Hormone replacement therapy with L-thyroxine promotes working memory and concentration in thyroidectomized female patients after differentiated thyroid carcinoma.

Objective: It is well established that long-term hypothyroidism is associated with cognitive deficits. Based on recent literature, we hypothesized that pharmacologically induced euthyroidism would lead to improved cognitive performance compared to a hypothyroid state. Methods: We analyzed data from 14 nondepressed thyroidectomized female patients after differentiated thyroid carcinoma during hypothyroidism (due to a four-week withdrawal of thyroid hormone, T1) and euthyroidism brought about by substitution with L-thyroxine (T2). At both measurement points, patients completed a cognitive test battery as our dependent measure and Beck's Depression Inventory to control depressive states. Results: A Wilcoxon signed-rank tests revealed a significant improvement in the Rey­Osterrieth complex figure test (cognitive reproduction), Z = −3.183, p = 0.001, and the D2 concentration score, Z = −1.992, p = 0.046 in euthyroidism compared to hypothyroidism. Conclusions: Our results confirm that hormone replacement therapy with L-thyroxine promotes cognitive reproduction and concentration in thyroidectomized female patients after differentiated thyroid carcinoma.

Should the dose of levothyroxine be changed in hypothyroidism patients fasting during Ramadan?

Background/aim: Muslims worship by fasting from predawn (suhoor) until sunset (iftar) for 30 days in the religious month of Ramadan. In addition to prolonged hunger, patients fasting with a diagnosis of hypothyroidism take their doses of levothyroxine (LT4) outside of daytime fasting hours. The purpose of our study is to compare the values of hypothyroid patients which have been obtained through thyroid function tests before and after Ramadan. Materials and methods: Ninety-seven patients; ranging from 18 to 65 years old, who were followed with a diagnosis of hypothyroidism, who fasted during Ramadan, and who had no change of their LT4 dose for at least 6 months were included in the study. Results: The median serum thyroid-stimulating hormone (TSH) level of patients prior to fasting was 2.19 mIU/L, while median serum TSH after fasting was 2.73 mIU/L. Serum TSH values after Ramadan increased significantly compared to those prior to Ramadan (P = 0.004). Conclusion: Our study demonstrates a significant increase in serum TSH levels after Ramadan but no significant change in serum free thyroxine (fT4) levels in hypothyroidism patients who are fasting. It may be appropriate to take precautions by making a small increase in LT4 dose before Ramadan in some hypothyroid patients wishing to fast.

Evaluation of left atrial volume and functions by real time three-dimensional echocardiography in patients with subclinical hypothyroidism before and after levothyroxine therapy.

BACKGROUND/AIMS: The cardiovascular system is one of the major targets of thyroid hormones. Subclinical hypothyroidism (SCH) is a common disease that can represent "early" thyroid failure. Our aim was to evaluate left atrial (LA) volume and functions in patients with SCH using real time three-dimensional echocardiography (RT3DE) and also to investigate changes in LA parameters after the levothyroxine treatment. METHODS: In total, 44 patients with SCH and 40 age- and gender-matched controls were studied. Assessments included history, physical examination and echocardiography. All patients with SCH were followed up with replacement therapy until the euthyroid status was achieved. RESULTS: In patients with SCH, LA total emptying volume, passive emptying volume, and passive ejection fraction were significantly reduced while LA minimal volume, active emptying volume, and active emptying fraction were significantly increased than in control group. Following the levothyroxine treatment, LA volume and function parameters were observed to be significantly improved. A negative correlation between the change of thyroid stimulating hormone (TSH) and change of LA active emptying volume and a positive correlation between the change of TSH level and change of LA passive emptying volume were found. CONCLUSION: It was shown that volume and functions of LA were impaired in patients with SCH. However, impaired parameters were improved after the levothyroxine treatment. These findings may be indicative of subclinical heart involvement that could lead to functional and structural changes in patients with SCH.

