Serum bone Gla protein (BGP) during treatment of hyperthyroidism and hypothyroidism. A longitudinal study

Serum bone gamma-carboxyglutamic acid-containing (Gla) protein (BGP) was measured before and with initially 2 weeks, later 4-8 weeks intervals for 20-58 weeks during treatment of patients with hyperthyroidism (n = 10) and hypothyroidism (n = 4). Biochemical euthyroidism was obtained in the hyperthyroid patients after a median of 3 weeks (range 1-8 weeks), and in the hypothyroid patients after a median of 17 weeks (range 10-27 weeks). Serum BGP levels closely followed the thyroid state, being high respectively low in the hyperthyroid and hypothyroid state and reaching a stable plateau just at the time biochemical euthyroidism was obtained. These data suggest that osteoblastic activity is enhanced in hyperthyroidism and reduced in hypothyroidism, and that normalization occurs in close conjunction with the normalization of the thyroid state, without any delay, indicating a direct effect on the function of the excisting osteoblasts by the thyroid hormones.     

Changes in the plasma and urine alpha human atrial natriuretic peptide (alpha hANP) concentration in patients with thyroid disorders

In order to assess the possible involvement of thyroid hormone in alpha human atrial natriuretic peptide (alpha hANP), we investigated the plasma and urine ANP concentration in patients with primary hyperthyroidism and hypothyroidism. Plasma and urine were extracted through Sep-Pak C18 cartridges and the urine ANP concentration was corrected by urine creatinine (cre. mg/dl) and expressed as fmol/mg.cre.. The plasma ANP concentration in patients with untreated hyperthyroidism (32.3 +/- 7.0 fmol/ml; n = 22) was higher than in normal subjects (p less than 0.01 vs control; 6.2 +/- 0.7 fmol/ml). After restoration to euthyroidism, the plasma ANP concentration (patients with treated hyperthyroidism) fell to normal (8.9 +/- 1.9 fmol/ml). The plasma ANP concentration in patients with untreated hypothyroidism (14.1 +/- 3.0 fmol/ml; n = 7) was higher than normal, but in two of them there was mild renal dysfunction and an incomplete right blundle branch block in the electrocardiogram. It was possible that these factors contributed to the observed increase in plasma ANP. However, a significant positive correlation was found between plasma ANP and free thyroxine (n = 40, r = 0.449; p less than 0.01) and free triiodothyronine (n = 40, r = 0.546; p less than 0.01). The urine ANP concentration in patients with untreated hyperthyroidism was markedly higher than in normal subjects (p less than 0.01), but in untreated hypothyroidism not significantly different from normal.     

Serum fructosamine in assessment of diabetic control and relation to thyroid function

Measurement of serum fructosamine using a Roche kit is a simple and reliable method for the estimation of glycated serum proteins. The value of serum fructosamine can be affected by hyperglycemia in diabetics and an abnormal turnover rate of serum protein in patients with thyroid dysfunction. We measured the serum fructosamine level in 18 normal control subjects, 71 diabetics (8 IDDM, 63 NIDDM) and 46 non-diabetic untreated patients with thyroid dysfunction (28 hyperthyroidism, 18 hypothyroidism). The serum fructosamine level was significantly increased in the diabetics compared with the normal control subjects (3.84 +/- 0.15 mmol/l vs 2.58 +/- 0.08; mean +/- SE, P less than 0.01). The serum fructosamine level in the diabetics was positively correlated with the fasting plasma glucose and HbAlc level, showing the highest correlation with fasting plasma glucose at 2 weeks before and with the HbAlc level at 2 weeks after serum fructosamine measurement. In the patients with thyroid dysfunction, the serum fructosamine level in hyperthyroidism (2.08 +/- 0.03 mmol/l) and hypothyroidism (3.11 +/- 0.07 mmol/l) were significantly lower (P less than 0.001) and higher (P less than 0.001) than the normal control subjects (2.58 +/- 0.08 mmol/l), respectively. Furthermore, the serum fructosamine level in these patients was negatively correlated with the level of serum thyroid hormones such as T3 (P less than 0.001) and T4 (P less than 0.001). It is concluded that measurement of serum fructosamine is clinically useful for the evaluation of shorter-term glycemic control in diabetics, but its level for diabetic patients with thyroid dysfunction must be cautiously interpreted.     

