L-thyroxine Replacement Therapy Research Articles

Changes in arterial stiffness, carotid intima-media thickness, and epicardial fat after L-thyroxine replacement therapy in hypothyroidism

Abstract Objective To assess the relationship between primary hypothyroidism and subclinical atherosclerosis and its potential changes with L-thyroxine replacement therapy. Methods A prospective cohort study including 101 patients with primary hypothyroidism and 101 euthyroid patients as controls was conducted from July 2011 to December 2013. Clinical, anthropometrical, biochemical, and ultrasonographic parameters were assessed at baseline and after one year of L-thyroxine replacement therapy. Results At baseline, hypothyroid patients had significantly greater values of blood pressure, total cholesterol, VLDL cholesterol, left ventricular mass, epicardial fat, and carotid intima-media thickness as compared to controls. Total cholesterol, VLDL cholesterol, ventricular diastolic function, epicardial fat, carotid intima-media thickness, carotid local pulse wave velocity, pressure strain elastic modulus, and β arterial stiffness index showed a significant and positive correlation with TSH levels. After one year of replacement therapy, patients with hypothyroidism showed changes in total cholesterol, VLDL cholesterol, TSH, carotid intima-media thickness, and arterial stiffness parameters. Conclusions Primary hypothyroidism is characterized by an increased cardiovascular risk. In these patients, L-thyroxine replacement therapy for one year is related to decreased dyslipidemia and improvement in markers of subclinical carotid atherosclerosis.

Modificaciones de la rigidez arterial, el grosor íntima-media carotídeo y la grasa epicárdica con tratamiento sustitutivo en el hipotiroidismo

ObjectiveTo assess the relationship between primary hypothyroidism and subclinical atherosclerosis and its potential changes with L-thyroxine replacement therapy. MethodsA prospective cohort study including 101 patients with primary hypothyroidism and 101 euthyroid patients as controls was conducted from July 2011 to December 2013. Clinical, anthropometrical, biochemical, and ultrasonographic parameters were assessed at baseline and after one year of L-thyroxine replacement therapy. ResultsAt baseline, hypothyroid patients had significantly greater values of blood pressure, total cholesterol, VLDL cholesterol, left ventricular mass, epicardial fat, and carotid intima-media thickness as compared to controls. Total cholesterol, VLDL cholesterol, ventricular diastolic function, epicardial fat, carotid intima-media thickness, carotid local pulse wave velocity, pressure strain elastic modulus, and β arterial stiffness index showed a significant and positive correlation with TSH levels. After one year of replacement therapy, patients with hypothyroidism showed changes in total cholesterol, VLDL cholesterol, TSH, carotid intima-media thickness, and arterial stiffness parameters. ConclusionsPrimary hypothyroidism is characterized by an increased cardiovascular risk. In these patients, L-thyroxine replacement therapy for one year is related to decreased dyslipidemia and improvement in markers of subclinical carotid atherosclerosis.

