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Biomedical subjects

P A Dahlberg

Publications and source records attributed to P A Dahlberg.

At least 19 recordsLinked to original sources
PubMed1991

Stressful life events and Graves' disease.

The role of stressful life events in the onset of Graves' disease (toxic diffuse goitre) is controversial. However, the numerous early clinical reports that supported such an association were not adequately controlled and specificity of the diagnosis could be questioned. Later studies have not shown a causal relation, but these studies were small, did not have proper controls, or epidemiological methods were inappropriate. To assess possible associations between life events, heredity, social support, and Graves' disease, we have done a population-based case-control study in a defined area with about 1 million inhabitants. Over 2 years, 208 (95%) of 219 eligible patients with newly-diagnosed Graves' disease and 372 (80%) of all selected matched controls answered an identical mailed questionnaire about marital status, occupation, drinking and smoking habits, physical activity, familial occurrence of thyroid disease, life events, social support, and personality. Compared with controls, patients claimed to have had more negative life events in the 12 months preceding the diagnosis, and negative life-event scores were also significantly higher (odds ratio 6.3, 95% confidence interval 2.7-14.7, for the category with the highest negative score). Individuals who had relatives with thyroid disease (especially first-degree and second-degree relatives) were more likely to have Graves' disease (3.6, 2.2-5.9). Slightly more patients than controls were divorced (1.8, 1.0-3.3) and reported a less frequent intake of alcohol (0.4, 0.2-0.8). When results were adjusted for possible confounding factors in multivariate analyses, risk estimates were almost unchanged. These findings indicate that negative life events and hereditary factors may be risk factors for Graves' disease.

Adult↗
PubMed1989

Thyrotropin-secreting pituitary adenomas: clinical and biochemical heterogeneity. Case reports and follow-up of nine patients.

STUDY OBJECTIVE: To evaluate the clinical and biochemical features of patients with TSH (thyroid-stimulating hormone, thyrotropin)-secreting pituitary tumors; to measure the biologic activity in vitro of circulating TSH from selected patients before and after pituitary surgery. DESIGN: Case series. SETTING: Patients in an endocrinology unit. PATIENTS: Nine patients with TSH-secreting pituitary tumors. MEASUREMENTS AND MAIN RESULTS: All patients had hyperthyroidism, elevated free thyroxine and triiodothyronine levels, and detected levels of TSH. The free alpha subunit, a tumor marker for neoplasms of gonadotropic or thyrotropic cell origin, was elevated in all nine patients. Seven of the nine patients had been treated with thionamides, radioactive iodine, or thyroidectomy for presumed primary hyperthyroidism. The delay from the initial treatment of hyperthyroidism to the correct diagnosis of a pituitary neoplasm was 6.2 +/- 4.8 (mean +/- SD) years. Two of the seven patients with macroadenomas died in the perioperative period (one at NIH, one at a referring hospital). Of the remaining five patients with macroadenomas, four have residual tumor and inappropriate TSH secretion, despite surgery and radiation therapy, at follow-up from 3.5 to 6 years. In contrast, the two patients with microadenomas are clinically cured 2.5 and 4 years after transsphenoidal adenomectomy. The biologic to immunologic (B/I) ratio of serum TSH, determined preoperatively in five patients with TSH-secreting tumors, was elevated compared with euthyroid subjects. In three patients the B/I ratio of serum TSH was also measured after pituitary surgery; in two the elevated B/I ratio returned to normal after successful pituitary adenomectomy, while in the third this ratio remained elevated after incomplete adenoma resection. CONCLUSIONS: With the routine availability of ultrasensitive TSH assays and their increasing use to confirm thyrotoxicosis from all causes, we expect that TSH-secreting pituitary tumors will be diagnosed earlier, before inappropriate antithyroid therapy, permitting an improved outcome.

Adenoma↗
PubMed1988

Postpartum thyroiditis.

