Administration Of Thyroid Research Articles

Multi-omics analysis of kidney, bone and bone marrow explored potential mechanisms of Erzhi Wan against osteoporosis with kidney-Yin deficiency

Osteoporosis (OP) is a metabolic bone disease that can lead to major health challenges. The theory of Traditional Chinese medicine believes that kidney-Yin deficiency (KYD) is the main cause of postmenopausal osteoporosis. This study was aimed to investigate the effect of EZW on anti-osteoporosis with KYD, and explore potential mechanisms from the perspective of the kidney, bone and bone marrow through analysis of metabolomics and proteomics. The model of OP with KYD was established by rats treated with bilateral ovariectomy (OVX), and then given intragastric administration of thyroid and reserpine to induce. Micro-CT was applied to determine the microstructures of bone. Serum levels associated with bone turnover markers and kidney-Yin deficiency were detected by enzyme-linked immunosorbent (ELISA) assay. The differential metabolites in the kidney, bone and bone marrow were analyzed by metabolomics. The differentially expressed proteins in these three tissues were detected via proteomics. The findings suggested that EZW could alleviate a variety of metabolites and proteins among the kidney, bone and bone marrow, primarily in amino acid metabolism, carbohydrate metabolism, nucleotide metabolism and lipid metabolism, thus leading to improvements of OP with KYD, which provided theoretical basis for clinical treatment of EZW on OP with KYD.

Abstract 16717: Managing Myxedema Coma: A Challenging Case of Cardiogenic Shock Culminating in Orthotopic Heart Transplantation

Background: Myxedema coma (MC) is a rare manifestation of severe hypothyroidism often seen in elderly female patients. While the sequelae of MC can lead to multi-organ involvement and eventual failure, irreversible Heart Failure (HF) is rarely seen. This case culminated in orthotopic heart transplant (OHT) for definitive treatment. Case Presentation: A 23-year-old male presented with worsening RUQ abdominal pain for 2 weeks. In the ED, he had PEA arrest and with ROSC, he was admitted to the CCU for presumed cardiogenic shock, with labs remarkable for lactate 7.5 mmol/L, pro-BNP 6104 pg/mL, and markedly elevated serum creatinine and LFTs. The patient exhibited HF symptoms for 9 months before admission, manifesting as worsening LE edema, fatigue, and weight gain. He was also noted to have untreated hypothyroidism with repeat TSH of 857 μIU/mL on admission, indicating MC as a potential trigger for worsening HF. TTE revealed severe biventricular dysfunction with global hypokinesis and LVEF of 10-15%. Inotropic support was initiated with dobutamine, with RHC showing CVP 11 mmHg, RV 23/11 mmHg, PA 32/22 mmHg, PCWP 25 mmHg, and CI 2.3 LPM/m 2 . Subsequent deterioration in CI and MVO2 necessitated IABP placement and vasopressor support, and later rescue VA-ECMO with atrial septostomy, aiming for OHT. Endocrine evaluation confirmed primary hypothyroidism, and the patient received high-dose levothyroxine, T3, and stress-dosed steroids. While there have been instances where cardiac consequences of myxedema HF were reversed by thyroid administration, his significantly dilated left ventricular internal dimension at end diastole, as well as complications of ECMO (bleeding) expedited his transplant evaluation. OHT was successfully performed on hospital day 14. Continuous improvement in thyroid function studies was observed throughout the treatment course with levothyroxine therapy. Discussion: Worsening HF in the setting of MC, particularly in a male patient, is an uncommon presentation that requires prompt action. This patient required mechanical support as an eventual bridge to OHT with simultaneous treatment for hypothyroidism, illustrating the complexity of the case and the interventions necessary for a positive outcome in an uncommon clinical scenario.

