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H Perrild

Publications and source records attributed to H Perrild.

At least 37 records · Page 2Linked to original sources

Comparative study of thyroid function and types of thyroid dysfunction in two areas in Denmark with slightly different iodine status.

OBJECTIVE: The pattern of thyroid dysfunction seems to depend on the iodine status of the population. Prevalence of thyroid dysfunction could be a parameter to consider when evaluating iodine deficiency disorders in a population. DESIGN: Comparative cross-sectional investigation in two regions in Denmark with marginally different iodine excretion. METHODS: A random selection of 4649 participants from the Civil Registration System in Denmark in age groups between 18 and 65 years were examined. Thyroid dysfunction was evaluated from blood samples and questionnaires, and compared with results from ultrasonography. RESULTS: Median iodine excretion was 53 microg/l in Aalborg and 68 microg/l in Copenhagen. Previously diagnosed thyroid dysfunction was found with the same prevalence in the regions. Serum TSH was lower in Aalborg than in Copenhagen (P=0. 003) and declined with age in Aalborg, but not in Copenhagen. Not previously diagnosed hyperthyroidism was found with the same overall prevalence in the regions, but in age >40 years hyperthyroidism was more prevalent in Aalborg (1.3 vs 0.5%, P=0.017). Not previously diagnosed hypothyroidism was found more frequently in Aalborg (0.6 vs 0.2%, P=0.03). Hyperthyroidism was more often associated with macronodular thyroid structure at ultrasound in Aalborg and hypothyroidism was more often associated with patchy thyroid structure in Copenhagen. CONCLUSIONS: Significant differences in thyroid dysfunction were found between the regions with a minor difference in iodine excretion. The findings are in agreement with a higher prevalence of thyroid autonomy among the elderly in the most iodine-deficient region.

Adolescent↗

Prevalence of thyroid peroxidase, thyroglobulin and thyrotropin receptor antibodies in a long-term follow-up of juvenile Graves disease.

OBJECTIVE: To relate the presence of thyroid peroxidase antibodies (TPO ab), thyroglobulin antibodies (Tg ab) and thyrotropin receptor antibodies (TSH-R ab) to the clinical course in a long-term follow-up of patients with juvenile Graves' disease (JGD). DESIGN: Patients with JGD were drawn from a Danish retrospective study and reexamined. RESULTS: A number of 105 patients were reexamined 4-21 years (median 10 years) after diagnosis. Three groups were formed: Gr.1: euthyroid patients with anti-thyroid drug (ATD) cessation more than 12 months before reexamination (n=41). Gr.2: patients still on ATD (n=24). Gr.3: subtotally thyroidectomized patients (n=40). Positive TPO ab titers were found in 75% of the patients. In 13% of the patients the titers were very high: >10,000 U/ml. Positive Tg ab were found in 51%. The prevalence of TPO ab and Tg ab was the lowest in group 3. Stimulating TSH-R ab titers were found in 13%. No patients had blocking TSH-R ab. The prevalence of TSH-R ab was 3% in the euthyroid patients, without surgery performed. 15% in the surgical patients, and 25% in the patients still on ATD. CONCLUSIONS: Many JGD patients were euthyroid at the long-term follow-up in spite of high TPO ab and Tg ab titers. Stimulating TSH-R ab were rare (13%). According to this presence of TPO ab, Tg ab or TSH-R ab does not predict the final outcome of JGD. Further studies are needed.

Adolescent↗

Diagnosis and treatment of the solitary thyroid nodule. Results of a European survey.

