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Biomedical subjects

M F Prummel

Publications and source records attributed to M F Prummel.

At least 37 records · Page 2Linked to original sources
PubMed2001

[Timely recognition and treatment of hypothyroidism in pregnant women: benefit for the child].

Three women aged 36, 34 and 33 years, with primary hypothyroidism were euthyroid whilst on levothyroxine treatment. Two women had previously received 131iodine therapy due to Graves' disease. During pregnancy the levothyroxine dose required to maintain a normal TSH level increased. The serum TSH-binding inhibiting immunoglobulins (TBII) activity was still very high (188 U/l) in one of the women, but decreased to 26 U/l in the last trimester. Foetal or neonatal thyrotoxicosis was not observed. The levothyroxine dose was decreased after delivery and none of the women experienced any adverse effects as a result of this. It is recommended that all women taking levothyroxine should have their serum TSH activity measured during the first trimester. The daily dose of levothyroxine required will usually increase by 50 micrograms during pregnancy. The determination of serum TBII activity is indicated in the case of Graves' disease; serum TBII values of > 40 U/l constitute a risk of foetal or neonatal thyrotoxicosis.

Adult↗
PubMed2001

[Pregnancy (conception) in hyper- or hypothyroidism].

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.

Adult↗
PubMed2001

The usefulness of quantitative orbital magnetic resonance imaging in Graves' ophthalmopathy.

BACKGROUND: Two-thirds of patients with Graves' ophthalmopathy (GO) respond to immunosuppressive treatment (prednisone or orbital irradiation), but one-third do not respond. Responders are likely to be in the active, oedematous stage of the eye disease, nonresponders in the inactive fibrotic stage. Clinical distinction between the two stages can be difficult. Quantitative magnetic resonance imaging (MRI) might be helpful in this respect, as T2 relaxation times are longer in oedematous than in fibrotic tissues. STUDY DESIGN: Prospective study on quantitative orbital MRI in healthy subjects and patients with moderately severe GO, evaluating T2 relaxation time of extraocular muscles (EOM): (a) in patients vs. controls, and (b) in patients, as a predictor of outcome to orbital irradiation. SUBJECTS AND MEASUREMENTS: Nine healthy volunteers and 64 consecutive patients with moderately severe untreated GO, who were euthyroid for > or = 2 months and qualified for orbital irradiation. T2 relaxation times were measured at the site of the largest diameter in all eight EOM of each subject. Baseline T2 values in patients were related to outcome of radiotherapy, as assessed by an independent observer 6 months later according to predefined criteria. RESULTS: T2 relaxation times of the eight EOM were longer in GO patients than in controls: median [range] 126 [52--250] vs. 88 [50--126] msec; P = 0.003. Per subject the single eye muscle with the longest T2 time was selected to represent active inflammation (excluding the lateral muscles for technical reasons). Again patients were different from controls: 160 [68--250] vs. 103 [86--115] msec, P < 0.001. In the group of 34 responders to subsequent radiotherapy, these T2 times tended to be longer than in the 30 nonresponding patients: 168 [108--250] vs. 138 [68--216] msec, P = 0.07. Using a cut-off value of 130 msec (derived from a receiver-operator-characteristics curve) a positive predictive value of 64% and a negative predictive value of 92% for the outcome of radiotherapy was calculated. CONCLUSION: Quantitative orbital magnetic resonance imaging was found to be less accurate in predicting successful outcome of radiotherapy than expected. It seems more useful in detecting the fibrotic end-stage than the active stage of Graves' ophthalmopathy. It is therefore of limited use in the decision whether or not to apply immunosuppression in patients with moderately severe Graves' ophthalmopathy.

Adult↗
PubMed2001

Interpretation and validity of changes in scores on the Graves' ophthalmopathy quality of life questionnaire (GO-QOL) after different treatments.