Effects of repetitive Iodine thyroid blocking on the foetal brain and thyroid in rats: a systems biology approach

A single administration of an iodine thyroid blocking agent is usually sufficient to protect thyroid from radioactive iodine and prevent thyroid cancer. Repeated administration of stable iodine (rKI) may be necessary during prolonged or repeated exposure to radioactive iodine. We previously showed that rKI for eight days offers protection without toxic effects in adult rats. However, the effect of rKI administration in the developing foetus is unknown, especially on brain development, although a correlation between impaired maternal thyroid status and a decrease in intelligence quotient of the progeny has been observed. This study revealed distinct gene expression profiles between the progeny of rats receiving either rKI or saline during pregnancy. To understand the implication of these differentially expressed (DE) genes, a systems biology approach was used to construct networks for each organ using three different techniques: Bayesian statistics, sPLS-DA and manual construction of a Process Descriptive (PD) network. The PD network showed DE genes from both organs participating in the same cellular processes that affect mitophagy and neuronal outgrowth. This work may help to evaluate the doctrine for using rKI in case of repetitive or prolonged exposure to radioactive particles upon nuclear accidents.

Proactive Complex Hormone Therapy in the Clinical Guideline for the Managing the Potential Donor Organs in BrainDead Donors

Goal of study: to improve hemodynamics, respiratory exchange and metabolism of potential donor organs by using combination of Lthyroxin, triiodothyronine, methylprednisolone, desmopressin acetate and insulin. Material and Methods: The clinical study included 98 potential donors (PD) with confirmed diagnosis of brain death. Braindead PD were divided into two groups: the 1st group included 43 PD with traumatic brain injury; the 2nd group included 55 PD with a stroke. PD from the 1st and 2nd groups were divided into two subgroups: main subgroup (n=18 and n=30) included those who received Lthyroxine, triiodothyronine and dessom pressin orally; control subgroup (n=25 and n=25) included those who did not receive these drugs. Hemodynamics, electrolytes, biochemical parameters, respiratory exchange and free triiodothyronine and thyroxine in blood were determined during the study. Results and discussion : In the course of the intensive therapy in control subgroups of both groups of PD the doses of noradrenalin and dopamine were not changed. However, the doses of noradrenalin and dopamine were decreased significantly in main subgroups of both groups during the course of the hormone therapy. There were no significant changes in hemodynamics in PD from both control subgroups, whereas in main groups hemodynamics parameters were decreased due to hormone therapy. Significant changes of blood pressure were observed in the main subgroups. Despite exogenous administration, in the main subgroups T3 remained at the lower limit of norm, whereas T4 increased. Improved hemodynamics and gas exchange were revealed in PD following hormone therapy that was important for the blood flow in organs. Following transplantation, in recipients of organs from control subgroup of PD the rejections of the transplants were significantly more frequent than rejections of organs from PD which comprized the main subgroup receiving hormones. Conclusion. Hormone administration to braindead PD with confirmed brain death led to significantly reduced doses of noradrenalin and dopamine and improved hemodynamics and gas exchange parameters. Oral administration of thyroid and hypophisis hormones to PD with confirmed brain death seems feasible.

Effect of thyroid hormone status and concomitant medication on statin induced adverse effects in hyperlipidemic patients.

