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Lipid and lipoprotein pattern in thyroid dysfunction and the effect of therapy.

Lipid and lipoprotein concentrations were studied in 12 hypothyroid and 11 hyperthyroid female subjects, both before and after therapy, and in 27 age matched female controls. Recognized clinical and laboratory criteria established the diagnosis. Lipoproteins, including the sub-fractions of the high density lipoproteins (HDL), were isolated by preparative ultracentrifugation, and the cholesterol (c) and protein (p) contents of each were determined. Total cholesterol, and in particular HDL-c, were elevated in the hypothyroid patients. The low density lipoprotein (LDL) -c/HDL-c ratio was 1.9 in this group, compared to 2.2 in the control group and 1.35 in the hyperthyroid patients. The HDL-2/HDL-3 ratio in the hypothyroid group was 3.75, as compared to 1.75 in the controls and 4.2 in the hyperthyroid group. Plasma triglycerides were moderately elevated in the hypothyroid patients and were significantly reduced in the hyperthyroid group. Total cholesterol was significantly lower in the hyperthyroid group as compared to the control group. Very low density (VLDL) cholesterol and protein were significantly increased and LDL and HDL cholesterol were reduced in the hyperthyroid patients. On rendering the patients euthyroid, most of these changes were reversed. Thyroid function profoundly affects lipoprotein concentration and composition. The change in the plasma HDL concentrations of the hypothyroid group questions the relationship of this group to arteriosclerosis. Therapy partially corrects the abnormalities, but complete correction may be related to duration of therapy.

Adolescent↗

Abnormal proinsulin levels in thyroid dysfunction measured by a sensitive proinsulin immunochemiluminoassay.

Abnormalities of carbohydrate metabolism in hyperthyroid patients have been long noted. Elevated proinsulin level is considered as an early marker of B-cell impairment. Proinsulin levels in hyperthyroid patients decreased after antithyroid drug therapy. However, proinsulin in hypothyroid patients was only rarely reported, and the difference was only demonstrated after glucose stimulation-there was a greater response of proinsulin secretion after thyroxine therapy-and the basal fasting proinsulin level was not different after therapy. One of the reasons might be that the assay was not sensitive enough to detect the change of basal proinsulin levels in patients with hypothyroidism after therapy. A newly developed immunochemiluminometric assay of proinsulin was used to demonstrate that the suppressed proinsulin level increased after thyroxine therapy in hypothyroid patients (4.2 +/- 2.4 vs. 10.0 +/- 5.6 pmol/L, p < 0.05; n = 7). On the other hand, our study also confirmed that the proinsulin levels decreased in hyperthyroid patients after antithyroid therapy by methimazole (27.8 +/- 26.0 vs. 15.8 +/- 15.7 pmol/L, p < 0.05; n = 12). In conclusion, proinsulin increased in hypothyroid patients after thyroxine therapy and decreased in hyperthyroid patients after methimazole therapy. The results demonstrated there is a high correlation between thyroid function and B-cell function in hypothyroid as well as hyperthyroid patients.

Adult↗

Risk factors and long-term course of thyroid dysfunction during antiviral treatments in 221 patients with chronic hepatitis C.

AIM: To identify the predictive factors of dysthyroidism during treatment for chronic viral hepatitis C and to evaluate the long-term outcome of these patients. METHODS: Patients treated for chronic viral hepatitis C between 1990 and 2001 were analyzed retrospectively. Patients with dysthyroidism before treatment and patients positive for hepatitis B surface antigen or human immunodeficiency virus antibodies were excluded. Dysthyroidism was defined by an abnormal serum TSH level on two separate occasions. RESULTS: 221 consecutive patients were included. Among them, a hundred were treated twice by interferon alpha, 21 had 3 treatments and 3 had 4 treatments. Fifteen of these patients (7%) had dysthyroidism during antiviral therapy. There was no significant difference in the frequency of dysthyroidism during the first and the second treatment [respectively 4,1% (N = 9) and 6% (N = 6)]. Female gender and the presence of antimicrosome or antithyroperoxydase (anti-TPO) antibodies before antiviral treatment were predictive factors of dysthyroidism. Treatment by interferon and ribavirin did not increase the risk of dysthyroidism compared to monotherapy with interferon. Pegylated interferon (N = 49) was not a risk factor compared to standard interferon. Thirteen patients had hypothyroidism (2 of them as a result of biphasic thyroiditis) and 2 had hyperthyroidism. The antiviral treatment was continued in 11 patients. Seven out of 13 patients with hypothyroidism required an indefinite treatment (follow-up: 15 to 90 months). CONCLUSIONS: In our series, 7% of patients with chronic viral hepatitis C had a dysthyroidism during antiviral therapy. Predictive factors were female gender and positive antimicrosome or anti-TPO antibodies before treatment. Absence of dysthyroidism during a first antiviral treatment did not preclude from the risk of dysthyroidism during a second treatment.