OBJECTIVE: The Graves' ophthalmopathy quality of life questionnaire (GO-QOL) is the first instrument available to measure health-related quality of life (HRQL) of patients with Graves' ophthalmopathy. The main objective of this study was to define a minimal clinically important difference (MCID) in score on the GO-QOL that can be considered an important improvement in HRQL by examining changes in GO-QOL scores in patients who subjectively report improvement from their treatment. A secondary objective was to test the longitudinal validity of the GO-QOL, using prespecified hypotheses about expected treatment effects. DESIGN: A prospective cohort study. PATIENTS: We included 164 patients who were scheduled for radiotherapy (23), orbital decompression (10 for sight loss, 38 for exophthalmos), eye muscle surgery (31), eyelid lengthening (43) or blepharoplasty (19). MEASUREMENTS: Patients completed the GO-QOL and three general HRQL questionnaires, before and three or six months after treatment, depending on the performed procedure. Clinical characteristics were collected from the medical records. Mean changes in GO-QOL scores and effect sizes were calculated after different treatments, and in subgroups of responders and nonresponders according to clinical characteristics and according to the patients themselves. RESULTS: A clinical response to treatment was associated with a change in GO-QOL scores of approximately 10--20 points after major treatments (radiotherapy or decompression), and with a change of approximately 3--10 points after minor surgery (eye muscle surgery, eyelid lengthening, blepharoplasty). Changes in GO-QOL scores of about 6--10 points were considered important improvements by the patients themselves. The direction and amount of change in GO-QOL scores after different treatments were in accordance with our prespecified hypotheses about treatment effects. Effect sizes in the GO-QOL subscales were generally higher than effect sizes of the general HRQL subscales, supporting the longitudinal validity of the GO-QOL. CONCLUSIONS: As a general guideline, one could consider a mean change of at least 6 points on one or both subscales an important change in daily functioning for patients. For more invasive therapies, a change of at least 10 points is recommended as a minimal clinically important difference.

Aged↗
PubMed2001

Suppression of serum TSH by Graves' Ig: evidence for a functional pituitary TSH receptor.

Antithyroid treatment for Graves' hyperthyroidism restores euthyroidism clinically within 1-2 months, but it is well known that TSH levels can remain suppressed for many months despite normal free T(4) and T(3) levels. This has been attributed to a delayed recovery of the pituitary-thyroid axis. However, we recently showed that the pituitary contains a TSH receptor through which TSH secretion may be down-regulated via a paracrine feedback loop. In Graves' disease, TSH receptor autoantibodies may also bind this pituitary receptor, thus causing continued TSH suppression. This hypothesis was tested in a rat model. Rat thyroids were blocked by methimazole, and the animals were supplemented with L-T(4). They were then injected with purified human IgG from Graves' disease patients at two different titers or with IgG from a healthy control (thyroid hormone binding inhibitory Ig, 591, 127, and < 5 U/liter). Despite similar T(4) and T(3) levels, TSH levels were indeed lower in the animals treated with high TSH receptor autoantibodies containing IgGs; the 48-h mean TSH concentration (mean +/- SEM; n = 8) was 11.6 +/- 1.3 ng/ml compared with 16.2 +/- 0.9 ng/ml in the controls (P < 0.01). The intermediate strength TSH receptor autoantibody-treated animals had levels in between the other two groups (13.5 +/- 2.0 ng/ml). We conclude that TSH receptor autoantibodies can directly suppress TSH levels independently of circulating thyroid hormone levels, suggesting a functioning pituitary TSH receptor.

Animals↗
PubMed2000

An evidence-based approach to the treatment of Graves' ophthalmopathy.

A recent survey demonstrated considerable controversy about the therapeutic approach to a patient with Graves' ophthalmopathy. Among various reasons for this disagreement is the lack of an accepted way to assess the outcome of a given therapeutic intervention. An evidence-based approach requires an objective and meaningful assessment of therapeutic outcomes in prospective, randomized studies in which confounding factors (e.g., smoking, disease activity, and state of the thyroid) are accounted for and controlled. On the basis of the available studies, a treatment approach can be selected.

Eye Diseases↗
PubMed2000

Both Th1- and Th2-derived cytokines in serum are elevated in Graves' ophthalmopathy.

