W M Wiersinga

University of Amsterdam, Amsterdam, North Holland, Netherlands

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Publications (313)1123.28 Total impact

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    A Boelen, M C Schiphorst, W M Wiersinga
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    ABSTRACT: In order to further delineate the role of cytokines in the pathogenesis of the low T3 syndrome, we studied the association between serum T3 and serum interferon gamma (IFN gamma), interleukin-8 (IL-8) and interleukin-10 (IL-10) in 99 consecutive patients hospitalised because of a wide variety of nonthyroidal diseases; none used drugs affecting thyroid hormone metabolism. Patients were divided in group A (normal serum T3 and T4), group B (subnormal serum T3 and normal T4) and group C (subnormal T3 and T4). Serum IFN gamma, IL-8 and IL-10 were not different between group A, B and C (with the exception of a small increase of IFN gamma in group B). Serum T3 was slightly related to serum IL-8 (r = 0.25, p < 0.05), but not to IFN gamma and IL-10. Stepwise multiple regression indicated that these serum cytokines were not independent determinants of the variability in serum T3. The results do not support any role of circulating IFN gamma, IL-8 or IL-10 in the pathogenesis of the low T3 syndrome during illness.
    Journal of endocrinological investigation 07/2014; 19(7):480-3. · 1.55 Impact Factor
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    ABSTRACT: Background:Optimal doses of iv glucocorticoids for Graves' orbitopathy (GO) are undefined.Methods:We carried out a multicenter, randomized, double-blind trial to determine efficacy and safety of three doses of iv methylprednisolone in 159 patients with moderate to severe and active GO. Patients were randomized to receive a cumulative dose of 2.25, 4.98, or 7.47 g in 12 weekly infusions. Efficacy was evaluated objectively at 12 wk by blinded ophthalmologists and subjectively by blinded patients (using a GO specific quality of life questionnaire). Adverse events were recorded at each visit.Results:Overall ophthalmic improvement was more common using 7.47 g (52%) than 4.98 g (35%; P = 0.03) or 2.25 g (28%; P = 0.01). Compared with lower doses, the high-dose regimen led to the most improvement in objective measurement of ocular motility and in the Clinical Activity Score. The Clinical Activity Score decreased in all groups and to the least extent with 2.25 g. Quality of life improved most in the 7.47-g group, although not reaching statistical significance. No significant differences occurred in exophthalmos, palpebral aperture, soft tissue changes, and subjective diplopia score. Dysthyroid optic neuropathy developed in several patients in all groups. Because of this, differences among the three groups were no longer apparent at the exploratory 24-wk visit. Major adverse events were slightly more frequent using the highest dose but occurred also using the lowest dose. Among patients whose GO improved at 12 wk, 33% in the 7.47-group, 21% in the 4.98-group, and 40% in the 2.25-group had relapsing orbitopathy after glucocorticoid withdrawal at the exploratory 24-wk visit.Conclusions:The 7.47-g dose provides short-term advantages over lower doses. However, this benefit is transient and associated with slightly greater toxicity. The use of a cumulative dose of 7.47 g of methylprednisolone provides short-term advantage over lower doses. This may suggest that an intermediate-dose regimen be used in most cases and the high-dose regimen be reserved to most severe cases of GO.
    The Journal of Clinical Endocrinology and Metabolism 10/2012; · 6.31 Impact Factor
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    ABSTRACT: The objective of this study was to evaluate prospectively the relationship between Yersinia enterocolitica (YE) infection and the development of overt autoimmune hypo- or hyperthyroidism (study A) and the de novo occurrence of thyroid antibodies (study B). This was a prospective cohort study of 790 euthyroid women who were first- or second-degree relatives of autoimmune thyroid disease (AITD) patients. Follow-up was 5 years, with annual assessments. Study A was a nested case-control study in which YE serological status was measured between cases {subjects who developed overt hypothyroidism [thyroid stimulating hormone (TSH) > 5·7 mU/l and free T4 (FT4) < 9·3 pmol/l] or overt hyperthyroidism (TSH < 0·4 mU/l and FT4 > 20·1 pmol/l)} and matched controls. For study B, 388 euthyroid women without thyroid antibodies at baseline were enrolled. The YE serological status was compared between subjects who developed thyroid peroxidase (TPO)-antibodies and/or thyroglobulin (Tg)-antibodies at 4-year follow-up and those who remained negative. For study A, the proportion of subjects positive for Yersinia enterocolitica outer membrane protein (YOP) immunoglobulin (Ig)G or YOP IgA did not differ between cases and controls at baseline. One year before the development of overt hypo- or hyperthyroidism, the proportion of subjects with YOP IgG was not different between cases and controls, but YOP IgA were less prevalent in cases. For study B, de novo occurrence of TPO (or TPO-antibodies and/or Tg-antibodies) did not differ between subjects in whom YOP IgG were positive or negative at baseline. Neither persistence nor emergence of YOP IgG at 4-year follow-up was associated with the occurrence of TPO-antibodies or Tg-antibodies. Similar results were observed with respect to YOP IgA. YE infection does not contribute to an increased risk of thyroid autoimmunity.