Human epidermal growth factor concentrations in urine, but not in saliva and serum, depend on thyroid state

To evaluate the effects of thyroid hormones on the concentration of epidermal growth factor (EGF), we determined values for the immunoreactive EGF concentration in the urine (U-irEGF) of newborn infants with congenital hypothyroidism (N = 19), and in urine, saliva and serum of adult patients with hypothyroidism (N = 11) and hyperthyroidism (N = 8). The values were expressed as SD score (SDS), i.e. deviation in SD units from their mean value of healthy subjects of the same age and sex. The SDS of relative U-irEGF (ng/mg creatinine) was lower (P less than 0.01) in newborn infants with congenital hypothyroidism (-0.8 +/- 0.2; mean +/- SEM) than in healthy infants. Their relative U-irEGF correlated with their serum T4 concentrations (r = 0.59, P less than 0.01). The SDS of relative U-irEGF was lower (P less than 0.01) in adult hypothyroid patients (-1.2 +/- 0.5) and higher (P greater than 0.05) in adult hypothyroid patients (0.9 +/- 0.6) than in healthy adult subjects. When subsequently euthyroid, their SDS of relative U-irEGF increased to -0.5 +/- 0.3 (P less than 0.01), and decreased to -0.7 +/- 1.1 (P less than 0.05), respectively. The irEGF concentrations in saliva and serum were not significantly different between the hypothyroid and hyperthyroid patients. Our results indicate that urinary excretion of irEGF in man is dependent on thyroid hormone.     

Prolonged ventricular repolarization measured by corrected QT interval (QTc) in subclinical hyperthyroidism.

Overt hyperthyroidism and hypothyroidism exert a major effect on cardiac function and on ECG. The influence of subclinical hyperthyroidism on the circulatory system is still under debate. Few studies examined the effect of thyroid hormones on ventricular repolarization measured by corrected QT interval (QTc). Longer QTc is associated with increased risk of arrhythmia and cardiac mortality. The aim of this study was to examine the influence of subclinical hyperthyroidism on ventricular repolarization measured by corrected QTc in a standard 12-lead electrocardiogram. The examined group consisted of thirty-two patients with subclinical hyperthyroidism; the controls were thirty-nine healthy individuals. In the group with subclinical hyperthyroidism, we observed a significant increase in heart rate (80.3 +/- 10.59 vs. 73.7 +/- 11.37 bpm, p < 0.05). The mean corrected QTc was 0.434 +/- 0.0207 seconds and 0.414 +/- 0.0208 in the examined groups and in controls, respectively (p < 0.001). QTc did not correlate with free thyroxin concentrations (p = 0.5084). Conclusion: Corrected QT intervals were significantly longer in patients with subclinical hyperthyroidism.     

Urinary 8-isoprostaglandin F(2alpha) level in Behçet's disease

Although its etiology remains unknown, the increased production of reactive oxygen species in Beh?et's disease (BD) have been reported. Furthermore, it has been suggested that vascular and endothelial tissue damage seen in BD is related to elevated reactive oxygen species generated by activated neutrophils from BD patients. To investigate the formation of lipid peroxidation in BD patients in vivo, urinary level of 8-isoprostaglandin F(2alpha) was quantitated by enzyme immunoassay after solid phase extraction in different clinical forms of BD patients. There was no difference in urinary level of 8-isoprostaglandin F(2alpha) between BD patient and healthy control group. There was also no difference in urinary levels of 8-isoprostaglandin F(2alpha) in subgroup analyses of BD patients, i.e. in mucocutaneous and vascular type BD patients; active and inactive BD patients. Contrary to the findings in literature, we found no difference in urinary level of 8-isoprostaglandin F(2alpha) between patients with systemic lupus erythematosus and healthy control group. These findings show no increase in lipid peroxidation despite the augmented formation of reactive oxygen species in BD patients. It may be interesting to assess formation of urinary level of 8-isoprostaglandin F(2alpha) in BD patients who do not take any medication.     

Bone turnover in overt and subclinical hyperthyroidism due to autonomous thyroid adenoma.

