Does well-controlled overt hypothyroidism increase the risk of total knee arthroplasty?

BACKGROUND: Overt hypothyroidism is widely accepted as a risk factor for adverse events following total knee arthroplasty (TKA). However, no prior study has preoperatively reversed hypothyroidism and reevaluated its risk. This retrospective study aimed at investigating whether well-controlled overt hypothyroidism would still increase the risk of TKA. METHODS: Between November 2009 and November 2016, patients diagnosed with overt hypothyroidism but well controlled and underwent TKA were compared with euthyroid TKA patients. Data were extracted from our departmental database. Chi-squared test and t-tests were used for comparisons. RESULTS: Hypothyroid patients had more blood loss and lower postoperative haemoglobin (Hb) and haematocrit level than the control group (all P < 0.05). Although the postoperative anaemia rate was lower in the control group (P = 0.01), there was no significant difference in the transfusion rate between the two groups (2.99% versus 7.46%, P = 0.10) or in the rates of other complications (P > 0.05). Interestingly, intramuscular venous thrombosis rate in hypothyroid patients was significantly lower than that in the control group (1.49% versus 9.70%, P = 0.00). Clinical outcome scores were comparable between the two groups throughout the course. And only one case of infection occurred in the hypothyroid patients. CONCLUSION: Well-controlled overt hypothyroidism did not increase the risk of TKA, except for perioperative blood loss. Surgeons should be aware that even if hypothyroidism is reversed, the risk of more perioperative blood loss still exists and that, consequently, perioperative blood management is still essential in this population.

Relation of Gut Microbes and L-Thyroxine Through Altered Thyroxine Metabolism in Subclinical Hypothyroidism Subjects.

Thyroxine metabolism is an important topic of pathogenesis research and treatment schedule of subclinical hypothyroidism (SCH). L-Thyroxine replacement therapy (LRT) is usually recommended for severe SCH patients only. Our previous studies reported that disordered serum lipid of mild SCH people could also benefit from LRT. However, the benefits were different among individuals, as shown by the variations in drug dosage that required to maintain thyroid-stimulating hormone (TSH) stability. Alternative pathways, such as sulfation and glucuronidation of iodothyronine, may play a role in thyroid hormones metabolism in peripheral tissues aside from thyroid. Conjugated thyroxine can be hydrolyzed and reused in tissues including gastrointestinal tract, in which gut microbiota are one of the most attractive physiological components. On this site, the roles of gut microbiota in thyroidal metabolism should be valued. In this study, a cross-sectional study was performed by analyzing 16S rDNA of gut microbiota in mild SCH patients treated with L-thyroxine or not. Subjects were divided by serum lipid level, L-thyroxine treatment, or L-thyroxine dosage, respectively. Relationship between gut microbiome and serum profile, L-thyroxine treatment, and dose were discussed. Other metabolic disorders such as type 2 diabetes and hypertension were also taken into consideration. It turned out that microbiome varied among individuals divided by dose and the increment of L-thyroxine but not by serum lipid profile. Relative abundance of certain species that were associated with thyroxine metabolism were found varied among different L-thyroxine doses although in relatively low abundance. Moreover, serum cholesterol may perform relevance effects with L-thyroxine in shaping microbiome. Our findings suggested that the differences in L-thyroxine dosage required to maintain TSH level stability, as well as the SCH development, which was displayed by the increased L-thyroxine doses in subsequent follow-up, had relationship with gut microbial composition. The reason may due to the differences in thyroxine metabolic capacity in gut. In addition, the metabolic similarity of iodothyronines and bile acid in gut also provides possibilities for the correlation between host's thyroxine and cholesterol levels. This study was registered with ClinicalTrials.gov as number NCT01848171.

Hashimoto Thyroiditis and Dyslipidemia in Childhood: A Review.

Hashimoto autoimmune thyroiditis (AIT) is the most common cause of acquired hypothyroidism in the pediatric population. Development of AIT is mediated mainly by cellular immune response directed toward thyroid autoantigens, leading to inflammation and impaired function of thyroid gland. Both thyroid dysfunction and inflammation affect the metabolism of plasma lipoproteins. The alterations in lipid profile worsen with the advancement of hypothyroidism, ranging from discrete changes in euthyroid AIT patients, to atherogenic dyslipidemia in the overt hypothyroidism. In this review, characteristics of dyslipidemia in pediatric AIT patients, and the consequences in respect to the risk for cardiovascular disease (CVD) development are discussed. Additionally, benefit of L-thyroxine treatment on serum lipid profile in pediatric AIT patients is addressed. Finally, potential usefulness of novel lipid biomarkers, such as proprotein convertase subtilisin/kexin type 9 (PCSK9), non-cholesterol sterols, low-density lipoprotein particle size and number, and high-density lipoprotein structure and functionality in AIT patients is also covered. Further longitudinal studies are needed in order to elucidate the long-term cardiovascular outcomes of dyslipidemia in pediatric patients with Hashimoto AIT.

Thyroid Function in Aging: A Discerning Approach.