Increased serum cytokine levels have been reported in patients with autoimmune thyroid disease, but less is known about their levels in patients with Graves' ophthalmopathy (GO). It is not known whether GO is a cell-mediated or humoral autoimmune disease. We investigated whether serum cytokines are elevated in GO patients and whether the cytokines were Th1- or Th2-derived. In addition, elevated cytokines might reflect the activity of GO, and thus we investigated whether cytokine levels could predict the clinical response to orbital radiotherapy. We studied 62 consecutive patients with moderately severe untreated GO and 62 healthy controls, matched for sex, age and smoking habits. Serum concentrations of IL-1RA, sIL-2R, IL-6, sIL-6R, tumour necrosis factor-alpha (TNF-alpha) RI and II and sCD30 were measured using highly sensitive ELISAs, in the patients before and 3 and 6 months after radiotherapy. All patients were euthyroid, with anti-thyroid drugs, before and during the entire study period. All baseline cytokine and cytokine receptor levels were significantly elevated in GO patients compared with healthy controls, except for IL-1RA. The levels did not correlate with parameters of the thyroid disease, nor with the duration, activity or severity of GO. However, backward logistic regression analysis showed that IL-6, sCD30 and TNFalphaRI were able to predict a beneficial response to orbital radiotherapy. We therefore conclude that both Th1- and Th2-derived cytokines are elevated in GO patients compared with its controls. IL-6, sCD30 and TNFalphaRI had some value for predicting therapeutic outcome to orbital irradiation, and may thus reflect active eye disease.

Adult↗
PubMed2000

Association of thyrotrophin receptor antibodies with the clinical features of Graves' ophthalmopathy.

OBJECTIVE: Graves' ophthalmopathy (GO) and Graves' hyperthyroidism are closely associated diseases and thought to be caused by the same autoimmune process. An obvious explanation for this would be the presence of autoantibodies reacting with an autoantigen present in the orbit and the thyroid gland. The TSH-Receptor (TSH-R) antibodies are a likely candidate, because they cause Graves' hyperthyroidism and the TSH-R appears to be present also in orbital tissues. If TSH-R antibodies are responsible for the ophthalmopathy one would expect their titres to correlate with clinical characteristics of the eye disease. The aim of the present study is to see whether TSH-R antibodies are related to the activity and severity of the thyroid-associated ophthalmopathy. DESIGN AND PATIENTS: TSH-R antibody levels were measured as TBII (TRAK assay), and TSI (cAMP response of a TSH-R transfected cell line) in serum of 63 patients with untreated moderately severe GO, accompanying Graves' thyroid disease; all patients had been euthyroid for > 2 months. RESULTS: TBII and TSI titres were strongly related to each other. TBII or TSI titres did not correlate with thyroidal or orbital disease duration, nor with TPO antibody levels. In contrast, we found a striking and highly significant correlation between the Clinical Activity Score (CAS) of the eye disease, and both TBII (r = 0.54; P < 0.0001) and TSI (r = 0.50; P < 0.0001). In addition, a weaker but significant relation was found between proptosis (in mm) and TBII (r = 0.36; P = 0.004) and TSI (r = 0.49; P = 0.0001). No correlation was found with eye muscle motility. CONCLUSION: TSH-R antibody levels correlate directly with clinical features of Graves' ophthalmopathy. The results support the hypothesis of a pathogenetic role of TSH-R antibodies and the TSH-R in the orbit of Graves' ophthalmopathy patients.

Antibodies↗
PubMed2000

Assessment of disease activity in Graves' ophthalmopathy by orbital ultrasonography and clinical parameters.

OBJECTIVE: To study if A-mode ultrasonography (US) in combination with the Clinical Activity Score (CAS) and duration of Graves' ophthalmopathy (GO) could predict the response to immunosuppression in Graves' ophthalmopathy. DESIGN: A prospective clinical study. PATIENTS AND METHODS: Fifty-six consecutive patients with moderately severe GO were treated with retrobulbar irradiation (10 fractions of 2 Gy). Before treatment the internal reflectivity in the extraocular eye muscles, the CAS, and the duration of Graves' ophthalmopathy were assessed and related to the therapeutic outcome 26 weeks after irradiation. RESULTS: Twenty-eight (50%) of the patients responded favourably to radiotherapy (four patients became worse, and 24 did not change), and the eye muscle echogenecity indeed tended to be lower in the responders than in the non-responders (P = 0.09). From a receiver operator characteristics curve, a cut-off value of 30% yielded a good positive predictive value of 85%, but the negative predictive value was only 60%. The CAS (>/= 4/10) had a positive predictive value of 65%, and a negative predictive value of 56%. When combining the ultrasound with the CAS, the positive predictive value increased to 74% and the negative predictive value to 72%. Adding the duration of eye symptoms (cut-off 18 months), the prediction of response further improved: positive predictive value 79%, and negative predictive value 89%. CONCLUSIONS: A-mode ultrasonography has a rather good positive predictive value, but its poor negative predictive value precludes its use as sole activity parameter. By adding the Clinical Activity Score and duration of Graves' ophthalmopathy, the negative predictive value increased considerably. By using this combination, inactive disease can be identified more precise, permitting rehabilitative surgery at an earlier stage in these patients.

