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Biomedical subjects

K Siersbaek-Nielsen

Publications and source records attributed to K Siersbaek-Nielsen.

At least 19 recordsLinked to original sources
PubMed2004

Relationship between mood and TSH response to TRH stimulation in bipolar affective disorder.

Moderate to severe depression and mania are associated with a reduced thyroid stimulating hormone (TSH) response to TSH releasing hormone (TRH). Continued reduction of this response after clinical recovery seems indicative of early relapse. The aim of the present study was to test the relationship between mild changes in mood and the TSH response to TRH stimulation in patients with bipolar affective disorder. Nineteen outpatients with bipolar affective disorder were followed prospectively for three years. Every third month, mood symptoms were rated using the 17-item Hamilton Depression Rating Scale (HAMD-17) and the Bech-Rafaelsen Mania Scale (BRMS). A TRH test was performed in connection with each rating session (IV injection of 200 microg TRH), and serum TSH was measured at 0, 20, and 60 min. The maximum TSH response (D-max TSH) and the temporal change in D-max TSH between succeeding rating sessions (DD-max TSH) were determined. Psychometric rating and TRH data were obtained for a total of 198 examinations. The temporal change in mood symptom rating score was negatively correlated with the temporal change in D-max TSH, thus suggesting that increasing severity of mood symptoms was related to a reduced TSH response to TRH stimulation. The temporal change in TSH response to TRH stimulation correlated with the actual score on an overall index of symptom severity. In conclusion, milder fluctuations in mood in bipolar affective disorder seem to correlate with the TSH response to TRH stimulation: Increasing severity of mood symptoms seems to be associated with reduced TSH response.

Adult↗
PubMed1998

Normalization of serum thyrotrophin by means of radioiodine treatment in subclinical hyperthyroidism: effect on bone loss in postmenopausal women.

BACKGROUND: Patients with subclinical hyperthyroidism (reduced serum TSH and normal free T4 and T3 concentrations) have slightly increased bone turnover and might have reduced bone mass, especially among postmenopausal women (due to concomitantly reduced oestrogen production), as also seen during suppressive L-T4 treatment. OBJECTIVE: We have evaluated whether normalization of serum TSH using radioiodine treatment (RAI) in postmenopausal women with a nodular goitre and subclinical hyperthyroidism, protects against bone loss? DESIGN: Prospective, non-randomized study, outpatients 2 years follow-up. PATIENTS: Postmenopausal women with a nodular goitre, biochemically subclinical hyperthyroidism (TSH < 0.2 mU/I, and signs of a growing goitre or compression symptoms. Sixteen were treated with RAI (median dose 555 MBq) (+RAI), whereas 12 were followed without treatment (-RAI). MEASUREMENTS: Serum TSH (third generation technology), free T4 and T3 indices, and bone mass (BMD) as measured by Dual Photon Absorptiometry (4 in each group) (only spine) or Dual X-ray Absorptiometry (DEXA) (both spine and hip), were measured yearly for up to 2 years. RESULTS: The two groups did not differ regarding age, thyroid hormone parameters, and absolute levels of BMD at spine and hip. RAI resulted in normalization of TSH in all 16 women, and FT4I as well as FT3I decreased to 78% after one year (P < 0.01). These parameters did not change in the untreated group, thus serum TSH remained reduced. BMD at the spine tended to increase (n.s.) after RAI to (median) 101.9% after one year, and 101.5% after 2 years. In contrast the -RAI group experienced a continued fall in BMD to 97.3% after one year, and 95.5% after 2 years, both reduced as compared to the +RAI group (P < 0.02). BMD of the hip also increased after RAI, to 102.3% after one year, and 101.7% after 2 years. In contrast BMD in the -RAI group decreased to 94.8% after one year, and 98.0% after 2 years, both lower than in the +RAI group (P < 0.01). CONCLUSIONS: Subclinical hyperthyroidism due to a nodular goitre in postmenopausal women resulted in a continued loss of bone mass of about 2% per year. Radioiodine treatment resulting in normalization of serum TSH prevented this continued bone loss for at least 2 years. Our study supports earlier intervention in such patients.

Aged↗
PubMed1997

Discrepancies between thyrotropin (TSH) measurement by four sensitive immunometric assays.