INSUFFICIENCY OF LEVOTHYROXINE THERAPY IN AUTOIMMUNE HYPOTHYROIDISM: EFFECT OF GLUCOCORTICOID ADMINISTRATION.

OBJECTIVE: The non-effectiveness of levothyroxine administration in hypothyroidism depends on many factors and mechanisms influencing its absorption in small intestins or bounding of circulating hormone with different active molecules. METHODS: Thyroid hormones, TSH, rT3, TGl, TPO-Ab, TG-Ab, were measured using commercially available assays. For anti-T4ab, radioiodine-labeled T4 was added to the patient's serum and the IgG fraction subsequently precipitated by addition of 15% polyethylene glycol. Background was determined by testing 100 control sera from individuals without autoimmune thyroid disease. RESULTS: A 42-year old woman (71.5 kg) with Hashimoto thyroiditis receiving levothyroxine (L-T4) 150 µg and liothyronine (L-T3) 37.5 µg was admitted to the hospital with clinical data of hypothyroidism, TSH-23.8 mU/L, FT4-6.18 pmol/L (n.range 9-19 pmol/L), TPO-Ab 696 IU/mL, TG-Ab 818 IU/mL, circulating T4- antibodies positive. She has a good adherence to medication, malabsorption or administration of other drugs were excluded. L-T4 absorption test revealed 44% increase of serum FT4 at 120 min after ingestion of 150 mcg L-T4 (2.1 mcg/kg). Methylprednisolone pulses of 500 mg i.v. administered in three consecutive days at equal doses of L-T4/L-T3 resulted in a rapid increase of FT4 to 14.5 pmol/L, fall of TSH to 0.18 mU/L and decrease of anti-T4 antibodies to referent range; TPO-Ab and TG-Ab also decreased significantly. Monotherapy by 150 mcg L-T4 was continued in the next three months. A recurrence of hypothyroidism with increase of circulating T4-Ab was observed 100 days later. New administrations of methylprednisolone two pulses of 500 mg revealed a similar normalization of thyroid hormones and anti-T4 antibodies. CONCLUSION: The data showed that T4-antibodies might be a cause of insufficient effects of levothyroxine therapy in autoimmune hypothyroidism. This could be overcome by glucocorticoid administration probably resulting in FT4 release from circulating immune complexes.

Left atrial phasic function and mechanics in women with subclinical hypothyroidism: the effects of levothyroxine therapy.

BACKGROUND: Left atrial (LA) mechanics has been poorly investigated in women with subclinical hypothyroidism (SHT), and the effect of levothyroxine therapy on LA deformation and function is unknown. AIM: To investigate LA phasic function and mechanics assessed by two-dimensional echocardiography (2DE) and speckle tracking in women with SHT, and to estimate the influence of levothyroxine therapy on LA remodeling. METHODS: We included 48 untreated women with SHT and 38 healthy control women of the same age. All the SHT patients received levothyroxine therapy and were followed for 1 year after euthyroid status was achieved. All the participants underwent laboratory analyses and complete 2DE examination. RESULTS: Left atrial total emptying fraction was significantly lower in the SHT patients at the baseline in comparison with the controls. LA passive emptying fraction gradually decreased from the controls, throughout the treated SHT patients, to the untreated SHT patients. LA active emptying fraction was lower in the controls than in the untreated and the treated SHT participants. 2DE LA longitudinal strain and systolic strain rate gradually decreased from the controls to the untreated SHT patients, whereas LA early diastolic strain rate significantly increased in the same direction. Late diastolic LA strain was lower in the controls than in the untreated and the treated SHT patients. CONCLUSION: Subclinical hypothyroidism significantly affects LA mechanics. Reservoir, conduit, and booster pump LA functions are all impacted by SHT. A 1-year levothyroxine therapy significantly improves, but does not completely restore LA phasic function and mechanics in the SHT patients.

Supraglottic Myxedema Presenting as a Complication of Hypothyroidism: A Case Report.

