Administración subcutánea de levotiroxina en hipotiroidismo refractario / Subcutaneous administration of levothyroxine in refrac tory hypothyroidism

Resumen El hipotiroidismo generalmente se puede tratar de manera efectiva con levotiroxina (LT-4) oral. Sin em bargo, el hipotiroidismo refractario al tratamiento con LT-4 es una condición clínica frecuente. Entre las causas se encuentra la falta de adherencia, interacciones con alimentos u otros medicamentos y enfermedades gas trointestinales, como enfermedad inflamatoria intestinal y síndromes de intestino corto. El aumento de la dosis oral de LT-4 no siempre es eficaz en estos escenarios. Por lo tanto, pueden ser necesarias otras vías de administración. En este reporte, evaluamos modalidades alternativas de tratamiento para el hipotiroidismo re fractario y presentamos dos pacientes con malabsorción intestinal tratadas con éxito mediante la administración subcutánea de LT-4.

Abstract Hypothyroidism can usually be treated effectively with oral levothyroxine (LT-4) supplementation. However, hypothyroidism refractory to treatment with LT-4 is a common clinical condition. Causes include poor com pliance, interactions with food or other medications, and gastrointestinal diseases, such as inflammatory bowel disease and short bowel syndromes. Increasing the oral dose of LT-4 is not always effective in these scenarios. Therefore, other routes of administration may be neces sary. In this report, we evaluate alternative treatment modalities for refractory hypothyroidism and present two patients with intestinal malabsorption successfully treated by subcutaneous administration of LT-4.

Obtener un mejor tratamiento para el paciente con hipotiroidismo

Introducción: El hipotiroidismo es una entidad de visita frecuente al endocrinólogo, establecer el mejor tratamiento es un desafío, a pesar del manejo adecuado y de un control hormonal óptimo, en ocasiones los pacientes continúan con los síntomas que afectan su calidad de vida, por lo que el tratamiento debe ser individualizado, basado en la mejor evidencia. Objetivo: Establecer las mejores opciones terapéuticas en las diferentes formas de presentación del hipotiroidismo. Métodos: Se realizó una búsqueda bibliográfica no sistemática en las bases de datos de PubMed, Medline, LILACS, EMBASE, Redalyc y guías internacionales. Los criterios de inclusión fueron publicaciones en inglés y español, en las que el título, palabras clave o resumen incluyen información pertinente al objetivo de estudio, periodicidad no mayor a los 5 años a excepción de las guías que son las últimas revisiones. En la búsqueda se obtuvieron 30 artículos de los cuales fueron 14 seleccionados. Conclusiones: Se establecieron las opciones terapéuticas con el fin de obtener un mejor tratamiento para el paciente hipotiroideo que debe ser individualizado y basado en la mejor evidencia, para alcanzar un control adecuado de su enfermedad, mejorar la calidad de vida y evitar complicaciones relacionadas con esta patología.

Introduction: Hypothyroidism is an entity that is frequently seen at the endocrinologist´s. establishing the best treatment is a challenge, despite proper management and optimal hormonal control, sometimes patients continue with symptoms which affect their quality of life, therefore that treatment should be individualized, based on the best evidence. Objective: To establish the best therapeutic options in hypothyroidism different forms of presentation. Methods: A non-systematic bibliographic search was carried out in PubMed, Medline, LILACS, EMBASE, Redalyc databases and in the international guidelines. The inclusion criteria were publications in English and Spanish, in which the title, keywords or abstract include relevant information to the objective of the study, with a periodicity of no more than 5 years, except for the guidelines that the latest revisions were used. In the search, 30 articles were retrieved, 14 which were selected. Conclusions: The therapeutic options were established in order to find better treatment for hypothyroid patients, which must be individualized and based on the best evidence, to achieve adequate control of the disease, to improve the quality of life and to avoid related complications.

Effects of discontinuation of levothyroxine sodium before radioactive iodine therapy after DTC on blood lipids and renal function in patients / 中华内分泌外科杂志