Adult↗

[Clinical studies on assay for Na-K ATPase in human blood cells. I. Erythrocyte Na-K ATPase assay in patients with thyroid dysfunction and in those with chronic renal failure].

A number of erythrocyte Na-K ATPase units were measured in 22 patients with hyperthyroid Graves' disease, 3 with primary hypothyroidism, 3 with simple obesity, 13 with chronic renal failure on hemodialysis, and 20 normal controls, using ouabain binding assay as described by DeLuise et al. The number of Na-K ATPase units, derived by maximal binding of 3H-ouabain, was decreased in patients with simple obesity (Mean +/- SD, 0.26 +/- 0.07 pmol/10(9) RBC), as compared with that in normal controls (0.39 +/- 0.10), and a significant negative correlation between the number of the binding sites and the ratio of the measured body weight to the optimal body weight calculated by the modified Broca's method was observed in normal controls and patients with obesity (r = -0.51, p less than 0.05). The results agreed closely with that reported by DeLuise et al and provided validation of our estimates of the erythrocyte Na-K pump units. The maximal 3H-ouabain binding was significantly diminished in patients with hyperthyroid Graves' disease (0.28 +/- 0.07) when compared with that in normal controls, while the bindings were significantly elevated in patients with hypothyroidism (0.91 +/- 0.26). These results were in disagreement with those previously reported by animal studies where Na-K ATPase was found to be stimulated by thyroid hormones. It might be possible to partly explain this discrepancy by the degradation of Na-K ATPase in erythrocytes in addition to the apparent differences between erythrocytes and the other tissues and by the length of time that the tissue was exposed to the action of the hormones. Therefore, erythrocyte from normal controls and patients with hyperthyroid Graves' disease were divided into low and high density portions by a discontinuous 'percoll' density gradient centrifugation, and the bindings of the erythrocytes in two portions were separately measured. The bindings of erythrocyte in the higher density portion, representing relatively old-aged erythrocyte, were diminished to 92 +/- 19% of the bindings of the original whole erythrocytes in normal controls. An even more marked reduction of the maximal bindings of 3H-ouabain in old-aged erythrocytes was observed in patients with hyperthyroid Graves' disease (72 +/- 26%). Moreover, this % reduction based on aging related significantly to serum T4 concentrations in those patients (r = 0.85, p less than 0.05). These findings suggest that the number of erythrocyte Na-K ATPase units may reflect the overall peripheral metabolic state, regulated by thyroid hormone-dependent thermogenesis.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗

A histomorphometric study of bone changes in thyroid dysfunction in rats.

Clinical studies in thyrotoxicosis reveal a state of high bone turnover leading, eventually, to osteoporosis. Recently there has been concern that thyroxine (T4) treatment may have a similar effect on bone. Rat models have been used to study the effects of T4 on bone, but the majority of studies have looked at the effects of T4 after only 3 weeks of treatment. The aim of this study was to evaluate histomorphometric changes in rats after 12 weeks of thyroxine overtreatment or 12 weeks of hypothyroidism compared with untreated control animals. Animals received either T4 200 micrograms/kg per day, 0.1% propylthiouracil, or vehicle for 12 weeks. Tetracycline was administered 1 week and 3 weeks prior to killing. Iliac crest bone was used for histomorphometry. Serum T4 measurements (taken at killing) confirmed hyper- and hypothyroidism in the appropriate animal groups (between group difference p < 0.001 by ANOVA). In hyperthyroid animals there was an increase in mineral apposition rate (MAR; 0.94 vs. 0.59 microns/day, p < 0.001) and mineral formation rate (MFR/BS; 0.24 vs. 0.12 x 10(-2) micron3/micron2 per day, p < 0.001) and a slight increase in eroded surfaces (ES/BS%; 1.54 vs. 1.36, p < 0.05) compared with controls, consistent with previous in vitro and in vivo observations. In hypothyroid rats there was a marked reduction in osteoid surfaces (OS/BS%; 1.7 vs. 24.8, p < 0.001) and MAR (0.3 vs. 0.59 micrograms/day, p < 0.001), a reduction in ES/BS% (0.51 vs. 1.36, p < 0.05), and an increase in cancellous bone volume (BV/TV%; 30.29 vs. 19.6, p < 0.05), suggesting that thyroid hormones are a requirement for normal bone turnover.(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of Variance↗

Clinical evidence for thyroid dysfunction in patients with seasonal affective disorder.