Parameters of bone turnover were measured in 20 premenopausal women affected by autonomous thyroid adenoma: 7 patients were suffering from overt hyperthyroidism with raised values of free thyroid hormones; 13 were clinically euthyroid and had normal values of free thyroid hormones. In all cases serum TSH concentrations were below the lower normal limit of our laboratory (< 0.4 mU/l). Eleven healthy premenopausal women were studied as a control group. Patients with overt hyperthyroidism disclosed a significant enhancement of both bone resorption (increased serum calcium and urinary excretion of hydroxyproline) and bone formation (increased serum levels of osteocalcin and alkaline phosphatase) when compared both to controls and to patients with subclinical hyperthyroidism. No significant alterations of bone metabolism parameters were found in patients with subclinical hyperthyroidism in comparison with controls. Therefore, in premenopausal women affected by autonomous thyroid adenoma the bone turnover appeared to be significantly increased when the serum values of free thyroid hormones were raised in the group of patients with overt hyperthyroidism.     

Increased erythrocyte catalase activity in patients with hyperthyroidism

Levels of human erythrocyte catalase activity were determined in 38 patients with thyroidal dysfunction. In patients with hyperthyroidism, erythrocyte catalase activities were found to be higher than the levels of normal subjects (P less than 0.001). In hypothyroidism, erythrocyte catalase activities were of the same order as those of normal subjects. Significantly high positive correlation was found between erythrocytes catalase activity and the levels of thyroxine (r = 0.5794, n = 36, P less than 0.001), and slight positive correlation was detected between catalase activity and the levels of triiodothyronine (r = 0.3978, n = 33, P less than 0.05). A decreased erythrocyte catalase activity was observed when erythrocytes lysate was incubated with thyroid hormones. It was suggested that erythrocyte catalase activity had close relationship with thyroid state, however, direct effect of thyroid hormones were not observed on erythrocyte catalase assay system in vitro.     

Color-Flow Doppler Sonography in Patients with Subclinical Thyroid Dysfunction

ObjectiveTo assess the value of color-flow Doppler sonography (CFDS) in evaluating intrathyroidal blood flow and velocity in patients with subclinical thyroid dysfunction.MethodsIn this prospective study, patients with subclinical hypothyroidism, patients with subclinical hyperthyroidism, and euthyroid patients without known thyroid autoimmune disease who served as controls were included. Subclinical thyroid dysfunction was defined as normal serum free thyroxine (FT₄) and free triiodothyronine (FT₃) in the presence of high (subclinical hypothyroidism), or lowsuppressed (subclinical hyperthyroidism) serum thyrotropin (TSH) levels. Serum FT₄, FT₃, TSH, and antibodies to thyroid peroxidase and thyroglobulin were measured in all participants. In addition, TSH receptor antibody levels were determined in patients with subclinical hyperthyroidism. All participants underwent conventional sonography and CFDS. Mean peak systolic velocity (PSV) and resistive index were obtained from multiple extranodular thyroid parenchyma samplings and inferior thyroid artery measurements.ResultsThe study population included 27 patients with subclinical hypothyroidism, 15 patients with subclinical hyperthyroidism, and 20 euthyroid patients. Patients with subclinical hypothyroidism had significantly higher mean intrathyroidal PSV values than control patients (19.9 ± 5.6 cm/s vs 15.7 ± 4.4 cm/s; P = .008), whereas patients with subclinical hyperthyroidism had significantly higher mean PSV values than control patients at the inferior thyroid artery level (29.7 ± 10.7 cm/s vs 21.9 ± 6.8 cm/s; P = .014). Compared with control patients, a greater proportion of patients with subclinical hypothyroidism and patients with subclinical hyperthyroidism had marked CFDS patterns (78% vs 15% [P <.001] and 53% vs 15%; [P <.001], respectively). A significant association was found between positivity for thyroid autoantibodies and intense CFDS patterns. No correlation was found between TSH or thyroid hormone levels and CFDS pattern or blood flow velocity.ConclusionWe have demonstrated that significantly increased thyroid blood flow velocity and vascularity are already present in patients with mild thyroid dysfunction.(Endocr Pract. 2010;16:376-381)     

Developmental expression of mRNAs from a rat C-erbA genomic locus.