Objective:To investigate the effect of levothyroxine withdrawal before radioiodine therapy on blood lipids and renal function in patients with differentiated thyroid carcinoma (DTC) after operation.Methods:From Mar. 2020 to Apr. 2022, 214 patients with differentiated thyroid cancer were enrolled in the General Surgery Department, Linyi Central Hospital, Shandong Province. All patients stopped taking levothyroxine sodium after total thyroidectomy. The thyroid function index, blood lipid index and renal function index were measured and compared before and after drug withdrawal (before operation) and after drug withdrawal (before radioiodine treatment). The patients were divided into groups according to the duration of drug withdrawal (drug withdrawal group for 3 weeks, drug withdrawal group for 4 weeks), and the differences of thyroid function index, blood lipid index, and renal function index among patients with different drug withdrawal time were compared. The measurement data in accordance with normal distribution were compared between groups, and independent sample t-test was performed. Results:The levels of free thyroxin T4 (FT 4) and free triiodothyronine (FT 3) in DTC patients decreased significantly ( t=57.60, 71.74,all P<0.001), and the levels of thyroid-stimulating hormone (TSH) increased significantly ( t=102.15, P<0.001). After drug withdrawal, the serum lipid index [triglyceride (TG), total cholesterol (TC), high-density lipoprotein (HDL), low density lipoprotein (LDL) ] and renal function index [blood urea nitrogen (BUN), serum creatinine (SCR) ] of DTC patients increased significantly ( t=20.17, 42.50, 12.13, 30.73, 16.09, 43.73, all P<0.001). The levels of FT 3 and FT 4 in the 4-week group were significantly lower than those in the 3-week group ( t=7.75 and 10.07, both P<0.001), and TSH was significantly higher than that in the 3-week group ( t=26.46, P<0.001). The levels of TG, LDL, HDL, TC, BUN and Scr in the 4-week group were significantly higher than those in the 3-week group ( t=10.13, 10.29, 8.53, 11.47, 10.54, 8.55, all P<0.001). Correlation analysis showed that the levels of FT 3 and FT 4 in DCT patients were negatively correlated with the levels of TG, LDL, HDL, TC, BUN and Scr ( r=-0.256, -0.189, -0.249, -0.314, -0.352, -0.231, -0.342, -0.259, -0.304, -0.216, -0.391, -0.271, P=0.011, 0.029, 0.007, 0.004, 0.015, 0.036, 0.002, 0.009, 0.019, 0.017, 0.016, 0.003), and the levels of TSH were correlated with TG, LDL, HDL, TC and BUN Scr level was positively correlated ( r=0.257, 0.308, 0.219, 0.311, 0.251, 0.271, P=0.006, 0.013, 0.032, 0.004, 0.006, 0.014) . Conclusion:Stopping levothyroxine sodium before radioactive iodine treatment after DTC can easily lead to dyslipidemia and decreased renal function in patients, and the longer the withdrawal time is, the more obvious the changes of blood lipids and renal function in patients, and the withdrawal time should be shortened in clinical treatment.

ffects of Zuogui Pills on kidney-yin deficiency syndrome of premature ovarian insufficiency rats / 国际中医中药杂志

Objective:To study the effects of Zuogui Pills on rats with kidney-yin deficiency syndrome of premature ovarian insufficiency.Methods:Totally 40 SD female unmated rats were randomly divided into blank group, model group, Zuogui Pills group and Bujiale group, with 10 rats in each group. Except for blank group, rats in other groups were subcutaneously injected with ZP3 and gavaged with levothyroxine sodium to induce kidney-yin deficiency syndrome model of premature ovarian insufficiency. At the same time of modeling, Zuogui Pills group and Bujiale group received corresponding drugs for gavage, and the other groups received corresponding solvent for gavage, once a day, for consecutive 21 days. On day 0, 7, 14 and 21, ear temperature and body weight of rats were measured, and the ovarian index, uterus index and thyroid index were calculated. Serum levels of adenosine cyclic phosphate (cAMP), cyclic guanosine phosphate (cGMP), Cortisol, follicle-stimulating hormone (FSH), luteinizing hormone (LH) and estradiol (E 2) were detected by ELISA. Pathological changes of ovary was observed with HE staining. Results:On day 14 and 21, compared with model group, the body weight of rats in Zuogui Pills group increased ( P<0.05), and the ear temperature decreased ( P<0.05); compared with model group, the ovarian index, uterine index and thyroid index of rats in Zuogui Pills group decreased ( P<0.05), the levels of serum cAMP/cGMP, cortisol, FSH and LH decreased ( P<0.05), and the level of E 2 increased ( P<0.05). Conclusion:Zuogui Pills have certain improvement effect on rats with kidney-yin deficiency syndrome induced by levothyroxine sodium tablets combined with ZP3.

No obvious symptoms in acute (eltroxin) thyroxine poisoning in euthyroid – A case report

Levothyroxine (T4) (Eltroxin) poisoning is a rare clinical entity which is usually asymptomatic. It can occur accidently, mostly in children, and can happen intentionally in adults with suicidal intention especially psychiatric patients. Thyrotoxicosis from an overdose of medicinal thyroid hormone is a condition that may be associated with a significant delay in onset of toxicity. However, severe symptoms such as respiratory failure, malignant hyperthermia, seizures, arrhythmia, and coma have been reported. In this case report, we present a patient who ingested high doses of levothyroxine i.e., 90 tab. of Eltroxin 100 mcg, for suicidal intension and admitted to intensive care unit. She is an euthyroid person but took these tablets, which her mother was taking Eltroxin tablets for hypothyroidism. Gastric lavage was done with activated charcoal, Inj. Hydrocortisone, Tab Propranolol and Tab Neomercazole administered. Despite ingestion of high dose of levothyroxine, thyrotoxicosis symptoms like palpitations resolved with appropriate treatment and the patient was discharged after complete recovery.

