The synthetic thyroid hormone, levothyroxine, protects cholinergic neurons in the hippocampus of naturally aged mice

The thyroid hormones, triiodothyronine and thyroxine, play important roles in cognitive func- tion during the mammalian lifespan. However, thyroid hormones have not yet been used as a therapeutic agent for normal age-related cognitive deficits. In this study, CD-1 mice （aged 24 months） were intraperitoneally injected with levothyroxine （L-T4; 1.6 gg/kg per day） for 3 consecutive months. Our findings revealed a significant improvement in hippocampal cyto- skeletal rearrangement of actin and an increase in serum hormone levels of L-T4-treated aged mice. Furthermore, the survival rate of these mice was dramatically increased from 60% to 93.3%. The Morris water maze task indicated that L-T4 restored impaired spatial memory in aged mice. Furthermore, level of choline acetyltransferase, acetylcholine, and superoxide dismutase were in- creased in these mice, thus suggesting that a possible mechanism by which L-T4 reversed cognitive impairment was caused by increased activity of these markers. Overall, supplement of low-dosage L-T4 may be a potential therapeutic strategy for normal age-related cognitive deficits.

Administration of Levothyroxine 45 - 60 Minutes before Breakfast Improves Biochemical Availability as Evidenced by Reduced Thyrotropin Levels

Introduction: Serum Thyrotropin (TSH) level is used to assess adequacy of levothyroxine dosing for patients with hypothyroidism. Some patients have raised TSH levels despite being on an adequate dose of levothyroxine (100 mcg/day - 200 mcg/day). Aim: To evaluated the effect of advising patients to take their levothyroxine 45 - 60 minutes before breakfast on raised serum TSH levels. Patients and Methods: Rather than increase the dose, patients with raised TSH levels were asked to take their levothyroxine at least 45 - 60 minutes before breakfast and other oral medications. Thyroid Function Tests were assessed at base line and repeated after two months. Results: Data from ten patients who presented between 2008 and 2010 were analyzed (9 females, 1 male): With median (IQR) age: 39 (33 - 49) years and duration of hypothyroidism: 6 (3 - 7.8) years. Median (IQR) levothyroxine dose was 175 (144 - 250) mcg, serum free-Thyroxine (free-T4): 13 (10.5 - 17.1) pmol/L and serum TSH: 12.63 (6.2 - 48.3) mIU/L. After two months all patients demonstrated biochemical improvement;a decrease in serum TSH to 3.15 (0.4 - 6.1) mIU/L accompanied by an increase in serum free-T4 to 17.7 (14.8 - 21.3) pmol/L. Both changes were statistically significant (p < 0.05 and p < 0.01, respectively). The median (IQR) percentage TSH reduction was 83.5 (40.3 - 95.8) mIU/L and this bore no significant correlation with the initial TSH level (rs = 0.2, p = 0.58). Conclusion: Changing levothyroxine administration to 45 - 60 minutes before breakfast and other oral medications reduced TSH levels by 40% - 96% in all patients. We recommend this advice for all patients with hypothyroidism on adequate doses of levothyroxine but still appear biochemically under-replaced.

A severe case of levothyroxine intoxication successfully treated in intensive care unit

Levothyroxine intoxication is a rare clinical entity which is usually asymptomatic. However, severe symptoms such as respiratory failure, malignant hyperthermia, seizures, arrhythmia, and coma have been reported. In this case report, a patient who ingested high dose (15 mg) levothyroxine for suicide and admitted to intensive care unit was presented. There was a decrease in Glasgow coma score in the follow-up. The patient was intubated due to acute respiratory failure. Gastric lavage, activated charcoal, methylprednisolone, cholestyramine and therapeuthic plasma exchange were administered. Despite ingestion of high dose of levothyroxine, thyrotoxicosis symptoms resolved with appropriate treatment and the patient was discharged from the intensive care unit.

Thyrotoxicosis after a massive levothyroxine ingestion: A case report

BACKGROUND The literature on thyrotoxicosis caused by excessive ingestion of exogenous thyroid hormone is limited,and most cases reported have involved pediatric clinical studies.CASE SUMMARY A 21-year-old woman initially presented with palpitation and chest tightness after an overdose of levothyroxine(10 mg).The patient transiently lost consciousness and developed atrial fibrillation during hospitalization.We used propylthiouracil to decrease the peripheral conversion of T4 to T3 and inhibit the synthesis of endogenous thyroxine,propranolol to control heart rate,hydrocortisone to correct severe thyrotoxicosis,and hemoperfusion to increase levothyroxine clearance.The patient recovered and was discharged.CONCLUSION For patients with thyrotoxicosis after taking excess levothyroxine,it is critical to monitor vital signs and initiate effective treatment.