Myxedema is a medical emergency with high mortality rates if not treated aggressively. Here, we present a middle-aged female with complaints of generalized body swelling for one year, shortness of breath, hoarseness of voice, neck swelling, and cough for 20 days. The patient was diagnosed to be having severe hypothyroidism with polyserositis. Contrast-enhanced computed tomography (CECT) of the neck and thorax revealed extensive soft tissue edema causing airway narrowing, bilateral pleural effusion, moderate pericardial effusion, and features of atypical pneumonia. The patient was started on levothyroxine and antibiotics as per cultures to which she had initially improved; however, she developed ventilator-associated pneumonia leading to sepsis, acute respiratory distress syndrome followed by refractory type 1 respiratory failure and succumbed.

Relationship Between Subclinical Hypothyroidism and the Risk of Cardiovascular Complications.

Subclinical hypothyroidism is characterized by raised thyroid-stimulating hormone levels in the presence of normal free thyroxine levels. When free thyroxine levels are normal and subclinical hypothyroidism is present, thyroid-stimulating hormone levels are elevated. The impact of subclinical hypothyroidism on the cardiovascular system has recently garnered attention because it is known that thyroid hormones impact the heart and its vasculature. There is compelling evidence linking subclinical hypothyroidism to increased cardiac risks, including changes in blood pressure and cholesterol. It is unclear whether subclinical hypothyroidism is associated with a higher risk of cardiovascular illnesses. In addition to discussing the advantages of levothyroxine therapy in delaying the onset of cardiovascular complications, this review makes the connection between subclinical hypothyroidism patients and the risk of cardiovascular complications-related death.

Subclinical Hypothyroidism in Patients with Obesity and Metabolic Syndrome: A Narrative Review.

The literature on the connection between obesity, metabolic syndrome, and subclinical hypothyroidism is critically analyzed in this narrative review. These conditions are frequently observed among adult populations and various studies and meta-analyses have assessed their association. The prevalence of subclinical hypothyroidism in obese individuals is higher than in non-obese subjects and this trend is more pronounced in unhealthy obesity phenotypes. However, the diagnosis and treatment of subclinical hypothyroidism can be difficult in obese patients. Exaggerated body fat is linked to thyroid hypoechogenicity as evident through ultrasonography and euthyroid obese people have greater TSH, FT3, and FT3/FT4 ratios than non-obese individuals in a euthyroid condition. Moreover, a reduced expression of the TSH receptor and altered function of deiodinases has been found in the adipose tissue of obese patients. Current data do not support the necessity of a pharmacological correction of the isolated hyperthyrotropinemia in euthyroid obese patients because treatment with thyroid hormone does not significantly improve weight loss and the increase in serum TSH can be reversible after hypocaloric diet or bariatric surgery. On the other hand, obesity is linked to elevated leptin levels. Inflammation can raise the risk of Hashimoto thyroiditis, which increases the likelihood that obese patients will experience overt or subclinical hypothyroidism. Both metabolic syndrome and subclinical hypothyroidism are associated with atherosclerosis, liver and kidney disease. Hence, the association of these two illnesses may potentiate the adverse effects noted in each of them. Subclinical hypothyroidism should be identified in patients with obesity and treated with appropriate doses of L-thyroxine according to the lean body mass and body weight. Randomized controlled trials are necessary to verify whether treatment of thyroid deficiency could counteract the expected risks.

Brain Fog in Hypothyroidism: What Is It, How Is It Measured, and What Can Be Done About It.

