Thyroid Diseases: Berghout A

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.

Muller AF, Berghout A. · Department of Internal Medicine, Diakonessenhuis Utrecht, Utrecht, The Netherlands. · Minerva Endocrinol. · Pubmed #14605606 No free full text.

Abstract: Autoimmune thyroiditis has important consequences for fertility, the occurrence of pregnancy complications, pregnancy outcome. Moreover autoimmune thyroiditis can aggravate during the postpartum period. Finally, the sequelae of autoimmune thyroiditis might have important consequences for the offspring. Several studies have shown an association between thyroid autoimmunity in earlyas opposed to beforepregnancy and subsequent "incidental" miscarriage. With respect to habitual abortion available data are more conflicting perhaps mild degrees of thyroid insufficiency - not detectable by routine thyroid testing - and not thyroid autoimmunity per se is causal in the association between the presence of thyroid antibodies and recurrent abortion. Autoimmune hypo- and hyperfunction during pregnancy are both related to obstetrical complications. It is important to note that treatment can - at least in part - reduce this excess risk associated with untreated hypo- or hyperthyroidism. Considering pregnancy outcome there are now data providing evidence that not only overt but also relatively mild and hitherto unrecognized states of thyroid failure are associated with persistent and significant impairment in neuropsychological performance of the offspring. Postpartum thyroiditis is clearly associated with the presence of TPO antibodies (i.e. autoimmune thyroiditis). Autoimmune thyroiditis is thus clearly associated with clinically relevant events, occurring before, during and after pregnancy. Screening should be considered; however further research is urgently needed.

Tielens E, Visser TJ, Hennemann G, Berghout A. · Medisch Centrum Rijnmond-Zuid, locatie Zuider, afd. Inwendige Geneeskunde, Rotterdam. · Ned Tijdschr Geneeskd. · Pubmed #12043444 No free full text.

Abstract: The most striking clinical effects of hyperthyroidism are on the heart. These effects concern both heart rate and function. The increased contractility is mainly based on the indirect inotropic effect of peripheral vasodilation as a consequence of hyperthyroidism. Although contractility at rest is enhanced in hyperthyroidism, cardiac reserve is decreased due to diminished chronotropic, inotropic and vasodilatory reserve. In hyperthyroid patients, the clinical impression is often that of a hyperadrenergic circulation. However, the sensitivity of the heart for catecholamines is not increased. The diminution of palpitations by beta-adrenergic blockers in hyperthyroid patients is due to both a decrease in heart rate and atrial extrasystoles, and is not the consequence of a normalisation of cardiac contractility. Heart failure is almost exclusively found in patients with pre-existing cardiac disease. In the case of serious heart failure a rapid reduction of circulating thyroid hormone by means of thyreostatics is important as well. There is no consensus as to whether patients with thyrotoxic atrial fibrillation should be treated with oral anticoagulants. However, most experts recommend oral anticoagulants for elderly patients (> 60 years) or patients with additional risk factors for embolism.

Muller AF, Drexhage HA, Berghout A. · Department of Immunology, Erasmus University Medical Center, 3015 GD Rotterdam, The Netherlands. · Endocr Rev. · Pubmed #11588143 links to  free full text

Abstract: 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.

Tielens E, Visser TJ, Hennemann G, Berghout A. · Zuiderziekenhuis, afd. Inwendige Geneeskunde, Rotterdam. · Ned Tijdschr Geneeskd. · Pubmed #10778718 No free full text.

Abstract: The clinical presentation of cardiac symptoms related to hypothyroidism is only rarely observed nowadays due to early diagnosis of hypothyroidism by easily available thyroid-stimulating hormone assays. A measurable abnormality of the left ventricle is the lengthened duration of contraction and relaxation, normalizing after restoration of euthyroidism. The ejection fraction and cardiac reserve are only slightly diminished in hypothyroidism. There is reversible diastolic disfunction. Pericardial effusion is a rare phenomenon. Diastolic hypertension due to hypothyroidism is the most frequent cause of endocrine hypertension. The relation between accelerated atherosclerosis and hypothyroidism is not definitively proven. Patients below age 65 and without cardiac risk factors can probably be treated with a full replacement dose of levothyroxin from the beginning. There is no increased risk of percutaneous transluminal coronary angioplasty or coronary artery bypass graft procedure in hypothyroid patients, either during or after the intervention.