Of 49 consecutive patients over a 21-mo period satisfying conservative criteria for seasonal affective disorder (SAD), a well-characterized syndrome involving seasonal neurovegetative dysregulation, 17 (35%) were found to have elevated serum TSH compatible with mild primary hypothyroidism (TSH > 4.6 microIU/ml). An additional eight patients (16%) met criteria for "conjectural" hypothyroidism (TSH > 3.5 microIU/ml or exaggerated TSH response to TRH). The frequency of cases with supranormal TSH within the SAD group, both with and without inclusion of the "conjectural" cases, proved statistically significant when compared to that within psychiatric patients not satisfying criteria for SAD (N = 381) or to that within the population at large. The author suggests that SAD may in part represent a reformulation in modern neuropsychiatric terms of a previously noted fall-winter decrement, both biochemical and clinical, among hypothyroid patients.

Female↗

Amiodarone-Induced thyroid dysfunction and ventricular tachyarrhythmias during long-term therapy in Japan.

In 232 Japanese patients receiving long-term amiodarone therapy for life-threatening ventricular tachyarrhythmias, hyperthyroidism and hypothyroidism developed in 29 patients (12.5%) and 25 patients (10.8%), respectively. In patients with hyperthyroidism, the recurrence of sustained ventricular tachycardia was significantly higher with thyrotoxicosis than in the euthyroid period (31% vs 3%, p<0.01). Holter monitoring showed that the average heart rate and ventricular premature complexes significantly increased with hyperthyroidism. On the other hand, there was no increase in the recurrence of ventricular tachyarrhythmia with hypothyroidism. There was no change in the dose or the plasma concentration of amiodarone or desethylamiodarone in the euthyroid period or when hyperthyroidism or hypothyroidism manifested. It is important to monitor for arrhythmia when hyperthyroidism develops during amiodarone therapy.

Adult↗

Thyroid dysfunction in newborns and infants living in an iodine-deficient area.

The region of Southern Poland is known as an iodine-deficient area. Iodine prophylaxis was discontinued in 1980/81. This fact was discovered as a result of the introduction of newborn mass screening for congenital hypothyroidism in 1985. In view of the large number of newly detected cases of Iodine Deficiency Disorders (IDD), we compared the neonatal populations of the Cracow and Nowy Sacz provinces. The prevalence of IDD was revealed as eight times higher in Nowy Sacz than in Cracow. The iodine urine excretion rates in those two provinces were similar. The paper discusses the cause of the discrepancy in IDD incidence. The final results show that the iodine deficiency detected in the Cracow and Nowy Sacz provinces is of moderate degree. Salt iodination in the region of southern Poland needs a new approach even before the year 2000, as planned in the WHO program.

Adolescent↗

Binding of plasma fibronectin to human polymorphonuclear leukocytes in normal subjects and patients with aplastic anemia and thyroid dysfunction.

The binding of iodine 125-labeled fibronectin to polymorphonuclear leukocytes (PMNs) from human peripheral blood was examined. The optimum temperature and time for the binding were 37 degrees C and 30 minutes, respectively. On increase in the amount of 125I-labeled fibronectin, its binding to PMNs became saturated. Scatchard analysis of data on binding indicated the presence of a single class of binding sites. PMNs from 15 normal subjects had approximately 6.3 +/- 1.6 x 10(3) sites per cell and a dissociation constant of 10.2 +/- 2.4 x 10(-9) mol/L, indicating that they had high affinity for soluble fibronectin. Arg-Gly-Asp-Ser inhibited the binding of fibronectin to PMNs, strongly suggesting that the fibronectin receptor is one of the Arg-Gly-Asp receptor family. The plasma level of fibronectin was higher in patients with hyperthyroidism and lower in patients with hypothyroidism than in normal subjects, without any significant change in the number of fibronectin binding sites of the PMNs. However, the number of binding sites of fibronectin on PMNs of patients with aplastic anemia was increased, probably because of sensitization of the PMNs with immune complex and other factors.

Anemia, Aplastic↗

[Thyroid dysfunction and goiter among immigrants from Ethiopia].

1131 immigrants from Gonder, Ethiopia were surveyed a year after arrival in Israel. The overall prevalence of goiter was 46.1%; the lowest rates (6.7%) were in infants (aged 1-2 years) and the peak prevalence in males was 56.7% (in those aged 12-14 years) and in females, 77.7% (in those aged 35-40). A significant decrease in goiter prevalence was observed after the age of 60 for both men (7.2%) and women (35%). The prevalence of hypothyroidism was 1.1%, 2% in children and 0.2% in adults. That of hyperthyroidism was 1.7%, 0.8% in children and 2.4% in adults. The high prevalence of goiter and hyperthyroidism with low prevalence of hypothyroidism probably resulted from the combined effects of food goitrogens and iodine deficiency in Ethiopia, with the latter playing only a minor role. Neither factor was in effect after arrival in Israel. Genetic and hormonal factors may contribute to the low prevalence of both goiter and hypothyroidism in the adult males. In view of the high prevalence of hyperthyroidism, iodine enrichment is not recommended for Ethiopian immigrants.