BACKGROUND AND OBJECTIVE: The optimum diagnostic and therapeutic strategy for the euthyroid patient with a solitary thyroid nodule is still a matter of debate. The aim was to assess the attitudes towards management of such patients in clinical centres throughout Europe by means of a questionnaire. DESIGN: The questionnaire was circulated to all clinical members of the European Thyroid Association (ETA). A case report was followed by diagnostic investigations and choice of therapy in the index case (a 42-year old woman with a solitary 2 x 3 cm thyroid nodule and no clinical suspicion of malignancy). Eleven variations of the basic case report were proposed in order to evaluate how each alteration would affect management. MATERIAL: 151 members replied to the letter and 110 individuals from 20 countries completed the questionnaire (corresponding to approximately two-thirds of the clinical members of the ETA). They represented clinicians who had diagnosed and treated more than 50 (76%) or less than 50 (24%) patients with nodular thyroid disease within the previous 6 months. RESULTS: Based on the index case, basal serum TSH was the routine choice of 99% and serum T4 and/or free T4 were included by 70% of the respondents. Almost 50% included determination of serum thyroid autoantibodies (TPOab: 47%, Tgab: 26%) and 43% measured serum calcitonin. Thyroid scintigraphy was used by 66% (99mTc: 86%, 123I: 10%, 131I: 4%), ultrasonography (US) by 80% (size: 75%, grey scale: 57%, Doppler: 33%). Scintigraphy in addition to US was used by 58%. Fine-needle aspiration biopsy (FNAB) was routinely used by 99% of the respondents, and performed under US-guidance by 42%. Based on the individually chosen diagnostic tests indicating a benign solitary thyroid nodule, a nonsurgical strategy was advocated by 77%. Despite controversies on L-T4 treatment this treatment was supported by more than 40% of the clinicians. Surgery was advocated by 23% and the preferred technique was hemithyroidectomy (70%). Clinical factors raising suspicion of thyroid malignancy (e.g. family history of thyroid cancer, history of external radiation, rapid nodule growth and a large nodule of 5 cm) lead the majority (70-91%; P < 0.000001) to disregard FNAB results and to choose a surgical strategy. CONCLUSIONS: The favoured diagnostic strategy in the workup of patients with a solitary thyroid nodule include determinations of serum TSH combined with serum T4 and/or free T4 followed by FNAB and US together with scintigraphy. A nonsurgical strategy was favoured by the majority supporting the use of L-T4 as the first choice. In case of clinical factors raising the likelihood of malignancy, the majority recommended diagnostic thyroidectomy despite FNAB suggesting a benign condition.

Adult↗

The prevalence of thyroid dysfunction in a population with borderline iodine deficiency.

OBJECTIVE: We lack information on the influence of borderline iodine deficiency on the occurrence of thyroid dysfunction. Iodine deficiency has been reported to facilitate the development of toxic nodular goitre, whereas a high iodine intake may increase the prevalence of autoimmune hypothyroidism. SUBJECTS AND METHODS: In a cross-sectional study of a random sample of the general population in our region with borderline iodine deficiency 2656 (65%) of 4073 men and women aged 41 to 71 years participated. Records were made of previous thyroidal illness. Blood samples were drawn for thyroid parameters and TPO Ab values. Iodine and creatinine was assessed in casual urine samples. RESULTS: Previous or present hyperthyroidism was reported by 1.4% of the participants whereas 0.6% had unknown biochemical hyperthyroidism. All cases of undiagnosed hyperthyroidism were among women. Previously diagnosed and treated hypothyroidism was reported by 1.0% and undiagnosed hypothyroidism was found in 0.4%. Subclinical hyperthyroidism was found in 1.3% and subclinical hypothyroidism in 0.7%. TPO Ab titres >200 kU/l were found in 16.9% of the women and 6.6% of the men, and 83% of participants with TSH >5 mU/l had TPO Ab titres >200 kU/l. Participants with TPO Ab titres between 100 and 200 kU/l had no increased frequency of thyroid dysfunction. The median iodine excretion rate was estimated as 103 microg/day. Serum TSH values were higher in women than in men and showed higher dispersion in women as well as in old age. Serum free T3 was found to be higher in women than in men and increased with age. Serum free T4 showed no sex difference but values increased with increasing age. CONCLUSION: In our region with borderline iodine deficiency more than 5% of the general population has clinical or subclinical thyroid dysfunction. We found a relatively high prevalence of hyperthyroidism, especially previously undiagnosed disease, but a low prevalence of hypothyroidism as would be expected in an area of iodine deficiency. Hypothyroidism was related to TPO Ab titres of >200 kU/l. Thyroid hormone levels varied with age and sex.

Adult↗

Validation of ultrasonography of the thyroid gland for epidemiological purposes.

