Wiersinga, W.M.

Prevalence of autoimmune thyroid dysfunction in postpartum psychosis (Article)

2011-02-01T00:00:00Z

Abstract. BACKGROUND: Postpartum psychosis is a life-threatening psychiatric emergency, which often occurs without significant premorbid symptoms. Although many studies have postulated an involvement of the immune and endocrine systems in the onset of postpartum psychosis, the specific aetiological factors have remained unknown. AIMS: To examine the hypothesis that autoimmune thyroid dysfunction may be associated with the onset of postpartum psychosis. METHOD: Thirty-one consecutive primiparous women with no prior psychiatric history were referred to our in-patient unit for postpartum psychosis. The control group (n = 117) comprised primiparous women with consecutive deliveries at a community practice. Blood samples were obtained from all participants at 4 weeks and 9 months postpartum. Thyroperoxidase antibody levels were quantified as immunological measures of autoimmune thyroid disease (AITD). Thyroid-stimulating hormone and free thyroxine levels were measured to assess clinical thyroid dysfunction. RESULTS: At 4 weeks postpartum and prior to the initiation of mood stabiliser therapy, 19% of women with postpartum psychosis had AITD compared with only 5% in the control group. Women with both postpartum psychosis and AITD had a dramatically higher risk of progression to clinical thyroid dysfunction (67%) than control participants with AITD (20%). CONCLUSIONS: Women with postpartum psychosis are at higher risk not only of AITD but also of clinical thyroid failure. These data implicate thyroid function as an important clinical outcome in patients with postpartum psychosis. Further, AITD represents a potentially strong aetiological factor for the development of postpartum psychosis. Therefore, screening for thyroperoxidase antibodies is warranted in patients with postpartum psychosis.

Pilot study on the assessment of the setpoint of the hypothalamus- pituitary-thyroid axis in healthy volunteers (Article)

2010-02-01T00:00:00Z

Objective: To determine the log-linear relationship between TSH and free thyroxine in healthy subjects, and the variation in baseline TSH/free thyroxine (FT4) combination in each individual. Subjects and methods: Twenty-one healthy volunteers (nine males and 12 females; mean age 60 years, range 51-74) were randomized to receive at 2300 h with 2-week intervals a single dose of placebo, 125 μg T4and 250 mg T4(arm 1, n = 10), or placebo, 25 μg triiodothyronine (T3) and 50 μg T3(arm 2, n = 11). Blood samples were taken in the morning (0800-1100 h) before and following the administration of the drug for the assessment of TSH, FT4and T3. Results: Intra- and inter-individual variation and the individuality index of the four baseline serum samples were respectively 21.6%, 41.9% and 0.52 for TSH; 9.9%, 16.5% and 0.60 for FT4; and 9.3%, 16.0% and 0.58 for T3. Substantial differences existed in the location of individual working points within the reference range. T4administration increased FT4(but not T3) and decreased TSH, resulting in a log-linear relationship (log TSH = 1.50-0.059xFT4, P<0.05) for the whole group. T3administration increased T3and decreased TSH (but not FT4), resulting in a log-linear relationship (log TSH = 0.790-0.245xT3, P<0.001) for the whole group. Log-linear relationships were not always significant when assessed for each subject separately. Conclusion: Individuality indices of TSH, FT4and T3are all ≤0.6, thereby limiting the usefulness of the population-based reference values. Accurate assessment of individual setpoints of the HPT axis was not possible with the applied single doses of T4or T3, and will require either prolonged administration or higher single doses of thyroid hormone.

Thr92Ala polymorphism in the type 2 deiodinase is not associated with T4 dose in athyroid patients or patients with Hashimoto thyroiditis (Article)

2009-08-01T00:00:00Z

Objective The type 2 deiodinase (D2)-Thr92Ala polymorphism has been associated with decreased D2 activity in some in vitro experiments but not in others. So far no association between the D2-Thr92Ala polymorphism and serum thyroid hormone levels has been observed in humans, but in a recent study in athyroid patients, it was suggested that patients homozygous for the Ala92allele needed higher T4 doses to achieve TSH suppression. We studied the association between the D2-Thr92Ala polymorphism with thyroid hormone levels and T4 dosage, in patients treated for differentiated thyroid carcinoma (DTC) and in a group of patients treated for Hashimoto thyroiditis. Design Cross-sectional study. Patients We studied 154 patients with DTC treated with TSH suppressive thyroid hormone replacement therapy for longer than 3 years and 141 patients with Hashimoto thyroiditis treated for at least 6 months with T4. Measurements In all patients, serum levels of TSH, free T4, T3 and reverse T3 were measured and genotypes of the D2-Thr92Ala polymorphism were determined by Taqman assay. Univariate regression analysis was performed to determine the relation between T4 dosages and the D2-Thr92Ala polymorphism corrected for age, gender, BMI and serum TSH levels. Results Both in DTC patients and Hashimoto patients, no association was observed between serum thyroid hormone levels or T4 dosages in presence of the D2-Thr92Ala polymorphism. Categorization of DTC patients according to degree of TSH suppression did not change these results. Conclusion The D2-Thr92Ala polymorphism is not associated with thyroid hormone levels or T4 dose in patients treated for DTC or Hashimoto thyroiditis.