Effect of Helicobacter pylori infection on standard dose of postoperative thyrotropin suppression therapy for differentiated thyroid cancer / 中华内分泌外科杂志

Objective:To study the effect of Helicobacter pylori (HP) infection on the standardized dose of postoperative thyrotropin suppression of differentiated thyroid carcinoma.Methods:A total of 82 patients diagnosed with differentiated thyroid carcinoma and receiving total thyroidectomy in Beijing Rehabilitation Hospital affiliated to Capital Medical University from Jan. 2019 to Jun. 2020 were enrolled in this study prospectively.19 patients with higher standardized dose of the thyrotropin suppression (>2.5 μg·kg -1·d -1) were selected as the experimental group, and 63 patients with the lower standardized dose of the thyrotropin suppression (≤2.5 μg·kg -1·d -1) were selected as the control group. The presence of HP infection was measured by C13 method, and the HP infection rate was compared between the two groups. The patients with HP infection in the experimental group received standard quadruple therapy to eradicate Helicobacter pylori. The standardized dose before and after treatment were observed and compared. Results:The HP infection rate in the experimental group (73.7%, 14/19) were significantly higher ( P<0.05) than those in the control group (31.7%, 20/63). In the experimental group, 14 patients with HP infection in the experimental group received standard quadruple therapy to eradicate HP. HP was successfully eradicated in 11 patients after the treatment (one patient quit the treatment before completion, the actual eradication rate was 84.6%) ; Eight weeks after the treatment, the dose adjustment of thyrotropin suppression reached steady-state in 13 patients completed the therapy. The average standardized dose was (2.15±0.25) μg·kg -1·d -1, significantly lower than that before treatment [ (2.89±0.21) μg·kg -1·d -1] ( P<0.05) . Conclusions:HP infection may be an important factor affecting the standardized dose of thyrotropin suppression in postoperative patients with thyroid cancer. For those patients with HP infection, eradication treatment of HP can significantly reduce the standardized dose and treatment-related complications.

Profile of Levothyroxine Replacement Therapy in Graves’ Disease patients with Hypothyroidism Post-Radioactive Iodine Ablation: Focus on different weight-based regimens / Journal of the ASEAN Federation of Endocrine Societies

Objective@#To evaluate the status of euthyroidism achieved among Thai patients with post-ablative hypothyroidism and to examine the difference between various weight-based daily levothyroxine (LT4) replacement regimens in these patients.@*Methodology@#We conducted a retrospective review of Thai patients with Graves’ disease (GD) who developed hypothyroidism following radioactive iodine treatment from 2016 to 2020 at Theptarin hospital. Daily LT4 dose was calculated based on actual body weight (ABW), ideal body weight (IBW), and estimated lean body mass (LBM).@*Results@#We reviewed a total of 271 patient records. Of these, 81.2% were females with a mean age of 40.8±11.7 years, LT4 intake duration of 27.1±14.6 months, and LT4 dose/kg ABW of 1.4±0.5 μg/kg/day. At the final follow-up, 62.4% of patients achieved thyroid-stimulating hormone (TSH) levels within the reference interval, 15.5% had TSH levels over, and 22.1% had TSH levels under the reference range. Obese patients required a lower daily LT4 dose relative to ABW and higher daily LT4 dose relative to IBW to attain euthyroidism (ABW 1.1±0.4 μg/kg/day and IBW 2.0±0.8 μg/kg/day). Estimated daily LT4 dose based on LBM showed a constant dosage of 2.0 μg/kg/day in all BMI categories.@*Conclusions@#Suboptimum LT4 replacement therapy was found in almost half of hypothyroid patients with GD treated with radioactive iodine. Estimated LBM was a better indicator for dosing calculation in these patients compared with ABW and IBW.

Effectiveness of early intervention with levothyroxine sodium in pregnancy complicated with hypothyroidism / 中华内分泌外科杂志

