The impairement of glucose metabolism is frequently associated in hyperthyroidism. The present study was performed to determine the effect of the thyroid hormone excess on insulin sensitivity and on insulin secretory function in vivo. Ten newly diagnosed hyperthyroid patients and fifteen healthy control subjects were subjected to frequently sampled intravenous glucose tolerance tests(FSIGT) after an overnight fast. Insulin sensitivity, represented by the insulin sensitivity index(S_1), was assessed by minimal model analysis of FSIGT data. Insulin secretion was measured by the total area under the insulin curve after glucose load.The results were as follows.1) The K_G values, which represent glucose tolerance, were not different between the hyperthyroid patients and the normals(2.2+-0.3 vs. 2.5+-0.3%/min, p>0.05).2) S_1 was significantly decreased in the hyperthyroid patients in comparison to the normals(7.5+-1.4 vs. 2.6+-0.3X10^-4 min^-1/uU/ml, p<0.05).3) The basal insulin concentration was higher in the hyperthyroid patients than in the normals(8.3+-2.4 vs. 4.6+-0.4 uU/ml, p=0.07). In addition, the insulin secretory response to a glucose load was increased in the hyperthyroid patients as evidenced by the peak plasma insulin level(168.2+-30.4 vs. 89.2+-13.9 uU/ml, p<0.05) and by the total area under the insulin curve(2641.1+-443.2 vs. 1696.7+-204.3 min uU/ml, p<0.05).These results clearly demonstrated that insulin sensitivity was impaired in these newly diagnosed hyperthyroid patients. However, glucose tolerance was maintained by the increased insulin secretion.
Glucose ; Glucose Tolerance Test ; Humans ; Hyperthyroidism ; Insulin Resistance ; Insulin ; Metabolism ; Plasma ; Thyroid Gland

OBJECTIVETo study the clinical characteristics, diagnosis and surgical effects of thyroid-stimulating hormone pituitary adenomas (TSH-omas).

METHODSThe clinical data of 19 patients (14 female and 5 male) with TSH-omas were analyzed retrospectively in this study from January 2001 to December 2008. The patients ranged from 20 to 70 years old (average 40.5 years old) and had disease histories from 1 to 228 months (average 55 months). Among these patients, 15 of them complained of thyrotoxicosis symptoms, while the other 4 patients' symptoms were associated with headache and/or visual disturbance caused by the tumor mass effect. Initially, 12 of the 15 patients with thyrotoxicosis symptoms were misdiagnosed with Grave's disease. As a result 2 of them received (131) Iodine, and one received subtotal thyroidectomy. All of these patients underwent transsphenoidal microsurgery.

RESULTSAverage follow-up period was 3.6 years (6 months-7 years). Pathological analysis of the surgical specimen showed pituitary adenoma in all patients, immunohistochemistry were positive for TSH in 17 cases, negative for TSH in 2, positive for growth hormone in 2, positive for prolactin in 1, and positive for adrenocorticotrophic hormone in 1. Postoperative MRI revealed that the tumors in 15 patients were removed totally, though 4 patients still had residual tumors. The thyroid hormone level tests suggested that 13 patients could be considered normal 3 months after their tumors were removed, though 2 of patients with normal postoperative MRI and thyroid hormones showed increased levels of TSH. For these 2 patients, tumors did not recur and their thyroid hormone levels returned to normal after pituitary radiotherapy. The cure rate was 11/19 after surgery and 13/19 after surgery plus pituitary radiotherapy.

CONCLUSIONSThe screening test for hyperthyroidism patients with high TSH levels is a key point to improve the accuracy rate in early diagnoses of TSH-omas. The transsphenoidal microsurgery is first choice to treat TSH-omas, while pituitary radiotherapy and somatostatin analogs are beneficially adjunctive therapies.