The special characteristics of postpartum thyroid syndromes are summarized in Table 8. Many of the cases will pass unnoticed, although a higher detection rate is to be expected if postpartum thyroid disease becomes better known among physicians and the general public. Screening in early pregnancy of women with a previous or family history of thyroid disease and in women with other autoimmune disorders (such as diabetes mellitus type 1) may be worthwhile. The initial manifestation of postpartum thyroiditis, often appearing during the first three months postpartum, is a thyrotoxic phase characterized by a low RAIU ('painless thyroiditis' or 'destruction-induced thyrotoxicosis'). Subsequently, a transient hypothyroid phase supervenes. In a small proportion of women hypothyroidism becomes permanent. After a subsequent pregnancy recurrence is the rule. Women who are genetically disposed to Graves' disease may experience thyrotoxicosis with a high RAIU usually appearing later than three months postpartum. As the thyroid function abnormalities are usually mild and transient it is often appropriate to withhold treatment. However, in women with pronounced symptoms treatment should be started. When the postpartum period has passed gradual withdrawal of treatment should be attempted. In women who have experienced postpartum thyroid dysfunction, the risk of developing permanent thyroid disease in later life seems important and therefore long-term follow-up is recommended.

Female↗
PubMed1987

Intrinsic bioactivity of thyrotropin in human serum is inversely correlated with thyroid hormone concentrations. Application of a new bioassay using the FRTL-5 rat thyroid cell strain.

We have developed a new bioassay for thyrotropin (TSH) in human serum to evaluate bioactivity in normal individuals and patients with different degrees of primary hypothyroidism. Unpurified TSH in serum showed no stimulation of cyclic AMP production in cultured FRTL-5 rat thyroid cells, but after immunopurification showed potent stimulatory activity. Immunoaffinity purification permitted up to 400-fold concentration of serum TSH, allowing bioactivity measurements even in certain normal sera. The limit of detection in the FRTL-5 bioassay was 10 microU of human TSH per 0.5 ml incubate, and half-maximal responses for standard human TSH was 102 +/- 26 (+/- SE) microU/0.5 ml. Immunoaffinity-purified serum TSH varied in bioactivity-to-immunoactivity (B/I) ratios from less than 0.25 to 1.21 among four euthyroid subjects and eight primary hypothyroid patients. An inverse correlation was found between B/I ratios of immunopurified basal TSH and the serum-free T4 (r = -0.7237, P less than 0.01), T4 (r = -0.6650, P less than 0.05), and T3 (r = -0.6382, P less than 0.05). B/I ratios of immunopurified TSH from three hypothyroid patients before and after acute stimulation by thyrotropin-releasing hormone showed no significant change, despite major changes in serum TSH. In summary, the present study shows an inverse relationship between the metabolic status of an individual and the intrinsic bioactivity of TSH.

Animals↗
PubMed1987

A sensitive thyrotropin (TSH) bioassay based on iodide uptake in rat FRTL-5 thyroid cells: comparison with the adenosine 3',5'-monophosphate response to human serum TSH and enzymatically deglycosylated bovine and human TSH.

A sensitive in vitro assay based on the uptake of 125I by the FRTL-5 rat thyroid cell line has been applied to the measurement of TSH bioactivity from different sources. In this bioassay various human pituitary reference preparations showed similar potencies; the limit of detection and the half-maximal response were 1.60 +/- 0.1 (+/- SE) and 9.70 +/- 0.40 microU/0.5 ml, respectively; however, when compared to pituitary TSH from other species, human TSH was 29- and 10-fold less biopotent than bovine and rat TSH, respectively. The iodide uptake response to TSH was inhibited by the presence of human serum in a dose-dependent fashion, but pretreatment of serum with 10% polyethylene glycol restored TSH activity. The iodide uptake response was compared to the stimulation of cAMP production in the measurement of serum TSH bioactivity from human samples after immunoaffinity purification. In the cAMP production bioassay, immunoaffinity-purified serum TSH showed increased bioactivity in patients with primary hypothyroidism and TSH-secreting pituitary tumor compared to that in normal subjects, while in the iodide uptake bioassay minimal differences were detected among the different groups. To investigate further structure-function relationships of TSH in FRTL-5 cells we studied the effects of deglycosylated purified pituitary bovine and human TSH on both bioassays. Using two new enzymes, peptide-N-glycosidase and endo-beta-N-acetylglucosaminidase F, we removed one carbohydrate chain from TSH alpha and all three chains from TSH, respectively. In the iodide uptake bioassay both enzymes induced a 2-fold decrease in TSH biopotency, while in the cAMP production bioassay this decrease was only present with peptide-N-glycosidase-treated TSH. In summary, 1) the iodide uptake bioassay system in FRTL-5 cells represents a valid and sensitive method for the measurement of TSH bioactivity from different sources and can be applied to serum samples with elevated TSH concentrations by simple pretreatment with polyethylene glycol without immunoaffinity purification; 2) the enzymatic removal of one carbohydrate chain from both bovine and human TSH significantly decrease their biological activity, assessed as cAMP production and iodide uptake response in FRTL-5 cells, while the removal of three carbohydrate chains induces a significant decrease only in the iodide uptake bioassay: and 3) the disparate results for cAMP and iodide uptake in both human samples and deglycosylated pituitary TSH suggest that in addition to cAMP, other second messengers may play a role in TSH action.

