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Biomedical subjects

A Berghout

Publications and source records attributed to A Berghout.

At least 19 recordsLinked to original sources

Thyroid autoimmunity and abortion: a prospective study in women undergoing in vitro fertilization.

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.

Abortion, Spontaneous

Characteristics of recovery from the euthyroid sick syndrome induced by tumor necrosis factor alpha in cancer patients.

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.

Aged

Cardiac function at rest in hypothyroidism evaluated by equilibrium radionuclide angiography.

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.

Adult

Thyroid size and thyroid function during pregnancy: an analysis.

An analysis of all available studies of thyroid size and function in pregnancy reveals that thyroid size, estimated by inspection and palpation or measured more accurately by ultrasonography, increases in pregnancy in areas of iodine deficiency but not in those with sufficient iodine. The increase in average thyroid size is within the normal range, and can partly be prevented by treatment with extra iodine or thyroxine. There is a slight transient increase in free thyroxine in the first trimester, probably as a result of physiological stimulation of thyroid function by human choriogonadotrophin. These levels then decrease by about 30% to low normal values in the second and third trimesters of pregnancy in both iodine-depleted and -replete areas. These changes resemble those of non-thyroidal illness and may well play a role in reducing energy expenditure during pregnancy. The increase in thyroid size in iodine-deficient areas is probably due to autoregulatory mechanisms of iodine on thyroid growth. The hypothesis is supported by the fact that, during pregnancy, thyroid volume and thyroid function adapt in a physiological way to meet the increased demands for iodine and energy.

Female

Diabetic patients with foot burns.

We describe six patients with non-insulin dependent (Type 2) diabetes mellitus (NIDDM) and thermal foot injury admitted to the Burn Centre in Rotterdam. They were all male with a mean age of 56.8 (range 47-63) years. The median patients' delay before admission was 27 (range 1-56) days. Five patients needed amputation. Healing of the wounds took a mean period of 9.5 (range 2-27) months. In two patients healing of the wounds took more than 1 year; these two patients also had recurrent foot burns. Neurological evaluation in four patients confirmed severe polyneuropathy and severe loss of heat pain, warmth, and cold sensation.

Burns

Irreversible gonadal damage in male survivors of pediatric Hodgkin's disease.

BACKGROUND: Gonadal damage in adult patients after chemotherapy for Hodgkin's disease is well documented, but data of patients treated before adulthood are scarce. METHODS: Gonadal and hormonal function were studied in 19 male long term survivors of Hodgkin's disease who were treated with mechlorethamine, vincristine, procarbazine, and prednisone (MOPP chemotherapy) before (n = 15) or during puberty (n = 4). The studies were performed a median of 10 years after treatment and repeated in the majority of the patients at the time of yearly visits. RESULTS: Germ cell damage was present in all patients. Semen analysis revealed azoospermia in 12 patients and oligospermia in 6; no recovery of spermatogenesis was seen at follow-up. Testicular size was small in all but one patient. Follicle-stimulating hormone levels were elevated (mean, 14.4 +/- 7.8 U/l) and increased over time (mean, 21.1 +/- 10.5 U/l, P < 0.001). In seven patients, luteinizing hormone (LH) was elevated, indicating Leydig cell dysfunction; also in four of those patients, plasma testosterone was decreased. In three other patients, the response of LH to gonadotropin-releasing hormone was exaggerated with a normal basal LH and testosterone. Comparing testicular function of prepubescent versus pubescent state at time of treatment appears to show a trend for improved outcome in the younger patients. CONCLUSIONS: Gonadal function of long term survivors of pediatric Hodgkin's disease treated with MOPP chemotherapy is severely impaired permanently.

Adolescent

Thyroid function and thyroid size in normal pregnant women living in an iodine replete area.