Ultrasonography of the thyroid is often used in epidemiological surveys, thus thorough characterization of the interobserver variation of the different parameters obtained is important. Various methods have been used for measuring thyroid volume, and different formulas have been used for calculation of thyroid volume from the measured dimensions. In this article, two principles of thyroid volume measurement are described in detail: the wellknown method based on the three axes of each lobe and a new principle based on planimetry in two planes. The interobserver variation of the examination and the measuring procedure in itself were tested on 25 participants in a population study. A comparison of postmortem ultrasonography of the thyroid and results of an autopsy was performed. Good correlation and agreement between observers was found for thyroid volume (r = 0.98) and prevalence of thyroid nodules (kappa = 0.72), whereas echogenecity and echopattern showed little agreement. The correlation of thyroid volume by ultrasonography to autopsy results was satisfactory (r = 0.93), but the volume tended to be slightly underestimated even when using the formula pi/6(= 0.52)*length*width*depth. No major differences were found between the performance of the two principles of volume calculation. We conclude that when the measuring procedure is well defined, results of ultrasonography are comparable between observers for thyroid volume and prevalence of thyroid nodules, but not for echogenecity or echopattern. The formula of length*depth*width*pi/6 is suitable for thyroid volume measurement.

Adolescent↗

Long-term follow-Up of an infant with thyrotoxicosis due to germline mutation of the TSH receptor gene (Met453Thr).

UNLABELLED: A 18-year clinical follow-up period in a male patient with a germline TSH-R gene mutation (Met453Thr) is described. Nonautoimmune thyrotoxicosis was diagnosed at the age of 7 months. The patient had exophthalmus, failure to thrive, advanced bone age and no goiter. Long-term antithyroid drug treatment (ATD) was necessary during childhood. At the age of 7 years he developed a goiter. Subtotal thyroidectomy was performed at the age of 9 years, followed by repeated ablative radiotherapy at the age of 9.5-13 years due to a toxic multinodular goiter. After 13 years ATD could be discontinued and the patient was euthyroid until 16 years of age, where L-thyroxine substitution had to be started. The exophthalmus diminished, and had disappeared at the age of 18 years, when CT scan of the orbit was performed. CONCLUSION: TSH-R mutation must be considered in early nonautoimmune thyrotoxicosis. A very aggressive treatment strategy is necessary.

Amino Acid Substitution↗

Cancer risk in individuals with benign thyroid disorders.

The risk of cancer was examined in a cohort of 57,326 individuals who were discharged from a Danish hospital with a diagnosis of myxedema, thyrotoxicosis, or goiter. Although the general risk of cancer was only slightly increased, the risk of several sites was significantly above expected. The risk of thyroid cancer especially, was increased with standardized incidence ratios among women of 2.1 (myxedema), 2.5 (thyrotoxicosis), and 6.6 (nontoxic goiter). The increase in risk was present even many years after discharge, indicating that surveillance was not the only explanation. Furthermore, an increased risk was noted for cancer of the kidney in women discharged with myxedema (standardized incidence ratios [SIR] = 1.8) and thyrotoxicosis (SIR = 1.3), for cancer of the bladder in women discharged with myxedema (SIR = 1.5) and nontoxic goiter (SIR = 1.3), and for cancer of the hematopoetic system in women discharged with myxedema (SIR = 1.4) and nontoxic goiter (SIR = 1.4). The findings indicate that thyroid disorders may be related to cancer risk of several specific sites other than the thyroid.

Adolescent↗

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↗

Clinical aspects and treatment of juvenile Graves' disease.

Thyrotoxicosis in childhood and adolescence is a rare disease most frequently due to Graves' disease, but non-autoimmune adenomatous goiters are also found. A strong correlation to HLA class II DRB1*0301 and a protective role of DRB1*0701 has been established in juvenile Graves' disease. The natural course of the disease seem to be remission in many, if enough observation time is allowed. Apart from goiter size and the severity of disease at onset, no certain prognostic factors has yet been identified. The treatment modality chosen is not evidence based, but rather tradition, personal experience and pragmatic handling of cases. Prospective, multicenter studies are still in need to answer the questions asked to ensure rational guidelines and consensus. Such studies should also address the essential problem of compliance, one of the important issues in longterm medical treatment.

Adolescent↗

HLA class II associations in juvenile Graves' disease: indication of a strong protective role of the DRB1*0701,DQA1*0201 haplotype.

Previous studies have shown that HLA-DRB1*0301 and DQA1*0501 are associated with susceptibility to Graves' disease. Ninety Danish patients with early onset of Graves' disease and 102-192 controls were analyzed for HLA-DR and -DQ to investigate if the same associations exist in the juvenile form of Graves' disease. Both DRB1*0301 and DQA1*0501 were highly significantly increased in the patients with relative risks of 8.0 and 4.6, which are higher than those seen in adults. Stratification showed that DRB1*0301 is more strongly associated than DQA1*0501. Surprisingly, the DRB1*0701,DQA1*0201 haplotype was completely absent from this group of patients, indicating a strong protective role of this haplotype in juvenile Graves' disease.

