, PD patients exhibited baseline ghrelin concentrations significantly lower than those found in patients on conservative management (3230 +/- 216 pg/ml, P < 0.0001). Men and women showed similar serum ghrelin levels in both HD (9845.9 +/- 1071 vs 9085 +/- 1194 pg/ml) and PD patients (3214 +/- 297 vs 3250 +/- 324 pg/ml). Hypertension and diabetes mellitus did not influence ghrelin levels. Serum GH levels were positively correlated with serum ghrelin concentrations in both HD (r = 0.46, P < 0.05) and PD (r = 0.53, P < 0.001) patients; however, no relationships between ghrelin, leptin, insulin and IGF I were found. CONCLUSIONS: These results suggest that PD is accompanied by a striking decrement in baseline ghrelin concentrations in comparison with values found both in HD and control patients. Further studies are necessary to determine mechanisms involved in ghrelin regulation in uraemic patients.

Adult↗
PubMed2006

Growth hormone and insulin-like growth factor binding protein-1 responses to oral glucose in patients with primary hyperparathyroidism.

BACKGROUND: GH and IGFBP-1 both play a role in glucose homeostasis. OBJECTIVE: To assess the GH and IGFBP-1 responses to an oral glucose load and their relationship with glucose homeostasis in patients with primary hyperparathyroidism. DESIGN: A cross-sectional study with a control group followed by a longitudinal study after parathyroidectomy. PATIENTS AND METHODS: We studied 15 patients with primary hyperparathyroidism (eight women, aged 59.6 +/- 2.2 years) and nine healthy normocalcaemic controls. All subjects were ambulatory and were studied as outpatients. Glucose, insulin, GH and IGFBP-1 were measured during an oral glucose (75 g) tolerance test (OGTT). RESULTS: Patients with hyperparathyroidism showed similar glucose responses to OGTT to those found in controls. Insulin responses were higher in patients (peak insulin 96.33 +/- 9.71 mU/l) in relation to values found in controls (58.11 +/- 9.03 mU/l; P < 0.01). Suppression of GH levels after OGTT was more marked in patients [nadir 0.03 (0.02-0.05) microg/l] than in normocalcaemic subjects [nadir GH 0.12 (0.08-0.42) microg/l; P = 0.002]. However, baseline IGFBP-1 concentration and its decrease after glucose load were similar in patients and controls. Normalization of calcium levels after parathyroidectomy was not followed by any significant changes in glucose, insulin and GH responses to OGTT. The minimum concentration of IGFBP-1 and the area under the curve (AUC) of IGFBP-1 after OGTT were higher after parathyroidectomy (3.34 +/- 0.69 microg/l and 8.94 +/- 1.72 microg x h/l, respectively) than at diagnosis (2.19 +/- 0.42 microg/l and 6.74 +/- 1.28 microg x h/l, respectively; P < 0.05). No correlation was found between PTH, calcium and phosphorus concentrations and GH and IGFBP-1 values in patients before or after normalization of calcium metabolism. CONCLUSION: GH and IGFBP-1 do not seem to be directly involved in the hyperparathyroidism-associated changes in carbohydrate metabolism. The postoperative changes in the depression of IGFBP-1 after OGTT remain to be elucidated.

Administration, Oral↗
PubMed2006

Peroxisome proliferator-activated receptor gamma agonists in renal disease.

Type 2 diabetes is a well recognised cause of chronic renal failure (CRF). Only few oral antidiabetic drugs can be used for treating type 2 diabetes in patients with CRF. Among them are repaglinide, a rapid-acting prandial insulin releaser, and peroxisome proliferator-activated receptor gamma (PPARgamma) agonists, such as rosiglitazone and pioglitazone. These compounds are metabolised in the liver, therefore accumulation of the drug and the risk of severe and prolonged hypoglycaemia are minimised. PPARgamma receptors are expressed in many tissues including the kidney. Recently, numerous healthful effects of PPARgamma agonists on several aspects related to renal function have been increasingly reported. These drugs have shown to possess many advantageous anti-inflammatory, haemodynamic, vascular and metabolic effects. In the present paper we have reviewed the more recent experimental studies that evaluated these potential beneficial effects of PPARgamma agonists on renal function and revised the results of their utilisation in patients with different degrees of renal impairment, in dialysis patients, and in patients with diabetes mellitus after kidney transplantation. Finally, tolerability and safety profile of PPARgamma agonists in patients with reduced glomerular filtration rate are also analysed.