Adolescent↗

New ultrafiltration method for free thyroxin compared with equilibrium dialysis in patients with thyroid dysfunction and nonthyroidal illness.

This new ultrafiltration method for free thyroxin in serum [FT4(U)] is based on radioimmunoassay of the free hormone fraction in ultrafiltrates obtained by centrifuging serum samples in Unisep Ultracent-10 ultrafiltration devices. We compared the results obtained with those by an equilibrium dialysis method [FT4(D)]. In 36 euthyroid healthy subjects, the mean FT4(U) concentration was 24.2 pmol/L and the mean FT4(D) concentration 14.8 pmol/L. In hyperthyroid and hypothyroid patients, results by the ultrafiltration method were also approximately twice as high as those obtained by the dialysis method. In 23 patients with various nonthyroidal illnesses, mean FT4(U) was 41.2 pmol/L and mean FT4(D) 19.8 pmol/L. The mean FT4(U)/FT4(D) ratio in patients with nonthyroidal illnesses (1.97) was not significantly higher than in control subjects (1.68), making it unlikely that the increase in serum FT4 is caused by weakly protein-bound and therefore dialyzable inhibitors of thyroxin binding to carrier proteins. However, two nonthyroidally ill patients with a clearly increased FT4(U) but a normal FT4(D) concentration might have had such inhibitors, whereas for two other nonthyroidally ill patients a high molar ratio of free fatty acids to albumin is a more likely explanation for increased FT4(U) and FT4(D) concentrations. On theoretical grounds, we consider the FT4(U) concentrations analytically more nearly accurate than FT4(D) values for all patient groups studied.

Adult↗

Serum cytokines and bone metabolism in patients with thyroid dysfunction.

Hyperthyroidism is associated with increased bone turnover. Besides the hormones of calcium metabolism, locally produced factors are important in maintaining normal bone metabolism. Interleukin-6 (IL-6), in particular, has a major influence on bone turnover. In this study, serum IL-6 and tumor necrosis factor-alpha (TNF-alpha) levels, as well as bone turnover markers and relationships between them, were investigated in hyperthyroidism and hypothyroidism. A total of 20 female patients with hyperthyroidism, 15 with subclinical hyperthyroidism, 16 with hypothyroidism, and 15 with subclinical hypothyroidism constituted the patient groups. In all, 15 age-matched healthy female volunteers were recruited as controls. When compared with controls, serum TNF-alpha levels showed no significant difference in any of the patient groups (P>.05). In the groups with hyperthyroidism and subclinical hyperthyroidism, IL-6 levels were significantly higher compared with control group values (P<.05). Hyperthyroid patients showed higher levels of alkaline phosphatase (ALP) and osteocalcin, and a higher urinary deoxypyridinoline/creatinine ratio, compared with controls (P<.05). In subclinical hyperthyroidism, only ALP was found to be higher compared with control values. No significant correlations were made in any group between serum IL-6 or TNF-alpha level and bone turnover markers. Results suggest that serum IL-6 level and markers of bone turnover rate seem to be increased in hyperthyroidism. This finding may support the role of IL-6 in induction of bone turnover in hyperthyroid states.

Biomarkers↗

Effect of thyroid dysfunction upon phospholipid composition and CDP-choline incorporation in mitochondria and microsomal fraction isolated from liver and brain of suckling rats.

The phospholipid composition and the in vitro incorporation of radioactive CDP-choline into phosphatidylcholine was studied in mitochondria and microsomal fraction obtained from liver and brain of 20 day old hyperthyroid or hypothyroid rats. The chemical composition of the subcellular membranes isolated from brain differed markedly in both conditions. In hyperthyroidism the microsomal fraction was slightly affected while the mitochondria were also affected, but not as severely as in hypothyroidism, in which the microsomal fraction showed no alterations. The incorporation of the radioactive precursor into brain mitochondria isolated from hyperthyroid rats was markedly decreased, while no changes were observed in microsomes. However, incorporation into brain microsomal fraction obtained from hypothyroid rats was increased, while no changes were observed in mitochondria. similar results were obtained in the studies performed with liver subcellular membranes from hyperthyroid animals while no changes were found in those from hypothyroid rats. Our results indicate that both experimental conditions affect in a different way the structure and function of brain mitochondria and microsomal fractions. They also give further support to our hypothesis that mitochondria have a certain degree of autonomy for the synthesis of phosphatidylcholine.

Animals↗