Adult↗
PubMed2000

Thyrotoxicosis as a predisposing factor for cerebral venous thrombosis.

Thyroid storm is a rare and life-threatening complication of untreated thyrotoxicosis. A number of neurological complications have been described in association with thyrotoxicosis. We report the case of a 28-year-old woman with a thyroid storm on the basis of Graves' disease and probably triggered by a surgical procedure. She developed cerebral venous thrombosis (CVT) of the left transverse and rectus sinus with a venous infarction of the left thalamus. Except for an increased factor VIII clotting activity there were no thrombophilic abnormalities. Similar cases have been described in the literature and the reported incidence of the combination of CVT and thyrotoxicosis is significantly higher than expected by chance alone (0.1 x 10(-6) per year vs. 0.0032 x 10(-6)/year). This case is consistent with the assumption that thyrotoxicosis, probably through a factor VIII-mediated hypercoagulability, may be a predisposing factor for the development of CVT.

Adult↗
PubMed2000

Expression of the thyroid-stimulating hormone receptor in the folliculo-stellate cells of the human anterior pituitary.

TSH secretion from the anterior pituitary is mainly regulated by TRH and thyroid hormones. We hypothesized that in addition the pituitary itself could modulate TSH production by sensing its own TSH release, enabling fine-tuning of TSH secretion. For such an ultra-short loop control, the pituitary should contain a TSH receptor (TSH-R). To find evidence for this we screened a human pituitary complementary DNA library with a digoxigenin-labeled TSH-R probe and found 2 positive clones of 32,000 plaques. One clone was sequenced and found to be completely identical to the thyroid TSH-R. Further proof was obtained by RT-PCR on a human anterior pituitary obtained at autopsy. In situ hybridization and immunohistochemistry confirmed the presence of TSH-R in the anterior pituitary at the messenger ribonucleic acid level as well as the protein level. Moreover, double labeling experiments revealed that TSH-R messenger ribonucleic acid as well as TSH-R protein colocalize with major histocompatibility complex class II expression of folliculo-stellate cells. We conclude that TSH-R is expressed in a subpopulation of folliculo-stellate cells in the human anterior pituitary. This finding suggests ultra-short loop regulation of TSH secretion. Putative recognition of the pituitary TSH-R by TSH-R antibodies might have clinical relevance in Graves' disease.

Adult↗
PubMed1999

Establishment of reference values for endocrine tests. II: Hyperprolactinemia.

BACKGROUND: In patients with hyperprolactinemia, the thyrotropin-releasing hormone (TRH) stimulation test is widely applied to distinguish prolactinoma from other causes of hyperprolactinemia. In the present study, we established reference values for the plasma concentration of prolactin (PRL) and its response to TRH. METHODS: Basal PRL and the PRL response to 400 micrograms TRH i.v. was determined in 50 subjects recruited from the general population, equally distributed according to sex and age between 20 and 69 years. PRL was determined by a fluoroimmunometric assay. Reference values are given as the observed range. RESULTS: Plasma concentrations of PRL were 4.0-25 micrograms/l (median: 10.0 micrograms/l) in women and 0.5-19.0 micrograms/l (median: 8.5 micrograms/l) in men (p = 0.11). The peak PRL concentration after stimulation with TRH was slightly higher in women (median: 51 micrograms/l) than in men (median: 41 micrograms/l; p = 0.04) and was reached at t = 20 min in all subjects. The relative increase in plasma PRL (median: 440%) did not show a statistically significant effect of age or sex. In 12 subjects (24%), the relative increase in plasma PRL was lower than 250%, which has traditionally been considered the minimum cutoff for a normal response. There were no effects of smoking and alcohol, but regular ingestion of liquorice was associated with lower basal (p = 0.03) and lower stimulated (p = 0.05) plasma concentrations of PRL. CONCLUSIONS: The present study provides reference values for basal and TRH-stimulated plasma concentrations of PRL.