OBJECTIVE: The interpretation of the changes in thyroid hormone concentrations during normal pregnancy is a matter of debate involving, in some geographical regions, enhanced thyroid activity in early pregnancy and a hypothyroid state in the third trimester. A clinically detectable increase in thyroid size has been found in areas of mild iodine deficiency ('goitre of pregnancy'), but not in iodine replete areas. DESIGN: A prospective study. We have studied thyroid size and function in normal pregnant women living in an iodine replete area. PATIENTS: Healthy women before and during a normal pregnancy resulting from artificial insemination (n = 10) and other women during the normal menstrual cycle (n = 11), in the iodine replete area of Amsterdam. MEASUREMENTS: Thyroid volume was measured by ultrasonography. Plasma T4, free T3, free reverse T3, TSH, thyroxine binding globulin, hCG, progesterone and thyroid autoantibodies were measured. RESULTS: Thyroid volume did not change during pregnancy (data given before pregnancy and during 1st, 2nd and 3rd trimesters, respectively: 10.3 +/- 5.1, 10.6 +/- 4.4, 9.6 +/- 3.8 and 9.4 +/- 3.0 ml, NS). Free T4 and free T3 levels declined during pregnancy (13.7 +/- 2.0, 13.5 +/- 4.1, 11.2 +/- 2.8, 10.2 +/- 1.6 pmol/l, P = 0.005; 4.55 +/- 0.63, 4.64 +/- 0.88, 3.72 +/- 0.67 and 4.01 +/- 0.75 pmol/l, P = 0.003), whereas free reverse T3 levels increased during pregnancy (0.16 +/- 0.04, 0.19 +/- 0.07, 0.14 +/- 0.03 and 0.20 +/- 0.07 pmol/l, P = 0.001). Thyroglobulin levels remained unchanged. Thyroid hormones and thyroid volume did not differ between follicular and luteal phases of the menstrual cycle. CONCLUSION: Thyroid volume does not increase during pregnancy in iodine-replete areas. The decrease in free T4 and free T3 and the increase in free reverse T3 concentrations during pregnancy resemble the changes in thyroid hormones seen in non-thyroidal illness. This could be a physiological adaptation enabling energy conservation during the high metabolic demands of pregnancy.

Environment

Randomized double-blind trial of prednisone versus radiotherapy in Graves' ophthalmopathy.

Corticosteroids are usually given for management of Graves' ophthalmopathy, but they have many and serious side-effects. By comparison, retrobulbar irradiation is well tolerated, although its efficacy has been evaluated only in uncontrolled studies. Therefore, we did a double-blind randomised trial, in which 28 patients with moderately severe Graves' ophthalmopathy were treated with a 3-month course of oral prednisone and sham irradiation, and 28 received retrobulbar irradiation (20 Gy) and placebo capsules. Therapeutic outcome, assessed twenty-four weeks after the start of treatment, was determined by the change in the highest NOSPECS class. A successful outcome was observed in 14 prednisone-treated and in 13 irradiated patients. Responders to treatment (but not nonresponders) in both groups showed improvements in total and subjective eye score and a decrease in eye-muscle volume. Response to either treatment was due largely to changes in soft-tissue involvement and eye-muscle motility. Mean elevation in responders to radiotherapy increased from 18.5 degrees (95% CI 14.8-22.2) at baseline to 21.8 degrees (18.6-25.0) at week twenty-four (p = 0.003), but did not change in prednisone responders. Side-effects were more frequent and severe during prednisone than during radiotherapy. Radiotherapy and oral prednisone appear to be equally effective as initial treatment in patients with moderately severe Graves' ophthalmopathy. In view of its better tolerability, radiotherapy should be considered the treatment of first choice.

Administration, Oral

Comparison of placebo with L-thyroxine alone or with carbimazole for treatment of sporadic non-toxic goitre.

The efficacy of treatment with TSH-suppressive doses of L-thyroxine (T4, 2.5 micrograms/kg body weight daily) either alone or combined with carbimazole (CBZ, 40 mg daily) was studied in 78 patients with sporadic non-toxic goitre in a prospective placebo-controlled double-blind randomised clinical trial. Treatment was given for 9 months, with 9 months of follow-up. A response to treatment as measured by ultrasonography was found in 58% of the T4 group, in 35% of the T4/CBZ group, and in 5% of the placebo group. The mean (SEM) decrease of thyroid volume at 9 months in the responders was 25% (2). After discontinuation of treatment, thyroid volume increased in the responders and had returned to base-line values after 9 months of follow-up. In the placebo group mean thyroid volume had increased by 6% (4) at 4 months, 20% (7) at 9 months, and 27% (8) at 18 months. The findings show that untreated sporadic non-toxic goitre continues to increase in size; T4 is effective in the treatment of the disorder; and the addition of CBZ has no therapeutic advantage.