Statins are effective treatment for the prevention of cardiovascular diseases and used extensively worldwide. However, adverse effects induced by statins are the major barrier of maximalizing cardiovascular risk reduction. Hypothyroidism and administration of drugs metabolized on the same cytochrome P450 (CYPP450) pathways where statin biotransformation occurs represent a significant risk factor for statin induced adverse effects including myopathy. Simvastatin, atorvastatin and lovastatin are metabolized by CYP3A4, fluvastatin by CYP2C9, while rosuvastatin by CYP2C9 and 2C19. We investigated the levels of the free thyroid hormones and CYP metabolism of concomitant medication in 101 hyperlipidemic patients (age 61.3 +/- 9.9 ys) with statin induced adverse effects including myopathy (56 cases; 55.4%), hepatopathy (39 cases; 38.6%) and gastrointestinal adverse effects (24 cases; 23.8%). Abnormal thyroid hormone levels were found in 5 patients (4.95%); clinical hypothyroidism in 2 and hyperthyroidism in 3 cases. 11 patients had a positive history for hypothyroidism (10.9%). Myopathy occured in one patient with hypothyroidism and two patients with hyperthyroidism. There were no significant differences in the TSH, fT4 and fT3 levels between patients with statin induced myopathy and patients with other types of adverse effects. 78 patients (77.2%) were administered drugs metabolized by CYP isoforms also used by statins (3A4: 66 cases (65.3%); 2C9: 67 cases (66.3%); 2C19: 54 cases (53.5%)). Patients with myopathy took significantly more drugs metabolized by CYP3A4 compared to patients with other types of adverse effects (p < 0.05). More myopathy cases were found in patients on simvastatin treatment (52% vs. 38%, ns.), while significantly less patients with myopathy were on fluvastatin treatment (13% vs. 33%, p < 0.05) compared to patients with other types of statin induced adverse effects. Both abnormal thyroid hormone status and administration of drugs metabolized by CYP3A4, 2C9 and 2C19 are common in our patients with statin induced adverse effects. Normalizing the thyroid hormone status and optimizing of the concomitant medication may reduce the risk of statin induced adverse effects.

安定ヨウ素剤投与時期の&lt;sup&gt;131&lt;/sup&gt;I甲状腺摂取率抑制効果の評価～体内動態モデルによる日本人を対象とした計算～

安定ヨウ素剤投与時期の&lt;sup&gt;131&lt;/sup&gt;I甲状腺摂取率抑制効果の評価～体内動態モデルによる日本人を対象とした計算～

Relationship betweenserum TSH and dyslipidemia

Objective To investigate the relationship between serum thyrotrophin(TSH)and dyslipidemia in subclinical hypothyroid and euthyroid subjects. Methods An epidemiological study on diabetes and thyroid diseases was performed in Dadong community, Shenyang city, in 2007. 110 subjects with subclinical hypothyroidism(SCH)and 1 240 euthyroid subjects were enrolled in the study. Neither history of thyroid diseases nor administration of thyroid-related and lipid-regulating medicines were reported in these subjects. The levels of serum thyroid hormones, lipids, fasting plasma glucose(FPG), and insulin were determined. Results (1)Patients with SCH had significantly lower HDL-C levels than those who were euthyroid.(2)According to the guideline of treatment of adult dyslipidemia in China, the lipid profiles were each categorized. Mean TSH levels were higher in subjects in the dyslipidemia subclass than subjects in the normal subclass. The differences were significant in high LDL-C subclass in overweight individuals. In euthyroid overweight women, mean TSH levels were significantly higher in high LDL-C subclass. In the euthyroid population, TSH was positively associated with total cholesterol in overweight population. The association was not modified by the homestasis model assessment for insulin resistance(HOMA-IR)values.(3)TSH was associated positively with serum triglycerides and negatively with serum HDL-C in women. TSH was positively associated with total cholesterol in overweight population and positively associated with total cholesterol and LDL-C in overweight women after adjustment for age, sex, and body mass index. Conclusion Raised serum TSH seems to be a risk factor of dyslipidemia in subclinical hypothyroid and euthyroid subjects, which is independent of insulin sensitivity. Key words: Thyrotropin; Total cholesterol; Low-density lipoprotein-cholesterol; Triglycerides; High-density lipoprotein-cholesterol