    Clinical & Experimental Immunology 07/2011; 165(1):38-43. · 3.28 Impact Factor
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    ABSTRACT: Oxygen free radicals and cytokines play a pathogenic role in Graves' orbitopathy. We carried out a randomized, double-blind, placebo-controlled trial to determine the effect of selenium (an antioxidant agent) or pentoxifylline (an antiinflammatory agent) in 159 patients with mild Graves' orbitopathy. The patients were given selenium (100 μg twice daily), pentoxifylline (600 mg twice daily), or placebo (twice daily) orally for 6 months and were then followed for 6 months after treatment was withdrawn. Primary outcomes at 6 months were evaluated by means of an overall ophthalmic assessment, conducted by an ophthalmologist who was unaware of the treatment assignments, and a Graves' orbitopathy-specific quality-of-life questionnaire, completed by the patient. Secondary outcomes were evaluated with the use of a Clinical Activity Score and a diplopia score. At the 6-month evaluation, treatment with selenium, but not with pentoxifylline, was associated with an improved quality of life (P<0.001) and less eye involvement (P=0.01) and slowed the progression of Graves' orbitopathy (P=0.01), as compared with placebo. The Clinical Activity Score decreased in all groups, but the change was significantly greater in the selenium-treated patients. Exploratory evaluations at 12 months confirmed the results seen at 6 months. Two patients assigned to placebo and one assigned to pentoxifylline required immunosuppressive therapy for deterioration in their condition. No adverse events were evident with selenium, whereas pentoxifylline was associated with frequent gastrointestinal problems. Selenium administration significantly improved quality of life, reduced ocular involvement, and slowed progression of the disease in patients with mild Graves' orbitopathy. (Funded by the University of Pisa and the Italian Ministry for Education, University and Research; EUGOGO Netherlands Trial Register number, NTR524.).
    New England Journal of Medicine 05/2011; 364(20):1920-31. · 54.42 Impact Factor
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    ABSTRACT: The biological function of thyrostimulin, consisting of the GPA2 and GPB5 subunit, is currently poorly understood. The recent observation that pro-inflammatory cytokines up-regulate the transcription of GPB5 in vitro suggested a role for thyrostimulin in the nonthyroidal illness syndrome, a state of altered thyroid hormone metabolism occurring during illness. In the present study, we used GPB5 knockout (GPB5(-/-) ) and wild-type (WT) mice to evaluate the role of GPB5 in the pituitary and hypothalamus during acute inflammation induced by lipopolysaccharide (LPS, bacterial endotoxin) administration. We evaluated serum thyroid hormones and mRNA expression of genes involved in thyroid hormone metabolism in the pituitary and in two hypothalamic regions; the periventricular region (PE) and the arcuate nucleus/median eminence region. As expected, LPS administration increased deiodinase type 2 mRNA in the PE, at the same time as decreasing pituitary thyrotrophin (TSH)β mRNA and serum thyroxine and triiodothyronine both in GPB5(-/-) and WT mice. GPB5 mRNA, but not GPA2 mRNA, markedly increased after LPS in the pituitary (200-fold) and hypothalamus of WT mice. In addition, we found large (>50%) suppression of TSH receptor (TSHR) mRNA in the pituitary and hypothalamus of WT mice but not in GPB5(-/-) mice. In conclusion, our results demonstrate in vivo regulation of central GPB5 transcription during acute illness. The observed differences between GPB5(-/-) and WT mice point to a distinct role for GPB5 in pituitary and hypothalamic TSHR suppression during acute illness.