Animals↗
PubMed2005

Spontaneous normalization of thyrotropin concentrations in patients with subclinical hypothyroidism.

CONTEXT: Patients with subclinical hypothyroidism may revert to normal TSH values. OBJECTIVE: The objective of this study was to examine the time course of the normalization of TSH levels in subclinical hypothyroidism. DESIGN: This was a prospective, observational study with no intervention, with a duration of follow-up of 12-72 months. SETTING: Outpatients visited an endocrinology clinic of a general hospital. PATIENTS: Forty patients (32 women, mean age 62.8 +/- 8.2 yr) with spontaneous subclinical hypothyroidism (TSH > 5 mU/liter and normal free T(4)) participated in the study. Each patient normalized their TSH values without T(4) therapy throughout the follow-up. MEASUREMENTS: TSH and free T(4) levels were evaluated every 6 months. RESULTS: Normalization occurred at a median time of 18 months (range, 6-60 months). Fifteen patients normalized their TSH levels during the first year of follow-up and 27 during the first 2 yr. Ten patients normalized their TSH values at the fourth or fifth year. Only four patients reverted to TSH values less than 2 mU/liter. Final TSH levels achieved by the patients were significantly correlated with the time elapsed until normalizing these levels (r = 0.367; P = 0.020). CONCLUSIONS: There is no clear pattern of TSH normalization, although most patients normalize their TSH values early in the follow-up. The final TSH reached seems to be related to the time of normalization.

Aged↗
PubMed2005

Goiter in adult patients aged 55 years and older: etiology and clinical features in 634 patients.

BACKGROUND: Goiter is common in older people, although the frequency of the different causes of goiter has not been well defined. Our aim has been to assess the frequency of the diverse etiologies of goiter in adult patients aged 55 years and older, and evaluate the relationships between etiology and age, sex, and goiter features. METHODS: We performed a descriptive, cross-sectional study in ambulatory patients in the setting of an endocrinology clinic. Six hundred thirty-four patients (544 women, 85.8%) with goiter, aged 55-91 years, were studied. RESULTS: Causes of goiter were nontoxic multinodular goiter (325 patients, 51.3%); toxic multinodular goiter (151 patients, 23.8%); solitary thyroid nodule (62 patients, 9.8%); toxic adenoma (32 patients, 5.0%); Graves' disease (27 patients, 4.3%); Hashimoto's thyroiditis (25 patients, 3.9%); simple goiter (8 patients, 1.3%); thyroiditis (3 patients, 0.5%); and thyroid-stimulating hormone-secreting pituitary adenoma (1 patient, 0.2%). Patients with multinodular goiter had greater thyroid size and longer time of evolution than those patients with uninodular disease. Most of the symptoms and signs associated with goiter were dependent on thyroid size and time of evolution. Age and sex conditioned the presence of retrosternal goiter and tracheal deviation, and previous therapy was related to retrosternal goiter and local symptoms. However, etiology was not associated with the presence of any symptom. CONCLUSION: Nontoxic and toxic multinodular goiter are the main etiologies of goiter in patients aged 55 years and older. Thyroid size is the main factor influencing the appearance of signs and symptoms, although age and sex are related with the presence of retrosternal goiter and tracheal deviation.

Age Factors↗
PubMed2005

Serum concentrations of leptin, adiponectin and resistin, and their relationship with cardiovascular disease in patients with end-stage renal disease.