Dilated cardiomyopathy associated with autoimmune disease of thyroid gland

Congestive heart failure is the main cause of cardiovascular morbidity and mortality with more than one million hospitalizations per year. Dilated cardiomyopathy is one of the main causes of congestive heart failure characterized by diminished function of the left, right or both ventricles and ejection fraction less than 40%. Numerous studies reported that the diseases of thyroid gland among the patients with dilated cardiomiopathy were very frequent: with prevalence from 18% to 49%. The impaired thyroid gland function was found as primary cause of cardiomyopathy in 1% of patients. At the same time, among patients with terminal dilated cardiomyopathy, euthyroid sick syndrome was very frequent with low values of T3. According to our results, 29.4% of patients with dilated cardiomyopathy also had autoimmunity disorder of thyroid gland with present antithyroglobin and antimicrosomal antibodies. These patients had lower ejection fraction and worse prognosis. In American College of Cardiology/American Heart Association guidelines for the evaluation and treatment of the congestive heart failure, evaluation of thyroid gland function was recommended; but the evaluation of antitireoglobulin antibodies and free T3 and free T4 was also essential, as was calculation of their ratio. This is the way to discover the autoimmunity disorder of thyroid gland and/ or "euthyroid sick syndrome". In patients with dilated cardiomyopathy and low-T3 syndrome, short-term administration of thyroid hormones resulted in improvement of ejection fraction, diminishing of symptoms and better survival.

The effects of the hormones of peripheral endocrine glands on the processes of behavior, learning, and memory.

The effects of systemic administration of thyroid, adrenal cortex, and sex hormones on learning ability, memory trace retention, and behavior were compared in male rats. These studies showed that thyroid, corticosteroid, and sex hormones had no effect on passive learning. Excess quantities of sex hormones disrupted active learning and subsequent reproduction of received information; an excess of thyroid hormone improved the acquisition and retention of the active avoidance habit. Increases in the levels of adrenal cortex hormones worsened active learning and the retention of memory traces, and also increased the level of behavioral activity.

Thyroid administration to reduce root resorption.

Thyroid administration to reduce root resorption.

Myocardial Infarction: Severe Reversible Ischemia and Shock Following Excess Thyroid Administration in a Man With Normal Coronary Arteries

To the Editor .—We read, with interest, the article by Bergeron et al in the June issue of theArchives. 1 We here at Truman Medical Center East, Kansas City, Mo, have recently seen a young man with congestive heart failure secondary to self-induced levothyroxine sodium (Synthroid) toxicity taken in an attempt to lose weight. Report of a Case .—A 35-year-old obese white male medical technician presented with congestive heart failure and atrial fibrillation. He denied prior myocardial infarction, elevated cholesterol levels, chest pain, or other symptoms of coronary artery disease. He complained of several days of increasing dyspnea on exertion, with leg edema, which led to shortness of breath at rest. On admission he denied use of any medication. Physical examination and chest roentgenogram confirmed the diagnosis of congestive heart failure. Once hospitalized, an aggressive diuresis ensued with the use of diuretics. He denied the use of thyroid medication

Myocardial infarction: severe reversible ischemia and shock following excess thyroid administration in a man with normal coronary arteries

Myocardial infarction: severe reversible ischemia and shock following excess thyroid administration in a man with normal coronary arteries

Myocardial Infarction, Severe Reversible Ischemia, and Shock Following Excess Thyroid Administration in a Woman With Normal Coronary Arteries

In the absence of fixed coronary artery disease, thyrotoxicosis is rarely associated with acute myocardial infarction and/or ischemia. There are no known reports on the association of acute myocardial infarction with iatrogenic or factitious thyrotoxicosis in the absence of fixed coronary artery stenosis or coronary artery spasm. A 68-year-old woman, clinically in a state of thyrotoxicosis as a result of taking 0.3 g/d of exogenous thyroid replacement, sustained a severe, reversible myocardial ischemic event. Echocardiographic and scintigraphic evaluations demonstrated a large apical dyskinetic region. Subsequently, after the original dose of levothyroxine sodium was reduced to 0.15 mg and the patient became euthyroid, two-dimensional echocardiography and scintigraphic and cardiac catheterization studies demonstrated normal left ventricular contractility and normal coronary anatomy. Coronary artery spasm was not induced by ergonovine maleate therapy. Exogenous thyroid administration may directly influence myocardial oxygen supply and demand, exclusive of coronary artery disease and coronary spasm. A critical imbalance may then result in acute myocardial ischemia and reversible left ventricular segmental wall motion abnormalities.