    Journal of Neuroendocrinology 02/2011; 23(4):310-9. · 3.51 Impact Factor
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    N Engl J Med. 01/2011; 364.
  • Laura Elbers, Maarten Mourits, Wilmar Wiersinga
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    ABSTRACT: It is still debated which treatment modality for Graves' hyperthyroidism (GH) is most appropriate when Graves' orbitopathy (GO) is present. The preference in our center has been always to continue antithyroid drugs for GH (as the block-and-replace [B-R] regimen) until all medical and/or surgical treatments for GO are concluded and the eye disease does not require any further therapy (except prescription of lubricants). This usually takes more than 2 years. The aim of this study was to evaluate the outcome of long-term B-R regimen for GH in GO patients by assessment (after discontinuation of B-R) of (a) the recurrence rate of GH and (b) the relapse rate of GO and its association with recurrent GH and/or (131)I therapy. A retrospective follow-up study was done among all patients referred to the Academic Medical Center in Amsterdam between 1995 and 2005 for GO. The inclusion criteria for the study were a history of GH and GO and a history of treatment for GH with a B-R regimen for more than 2 years. The exclusion criteria were a history of (131)I therapy or thyroidectomy before the end of GO treatment. A questionnaire was sent to 255 patients and returned by 114. Of these patients, 73 qualified for the study. Recurrences of GH and/or GO as indicated by returned questionnaires were checked with treating physicians. Patients were treated with B-R for a median of 41 months (range: 24-132). The median follow-up after discontinuation of the B-R regimen was 57 months (range: 12-170). Recurrent GH occurred in 27 of the 73 study patients (37%) at a median of 3 months (range: 1-65) after withdrawal of antithyroid drug therapy. Nineteen of the 27 patients with recurrent hyperthyroidism were treated with (131)I therapy. A relapse of GO was not encountered in any of the 73 patients. The study suggests that long-term B-R treatment of GH in GO patients is associated with a recurrence rate of hyperthyroidism of about 37%. With the regimen employed, recurrence of hyperthyroidism and recurrence of hyperthyroidism followed by treatment with (131)I appears not to be a likely cause of relapse of GO. The data suggest that B-R treatment of GH until GO has become inactive and does not require any further treatment is a feasible option and does not jeopardize the improvement that occurred in GO.
    Thyroid: official journal of the American Thyroid Association 12/2010; 21(3):279-83. · 2.60 Impact Factor
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    ABSTRACT: Glucocorticoid prophylaxis is required in some instances after radioiodine (RAI) treatment for Graves' hyperthyroidism to prevent progression of Graves' orbitopathy (GO). However, no randomized clinical trial has been performed to ascertain the optimum glucocorticoid therapy. Aim of this study was to perform a questionnaire-based survey of glucocorticoid prophylaxis among European thyroidologist members of the European Thyroid Association. Eighty-two responses from 25 European Countries were received. Two respondents did not prescribe steroids in any clinical scenario, while 8 gave the drug to all patients receiving RAI therapy. The majority of respondents only gave glucocorticoids to patients showing some degree of ocular involvement or if risk factors for the progression of GO after RAI were present (e.g., cigarette smoking); 24% of responses indicated that clinicians would not give glucocorticoids if patients were thought to have no GO or inactive GO. Ninety-one percent of clinicians used prednisone (53%) or prednisolone (38%). The mean starting dose [given for 16 days (range 2-60 days)] was 37.6 mg prednisone or prednisone-equivalent (range 15-80 mg). Overall, the results of this survey showed a wide diversity in the regimens used, in terms of timing of initiation of treatment, duration of treatment, cumulative doses of administered glucocorticoids and monitoring of side-effects of glucocorticoid treatment. The results of this study underscore the need for randomized clinical trials to ascertain the optimum regimen of prophylactic glucocorticoid therapy.