Animals↗
PubMed1987

The postpartum period constitutes an important risk for the development of clinical Graves' disease in young women.

In the present study, 93 consecutive women, 20-40 years of age, referred to our clinic from 1976-85 with Graves' disease, were examined with respect to a possible relation between onset of disease and previous pregnancy. An increased relative risk of 6.5 (3.8-11.0, 95% confidence interval) of developing Graves' disease within one year following delivery was found. After excluding the nulliparous women, almost 2 out of 3 women who developed Graves' disease in the principal child-bearing age of 20-35 years had a postpartum onset, suggesting an important role of immunomodulatory events following delivery for the development of this disease in young women. Future studies will ascertain to which extent the recognition of postpartum Graves' disease has implications on the choice of therapy in this group of women.

Adult↗
PubMed1986

Maternal TSH-receptor antibodies and TSH antibodies in screening for congenital hypothyroidism.

Serum samples from 30 mothers who had given birth to at least one child with a positive neonatal thyrotropin (TSH) screening test were analysed for TSH-receptor antibodies. One mother with hypothyroidism after thyroiditis who had two sons who had had transient congenital hypothyroidism, showed significantly elevated concentrations of TSH receptor blocking IgG antibodies in her serum. The three daughters of another mother had neonatal hyperthyrotropinaemia but normal thyroid hormone levels. This woman had elevated serum levels of TSH but was clinically and biochemically euthyroid. The apparent hyperthyrotropinaemia in this family was due to an artifact in the TSH radioimmunoassay caused by maternal anti-TSH IgG antibodies. It is obvious that placental transfer of maternal IgG antibodies to the thyroid TSH receptor is one cause of transient congenital hypothyroidism. Likewise, maternal IgG directed against TSH interferes with radioimmunoassays of TSH and the results may be falsely interpreted as hyperthyrotropinaemia. It is concluded that in neonatal hyperthyrotropinaemia analysis of the mother's serum is indicated, and that maternal TSH receptor blocking antibodies must be considered as a cause of congenital hypothyroidism, especially if the mother has a history of thyroid dysfunction.

Congenital Hypothyroidism↗
PubMed1985

Thyroxine, methimazole, and thyroid microsomal autoantibody titres in hypothyroid Hashimoto's thyroiditis.

Ten hypothyroid patients with Hashimoto's thyroiditis were treated with methimazole 30 mg in addition to thyroxine 0.15 mg daily. Another 10 hypothyroid patients with Hashimoto's thyroiditis were given thyroxine 0.15 mg alone. After 22 weeks of treatment significant decreases in thyroid microsomal autoantibody titres were observed in both groups (p less than 0.01). There was no difference in the mean change in titre between the two groups. When the patients treated with methimazole were subsequently given thyroxine 0.15 mg alone for a further 22 weeks no additional change in titre was observed. The data suggest that thyroxine, by normalising serum thyroid stimulating hormone concentrations, may reduce the autoantigenic properties of the thyrocytes with a subsequent decrease in autoantibody titres.

Adult↗
PubMed1985

Effect of thiocyanate levels in milk on thyroid function in iodine deficient subjects.