BACKGROUND AND OBJECTIVE: High levels of some adipocytokines have been reported in patients with chronic renal failure, but little information is available on adipocytokine concentrations in uraemic patients under different modalities of therapy. Our aims were (1) to quantify the serum concentrations of leptin, adiponectin and resistin in uraemic patients on peritoneal dialysis (PD) and haemodialysis (HD), in comparison with patients on conservative management, and (2) to study the relationships between adipocytokine levels and previous atherosclerotic vascular disease. PATIENTS AND MEASUREMENTS: We studied 82 dialysis patients treated by PD (n = 44, 23 males and 21 females, mean age 54.4 +/- 1.8 years) or HD (n = 38, 22 males and 16 females, age 60.8 +/- 1.6 years). A group of 19 uraemic patients on conservative management served as the control. Serum concentrations of leptin, adiponectin and resistin were measured in all subjects. Information on vascular disease (cerebral vascular, peripheral vascular and heart disease) was obtained from a detailed medical history. RESULTS: PD patients showed significantly higher serum leptin concentrations [median (interquartile range), 28.7 (13.0-71.9) microg/l] than those found in patients on HD [9.7 (4.7-31.9) microg/l, P < 0.01] or in conservative management [5.9 (4.3-38.6) microg/l, P < 0.05]. Adiponectin concentrations were similar in the three groups of patients (mean +/- SEM, 48.0 +/- 4.5 mg/l in PD, 57.7 +/- 4.4 mg/l in HD, and 44.4 +/- 7.0 mg/l in controls, NS). Patients treated by both PD and HD exhibited resistin concentrations significantly higher than those found in controls (26.3 +/- 0.99 and 27.5 +/- 1.4 microg/l, respectively, vs. 17.3 +/- 1.0 microg/l, P < 0.001). Leptin concentrations were positively correlated with body mass index (BMI) (r = 0.287, P < 0.01) and adiponectin levels were negatively related to BMI (r = -0.416, P < 0.001) and the homeostatic model assessment (HOMA-R) index (r =-0.216, P < 0.05). Leptin, adiponectin and resistin levels in patients with previous vascular events were similar to those found in patients without these complications. Logistic regression analysis did not demonstrate any relationship between serum adipocytokine concentrations and the presence of vascular disease of any type. A significant relationship between resistin and heart disease [odds ratio (OR) 1.80 (1.03-3.15), P = 0.039] was found when analysing subgroups of patients. CONCLUSIONS: These data suggest that leptin levels are higher in PD patients, and resistin levels are higher in PD and HD patients in relation to patients on conservative management, whereas adiponectin concentrations are similar in the three groups. These results do not support the presence of a clinically relevant relationship between adipocytokines and previous episodes of vascular disease in the whole population or in patients classified in subgroups, with the only exception of a relationship between resistin levels and heart disease.

Adiponectin↗
PubMed2004

Resolution of macroprolactinoma-induced symptomatic hydrocephalus following cabergoline therapy.

A 71-year-old man was referred because of memory loss. Magnetic resonance imaging showed a pituitary macroadenoma associated with hydrocephalus. Marked hyperprolactinaemia was present. After 2 months of cabergoline therapy, magnetic resonance imaging showed tumour shrinkage with resolution of the hydrocephalus. We report, for the first time, the adequate and rapid clinical response of a macroprolactinoma-induced symptomatic hydrocephalus in an elderly man to a low and once-a-week dose of cabergoline therapy. Medical therapy with this dopamine agonist in this particular patient was so effective that ventriculo-peritoneal shunting could be avoided.

Adenoma↗
PubMed2004

Growth hormone, IGF-I and its binding proteins (IGFBP-1 and -3) in adult uraemic patients undergoing peritoneal dialysis and haemodialysis.