Adult ; Aged ; Female ; Humans ; Hyperthyroidism ; metabolism ; Male ; Middle Aged ; Pituitary Neoplasms ; diagnosis ; metabolism ; surgery ; Retrospective Studies ; Thyrotropin ; metabolism ; Young Adult

OBJECTIVE: To investigate the effect of the course and menopause on the change of bone mineral density (BMD) in female patients with hyperthyroidism. METHODS: BMDs of hip and lumbar vertebrae were measured by dual-energy X-rays absorptiometry(DEXA) in the female patients (n=192, aged 14 approximately 72). Patients were divided into 2 groups (premenopausal and postmenopausal)and 2 subgroups(short-course and long-course). The BMDs were compared between those of age-matched, weight-matched, height-matched and body mass index matched control subgroups. RESULTS: In the premenopausal hyperthyroidic patients, only the BMDs of the second and total lumbar vertebrae with long-course were significantly lower than those of short-course group(P< 0.05). In the post-menopausal group with the long-course,each BMD measured had a lower level compared with that with short-course, of which the hip and the second lumber vertebrae were evident (P< 0.01). CONCLUSION The course and menopause have an effect on the BMDs in female patients with hyperthyroidism.
Adolescent ; Adult ; Aged ; Bone Density ; Female ; Hip Joint ; Humans ; Hyperthyroidism ; metabolism ; Lumbar Vertebrae ; Menopause ; metabolism ; Middle Aged

PURPOSE: Dynamics of bone mineral density(BMD) and bone metabolism in children and adolescents with hyperthyroidism have not been thoroughly investigated. The aim of this study was to study how the improvement of thyroid function with antithyroid treatment influenced bone metabolism and BMD in children and adolescents with hyperthyroidism. METHODS: Serum levels of osteocalcin(OC), bone-specific alkaline phosphatase(b-ALP), and carboxyterminal telopeptide of type 1 collagen(ICTP) were measured just before, and six, and 12 months after commencement of methimazole treatment in 12 subjects(aged 4.4-15.6 years) with serial measurement of femoral and lumbar BMD. RESULTS: A significant increase in BMD and its SDS of the femur and lumbar spine was observed during the first six months(P<0.01; P<0.05) and the next six months of treatment(P<0.01; P<0.01). Serum levels of OC and b-ALP, and their SDSs before treatment were higher than the normal values. OC decreased significantly at 12 months(P<0.05), whereas b-ALP did not show any significant change during treatment. Serum levels of ICTP and its SDS before treatment were higher than normal values, but decreased into the normal range at six months of treatment(P<0.01), and remained stable during the next six months. CONCLUSION: This study demonstrates that hyperthyroidism increases bone turnover, decreases the relative rate of bone formation vs resorption, and decreases BMD in children and adolescents. These data also suggest that bone formation exceeds bone resorption within six months of antithyroid treatment and a significant increase of BMD occurs continuously during the first 12 months of treatment.
Adolescent* ; Bone Density* ; Bone Resorption ; Child* ; Femur ; Humans ; Hyperthyroidism* ; Metabolism* ; Methimazole ; Osteogenesis ; Reference Values ; Spine ; Thyroid Gland*

Decreased glucose tolerance is often found in patients with thyrotoxicosis but the pathogenetic mechanisms are poorly understood. Since the concentrations of free fatty acid are usually elevated due to increased lipolysis in thyrotoxicosis, the preferential oxidation of the free fatty acids may explain the decreased glucose tolerance in hyperthyroidism. The aim of this study was to investigate whether lowering plasma free fatty acid(FFA) by acipimox, a long-acting antilipolytic agent, could affect glucose metabolism in thyrotoxicosis. We performed intravenous glucose tolerance test with acipimox or placebo in 6 untreated thyrotoxicmen and 6 age-and body mass index(BMI)-matched controls. The following results were obtained.1) The basal plasma FFA concentration in thyrotoxic patients were significantly higher than those in controls(997.0+-303.4 uEq/L vs. 290.5+-169.1 uEq/L; p<0.01). 2) Plasma FFA concentrations decreased rapidly with acipimox ingestion in both controls and thyrotoxic patients.3) Plasma glucose concentrations were significantly lower with acipimox ingestion than with placebo in thyrotoxic patients from 17min after intravenous glucose load and to the end of the study.4) Plasma insulin concentrations in thyrotoxic patients with acipimox ingestion were higher at 5, 7 min after iv glucose load.5) In thyrotoxic patients, glucose disappearance rate(K_glucose) in acipimox treatment was significantly higher than that in placebo treatment(2.44+-0.84 vs. 1.58+-0.37;p<0.05). 6) K_glucose values were inversely correlated with basal FFA concentrations(r=-0.58, p<0.05). In summary, in thyrotoxic patients with elevated plasma FFA levels, acipimox lowered plasma FFA, which in turn improved glucose tolerance.
Blood Glucose ; Eating ; Fatty Acids, Nonesterified ; Glucose ; Glucose Tolerance Test ; Humans ; Hyperthyroidism ; Insulin ; Lipolysis ; Metabolism ; Plasma ; Thyrotoxicosis

