Thyroid Diseases: Wiersinga WM

Muller AF, Berghout A, Wiersinga WM, Kooy A, Smits JW, Hermus AR, Anonymous00181. · Diakonessenhuis Utrecht, Utrecht, the Netherlands. · Neth J Med. · Pubmed #18349473 links to  free full text

Abstract: Thyroid function disorders are common with a female to male ratio of 4 to 1. In adult women primary hypothyroidism and thyrotoxicosis have a prevalence of 3.5/1000 and 0.8/1000, respectively. This guideline is aimed at secondary care providers especially internists, but also contains relevant information for interested general practitioners and gynaecologists. A multidisciplinary working group, containing delegates of professional and patient organisations, prepared the guideline. According to principles of 'evidence-based medicine' available literature was studied and discussed. Considering the availability and quality of published studies a practical advice was formulated. For a full overview of the literature and considerations the reader is referred to the original version of the guideline (accessible through NIV-net). In this manuscript we have aimed to provide the practicing internist with practical and 'as evidence-based as possible' treatment guidelines with respect to thyroid function disorders.

Bartalena L, Baldeschi L, Dickinson AJ, Eckstein A, Kendall-Taylor P, Marcocci C, Mourits MP, Perros P, Boboridis K, Boschi A, Currò N, Daumerie C, Kahaly GJ, Krassas G, Lane CM, Lazarus JH, Marinò M, Nardi M, Neoh C, Orgiazzi J, Pearce S, Pinchera A, Pitz S, Salvi M, Sivelli P, Stahl M, von Arx G, Wiersinga WM. · Department of Clinical Medicine, University of Insubria, Varese, Italy. · Thyroid. · Pubmed #18341379 No free full text.

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Wiersinga WM, Prummel MF. · No affiliation provided · J Clin Endocrinol Metab. · Pubmed #11157999 links to  free full text

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Wiersinga WM. · Department of Endocrinology & Metabolism, Academic Medical Center, University of Amsterdam, the Netherlands. · Hormones (Athens). · Pubmed #17724003 links to  free full text

Abstract: Thyroid nodules in childhood and adolescence are less prevalent but more often malignant than in adulthood. Malignant nodules are predominantly papillary cancers; benign nodules are mostly solid colloid nodules/adenomas, but can be cystic or due lymphocytic thyroiditis. Previous neck irradiation (nowadays mostly encountered in childhood cancer survivors) is a clear risk factor for developing nodules. Neck irradiation for childhood Hodgkin's disease has a relative risk of 27 for the development of thyroid nodules. Female sex, a thyroid radiation dose>or=2500 cGy, and time since irradiation of >or=10 yr are independent risk factors. This subset of patients deserves long-term follow-up. The diagnostic steps for thyroid nodules in children and adolescents are not different from those in adults. First, history and physical examination should identify risk factors for malignancy of the nodule. Second, thyroid function should be assessed by serum TSH, followed by a thyroid scan in the case of a suppressed TSH. Serum calcitonin might be measured if there is suspicion of medullary thyroid carcinoma (e.g. a family history of MEN). Thyroid ultrasound is useful, especially in guidance of FNAC for optimal results, but presently should not be used for final decisions on the benign or malignant nature of the nodule. FNAC has the highest diagnostic accuracy in recognizing malignant nodules and should be applied in all nodules>or=1 cm and in nodules<1 cm only if there is suspicion for cancer (e.g. by ultrasound characteristics). Surgery is the most cost-effective treatment option for thyroid nodules, solving the problem fast. Levothyroxine treatment has a low efficacy. Experience with other treatment options like ethanol injection or laser therapy is still limited.

Wiersinga WM. · Department of Endocrinology and Metabolism, Academic Medical Center, University of Amsterdam, The Netherlands. · Ann Endocrinol (Paris). · Pubmed #17689474 No free full text.

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Wiersinga WM. · Department of Endocrinology and Metabolism, Academic Medical Center, University of Amsterdam, The Netherlands. · Nat Clin Pract Endocrinol Metab. · Pubmed #17452966 No free full text.