Adult

HLA-DR4 associated response to corticosteroids in Graves' ophthalmopathy patients.

Fifty-seven patients with severe Graves' ophthalmopathy were treated with corticosteroids. Therapeutic outcome was assessed according to predetermined criteria as response (n = 37) or non-response (n = 20) to therapy. Patients were typed for HLA-A, -B, -C, -DR and -DQ. HLA-DR4 was completely absent in the 20 non-responder patients (corrected p value = 0.042). In the responder group 14 of the 37 patients were HLA-DR4 positive. This study shows that in Graves' ophthalmopathy patients the presence of HLA-DR4 is associated with a good response to corticosteroid therapy. The frequency of HLA-DR4 in the Graves' ophthalmopathy population as a whole, however, was not different from normal (25% versus 26%). But as reported previously, the frequency of HLA-DR3 was significantly increased in the Graves' ophthalmopathy patients when compared to healthy blood donors (47% versus 24%, corrected p value = 0.02). No significant deviations were found in the HLA-A, -B, or -C loci.

Adrenal Cortex Hormones

Interrelationships between age, thyroid volume, thyroid nodularity, and thyroid function in patients with sporadic nontoxic goiter.

PURPOSE: To test the hypothesis that during the natural history of sporadic nontoxic goiter (SNG), a diffuse goiter precedes a multinodular goiter with gradual development of autonomous thyroid function. PATIENTS AND METHODS: A cross-sectional survey of 102 consecutive patients with SNG (seven male, 95 female) was performed. Thyroid volume was measured by ultrasonography, and plasma thyroid-stimulating hormone (TSH) by a sensitive assay (TSH immunoradiometric assay). RESULTS: Patients with a multinodular goiter were older and had a larger thyroid volume than patients with a diffuse or uninodular goiter. Plasma free thyroxine (T4) and total triiodothyronine (T3) were higher and plasma TSH was lower in patients than in normal subjects. Free T4 was higher in the subgroup of patients with a multinodular goiter and a decreased TSH response to thyrotropin-releasing hormone. Plasma TSH (y, in mU/L) was negatively related to thyroid volume (x, in mL): y = 8.2x-0.667 (r = 0.578, p less than 0.001). Thyroid volume (y, in mL) was positively related to age (x, in years): y = -21.8 + 2.0x (r = 0.455, p less than 0.001); and to duration of goiter (x, in years): y = 40.6 + 2.1x (r = 0.505, p less than 0.001). The annual increase in thyroid volume was calculated at 4.5%. CONCLUSION: The data suggest a continuous growth of SNG and provide support for the concept of increasing thyroid nodularity and autonomy of thyroid function--related to increasing thyroid volume--during the natural history of this disorder.

Adult

Orbital decompression for Graves' ophthalmopathy by inferomedial, by inferomedial plus lateral, and by coronal approach.

To test the efficacy and safety of orbital decompression for Graves' ophthalmopathy, the authors studied the records of 60 consecutive patients who were operated on for dysthyroid optic neuropathy or for rehabilitative purposes. Patients decompressed for neuropathy were older, had less proptosis, and a shorter duration of eye disease than patients operated on for disfigurement. The authors compared the results of three surgical procedures including the inferomedial, the inferomedial plus lateral, and the coronal approach. Regarding improvement of visual function, no difference was found between the three techniques. Patients in whom vision failed to recover had a high prevalence of diabetes mellitus. Proptosis reduction varied from 1 to 9 mm, depending on the number of walls decompressed. There was no net change in the prevalence of diplopia. Persistent complications were seen in less than 5% of all decompressions. The authors conclude that orbital decompression for Graves' ophthalmopathy is safe and efficacious, regardless of surgical procedure. However, the coronal approach gives the best cosmetic results.

Adult

Extraocular muscle surgery for Graves' ophthalmopathy: does prior treatment influence surgical outcome?