Background: Triiodothyronine(T3) is a hormone secreted from thyroid gland which exerts a stimulating effect on metabolism. The disorder of thyroid system brings about several serious diseases like hypothymidism or hyperthyroidism. Therefore, the determination of T in blood is very important on monitoring thyroid function. Methods: Rabbit anti-T3 antibody was generated by immunization of T-BSA as an immunogen and purified hom antisera using Affi-gel protein A kit. The titer and specificity of purified antibody were characterized. To detect T3, competitive ELISA was performed using anti-T3 antibody and T3-HRP conjugate which was synthesized by glutaraldehyde method. The sensitivity and precision assay wer~e deterrnined and compared with that of RIA. Results: The titer of purified anti-T3 antibody was about 1:100 and the optimal dilution of T3- HRP conjugate was 1:1000. When the standard curve was constructed by ELISA, its sensitivity was about 0.5ng/ml. The eoefficient variations of intra- and inter-assay were 4.9~9.3% and 7.5~13.8%, respectively. The results obtained by ELISA and RIA correlated well with each other(n =50, r= 0.97), The linear regression equation was y= 1.09*0.08(P<0.01). Conclusion: We successfully developed a method for the measurement of T3 on ELISA which was based on competitive reaction between antigen(T3) and enzyme labeled antigen(T3-HRP). These results demonstrated that competitive ELISA is a convenient, fast, reproducible and aecurate method for the determinstion of T in serum and can be used as practical alternative to RIA.
Enzyme-Linked Immunosorbent Assay ; Glutaral ; Hyperthyroidism ; Immune Sera ; Immunization ; Linear Models ; Metabolism ; Methods ; Sensitivity and Specificity ; Staphylococcal Protein A ; Thyroid Gland ; Triiodothyronine

Thyroid hormone plays an important role in bone remodeling. In overt hyperthyroidism, excess thyroid hormone accelerates bone turnover and shortens the normal bone remodeling cycle, leading osteoporosis and increased fracture risk. Several population and case-control studies have demonstrated that a prior history of hyperthyroidism is an independent risk factor for hip and vertebral fracture. In contrast, bone remodeling cycle is prolonged to almost 2 years with an increase in mineralized cortical bone in overt hypothyroidism. Some cross-sectional and longitudinal studies have suggested that thyroid hormone replacement could decrease bone mineral density in overt hypothyroidism. However, this effect might be interpreted as an adaptive mechanism on decreased bone turnover in preexistent hypothyroidism, and not as thyroid hormone induced bone loss. The effect of thyroid hormone replacement for hypothyroidism on fracture risk has not been investigated well. However, excessive thyroid hormone treatment might be increased the risk of fracture.
Bone Density ; Bone Remodeling ; Case-Control Studies ; Hip ; Hyperthyroidism ; Hypothyroidism ; Longitudinal Studies ; Metabolism ; Miners ; Osteoporosis ; Risk Factors ; Thyroid Gland

OBJECTIVE: To investigate the effect of pinggan-qianyang (PGQY), a Chinese medicine, on hypothalamic proteome in the hyperthyroid rats with hyperactivity of liver-yang, and to explore its mechanism. METHODS: The rat model was established by intraperitoneal injection of levo-thyroxine (L-T4) and fuzi decotion. All the quantitative and qualitative changes of the protein expressions were compared among the normal group,the model group and the treatment group by proteomic techniques. RESULTS: The protein spots in the 3 groups were mainly displayed at the isoelectric point (pI) 3 approximately 10, and the molecular weights were 13.8 approximately 98.8 kD.Compared with the normal group, 6 spots of protein expression increased and 10 decreased in the model group. All the changed protein in the model group returned to normal level after PGQY treatment. Mass-spectrometer and bio-informatics indicated that these proteins were Prohibitin, Peroxiredoxin-6, histidine triad nucleotide-binding protein 1, protein-tyrosine-phosphatase, predicted protein, profilin-2, peroxir doxin-II, heat shock protein-27, and annexin-A1. CONCLUSION There are differences in the expression of hypothalamus proteins in the hyperthyroid rats with hyperactivity of liver-yang after the treatment with PGQY, and the 9 identified protein spots may be associated with the mechanism of PGQY.
Animals ; Drugs, Chinese Herbal ; therapeutic use ; Female ; Hyperthyroidism ; drug therapy ; metabolism ; Hypothalamus ; metabolism ; Male ; Medicine, Chinese Traditional ; Nerve Tissue Proteins ; metabolism ; Peroxiredoxin VI ; metabolism ; Phytotherapy ; Proteome ; metabolism ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Repressor Proteins ; metabolism