OBJECTIVE: The GH/IGF axis is altered in chronic renal failure (CRF). CRF patients usually show normal or high serum concentrations of GH and IGF-I, whereas all IGF binding proteins (IGFBP-1 to -6), except IGFBP-5, considerably increase with declining renal function. The aims of the present study were to quantify serum concentrations of GH, IGF-I, IGFBP-1 and IGFBP-3 in a group of patients with CRF, and determine whether there were differences according to the type of dialysis, that is, peritoneal dialysis (PD) and haemodialysis (HD). DESIGN: A cross-sectional study in the setting of a dialysis unit of a general hospital. PATIENTS AND MEASUREMENTS: We studied 108 dialysis patients treated by PD (n = 54, 32 males and 22 females, mean age 61.0 +/- 1.4 years) or HD (n = 54, 31 males and 23 females, age 62.6 +/- 1.5 years). A group of 42 healthy subjects of similar age, sex and body mass index (BMI) served as the control group. Baseline serum concentrations of GH, insulin, IGF-I, IGFBP-1 and IGFBP-3 were measured in all patients and control subjects. RESULTS: Fasting serum concentrations of IGF-I and its binding proteins (IGFBP-1 and IGFBP-3) were significantly higher in dialysis patients than in subjects with normal renal function. IGF-I (248.9 +/- 23.4 vs. 205.5 +/- 15.5 micro g/l, NS), IGFBP-3 (5.6 +/- 0.4 vs. 5.5 +/- 0.2 mg/l, NS) and IGFBP-1 (36.1 +/- 5.9 vs. 44.1 +/- 6.5 micro g/l, NS) concentrations were similar in both groups of dialysis (PD vs. HD) patients. However, GH (2.3 +/- 0.3 vs. 1.1 +/- 0.1 micro g/l, P < 0.001) and insulin (40.4 +/- 4.5 vs. 30.1 +/- 3.1 micro U/ml, P < 0.05) levels were significantly higher in the PD group than in the HD group. Both groups of dialysis patients showed significantly higher levels of insulin than healthy subjects (14.7 +/- 1.9 micro U/ml, P < 0.0001 and P < 0.01 for PD and HD, respectively). In both groups of dialysis patients, IGF-I correlated inversely with IGFBP-1 (PD group r = -0.46, P = 0.0006; HD group r = -0.57, P = 0.0001) and directly with IGFBP-3 (PD group r = 0.44, P = 0.001; HD group r = 0.73, P = 0.001). No correlation between insulin and IGFBP-1 was found in any of the groups studied. CONCLUSIONS: These findings demonstrate that adult dialysis patients have elevated IGF-I, IGFBP-1 and IGFBP-3 serum concentrations compared with subjects with normal renal function. Only GH and insulin show statistically significant differences in relation to type of dialysis. Finally, the negative correlation between IGF-I and IGFBP-1 and the positive correlation between IGF-I and IGFBP-3 are maintained in both groups of adult dialysis patients.

Analysis of Variance↗
PubMed2004

Spontaneous subclinical hypothyroidism in patients older than 55 years: an analysis of natural course and risk factors for the development of overt thyroid failure.

We aimed to analyze the natural course of subclinical hypothyroidism, quantify the incidence rate of overt hypothyroidism, and evaluate the risk factors for the development of definitive thyroid failure in elderly patients. One hundred seven patients (93 women and 14 men) over age 55 yr with subclinical hypothyroidism and no previous history of thyroid disease were prospectively studied. Subjects were followed up for 6-72 months (mean, 31.7 months) with repeated determinations of TSH and free T(4). Twenty-eight patients (26.8%) developed overt hypothyroidism, and 40 (37.4%) showed normalization of their TSH values. The incidence rate of overt hypothyroidism was 9.91 cases per 100 patient-years in the whole population, and 1.76, 19.67, and 73.47 cases per 100 patient-years in subjects with initial TSH values between 5.0-9.9, 10.0-14.9, and 15.0-19.9 mU/liter, respectively. Kaplan-Meier analysis showed that the development of definitive thyroid hypofunction was significantly related to the presence of symptoms of hypothyroidism, goiter, positive thyroid antibodies (P < 0.05), and mainly low normal free T(4) (P < 0.01) and high TSH (P < 0.0001) concentrations at baseline. A stepwise multivariate Cox regression analysis showed that the only significant factor for progression to overt hypothyroidism was serum TSH concentration (P < 0.0001). In conclusion, TSH concentration is the most powerful predictor for the outcome of spontaneous subclinical hypothyroidism in patients over age 55 yr. Subjects with mildly elevated TSH have a low incidence rate of overt hypothyroidism. We recommend follow-up with clinical and biochemical monitoring in these patients.

Aged↗
PubMed2004

Lipoatrophic diabetes in an elderly woman: clinical course and serum adipocytokine concentrations.