The thyroid hormone receptor alpha gene is alternatively spliced to give the alpha receptor and a variant which does not bind thyroid hormones. An additional alpha-like receptor (Rev-erbA alpha) is transcribed on the opposite strand and overlaps the unique variant sequence. The alpha receptor in rat brain reaches peak levels 5-15 days after birth. The variant remains high from 2 days before birth to old age. The Rev-erbA alpha mRNA increases beginning 5 days after birth, maximizing in adulthood. Thyroid hormone decreases and hypothyroidism increases the level of these 3 messages. We conclude that the levels of these messages are similarly controlled by thyroid hormone but have different ontogenetic controls. No functional results can be seen in vivo from potential anti sense pairing of Rev-erbA alpha with the variant.     

Leptin,NPY, Melatonin and Zinc Levels in Experimental Hypothyroidism and Hyperthyroidism: The Relation to Zinc

Since zinc mediates the effects of many hormones or is found in the structure of numerous hormone receptors, zinc deficiency leads to various functional impairments in the hormone balance. And also thyroid hormones have important activity on metabolism and feeding. NPY and leptin are affective on food intake and regulation of appetite. The present study is conducted to determine how zinc supplementation and deficiency affect thyroid hormones (free and total T3 and T4), melatonin, leptin, and NPY levels in thyroid dysfunction in rats. The experiment groups in the study were formed as follows: Control (C); Hypothyroidism (PTU); Hypothyroidism+Zinc (PTU+Zn); Hypothyroidism+Zinc deficient; Hyperthyroidism (H); Hyperthyroidism+Zinc (H+Zn); and Hyperthyroidism+Zinc deficient. Thyroid hormone parameters (FT₃, FT₄, TT₃, and TT₄) were found to be reduced in hypothyroidism groups and elevated in the hyperthyroidism groups. Melatonin values increased in hyperthyroidism and decreased in hypothyroidism. Leptin and NPY levels both increased in hypo- and hyperthyroidism. Zinc levels, on the other hand, decreased in hypothyroidism and increased in hyperthyroidism. Zinc supplementation, particularly when thyroid function is impaired, has been demonstrated to markedly prevent these changes.     

Changes of serum angiotensin-I-converting enzyme in patients with thyroid disorders

In 149 subjects (63 euthyroid, 21 hyperthyroid, 26 with autonomous nodules, subdivided into 20 euthyroid and 6 hyperthyroid, 17 hypothyroid subjects and 22 women taking estrogens) the serum angiotensin-I-converting enzyme (SACE) was spectrophotometrically measured and correlated with age, systolic and diastolic blood pressure, free thyroid hormones (FT4, FT3) and delta TSH level. In patients with diffuse hyperthyroidism and with regional autonomy, systolic blood pressure was elevated. The highest values for FT4 and FT3 were found in patients with hyperthyroidism and hyperthyroid autonomous nodules. SACE correlated with age for the euthyroid control group (p less than 0.05). In this group, SACE levels were higher in men than in women (p less than 0.02). Regarding all 149 subjects together, significant linear correlations between SACE and systolic blood pressure as well as with FT4 and FT3 concentrations could be demonstrated (p less than 0.01-0.001). Among the individual groups the mean SACE activities were significantly elevated in hyperthyroid patients (p less than 0.01). No significant differences could be observed between controls and euthyroid subjects with autonomous nodules as well as in hypothyroid cases. In comparison to euthyroid patients the mean SACE levels of hyperthyroid patients with autonomy were significantly (p less than 0.05) elevated. The SACE activities of women taking estrogens for contraception did not differ significantly from SACE in age-matched female controls.     

Prevalence of hypergastrinemia in patients with hyper- and hypothyroidism: impact for calcitonin?

OBJECTIVES: To evaluate the prevalence of hypergastrinemia in patients with hyperthyroidism and hypothyroidism and to determine whether gastrin-induced hypercalcitonemia could explain the high prevalence of thyroid C-cell hyperplasia among patients with hyperthyroidism. METHODS: Concentrations of gastrin and of hCT were determined by commercially available radioimmunoassays. RESULTS: Elevated serum concentrations of gastrin were found in 17 of 161 (10.5%) patients with manifest hyperthyroidism (Graves' disease) and in 4 of 37 (10.8%) and 23 of 255 (9.0%) patients with manifest or subclinical hypothyroidism, respectively. Only 2 cases of hypergastrinemia of 255 subclinically hypothyroid patients (0.8%) could not be linked to thyroid autoimmune disease by either biochemical or sonographic criteria. Four patients with Graves' disease presented elevated plasma concentrations of calcitonin, but none of these patients also had an elevated serum gastrin. CONCLUSIONS: The prevalence of hypergastrinemia in autoimmune thyroid disease is about 10%. The determination of gastrin in subclinical hypothyroidism is not cost-effective in the absence of biochemical and/or sonographic markers of autoimmune thyroid disease. The determination of gastrin is of no use to predict the presence of C-cell hyperplasia commonly seen in patients with Graves' disease.     