Background: Some levothyroxine (LT4)-treated hypothyroid patients report a constellation of persistent and distressing cognitive symptoms that has been termed brain fog. This narrative review focuses on attempts to define and measure hypothyroid-associated brain fog, summarize possible etiologies and contributing factors, present treatment options, and propose avenues for future research. Methods: Published literature was reviewed to summarize available information on patient-reported symptoms associated with brain fog in hypothyroidism, as well as objective evidence of impairment based on neurocognitive testing and functional imaging studies. Given the limited information specific for hypothyroid-associated brain fog, relevant data from other medical conditions associated with brain fog were also reviewed and incorporated into recommendations for clinical care and future research areas. Results: Hypothyroid-associated brain fog has not been well defined or quantitated, and the underlying pathophysiology is unclear. Symptoms vary among patients but commonly include fatigue, depressed mood, and cognitive difficulties in the areas of memory and executive function. Symptoms often predate the diagnosis of hypothyroidism, and the magnitude of cognitive impairment can range from mild to severe. Regardless of severity, these symptoms are associated with impaired quality of life and cause dissatisfaction with treatment, so often lead to requests for alternate therapies. Disease-specific and psychological factors impact the experience of brain fog in complex ways, including potential limitations in LT4 monotherapy, self-knowledge of a disease state, and expectations for therapeutic effects. Conclusions: Brain fog is a variable symptom complex in people with hypothyroidism, causing significant distress and diminished quality of life. In the absence of proven therapies, individualized treatment plans are recommended, which incorporate thyroid-specific, general medical, and psychosocial approaches. In particular, cognitive rehabilitation is an underutilized technique that is beneficial in other medical conditions associated with brain fog and could improve symptoms in hypothyroid people. The limitations in our current knowledge and questions presented throughout this review highlight a major need for clinical research in this understudied area. Future research should include attention to standardization of survey instruments to quantitate brain fog in hypothyroid people, as well as rigorously designed intervention studies.

Treatment with Intramuscular Levothyroxine in Refractory Hypothyroidism.

INTRODUCTION: Orally and daily levothyroxine (LT4) is the treatment of choice for hypothyroidism. In the majority of cases, the lack of effectiveness by this way may be due to poor adherence; however, gastrointestinal malabsorption may explain more cases of thyroxine refractoriness than previously reputed, due to the number of occult forms of these disorders. CASE PRESENTATION: A 55-year-old white man with a diagnosis of low risk of recurrence of follicular variant of papillary thyroid carcinoma was treated with total thyroidectomy, 30 mCi iodine 131, and oral LT4. A year before he presented a gastric adenocarcinoma that required a partial gastrectomy. He evolved with multiple episodes of intestinal subocclusion that had to be treated with enterectomy in the first instance, then digestive rest and total parenteral nutrition. In spite of having made increases in oral LT4 dose (3 µg/kg), the patient persisted with a thyroid-stimulating hormone level >100 mIU/L. For this reason, we decided to administer intramuscular LT4. CONCLUSION: Since there are no guidelines or consensus of intramuscular LT4 use, our experience and how we decided the dose and way of administration are presented in this article to contribute to future cases.

Reversible morbidity markers in subclinical hypothyroidism.

IMPORTANCE: Subclinical hypothyroidism (SCH) is a common clinical entity with a putative role in a wide range of disorders. The impact of SCH on mortality and markers of morbidity has been demonstrated, but studies have shown inconsistent results. Evidence regarding the effect of levothyroxine treatment on reversing morbidity markers is emerging, but the value of treatment is still unclear. OBJECTIVE: The objectives of this review were to assess recent, high-quality studies evaluating the role of SCH in cardiovascular health, cognition, mood, pregnancy, anemia, and renal disease; to examine the effects of levothyroxine on reducing mortality or reversing markers of morbidity in these conditions; and to consider how new research insights may help guide clinical practice. EVIDENCE REVIEW: A PubMed search was conducted (using 'subclinical hypothyroidism' [Title/Abstract] AND morbidity [MeSH Subheading] as search criteria) and was restricted to human studies published in the English language between 1990 and 2013. Subsequent searches of retrieved articles yielded further studies, which were included based on quality. Emphasis was given to large observational studies, well-conducted meta-analyses, and randomized controlled trials. FINDINGS: The difficulty of diagnosing SCH, particularly in the elderly, may underlie many of the conflicting results seen in the literature. Increased understanding of the at-risk patient population will result in better selection of study subjects and, likely, unequivocal results. Regardless of the current confusion, emerging evidence suggests that certain markers of morbidity are reversed by levothyroxine therapy across the disorders examined here. CONCLUSION AND RELEVANCE: Future large, well-controlled studies will not only clarify the role of SCH but also help identify patients for whom levothyroxine treatment will provide the most benefit.

