Evaluation of cardiac ischaemia in cardiac asymptomatic newly diagnosed untreated patients with primary hypothyroidism

BACKGROUND: Hypothyroidism is regarded as a risk factor for coronary artery disease. Possible factors involved in this association are hyperlipidaemia and hypertension, both occurring with increased frequency in hypothyroid patients. The aim of our study was to evaluate signs/symptoms of cardiac ischaemia in untreated hypothyroid patients without angina pectoris, since this has never been performed before. METHODS: 51 consecutive cardiac asymptomatic patients (mean age 47, range 22 to 86 years) were studied by dobutamine stress echocardiography and bicycle ergometry. RESULTS: Mean values of body mass index, resting heart rate and blood pressure were 28.5 kg/m2, 68 beats/min and 129/81 mmHg, respectively. Median TSH was 51.9 mU/l, mean FT4 7.3 +/- 2.9 pmol/l (mean +/- SD), TT3 1.6 +/- 0.6 nmol/l and total cholesterol was 5.8 +/- 1.6 mmol/l. None of the patients had symptoms of angina pectoris during dobutamine stress echocardiography or bicycle ergometry and no evidence of myocardial ischaemia was demonstrated. Exercise tolerance, assessed by dividing the maximum achieved workload by the target performance (depending on body height, sex and age), was diminished in 38% of patients, and significantly related to the degree of hypothyroidism. CONCLUSION: No angina pectoris or cardiac ischaemia at exercise or stress was found in cardiac asymptomatic hypothyroid patients. The precise role of hypothyroidism as a risk factor for coronary artery disease should be further elucidated

Postpartum thyroiditis and autoimmune thyroiditis in women of childbearing age: recent insights and consequences for antenatal and postnatal care

Postpartum thyroiditis is a syndrome of transient or permanent thyroid dysfunction occurring in the first year after delivery and based on an autoimmune inflammation of the thyroid. The prevalence ranges from 5-7%. We discuss the role of antibodies (especially thyroid peroxidase antibodies), complement, activated T cells, and apoptosis in the outbreak of postpartum thyroiditis. Postpartum thyroiditis is conceptualized as an acute phase of autoimmune thyroid destruction in the context of an existing and ongoing process of thyroid autosensitization. From pregnancy an enhanced state of immune tolerance ensues. A rebound reaction to this pregnancy-associated immune suppression after delivery explains the aggravation of autoimmune syndromes in the puerperal period, e.g., the occurrence of clinically overt postpartum thyroiditis. Low thyroid reserve due to autoimmune thyroiditis is increasingly recognized as a serious health problem. 1) Thyroid autoimmunity increases the probability of spontaneous fetal loss. 2) Thyroid failure due to autoimmune thyroiditis-often mild and subclinical-can lead to permanent and significant impairment in neuropsychological performance of the offspring. 3) Evidence is emerging that as women age subclinical hypothyroidism-as a sequel of postpartum thyroiditis-predisposes them to cardiovascular disease. Hence, postpartum thyroiditis is no longer considered a mild and transient disorder. Screening is considered

Cardiac and metabolic effects in patients who present with a multinodular goitre

Twenty-six consecutive patients who presented with clinically euthyroid multinodular goitre were studied for an overnight fasting serum lipid profile and 24 h Holter monitoring. Mean serum TSH was 0.6 +/- 0.4 vs 2.4 +/- 1.3 mU/l (p < 0.0001) and mean TT3 2.4 +/- 0.4 vs 2.0 +/- 0.5 nmol/l (p = 0.009) in patients vs controls (n = 15) while mean FT4 was not different from controls. Total serum HDL, LDL cholesterol and triglycerides were lower in patients but creatinine, ferritin and SHBG levels did not differ between patients and controls. The 24-hour ambulatory continuous ECG recordings did not demonstrate significant differences in mean, minimal and maximal heart rate between the study and the control group. Nocturnal heart rate, measured between 23.00 and 06.00 hours, also showed no differences between the two groups. Atrial fibrillation was absent in both the study and the control group. Premature atrial and ventricular complexes occurred equally frequently in both groups. Comparison of patients with a serum TSH below 0.4 mU/l (n = 11) and patients with a TSH above 0.4 mU/l revealed no differences. In conclusion, in consecutive patients who present with multinodular goitre, effects were found on the lipid profile, but not on the heart. It is argued that in this type of patients, cardiac effects depend on the degree of subclinical hyperthyroidism

Ischaemic heart disease in Turkish migrants with type 2 diabetes mellitus in The Netherlands: wait for the next generation?