A comparison of four different commercial immunometric thyrotropin (TSH) assays (Amerlite R TSH-30 Ultrasensitive assay from Kodak, BeriLux R hTSH from Behring Werke, Delfia R hTSH Ultra from Wallac and IMX R Ultrasensitive hTSH from Abbott) was made by measuring serum TSH in 81 consecutive patients referred to hospital for various reasons with a serum TSH less than 0.8 mlU/l in the IMX assay. The analytical and functional assay sensitivities of each of the assays were analysed. Even though three of the methods had a sensitivity corresponding to third generation assays, we could only demonstrate an overall agreement of serum TSH when comparing two of the kits. The measurements in Delfia Ultra and Berilux showed good agreement (P = 0.7, paired t-test and bias = 0.003 mIU/l), while the comparisons between the other assays showed different measurements (P < 0.00001, paired t-test and bias more than 0.07 mIU/l). Differences in the calibrators used in the assays might explain some of the discrepancy, although all methods were calibrated according to the same international standard. Also, differences in the specificity of the TSH monoclonal antibodies used in the assays might be an evident explanation and further studies of the specificity of the monoclonal antibodies are needed. An international collaborative study to clarify reasons for the differences between the TSH assays and to standardize the measurements is recommended.

Adolescent↗
PubMed1996

Serum free 3,5,3'-triiodothyronine (T3) in non-thyroidal somatic illness, as measured by ultrafiltration and immunoextraction.

UNLABELLED: Serum free 3,5,3'-triidothyronine (T3) levels are regularly reported reduced in patients with non-thyroidal, somatic illnesses (NTI). However most free T3 assays have serious methodologically shortcoming. From a theoretical point of view, ultrafiltration may be the most reliable technique at present, and we have previously reported unaltered serum free T3 levels in NTI. A newly commercialized assay suitable for routine use (Amerlite MAB free T3) has demonstrated promising results in NTI sera, and we thus compared these two methods in a large group of NTI patients not treated with glucocorticoids or dopamine (n = 120), as well as in 66 healthy controls and 8 patients on prolonged dopamine infusion. In both assays free T3 levels were unaltered in NTI (NTI versus controls (mean), Amerlite MAB free T3: 5.47 versus 5.32 pmol/l; ultrafiltration free T3; 6.99 versus 7.60 pmol/l). Free T3 levels outside normal range were found in 14% using the Amerlite MAB free T3 assay and 2% using the ultrafiltration assay. The two methods correlated in all subjects (n = 194) (r = 0.32 (P < 0.001) as well as in NTI patients (r = 0.34 (P < 0.001). No correlations to serum T4 levels were found, and patients with serum T4 levels below or above 70 nmol/l, had similar free T3 concentrations in both assays. Patients on dopamine infusion had reduced serum free T3 levels (both assays), but the values were still within the normal range. CONCLUSION: Serum free T3 levels were unaltered in NTI patients using both assays, and the Amerlite MAB free T3 assays seems useable during diagnostic work-up for possible thyroid disease in hospitalized patients with other somatic illnesses, despite the fact that this assay has some shortcomings, which are an integral part of all immunoextraction assays.

Humans↗
PubMed1995

Development of hyperthyroidism in nodular goiter and thyroid malignancies in an area of relatively low iodine intake.

A high incidence of toxic nodular goiter has recently been described in areas of relatively low iodine intake. We studied the development of hyperthyroidism in nodular goiter and thyroid malignancies in an area of relatively low iodine intake (median 87 micrograms/h). The material comprised a total of 557 patients admitted to our department in the period 1978-88. The follow-up material consisted of 214 patients with a median age of 55 yr (19-86). Eighty-eight percent were females. The period of observation was 33 months (1-205). All patients had technetium thyroid scans, serum T3, serum T4, T3 uptake test and serum TSH performed. TRH tests were performed in 58 patients. During the follow-up period 45 initially euthyroid patients became hyperthyroid (18%). The incidence increased with age, and the median age in the group, who developed hyperthyroidism, was 65 yr. An estimated minimal incidence of toxic nodular goiter was 23/100,000/yr. Contrary to previous assumption, hyperthyroidism developed frequently in elderly patients with nodular goiter in a low iodine intake area. Thyroid cancer was found in 13 patients corresponding an estimated incidence of 1.5/100,000/yr. The cancer incidence was very low compared to other nordic countries with high iodine intake. This finding may suggest a possible influence of iodine intake on the incidence of thyroid cancer.

Adult↗
PubMed1993

Free thyroxine measured in undiluted serum by dialysis and ultrafiltration: effects of non-thyroidal illness, and an acute load of salicylate or heparin.