Abstract: Management of Graves' ophthalmopathy is preferably done in a multidisciplinary setting. Smoking is associated with worse disease outcome. (131)I therapy for hyperthyroidism can also worsen ophthalmopathy, especially if administered during active disease or to patients who smoke or have severe hyperthyroidism, or those with high levels of TSH-receptor-binding inhibitory immunoglobulins. Coadministration of steroids and (131)I therapy is recommended for such high-risk patients. (131)I therapy is safe for patients with inactive Graves' ophthalmopathy. Subtotal thyroidectomy and antithyroid drugs show no benefit or harm to eye changes. There is no good evidence that total thyroid ablation has additional benefit. Artificial teardrops, dark glasses and prisms are very helpful. Dysthyroid optic neuropathy is best treated with intravenous pulsed methylprednisolone; if visual functions do not recover, urgent surgical decompression is indicated. A wait-and-see policy is recommended in mild Graves' ophthalmopathy because the natural history of this condition reveals a tendency to resolve spontaneously. Active, moderately severe Graves' ophthalmopathy qualifies for immunosuppression: intravenous pulsed methylprednisolone is more efficacious and has fewer side effects than oral steroids. Once the disease is inactive, rehabilitative surgery has much to offer. Quality of life is seriously limited in patients with Graves' ophthalmopathy, and remains restricted even after all treatments. Consequently, there is an urgent need for improved treatment modalities, and antibody therapy has shown promise in this respect.

Anonymous00251, Wiersinga WM, Perros P, Kahaly GJ, Mourits MP, Baldeschi L, Boboridis K, Boschi A, Dickinson AJ, Kendall-Taylor P, Krassas GE, Lane CM, Lazarus JH, Marcocci C, Marino M, Nardi M, Neoh C, Orgiazzi J, Pinchera A, Pitz S, Prummel MF, Sartini MS, Stahl M, von Arx G. · Department of Endocrinology, Academic Medical Centre, Amsterdam, The Netherlands. · Eur J Endocrinol. · Pubmed #16914591 links to  free full text

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Fliers E, Alkemade A, Wiersinga WM, Swaab DF. · Department of Endocrinology and Metabolism, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands. · Prog Brain Res. · Pubmed #16876576 No free full text.

Abstract: The role of the human hypothalamus in the neuroendocrine response to illness has only recently begun to be explored. Extensive changes in the hypothalamus-pituitary-thyroid (HPT) axis occur within the framework of critical illness. The best-documented change in the HPT axis is a decrease in serum concentrations of the biologically active thyroid hormone triiodothyronine (T3). From studies in post-mortem human hypothalamus it appeared that low serum T3 and thyrotropin (TSH) during illness (nonthyroidal illness, NTI) are paralleled by decreased thyrotropin-releasing hormone (TRH)mRNA expression in the hypothalamic paraventricular nucleus (PVN), pointing to a major alteration in HPT axis setpoint regulation. A strong decrease in TRHmRNA expression is also present in the PVN of patients with major depression as well as in glucocorticoid-treated patients. By inference, hypercortisolism in hospitalized patients with severe depression or in critical illness may induce down-regulation of the HPT axis at the level of the hypothalamus. In order to start defining the determinants and mechanisms of these setpoint changes in various clinical conditions, it is important to note that an increasing number of hypothalamic proteins appears to be involved in central thyroid hormone metabolism. In recent studies, we have investigated the distribution and expression of thyroid hormone receptor (TR) isoforms, type 2 and type 3 deiodinase (D2 and D3), and the thyroid hormone transporter monocarboxylate transporter 8 (MCT8) in the human hypothalamus by a combination of immunocytochemistry, mRNA in situ hybridization and enzyme activity assays. Both D2 and D3 enzyme activities are detectable in the mediobasal hypothalamus. D2 immunoreactivity is prominent in glial cells of the infundibular nucleus/median eminence region and in tanycytes lining the third ventricle. Combined D2, D3, MCT8 or TR immunocytochemistry and TRHmRNA in situ hybridization indicates that D3, MCT8 and TRs are all expressed by TRH neurons in the PVN, whereas D2 is not. Taken together, these results suggest that the prohormone thyroxine (T4) is taken up in glial cells that convert T4 into the biologically active T3 via the enzyme D2; T3 is subsequently transported to TRH producing neurons in the PVN where it may bind to TRs and/or may be degraded into inactive iodothyronines by D3. This model for thyroid hormone action in the human hypothalamus awaits confirmation in future experimental studies.