Adult↗
PubMed1999

Test-retest reliability of the GO-QOL: a disease-specific quality of life questionnaire for patients with Graves' ophthalmopathy.

To assess the test-retest reliability of a recently developed disease-specific quality of life questionnaire for evaluative studies in patients with Graves' ophthalmopathy (the GO-QOL), measuring visual functioning and psychosocial consequences of changed appearance. Ninety-three patients were included and completed the GO-QOL. Additional information on general quality of life and disease characteristics was obtained. Construct validity and internal consistency of the two subscales was determined, based on principal component analyses, Cronbach's alpha's and correlations with MOS-24, three subscales of the SIP, and clinical measures. Eighty-nine patients completed a second GO-QOL after two weeks including four additional questions about perceived changes in health status. Test-retest reliability was assessed by calculating intraclass correlation coefficients (ICCs) and limits of agreement, using several definitions of stable patients. Slight modifications from the original questionnaire were evaluated for their effect on the validity and reliability. The construct validity of the two subscales was confirmed and Cronbach's alpha's were 0.89 for visual functioning and 0.87 for appearance. The substantial ICCs found for both scales of the GO-QOL (ICCs above 0.80) reflect that the errors of measurement were relatively small, which supports the value of this questionnaire for clinical studies with relatively small sample sizes. The modification of the appearance scale improved the validity of the scale and resulted in less missing values. Following the recommendations of the joint committee of thyroid associations, we recommend the inclusion of HRQL-measures in clinical studies that evaluate treatments for patients with GO. The GO-QOL is a promising tool for this purpose.

Adolescent↗
PubMed1999

Octreotide-scintigraphy is a disease-activity parameter in Graves' ophthalmopathy.

OBJECTIVE: It is thought that immunosuppressive treatment of Graves' ophthalmopathy should be restricted to patients with active eye disease, but assessing disease activity is difficult. Octreotide scintigraphy has been claimed to differentiate active from inactive disease. Here we study the intraobserver variability and diagnostic accuracy of the quantitative measurement of orbital octreotide uptake. PATIENTS AND DESIGN: Twenty-two consecutive patients with moderately severe ophthalmopathy were treated with retrobulbar radiotherapy. Pretreatment octreotide scintigraphic data were related to the response at six months after radiotherapy, using Receiving-Operator-Characteristic curves. MEASUREMENTS: Octreotide uptake was measured at 4 and 24 h after i.v. injection of approximately 3 mCi (= 111 MBq; range 75-150 MBq) 111Indium-DTPA-Octreotide with a neuro-SPECT camera. Counts were measured in fixed regions-of-interest in 4 transversal slices of the orbit, the temporal and the occipital area. Measurements were done twice and intraobserver variability was analysed by coefficients of variations (CV). Uptake is expressed as orbital/background ratio. The nature of the temporal uptake was studied by matching an octreoscan with a technetium scan and MRI. RESULTS: Intra-observer variability of measuring octreotide uptake was acceptable, and the coefficient of variation slightly better using the orbital/occipital ratio (11%), than the orbital/temporal ratio (16%). From matching studies it appears that the temporal uptake takes place, in part, in the parotid gland. The orbital/occipital ratio was used to predict the outcome of radiotherapy. Mean (+/- SD) uptake on the 4 h scan was higher in responders (2.2 +/- 0.66) than in nonresponders (1.7 +/- 0.39; P = 0.04). From the Receiving-Operator-Characteristic curve we determined a cut-off value of 1.85, which yielded a positive predictive value of 92% and a negative predictive value of 70%. The 24 h scan could not predict a response. CONCLUSION: Quantitative measurement of orbital octreotide uptake is possible. Using the orbital/occipital ratio on the 4 h scan, the octreoscan seems useful in predicting response to subsequent radiotherapy. The 24 h scan seems not to be useful in predicting therapeutic outcome.

Adult↗