In vitro dilution of serum during processing of a free T4 assay explains to some extent the divergent results obtained in non-thyroidal illness. If serum from such patients contains low affinity T4 protein binding inhibitors, as has been suggested, in vitro dilution will result in spuriously reduced serum free T4 measurements. If these inhibitors cross the dialysis membrane in an equilibrium dialysis assay, their inhibitory effect will be weakened, and in vitro free T4 levels will decrease, even in undiluted serum. In contrast, ultrafiltration methods on undiluted serum seem accurate. We have compared a new, commercially available dialysis technique with an in-house ultrafiltration method for free T4 measurements in undiluted serum. Control subjects (n = 41) had 14% higher free T4 (P < 0.02) by ultrafiltration. Non-thyroidally ill patients not receiving glucocorticoids or dopamine (n = 54) had unaltered free T4 levels, 28.4 +/- 10.3 pmol/l (dialysis) and 31.0 +/- 10.3 pmol/l (ultrafiltration). Dopamine infusion in somatic ill patients (n = 11) resulted in reduced free T4 in both assays but only significantly for dialysis, and subjects with familial dysalbuminemic hyperthyroxinemia (n = 8) had unaltered free T4 levels in both assays. Salicylate (1.5 g) given orally 09:00 h. (n = 5) resulted within 30 min, in increased (P < 0.01) free T4 as measured by both techniques, although more pronounced and sustained as measured by ultrafiltration. Serum TSH decreased concomitantly (P < 0.01). These findings were confirmed when salicylate was administered at 13:00 h. (n = 8). The dialysis procedure resulted in a decrease in serum salicylate of 14% (P < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Nuclear 3,5,3'-triiodothyronine receptor binding in mononuclear blood cells from patients with malignant blood diseases and small cell carcinoma of the lung.

We have previously demonstrated enhanced daily turnover of thyroid hormones in patients with hypermetabolic symptoms due to malignant haematologic disorders or small cell carcinoma of the lung. We hypothesized that some of these symptoms might be due to enhanced peripheral effects of T3. We therefore studied the nuclear T3 receptor binding in circulating mononuclear blood cells in 5 patients with malignant haematologic disorders, 5 with untreated small cell carcinoma of the lung, and 11 healthy controls. Maximal binding capacity of T3 (MBC) was increased 2.5 times in the diseased patients, (median (range)) 110 fmol/mg DNA (75-519) in the haematologic group (p < 0.01), 106 fmol/mg DNA (47-490) (p < 0.10) in small cell carcinoma patients, as compared to 43 fmol/mg DNA (26-94) in controls. The affinity constant Ka of bound T3 was reduced to one-third in the diseased patients. No differences were found between serum thyroid hormone or TSH levels. It is hypothesized, that previously demonstrated enhanced turnover of thyroid hormones in these states of disease might in part be due to increased peripheral consumption of thyroid hormones, including enhanced receptor binding of T3.

Carcinoma, Small Cell↗
PubMed1991

Acupuncture in the treatment of Graves' ophthalmopathy. A blinded randomized study.

Seventeen patients with Graves' ophthalmopathy, all euthyroid for at least one year, were included in a blinded trial to test the effect of acupuncture twice a week during two months on the eye disease, assessed by an ophthalmologist and computed tomography of the eye muscle volume. No significant change was found in eye muscle volume, Hertel measure, palpebral aperture, intraocular pressure, Hess chart, nor was there any statistically significant improvement of the irritative conjunctival symptoms.

Acupuncture Therapy↗
PubMed1990

Improved sensitivity of serum thyrotropin measurements. Studies on serum sex hormone-binding globulin in patients with reduced serum thyrotropin.

Most serum TSH assays have a working sensitivity (i.e. the lowest TSH value with an inter-assay coefficient of variation below 10%) around 0.15-0.4 mU/l, which also is the critical area for cut off for further thyroid profile testing when serum TSH is used as a "first line test". A new assay (BeriLux hTSH) based on chemiluminescence was evaluated, and demonstrated a theoretical sensitivity (mean + 2 SD of the zero standard) of 0.005 mU/l and a working sensitivity as low as 0.04 mU/l. Reference range was 0.18-2.60 mU/l (N = 33). Sixty-eight percent (13/19) of hyperthyroid patients had serum TSH less than 0.005 mU/l, all had serum TSH less than 0.037 mU/l. We studied two groups of patients with normal free T4 and T3 indices but serum TSH less than 0.15 mU/l as measured by an immunoradiometric assay. Thirty-five percent (7/20) of patients with nontoxic goitre and 5% (1/20) of L-T4 treated patients had serum TSH less than 0.005 mU/l; and in 60% (11/20) and 30% (6/20), respectively, the levels overlapped the total range for hyperthyroidism. Serum levels of sex hormone-binding globulin expressed as percent of the reference median for the relevant sex (SHBG%) were elevated in both groups of patients (p less than 0.01). Approximately 50% of those with serum TSH overlapping the hyperthyroid range had serum SHBG% levels above reference range. In conclusion, this assay seems superior to most previously reported assays concerning working sensitivity, but it still leaves us with a group of clinically euthyroid patients who has unmeasurably low serum TSH.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1989