    Journal of endocrinological investigation 06/2010; 33(6):409-13. · 1.65 Impact Factor
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    ABSTRACT: To determine the log-linear relationship between TSH and free thyroxine in healthy subjects, and the variation in baseline TSH/free thyroxine (FT(4)) combination in each individual. 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 microg T(4) and 250 microg T(4) (arm 1, n=10), or placebo, 25 microg triiodothyronine (T(3)) and 50 microg T(3) (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, FT(4) and T(3). 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 FT(4); and 9.3%, 16.0% and 0.58 for T(3). Substantial differences existed in the location of individual working points within the reference range. T(4) administration increased FT(4) (but not T(3)) and decreased TSH, resulting in a log-linear relationship (log TSH=1.50-0.059xFT(4), P<0.05) for the whole group. T(3) administration increased T(3) and decreased TSH (but not FT(4)), resulting in a log-linear relationship (log TSH=0.790-0.245xT(3), P<0.001) for the whole group. Log-linear relationships were not always significant when assessed for each subject separately. Individuality indices of TSH, FT(4) and T(3) are all <or=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 T(4) or T(3), and will require either prolonged administration or higher single doses of thyroid hormone.
    European Journal of Endocrinology 11/2009; 162(2):323-9. · 3.69 Impact Factor
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    ABSTRACT: We have previously shown that skeletal muscle deiodinase type 2 (D2) mRNA (listed as Dio2 in MGI Database) is upregulated in an animal model of acute illness. However, human studies on the expression of muscle D2 during illness report conflicting data. Therefore, we evaluated the expression of skeletal muscle D2 and D2-regulating factors in two mouse models of illness that differ in timing and severity of illness: 1) turpentine-induced inflammation, and 2) Streptococcus pneumoniae infection. During turpentine-induced inflammation, D2 mRNA and activity increased compared to pair-fed controls, most prominently at day 1 and 2, whereas after S. pneumoniae infection D2 mRNA decreased. We evaluated the association of D2 expression with serum thyroid hormones, (de-)ubiquitinating enzymes ubiquitin-specific peptidase 33 and WD repeat and SOCS box-containing 1 (Wsb1), cytokine expression and activation of inflammatory pathways and cAMP pathway. During chronic inflammation the increased muscle D2 expression is associated with the activation of the cAMP pathway. The normalization of D2 5 days after turpentine injection coincides with increased Wsb1 and tumor necrosis factor alpha expression. Muscle interleukin-1beta (Il1b) expression correlated with decreased D2 mRNA expression after S. pneumoniae infection. In conclusion, muscle D2 expression is differentially regulated during illness, probably related to differences in the inflammatory response and type of pathology. D2 mRNA and activity increases in skeletal muscle during the acute phase of chronic inflammation compared to pair-fed controls probably due to activation of the cAMP pathway. In contrast, muscle D2 mRNA decreases 48 h after a severe bacterial infection, which is associated with local Il1b mRNA expression and might also be due to diminished food-intake.
    Journal of Endocrinology 09/2009; 203(2):263-70. · 3.59 Impact Factor
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    ABSTRACT: Lymphocyte membrane markers were studied in 54 Graves' ophthalmopathy patients (22 hyperthyroid, 22 euthyroid, 10 hypothyroid) and 13 healthy controls. The results show that in these patients there is a significant increase in B cells but no overall abnormalities in the levels of peripheral T cells, helper T cells or suppressor T cells. When the patients are subdivided according to ocular symptoms or thyroid function, some subgroups do, however, show abnormal T cell distribution. Patients with subclinical hyperthyroidism have fewer peripheral T cells and helper T cells than normal controls, but normal levels of B cells. Patients with chemosis only have significantly more suppressor cells and slightly less helper cells and therefore an abnormal helper to suppressor cell ratio when compared to healthy controls. Patients presenting with chemosis, proptosis and extra-ocular muscle involvement have significantly fewer peripheral T cells than healthy controls. Normal levels of B cells are found in patients with symptoms in four or more of the NOSPECS classes 2 to 6.
    Orbit 07/2009; 3(4):229-235.