This study was designed to investigate the effects of iron supplementation on the parameters of oxidative stress in the skeletal muscle tissue of hyperthyroidism induced rats. Hyperthyroidism was found to cause an increase in thiobarbituric acid-reactive substances (TBARS) and copper zinc superoxide dismutase (Cu, Zn SOD) activity, but decreases in the glutathione-peroxidase (GSH Px) activity and glutathione (GSH). Iron supplementation caused an increase in TBARS and a decrease in GSH. Iron supplementation in hyperthyroid rats attenuated the hyperthyroid state, but lowered the plasma ferritin level, which is considered an indicator of thyroid hormone action. Iron supplementation caused no additional increase in the TBARS in hyperthyroid rats, ameliorated the decrease in GSH content and abolished the induction of Cu, Zn SOD. Our findings suggested no increase, but a decrease, in the risk of oxidative stress in iron supplemented hyperthyroid rats. Whether supplementation of iron would have similar effects in humans should be further investigated in clinical studies.
Animals ; Glutathione/metabolism ; Human ; Hyperthyroidism/*metabolism ; Iron/*pharmacology ; Lipid Peroxidation/drug effects ; Male ; Muscle, Skeletal/*metabolism ; Oxidative Stress/*drug effects ; Rats ; Rats, Wistar ; Superoxide Dismutase/metabolism ; Thiobarbituric Acid Reactive Substances/metabolism ; Triiodothyronine/blood

The elevated plasma level of thyroxin and/or triiodothyronine in hyperthyroidism not only induces a transition from the innervated slow-twitch muscle fibers to fast-twitch fibers, but also changes the contractile function in transition muscle fibers. So the muscle weakness of thyrotoxic myopathy would relate to alteration in fatigability of tetanic contraction in muscles, especially in slow-twitch fibers. The aim of the present study was to observe the extent of fatigue of soleus in 4-week hyperthyroid rats and elucidate its underlying mechanism. The isolated soleus muscle strips were perfused in Krebs-Henseleit solution with or without an inhibitor of sarcoplasmic reticulum Ca(2+)-ATPase (SERCA), cyclopiazonic acid (CPA). The contractile function of soleus was observed in twitch and intermittent tetanic contraction. The body weight in 4-week hyperthyroid rats decreased as compared with that in the control group [(292±13) g vs (354±10) g], but there was no difference between hyperthyroid and control groups in the wet weight of soleus [(107.3±8.6) mg vs (115.1±6.9) mg]. The time to peak tension (TPT) and time from peak tension to 75% relaxation (TR(75)) in twitch contraction were shortened in the soleus of hyperthyroid rats, and the TR(75) of tetanic contraction was also shortened as compared with that in the control group [(102.8±4.1) ms vs (178.8±15.8) ms]. The optimal stimulation frequency at which a maximal tension of tetanic contraction happened was shifted from 100 Hz in the control group to 140 Hz in hyperthyroid group. The soleus of hyperthyroid rat was easier to fatigue than that of the control rat during intermittent tetanic contraction. The SERCA activity also increased in soleus of hyperthyroid rat. The TR(75) in tetanic contraction was prolonged and showed an increased fatigue resistance in the soleus of control and hyperthyroid groups treated with 1.0 μmol/L CPA. The fatigue resistance of tetanic contraction in the soleus of hyperthyroid rat increased further with 5.0 μmol/L CPA treatment, but the resting tension kept rising. The 10 μmol/L CPA reduced the fatigue resistance of tetanic contraction in the soleus of hyperthyroid rat. The above results demonstrate that the SERCA activity in soleus can also influence the relaxation duration of twitch contraction like that in the myocardium. The SERCA activity in slow-twitch fibers is possibly involved in the regulation of fatigue resistance of intermittent tetanic contraction.
Animals ; Fatigue ; Glucose ; Hyperthyroidism ; enzymology ; In Vitro Techniques ; Muscle Contraction ; Muscle Fibers, Slow-Twitch ; enzymology ; physiology ; Muscle, Skeletal ; enzymology ; physiology ; Rats ; Sarcoplasmic Reticulum Calcium-Transporting ATPases ; metabolism ; Tromethamine