Adolescent↗

Human thyroid epithelial cells cultured in monolayers. I. Decreased thyroglobulin and cAMP response to TSH in 12-week-old secondary and tertiary cultures.

An in vitro system of secondary and tertiary cultures of human thyroid epithelial cells (TFECs) in monolayer is described. The function of the cells was evaluated by the second messenger cAMP and the end product thyroglobulin (Tg). The Tg production from the cells was measured in the supernatant by a newly developed enzyme-linked immunosorbent assay. The TFECs in secondary monolayer cultures had preserved the ability to produce Tg and cAMP despite lack of polarization. Furthermore, a preserved ability of TSH-stimulated production of Tg and cAMP in 12-week-old secondary and tertiary cultures was found. However, the Tg and cAMP levels decreased gradually with the age of the cultures. In the secondary culture the TSH-stimulated Tg production decreased from 253 ng/micrograms DNA (205-263) after 3 weeks to 18 ng/micrograms DNA (6-81), P < 0.001, n = 6 after 12 weeks and TSH-stimulated cAMP production from 660 pmol/micrograms DNA (500-840) to 60 (40-200), P < 0.001, n = 6. The decreased responsiveness of long-term cultures results in preference of short-term secondary cultures, which provide a more suitable experimental model for in vitro investigation of human thyroid cell functions.

Cells, Cultured↗

Human thyroid epithelial cells cultured in monolayers. II. Influence of serum on thyroglobulin and cAMP production.

An in vitro system of secondary cultures of human thyroid follicular epithelial cells in monolayer is described. The 72-h influence of serum and six supplements (thyrotropin, insulin, somatostatin, transferrin, hydrocortisone, glycyl-histidyl-lysine acetate) on growth and function in presence of 3-isobutyl-L-methyl-xanthine (IBMX) was investigated. The function of the cells was evaluated by production of the second messenger adenylate cyclase (cAMP) and the end product thyroglobulin (Tg). Growth was measured as the 3H-thymidine uptake of the cells. Three days of TSH-depletion preceeded the experiments. In presence of IBMX TSH stimulated cAMP production, while stimulation of Tg was only present in some cultures. In absence of IBMX TSH always stimulated the Tg production. The stimulation was independent of the presence of the other five investigated nutritional factors in physiological concentrations. TSH in concentrations from 0.1-10 U/1 stimulated the 72ih 3H-thymidine uptake of the cells. The TSH-stimulated production of Tg and cAMP decreased significantly with increasing concentrations of fetal calf serum (0-10%), (tau = 0.49, P < 0.001, n = 6-29 and tau = 0.75, P < 0.001, n = 6-29, respectively). Thus, serum as a complex, variable and not fully characterized mixture of hormones and growth factors was crucial to the attachment of the cells to the substrate, but inhibited differentiated functions of the human thyroid cells.

1-Methyl-3-isobutylxanthine↗

Microfluorometric kinetic analysis of cathepsin B activity in single human thyroid follicular epithelial cells using image analysis and continuous monitoring.

The activity of a cysteine proteinase, cathepsin B (EC 3.4.22.1), was determined in unfixed single human thyroid follicular epithelial cells at room temperature using an image analysis system. The formation of the reaction product was monitored every minute by measuring the increasing fluorescence intensity of emitted light from a Schiff-base product formed by the substrate N-CBZ-ala-arg-arg-4-methoxy-2-naphthylamide and the coupling agent 5-nitrosalicylaldehyde. Non-specific fluorescent signals were eliminated by adjusting the video signal to zero using leupeptin, a specific inhibitor of cathepsins B, H and L. The enzyme activity was expressed as fluorescence intensity versus time. After a mean lag period of 5 min (range 4-8 min, n = 4), the enzyme activity increased linearly lasting on average 5 min (range 3-8 min), followed by a marked decrease in reaction rate for 3 min (range 1-4 min), and another linear increase for 11 min (range 8-14 min). The second linear part of the curve was not as steep as the first one. The reaction velocity recorded in individual granules resulted either in a biphasic curve or straight line, suggesting the presence of two distinct organelle compartments with differences in membrane permeability. It is concluded that human thyroid follicular epithelial cells in culture exhibit cathepsin B activity which can be monitored continuously by videomicrofluorometry without interference from non-specific fluorescence.