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    ABSTRACT: The B-lymphocyte subset distribution was studied in 52 Graves' ophthalmopathy patients and 13 healthy controls. In a previous study an increase in total peripheral blood B cells was found in these patients when compared to controls (p < 0.001). In the present study the patients were classified according to their ocular symptoms, using the NOSPECS classification (five groups) or according to their thyroidal disease state (seven groups). The B cell subset distribution was studied for each of the subgroups. The B cell increase is polyclonal; both kappa and lambda bearing B cell numbers are increased. A significant increase of IgG-bearing B-cells is seen in seven out of ten patient subgroups. lncreased levels of IgM- and/ or IgD-bearing cells are found only in three out of ten patient subgroups and increased levels of IgA-bearing cells are found in two out of ten patient subgroups. In 42 of the 52 Graves' ophthalmopathy patients the serum immunoglobulin levels were studied and correlated with the B-cell abnormalities. Serum IgG levels were normal in all the patients. Increased levels of serum IgM were found in five subgroups and increased serum IgA levels in one subgroup. In conclusion, in Graves' ophthalmopathy patients mainly IgG kappa and IgG lambda bearing B-cells seem to proliferate in response to an as yet unknown signal. This B-cell proliferation occurs independently of the thyroidal or ocular symptoms. This polyclonal activation does not, however, appear to result in active secretion of immunoglobulins by the majority of the B-cells.
    Orbit 07/2009; 5(1):7-14.
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    ABSTRACT: For many years, the treatment of X-linked childhood cerebral adrenoleukodystrophy (XALD) consisted of hydrocortisone replacement and a mixture of short chain-fatty acids, known as 'Lorenzo's oil'. Recently, bone marrow transplantation (BMT) has also been used. We report the case of a patient affected by XALD who developed Graves' hyperthyroidism (GH) and Graves' orbitopathy (GO) after BMT and who we could follow-up for 6.5 years afterwards. A boy affected by XALD was treated at the age of 6 years, with a whole BMT from his sister. One year after BMT, the transplanted patient presented TSH at the lower normal value and 3 years later he developed thyrotoxicosis. After a further 2 years, the patient developed GO, which showed clinical evidence of reactivation 5 years after its onset as a consequence of an attempt to treat thyrotoxicosis by means of I(131) (300 MBq). Seven years after BMT, the donor showed alterations of thyroid autoimmunity and 1 year thereafter she developed GH. She never presented GO during a subsequent 5 year follow-up. This case illustrates that autoimmunity originating from a pre-symptomatic donor can be transferred into the host during allogeneic stem cell transplantation. In cases where autoimmune phenomena are recognized in the donor prior to donation, alternative donors or T-cell manipulation of the graft might be considered.
    European Journal of Endocrinology 06/2009; 161(2):369-73. · 3.69 Impact Factor
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    ABSTRACT: Plasma insulin-like growth factor (IGF-I) concentration can be used as a rough indicator of the growth-hormone status. However, for the diagnosis of growth hormone deficiency, dynamic tests are required. The growth hormone (GH) response in the insulin tolerance test (ITT) is considered to be the gold standard in this respect. An alternative for the ITT is the GHRH/ GHRP-6 test, which has fewer side effects. In this study we established reference values for IGF-I levels and for the GH response in both dynamic tests. We studied 296 subjects recruited from the general population, equally distributed according to sex and aged between 20 and 70 years. Serum IGF-I level was measured in all subjects and an insulin tolerance test (0.15 U/kg Actrapid iv) and GHRH/GHRP-6 test (1 microg GHRH/kg and 1 microg GHRP-6/kg) were performed in 49 subjects. In multivariate analyses both IGF-I and the GH response in the ITT were significantly influenced by age, whereas the GH response in the GHRH/GHRP-6 test was significantly affected by BMI. There was no sex difference in IGF-I and in the GHRH/GHRP-6 test, but in the ITT males had a higher GH peak. There was a significant correlation between the GH responses in both tests, and the GH response was significantly higher in the GHRH/GHRP-6 test than in the ITT. Age-adjusted reference values were established for each test. We have established age-adjusted reference values for serum IGF-I and for the GH response in the ITT and GHRH/GHRP-6 test.