Generalized lipodystrophy is a rare disorder of adipose tissue, whose etiology remains unknown. Pathophysiology of this disorder is characterized by generalized loss of body fat associated with an infrequent form of diabetes mellitus (lipoatrophic diabetes). Main features of this form of diabetes mellitus are the severe insulin resistance and the absence of ketoacidosis. Lipodystrophy can be congenital or acquired. In the acquired form, metabolic disturbances usually begin in the first years of life and the response to conventional treatment is very poor. Some alterations in serum adipocytokines have been described in this disease. We report the case of a 74-year-old woman with acquired generalized lipodystrophy who presented with low-normal serum concentrations of leptin, low adiponectin and resistin levels, and high serum levels of TNF alpha. Patient was initially treated with fenofibrate, metformin and high doses of subcutaneous insulin achieving an adequate metabolic control. During this period, serum adipocytokines were periodically measured. We comment on the different etiopathogenic mechanisms and the therapeutic modalities of this rare syndrome.

Adiponectin↗
PubMed2004

Ghrelin plasma levels and appetite in peritoneal dialysis patients.

Anorexia-associated malnutrition is a severe complication that increases mortality in peritoneal dialysis (PD) patients. Ghrelin is a recently-discovered orexigenic hormone with actions in brain and stomach. We analyzed, in 42 PD patients, the possible relationship between ghrelin and appetite regulation with regard to other orexigens [neuropeptide Y (NPY), NO3] and anorexigens [cholecystokinin (CCK), leptin, glucose-dependent insulinotropic peptide (GIP), tumor necrosis factor alpha (TNFalpha)]. All orexigens and anorexigens were determined in plasma. Eating motivation was evaluated using a visual analog scale (VAS). The patients were divided into three groups: those with anorexia (n = 12), those with obesity associated with high intake (n = 12), and those with no eating behavior disorders (n = 18). A control group of 10 healthy volunteers was also evaluated. Mean plasma levels of ghrelin were high (3618.6 +/- 1533 mg/mL), with 36 patients showing values above the normal range (< 2600 mg/mL). Patients with anorexia had lower ghrelin and NPY levels and higher peptide-C, CCK, interleukin-1 (IL-1), TNFalpha, and GIP levels than did the other patients. Patients with anorexia also had an early satiety score and low desire and pleasure in eating on the VAS and diet survey. We observed significant positive linear correlations between ghrelin and albumin (r = 0.43, p < 0.05), prealbumin (r = 0.51, p < 0.05), transferrin (r = 0.4, p < 0.05), growth hormone (r = 0.66, p < 0.01), NO3 (r = 0.36, p < 0.05), and eating motivation (VAS). At the same time, negative relationships were observed between blood ghrelin and GIP (r = -0.42, p < 0.05), insulin (r = -0.4, p < 0.05), leptin (r = -0.45, p < 0.05), and creatinine clearance [r = -0.33, p = 0.08 (nonsignificant)]. Ghrelin levels were not related to Kt/V or to levels of CCK and cytokines. Ghrelin plasma levels are elevated in PD patients. Uremic patients with anorexia show relatively lower ghrelin plasma levels than the levels seen in obese patients or in patients with normal appetite. The role of ghrelin in appetite modulation is altered in uremic PD patients, and that alteration is possibly associated with disorders in insulin and growth hormone metabolism.

Adult↗
PubMed2003

Serum concentrations of adipocytokines in patients with hyperthyroidism and hypothyroidism before and after control of thyroid function.