To utilize the antibacterial effect of the lactoperoxidase system to prevent bacterial spoilage of raw milk it is necessary to increase the thiocyanate concentration of the milk. Thiocyanate has, however, a potent antithyroid effect which is enhanced by iodine deficiency. In this study the thyroid function has been studied, before and after 4 weeks daily administration of 250 ml of such treated milk, in 55 goitrous subjects living in an endemic goiter region of western Sudan. The iodine content was 0.1 mg/l and the thiocyanate content was either 3.6 mg/l (n 19) or 19 mg/l (n 36) in the milk. At the start of the experiment all subjects were iodine deficient with a urinary excretion of 40-50 micrograms/g creatinine. After 4 weeks daily intake of 4.75 mg of thiocyanate by way of milk the serum thiocyanate level increased by approximately 1.7 mg/l. Both at the beginning and at the end of the experimental period the serum levels of thyroxine, triiodothyronine and TSH were in the normal range for all subjects. After 4 weeks the TSH levels had decreased significantly, (from 2.6 +/- 0.2 to 2.1 +/- 0.2 mU/l, p less than 0.001) probably as an effect of the supplementary intake of iodine. The thyroid hormone levels remained unchanged during the experimental period. In conclusion, the intake of milk with an iodine concentration of 0.1 mg/l and a thiocyanate concentration of 19 mg/l does not have a negative effect on the thyroid function in iodine deficient subjects.

Adolescent↗
PubMed1985

Influence of the HLA-DR4 antigen and iodine status on the development of autoimmune postpartum thyroiditis.

HLA-A, -B, and -DR antigens were determined in all 50 women with a serum thyroid microsomal hemagglutination antibody (MsAb) titer equal to or greater than 1:100 in the first trimester of pregnancy in a population of 733 pregnant women. The DR4 antigen was found in 58.0% of the women compared to 33.7% in control subjects, which corresponds to a relative risk of 2.71 (P less than 0.01 by X2 test). The MsAb-positive women were examined regularly during the year after delivery for the development of thyroid dysfunction. The DR4 antigen frequency was found to be even higher, 69.0% (relative risk = 4.36; P less than 0.001), among the 29 women who developed hypothyroidism in the postpartum period. No other HLA antigen deviations were found among those 15 hypothyroid women in whom an initial thyrotoxic phase occurred before hypothyroidism. The B8, DR3 haplotype was found in 3 of 5 women who developed Graves' thyrotoxicosis alone. Urinary iodine excretion measured in some MsAb-positive women 3 (n = 19) or 6 months (n = 29) postpartum, respectively, was compatible with leakage of thyroid iodine during the initial destruction-induced thyrotoxic phase of postpartum thyroiditis, followed by low iodine excretion during the subsequent hypothyroid phase. We conclude that genes coding for the DR4 antigen may have a regulatory influence on MsAb production, which in turn affects the development of postpartum hypothyroidism. Thyroid iodine content and iodine intake also may have an impact on the severity of the thyrotoxic and the hypothyroid phases of autoimmune postpartum thyroiditis.

Adult↗
PubMed1985

Thyrotropin-releasing hormone testing during antithyroid drug treatment of Graves' disease as an indicator of remission.

In 74 patients with hyperthyroid Graves' disease, TRH tests were undertaken every third month during the course of a standardized antithyroid drug and T4 treatment program. The antithyroid drug dose was reduced gradually and finally withdrawn when persistently normal TSH responses were obtained. In 46 patients (62%), such normal responses occurred and therapy was discontinued after a mean treatment period of 13 months (range, 5-24 months). In the remaining unresponsive 28 patients (38%), therapy was gradually withdrawn after 2 yr of treatment (mean treatment period, 27 months; range, 25-36 months; P = 0.0001 vs. the other group). The mean overall follow-up period after cessation of treatment was 65 months (range, 32-100 months) and did not differ between the TRH-responsive and TRH-unresponsive group. In the TRH-responsive group, 12 relapses (26%) occurred 23 months (range, 6-45 months) after discontinuation of therapy, in contrast to 20 relapses (71%) after 6 months (range, 0-12 months) in the TRH-unresponsive group. The differences in relapse rates and time duration until relapse are highly significant (P = 0.0003 and P = 0.0001, respectively). Small but significant differences in serum T3 and T4 levels were found between the groups throughout the treatment periods, emphasizing the importance of thyroid hormone levels in regulating the pituitary responsiveness to TRH. It is concluded that regular TRH tests during antithyroid drug treatment are useful in deciding the dose and duration of therapy and in predicting the likelihood of remission.

