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1.
Eur J Endocrinol ; 173(4): 507-15, 2015 Oct.
Article in English | MEDLINE | ID: mdl-26169304

ABSTRACT

OBJECTIVE: Many patients treated for primary hypothyroidism have an unexplained reduced quality of life (QOL). We studied the relation between QOL and various parameters in treated hypothyroid patients. DESIGN AND METHODS: QOL analysis was done in 90 consecutive patients (77.8% females) treated for primary hypothyroidism. QOL was measured by the questionnaires Short-Form 36, Hospital Anxiety and Depression Scale and MFI20. Post hoc analysis was performed on the relation of QOL at baseline and BMI, thyroid hormones and other serum values. QOL in patients was also compared to the general population. RESULTS: QOL was decreased compared to the general population. We found an inverse relationship between QOL and BMI. A relationship between QOL and serum thyroid parameters or auto-antibodies could not be found. Higher sex hormone binding globulin (SHBG) levels corresponded with a better QOL, which is explained by the negative association of SHBG with body weight and BMI. CONCLUSIONS: A decreased QOL in hypothyroid patients on thyroxine treatment is related to a higher body weight (BMI). Weight gain needs more attention in the treatment of hypothyroidism.


Subject(s)
Anxiety/psychology , Depression/psychology , Hypothyroidism/psychology , Obesity/psychology , Quality of Life/psychology , Thyrotropin/blood , Thyroxine/blood , Triiodothyronine/blood , Adult , Anxiety/blood , Anxiety/complications , Autoantibodies/blood , Autoantigens/immunology , Body Mass Index , Depression/blood , Depression/complications , Female , Hormone Replacement Therapy/methods , Humans , Hypothyroidism/blood , Hypothyroidism/complications , Hypothyroidism/drug therapy , Immunoglobulins, Thyroid-Stimulating/blood , Iodide Peroxidase/immunology , Iron-Binding Proteins/immunology , Male , Middle Aged , Obesity/blood , Obesity/complications , Overweight/blood , Overweight/complications , Overweight/psychology , Sex Hormone-Binding Globulin/metabolism , Thyroxine/administration & dosage
2.
Ned Tijdschr Geneeskd ; 156(12): A4404, 2012.
Article in Dutch | MEDLINE | ID: mdl-22436525

ABSTRACT

Over the years the Netherlands has become a country with a population comprising over 20% of immigrants. Immigrants differ from natives in both biological and cultural aspects, amongst others in laboratory results, but also in level of participation in clinical trials, and treatment outcomes. It is important for physicians to keep these differences between ethnic groups in mind. The authors argue that specific reference ranges for subgroups should be established.


Subject(s)
Blood Chemical Analysis/standards , Ethnicity , Humans , Reference Values
3.
Brain Behav Immun ; 25(6): 1206-13, 2011 Aug.
Article in English | MEDLINE | ID: mdl-21443944

ABSTRACT

OBJECTIVES: We recently described a monocyte pro-inflammatory state in patients with bipolar disorder (BD). We hypothesized that the CD4(+)T cell system is also activated and determined percentages of Th1, Th2, Th17 and CD4(+)CD25(high)FoxP3(+) regulatory T cells. METHODS: We carried out a detailed FACS analysis to determine the various T cell subsets and used frozen stored peripheral blood mononuclear cells (PBMC) of 38 BD patients (of whom we previously had tested monocytes for pro-inflammatory gene expression (Drexhage et al., 2010b; Padmos et al., 2008)) and of 22 age/gender matched healthy controls (HC). In addition the cytokines CCL2, IL-1ß, IL-6, TNF-α, PTX3, IL-10, IFN-γ, IL-17A, IL-4, IL-5 and IL-22 were measured in serum. RESULTS: (a) Serum sCD25 levels and percentages of anti-inflammatory CD4(+)CD25(high)FoxP3+ regulatory T cells were higher, the latter in BD patients <40 years of age. Percentages of Th1, Th2 and Th17 cells were normal. (b) Of the pro-inflammatory monocyte cytokines CCL2 and PTX3 were raised in serum. (c) The monocyte pro-inflammatory state and the raised percentages of CD4(+)CD25(high)FoxP3(+) regulatory T cells occurred independently from each other. (d) In BD patients positive for thyroid autoimmune disease a significantly reduced percentage of CD4(+)CD25(high)FoxP3(+) regulatory T cells was found as compared to BD patients without AITD. CONCLUSION: Our data show an enhancement of pro-inflammatory monocyte and anti-inflammatory T cell forces in BD patients. A lack of anti-inflammatory T cell forces co-occurred with AITD in BD patients.