[Hypophyseal hyperthyroidism. Non-tumoral hypersecretion of thyroid stimulating hormone with clinical hyperthyroidism].

A case of hyperthyroidism due to inappropriate TSH secretion in a 45-year-old man is presented. The diagnosis was confirmed by measurement of increased serum TSH values using three different assays, increased T4 and T3 values, the clinical picture, and the effect of anti-thyroid treatment. Nuclear magnetic resonance and computerized tomographic scans of the pituitary fossa showed no abnormalities. Treatment with long-term oral thyrotropin-releasing hormone, oral triiodothyronine, and short-term subcutaneous Sandostatin injections resulted in partial suppression of TSH without however adequate clinical effect. Treatment with thyroxin, bromocriptine, and triiodothyroacetic acid did not alter the parameters. It is concluded, that the inappropriate TSH secretion may be due to a pituitary microadenoma.

Humans↗
PubMed1989

Concentrations of thyroxine, 3,5,3'-triiodothyronine, 3,3',5'-triiodothyronine, 3,3'-diiodothyronine, and 3',5'-diiodothyronine in human red blood cells.

A simple and rapid method for the estimation of cellular concentration of thyroxine (T4), 3,5,3'-triiodothyronine (T3), 3,3',5'-triiodothyronine (rT3), 3,3'-diiodothyronine (3,3'-T2), and 3',5'-diiodothyronine (3',5'-T2) as well as their distribution between cytosol and membranes in human red blood cells (RBC) is presented. Concentrations of iodothyronines in RBC (RBC-T) were calculated by multiplying the total serum concentrations by the ratio of radioactivity in equal volumes of packed RBCs and serum, pre-incubated with 125I-labelled iodothyronines of high specific activity. Plasma and RBC were separated by centrifugation in capillary glass tubes. The separation of membranes and cystosol was performed by hypotone lysis and centrifugation. The median RBC-T of T4, T3, rT3, 3,3'-T2, and 3',5'-T2 from 17 euthyroid subjects were 360 pmol/l, 156 pmol/l, 2.77 pmol/l, 6.81 pmol/l, and 2.17 pmol/l, respectively. The cytosol/cytosol + membrane ration were 66%, 40%, 84%, 77%, and 97%, respectively. The differences in RBC-T were not similar to the differences in free serum concentrations. The ratio of RBC-T to free serum concentration differed considerably between T4 (16.6), T3 (24.4), and 3,3'-T2 (15.5) as compared to rT3 (5.8) and 3',5'-T2 (2.6). Data on three patients with thyroid diseases suggested that RBC-T values were increased in hyperthyroidism and decreased in hypothyroidism, whereas the cytosol/cytosol + membrane-ratio was unaltered.

Adult↗
PubMed1988

Interleukin-1 affects the function of cultured human thyroid cells.

Cytokines are peptide hormones essential for cellular communication in the immune response. The purpose of this study was to investigate the influence of cytokines, especially recombinant interleukin 1 beta (rIL-1 beta), on human thyroid cells. Thyroglobulin (Tg) was measured by a double antibody radioimmunoassay, and cyclic AMP (cAMP) by a competitive protein binding assay. Supernatants from unstimulated and phytohaemagglutinin-stimulated blood mononuclear cells were added to human thyroid cells cultured in monolayers. A dose-dependent inhibition of the secretion of Tg and cAMP was demonstrated. Both subcultured and primary cultured cells incubated with rIL-1 beta at pharmacological levels (10(-1)-10(2) U/ml) exhibited an inhibition of Tg and cAMP secretion, while at physiological levels (10(-5)-10(-3) U/ml), the secretion of Tg was enhanced. The similar stimulation of cAMP was demonstrated in subcultures. These in vitro studies suggest that IL-1 beta may play a role in the pathogenesis of autoimmune thyroid diseases. Further, the stimulations at low concentrations indicate that IL-1 beta may regulate the function of the thyroid gland under physiological conditions.