Adult↗
PubMed1985

The effectiveness of oral iodized oil in the treatment and prophylaxis of endemic goiter.

In a longitudinal study carried out for 2 yr in the Darfur region, western Sudan, 2316 school children received a single dose of 2 capsules of iodized oil (400 mg iodine) orally, and 1161 school children received 1 ml of the same preparation im (475 mg iodine); 2393 school children served as controls. One year after treatment, goiter prevalence was reduced from 67.0% to 36.0% among the children who had received oral iodized oil and from 71.0% to 42.0% in those who received it im. The prevalence in the control group did not change. The prevalences in each group were approximately the same 2 yr after treatment. Urinary iodine excretion increased after treatment and remained significantly higher than the initial value during the trial. In subjects from rural Darfur, serum T4 levels were increased 1 yr after treatment with oral iodized oil (P less than 0.001) and im iodized oil (P less than 0.01), and remained high in the former (P less than 0.05) but not in the latter. This increase was accompanied by reduction of serum T3 and TSH levels. Sialadenitis occurred in 3.7% of the children who received oral iodized oil. Thyroid antibodies were not detected before treatment, but microsomal antibodies were detected in 2 of the 128 subjects studied who received iodized oil orally. Comparable results occurred when oral and im iodized oil were given to 841 individuals covering a wider age range. It is concluded that a single oral dose of iodized oil is effective in the correction of iodine deficiency, reducing the goiter size and preventing the recurrence of goiter for at least 2 yr.

Administration, Oral↗
PubMed1985

Differences in aetiology and thyroid function in endemic goitre between rural and urban areas of the Darfur region of the Sudan.

To investigate further the possible causes of the difference in goitre frequency between the rural and urban areas of Darfur region in the Sudan, urinary iodine excretion (UIE) and thyroid hormone concentrations were measured in 97 goitrous and 31 non-goitrous subjects from rural Darfur, 62 goitrous subjects from urban Darfur and 37 non-goitrous subjects from Khartoum. The mean UIE was equally low in goitrous subjects from rural Darfur (56.2 +/- 43.1 micrograms/g creatinine) and urban Darfur (46.3 +/- 20.7 micrograms/g creatinine) and both values were lower than that in the non-goitrous subjects from Khartoum (83.6 +/- 41.9 micrograms/g creatinine). Subjects from rural Darfur also had lower mean serum thyroxine and higher triiodothyronine and thyroid stimulating hormone levels. The mean serum thiocyanate level of 3.2 mg/l in goitrous subjects from rural Darfur was significantly higher than the values of 1.8 ng/ml in goitrous subjects from urban Darfur (P less than 0.001) and 1.7 mg/l in non-goitrous subjects from Khartoum (P less than 0.001). It is concluded that the additional contribution of goitrogenic factors in rural Darfur induces thyroid anomalies to a greater degree than are most likely caused by the iodine deficiency alone in subjects from urban Darfur.

Adolescent↗
PubMed1985

High muscle lipoprotein lipase activity in thyrotoxic patients.

Serum lipoprotein metabolism was studied in 7 women before and after treatment for thyrotoxicosis. Of the lipoprotein lipids, the triglyceride concentration in the low density lipoproteins (LDL) (P less than 0.01) and the cholesterol concentration in both LDL (P less than 0.01) and the high density lipoproteins (HDL) (P less than 0.05) increased significantly during treatment. These changes were accompanied by increases in apolipoprotein B (P less than 0.01) and A-I (P less than 0.05) concentrations in serum. Muscle lipoprotein lipase activity (LPLA) was increased in the thyrotoxic state by 46% (P less than 0.05) compared with the value after the patients had been rendered euthyroid, but adipose tissue LPLA was only 8% higher (ns) in the former state. The capacity for removal of exogenous fat, as determined by the fractional elimination rate (K2) at an iv fat tolerance test, was 23% higher in the thyrotoxic than in the euthyroid state (ns). It is suggested that the increase in muscle LPLA in the thyrotoxic state may be due to enhanced sensitivity to catecholamines. This may contribute to the increased capacity for plasma triglyceride turnover in thyrotoxicosis.

Adipose Tissue↗