Subject(s)
Bipolar Disorder/immunology , Leukocytes, Mononuclear/immunology , T-Lymphocyte Subsets/immunology , Adult , Antigens, Differentiation, T-Lymphocyte/analysis , Bipolar Disorder/complications , Bipolar Disorder/genetics , Cytokines/blood , Female , Flow Cytometry , Gene Expression Profiling , Humans , Immunophenotyping , Inflammation , Lymphocyte Activation , Lymphocyte Count , Male , Middle Aged , RNA, Messenger/blood , T-Lymphocytes, Regulatory/immunology , Thyroiditis, Autoimmune/complications , Thyroiditis, Autoimmune/immunology
4.
Arch Intern Med ; 170(22): 1996-2003, 2010 Dec 13.
Article in English | MEDLINE | ID: mdl-21149757

ABSTRACT

BACKGROUND: Levothyroxine sodium is widely prescribed to treat primary hypothyroidism. There is consensus that levothyroxine should be taken in the morning on an empty stomach. A pilot study showed that levothyroxine intake at bedtime significantly decreased thyrotropin levels and increased free thyroxine and total triiodothyronine levels. To date, no large randomized trial investigating the best time of levothyroxine intake, including quality-of-life evaluation, has been performed. METHODS: To ascertain if levothyroxine intake at bedtime instead of in the morning improves thyroid hormone levels, a randomized double-blind crossover trial was performed between April 1, 2007, and November 30, 2008, among 105 consecutive patients with primary hypothyroidism at Maasstad Hospital Rotterdam in the Netherlands. Patients were instructed during 6 months to take 1 capsule in the morning and 1 capsule at bedtime (one containing levothyroxine and the other a placebo), with a switch after 3 months. Primary outcome measures were thyroid hormone levels; secondary outcome measures were creatinine and lipid levels, body mass index, heart rate, and quality of life. RESULTS: Ninety patients completed the trial and were available for analysis. Compared with morning intake, direct treatment effects when levothyroxine was taken at bedtime were a decrease in thyrotropin level of 1.25 mIU/L (95% confidence interval [CI], 0.60-1.89 mIU/L; P < .001), an increase in free thyroxine level of 0.07 ng/dL (0.02-0.13 ng/dL; P = .01), and an increase in total triiodothyronine level of 6.5 ng/dL (0.9-12.1 ng/dL; P = .02) (to convert thyrotropin level to micrograms per liter, multiply by 1.0; free thyroxine level to picomoles per liter, multiply by 12.871; and total triiodothyronine level to nanomoles per liter, multiply by 0.0154). Secondary outcomes, including quality-of-life questionnaires (36-Item Short Form Health Survey, Hospital Anxiety and Depression Scale, 20-Item Multidimensional Fatigue Inventory, and a symptoms questionnaire), showed no significant changes between morning vs bedtime intake of levothyroxine. CONCLUSIONS: Levothyroxine taken at bedtime significantly improved thyroid hormone levels. Quality-of-life variables and plasma lipid levels showed no significant changes with bedtime vs morning intake. Clinicians should consider prescribing levothyroxine intake at bedtime. TRIAL REGISTRATION: isrctn.org Identifier: ISRCTN17436693 (NTR959).


Subject(s)
Hormone Replacement Therapy/methods , Hypothyroidism/drug therapy , Thyroid Hormones/blood , Thyrotropin/blood , Thyroxine/administration & dosage , Adult , Aged , Body Mass Index , Creatinine/blood , Cross-Over Studies , Double-Blind Method , Drug Administration Schedule , Female , Heart Rate , Humans , Hypothyroidism/blood , Lipids/blood , Male , Middle Aged , Netherlands , Quality of Life , Surveys and Questionnaires , Thyroxine/blood , Triiodothyronine/blood
5.
J Clin Endocrinol Metab ; 95(4): 1962-71, 2010 Apr.
Article in English | MEDLINE | ID: mdl-20147583