Polymorphisms in the brain-specific thyroid hormone transporter OATP1C1 are associated with fatigue and depression in hypothyroid patients (Article)

2008-11-01T00:00:00Z

Introduction: Some hypothyroid patients continue to have significant impairments in psychological well-being, despite adequate treatment with levothyroxine (LT4). T4 transport across the blood-brain barrier is one of the crucial processes for thyroid hormone action in the brain. OATP1C1, a thyroid hormone transporter expressed at the blood-brain barrier, is considered to play a key role in delivering serum T4 to the brain. Objective: To examine whether polymorphisms in OATP1C1 are determinants of well-being, neurocognitive functioning and preference for replacement therapy with a combination of LT4 and liothyronine (LT3). Design and participants: We studied 141 patients with primary autoimmune hypothyroidism, adequately treated with LT4 monotherapy and participating in a randomized clinical trial comparing LT4 therapy with LT4-LT3 combination therapy. Outcome measurements: Different questionnaires on well-being and neurocognitive tests were performed at baseline. Serum thyroid parameters, OATP1C1-intron3C > T, OATP1C1-Pro143Thr and OATP1C1-C3035T polymorphisms were determined. Results: Allele frequencies of the OATP1C1 polymorphisms in patients with primary hypothyroidism were similar to those of healthy controls. Both the OATP1C1-intron3C > T and the OATP1C1-C3035T polymorphism, but not the OATP1C1-Pro143Thr polymorphism, were associated with symptoms of fatigue and depression. OATP1C1 polymorphisms were not associated with measures of neurocognitive functioning or preference for combined LT4-LT3 therapy. Conclusions: OATP1C1 polymorphisms are associated with fatigue and depression, but do not explain differences in neurocognitive functioning or appreciation of LT4-LT3 combination therapy. Future studies are needed to confirm these findings.

Type 3 deiodinase is highly expressed in infiltrating neutrophilic granulocytes in response to acute bacterial infection (Article)

2008-10-01T00:00:00Z

Background: Macrophages and polymorphonuclear cells (PMNs) play an important role in the first line of defense against bacteria by infiltrating the infected organ in order to clear the harmful pathogen. Our earlier studies showed that granulocytes express type 3 deiodinase (D3) when activated during a turpentine-induced abscess. We hypothesized that D3 expression by granulocytes may also occur during bacterial infection. Methods: In order to test this hypothesis, we used the following experimental infection models: peritonitis induced by Escherichia coli and acute pneumonia induced by Streptococcus pneumoniae. Results: E. coli-induced peritonitis was characterized by infiltration in the liver by inflammatory cells with abundant immunocytochemical D3 expression while no staining was present in hepatocytes of infected or control mice. Acute pneumonia induced by S. pneumoniae resulted in inflamed lungs characterized by numerous infiltrating granulocytes expressing D3 while no D3 staining was present in lung sections without an infiltrate. Serum thyroid hormones were negatively correlated to bacterial outgrowth in both lung and spleen, and thus to the severity of illness. Conclusion: Infiltrating granulocytes during acute bacterial infection express D3. Our work supports the hypothesis that D3 plays an important role during chemical and bacterial inflammation. Whether the resulting decreased local bioavailability of thyroid hormones or rather the increased local availability of iodide is an important element of the innate immune response remains to be studied.

Thyroid hormone receptor isoforni expression in livers of critically ill patients (Article)

2007-02-01T00:00:00Z

Objective: The THRA gene encodes two isoforms of the thyroid hormone receptor (TR), TRα1 and TRα2. The ratio of these splice variants could have a marked influence on T3-regulated gene expression, especially during illness. Design: We studied the expression of the isoforms TRβ1, TRα1, and TRα2 and 5′-deiodinase in postmortem liver biopsies of 58 patients who were critically ill and died in the intensive care unit (ICU). All mRNA levels were determined using real-time PCR. Main outcome: All ratios of the biopsies were higher than those found in three normal liver biopsies due to an increased TRα1 level. The TRα1/TRα2 ratio increased with age and severity of illness following the equation: TRα1/TRα2 ratio = - 1.854 + (0.0323×age) + (0.0431×Therapeutic Intervention Scoring System score) indicating that 28% of the changed TRα1/TRα2 ratio can be predicted by these clinical variables. There was no effect of randomization to intensive insulin therapy or glucocorticoid or thyroid hormone treatment on the TRα1/TRα2 ratio or TRβ1. Furthermore, no relation was seen between the expression levels of the 5′-deiodinase mRNA and TR isoforms or the triiodothyronine (T3) levels. Conclusion: It appears that in critically ill patients the ratio of TRα1/TRα2 expression increases with age and severity of illness, possibly indicating a mechanism to enhance sensitivity to T3in the oldest and sickest patients.

The future endocrine patient. Reflections on the future of clinical endocrinology (Article)

2003-01-01T00:00:00Z

In recent years the future position of clinical endocrinology has been extensively discussed by Western European endocrine societies. Clinical endocrinology seems to suffer from being too intellectual, generating too little income, and lacking too few spectacular interventions. In this manuscript we describe 'the endocrine patient' of the past, the present, and the future. Complete therapeutic breakthroughs resulting in 'cure' are compared with 'halfway technologies' which help in creating the (life-long) chronic endocrine patient. The potential use of molecular diagnostics in optimalizing hormone replacement therapy is discussed. Clinical endocrinology is at risk of developing into a subspecialty where life-style drugs created for new diseases or conditions are offered, but also actively pursued by otherwise healthy individuals (e.g. in normal short stature, regulation of appetite, body composition, sexuality, reproduction and aging). The potential opportunities and risks for clinical endocrinology in creating 'the endocrine patient' of the future are discussed.