We analysed the results of extraocular muscle surgery in 38 patients with stable Graves' ophthalmopathy. Fixed sutures were used in all patients. A useful field of binocular single vision was achieved in 27 patients (71%) after one operation and in seven patients (18%) after more than one, whereas double vision was persistent in four (11%). No recurrence of diplopia was seen during one year of follow-up. No differences were found in duration of eye disease, angle of deviation, or in prior forms of treatment between patients who responded well to a single operation and those who needed more surgical procedures or those who responded less well. We conclude that, although the individual outcome cannot be predicted, every patient with diplopia and stable Graves' ophthalmopathy has an 89% chance of binocular single vision after extraocular muscle surgery. Prior treatment does not appear to influence this outcome.

Adult

A diminished adherence of blood lymphocytes of patients with thyroid autoimmune disease to high endothelial venules in the thyroid and the thyroid-draining lymph nodes.

The function of high endothelial venules (HEVs), present in the T-cell area of lymphoid tissue is to attract lymphocytes to secondary lymphoid organs ("homing"). In Graves' disease, sporadic goitre and lymphocytic thyroiditis HEVs develop in the thyroid. To study the "homing" of peripheral blood lymphocytes (PBL) of healthy individuals and thyroid patients to the thyroid area we studied the adherence of PBL of such individuals to HEVs present in Hashimoto's goitres and to HEVs in thyroid draining lymph nodes. A modification of the in vitro "homing assay" described by Stamper and Woodruff (J Exp Med 144: 823) was used. The number of PBL of patients with Graves' disease which adhered to thyroidal and thyroid-draining lymphnode HEVs was significantly (p less than or equal to 0.001, Wilcoxon test) less than that of healthy control PBL's; in the case of thyroid HEVs 12 (mean, sd 8, n = 18) patient lymphocytes adhered to 35 HEVs vs 19 (mean, sd 7, n = 16) healthy control lymphocytes; in the case of thyroid lymphnode HEVs 20 (mean, sd 12, n = 15) patient lymphocytes adhered vs 35 (mean, sd 9, n = 9) healthy control lymphocytes. PBL of a few sporadic goitre (n = 5) and atrophic lymphocytic thyroiditis (n = 2) patients also showed a diminished adherence to thyroidal HEVs. We also studied the homing capability of lymphocyte suspensions isolated from the thyroid glands of three Graves' disease patients; these infiltrated cells showed a normal adherence pattern to thyroidal HEVs. We favour the idea that the data should be explained by a redistribution of lymphocytes possessing "thyroid-specific-homing-receptors" from the circulation to the thyroid area in patients with thyroid autoimmune disease.

Adolescent

Effect of abnormal thyroid function on the severity of Graves' ophthalmopathy.

Many clinicians have the impression that treatment of thyroid dysfunction ameliorates ophthalmopathy in Graves' disease. The aim of our study was to relate thyroid function to the severity of Graves' ophthalmopathy. We studied 90 patients with Graves' ophthalmopathy and Graves' hyperthyroidism in whom severity of Graves' ophthalmopathy and thyroid function (regardless of antithyroid treatment) were assessed when referred to our institution. Patients were assigned to four groups (A through D) with increasingly severe Graves' ophthalmopathy using Total Eye Score based on the NOSPECS classification. The percentage of dysthyroid patients in each group was determined: group A had 23% dysthyroid patient (5); group B, 32% (9); group C, 61% (14); and group D, 47% (8). More dysthyroid patients were in the groups with severe Graves' ophthalmopathy. We also compared the severity of Graves' ophthalmopathy between euthyroid (n = 54) and dysthyroid (n = 36) patients: euthyroid patients had less proptosis (19.9 +/- 3.5 vs 20.8 +/- 3.4 mm), better visual acuity (0.93 +/- 0.17 vs 0.88 +/- 0.18), and lower Total Eye Score (8.6 +/- 6.6 vs 10.6 +/- 6.6). We conclude that dysthyroidism is associated with more severe Graves' ophthalmopathy. Our findings suggest that meticulous control of thyroid function also during antithyroid treatment is important in the management of Graves' ophthalmopathy.

Adult