Objective:To investigate the effectiveness of early levothyroxine intervention in pregnancy complicated with hypothyroidism.Methods:A retrospective analysis was performed on 132 pregnant patients with hypothyroidism admitted to the Department of Endocrinology, Anyang People’s Hospital from Nov. 2018 to Sep. 2021. Among them, 68 cases with levothyroxine sodium early intervention were included in the intervention group, and 64 cases without intervention were included in the non-intervention group. The differences in vascular endothelial function indexes, thyroid function indexes, and blood lipid indexes before and after treatment in the intervention group were compared with those in the non-intervention group. The incidence of obstetric complications such as preeclampsia, fetal growth restriction, and adverse pregnancy outcomes of abortion and neonatal asphyxia were compared between the two groups. SPSS 21.0 software was used to process data, measurement data were subjected to t test, and enumeration data were subjected to χ 2 test. Results:After treatment, the endothelium-dependent brachial artery blood flow-mediated vasodilation index (FMD) index, nitric oxide (NO) , and endothelin-1 (ET-1) levels in the intervention group were significantly better than those in the non-intervention group [ (10.37%) ±1.54%) vs (7.25% ± 1.09%) , (60.85 ± 7.03) umol/L vs (39.11 ± 4.31) umol/L, (112.96 ± 13.58) umol/L vs (238.85 ± 26.05) umol/L]. After treatment, the serum thyroid stimulating hormone (TSH) in the intervention group was significantly lower than that in the non-intervention group [ (2.25±0.26) mU/L vs (8.79±1.60) mU/L] ( P<0.001) . After treatment, the levels of total cholesterol (TC) , triacylglycerol (TG) and low-density lipoprotein cholesterol (LDL-C) in the intervention group were significantly lower than those in the non-intervention group [ (3.52±0.91) mmol/L vs (6.51±1.31) mmol/L L, (1.30±0.31) mmol/L vs (1.44±0.36) mmol/L, (2.29±0.31) mmol/L vs (3.32±0.44) mmol/L] ( P<0.001, P=0.036, P<0.001) . The incidence of obstetric complications such as preeclampsia, fetal growth restriction, premature rupture of membranes, and abnormal amniotic fluid volume in the intervention group were significantly lower than those in the non-intervention group (5.88% vs 17.19%, 1.47% vs 9.38%, 10.29% vs. 23.44%, 2.94% vs 12.50%) ( P=0.041, 0.043, 0.043, 0.038) ; the incidence of miscarriage, premature birth, neonatal asphyxia, cesarean section and other adverse pregnancy outcomes in the intervention group were significantly lower than those in the non-intervention group (1.47% vs 9.38%, 4.69% vs 15.36%, 2.94% vs 10.94%, 57.35% vs 75.00%) ( P=0.043, 0.031, 0.038, 0.033) . Conclusion:Early intervention with levothyroxine in pregnancy complicated with hypothyroidism is beneficial to improve thyroid function, reduce blood lipid level, protect vascular endothelial function, reduce related obstetric complications, and reduce the incidence of adverse pregnancy outcomes for mothers and infants.

A practical contemporary approach to decision-making on subclinical hypothyroidism

ABSTRACT Subclinical hypothyroidism (Shypo) is an increasingly frequent condition in common medical practice. Its diagnosis continues to pose a challenge since a series of non-thyroidal and temporary conditions can elevate serum TSH levels. In addition, the consequences of Shypo are still up for debate. Although detrimental cardiovascular effects have been consistently demonstrated in the young, they are less evident in older adults (65-79 years), and even more so in the oldest old (≥80 years). In the absence of evidence of any benefits of treating Shypo in patients' clinical manifestations and unfavorable outcomes, the most effective decision-making approach should include a thorough investigation of the patient's condition integrating all relevant clinical data, such as TSH levels, age, quality of life, comorbidities, cardiovascular risk, safety, and personal preferences. The decision-making process needs to take into account the risk of levothyroxine overtreatment and the resulting adverse consequences, such as reduction of bone mineral density, heart failure, and atrial fibrillation. Hence, current evidence suggests that individuals with TSH > 10 mU/L, who test positive for TPO Ab or are symptomatic may benefit from levothyroxine treatment. However, a more cautious and conservative approach is required in older (≥65 years of age), and oldest-old (≥80 years) patients, particularly those with frailty, in which the risk of treatment can outweigh potential benefits. The latter may benefit from a wait-and-see approach.

Iraqi Propolis, Carbimazole, Levothyroxine and their Propolis Combinations Effects on Renal Histopathological Parameters in Female Rats

Abstract Iraqi propolis (PR) have powerful antioxidants, free radical scavenger and anti-inflammatory constituents makes it to have a protective effect on renal function. The aim of this study is to evaluate the possible protective effect of Iraqi propolis (PR) on renal toxicity induced by Carbimazole (CB) and levothyroxine (TR) in rats. Forty-two adult female albino rats randomized into six groups: control, PR, CB, TR, PR + CB and PR +TR. Rats orally treated by gavage for six weeks. Haematological and histopathological analyses performed. A significant increase in hemoglobin percentage, RBC count and Haematocrit percentage after exposure to PR + CB and PR + TR combinations compared to control. CB dose of 0.01mg /g for six weeks causes renal damage in female rats and TR dose of 0.1µg/g for six weeks causes renal degenerative effects. Rats treated with PR+TR show normal appearance in kidney tissue, glomeruli and renal tubules compared to thyroxin group alone. In addition, PR+ CB treatment show more improvement in renal tissue, normal glomeruli and renal tubules compared to CB alone. It is concluded that PR combination with CB or TR might have an effect on the blood, further studies needed to confirm this effect on human to be used for anemia accompanied thyroid disruptions. In addition, further studies needed to confirm renal protective effect on human to be used for this effect.

Un inusual caso de granuloma piogeno oral multiple, ¿asociado a tratamiento con levotiroxina? / An unusual case of multiple oral pyogenic granuloma, ¿associated with treatment with levothyroxin?