Myocardial infarction, severe reversible ischemia, and shock following excess thyroid administration in a woman with normal coronary arteries

• In the absence of fixed coronary artery disease, thyrotoxicosis is rarely associated with acute myocardial infarction and/or ischemia. There are no known reports on the association of acute myocardial infarction with iatrogenic or factitious thyrotoxicosis in the absence of fixed coronary artery stenosis or coronary artery spasm. A 68-year-old woman, clinically in a state of thyrotoxicosis as a result of taking 0.3 g/d of exogenous thyroid replacement, sustained a severe, reversible myocardial ischemic event. Echocardiographic and scintigraphic evaluations demonstrated a large apical dyskinetic region. Subsequently, after the original dose of levothyroxine sodium was reduced to 0.15 mg and the patient became euthyroid, two-dimensional echocardiography and scintigraphic and cardiac catheterization studies demonstrated normal left ventricular contractility and normal coronary anatomy. Coronary artery spasm was not induced by ergonovine maleate therapy. Exogenous thyroid administration may directly influence myocardial oxygen supply and demand, exclusive of coronary artery disease and coronary spasm. A critical imbalance may then result in acute myocardial ischemia and reversible left ventricular segmental wall motion abnormalities. (<i>Arch Intern Med</i>1988;148:1450-1453)

Study of ventricular isomyosins during normal and thyroid hormone induced cardiac growth

We have detected and isolated by the immunoadsorption technique two variants of myosin heavy chains (HC α and HC β) from ventricles of normal rabbit. The two variants differ in at least four antigenic determinants and in several proteolytic fragments. Quantitation of myosin heavy chains using specific monoclonal antibodies in a radioimmunoassay revealed that the proportion of the two variants changes with rabbit age, and after thyroid administration. In newborn rabbits, HC α forms 50% of the total heavy chains; with increasing age, this percentage decreases. Administration of thyroid hormone results in replacement of HC β by HC α. Moreover, our analysis has shown that the variant of myosin synthesized by hyperthyroid animals is identical to the HC α found in the ventricles of young euthyroid rabbits.

Morphometric changes in the lungs of rats following adrenalectomy supplemented by desiccated thyroid.

AbstractStudies were conducted to assess the effects of thyrotoxicosis on the lung of the adult adrenalectomized rat. The animals were divided into four groups of seven animals each: Adrenalectomized animals receiving desiccated thyroid in their food for 8 weeks, adrenalectomized animals, and sham‐operated animals receiving regular laboratory chow. Unoperated animals were used as controls. There were no differences in the pressure‐volume curves or morphometric parameters between unoperated‐control and sham‐operated animals; therefore they will be collectively reported as control animals. Lung volume in the thyroid‐treated animals showed an increase of 19% in pressure‐volume studies when compared with the other groups. Lung volume determined morphometrically demonstrated a 19% increase in volume when adrenalectomized thyroid‐treated rats were compared with control amimals, and a 29% increase compared with adrenalectomized animals. The thyroid‐treated animals also showed an alveolar surface density (Sva) increase of 58% over control and 28% over adrenalectomized animals. In addition, alveolar surface area (Sa) of the treated animals was 89% greater than control and 65% greater than adrenalectomized animals. The marked difference in the surface‐to‐volume ratio indicates that alveoli were smaller and more numerous in the lungs from the thyroid‐treated animals. These results are readily apparent in examination of light microscopic sections of the lung specimens from the four groups of animals. These findings indicate that chronic thyroid administration results in a significant increase in lung volume, which we attribute to increased alveolar partitioning.

Role of thyroid hormones in the normal and glucocorticosteroid hormone-induced evolution of carbamoylphosphate synthase (ammonia) and arginase activity in perinatal rat liver.