Systematic review of Yougui pills combined with levothyroxine sodium in the treatment of hypothyroidism

BACKGROUND Yougui pills have long been used to treat hypothyroidism,usually in combination with levothyroxine sodium in clinical treatment,while their clinical efficacy and safety are still controversial when compared to levothyroxine treatment alone.AIM To explore the clinical efficacy and safety of Yougui pills combined with levothyroxine sodium in the treatment of hypothyroidism.METHODS This meta-analysis was performed in accordance with the PRISMA guidelines.Randomized controlled trials on Yougui pills in the treatment of hypothyroidism published from 2008 to May 2021 were searched in a total of 8 databases(4 databases in Chinese and 4 databases in English).The quality of the included studies was evaluated according to the Cochrane risk assessment tool.Weighted mean difference(WMD)was used for continuous variables,and relative risk(RR)was used for binary variables.Data were extracted,and the meta-analysis was conducted with the statistical software of Stata15.0 and RevMan5.0.RESULTS A total of 140 articles were retrieved,and 9 of them were finally included,with a total sample size of 936 cases.The main meta-analysis results are as follows:(1)The group of Yougui pills combined with levothyroxine sodium had a significantly higher overall response rate than the group of levothyroxine sodium(RR=1.20,95%CI 1.12,1.28,P<0.00001);(2)Yougui pills combined with levothyroxine sodium achieved significantly better efficacy than levothyroxine sodium alone in alleviating adverse symptoms[standard mean difference(SMD)=-1.10,95%CI:-1.37,-0.84,P<0.00001];(3)The level of thyrotropin stimulating hormone in the group of Yougui pills combined with levothyroxine sodium was significantly lower than in the control group of levothyroxine sodium(WMD=-1.38,95%CI:-2.10,-0.67,P=0.00001);(4)The level of free triiodothyronine in the group of Yougui pills combined with levothyroxine sodium was higher than that in the control group of levothyroxine sodium(WMD=0.41,95%CI:0.03,0.79,P=0.03);(5)The level of free thyroxine in the group of Yougui pills combined with levothyroxine sodium was significantly higher than that in the control group of levothyroxine sodium(SMD=0.83,95%CI:0.44,1.22,P≤0.0001);and(6)The adverse reactions in the group of Yougui pills combined with levothyroxine sodium were significantly less than those in the control group of levothyroxine sodium(RR=0.33,95%CI:0.20,-0.53,P<0.00001).CONCLUSION In the treatment of hypothyroidism,the combination of Yougui pills with levothyroxine sodium may be better than levothyroxine sodium treatment alone.

Suicide attempt of an overt hypothyroid patient with levothyroxine:A case report

Rationale: Levothyroxine is the most commonly used agent in thyroid hormone replacement therapy. Although there are many hypothyroid patients who use levothyroxine as a treatment, high level of thyroid stimulating hormone is found in a limited number of levothyroxine overdose cases worldwide.Patient concern: A 34-year-old male patient taking 4.5 mg levothyroxine for suicide. Diagnosis: Overdose of levothyroxine. Interventions: The patient was admitted to the intensive care unit for follow-up treatment. Cardiac rithym and vital parameters of patient were closely monitored. Outcomes: The patient discharged without any life-threatening complications. Lessons: Patient with initial high thyroid stimulating hormone levels may not be in hyperthyroidism crisis by levothyroxine poisoning.

Prenatal Diagnosis and Management of Fetal Goiter Treated Successfully with Intra-Amniotic Levothyroxine

Goiter is an enlargement of the thyroid gland which can be associated with a number of complications both for the mother and the fetus. A 34-year-old pregnant woman with normal thyroid function was referred to our Department of Obstetrics and Gynecology at Microcitemico Pediatric Hospital, Cagliari, for suspected fetal goiter at 32 gestational weeks. The case was monitored regularly by ultrasound and treated successfully with intra-amniotic levothyroxine (L-T4) administration. Fetal goiter was observed to decrease after this treatment and the thyroid ultrasound findings were also normal both at birth and in subsequent follow-ups. Our case report confirms the feasibility of conservative treatment with L-T4, which can effectively prevent complications related to fetal goiter.