OBJECTIVE: To study the prevalence of ischaemic heart disease in Turkish and Surinam-Asian migrants with type 2 diabetes mellitus in the Netherlands as compared with Europeans. METHODS: In a consecutive case-control study, 59 Turkish and 62 Surinam-Asian patients were compared with 185 Europeans referred to a diabetes clinic for treatment of type 2 diabetes in the period 1992 to 1998. Main outcome measures were ischaemic heart disease and its associated risk factors. RESULTS: The prevalence of ischaemic heart disease was lower (9%) in the Turks (p < 0.02), but higher (29%) in the Surinam-Asians compared with the Europeans (23%). The Turks (52 +/- 10 years) and Surinam-Asians (46 +/- 12 years) were younger than the Europeans (64 +/- 11 years, p < 0.001). Body mass index was 32 +/- 5 (p < 0.001) in the Turks, 27 +/- 5 in the Surinam-Asians (p < 0.05) and 29 +/- 5 in the Europeans. Turkish patients smoked less (23%, p < 0.05) and used less alcohol (4%, p < 0.05) than the Europeans. Proteinuria was found in 24% of the Turks (p < 0.05), 37% of the Surinam-Asians (NS) and 46% of the Europeans. In univariate analysis ischaemic heart disease was related to Turkish origin, OR 0.34 (0.14-0.83) p < 0.02, to Surinam-Asian origin, OR 1.84 (1.00-3.38) p = 0.05, and smoking, OR 1.78 (1.18-2.68) p < 0.01. Other variables were not related to ischaemic heart disease. Multivariate analysis in a model with ethnicity and smoking showed significant relations between ischaemic heart disease and Turkish ethnicity, OR 0.19 (0.06-0.65) p = 0.007, Surinam-Asian origin, OR 2.77 (1.45-5.28) p = 0.002, and smoking, OR 1.79 (1.20-2.66) p = 0.004. CONCLUSION: Type 2 diabetes mellitus in different ethnic groups results in a significant difference in incidence of ischaemic heart disease. The most remarkable finding is a low incidence of ischaemic heart disease in the Turkish patients with type 2 diabetes, independent of smoking. The high prevalence of ischaemic heart disease in young migrant Asians with diabetes is confirmed

Decrease of free thyroxine levels after controlled ovarian hyperstimulation

Controlled ovarian hyperstimulation could lead to opposing effects on thyroid function. Therefore, in a prospective study of 65 women undergoing controlled ovarian hyperstimulation, thyroid hormones, T4-binding globulin, TPO antibodies, gonadotropins, estradiol, and PRL were measured before and after controlled ovarian hyperstimulation. After ovarian stimulation (mean +/- SE of mean): free T4 decreased, 14.4 +/- 0.2 vs. 12.9 +/- 0.2 pmol/L (P < 0.0001); thyroid-stimulating hormone increased, 2.3 +/- 0.3 vs. 3.0 +/- 0.4 mU/L (P < 0.0001); T4-binding globulin increased, 25.2 +/- 0.7 vs. 33.9 +/- 0.9 mg/L (P < 0.0001); total T4 increased, 98.1 +/- 2.3 vs. 114.6 +/- 2.5 nmol/L (P < 0.0001); total T3 increased, 2.0 +/- 0.04 vs. 2.3 +/- 0.07 nmol/L (P < 0.0001); TPO antibodies decreased, 370 +/- 233 U/mL vs. 355 +/- 224 U/mL (P < 0.0001); LH decreased, 8.1 +/- 1.1 vs. 0.4 +/-0.1 U/L (P < 0.0001); FSH did not change, 6.5 +/- 0.6 vs. 7.9 +/- 0.9 U/L (P = 0.08); human CG increased, <2 +/- 0.0 vs. 195 +/- 16 U/L (P < 0.0001); estradiol increased, 359.3 +/- 25.9 pmol/L vs. 3491.8 +/-298.3 pmol/L (P < 0.0001); and PRL increased, 0.23 +/- 0.02 vs. 0.95 +/- 0.06 U/L (P < 0.0001). Because low maternal free T4 and elevated maternal thyroid-stimulating hormone levels during early gestation have been reported to be associated with impaired psychomotor development in the offspring, our findings indicate the need for additional studies in the children of women who where exposed to high levels of estrogens around the time of conception

An Inflammatory Gene-Expression Fingerprint in Monocytes of Autoimmune Thyroid Disease Patients

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 Fc alpha 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. (J Clin Endocrinol Metab 95: 1962-1971, 2010

Effects of Evening vs Morning Levothyroxine Intake A Randomized Double-blind Crossover Trial

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