Roos A, Linn-Rasker SP, van Domburg RT, Tijssen JP, Berghout A. · Department of Internal Medicine, Medical Centre Rijnmond-Zuid, Rotterdam, Department of Cardiology, Erasmus Medical Centre, Rotterdam, the Netherlands. · Arch Intern Med. · Pubmed #16087818 links to  free full text

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

Feelders RA, Swaak AJ, Romijn JA, Eggermont AM, Tielens ET, Vreugdenhil G, Endert E, van Eijk HG, Berghout A. · Department of Internal Medicine I, University Hospital, Rotterdam, The Netherlands. · Metabolism. · Pubmed #10094108 No free full text.

Abstract: Cytokines have been implicated in the pathogenesis of the euthyroid sick syndrome. Isolated limb perfusion (ILP) with recombinant human tumor necrosis factor alpha (rTNF) and melphalan in patients with melanoma or sarcoma is accompanied by high systemic TNF levels. We examined the prolonged effects (7 days) of ILP on thyroid hormone metabolism with respect to induction and recovery of the euthyroid sick syndrome in six cancer patients. After ILP, when the limb is reconnected to the systemic circulation, leakage of residual rTNF resulted in systemic peak levels at 10 minutes postperfusion followed by a parallel increase in plasma interleukin-6 (IL-6) and cortisol, with maximum levels at 4 hours (P < .05). A rapid decrease was observed at 5 minutes for plasma triiodothyronine (T3), reverse T3 (rT3), thyroxine (T4), and thyroxine-binding globulin (TBG) (P < .05), whereas free T4 (FT4) and T3-uptake showed a sharp increase, with peak levels at 5 minutes (P < .05). T3, T4, and TBG levels remained low until 24 hours after ILP In contrast, rT3 increased above pretreatment values to maximum levels at 24 hours (P < .05). Plasma thyrotropin (TSH) showed an initial decrease at 4 hours postperfusion (P < .05) but exceeded pretreatment values from day 1 to day 7 (by +94%+/-43% to +155%+/-66%, P < .05), preceding the recovery of T4 and T3 levels. T3 and rT3 returned to initial values at day 4. T4 and TBG levels recovered at day 2. T4 exceeded basal values at days 5 to 7 (P < .05). It is concluded that ILP with rTNF induces a euthyroid sick syndrome either directly or indirectly through other mediators such as IL-6 or cortisol. The recovery from this euthyroid sick syndrome is, at least in part, TSH-dependent, since the prolonged elevation of TSH values preceded and persisted during the normalization of T3 and the elevation of T4 levels. This biphasic pattern of induction of and recovery from the euthyroid sick syndrome may be a general feature of nonthyroidal disease. The euthyroid sick syndrome should be interpreted not only in relation to the presence of nonthyroidal diseases but also in relation to the recovery from these diseases.

Muller AF, Verhoeff A, Mantel MJ, Berghout A. · Department of Internal Medicine, Zuiderziekenhuis Rotterdam, The Netherlands. · Fertil Steril. · Pubmed #9935112 No free full text.

Abstract: OBJECTIVE: To determine whether an association exists between the presence of thyroid peroxidase (TPO) antibodies before pregnancy and miscarriage in women without a history of habitual abortion. DESIGN: Prospective study and nested case-control study. SETTING: Inner-city teaching hospital. PATIENT(S): Four hundred eighty-nine women in an IVF program. INTERVENTION(S): In the prospective study, we measured levels of TPO antibodies and TSH. In the nested case-control study, we also measured levels of anticardiolipin antibodies. MAIN OUTCOME MEASURE: Miscarriage. RESULT(S): One hundred seventy-three women were observed, of whom 31% (54/173) became pregnant. Pregnancy occurred in 48% (12/25) of the antibody-positive women and in 28% (42/148) of the antibody-negative women. Among those who became pregnant, miscarriage occurred in 33% (4/12) of TPO antibody-positive women and in 19% (8/42) of TPO antibody-negative women. The TSH level was abnormal (<0.2 microIU/mL) in only one of the TPO antibody-positive women who miscarried. The presence of anticardiolipin antibodies was not associated with miscarriage. CONCLUSION(S): No association was found between the presence of TPO antibodies before pregnancy and miscarriage in women without a history of habitual abortion. The presence of TPO antibodies did not adversely affect a woman's chances of becoming pregnant.

Bolk N, Visser TJ, Kalsbeek A, van Domburg RT, Berghout A. · Department of Internal Medicine, Erasmus Medical Centre, Rotterdam, The Netherlands. · Clin Endocrinol (Oxf). · Pubmed #17201800 No free full text.