Protective effect of levothyroxine on myocardial and cerebral ischemia reperfusion injury during surgery under cardiopulmonary bypass

Objective:To study the protective effect of levothyroxine on myocardial and cerebral ischemia reperfusion injury during surgery under cardiopulmonary bypass.Methods: Patients who underwent valve replacement under cardiopulmonary bypass in Mianyang Central Hospital between March 2015 and December 2017 were selected and randomly divided into the Euthyrox group who received preoperative levothyroxine therapy and the control group who received routine preoperative intervention. The myocardial and cerebral injury indexes, pro-inflammatory and adhesion molecules as well as antioxidant indexes were measured before operation and 12 h after operation.Results: Twelve hours after operation, serum cTnI, LDH, CK-MB, H-FABP, NSE, S100B, CD11b/CD18, sP-selectin, IL-1 and IL-10 contents as well as SjvO2 levels of both groups were higher than those before operation whereas Cu-Zn SOD, CAT and GSH-Px contents were lower than those before operation, and serum cTnI, LDH, CK-MB, H-FABP, NSE, S100B, CD11b/CD18, sP-selectin, IL-1 and IL-10 contents as well as SjvO2 level of Euthyrox group were lower than those of control group whereas Cu-Zn SOD, CAT and GSH-Px contents were higher than those of control group.Conclusions:Levothyroxine has protective effect on the myocardial and cerebral ischemia reperfusion injury induced by inflammation and oxidative stress during surgery under cardiopulmonary bypass.

EFFECTS OF LEVOTHYROXINE ON BONE METABOLISM IN PATIENTS WITH DIFFERENTIATED THYROID CANCER AFTER OPERATION AND ^(131)I ABLATION

Objective To investigate the effects of substitutive and suppressive doses of levothyroxine on bone metabolism in patients with differentiated thyroid carcinoma after surgery and 131I ablation. Methods The patients, who had received levothyroxine(L-T4) for at least 3 years for treating their differentiated thyroid carcinoma after surgery and 131I therapy, were classified into substitutive group and suppressive group according to the levels of serum free triiodothyronine (FT3), free thyroxine (FT4), thyroid-stimulating hormone (TSH). We compared the levels of FT3, FT4, TSH, serum parathyroid hormone (PTH), serum calcium (Ca), serum phosphate (P), serum alkaline phosphates (ALP) and Bone mineral density (BMD) to those of healthy volunteers well matched for sex, age, menopausal status, and body mass index (BMI). Results No significant differences were found in the bone density and biochemical parameters of bone metabolism of the subjects treated with substitutive or suppressive doses of L-T4 compared with the control subgroup. No significant differences were observed among the subgroups according to accumulative doses of 131I. No bone fracture was found in all the patients. Conclusion The substitutive and suppressive doses of L-T4 are safe and necessary for patients with differentiated thyroid carcinoma after surgery and 131I therapy. Such treatment for 3 years is not associated with increased risk of osteoporosis. Much longer term of follow up is still needed in patients receiving substitutive and suppressive doses of L-T4.

Does the use of double hormone replacement therapy for trauma patient organ donors improve organ recovery for transplant

BACKGROUND With an ongoing demand for transplantable organs,optimization of donor management protocols,specifically in trauma populations,is important for obta-ining a high yield of viable organs per patient.Endocrine management of brain-dead potential organ donors(BPODs)is controversial,leading to heterogeneous clinical management approaches.Previous studies have shown that when levo-thyroxine was combined with other treatments,including steroids,vasopressin,and insulin,BPODs had better organ recovery and survival outcomes were increased for transplant recipients.AIM To determine if levothyroxine use in combination with steroids in BPODs increased the number of organs donated in trauma patients.METHODS A retrospective review of adult BPODs from a single level 1 trauma center over ten years was performed.Exclusion criteria included patients who were not solid organ donors,patients who were not declared brain dead(donation after circulatory death),and patients who did not receive steroids in their hospital course.Levothyroxine and steroid administration,the number of organs donated,the types of organs donated,and demographic information were recorded.Univariate analyses were performed with P<0.05 considered to be statistically significant.RESULTS A total of 88 patients met inclusion criteria,69(78%)of whom received levothyroxine and steroids(ST/LT group)vs 19(22%)receiving steroids without levothyroxine(ST group).No differences were observed between the groups for gender,race,pertinent injury factors,age,or other hormone therapies used(P>0.05).In the ST/LT group,68.1%(n=47)donated a high yield(3-5)of organ types per donor compared to 42.1%(n=8)in the ST group(P=0.038).There was no difference in the total number of organ types donated between the groups(P=0.068).CONCLUSION This study suggests that combining levothyroxine and steroid administration increases high-yield organ donation per donor in BPODs in the trauma patient population.Limitations to this study include the retrospective design and the relatively small number of organ donors who met inclusion criteria.This study is unique in that it mitigates steroid administration as a confounding variable and focuses specifically on the adjunctive use of levothyroxine.