OBJECTIVE: Adipose tissue is a hormonally active system that produces and releases different bioactive substances. Leptin, adiponectin and resistin are some of the recently discovered adipocytokines that participate in the regulation of intermediate metabolism. The aim of this study was to evaluate the circulating levels of leptin, adiponectin and resistin in patients with thyroid dysfunction before and after normalization of thyroid function with appropriate therapy. PATIENTS AND MEASUREMENTS: We studied 20 patients with hyperthyroidism (16 women and 4 men; mean age 47.2 +/- 3.9 years) and 20 patients with hypothyroidism (17 women and 3 men; 51.5 +/- 4.1 years). A group of 20 euthyroid subjects served as control group. Patients were evaluated at the time of diagnosis and again after normalization of thyroid function with appropriate therapy. Serum concentrations of free T4 (FT4), total T3, TSH, insulin, leptin, adiponectin and resistin were measured in all subjects. RESULTS: Hyperthyroid patients showed significantly decreased leptin levels in comparison with controls (11.0 +/- 1.1 vs. 30.4 +/- 5.0 microg/l, P < 0.001). No significant differences in adiponectin levels between hyperthyroid and control groups were found (27.8 +/- 4.0 vs. 46.0 +/- 12.0 mg/l, NS). Patients with hyperthyroidism exhibited reduced resistin levels in comparison with euthyroid subjects (6.4 +/- 0.8 vs. 8.4 +/- 0.7 microg/l, P < 0.05). Normalization of circulating thyroid hormone was accompanied by a nonsignificant increase in leptin levels (12.9 +/- 1.7 microg/l, P < 0.01 vs. control) and no significant modification both in adiponectin (32.0 +/- 7.1 mg/l, NS) and resistin (5.4 +/- 0.7 microg/l, NS) levels. Adjustment of adipocytokine concentrations for body mass index (BMI) showed that treatment of hyperthyroidism induced a significant reduction in adjusted resistin concentrations (0.21 +/- 0.03 vs. 0.28 +/- 0.03 microg/l/BMI units, P < 0.05), with no changes in adjusted leptin and adiponectin. Hypothyroid patients showed significantly lower leptin levels compared with the controls (16.0 +/- 3.5 vs. 30.4 +/- 5.0 microg/l, P < 0.05). Adiponectin levels in patients with hypothyroidism (71.8 +/- 16.0 mg/l) were similar to those in the control group and were not modified with therapy. Resistin levels were significantly reduced among hypothyroid patients (5.8 +/- 1.0 microg/l, P < 0.05), and were not increased after levothyroxine therapy. A significant rise in BMI-corrected leptin levels was observed after replacement therapy, with no changes in adiponectin- and resistin-corrected values. CONCLUSIONS: The results suggest that (1) low serum leptin levels are present in both hyperthyroid and hypothyroid patients but are only increased after therapy in the latter; (2) resistin might be implicated in the insulin resistance state that accompanies thyrotoxicosis; and (3) inadequate secretion of adiponectin seems to have no role in metabolic changes associated with thyroid dysfunction.

Adiponectin↗
PubMed2003

New drugs for the treatment of hypercholesterolaemia.

Endogenous and exogenous pathways determine plasma levels of cholesterol and lipoproteins. Plasma cholesterol levels and coronary heart disease risk can be reduced pharmacologically by decreasing cholesterol synthesis, increasing its elimination and/or reducing its absorption from the intestine. The more profound knowledge about cholesterol homeostasis has allowed the development of several lipid-lowering drugs with different mechanisms of action, with the purpose of reducing both morbidity and mortality associated with coronary heart disease. Two new and more potent 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins), also called superstatins (rosuvastatin and pitavastatin), are being studied for their ability to improve lipid profiles. Rosuvastatin is a potent, hepato-selective and relatively hydrophilic statin with a low propensity for muscle toxicity and drug interactions. Pitavastatin is another statin with a high oral bioavailability and minimal propensity for cytochrome p450-mediated drug interactions. Rosuvastatin seems to be more potent than other available statins while pitavastatin presents with a similar potency to that of atorvastatin. Another promising approach for lowering total and low-density lipoprotein cholesterol levels is inhibition of cholesterol absorption. A wide variety of new agents with the capacity for inhibiting the intestinal cholesterol absorption is currently being investigated. Ezetimibe is a selective cholesterol absorption inhibitor whose clinical efficacy has been recently demonstrated both in monotherapy and in combination with other lipid-lowering drugs. Colesevelam, a new bile acid sequestrant, has shown a clinical efficacy similar to that of other resins, with minimal gastrointestinal side effects, improving tolerability and patient compliance. Other lipid-lowering drugs with the ability to act at the enterocyte level, such as avasimibe and implitapide, are currently being investigated in humans.

Absorption↗
PubMed2003

The role of the novel adipocyte-derived hormone adiponectin in human disease.