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

Roos A, Zoet-Nugteren SK, Berghout A. · Department of Medicine, Rijnmond-Zuid Medical Centre, Rotterdam, The Netherlands. · Neth J Med. · Pubmed #15813421 links to  free full text

Abstract: 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.

den Hollander JG, Wulkan RW, Mantel MJ, Berghout A. · Department of Internal Medicine, Medical Centre Rotterdam Zuid, Groene Hilledijk 315, 3075 EA Rotterdam, the Netherlands. · Clin Endocrinol (Oxf). · Pubmed #15807872 No free full text.

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

Santoe MF, Van Houten AA, Muller AF, Berghout A. · Medisch Centrum Rijnmond Zuid, locatie Zuider, afd. Interne Geneeskunde, Groene Hilledijk 315, 3075 EA Rotterdam. · Ned Tijdschr Geneeskd. · Pubmed #15326651 No free full text.

Abstract: A 27-year-old woman was first referred at the age of 14 with cosmetic complaints due to an echographically diffuse, euthyroid goitre. Tests for antibodies against thyroid peroxidase and thyroglobulin were positive. Thyroid-suppression therapy with levothyroxine resulted in regression of the goitre. At the age of 26 there was a transitory recurrence of the goitre during a pregnancy, during which time the thyroid peroxidase antibodies became strongly positive. Six months post partum the goitre recurred again, accompanied by pain in the throat and fever. The C-reactive protein level was strongly elevated. Serology established the diagnosis of viral thyroiditis due to a Coxsackie-B virus. The size of the goitre decreased after treatment with acetylsalicylic acid and prednisone. Two months later the goitre again showed further growth, now in association with cervical lymphadenopathy and an enlarged left parotid gland. Histology revealed a non-Hodgkin lymphoma of the type diffuse large B-cell (stage II), very likely a primary thyroid lymphoma. The lymphoma was refractory to cyclophosphamide-doxorubicin-vincristine-prednisolone (CHOP); this was followed by intensive chemotherapy and autologous stem-cell transplantation, resulting finally in a complete remission. The goitre disappeared and thyroid peroxidase antibodies were no longer detectable. Primary thyroid lymphoma is a rare disease, but autoimmune thyroiditis appears to be an important predisposing factor.

Berghout A, van de Wetering J, Klootwijk P. · Department of Internal Medicine, Medical Centre Rijnmond-Zuid, location Zuider, Groene Hilledijk 315, 3075 EA Rotterdam, The Netherlands. · Neth J Med. · Pubmed #14708909 links to  free full text

Abstract: 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.

Canning MO, Grotenhuis K, De Haan-Meulman M, De Wit HJ, Berghout A, Drexhage HA. · Department of Immunology, Erasmus University Rotterdam, The Netherlands. · Clin Exp Immunol. · Pubmed #11472420 links to  free full text

Abstract: Blood monocytes of patients with thyroid autoimmune disease (TAID) display defects in rearranging their cortical actomyosin cytoskeleton ('polarize') in response to chemoattractants. Such rearrangements also take place after the adherence of monocytes to the extracellular matrix (ECM). It is therefore not surprising that monocytes are primed after fibronectin (FN) adherence, displaying an enhanced polarization toward chemoattractants. We investigated the integrin expression and chemoattractant-induced polarization of monocytes of TAID patients before and after FN adherence. Since cytoskeletal rearrangements are also required during the transition of monocytes into veiled antigen-presenting cells (VCs), we investigated such transition of FN-adherent monocytes of TAID patients. Adherent and nonadherent monocyte populations from TAID patients and healthy controls were subjected to a polarization test with the chemoattractant fMLP (or MCP-1), FACS analyses (FITC-labelled FN, CD29, CD49e, d, b and a) and tested for their capability to develop into veiled APC. Monocytes of healthy individuals showed an improved chemoattractant-induced cell polarization after FN adherence, not reflected by TAID monocytes, in which chemoattractant-induced polarization worsened. Monocytes of healthy individuals up-regulated CD49e and d integrins and their capability to bind FITC-labelled FN after adherence to a FN-coated plate, as well as enhancing their capability to generate T cell-stimulatory VCs. Monocytes of TAID patients did not. These data indicate that integrin- (and chemokine-) mediated functions are hampered in monocytes of TAID patients. Because integrin action is pivotal to processes such as monocyte adherence to endothelial cells, uropod formation, migration into tissues and differentiation into APC and macrophages, these defects might underly immune dysbalances important in thyroid autoimmune development.