    The Netherlands Journal of Medicine 05/2009; 67(4):127-33. · 2.21 Impact Factor
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    ABSTRACT: To examine the relationship between maternal TSH and free thyroxine (FT(4)) concentrations in early pregnancy and the risk of miscarriage, fetal or neonatal death. Cohort study of 2497 Dutch women. TSH, FT(4), and thyroid peroxidase antibodies concentrations were determined at first booking. Child loss was operationalized as miscarriage, fetal or neonatal death. Women with overt thyroid dysfunction were excluded. Twenty-seven cases of child loss were observed. The mean TSH and FT(4) level in the women with child loss was 1.48 mU/l and 9.82 pmol/l compared with 1.11 mU/l and 9.58 pmol/l in women without child loss. The incidence of child loss increased by 60% (OR=1.60 (95% confidence interval (CI): 1.04-2.47)) for every doubling in TSH concentration. This association remained after adjustment for smoking, age, parity, diabetes mellitus, hypertension, previous preterm deliveries, and previous preterm stillbirth/miscarriage (adjusted odds ratio=1.80 (95% CI: 1.07-3.03)). This was not true for FT(4) concentrations (OR=1.41 (95% CI: 0.21-9.40); P=0.724). In a cohort of pregnant women without overt thyroid dysfunction, the risk of child loss increased with higher levels of maternal TSH. Maternal FT(4) concentrations and child loss were not associated.
    European Journal of Endocrinology 04/2009; 160(6):985-91. · 3.69 Impact Factor
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    ABSTRACT: The diagnosis of phaeochromocytoma is based on the demonstration of catecholamine excess. Urine and plasma metanephrine measurements are highly sensitive tests for the diagnosis of phaeochromocytoma, but moderate elevations in metanephrines lack optimal specificity. In this study we aimed to evaluate the diagnostic value of additional tests, i.e. glucagon stimulation and clonidine suppression test, in patients with moderately elevated catecholamines and/or metanephrines. Patients with suspected phaeochromocytoma with moderately elevated catecholamines and/or metanephrines in plasma or urine were subjected to the glucagon stimulation and clonidine suppression test. The presence of phaeochromocytoma was confirmed by histology and the absence by a disease-free extended follow-up. Fifty-five patients were included. Phaeochromocytoma was diagnosed in 11 patients. The follow-up period in patients without phaeochromocytoma was 56 (19 to 154) months. The sensitivity of the glucagon test was 30% and the specificity 100%. The clonidine test had no discriminative power, because the area under the ROC curve was not significantly different from 0.5. The clonidine suppression test without normetanephrine measurements and the glucagon stimulation test are not sensitive enough to safely exclude phaeochromocytoma in patients with mildly elevated plasma or urine catecholamines.
    The Netherlands Journal of Medicine 04/2009; 67(3):91-5. · 2.21 Impact Factor
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    ABSTRACT: To establish the diagnostic performance of the prolonged fasting test in patients suspected of insulinoma. We included all patients who were referred to our department between August 1995 and August 2006 with a clinical suspicion of insulinoma. Insulinoma was diagnosed by a positive Whipple's triad during the prolonged fast in combination with an insulin/C-peptide ratio below 1. The presence of insulinoma was confirmed by histopathological data, which was considered the golden standard. If the prolonged fast was negative, long-term follow-up was obtained. Ten patients had a positive Whipple's triad during the prolonged fast: eight had a histologically proven insulinoma, and two had factitious hypoglycaemia (insulin/C-peptide ratio >1.0) One additional patient likely had an insulinoma, but the Whipple's triad remained absent at up to 56 hours of fasting. Follow-up (median 53 months (3 to 142) in 76% of patients with a negative fasting test revealed no missed cases of insulinoma. During the prolonged fast the glucose, insulin and C-peptide concentrations overlapped in patients with and without insulinoma. In our centre, the prolonged fasting test defined as a positive Whipple's triad in combination with an insulin/C-peptide ratio <1 had a sensitivity of 88.9% and a specificity of 100% for the diagnosis of insulinoma.
    The Netherlands Journal of Medicine 01/2009; 67(7):274-8. · 2.21 Impact Factor
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    ABSTRACT: 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 Ala(92) allele 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. Cross-sectional study. 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. 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. 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. The D2-Thr92Ala polymorphism is not associated with thyroid hormone levels or T4 dose in patients treated for DTC or Hashimoto thyroiditis.