The thyroid gland and the process of aging

The endocrine organs, including the thyroid gland, undergo important functional changes during aging. It is known that the prevalence of thyroid disorders increases with age. Importantly, subclinical disturbances of thyroid function are more frequent than overt diseases in the elderly. Moreover, the clinical course of thyroid diseases in elderly people differs from that observed in younger subjects; namely, symptoms are more subtle and are often attributed to normal aging, and therefore, require special attention in elderly individuals. One of the subclinical thyroid function disturbances is subclinical hypothyroidism, which is characterized by normal free thyroxine (FT4) and increased thyrotropin (TSH) levels. The prevalence of subclinical hypothyroidism increases with aging and ranges from 3 to 16 % in individuals aged 60 years and older [1]. In contrast to overt hypothyroidism, the subclinical hypothyroidism in elderly subjects is not associated with impairment of physical and cognitive function, depression, metabolic disturbances or poor quality of life [2,3]. Subclinical hypothyroidism is also not associated with the increased overall mortality risk [2]. Moreover, there is not association between subclinical hypothyroidism and incident coronary heart disease (CHD), heart failure (HF) or cardiovascular (CV) mortality [4]. Similarly, total mortality was not increased in subjects with subclinical hypothyroidism, although the risk of CHD events and of CHD mortality increased with TSH levels 10 mU/L or higher [5]. Importantly, a quite high rate of reversion of subclinical hypothyroidism to euthyroidism in individuals aged at least 65 years with lower baseline TSH levels (4.5-6.9 mU/L) and antithyroid peroxidase antibody (TPOAb) negativity (≤ 37 IU/L) was observed [6]. In turn, higher TSH levels and TPOAb positivity were independently associated with lower chance of reversion to euthyroid status; TSH levels ≥10 mU/L were independently associated with progression to overt hypothyroidism [6]. There are obvious indications for overt hypothyroidism treatment. In turn, indications for treatment of subclinical hypothyroidism are still quite controversial. Nevertheless, the replacement therapy with L-thyroxine is not uniformly recommended in elderly people with subclinical hypothyroidism. For example, L-thyroxine replacement therapy did not improve cognitive function in elderly individuals with subclinical hypothyroidism [7]. Moreover, despite improvement of lipid profile due to treatment of L-thyroxine in subclinical hypothyroidism, there is no clear evidence that this beneficial effect can be associated with decreased cardiovascular or all-cause mortality in elderly patients [8]. Intriguingly, thyroid hypofunction, as well as elevated thyrotropin (TSH) levels may contribute to the extended lifespan. A potential contribution of TSH and thyroid hormones to lifespan regulation was observed in the studies performed on thyroid disease-free population of Ashkenazi Jews, characterized by exceptional longevity (centenarians). For example, the higher serum TSH level in these individuals in comparison with the control groups was observed [9]. Thus, increased serum TSH level seems to be associated with extreme longevity [9]. Moreover, two single nucleotide polymorphisms (SNPs) in TSH receptor (TSHR) gene (namely rs10149689 and rs12050077) were associated with increased TSH level in Ashkenazi Jewish centenarians and their offspring [10]. Also, an inverse correlation between FT4 and TSH levels in centenarians was reported [9] which may suggest a potential role of decreased thyroid function in lifespan regulation, leading to extended longevity. The findings obtained in the Leiden Longevity Study actually show the associations between low thyroid activity and exceptional familial longevity [11]. Also in animals, a reduced thyroid function with low levels of T4 seems to be associated with extended longevity [12-14]. A very severe thyroid hypofunction was observed in Ames dwarf (df/df) mice. These animals are characterized by mutations at the Prop-1 (Prophet of pituitary factor 1) gene and demonstrate a lack of growth hormone (GH), prolactin and TSH. These features may unexpectedly contribute to remarkable longevity in Ames dwarf mice [12]. Furthermore, severe hypothyroid Ames dwarfs and mice with targeted disruption of the growth hormone (GH) receptor/GH binding protein gene (GH receptor knockout; GHRKO) with mild thyroid hypofunction, have decreased thyroid follicle size which may explain decreased thyroid hormone levels in these long-lived mutants [15]. In conclusion, the altered thyroid function may play, via different mechanisms [16], a relevant role in lifespan regulation. Namely, decreased thyroid function may lead to extended longevity.

Clinical and Social Concerns in Treated Patients with Primary Hypothyroidism in Basrah: A Cross Sectional Study

Background: Despite available treatment for hypothyroidism, L-thyroxine replacement therapy in a biochemically appropriate dose does not necessarily relieve patients' symptoms and complaints. The aim of the study was to evaluate the concerns of patients treated with hypothyroidism and to correlate these concerns with different patient characteristics and thyroid biochemical control. Subjects and Methods: one hundred eighteen treated primary hypothyroid patients attending Al-Faiha Specialized Diabetes, Endocrine and Metabolism Center (FDEMC) in Al-Basrah were entering a questionnaire designed to capture personal, anthropometric, biochemical and clinical data. Twenty-four concerns were questioned to the patients who score these concerns on a 4 point Likert scale. Results: The most scored patients' concerns were fatigue, neuropathic pain, lack of weight loss, cold intolerance, breathing problems, and swallowing problems. No statistically significant relations were existed between these concerns and thyroid stimulating hormone (TSH) control, except for a high TSH group which were highly likely to have concerns of feeling sick (OR: 0.27, 95%CI 0.54 to 2.0, p=0.001), neuropathic pain (OR: 0.4, 95%CI 0.17 to 1.6, p=0. 01), cold intolerance (OR: 0.35, 95%CI 0. 0.3 to 1.7, p=0.005), and hair problems (OR: 0.26, 95%CI 0.6 to 2.1, P<0.0001). A significant correlation existed between duration of the hypothyroidism and patients' concerns of swelling of the hands and feet (R=0.7 P<0.0001), memory problems (R=0.4 P<0.0001), hearing disturbance (R=0. 38 P<0.0001), and hair problems (R=0. 3 P=0.001). Age significantly affects patients' concerns of memory problems (R=0. 6 P<0.0001), swelling of the hands and feet (R=0.4 P<0.0001), and hearing disturbance (R=0.37 P<0.0001). Positive correlation was present between low density lipoprotein cholesterol level and patients' concerns of cold intolerance (R=0.3 P=0.001), hair problems (R=0. 28 P=0.003), feeling sick (R=0. 2 P=0. 02), and neuropathic pain (R=0.18 P=0.04). The total cholesterol level also showed a positive correlation with patients' concerns of cold intolerance (R=0.3 P=0.001), hair problems (R=0. 25 P=0.01), neuropathic pain (R=0. 22 P=0. 01), and fatigue (R=0. 2 P=0.04). Conclusion: We cannot rely on the TSH level alone as a marker of optimal treatment outcome in patients with primary hypothyroidism because it does not reflect the concern status of the patients.