Cathepsin B↗

Immunocytochemical localisation of tumor necrosis factor alpha in thyroid tissues from patients with neoplastic or autoimmune thyroid disorders.

It is disputed to what extent tumor necrosis factor-alpha is present in the thyroid follicular epithelial cells and/or in the interstitial cells in different disorders of the thyroid gland. We describe the immunohistochemical detection of tumor necrosis factor-alpha using formaldehyde fixed and paraffin embedded tissue and a polyclonal anti-serum with high tumor necrosis factor-alpha neutralising activity. We examined the distribution of tumor necrosis factor-alpha in interstitial cells and follicular epithelial cells in thyroid carcinomas, adenomas, non-toxic multinodular goiters and autoimmune thyroid diseases. Tumor necrosis factor-alpha was demonstrated in thyroid follicular epithelial cells, most frequently in non-toxic multinodular goiters (six of seven patients) and less frequently in adenomas (three of nine patients), papillary carcinomas (two of five patients), follicular carcinomas (one of five patients), Hashimoto's disease (one of six patients) and Grave's disease (one of seven patients). Tumor necrosis factor-alpha producing interstitial cells were found in two thirds of patients with all six thyroid diseases.

Adenocarcinoma, Follicular↗

Iodine. Do we need an enrichment program in Denmark?

A working group was established to evaluate the need for iodine enrichment in Denmark. Judged from studies of urinary iodine excretion and one dietary survey the intake of iodine in Denmark is low compared with recommended intakes. The occurrence of non-toxic goitre is relatively high; between 9 and 13% in elderly women. Furthermore, a high occurrence of toxic goitre has been seen in the western part of Denmark. On the other hand, an increased or a high intake of iodine may lead to hyperthyroidism and thyroiditis. The working group concluded that an increase in iodine intake in the Danish population is needed and the best way to achieve this is to iodize all salt. To avoid side effects of a sudden large increase in iodine intake the initial amount of iodine in salt will only be 2 ppm.

Animals↗

[Reduced frequency of amputation in diabetic patients].

The number of major amputations performed for vascular disease in Bispebjerbx Hospital, Copenhagen, has decreased from 122 to 29 per year during the period 1981 to 1994. In diabetic patients the frequency decreased from 25.5/100,000 to 5.5/100,000, i.e. a reduction of 78 percent, and in non diabetics it decreased from 42.2/100,000 to 14.6/100,000, i.e. a reduction of 65 percent. During the period vascular surgery has become a surgical specialty (1983), bypass to infra-popliteal arteries (from 1988) and graft surveillance by colour duplex scanning (from 1983) has become routine and in 1993 a diabetic foot center was established. Initial experience with a diabetic foot center in a vascular surgery unit is reported.

Adult↗

Immunocytochemical localisation of interleukin-1 alpha and interleukin-6 in thyroid tissues from patients with neoplastic or autoimmune thyroid disorders.

We describe the distribution of interleukin-6 and interleukin-1 alpha in thyroid tissues obtained from patients with autoimmune diseases or neoplastic thyroid disorders employing immunohistochemistry in sections from paraffin embedded tissue blocks. Interleukin-6 was found in thyroid follicular epithelial cells (TFEC) from papillary carcinomas (four of five patients) but not in follicular carcinomas (five patients). Interleukin-6 was also detected in non-toxic multinodular goiters (four of seven patients), in patients with Graves' disease who did not have an early recurrence of hyperthyroidism after surgery (three of four patients), in follicular adenomas (five of nine patients), in Hashimoto's thyroiditis (two out of six patients, both belonging to a group of three with an early stage of the disease), and in paraadenomatous tissues (in three of nine patients). Interleukin-1 alpha positive TFEC were found less frequently than interleukin-6, and only in tissues with interleukin-6 positive TFEC. Only few interleukin-6 and interleukin-1 alpha positive interstitial cells were found, even in the lymphocyte infiltrates (in both the autoimmune, benign or malignant disorders). In conclusion, both interleukin-6 and interleukin-1 alpha could be demonstrated in TFEC from patients with autoimmune diseases, benign neoplasms or papillary carcinoma, whereas follicular cancer tissues were without interleukin-6 and interleukin-1 alpha. In contrast with previous studies, interleukin-6 and interleukin-1 alpha were demonstrated in TFEC from patients with both Graves' disease and Hashimoto's thyroiditis, and the presence of these cytokines was related to the stage of the autoimmune process.

Adenoma↗