Measurement of serum thyroxine binding prealbumin in various thyroidal states by radioimmunoassay

Serum thyroxine binding prealbumin (TBPA) levels in various thyroidal states were examined by radioimmunoassay (RIA). This technique is highly sensitive, accurate and reproducible. The normal mean (+/- 2SD) level of serum TBPA is 26.9 +/- 8.0 mg/dl (29.4 +/- 5.2 in men and 24.9 +/- 7.6 mg/dl in women). Serum TBPA levels in pregnant women were significantly lower than in normal females (P less than 0.05). Serum TBPA levels in patients with untreated hyperthyroidism were 12.9 +/- 4.0 mg/dl (mean +/- SD) and in patients with untreated hypothyroidism were 25.2 +/- 4.7 mg/dl (mean +/- SD). The mean TBPA concentrations in untreated hyperthyroidism were significantly lower than that for normal population (P less than 0.01), but untreated hypothyroidism was almost within normal range. The changes in TBPA levels in hyperthyroidism and hypothyroidism were similar to those in TBG levels. In untreated hyper- and hypothyroidism, restoration to euthyroidism by treatment was uniformly accompanied by a normalization of serum TBPA and TBG levels. A negative correlation between serum thyroid hormone binding protein (TBG and TBPA) and free thyroxine was observed in patients with hyperthyroidism. The coefficient of correlation between TBPA and free thyroxine was -0.80 (P less than 0.01) and between TBG and free thyroxine -0.58 (P less than 0.01). From these experiments it appears that not only TBG but also TBPA may play an important role in the regulation of the free thyroxine concentration in response to various thyroidal states.     

Increased urinary excretion of 8-iso-prostaglandin F2alpha in patients with HFE-related hemochromatosis: a case-control study

The hypothesis according to which iron overload could be harmful has been extensively and controversially discussed in the literature. One underlying pathological mechanism may be elevated oxidative stress. Thus, we studied the correlation between hemochromatosis and an established marker of oxidative stress, 8-iso-prostaglandin F2alpha (8-iso-PGF2alpha, iPF2alpha-III, 15-F2t-IsoP). We enrolled 21 patients with hemochromatosis, positive for the homozygous C282Y mutation in the HFE gene, and 21 healthy controls frequency-matched by age and gender in a case-control study design. The objective was to show that iron overload in HFE-related hemochromatosis is associated with increased oxidative stress assessed through 8-iso-PGF(2alpha) urinary excretion, and that oxidative stress is impacted by iron-removal treatment (phlebotomy). Study parameters were transferrin saturation, 8-iso-PGF(2alpha) urine excretion, transferrin, ferritin, serum iron, and vitamins A and E for all participants. Iron concentration in the liver and non-transferrin-bound iron were measured in patients only. We found a significant difference in 8-iso-PGF2alpha in patients (245 [interquartile range 157-348] pg/mg creatinine) compared with controls (128 [106-191] pg/mg creatinine, P = 0.002). Vitamin A was significantly reduced in cases (0.34 [0.25-1.83] microg/ml compared to 3.00 [2.11-3.39] microg/ml, P < 0.001), while vitamin E did not show a significant difference in cases (14.7 [11.5-18.1] microg/ml) compared with controls (14.9 [13.1-19.2] microg/ml, P = 0.52). After phlebotomy treatment and normalization of the iron parameters in the hemochromatosis group, serum vitamin A levels were significantly increased (1.36 [1.08-1.97] microg/ml, P = 0.035 vs. baseline, P < 0.001 vs. controls) and 8-iso-PGF2alpha urinary excretion was lowered to control levels (146 [117-198] pg/mg creatinine, P = 0.38 vs. controls). In our study, HFE-related hemochromatosis was associated with increased oxidative stress and hypovitaminemia A in C282Y homozygotes. The increased oxidative stress was reversible by normalization of the iron load by phlebotomy. Thus, phlebotomy is an effective and adequate means for reducing oxidative stress in these patients.     