ABSTRACT

CONTEXT: In monocytes of patients with autoimmune diabetes, we recently identified a gene expression fingerprint of two partly overlapping gene clusters, a PDE4B-associated cluster (consisting of 12 core proinflammatory cytokine/compound genes), a FABP5-associated cluster (three core genes), and a set of nine overlapping chemotaxis, adhesion, and cell assembly genes correlating to both PDE4B and FABP5. OBJECTIVE: Our objective was to study whether a similar monocyte inflammatory fingerprint as found in autoimmune diabetes is present in autoimmune thyroid disease (AITD). DESIGN AND PATIENTS: Quantitative PCR was used for analysis of 28 genes in monocytes of 67 AITD patients and 70 healthy controls. The tested 28 genes were the 24 genes previously found abnormally expressed in monocytes of autoimmune diabetes patients plus four extra genes found in whole-genome analysis of monocytes of AITD patients reported here. RESULTS: Monocytes of 24% of AITD and 50% of latent autoimmune diabetes of adults (LADA) patients shared an inflammatory fingerprint consisting of the set of 24 genes of the PDE4B, FABP5, and overlapping gene sets. This study in addition revealed that FCAR, the gene for the Fcalpha receptor I, and PPBP, the gene for CXCL7, were part of this proinflammatory monocyte fingerprint. CONCLUSIONS: Our study provides an important tool to determine a shared, specific proinflammatory state of monocytes in AITD and LADA patients, enabling further research into the role of such proinflammatory cells in the failure to preserve tolerance in these conditions and of key fingerprint genes involved.


Subject(s)
Inflammation/genetics , Monocytes/metabolism , Thyroiditis, Autoimmune/genetics , Adolescent , Adult , Aged , Aged, 80 and over , Biomarkers/analysis , Blood Proteins/metabolism , Cluster Analysis , DNA Fingerprinting , Diabetes Mellitus, Type 1/metabolism , Enzyme-Linked Immunosorbent Assay , Female , Graves Disease/genetics , Hashimoto Disease/genetics , Humans , Inflammation/metabolism , Male , Middle Aged , Reverse Transcriptase Polymerase Chain Reaction , Young Adult
9.
Clin Endocrinol (Oxf) ; 66(1): 43-8, 2007 Jan.
Article in English | MEDLINE | ID: mdl-17201800

ABSTRACT

OBJECTIVE: Standard drug information resources recommend that l-thyroxine be taken half an hour before breakfast on an empty stomach, to prevent interference of its intestinal uptake by food or medication. We observed cases in which TSH levels improved markedly after changing the administration time of l-thyroxine to the late evening. We therefore conducted a pilot-study to investigate whether l-thyroxine administration at bedtime improves TSH and thyroid hormones, and whether the circadian rhythm of TSH remains intact. DESIGN Patients were studied on two occasions: on a stable regimen of morning thyroxine administration and two months after switching to night-time thyroxine using the same dose. On each occasion patients were admitted for 24 h and serial blood samples were obtained. PATIENTS: We investigated 12 women treated with l-thyroxine because of primary hypothyroidism, who used no medication known to interfere with l-thyroxine uptake. MEASUREMENTS: Patients were admitted to hospital and blood samples were obtained at hourly intervals for 24 h via an indwelling catheter. Following this first hospital admission, all women were asked to switch the administration time from morning to bedtime or vice versa. After 2 months they were readmitted for a 24-h period of hourly blood sampling. Blood samples were analysed for serum TSH (immunometric assay), FT4 and T3 (competitive immunoassay), T4 and rT3 (radioimmunoassay), serum TBG (immunometric assay) and total protein and albumin (colourimetric methods). RESULTS: A significant difference in TSH and thyroid hormones was found after switching to bedtime administration of l-thyroxine. Twenty-four-hour average serum values amounted to (mean +/- SD, morning vs bedtime ingestion): TSH, 5.1 +/- 0.9 vs 1.2 +/- 0.3 mU/l (P < 0.01); FT4, 16.7 +/- 1.0 vs 19.3 +/- 0.7 pmol/l (P < 0.01); T3, 1.5 +/- 0.05 vs 1.6 +/- 0.1 nmol/l (P < 0.01). There was no significant change in T4, rT3, albumin and TBG serum levels, nor in the T3/rT3 ratio. The relative amplitude and time of the nocturnal TSH surge remained intact. CONCLUSIONS: l-thyroxine taken at bedtime by patients with primary hypothyroidism is associated with higher thyroid hormone concentrations and lower TSH concentrations compared to the same l-thyroxine dose taken in the morning. At the same time, the circadian TSH rhythm stays intact. Our findings are best explained by a better gastrointestinal uptake of l-thyroxine during the night.