RESUMEN El Granuloma piógeno (GP) es una lesión tumoral, no neoplásica, vascular, generalmente solitaria, que se presenta en la cavidad oral o piel, la etiología aún no está muy clara, se considera que es una lesión reactiva a varios estímulos de bajo grado, entre los cuales podemos contar traumas repetidos, agresiones, factores hormonales y ciertos fármacos. El GP múltiple, es un fenómeno raro, generalmente asociado al uso de drogas, como la carbamacepina, ciclosporina, retinoides, levotiroxina, etc. Se presenta el caso de una paciente de 50 años, referida por presentar aumento de volumen en reborde alveolar del primer, tercer y cuarto cuadrantes; con antecedentes de psoriasis eritrodermica e hipotiroidismo, en tratamiento con levotiroxina aproximadamente seis meses antes que se presenten las lesiones; se realiza exeresis quirúrgica y curetaje subperiostico, se enviaron las muestras a anatomía patológica, confirmándose el diagnóstico definitivo de GP; por los antecedentes, y la aparición casi simultánea de las lesiones en múltiples cuadrantes, se sospecha que estas, están asociadas al consumo terapéutico de levotiroxina para el hipotiroidismo.

SUMMARY Pyogenic Granuloma (GP) is a tumorous, non-neoplastic, vascular, generally solitary lesion that presents itself in the oral cavity or skin, the etiology is still not very clear, it is considered to be a reactive lesion to several low grade stimuli, among which we can count repeated trauma, aggressions, hormonal factors and certain drugs. The multiple GP, is a rare phenomenon, generally associated with the use of drugs, such as carbamacepine, cyclosporine, retinoids, levothyroxine, etc. It presents the case of a patient of 50 years, referred for presenting increased volume in alveolar ridge of the first, third and fourth quadrants, with a history of erythrodermic psoriasis and hypothyroidism, in treatment with levothyroxine approximately six months before the lesions occur; Surgical exeresis and subperiosteal curettage is performed, samples were sent to pathological anatomy, confirming the definitive diagnosis of GP; because of the history, and the almost simultaneous appearance of the lesions in multiple quadrants, it is suspected that these are associated with the therapeutic consumption of levothyroxine for hypothyroidism.

A prospective study on evaluation of maternal and foetal outcomes of hypothyroidism with levothyroxine and prevalence of hypothyroidism in pregnancy in a tertiary care teaching hospital in Kerala

Background: Pregnancy influences a profound alteration in thyroid function and hypothyroidism has a massive impact on adverse pregnancy outcomes. An appropriate treatment with appropriate dose of levothyroxine is much essential during pregnancy. The present study evaluates the effect of levothyroxine dose in preventing maternal and foetal outcomes and the prevalence of hypothyroidism among pregnant women.Methods: 1500 antenatal women with singleton gestation attending outpatient of Obstetrics and Gynaecology Department, were analysed. Apart from routine obstetrical investigations, thyroid stimulating hormone (TSH) tests were done at the first antenatal visit. Patients were followed up till delivery after levothyroxine treatment. Their obstetrical and perinatal outcomes were noted. TSH estimation was done 3 days after delivery in new-borns to screen for neonatal thyroid disorders.Results: The prevalence of hypothyroidism was 10.54%. The common adverse maternal and foetal complications were preeclampsia (15.19%) and low birth weight babies (17.72%) respectively. The mean age of pregnant women was 26.66 years. As age advances there is an increased risk of developing hypothyroidism in pregnancy. Levothyroxine 25 ?g daily was highly prescribed in 63.92% hypothyroid patients.Conclusions: Overall, the prevalence of hypothyroidism was high. Since maternal and foetal complications were higher in patients with hypothyroidism, levothyroxine treatment had decreased the risk of maternal and foetal outcome. Pre-pregnancy screening should be implemented at least in patients with high risk factors for thyroid dysfunction. Universal screening for new-borns is also recommended to detect hypothyroidism. Expert decisions and cost-effectiveness studies will promulgate the impact of universal screening.

Aerobic exercise combined with levothyroxine and vitamin d3 relieves osteoporosis in subclinical hypothyroidism rats / 中国组织工程研究