Brabant G, Beck-Peccoz P, Jarzab B, Laurberg P, Orgiazzi J, Szabolcs I, Weetman AP, Wiersinga WM. · Abteilung Gastroenterologie, Hepatologie und Endokrinologie, Medizinische Hochschule, Hannover, Germany. · Eur J Endocrinol. · Pubmed #16645008 links to  free full text

Abstract: Mild forms of hypothyroidism--subclinical hypothyroidism--have recently been discussed as being a risk factor for the development of overt thyroid dysfunction and for a number of clinical disorders. The diagnosis critically depends on the definition of the upper normal limit of serum TSH as, by definition, free thyroxine serum concentrations are normal. Cut-off levels of 4-5 mU TSH/l have been conventionally used to diagnose an elevated TSH serum concentration. Recent data from large population studies have suggested a much lower TSH cut-off with an upper limit of 2-2.5 mU/l but application of strict criteria for inclusion of subjects from the general population studies aiming at assessing TSH reference intervals (no personal or family history of thyroid disease, no thyroid antibodies and a normal thyroid on ultrasonography) did not result in an unequivocal upper limit of normal TSH at 2.0-2.5 mU/l. When summarizing the available evidence for lowered upper TSH cut-off values and their potential therapeutic implications there is presently insufficient justification to lower the upper normal limit of TSH and, for practical purposes, it is still recommended to maintain the TSH reference interval of 0.4-4.0 mU/l. Classifying subjects with a TSH value between 2 and 4 mU/l as abnormal, as well as intervening with thyroxine treatment in such subjects, is probably doing more harm than good.

Wiersinga WM. · Department of Endocrinology and Metabolism, Academic Medical Center, University of Amsterdam, The Netherlands. · Pediatr Endocrinol Rev. · Pubmed #16444185 No free full text.

Abstract: Childhood Graves' ophthalmopathy (GO) is a rare event: incidence rates (cases per 100,000 population per year) are in the age groups 5-9, 10-14 and 15-19 years for females 3.5, 1.8 and 3.3 respectively, and for males 0, 1.7 and 0. The severity of childhood GO appears to be less than that of adulthood GO, presumably explained by the lower prevalence of smoking in children. IGF-I stimulates collagen synthesis and glucosaminoglycan production by orbital fibroblasts. Serum concentrations of free and total IGF-I and IGF-2 and of the three IGF-binding proteins in GO patients are similar to those of the controls. Increased IGF levels in retrobulbar tissues may thus represent autocrine or paracrine activity in theory susceptible to reduction by somatostatin analogues. Whereas orbital octreoscans are useful in the assesment of disease activity of GO, the efficacy of somatostatin analogues in the treatment of GO is rather modest - possibly related to their almost absent affinity for sst 1 and sst 4 receptors. The new compound SOM 230 might be much more effective in this respect.

Prummel MF, Wiersinga WM. · Department of Endocrinology and Metabolism, F5-169 Academic Medical Center, Meibergdreef 9, Amsterdam 1105 AZ, The Netherlands. · Best Pract Res Clin Endocrinol Metab. · Pubmed #15826919 No free full text.

Abstract: Thyroid peroxidase (TPO) is a key enzyme in the formation of thyroid hormones and a major autoantigen in autoimmune thyroid diseases. Titers of TPO antibodies also correlate with the degree of lymphocytic infiltration in euthyroid subjects, and they are frequently present in euthyroid subjects (prevalence 12-26%). Even within the normal range for thyrotropin (TSH), TPO antibody titers correlate with TSH levels, suggesting that their presence heralds impending thyroid failure. Assays for serum TPO antibodies have become much more sensitive, and very low titers can be found in virtually all subjects. However, titers above an assay-dependent cut-off are a clear risk factor for hypothyroidism; in the Whickham survey the annual risk of developing hypothyroidism in TPO-positive women with normal thyrotropin levels was 2.1%. Measuring TPO antibodies in euthyroid subjects can be used to identify subjects with increased risk for hypothyroidism: e.g. as triage to measure thyrotropin. This could be done in women who wish to become pregnant and those with an increased risk per se who are pregnant (to predict first trimester hypothyroidism, and postpartum thyroid dysfunction), patients with other autoimmune diseases, subjects on amiodarone, lithium, or interferon-alpha, and in relatives of patients with autoimmune thyroid diseases.