Subject(s)
Circadian Rhythm , Hypothyroidism/blood , Hypothyroidism/drug therapy , Thyroxine/administration & dosage , Thyroxine/blood , Adult , Aged , Analysis of Variance , Blood Proteins/analysis , Drug Administration Schedule , Female , Humans , Middle Aged , Pilot Projects , Serum Albumin/analysis , Thyrotropin/blood , Thyroxine/therapeutic use , Thyroxine-Binding Proteins/analysis , Triiodothyronine/blood , Triiodothyronine, Reverse/blood
10.
Crit Care ; 9(5): 531-2; author reply 531-2, 2005 Oct 05.
Article in English | MEDLINE | ID: mdl-16277744

ABSTRACT

: We read with interest the article by Villa and coworkers 1 advocating the use of cystatin C as a measure of glomerular filtration rate (GFR) in critically ill patients. However, we should like to draw attention to several flaws in this study. First, Villa and coworkers compared cystatin C with creatinine as a measure of GFR, using body surface corrected creatinine clearance as, what they call, a 'gold standard'. However, in the Discussion section of that report inulin and iothalamate clearances are mentioned as gold standards, but they were not used by these investigators. The use of body surface area corrected creatinine clearance is questionable in both obese and excessively lean individuals because the correlation between surface area and lean body mass may be lost. Both types of patients are frequently encountered in intensive care. Second, Villa and coworkers employ a cutoff of 80 ml/min to identify renal dysfunction, whereas a value of 50 ml/min is generally accepted 2. This could have a major influence on the presented results. Third, patients with thyroid disorders or on corticosteroid therapy were excluded. Almost all patients with critical illness have low tri-iodothyronine values because of changes in thyroid hormone metabolism ('nonthyroidal illness'), thus making recognition of thyroid disorders problematic. Finally, we showed 3 that, in patients with thyroid dysfunction, cystatin C is not a suitable measure of GFR. In hypothyroidism creatinine levels are elevated but cystatin C levels are low, whereas in hyperthyroidism creatinine levels are low and cystatin C levels elevated. Taken together, we disagree with the authors that cystatin C could be used as a marker of GFR in intensive care patients.


Subject(s)
Cystatins/blood , Renal Insufficiency/diagnosis , Biomarkers/blood , Creatinine/blood , Cystatin C , Glomerular Filtration Rate , Humans , Intensive Care Units , Thyroid Diseases/diagnosis
12.
Arch Intern Med ; 165(15): 1714-20, 2005.
Article in English | MEDLINE | ID: mdl-16087818

ABSTRACT

BACKGROUND: The treatment of hypothyroidism with levothyroxine is effective and simple; however, recommendations for the starting dose vary considerably. To our knowledge, the levothyroxine starting dose has never been studied prospectively. METHODS: We conducted a prospective, randomized, double-blind trial that compared a full starting levothyroxine dose of 1.6 mug/kg with a low starting dose of 25 mug (increased every 4 weeks) in patients with newly diagnosed cardiac asymptomatic hypothyroidism. Safety was studied by documenting cardiac symptoms and events, and efficacy was studied by monitoring thyrotropin and free thyroxine levels and by assessing improvement of signs and symptoms and quality of life. RESULTS: Seventy-five consecutive patients were enrolled, of whom 50 underwent randomization. At baseline, the severity of hypothyroidism and age were comparable in the full-dose (n = 25) vs the low-dose group (n = 25): thyrotropin, 61 vs 48 mIU/L; free thyroxine, 0.56 vs 0.64 ng/dL (7.2 vs 8.2 pmol/L); and age, 47 vs 47 years. No cardiac complaints or events were documented during treatment or at bicycle ergometry at baseline, 12 weeks, or 24 weeks. Euthyroidism was reached in the full-dose vs the low-dose group in 13 vs 1 (4 weeks), 19 vs 3 (8 weeks), 19 vs 9 (12 weeks), 20 vs 14 (16 weeks), 20 vs 18 (20 weeks), and 21 vs 20 (24 weeks) patients (P = .005). However, signs and symptoms of hypothyroidism and quality of life improved at a comparable rate. CONCLUSION: A full starting dose of levothyroxine in cardiac asymptomatic patients with primary hypothyroidism is safe and may be more convenient and cost-effective than a low starting dose regimen.