    Clinical Endocrinology 12/2008; 71(2):279-83. · 3.35 Impact Factor
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    ABSTRACT: To compare the outcome of various surgical approaches of orbital decompression in patients with Graves' orbitopathy (GO) receiving surgery for disfiguring proptosis. Data forms and questionnaires from consecutive, euthyroid patients with inactive GO who had undergone orbital decompression for disfiguring proptosis in 11 European centres were analysed. Eighteen different (combinations of) approaches were used, the swinging eyelid approach being the most popular followed by the coronal and transconjunctival approaches. The average proptosis reduction for all decompressions was 5.0 (SD 2.1) mm. After three-wall decompression the proptosis reduction was significantly greater than after two-wall decompression. Additional fat removal resulted in greater proptosis reduction. Complications were rare, the most frequent being worsening of motility, occurring more frequently after coronal decompression. The average change in quality of life (QOL) in the appearance arm of the GO-QOL questionnaire was 20.5 (SD 24.8) points. In Europe, a wide range of surgical approaches is used to reduce disfiguring proptosis in patients with GO. The extent of proptosis reduction depends on the number of walls removed and whether or not fat is removed. Serious complications are infrequent. Worsening of ocular motility is still a major complication, but was rare in this series after the swinging eyelid approach.
    The British journal of ophthalmology 12/2008; 93(11):1518-23. · 2.92 Impact Factor
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    ABSTRACT: A 53-year-old woman presented with fever accompanied by chills and an extremely painful swelling of her right thyroid lobe. She was initially diagnosed as having subacute thyroiditis, but after 14 days her disease appeared to be caused by a destructive suppurative thyroiditis due to Salmonella group C. A pre-existing hyperplastic nodule in the right thyroid lobe was the predisposing factor. Antibiotics were given for several weeks and surgical drainage was performed. Finally a hemithyroidectomy was done to eliminate the predisposing factor.
    Nederlands tijdschrift voor geneeskunde 10/2008; 152(38):2084-7.

Publication Stats

8k Citations
1,123.28 Total Impact Points


  • 1984–2014
    • University of Amsterdam
      • • Faculty of Medicine AMC
      • • Department of Clinical Epidemiology and Biostatistics
      • • Department of Endocrinology
      • • Department of Medicine
      Amsterdam, North Holland, Netherlands
  • 2011
    • AHEPA University Hospital
      Saloníki, Central Macedonia, Greece
    • Università di Pisa
      Pisa, Tuscany, Italy
    • Johannes Gutenberg-Universität Mainz
      • I. Department of Medicine
      Mayence, Rheinland-Pfalz, Germany
  • 2010
    • Cardiff University
      • Centre for Endocrine and Diabetes Sciences
      Cardiff, WLS, United Kingdom
  • 1986–2009
    • Academisch Medisch Centrum Universiteit van Amsterdam
      • Department of Endocrinology and Metabolism
      Amsterdamo, North Holland, Netherlands
  • 2006
    • Hannover Medical School
      • Department of Gastroenterology, Hepatology and Endocrinology
      Hannover, Lower Saxony, Germany
  • 2005–2006
    • General Hospital Thessaloniki
      Saloníki, Central Macedonia, Greece
    • Università degli Studi di Siena
      Siena, Tuscany, Italy
    • Koninklijke Nederlandse Akademie van Wetenschappen
      Amsterdamo, North Holland, Netherlands
  • 1993–2006
    • Academic Medical Center (AMC)
      Amsterdamo, North Holland, Netherlands
  • 2003–2004
    • Università degli Studi dell'Insubria
      Varese, Lombardy, Italy
    • Erasmus MC
      • Department of Endocrinology
      Rotterdam, South Holland, Netherlands
  • 2001
    • Ziekenhuis Tjongerschans
      Heerenveen, Friesland, Netherlands
  • 1994–1999
    • Erasmus Universiteit Rotterdam
      • Department of Pediatric Surgery
      Rotterdam, South Holland, Netherlands
  • 1998
    • GGD Brabant Zuidoost
      Helmond, North Brabant, Netherlands
  • 1997
    • University Medical Center Utrecht
      • Department of Ophthalmology
      Utrecht, Provincie Utrecht, Netherlands
  • 1988
    • VU University Amsterdam
      • Department of Pathology
      Amsterdam, North Holland, Netherlands