Prummel MF, Wiersinga WM. · Department of Endocrinology and Metabolism, F5-171 Academic Medical Center, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands. · Eur J Endocrinol. · Pubmed #15191343 links to  free full text

Abstract: To ascertain the strength of the association between thyroid autoimmunity and miscarriage, we performed a meta-analysis of both case-control and longitudinal studies performed since 1990 when this association was first described. A clear association between the presence of thyroid antibodies and miscarriage was found with an odds ratio (OR) of 2.73 (95 % confidence interval (CI), 2.20-3.40) in eight case-control and ten longitudinal (OR, 2.30; 95 % CI, 1.80-2.95) studies. This association may be explained by a heightened autoimmune state affecting the fetal allograft, of which thyroid antibodies are just a marker. Alternatively, the association can be partly explained by the slightly higher age of women with antibodies compared with those without (mean+/-S.D. age difference, 0.7+/-1.0 years; P<0.001). A third possibility is mild thyroid failure, as thyroid-stimulating hormone (TSH) levels in antibody-positive but euthyroid women are higher than in antibody-negative women: difference 0.81+/-0.58 mU/l (P=0.005). Randomized clinical trials with l-thyroxine (aiming at TSH values between 0.4 and 2.0 mU/l) and with selenium (to decrease antibodies against thyroid peroxidase) are clearly needed to elucidate further the nature of this association.

Bartalena L, Wiersinga WM, Pinchera A. · Department of Clinical Medicine, University of Insubria, Varese, Italy. · J Endocrinol Invest. · Pubmed #15165007 No free full text.

Abstract: Graves' ophthalmopathy (GO) is an autoimmune orbital disorder most commonly associated with Graves' disease. Recent studies have underscored the role that orbital cells, particularly fibroblasts and adipocytes, play in causing the increase in orbital content responsible for clinical manifestations of the disease. GO seems to be related to autoimmune reactions triggered by autoreactive T lymphocytes of thyroid origin, which recognize antigen(s) shared by thyroid and orbit. The nature of the antigen (or antigens) involved is not fully understood, but TSH receptor is likely to be involved. Cytokines secreted by T lymphocytes, macrophages and fibroblasts play an essential role in perpetuating the disease. Animal models of GO have been developed, but results have not clarified GO pathogenesis yet. Progress in the management of the ophthalmopathy has been very limited, and glucocorticoids, orbital radiotherapy and orbital decompression remain the mainstays in GO treatment. Novel treatments, such as somatostatin analogues, antioxidants, cytokine antagonists are currently under investigation, as well as the effects of total thyroid ablation. Cessation of smoking currently represents the only form of GO (secondary and tertiary) prevention.

Wiersinga WM, Prummel MF, Terwee CB. · Department of Endocrinology and Metabolism, Academic Medical Center, University of Amsterdam, The Netherlands. · J Endocrinol Invest. · Pubmed #15165002 No free full text.

Abstract: General health-related quality of life is markedly impaired in patients with Graves' ophthalmopathy (GO), and even worse than in patients with other chronic conditions like diabetes, emphysema or heart failure. A disease-specific quality-of-life questionnaire for GO has been developed, the so-called GO-QOL, consisting of two subscales: one for visual functioning (8 questions referring to limitations due to decreased visual acuity and/or diplopia) and one for appearance (8 questions referring to limitations in psychosocial functioning due to changes in appearance). The GO-QOL was found to be a valid and reliable instrument. A minimal clinically important difference (MCID) in the GO-QOL score was derived from data obtained before and after specific eye treatments. Based on the patient's opinions, changes of > or = 6 points (minor surgery) or > or = 10 points (surgical decompression, immunosuppression) are recommended as MCID. It is concluded that the GO-QOL is an useful instrument for measuring changes over time in visual functioning and appearance of GO patients. The GO-QOL is available in six languages, and can be used as a separate outcome measure in clinical studies.

Hoogendoorn EH, Wiersinga WM, Prummel MF, den Heijer M, Corstens FH, Hermus AR. · Afd. Endocriene Ziekten, Universitair Medisch Centrum St Radboud, Postbus 9101, 6500 HB Nijmegen. · Ned Tijdschr Geneeskd. · Pubmed #15160563 No free full text.

Abstract: Subclinical hyperthyroidism is defined as the presence of serum free thyroxine (T4) and triiodothyronine (T3) levels within the reference range and a reduced serum thyrotrophin (TSH) level. Evidence is accumulating that it has important clinical effects. Randomised clinical trials are needed to answer the question whether or not treatment of subclinical hyperthyroidism prevents cardiac problems, especially atrial fibrillation, and preserves bone mineral density. A randomised, Dutch multicentre trial has recently been started. Its goal is to study whether radioiodine treatment prevents the development of atrial fibrillation and prevents decreases in bone mineral density.