Adiponectin, also called GBP-28, apM1, AdipoQ and Acrp30, is a novel adipose tIssue-specific protein that has structural homology to collagen VIII and X and complement factor C1q, and that circulates in human plasma at high levels. It is one of the physiologically active polypeptides secreted by adipose tIssue, whose multiple functions have started to be understood in the last few Years.A reduction in adiponectin expression is associated with insulin resistance in some animal models. Administration of adiponectin has been accompanied by a reduction in plasma glucose and an increase in insulin sensitivity. In addition, thiazolidinediones, drugs that enhance insulin sensitivity through stimulation of the peroxisome proliferator-activated receptor-gamma, increase plasma adiponectin and mRNA levels in mice. On the other hand, this adipocyte protein seems to play a protective role in experimental models of vascular injury. In humans, adiponectin levels are inversely related to the degree of adiposity and positively associated with insulin sensitivity both in healthy subjects and in diabetic patients. Plasma adiponectin levels have been reported to be decreased in some insulin-resistant states, such as obesity and type 2 diabetes mellitus, and also in patients with coronary artery disease. On the contrary, chronic renal failure, type 1 diabetes and anorexia nervosa are associated with increased plasma adiponectin levels. Concentrations of plasma adiponectin have been shown to correlate negatively with glucose, insulin, triglyceride levels and body mass index, and positively with high-density lipoprotein-cholesterol levels and insulin-stimulated glucose disposal. Weight loss and therapy with thiazolidinediones increased endogenous adiponectin production in humans. Adiponectin increases insulin sensitivity by increasing tIssue fat oxidation, resulting in reduced circulating fatty acid levels and reduced intracellular triglyceride contents in liver and muscle. This protein also suppresses the expression of adhesion molecules in vascular endothelial cells and cytokine production from macrophages, thus inhibiting the inflammatory processes that occur during the early phases of atherosclerosis. In view of these data, it is possible that hypoadiponectinemia may play a role in the development of atherosclerotic vascular disease. In summary, the ability of adiponectin to increase insulin sensitivity in conjunction with its anti-inflammatory and anti-atherogenic properties have made this novel adipocytokine a promising therapeutic tool for the future, with potential applications in states associated with low plasma adiponectin levels.

Adipocytes↗
PubMed2002

Serum concentrations of tumour necrosis factor-alpha (TNF-alpha) and soluble TNF-alpha receptor p55 in patients with hypothyroidism and hyperthyroidism before and after normalization of thyroid function.

BACKGROUND: Tumour necrosis factor-alpha (TNF-alpha) is a cytokine with numerous immunological and metabolic activities. Receptors for TNF-alpha have been demonstrated in thyroid follicular cells and TNF-alpha and its receptors have been implicated in the cytotoxic mechanisms that characterize the thyroid destruction in autoimmune thyroid disease. In patients with Graves' disease, serum levels of TNF-alpha have been reported to be elevated and administration of TNF-alpha to humans has been shown to induce hormonal alterations resembling those seen in the nonthyroidal illness syndrome. OBJECTIVE: To evaluate serum concentrations of TNF-alpha and the soluble receptor for TNF-alpha (sTNFR-I) in a group of patients with thyroid dysfunction before and after normalization of thyroid function with appropriate therapy. DESIGN: We studied 20 patients with hypothyroidism (18 women and 2 men, mean age +/- SD, 48.8 +/- 16.1 years) and 20 patients with hyperthyroidism (14 women and 6 men, age 44.6 +/- 15.9 years). Patients were assessed at the time of diagnosis and again after normalization of thyroid function tests with appropriate therapy. A group of 20 healthy subjects (15 women and 5 men, age 44.9 +/- 15.1 years) were also studied as a control group. SETTING: All subjects were ambulatory and were studied as outpatients during visits to the endocrinology clinic. MEASUREMENTS: Serum concentrations of free T4 (FT4), total T3, TSH, TNF-alpha and sTNFR-I were measured in all subjects. TNF-alpha and sTNFR-I were measured using a quantitative enzyme immunoassay. RESULTS: In patients with hypothyroidism serum concentrations of TNF-alpha (3.17 +/- 1.18 pg/ml) and sTNFR-I (1273 +/- 364 pg/ml) were significantly higher than those found in controls (2.42 +/- 0.76 pg/ml, P < 0.05, and 971 +/- 235 pg/ml, P < 0.01, respectively). Normalization of thyroid function with l-thyroxine therapy did not significantly modify TNF-alpha or sTNFR-I levels. There were no differences in pre- and post-therapy values of TNF-alpha and sTNFR-I in patients with autoimmune (n = 14) or nonautoimmune (n = 6) hypothyroidism. Before therapy, patients with hyperthyroidism showed elevated serum concentrations of TNF-alpha (3.36 +/- 1.21 pg/ml; P < 0.01) and sTNFR-I (2274 +/- 579 pg/ml; P < 0.001) in relation to the control group. Treatment of hyperthyroidism was accompanied by a normalization of TNF-alpha levels (2.46 +/- 0.89 pg/ml; P < 0.001) and by a significant decrease in sTNFR-I concentrations (1369 +/- 475 pg/ml; P < 0.001). Post-therapy levels of TNF-alpha and sTNFR-I showed a significant correlation with loss of weight (r = 0.674, P < 0.01, and r = 0.629, P < 0.01, respectively) in hypothyroid patients. No correlation between these parameters was found in the group of patients with hyperthyroidism. CONCLUSIONS: In summary, these results confirm the relevance of activation of the TNF-alpha system in patients with thyroid dysfunction, as high plasma concentrations of TNF-alpha and sTNFR-I have been demonstrated in patients with hypothyroidism or hyperthyroidism. Treatment of hyperthyroidism is accompanied by a significant reduction in the previously elevated concentrations of both TNF-alpha and sTNFR-I. However, these changes are not seen when normalizing thyroid function in patients with hypothyroidism.