BACKGROUND: Levothyroxine can significantly improve the symptoms of subclinical hypothyroidism, and some studies have pointed out that levothyroxine can partially improve the abnormal bone metabolism of experimental rats, but the therapeutic effect of levothyroxine on subclinical hypothyroid osteoporosis is rarely studied. OBJECTIVE: To observe the effects of aerobic exercise combined with levothyroxine and vitamin D3 on the symptoms of osteoporosis in subclinical hypothyroidism rats. METHODS: Wistar rats were divided into blank control group, sham-operated group and model group. The thyroid function was measured to determine whether the model was successfully established. The model group rats were further divided into eight groups: non-treatment group, exercise group, L-thyroxine group, vitamin D3 group, exercise + levothyroxine group, exercise + vitamin D3 group, levothyroxine + vitamin D3 group and exercise + levothyroxine + vitamin D3 group, with another normal control group. At the 52th day after treatments, the bone resorption markers, β isomer of C-terminal telopeptide of type I collagen (β-CTX) and tartrate-resistant acid phosphatase-5b (TRACP-5b), and the bone formation markers, bone-specific alkaline phosphatase (BLAP), type I procollagen amino-terminal propeptide (PINP), and serum osteocalcin (BGP) were detected. Bone mineral density of the rat skull, spine, upper limb and lower limb was scanned. Serum calcium and phosphorus levels and cathepsin K level in the right femur were measured. Hematoxylin-eosin staining of the rat femoral head was performed. RESULTS AND CONCLUSION: At the modeling stage, serum thyroid-stimulating hormone (TSH) level of rats in the model group was significantly higher than that in the sham-operated group and blank control group (P < 0.05). But there was no significant difference in serum T3 and T4 among the groups, indicating that the subclinical hypothyroidism rat model was successfully established. After treatment, compared with the rats without levothyroxine treatment, serum TSH levels in the rats of the levothyroxine group, the levothyroxine + vitamin D3 group, the exercise + levothyroxine group and the exercise + levothyroxine + vitamin D3 group were significantly decreased (P < 0.05), while the levels of T3 and T4 were not significantly changed. But the levels of β-CTx, TRACP-5b, BLAP, PINP, BGP and BMD in rats with levothyroxine treatment were significantly increased compared with those without levothyroxine treatment (P < 0.05). And the rats in the exercise + L-thyroxine + vitamin D3 group had the most significant improvement on the bone metabolism indexes and BMD (P < 0.05). Serum calcium and phosphorus levels of the rats in the levothyroxine + vitamin D3 group and the exercise + levothyroxine + vitamin D3 group were significantly higher than those in other groups with no vitamin D3 (P < 0.05). The rats in the levothyroxine group, the exercise + levothyroxine group, the levothyroxine + vitamin D3 and the exercise + levothyroxine group + vitamin D3 had the lower level of Cathepsin K level in femoral tissue than those in the other groups (P < 0.05). Moreover, the morphology of bone trabecular tissue was significantly improved in the rats with levothyroxine treatment than those with no levothyroxine treatment. To conclude, subclinical hypothyroidism can lead to osteoporosis in rats. Supplementation of levothyroxine is the most critical step of the treatments. Vitamin D3 can relieve osteoporosis by increasing serum calcium and phosphorus levels. Aerobic exercise can significantly enhance the improvement effect of levothyroxine and vitamin D3 on subclinical hypothyroidism osteoporosis. Therefore, comprehensive treatment of levothyroxine, vitamin D3 and aerobic exercise should be emphasized in the treatment of subclinical hypothyroidism osteoporosis.

A Review: Mechanistic Insights Into The Effect Of Thyroid Disorders On Estrogen Level And Bone Mineral Density

Thyroid hormone serves as an indispensable component for the optimum functioning of various biological systems. They curb body’s metabolism, regulates the estrogen level, regulates bone turnover, essential for skeletal development and mineralization. Within the scope of knowledge, it is intimately familiar that thyroid disorders have widespread systemic manifestations, among which in hypothyroidism, even though elevated TSH (thyroid-stimulating hormone) may reduce estrogen level which in turn stimulates osteoclasts and thus cause osteoporosis, while hyperthyroidism accelerates bone turnover. Hypothyroidism does not directly interfere with the skeletal integrity, but treatment with levothyroxine for the suppression of TSH to bring the hypothyroid patient to euthyroid state for a long haul; lead to simultaneous reduction in bone mass and in (bone mineral density) BMD. After the initial relevation of the correlation between thyroid disorders and osteoporosis in numerous studies have emphasized that both hypo and hyperthyroidism either directly or indirectly affects the bone mineral density or leads to the progression of osteoporosis. Therefore the present study is aimed and so designed to review all the possible associations between them and the impact of thyroid disorders on estrogen level and bone mineral density. The main findings of this review indicate that both excesses as well as deficiency of thyroid hormone can be potentially deleterious for bone tissue.

Levothyroxine versus levothyroxine with iodine in reduction of thyroid nodule volume: a double-blind randomized controlled trial

@#<p><strong>Objective: </strong>To compare levothyroxine alone and in combination with iodine on thyroid nodule volume reduction.</p><p><strong>Methods: </strong></p><p><strong>Design:           </strong>Double-Blind Randomized Controlled Trial</p><p><strong>Setting:           </strong>Tertiary Government Hospital</p><p><strong>Participants: </strong>Nineteen (19) euthyroid patients age 19-54 with at least 1 cytologically benign thyroid nodule were randomized to receive either levothyroxine + iodine or levothyroxine + placebo, taken once a day for 6 months with ultrasound and thyroid stimulating hormone monitoring on the 3rd and 6th month of intervention.</p><p><strong>Results: </strong>Main outcome measures included thyroid nodule volume reduction after six months of intervention. The mean change in volume from baseline to six months of levothyroxine + iodine group showed no statistically significant difference in nodule volume across time between  levothyroxine + placebo group, -0.010 ± 1.250 (CI -0.521 - 0.501) versus 0.507 ± 1.128 (CI 0.025 - 0.990), p=.158.  There were also new nodules (4 nodules) in the placebo group and none in the iodine group. No major adverse events were noted during the study.</p><p><strong>Conclusion: </strong>The two groups did not significantly differ in terms of nodule volume reduction.</p><p><strong>Keywords:</strong> thyroid nodule, prevention and control; drug therapy; iodine compounds, therapeutic use; levothyroxine, therapeutic use</p>