Screening of geriatric patients for thyroid dysfunction with thyrotropin-releasing-hormone test, sensitive thyrotropin and free thyroxine estimation

Hospitalized geriatric patients (N = 354) from an iodine-deficient area were screened with sensitive thyrotropin (TSH), free and total thyroxine (FT4, T4) and total triiodothyronine (T3) to determine the occurrence rate of clinical and subclinical thyroid dysfunction. The diagnostic value of the tests was compared to each other and to that of the thyrotropin-releasing-hormone test (TRH-test) in order to find the optimal first line screening test in geriatric patients. Clinical hyperthyroidism was found in 13, subclinical hyperthyroidism in 10, overt hypothyroidism in 6 and subclinical hypothyroidism in 8 cases. 20.6% of the patients were euthyroid but had subnormal TSH response to TRH, as a sign of possible thyroid autonomy. The low occurrence rate of clinical thyroid disorders (4.8%) does not justify the screening of geriatric patients in general, but the high probability of thyroid autonomy makes reasonable the investigation of every geriatric patient before iodine administration. Suppressed basal TSH and high FT4 were found to be both sensitive and specific in diagnosing clinical hyperthyroidism, but the predictive value was insufficient; elevated T4 and T3 are specific, but not sensitive. Basal TSH is sensitive, specific and has a good predictive value in diagnosing euthyroidism, whereas normal T4, FT4 or T3 are not specific enough for euthyroidism. Basal TSH is better as a first line test of thyroid function than FT4. A normal basal TSH confirms euthyroidism by itself. Other tests (TRH test, T4, FT4, T3) are necessary to elucidate the clinical importance of a subnormal or suppressed basal TSH.     

TSBAb (TSH-stimulation blocking antibody) and TSAb (thyroid stimulating antibody) in TSBAb-positive patients with hypothyroidism and Graves' patients with hyperthyroidism.

There are two types of TSH receptor antibodies (TRAb); thyroid stimulating antibody (TSAb) and TSH-stimulation blocking antibody (TSBAb). TSAb causes Graves' hyperthyroidism. TSBAb causes hypothyroidism. Both TSAb and TSBAb block TSH-binding to thyroid cells as TSH receptor antibodies (TRAb). TSBAb-positive patients with hypothyroidism and Graves' patients with hyperthyroidism may have both TSBAb and TSAb. We studied TSBAb and TSAb in 43 TSBAb-positive patients with hypothyroidism and in 55 untreated Graves' patients with hyperthyroidism. TSBAb-activities were expressed as percentage inhibition of bovine (b) TSH-stimulated cAMP production by test IgG. Two formulas were used to calculate TSBAb-activities; TSBAb-A (%) = [1 - (c - b)/(a - b)] x 100 and TSBAb-B (%) = [1 - (c - d)/(a - b)] x 100, where a: cAMP generated in the presence of normal IgG and bTSH, b: cAMP generated in the presence of normal IgG, c: cAMP generated in the presence of test IgG and bTSH, and d: cAMP generated in the presence of test IgG. TSAb (%) = [d/b] x 100. All of the 43 TSBAb-positive patients with hypothyroidism had strongly positive TSBAb-A and -B. Some of them had weakly positive TSAb (<240%). All 55 untreated Graves' patients had positive TSAb (205-2509%). Some of them had both TSAb and TSBAb. TSBAb-positive patients with hypothyroidism had a limited distribution of TSBAb- and TSAb-activities (TSBAb-A + 75 - + 103%, TSBAb-B + 87 - + 106%, TSAb 92-240%), but Graves' patients with hyperthyroidsim had a wide distribution of TSAb- and TSBAb-activities (TSAb 205-2509%, TSBAb-A - 158 - + 43%, TSBAb-B - 14 - + 164%). TSBAb-A ignores TSAb activity in serum, and might give low TSBAb activity. However, TSBAb-A clearly differentiates TSBAb-positive patients with hypothyroidism from Graves' patients with hyperthyroidism; thus, we favor TSBAb-A over TSBAb-B. Some of TSBAb-positive patients with hypothyroidism and Graves' patients with hyperthyroidism have both TSBAb and TSAb.     