Subject(s)
Hypothyroidism/drug therapy , Thyroxine/administration & dosage , Adult , Aged , Double-Blind Method , Half-Life , Humans , Male , Middle Aged , Prospective Studies , Quality of Life , Thyrotropin/blood
13.
Clin Endocrinol (Oxf) ; 62(4): 423-7, 2005 Apr.
Article in English | MEDLINE | ID: mdl-15807872

ABSTRACT

OBJECTIVE: Renal function is profoundly influenced by thyroid status; however, this has not been studied in detail in human subjects. The purpose of the present study was to determine the relationship between renal function and thyroid status before and after treatment for hypothyroidism and hyperthyroidism, respectively. DESIGN AND PATIENTS: In 37 consecutive hypothyroid and 14 hyperthyroid patients renal function as measured by plasma creatinine and glomerular filtration rate (GFR) [based on the modification of diet in renal disease (MDRD) formula] was determined before treatment and after regaining euthyroidism. RESULTS: Renal function improved significantly during treatment of hypothyroidism and decreased during treatment of hyperthyroidism. There was a strong correlation between the change in thyroid status determined as the ratio log(10)(fT4 post-treatment/fT4 pretreatment) and the change in renal function as a result of therapy expressed as serum creatinine (r(2) = 0.81, P < 0.0001) and estimated GFR (0.69, P < 0.0001). CONCLUSION: The kidney is an important target of thyroid hormone action.


Subject(s)
Hyperthyroidism/complications , Hypothyroidism/complications , Kidney/physiopathology , Antithyroid Agents/therapeutic use , Creatinine/blood , Female , Glomerular Filtration Rate , Humans , Hyperthyroidism/drug therapy , Hyperthyroidism/physiopathology , Hypothyroidism/drug therapy , Hypothyroidism/physiopathology , Male , Middle Aged , Prospective Studies , Regression Analysis , Thyrotropin/blood , Thyroxine/blood , Thyroxine/therapeutic use
15.
Lancet ; 359(9318): 1643-7, 2002 May 11.
Article in English | MEDLINE | ID: mdl-12020524

ABSTRACT

BACKGROUND: Diagnostic strategies for pulmonary embolism are complex and consist of non-invasive diagnostic tests done to avoid conventional pulmonary angiography as much as possible. We aimed to assess the diagnostic accuracy of magnetic resonance angiography (MRA) for the diagnosis of pulmonary embolism, using conventional pulmonary angiography as a reference method. METHODS: In a prospective study, we enrolled 141 patients with suspected pulmonary embolism and an abnormal perfusion scan. Patients underwent MRA before conventional pulmonary angiography. Two reviewers, masked with respect to the results of conventional pulmonary angiography, assessed MRA images independently. Statistical analyses used chi(2) and 95% CI. FINDINGS: MRA was contraindicated in 13 patients (9%), and images were not interpretable in eight (6%). MRA was done in two patients in whom conventional pulmonary angiography was contraindicated. Thus, MRA and conventional pulmonary angiography results were available in 118 patients (84%). Prevalence of pulmonary embolism was 30%. Images were read independently in 115 patients, and agreement obtained in 105 (91%), kappa=0.75. MRA identified 27 of 35 patients with proven pulmonary embolism (sensitivity 77%, 95% CI 61-90). Sensitivity of MRA for isolated subsegmental, segmental, and central or lobar pulmonary embolism was 40%, 84%, and 100%, respectively (p<0.01 for isolated subsegmental vs segmental or larger pulmonary embolism). However, subgroups contained small numbers. MRA identified pulmonary embolism in two patients with normal angiogram (98%, 92-100). INTERPRETATION: MRA is sensitive and specific for segmental or larger pulmonary embolism. Results are similar to those obtained with helical computed tomography, but MRA has safer contrast agents and does not involve ionising radiation. MRA could become part of the diagnostic strategy for pulmonary embolism.


Subject(s)
Angiography/methods , Magnetic Resonance Angiography , Pulmonary Embolism/diagnosis , Adolescent , Adult , Aged , Aged, 80 and over , Chi-Square Distribution , Contrast Media , Female , Gadolinium , Humans , Imaging, Three-Dimensional , Male , Middle Aged , Prospective Studies , Pulmonary Artery/diagnostic imaging , Pulmonary Embolism/diagnostic imaging , Sensitivity and Specificity
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