Hipotiroidismo refractario a tratamiento / Refractory hypothyroidism

En pacientes con hipotiroidismo en tratamiento con levotiroxina (LT4) no es infrecuente encontrar un grupo que presenta niveles persistentemente elevados de tirotropina (TSH), fenómeno que se conoce como hipotiroidismo refractario. La causa más frecuente de éste es la falta de adherencia al tratamiento, sin embargo deben sospecharse otras causas como condiciones de malabsorción, pérdida urinaria aumentada de proteínas, entre otras, que si bien son menos frecuentes, no dejan de ser importantes. Un enfoque metodológico y escalonado permitirá identificar la causa, evitando así escalar innecesariamente en la dosis del medicamento para alcanzar niveles normales de TSH y el aumento del riesgo secundario a una exposición prolongada a niveles subterapéuticos

In patients undergoing treatment with levothyroxine it is not infrequent to find some whose thyrotropin (TSH) levels remain high, a phenomenon known as refractory hypothyroidism. The most frequent cause is poor compliance, however other causes such as malabsorption and proteinuria, although less common, should not be forgotten. Amethodological and staged approach should identify the cause, thereby avoiding unnecessary increases in medication in an effort to achieve normal TSH levels and diminishing the risk of prolonged exposure to sub-therapeutic levels.

Hipotiroidismo refractario idiopático: un caso clínico / Idiopathic refractory hypothyroidism: case report

Introducción: El hipotiroidismo constituye una patología frecuente, y su tratamiento habitual es el suplemento de levotiroxina (LT4) oral (VO). Sin embargo, existen casos inhabituales donde no es posible corregir esta condición a pesar de la utilización de LT4 en dosis alta. El hipotiroidismo refractario se define como la persistencia del hipotiroidismo a pesar del uso de LT4 > 1,9 ug/kg/día. La prevalencia del hipotiroidismo refractario no ha sido suficientemente documentada hasta ahora. Descripción del caso: Mujer de 53 años con antecedentes de hipotiroidismo, obesidad, dislipidemia, hipertensión arterial e insulinorresistencia. Fue derivada desde APS a nivel terciario por hipotiroidismo persistente a pesar del uso de LT4 800 ug/día y liotironina 80 ug/día. En forma ambulatoria se descartaron distintas causas, como mala adhesión al tratamiento, pseudo-malabsorción, síndromes de malabsorción; interacciones farmacológicas o interacciones alimentarias. Ante esto, y manteniéndose en su condición, se decide hospitalizar. Durante la hospitalización se prueban distintas fórmulas de administración. Finalmente, se logra respuesta adecuada con LT4 por vía rectal 100 ug/día asociado a 100 ug c/12 horas VO. Discusión: A pesar de no contar con herramientas óptimas para enfrentar este caso, se logró aplicar una estrategia sistemática especializada, que permitió un buen manejo de la paciente. Luego de probar distintas formulaciones de hormonas tiroideas, se logró respuesta mediante la administración por vía rectal, lo cual sugiere que esta paciente presentaba algún trastorno celular/bioquímico intestinal alto, que impedía la absorción óptima de LT4 VO. Conclusiones: La principal fortaleza de este trabajo consiste en la demostración de la utilidad práctica, en un contexto de recursos limitados, de una estrategia de estudio y tratamiento sistemático del hipotiroidismo refractario, lo cual ha sido escasamente publicado en la literatura internacional. Además, se recalca la importancia de una intervención especializada oportuna para evitar los riesgos sistémicos asociados a dosis altas de hormonas tiroideas.

Introduction: Hypothyroidism is a common condition, and its usual treatment is the supplement of oral levothyroxine (po). However, there are unusual cases where it is not possible to correct this condition despite the use of high-dose levothyroxine. Refractory hypothyroidism is defined as the persistence of hypothyroidism despite the use of levothyroxine > 1.9 ug/kg/ day. The prevalence of refractory hypothyroidism has not been sufficiently documented so far. Case description: 53 year old woman with a history of hypothyroidism, obesity, dyslipidemia, hypertension and insulin resistance. She was sent from primary care to tertiary level due to persistent hypothyroidism despite the use of 800 ug/day levothyroxine and liothyronine 80 ug/ day. On an outpatient basis, different causes were excluded as poor adherence to treatment, pseudo-malabsorption, malabsorption syndromes; drug interactions or food interactions. Given this, and staying on her condition, it was decided to hospitalize. Different forms of administration were tested during hospitalization. Finally, got adequate response with levothyroxine rectally 100 ug/day associated with 100 ug po bid. Discussion: Despite not having optimum tools to deal with this case, it was succeeded thanks to the implementation of a specialized systematic strategy. After testing different formulations of thyroid hormones, a positive response by rectal administration was achieved, which suggests that this patient presented any high intestinal cell/biochemist disorder that prevented the optimal absorption of levothyroxine po. Conclusions: The main strength of this work consists in demonstrating the practical utility, in a context of limited resources, of a study and systematic treatment strategy of refractory hypothyroidism, which has barely been published in the international literature. It is also highlighted the importance of an early specialized intervention to prevent the systemic risks associated with high doses of thyroid hormones.