Hyperthyroidism and cation pumps in human skeletal muscle

Skeletal muscle constitutes the major target organ for the thermogenic action of thyroid hormone. We examined the possible relation between energy expenditure (EE), thyroid status, and the contents of Ca2+-ATPase and Na+-K+-ATPasein human skeletal muscle. Eleven hyperthyroid patients with Graves' disease were studied before and after medical treatment with methimazole and compared with eight healthy subjects. Muscle biopsies were taken from the vastus lateralis muscle, and EE was determined by indirect calorimetry. Before treatment, the patients had two- to fivefold elevated total plasma T3 and 41% elevated EE compared with when euthyroidism had been achieved. In hyperthyroidism, the content of Ca2+-ATPase was increased: (mean +/- SD) 6,555 +/- 604 vs. 5,212 +/- 1,580 pmol/g in euthyroidism (P = 0.04) and 4,523 +/- 1,311 pmol/g in healthy controls (P = 0.0005). The content of Na+-K+-ATPase showed 89% increase in hyperthyroidism: 558 +/- 101 vs. 296 +/- 34 pmol/g (P = 0.0001) in euthyroidism and 278 +/- 52 pmol/g in healthy controls (P < 0.0001). In euthyroidism, the contents of both cation pumps did not differ from those of healthy controls. The Ca2+-ATPase content was significantly correlated to plasma T3 and resting EE. This provides the first evidence that, in human skeletal muscle, the capacity for Ca2+ recycling and active Na+-K+ transport are correlated to EE and thyroid status.     

Reduced serum acylated ghrelin levels in patients with hyperthyroidism

BACKGROUND AND OBJECTIVE: Recent studies have revealed that circulating ghrelin levels seem to play a role in energy homeostasis. The effect of hyperthyroidism on ghrelin levels is not fully known. METHODS: Serum levels of ghrelin and its relationship with insulin resistance were evaluated in 48 patients with hyperthyroidism and 43 euthyroid healthy controls. Thyroid hormones, insulin, glucose, ghrelin levels and lipid parameters were measured in all subjects. Insulin sensitivity was determined using the homeostasis model assessment. RESULTS: Serum ghrelin levels were significantly decreased in hyperthyroid patients than in controls (32.5 +/- 23.3 vs. 54.1 +/- 35.5 pg/ml, p < 0.001). Circulating ghrelin levels significantly correlated with age (r = -0.26, p = 0.01), fasting glucose (r = -0.21, p = 0.01), free triiodothyronine (r = -0.18, p = 0.04), free thyroxine (r = -0.23, p = 0.02) and thyroid stimulating hormone (r = 0.21, p = 0.04), but not with blood pressure, body mass index, lipid parameters, insulin and homeostasis model assessment (p > 0.05). Multiple regression analysis revealed glucose level to be the most important predictor of circulating ghrelin level. CONCLUSION: These results indicate that hyperthyroidism has effect on serum ghrelin levels. Further studies are needed for the exact mechanism.     

Catecholamine and thyroid hormone metabolism in a case of anorexia nervosa

Alterations in catecholamine (CA) and thyroid hormone metabolism were examined in a 12-year-old girl with anorexia nervosa during 3 months of treatment. According to her body weight change, the observation period was divided into 3 stages: initial emaciation (stage 1), stable maintenance of the -30% level of the previous weight (stage 2) and convalescent stage (stage 3). Stage 1 was characterized by relatively high urinary norepinephrine (NE) and epinephrine (E) but low dopamine (DA) excretion, elevated plasma DA-beta-hydroxylase (DBH) activity and reduced serum thyroid hormones, especially the triiodothyronine (T3) level. In stage 2, urinary CAs were markedly suppressed, while serum thyroid hormones gradually increase. In stage 3, a great increase in DA excretion, a fall in plasma DBH activity and normalization of thyroid hormones were observed. In the low T3 state below 60 ng/dl, urinary NE + E/DA ratios were elevated and widely fluctuated (0.58 +/- 0.30, SD), but were gradually decreased and completely stabilized in the normal T3 state (0.07 +/- 0.02, P less than 0.001). These results indicate that (1) although total CA production was depressed in anorexia nervosa, a change from an adrenergic-dominant to a dopaminergic-dominant state occurs in accordance with body weight gain, and (2) this shift in the CA profile is associated with concomitant recovery of reduced thyroid hormone concentrations. Thus, as for the energy expenditure, compensatory changes were observed in CAs and thyroid hormones in relation to caloric restriction.