Liver injury induced by levothyroxine tablets in a patient with hypothyroidism

To the Editor: On March 9, 2018, a 31-year-old woman presented with liver dysfunction after thyroid cancer surgery. She was physically healthy;had no chronic diseases, such as hypertension and diabetes;had no history of infectious diseases, such as hepatitis and tuberculosis;had no history of drugs, food allergies, smoking, and alcohol consumption;and presented no obvious complaints during the disease course. B-ultrasound in the physical examination 3 years prior showed “left thyroid-occupying position.” On February 5, 2018, she had undergone surgery at our hospital. Laboratory findings on February 6, 2018 revealed white blood cells (WBCs) 9.06 × 10^9/L (3.50–9.50 × 10^9/L);neutrophils (NEs) 5.66 × 10^9/L (1.80–6.30 × 10^9/L);triiodothyronine (T3) 0.94 (0.80–2.00) ng/mL;thyroxine (T4) 6.4 (5.1–14.1)μg/dL;free T3 (FT3) 3.95 (3.10–6.80) pmol/L;free T4 (FT4) 15.57 (12.00–22.00) pmol/L;thyroid-stimulating hormone (TSH) 2.56 (0.27–4.20) mU/L;thyroid peroxidase antibody (TPOAb) 8.2 (0–34.0) IU/mL;thyroglobulin antibody (TgAb)<10 (≤115) IU/mL;total bilirubin (T-BIL) 21.5 (5.0–22.0)μmol/L;direct bilirubin (D-BIL) 6.3 (0–10.2)μmol/L;alanine transaminase (ALT) 27.5 (7.0–40.0) U/L;aspartate transaminase (AST) 22.7 (13.0–35.0) U/L;and alkaline phosphatase (ALP), 48.9 (35.0–100.0) U/L. Hepatitis C antibody, hepatitis B surface antigen, and hepatitis B core antibody immunoglobulin M tested negative. On February 7, 2018, intra-operative pathology during left thyroidectomy indicated micro-papillary carcinoma. On February 11, 2018, she was discharged and prescribed levothyroxine tablets A (LTA;Merck KGaA, Darmstadt, Germany) 100 μg and calcium carbonate D3 tablets (CC-D3;Pfizer, China) 600 mg once daily.

Effect of levothyroxine replacement therapy on improving diffused left ventricular myocardial lesions in patients with hypothyroidism

Objective To study the effect of levothyroxine replacement therapy on improving diffused left ventricular myocardial lesions and cardiac function in patients with hypothyroidism.Methods Our research included 2groups:Hypothyroidism group,n=20,newly diagnosed patients and Control group,n=17,normal healthy subjects.Diffused left ventricular myocardial lesions

Subclinical Hypothyroidism, Its Manifestations and Management a Case Report

Introduction: Thyroid states can be associated with psychiatric manifestations, be it hypothyroid, hyperthyroid or even euthyroid. The effect of depression is significant in subclinical hypothyroidism. Sometimes, its signs and symptoms are indistinguishable from Major Depressive Disorder. Our immunological system and early embryologic origins also play a role in the coexistence of other comorbidities like Pernicious Anemia. Case: A 35-year-old Hispanic female presented with significant low mood, somnolence, weight gain, increased hunger, cold intolerance and epigastric pain. It is important to note the variety of clinical manifestations of our hypothyroidism patient to understand its associations and help us with a better approach to treatment. Discussion: Standard approaches to treatment of Subclinical Hypothyroidism will depend mostly on laboratory findings such as TSH levels and free T4. Individualized therapy chosen for our patient was based on his mood symptoms, laboratory findings and coexistence of Pernicious Anemia. The use of daily 0.025 mg of levothyroxine, 10 mg of escitalopram oxalate and weekly injections of cyanocobalamin were treatments of choice. Conclusion: During follow up of our patient, we can conclude that Levothyroxine and Escitalopram Oxalate were able to improve hypothyroidism symptoms, reduce thyroglobulin and peroxidase antibodies and improve mood symptoms including cognitive functions. In addition to this, weekly cyanocobalamin injections were integrated into the management. As parietal cell antibodies decreased, gastrointestinal symptoms also disappeared. By addressing the concerns of our patient, we improved quality of care, and this is reflected in the patient’s wellbeing in physical and psychological.