Investigation of Prediction Model for Optimal Initial Dose of Levothyroxine in Differentiated Thyroid Cancer Patients after Surgery / 中国药房

OBJECTIVE： To construct prediction model for initial dose of levothyroxine （L-T4） in differentiated thyroid cancer （DTC） patients after surgery. METHODS： A total of 100 DTC patients underwent surgery were selected from thyroid and breast surgery department in Nanjing Drum Tower Hospital. General information of patients such as gender， age， height， body mass， body mass index （BMI） and regular follow-up information after discharge were collected. Related data of thyroid function and adjusted dose of L-T4 were recorded. Single factor variance analysis and t-test were used to analyze the predictors that had significant correlation with the initial dose of L-T4. The prediction model of L-T4 initial dose was established by linear regression analysis， and was verified by prospective experiments. RESULTS： The initial dose of L-T4 in DTC post-surgery patients were significantly correlated with age （P＝0.01，F＝3.993）， body weight （P＜0.001，F＝6.910） and BMI （P＜0.001，F＝7.698）. Linear regression analysis showed that prediction model of initial dose of L-T4 was L-T4（μg/kg）＝2.971-0.033×BMI-0.005×age. DTC post-operative patients were given L-T4 empirically， and only 16％ （16/100） of the patients met the criteriaat the first follow-up  of thyroicl function. In the validation test， L-T4 was given at the initial dose calculated by the prediction model， and 63.7％      （44/69） of the patients reached the standard at the first follow-up. CONCLUSIONS： The established prediction model of L-T4 initial dose after DTC surgery has a certain practicality.

Association of Thyroid Status with Pregnancy Induced Hypertension and Impact of Levothyroxine Treatment

Background:Pregnancy induced hypertension is an important cause of maternal and fetal morbidity and mortality affecting 5-10% of pregnancies.PIH is more frequently associated with elevated TSH. Hypothyroidism is one of the causes of hypertension in nonpregnant state. Hypertension is completely reversible in 50% cases of hypothyroidism by levothyroxine therapy. Treating hypothyroidism in pregnancy may help to reduce PIH prevalence. Objectives- This is an observational study to find out association of PIH with hypothyroidism and to know result of levothyroxine treatment on PIH prevalence and its severity. Methods: 75 singleton pregnancies with PIH admitted to labour ward, evaluated with their TSH status in groupA. In Group B, 75 singleton pregnancies with subclinical or overt hypothyroidism treated with levothyroxine to maintain euthyroid state throughout pregnancy and observed for development of PIH. Overt hypothyroidism considered when TSH value ≥10 and subclinical hypothyroidism when TSH value between 3 and 10.. Result: Overt and subclinical hypothyroidism was present in 12% (9 out of 75) and 57.3%(43 out of 75) cases of PIH respectively. In group B, all hypothyroid pregnancies treated with levothyroxine throughout pregnancy, prevalence of PIH was 6.66% (5 out of 75) . Significant association of PIH and hypothyroidism demonstrated by Fisher’s exact test (p<0.001). PIH prevalence significantly reduced in treatment group demonstrated by chi square test (p<0.001). Conclusion: Subclinical and overt hypothyroidism prevalence is significantly high among PIH patients. Treating subclinical and overt hypothyroidism in pregnancy, reduces prevalence of PIH and its severity.

Association of hemoglobin level with thyroid-stimulating hormone in different trimester pregnant women with subclinical hypothyroidism / 中华内分泌代谢杂志

To investigate the association between hemoglobin ( Hb ) and thyroid-stimulating hormone ( TSH) levels in different trimester pregnant women with subclinical hypothyroidism (SCH). 62 pregnant women, who were diagnosed as SCH when they had their first antenatal care and eventually delivered in the Affiliated Quanzhou First Hospital of Fujian Medical University from March 2013 to December 2014, were enrolled in this study. These subjects were divided into three groups according to weeks of gestation when they had their first prenatal care:including first trimester (n＝24), second trimester (n＝17), and third trimester (n＝21) groups. All SCH pregnant women were treated with levothyroxine ( L-T4). The clinical and laboratory data in the first antenatal care and antepartum period were collected. Association of Hb level with other clinical and laboratory data were analyzed. Compared to baseline, the levels of TSH, γ-glutamyl transpeptidase, alanine aminotransferase, and total cholesterol were lower (all P<0.05), and the levels of Hb were higher (P<0.05), after treated with L-T4in three groups. Pearson correlation analysis showed that the level of Hb was negativly correlated with TSH in all pregnancies or in third trimester groups (r＝－0.394,－0.308,－0.537 and－0.453 respectivly, all P<0.05). Multivariate regression analysis indicated that the level of Hb was independently associated with TSH and body mass index in pregnant women with SCH. In pregnant women with SCH, the higher TSH and body mass index levels are correlated with increased risk of anemia. L-T4treatment may ameliorate anemia during pregnancy.