Tielens ET, Pillay M, Storm C, Berghout A. · Department of Internal Medicine, Zuiderziekenhuis, Rotterdam, The Netherlands. · Am J Cardiol. · Pubmed #11078310 No free full text.

Abstract: The aim of the present study was to investigate in hypothyroid patients the reversibility of the prolongation of electromechanical delay and of the impairment of early diastolic relaxation as measured by radionuclide ventriculography after restoration of euthyroidism. We also evaluated Doppler echocardiography in relation to scintigraphic findings. Twenty-six consecutive hypothyroid patients were studied at diagnosis and after treatment. The time to peak ejection decreased (161 +/- 6 vs 145 +/- 5 ms; p = 0.03) without changes in global systolic function (ejection fraction). The peak filling rate was reversible as well: 2.6 +/- 0.1 versus 3.0 +/- 0.2 end-diastolic volume/s; p = 0.003. No significant changes in systolic and diastolic cardiac function or ventricular geometry were detected by Doppler echocardiography. However, subanalysis of profoundly hypothyroid patients (free T4 < 4.5 pmol/L, n = 8) revealed a decrease in the septal wall thickness (9.9 +/- 0.7 vs 8.3 +/- 0.4 mm, p = 0.01) and increases in early peak transmitral inflow velocity (53 +/- 4 vs 65 +/- 4 cm/s, p = 0.03), as well as left ventricular end-diastolic diameter (4.8 +/- 0.1 vs 5.1 +/- 0.2 cm, p < 0.05) after treatment. Thus, in primary hypothyroidism, a subtle reversible prolongation of contraction without major changes in global systolic function and a decrease in early active relaxation is observed by radionuclide ventriculography. Echocardiography shows changes only in severely hypothyroid patients.

Tielens ET, Pillay M, Storm C, Berghout A. · Department of Internal Medicine, Zuiderziekenhuis Rotterdam, The Netherlands. tielens@igrnl · Clin Endocrinol (Oxf). · Pubmed #10468910 No free full text.

Abstract: OBJECTIVE: Previous studies have suggested that hypothyroidism affects both systolic and diastolic cardiac function. We have applied equilibrium radionuclide angiography to the study of heart function at rest in hypothyroidism. DESIGN: A prospective study, evaluating cardiac function at rest in primary hypothyroidism. METHODS: Cardiac function was studied by means of equilibrium radionuclide angiography. Screening echo-Doppler examinations were performed on each patient. PATIENTS: Twenty-six consecutive untreated hypothyroid patients without clinical or echocardiographic cardiac disease and 20 healthy matched controls. RESULTS: Between patients and controls, the time to peak emptying rate (161 +/- 6 msec vs. 144 +/- 6 msec, P < 0.05) and the time to peak filling rate (188 +/- 6 msec vs. 170 +/- 5 msec, P < 0.05), were the only discriminatory parameters. In hypothyroid patients, a trend towards a decrease in diastolic cardiac function, expressed as peak filling rate, was observed: 2.6 +/- 0.1 End Diastolic Volume (EDV)/s vs. 3.0 +/- 0.1 EDV/s, P = 0.06. Within the hypothyroid patient group, the time to peak emptying rate was more prolonged in patients with lower free thyroxine levels (R = -0.60, F = 13.5, P < 0.001). Peak filling rate was decreased in patients with lower free thyroxine levels (R = 0.51, F = 8.4, P < 0.01) whereas the time to peak filling rate was more prolonged (R = -0.62, F = 15, P < 0.001). CONCLUSION: In a large group of consecutive patients presenting with primary hypothyroidism, even in the absence of clinical cardiac disease and echocardiographic abnormalities, clear changes in myocardial performance at rest were observed. The most obvious effect of thyroid hormone deficiency on the heart was a lengthening of both systolic and early diastolic time characteristics. Diastolic rather than systolic cardiac function was influenced by hypothyroidism.

Berghout A, Peeters RP. · No affiliation provided · Ned Tijdschr Geneeskd. · Pubmed #17288349 No free full text.

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Wulkan R, den Hollander J, Berghout A. · No affiliation provided · Crit Care. · Pubmed #16277744 links to  free full text

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

Berghout A, Wulkan RW, den Hollander JG. · No affiliation provided · N Engl J Med. · Pubmed #16120867 No free full text.

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den Hollander JG, Wulkan RW, Mantel MJ, Berghout A. · No affiliation provided · Clin Chem. · Pubmed #12928251 links to  free full text

This publication has no abstract.