Treatment and follow-up of children with transient congenital hypothyroidism

Objective： To study the clinical therapy and prognosis in children with transient congenital hypothyroidism （CH）. Methods： Fifty-seven children with CH diagnosed after neonatal screening were treated with low-dosage levothyroxine （L-T4）. Follow-up evaluation included the determination of TT3, TT4 and TSH serum levels and the assessment of thyroid gland morphology, bone age, growth development and development quotients （DQ）. A full check-up was performed at age 2, when the affected children first discontinued the L-T4 treatment for 1 month, and one year later. Development quotients were compared with a control group of 29 healthy peers. Results： The initial L-T4 dosage administered was 3.21-5.81μg/（kg·d） with an average of （16.25±3.87）μg/d. Mean duration of therapy was （28.09±9.56） months. No significant difference was found between study group and control group in the DQ test （average score （106.58±14.40） vs （102.4±8.6）, P〉0.05） and 96.49% of the CH children achieved a test score above 85. Bone age, 99mTc scans and ultrasonographic findings were all normal, and evaluation of physical development was normal too, as were the serum levels of TT3, TT4 and TSH after one year of follow-up. Conclusion： AL-T4 dosage of 3.21-5.81μg/（kg·d） was found sufficient for the treatment of transient CH. The treated children showed satisfactory overall mental and physical development at age 2. So it is possible for CH children to stop taking medicine if their laboratory findings and physical development are all normal after regular treatment and 2-3 years of follow-up.

Hypothyroidism in Childhood and Adolescence

Juvenile hypothyroidism is an unfrequent form of hypothyroidism that affects children. If not diagnosed and treated properly, it may cause severe neurological disorders during growth. The most frequent difficulties are found in school performance, difficulties in concentration, hyperactivity or fatigue and damage on the onset of puberty. Starting levothyroxine as a drug of choice is essential, and it should be made according to the age and weight of the child. Laboratory tests for control should be requested periodically, along with a strict control of the child’s development and growth. The family-doctor relationship, along with a clear guidance on the importance of treatment, is critical to achieve a successful treatment. This article is a review about the main clinical features of hypothyroidism in childhood, especially in developing countries, providing key aspects of adherence and characteristics of its follow-up.

A Case Report of Hypothyroidism and Pericardial Effusion

The pericardial sac is made of two layers: the visceral and parietal pericardium. Located between these two layers, the pericardial cavity is found. It contains around 15 to 50 mL of a liquid secreted by mesothelial cells. Pericardial effusion is described as the accumulation of liquid within the pericardial cavity, exceeding the previous mentioned quantity. It has multiple causes, such as malignancy, infectious origins, inflammation, and others, such as hypothyroidism. One of the multiple clinical manifestations associated with hypothyroidism is pericardial effusion. It is related to the severity and duration of the disease, being more frequent in congenital hypothyroidism or cases of a long history of hypothyroidism, as well as clinical hypothyroidism. It can present a clinical challenge mainly due to the discordance between the total volume of the effusion and the clinical symptoms shown by the patient. The main objective of this work is to present a case of a forty-two-year-old male with hypothyroidism-associated pericardial effusion which resolved satisfactorily with hormone replacement therapy.

Evaluation and management of the child with hypothyroidism

Background Thyroid hormones are critical for early neurocognitive development as well as growth and development throughout childhood.Prompt recognition and treatment of hypothyroidism is,therefore,of utmost importance to optimize physical and neurodevelopmental outcomes.Data sources A PubMed search was completed in Clinical Queries using the key terms 'hypothyroidism'.Results Hypothyroidism may be present at birth (congenital hypothyroidism) or develop later in life (acquired hypothyroidism).Thyroid dysgenesis and dyshormonogenesis account for approximately 85% and 15% of permanent cases of congenital primary hypothyroidism,respectively.More than 95% of infants with congenital hypothyroidism have few,if any,clinical manifestations of hypothyroidism.Newborn screening programs allow early detection of congenital hypothyroidism.In developed countries,Hashimoto thyroiditis is the most common cause of goiter and acquired hypothyroidism in children and adolescents.Globally,iodine deficiency associated with goiter is the most common cause of hypothyroidism.Central hypothyroidism is uncommon and may be associated with other congenital syndromes and deficiencies of other pituitary hormones.Familiarity of the clinical features would allow prompt diagnosis and institution of treatment.Conclusions To optimize neurocognitive outcome in infants with congenital hypothyroidism,treatment with levothyroxine should be started as soon as possible,preferably within the first 2 weeks of life.Children with acquired hypothyroidism should also be treated early to ensure normal growth and development as well as cognitive outcome.The target is to keep serum TSH < 5 mIU/L and to maintain serum free T4 or total T4 within the upper half of the age-specific reference range,with elimination of all symptoms and signs of hypothyroidism.