Prummel MF, Strieder T, Wiersinga WM. · Department of Endocrinology and Metabolism, F5-171, Academic Medical Center, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands. · Eur J Endocrinol. · Pubmed #15132715 links to  free full text

Abstract: Genetic factors play an important role in the pathogenesis of autoimmune thyroid disease (AITD) and it has been calculated that 80% of the susceptibility to develop Graves' disease is attributable to genes. The concordance rate for AITD among monozygotic twins is, however, well below 1 and environmental factors thus must play an important role. We have attempted to carry out a comprehensive review of all the environmental and hormonal risk factors thought to bring about AITD in genetically predisposed individuals. Low birth weight, iodine excess and deficiency, selenium deficiency, parity, oral contraceptive use, reproductive span, fetal microchimerism, stress, seasonal variation, allergy, smoking, radiation damage to the thyroid gland, viral and bacterial infections all play a role in the development of autoimmune thyroid disorders. The use of certain drugs (lithium, interferon-alpha, Campath-1H) also increases the risk of the development of autoimmunity against the thyroid gland. Further research is warranted into the importance of fetal microchimerism and of viral infections capable of mounting an endogenous interferon-alpha response.

Schlumberger M, Berg G, Cohen O, Duntas L, Jamar F, Jarzab B, Limbert E, Lind P, Pacini F, Reiners C, Sánchez Franco F, Toft A, Wiersinga WM. · Institut Gustave Roussy, Villejuif, France. · Eur J Endocrinol. · Pubmed #14763906 links to  free full text

Abstract: OBJECTIVE: Because differentiated (follicular and papillary) thyroid cancer (DTC) may recur years after initial treatment, the follow-up of patients with DTC is long term. However, this population has changed, with more individuals being discovered at an earlier stage of the disease, so that previous follow-up protocols based mostly on data from high-risk patients no longer apply. We sought to develop an improved protocol for the follow-up of low-risk patients with DTC based on the findings of recent studies. METHODS: We analysed recent literature on the follow-up of DTC. RESULTS: Recent large studies have produced three important findings: (i) in patients with low-risk DTC with no evidence of disease up to the 6- to 12-month follow-up, diagnostic whole-body scan adds no information when serum thyroglobulin (Tg) is undetectable and interference from anti-Tg antibodies is absent; (ii) use of recombinant human thyroid-stimulating hormone to aid Tg measurement is effective and provides greater safety, quality-of-life and work productivity than does levothyroxine withdrawal with its attendant hypothyroidism; and (iii) ultrasonography performed by an experienced operator is the most sensitive means of detecting neck recurrences of DTC. CONCLUSIONS: We present a revised follow-up protocol for low-risk patients taking into account the above findings. This protocol should help clinicians enter a new era of monitoring characterized by greater safety, simplicity, convenience and cost savings.

Corssmit EP, Wiersinga WM. · Academisch Medisch Centrum/Universiteit van Amsterdam, afd. Endocrinologie en Stofwisselingsziekten, Amsterdam. · Ned Tijdschr Geneeskd. · Pubmed #12845835 No free full text.

Abstract: Subclinical hypothyroidism is associated with aspecific complaints such as tiredness, cognitive and depressive complaints, subtle disturbances in lipid values, an increased risk of cardiovascular disease, ovulatory dysfunction and a negative effect on foetal psychomotor development and pregnancy outcome. Subclinical hyperthyroidism is associated with atrial fibrillation, osteoporosis and dementia. Not enough prospective randomised studies with hard outcomes are available to provide evidence-based general recommendations. Therefore, the decision as to whether or not a patient should be treated needs to be made on an individual basis. For subclinical hypothyroidism it is advisable to consider treatment in the case of positive thyroid peroxidase antibody tests, a TSH concentration higher than 10 mU/l, the presence of one or more risk factors for cardiovascular disease, infertility on the basis of ovulatory dysfunction, and pregnancy. In the case of complaints of tiredness and certainly in the case of depression or cognitive dysfunction, a 3-month trial treatment can be considered. This leads to a decrease of the complaints in about 25% of cases. As negative effects are associated with the treatment, we advise an expectant approach in all other cases with a yearly monitoring of the TSH concentration. For subclinical hyperthyroidism it is advisable to consider treatment in the case of a nodular goitre, and especially in the case of atrial fibrillations. If subclinical hyperthyroidism persists in the absence of nodular thyroid disease, an expectant approach appears to be justified.