Thyroid disease, increasingly common among the general population, is also rising among the elderly, which, given that the global population is aging, constitutes a serious public health issue that needs to be urgently addressed. The most common thyroid disease in younger and older individuals alike is hypothyroidism, including subclinical (SCH) and overt disease. Since TSH tends to increase with age due to intrinsic changes of thyroid metabolism and the gradual resetting of the hypothalamic-pituitary-thyroid axis, the diagnosis of "true" hypothyroidism is challenging, another difficulty being distinguishing disease-specific from aging-associated clinical symptoms. Hypothyroidism in the elderly may cause or exacerbate macrocytic anemia, hypercholesterolemia and kidney dysfunction, therefore careful clinical and biochemical control is necessary. Meanwhile, as an increase of TSH in the old and very old has been associated with longevity, a resetting of the TSH normal range according to age is strongly required before any diagnosis is made and treatment is implemented. Levothyroxine, which remains the treatment of choice, should be initiated in the old at TSH>10 mIU/l, starting with 25 µg/daily followed by cautious upward titration. Recent data (the TRUST study) revealed that treatment of SCH in the elderly does not improve hypothyroid symptoms and the tiredness score when compared with a placebo group. Hyperthyroidism is associated with increased mortality in the aged, this dependent upon type and adequacy of treatment. Treatment should be seriously considered in older patients who have endogenous subclinical hyperthyroidism with a TSH between 0.1 and 0.4 mIU/L, with regular monitoring being strongly advised.

Thyroid function in children and adolescents with Hashimoto's thyroiditis after l-thyroxine discontinuation.

OBJECTIVE: Thyroid function may recover in patients with Hashimoto's thyroiditis (HT). DESIGN: To investigate thyroid function and the need to resume l-thyroxine treatment after its discontinuation. SETTING: Nine Italian pediatric endocrinology centers. PATIENTS: 148 children and adolescents (25 m and 123 f) with HT on treatment with l-thyroxine for at least one year. INTERVENTION AND MAIN OUTCOME MEASURE: Treatment was discontinued in all patients, and serum TSH and fT4 concentrations were measured at the time of treatment discontinuation and then after 2, 6, 12 and 24 months. Therapy with l-thyroxine was re-instituted when TSH rose >10 U/L and/or fT4 was below the normal range. The patients were followed up when TSH concentrations were between 5 and 10 U/L and fT4 was in the normal range. RESULTS: At baseline, TSH was in the normal range in 139 patients, and was between 5 and 10 U/L in 9 patients. Treatment was re-instituted after 2 months in 37 (25.5%) patients, after 6 months in 13 patients (6.99%), after 12 months in 12 patients (8.6%), and after 24 months in an additional 3 patients (3.1%). At 24 months, 34 patients (34.3%) still required no treatment. TSH concentration >10 U/L at the time of diagnosis was the only predictive factor for the deterioration of thyroid function after l-thyroxine discontinuation. CONCLUSIONS: This study confirms that not all children with HT need life-long therapy with l-thyroxine, and the discontinuation of treatment in patients with a TSH level <10 U/L at the time of diagnosis should be considered.

Evaluation of Selected Atherosclerosis Risk Factors in Women with Subclinical Hypothyroidism Treated with L-Thyroxine.

BACKGROUND: Subclinical hypothyroidism (SCH) is a common endocrine disorder, probably increasing cardiovascular (CV) risk. However, the relation between SCH and atherosclerosis risk factors remains unclear. OBJECTIVES: The aim of the study was to evaluate selected atherosclerosis risk factors in women with SCH in comparison to a group of healthy women and women with overt hypothyroidism, as well as to investigate the influence of L-thyroxine replacement on those risk factors. MATERIAL AND METHODS: The study group consisted of 187 obese women aged between 50 and 70 years: 100 women with SCH, 45 women with overt hypothyroidism and 42 women with TSH level in reference ranges. Anthropometric parameters were evaluated. Laboratory tests included thyroid hormones concentrations, lipid profile with apolipoproteins, CRP, homocysteine. Atherosclerotic indexes were calculated: LDL C/HDL C ratio, apoA1/apoB ratio and Castelli risk index. Women with hypothyroidism were given L-thyroxine treatment and after 6 months in euthyroidism the evaluation was repeated. RESULTS: Total cholesterol, LDL-cholesterol and triglycerides concentrations as well as LDL-C/HDL-C ratio and Castelli index were higher in SCH than in controls and decreased after L-thyroxin substitution. All of the calculated atherosclerosis indexes showed significant positive correlations with TSH concentration in SCH group. Also in this group the systolic and diastolic blood pressure decreased significantly after treatment. CONCLUSIONS: Dyslipidemia in obese SCH women is not severe, but if untreated for many years, it may lead to atherosclerosis. Substitution therapy improves the lipid profile, changing the relations between protective and proatherogenic fractions of serum lipids, and optimises blood pressure.

Effect of L-thyroxine treatment versus a placebo on serum lipid levels in patients with sub-clinical hypothyroidism.

Sub-clinical hypothyroidism is a common disease and whether L-thyroxine replacement treatment improves serum lipid levels in affected patients remains controversial. Thus, the aim of the present meta-analysis was to assess the effect of L-thyroxine therapy on serum lipid levels in sub-clinical hyperthyroidism. Relevant randomized controlled trials (RCTs) containing continuous data, published until July 2015 were retrieved from the Cochrane Library, PubMed, Medline, Google Scholar and Embase databases and subjected to meta-analysis using Review Manager software version 5.2 (The Nordic Cochrane Centre, Copenhagen, Denmark). Seven RCTs comprising 319 patients were included. The overall methodological quality of the RCTs was good. Statistical analysis revealed that serum low-density lipoprotein-cholesterol (LDL-C) levels were significantly decreased after L-thyroxine treatment [mean difference (MD): -0.23; 95% confidence interval: -0.44, -0.03; P=0.02], while changes of total cholesterol (TC), triglyceride (TG) and high-density lipoprotein-cholesterol (HDL-C) were not significant (MD: -0.18, P=0.09; MD: -0.02, P=0.78; and MD: -0.06, P=0.14, respectively). In conclusion, the meta-analysis performed in the present study revealed that compared with placebo treatment, L-thyroxine significantly improved serum LDL-C levels in patients with sub-clinical hypothyroidism, while not significantly affecting TC, TG and HDL-C levels.