Administration of thyroid hormones causes a dose-dependent increase in carbamoylphosphate synthase (ammonia) and arginase activities in fetal rat liver but not in neonatal rat liver. Simultaneous administration of thyroid and glucocorticosteroid hormones enhances enzyme accumulation still further in the fetus. When administered before birth, the relative potencies of T4 and reverse T3, compared to T3 are 20--25% and 1--20%, respectively. Both before and after birth, thyroid hormones enhance DNA content of the liver. Hypophysectomy of rat fetus reduces the carbamoylphosphate synthase activity level in hepatocytes to 30--40% of that in intact animals. Thyroid and glucocorticosteroid hormone administered individually to hypophysectomized animals stimulate enzyme activity 2- to 3-fold; and if administered simultaneously, 4- to 6-fold. Premature delivery with continuation of thyroid and/or glucocorticosteroid hormone treatment started before birth shows uninterrupted enzyme accumulation profiles. Delaying birth by progesterone treatment of the dam leads to uninterrupted but reduced rates of enzyme accumulation in hepatocytes.

Studies of isolated fetal mouse hearts in organ culture. Evidence for a direct effect of triiodothyronine in enhancing cardiac responsiveness to norepinephrine.

Definitive confirmation or denial of the hypothesis that thyrotoxic hearts are supersensitive to catecholamines has been difficult to obtain, largely because secondary alterations in neural and humoral factors that occur after thyroid administration in vivo may obscure the primary changes induced by the hormone on the myocardium itself. To study the direct action of thyroid hormone apart from secondary factors, thyrotoxicosis should be induced in isolated hearts in vitro, but the slow onset of thyroid action plus the rapid deterioration of conventional in vitro preparations have precluded such experiments.Recen'ly a method was developed for maintaining intact, spontaneously-beating hearts from late-fetal mice in organ culture for several weeks. When 5 x 10(-7) to 5 x 10(-6)m l-triiodothyronine is added to the culture medium arrhythmias and or tachycardia gradually appear, just as in thyrotoxicosis in vivo. Accordingly, these "thyrotoxic" hearts were used in the present experiments to test for altered responsiveness to norepinephrine. Dose-response curves to norepinephrine were identical for hearts maintained for 3 hr in triiodothyro-nine-treated or control medium. After 2 days, however, the curve was shifted to the left in triiodothyronine-treated hearts. Thus, 10(-8)m norepinephrine increased the atrial rate by 20+/-6.1 (sem) beats/min in hearts exposed to 5 x 10(-6)m triiodothyronine and by 1+/-3.0 in control hearts (P < 0.02); 10(-7)m norepinephrine raised the rate by 79+/-22.3 in treated hearts vs. 17+/-9.8 in controls (P < 0.05). At maximal doses (10(-6)m norepinephrine), increases were identical. In addition, norepinephrine (10(-8)-10(-6)m) induced arrhythmias in 56% of treated hearts vs. 14% of controls (P < 0.01). Thus, in a precisely controlled environment free of differences in neural and humoral factors, triiodothyronine can act directly on the fetal mouse heart to enhance sensitivity to norepinephrine.

Effect of hormonal state on cell number and functional maturation of the brain.

IT is known that thyroid administration interferes with postnatal cell formation1 and affects the functional maturation of the brain2,3. Glucocorticoids also inhibit cell division in the brain4–6, but the ultimate behavioural consequences of treatment during infancy with thyroid and with adrenocortical hormones seem to be different2,7. In attempting to understand these differences a study was made of the effects of cortisol on postnatal cell formation in the rat brain. Further details are given elsewhere8.

Thyroid hormone influence upon lung surfactant metabolism.

Thyroid administration and thyroidectomy in the rat profoundly affect the morphological characteristics of the type II pneumonocyte and the quantitative harvest of lung surfactant obtained from alveolar washings. The correlation of the ultrastructural changes with quantitative alterations in lung surfactant is evidence that the lamellar bodies within this cell are the source of the surface-active phospholipids utilized at the air-liquid interphase of lung alveoli. Our findings suggest that in the rat, L-thyroxine may be a potent regulator of lung surfactant metabolism.