Fliers E, Wiersinga WM. · Department of Endocrinology and Metabolism, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands. · Rev Endocr Metab Disord. · Pubmed #12766541 No free full text.

This publication has no abstract.

Wiersinga WM, Bartalena L. · Department of Endocrinology and Metabolism, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands. · Thyroid. · Pubmed #12487767 No free full text.

Abstract: Graves' ophthalmopathy is clinically relevant in approximately 50% of patients with Graves' disease, severe forms affecting 3%-5% of patients. Two age peaks of incidence are observed in the fifth and seventh decades of life, with slight differences between women and men. The disease is more frequent in women than in men, although the female-to-male ratio is only 1:4 in severe forms of eye disease. The natural history of Graves' ophthalmopathy is incompletely defined, but in many instances, especially in mild forms, the disease may remit or improve spontaneously. The onset of the ophthalmopathy is in most cases concomitant with the onset of hyperthyroidism, but eye disease may precede or follow hyperthyroidism. Cigarette smoking plays an important role in the occurrence of the ophthalmopathy, and is also associated with a higher degree of disease severity and a lower effectiveness of its medical treatment. Primary prevention (i.e., avoidance of the occurrence of the ophthalmopathy) is presently not feasible, but smoking withdrawal in relatives of patients with Graves' disease might be important. In terms of secondary prevention (i.e., avoidance of progression of subclinical eye disease into overt and severe ophthalmopathy) in addition to refraining from smoking, early and accurate control of thyroid dysfunction (both hyperthyroidism and hypothyroidism), as well as early diagnosis and treatment of mild eye disease are important. As to the role that management of hyperthyroidism may play in the course of Graves' ophthalmopathy, while antithyroid drugs and thyroidectomy are not disease-modifying treatments, radioiodine therapy causes a progression of the ophthalmopathy in approximately 15% of patients, especially high-risk patients, who smoke, have severe hyperthyroidism or uncontrolled hypothyroidism, high levels of thyrotropin (TSH)-receptor antibody, or preexisting eye disease. However, the risk of radioiodine-associated progression of the opthalmopathy can be eliminated by concomitant treatment with middle-dose glucocorticoids. In terms of tertiary prevention (i.e., avoidance of deterioration and complications of overt disease) early immunosuppressive treatment or orbital decompression, as appropriate, are essential tools. Smoking withdrawal may increase the effectiveness of immunosuppressive treatment.

Wiersinga WM, Prummel MF. · Dept Endocrinology and Metabolism, Academic Medical Center F5-171, Meibergdreef 9, 1105 Amsterdam, The Netherlands. · Trends Endocrinol Metab. · Pubmed #12163229 No free full text.

Abstract: The past decade has witnessed great progress in our understanding of Graves' opthalmopathy (GO), although its precise immunopathogenesis remains an enigma. Several clinical studies have provided a more rational basis for treatment of this distressing disease, which significantly lowers the quality of life. A management plan tailored to the patient's needs can be devised according to the severity and activity of the eye disease. In active GO, immunosuppression might be considered. The combination of intravenous pulses of methylprednisolone and retrobulbar irradiation improves eye changes in 88% of patients, and is well tolerated. Once the disease has become inactive, rehabilitative surgery could be performed (orbital decompression, strabismus surgery and eyelid surgery, in that order). The patient should be reassured that functional and cosmetic improvement of eye changes is feasible, but restoration can require one to two years. To a certain extent, refraining from smoking prevents the development or worsening of GO.

Wiersinga WM. · Department of Endocrinology and Metabolism, Academic Medical Center, University of Amsterdam, The Netherlands. · J Pediatr Endocrinol Metab. · Pubmed #11964025 No free full text.

Abstract: Thyroid cancer is rare below the age of 16 years, with an annual incidence of 0.02-0.3 cases per 100,000. Papillary and follicular thyroid cancer in childhood and adolescence is more advanced upon presentation than in adults, as evident from a higher frequency of extra-thyroidal spread. The recurrence rate is also higher. Nevertheless, the prognosis for survival in children and adolescents is better than in adults; why this is so remains unclear. An approximately 30-fold increase in the incidence of thyroid cancer has been observed in children exposed to the fallout of the Chernobyl accident, especially in the age group of <1 year at the time of the disaster. Medullary thyroid cancer in childhood and adolescence occurs mainly as part of the MEN2 syndrome. Early detection by DNA mutation analysis and treatment by prophylactic thyroidectomy results in a potential normal life expectancy. Consequences in adult life relate to long-term complications of thyroid surgery, 131I treatment and TSH-suppressive doses of L-T4.