Autoimmune Diseases↗
PubMed1988

Insulin/C-peptide response to intravenous glucagon. A dose-response study in normal and non-insulin-dependent diabetic subjects.

The C-peptide and insulin secretory responses to increasing doses of iv glucagon (1, 2, 5, 10 micrograms/kg body weight and 1 mg (only diabetics] were investigated in six lean non-insulin-dependent diabetic patients and six normal subjects, matched for body weight and fasting blood glucose concentrations. A well defined relationship between glucagon dose and the C-peptide/insulin response was observed in both groups. The course of the dose-response curves was significantly different in diabetics. The maximal obtainable C-peptide response (E-max) was reduced to 53% of the response in normal subjects (P = 0.037), and the insulin response was reduced to 52% (P = 0.014). E-max was reached in diabetics with only 10 micrograms/kg of glucagon, whereas higher doses seem to be needed in the control group. However, the glucagon dose causing 50% of E-max (ED50) was not significantly higher. Thus, the widely accepted use of 1 mg of glucagon to test residual beta cell function secures a maximal response of both insulin and C-peptide in non-insulin-dependent diabetic subjects. In addition, our data support the theory that beta cell deficiency is a basic feature of non-insulin-dependent diabetes.

Blood Glucose↗
PubMed1987

Increased sympathetic tone in forearm subcutaneous tissue in primary hypothyroidism.

Sympathetic reflex regulation of subcutaneous blood flow (SBF) in the forearm was studied in eight patients with primary hypothyroidism. Diastolic arterial pressure was greater than or equal to 95 mmHg in five patients. SBF was determined by local clearance of Na99mTcO4. Sympathetic vasoconstriction normally seen after lowering the forearm 40 cm below heart level was absent since SBF only decreased by 4% (+/- 7%, P greater than 0.1) during these conditions. In head-up vertical position we noticed a diminished baroreceptor response as SBF at heart level was reduced by 11% (+/- 7%, P greater than 0.1) compared to supine position. After proximal local anaesthesia SBF increased by 351% (+/- 81%, P less than 0.01) and disclosed a normal vasoconstrictor response as SBF was reduced by 53% (+/- 5%, P less than 0.01) during arm lowering. Five of the treated patients were restudied in the euthyroid state. Mean arterial pressure was reduced in mean by 20 mmHg (+/- 6 mmHg, P less than 0.02) during treatment and a significant vasoconstriction was observed both during arm lowering (SBF = -52% (+/- 6%, P less than 0.02)) and in head-up vertical position (SBF = -45% (+/- 11%, P less than 0.02)). In conclusion sympathetic vasoconstrictor activity in adipose tissue is markedly increased in primary hypothyroidism. Sympathetic tone and arterial pressure are reduced during treatment.

Adult↗
PubMed1987

Relationships between serum thyrotropin, serum free thyroxine (T4), and 3,5,3'-triiodothyronine (T3) and the daily T4 and T3 production rates in euthyroid patients with multinodular goiter.

Serum TSH, as measured by a sensitive assay, and serum free T4 and T3, as measured by an ultrafiltration technique, were compared in 14 euthyroid patients with multinodular goiter and 14 normal subjects. T4 and T3 turnover studies also were performed, using the single injection, noncompartmental approach. The goitrous patients had serum free T3 levels within the normal range, but their median serum T3 level was increased compared to that in the normal subjects [goitrous patients, 5.48 pmol/L (range, 4.41-9.03); normal subjects, 4.12 pmol/L (range, 2.58-5.78); P less than 0.01]. The T3 production rate (PR) also was elevated in the patients (median, 39.4 nmol/day X 70 kg; range, 28.7-70.5) compared to that in the normal subjects 31.1 nmol/day X 70 kg; range, 24.4-45.2); P less than 0.05). No differences were found between the two groups with regard to serum free T4 levels or T4 PRs. Serum TSH levels in the patients were reduced (median, 0.20 mU/L; range, less than 0.05-1.6) compared to those in normal subjects (1.8 mU/L; range, 0.36-5.1; P less than 0.01). A significant inverse correlation was found between serum TSH levels and free T3 levels (r = 0.70; P less than 0.001), whereas serum TSH did not correlate with serum free T4 or the PR of T4 or T3. Our data suggest that clinically and biochemically euthyroid patients with multinodular goiter have slight T3 hyperproduction, and TSH secretion in the patients studied was more closely related to serum free T3 levels than to serum free T4 levels or the T3 or T4 PR.

Adult↗