Diagnosis and Management of Subclinical Hypothyroidism in Elderly Adults: A Review of the Literature.

The estimated prevalence of subclinical hypothyroidism (SCH) in the general population is 3% to 8%. As the average age of the population in the United States and other countries continues to increase, the overall prevalence of SCH may also be expected to increase. Although age-related changes in thyroid function are well described, normal thyroid-stimulating hormone (TSH) reference limits, derived for age-specific populations, are not routinely used to identify thyroid dysfunction in elderly adults. Therefore, currently accepted values for the upper limit of normal of TSH may be inappropriate for diagnosing SCH in individuals aged 65 and older, resulting in potential overestimation of the prevalence of SCH in this population. This review discusses the current evidence of the effects of SCH on cardiovascular health and neuropsychiatric function in older adults. Although the results of some studies are conflicting, the overall evidence suggests that the consequences of SCH may be different for elderly adults than for younger populations. Treatment of SCH in older individuals requires special consideration with regard to thyroid hormone replacement therapy and expected clinical outcomes. Although careful identification of individuals with persistent SCH who could benefit from levothyroxine treatment is necessary, current evidence suggests that individuals with TSH levels greater than 10 mIU/L who test positive for antithyroid antibodies or are symptomatic may benefit from levothyroxine treatment to reduce the risk of progression to overt hypothyroidism, decrease the risk of adverse cardiovascular events, and improve their quality of life. After treatment is initiated, careful monitoring is essential.

Utility of C-terminal Telopeptide in Evaluating Levothyroxine Replacement Therapy-Induced Bone Loss.

BACKGROUND: Levothyroxine (LT4) therapy has shown to have effects on bone metabolism though its deleterious effect on bone remodeling is debatable. This study was aimed at assessing the diagnostic utility of the bone remodeling marker C-terminal telopeptide (CTx) in detecting early bone loss. MATERIALS AND METHODS: In this case-control study, 84 premenopausal women of 30-45 years of age were selected. Out of them, 28 were recently diagnosed of hypothyroidism (not on LT4), 28 were on LT4 replacement therapy (100-200 µg/day) for more than five years, and 28 had euthyroid. Plasma CTx levels were estimated. Bone mineral density (BMD) was measured by quantitative ultrasound (QUS) method. Pearson's coefficient of correlation and ANOVA were used for statistical analysis. RESULTS: CTx was most elevated in LT4-treated group (0.497 ± 0.209 ng/mL). It showed a significant negative correlation with T-score and Z-score of BMD values. In the treatment group of more than 150 µg/day, CTx showed significantly negative correlation with TSH (r = -0.462, P = 0.047). CONCLUSION: LT4 therapy induces bone loss in hypothyroid patients. CTx levels can measure such bone loss along with BMD. Regular monitoring of CTx with adjustment in LT4 doses may help delay osteoporosis induced by prolonged LT4 replacement therapy.

Thyroid function and obesity.

Important interaction exists between thyroid function, weight control, and obesity. Several mechanisms seem to be involved, and in studies of groups of people the pattern of thyroid function tests depends on the balance of obesity and underlying thyroid disease in the cohort studied. Obese people with a normal thyroid gland tend to have activation of the hypothalamic-pituitary-thyroid axis with higher serum TSH and thyroid hormones in serum. On the other hand, small differences in thyroid function are associated with up to 5 kg difference in body weight. The weight loss after therapy of overt hypothyroidism is caused by excretion of water bound in tissues (myxoedema). Many patients treated for hyperthyroidism experience a gain of more weight than they lost during the active phase of the disease. The mechanism for this excessive weight gain has not been fully elucidated. New studies on the relation between L-T3 therapy and weight control are discussed. The interaction between weight control and therapy of thyroid disease is important to many patients and it should be studied in more detail.