Fliers E, Alkemade A, Wiersinga WM. · Department of Endocrinology and Metabolism, University of Amsterdam, Amsterdam, 1105 AZ, The Netherlands. · Best Pract Res Clin Endocrinol Metab. · Pubmed #11800517 No free full text.

Abstract: In severe illness, profound changes occur in the hypothalamic-pituitary-thyroid axis. The observed decrease in serum concentration of both thyroid hormones and thyrotropin (TSH) are not compatible with a negative feedback loop and suggest a major change in setpoint regulation of the hypothalamic-pituitary-thyroid axis. This is supported by post mortem studies showing a decreased expression of thyrotropin-releasing hormone in the hypothalamic paraventricular nucleus of patients with a decreased serum T3 level. In critical illness, serum T3 may even become undetectable without giving rise to an elevated concentration of serum TSH. It is currently not clearly established whether this reflects an adaptation of the organism to illness or instead a potentially harmful condition leading to hypothyroidism at tissue level. There is thus a need for randomized clinical trials in critically ill patients to investigate whether they may benefit from a normalization of thyroid hormone concentration. Recent clinical studies in these patients involving the administration of hypothalamic peptides open up new ways of achieving this.

Wiersinga WM. · Academisch Medisch Centrum/Universiteit van Amsterdam, afd. Inwendige Ziekten, onderafd. Endocrinologie en Metabolisme, Meibergdreef 9, 1105 AZ Amsterdam. · Ned Tijdschr Geneeskd. · Pubmed #11379397 No free full text.

Abstract: The thyroid-stimulating hormone receptor (TSH-R) gene appears to be very sensitive to mutagenesis, in view of the vast number of reported mutations. Loss-of-function germline mutations occur preferentially in the hormone-binding extracellular domain of the TSH-R, resulting in familial TSH resistance. Gain-of-function germline mutations occur preferentially in the transmembrane domain of the TSH-R, resulting in familial non-autoimmune hyperthyroidism. Familial gestational hyperthyroidism is due to a mutant TSH-R which is hypersensitive to chorionic gonadotropin. Somatic gain-of-function mutations are a major cause of toxic thyroid adenomas.

Corssmit EP, Wiersinga WM, Boer K, Prummel MF. · Afd. Endocrinologie en Metabolisme, Academisch Medisch Centrum/Universiteit van Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam. · Ned Tijdschr Geneeskd. · Pubmed #11332254 No free full text.

Abstract: Pregnancy is accompanied by changes in thyroid function. Due to the increased synthesis of thyroid binding globulin and the thyroid-stimulating effect of human chorionic gonadotrophin (hCG), serum concentrations of thyroid hormones will increase in the first trimester of pregnancy (total T4, T3). Free T4 levels decrease during the latter half of pregnancy. Hyperthyroidism during pregnancy is usually due to Graves' disease. Definitive therapy may be considered for cases prior to pregnancy, although a medical management as would be given during pregnancy is an equally good option. The medical management of hyperthyroidism consists of a monotherapy with thyreostatics in which the recommended dose needs to be adjusted on the basis of free T4 in the high-normal and thyroid stimulating hormone (TSH) in the low-normal area so as to minimise the risk of foetal hypothyroidism. The transplacental passage of maternal TSH receptor stimulating antibodies may cause foetal hyperthyroidism. Another cause of maternal hyperthyroidism during pregnancy is 'gestational transient thyrotoxicosis', which is associated with high hCG levels during the first trimester of pregnancy. It is nearly always accompanied by hyperemesis gravidarum. Hypothyroidism in pregnancy has negative consequences for the foetus. If the hypothyroidism is apparent prior to pregnancy, it should be corrected before conception (target TSH value of 1 mU/l). If discovered during pregnancy, treatment with levothyroxine should be started as soon as possible. In the case of a pre-existing hypothyroidism a 25-50% increase in the levothyroxine dosage is often needed during the first trimester of pregnancy. This is possibly due to an increased requirement. An adequate serum concentration of T4 is necessary for foetal brain development.