Adult↗
PubMed2002

Hypothyroidism in patients older than 55 years: an analysis of the etiology and assessment of the effectiveness of therapy.

BACKGROUND: Several epidemiological studies on the prevalence of hypothyroidism in the elderly have been reported; however, extensive series of elderly patients with thyroid dysfunction have not been studied. Our aim has been to assess the relative frequency of the diverse causes of hypothyroidism in a group of patients older than 55 years and the adequacy of control of thyroid function attained by levothyroxine therapy. METHODS: We performed a descriptive, observational, cross-sectional study in the setting of a hospital endocrinology clinic. From a total of 1581 patients older than 55 who were complaining of a thyroid disorder, we studied a group of 655 patients with hypothyroidism. There were 559 women (85.3%, age 65.01 +/- 7.90 years) and 96 men (14.7%, 65.36 +/- 8.39 years). In every patient, we collected etiology, presence of goiter, time of evolution from diagnosis and from therapy prescription, previous and present treatments, current thyroid functional status (free thyroxine and thyrotropin concentration), adequacy of disease control, and thyroid autoimmune status. RESULTS: The causes of hypothyroidism were as follows: autoimmune thyroiditis, 308 (47.0%); postoperative hypothyroidism, 175 (26.7%); therapy for previous thyrotoxicosis, 63 (9.6%); thyrotropin deficiency, 15 (2.3%); iodine excess, 6 (0.9%); subacute thyroiditis, 2 (0.3%); and unknown etiology, 86 (13.1%) patients. Most patients with autoimmune thyroiditis were positive for thyroid peroxidase antibodies at the time of the study (94.4%). Mean (+/- SD) age at diagnosis was 61.8 +/- 9.4 years in men and 59.8 +/- 9.7 years in women. Median (range) duration of hypothyroidism was 1.4 (0-18) years in men and 3 (0-45) years in women ( p <.05). Adequacy of therapy was studied in 385 patients treated with replacement doses of levothyroxine. Two hundred and sixty (67.5%) of these subjects attained good control, whereas 125 (32.5%) showed inadequate control of the disease at the time of the study. A model of logistic regression showed that adequacy of therapy was dependent on the duration of therapy, but independent of age, gender, degree of hypothyroidism, etiology, autoimmune status, age at diagnosis, and dose of levothyroxine. A 2-year follow-up study performed in 56 newly diagnosed patients showed that an adequate control of hypothyroidism was attained in 35 (62.5%) patients at 6 months, in 46 (82.1%) patients at 1 year, and in 49 (87.5%) at 2 years of therapy with levothyroxine. CONCLUSIONS: Autoimmune thyroiditis and postoperative hypothyroidism are the main causes of thyroid hypofunction in patients older than 55 years. The time from starting therapy is the main determinant of the adequacy of control of thyroid hypofunction in this population. With effective therapy and appropriate monitoring, more than 80% of the patients showed adequate control within 1 year of follow-up.

Cross-Sectional Studies↗