Mechanism of subclinical hypothyroidism accelerating endothelial dysfunction (Review).

The association between subclinical hypothyroidism (SH) and cardiovascular disease has received increasing attention in recent years. The predisposition of patients with SH to endothelial dysfunction, an early sign of atherosclerosis, has been observed. This predisposition may be partially explained by the factors also found in patients with SH, including changes in lipid profile, low grade chronic inflammation, oxidative stress and insulin resistance. The proportional risks of endothelial dysfunction to thyroid stimulating hormone (TSH) also indicate that the action of TSH on extra thyroidal-stimulating hormone receptor (TSHR) is a possible mechanism underlying the correlation, which has later been supported by the associated basic studies. L-thyroxine replacement therapy appears to improve the aforementioned aspects, whereas there remain certain controversies, particularly for the elderly. Thus, more study data are required to confirm the benefit of L-thyroxine treatment for patients with SH.

Tuméfaction submandibulaire quatre ans après thyroïdectomie totale

Submandibular swelling most frequently involves the submandibular gland. It is often due to lithiasis or to tumor. Some rare cases of submandibular swelling have been reported such as submandibular localizations of thyroid lesions. Our case study concerns one of these rare occurrences. A 47-year-old female patient consulted for a right-sided submandibular mass progressively increasing in size during the previous 2 years. The patient had undergone a total thyroidectomy, 4 years before consulting, for a toxic multinodular goiter THAT had been treated by L-thyroxin replacement therapy per os since the surgery. TSH and LT4 levels were normal. A CT scan revealed a large tumor in the right submandibular space with heterogeneous contrast. Fine needle cytopuncture allowed observing follicular cellules suggesting thyroid origin. The cervicotomy confirmed the diagnosis of an ectopic goiter. Thyroid disorders may in rare cases concern the submandibular space. A history of thyroid disorders should be taken into account for the etiological diagnosis of unusual submandibular masses in maxillo-facial surgery.

Thyroid function in respiratory failure patients

BackgroundThe non thyroidal illness syndrome (NTIS) represents a risk factor for prolonged mechanical ventilation in mechanically ventilated, critically ill patients admitted to the ICU. It is unclear, whether the NTIS is only a biochemical prognostic marker or it actually contributes to the development and progression of respiratory failure. AimTo assess the thyroid function in patients with respiratory failure and to evaluate the impact of thyroid dysfunction as well as thyroid hormone replacement therapy on patients’ outcome. Patients and methodsThe study was conducted on 100 patients (51 females and 49 males), they were divided into two groups, Group A (respiratory failure group), who were admitted to the Respiratory ICU (RICU) and group B (non-respiratory failure group) who were admitted to the Inpatient Chest Department of Zagazig University Hospitals Egypt. The respiratory failure group (Group A) included sixty-four (64) patients with respiratory failure (according to ABG parameters) 30 males and 34 females. They included 30 patients with acute exacerbation of COPD, 5 patients with acute severe bronchial asthma, 5 patients with severe pneumonia, 4 patients with acute pulmonary embolism, 8 patients with ARDS and 12 patients with acute exacerbation of IPF. This respiratory failure group included 43 patients who were on invasive mechanical ventilation and 21 respiratory failure patients who were non-mechanically ventilated. Group (B) included thirty-six (36) patients without respiratory failure according to ABG parameters as a control group (19 males and 17 females). There were 11 patients with acute exacerbation of COPD, 10 patients with exacerbated bronchial asthma, 6 patients with exacerbated IPF, 6 patients with pneumonia and 3 patients with acute pulmonary embolism. All patients were subjected to calculation of APACHE Π score, PaO2/FiO2 ratio and estimation of thyroid hormones (TSH, free T3 and free T4) at the 1st, 3rd and 10th day of admission. Those who were still having ESS at the 10th day (16 patients) and were not improving clinically, were subdivided randomly into two subgroups. Each of them comprised 8 patients. One group was given l-thyroxin replacement therapy (The replacement group) beside conventional appropriate management. The other group (8 patients) was followed by conventional appropriate management only without replacement therapy (The non-replacement group). l-Thyroxine 100μg daily is administered for 7weeks. At the 7th week, a fourth set of thyroid hormone estimation was done for the patients of the replacement and non-replacement groups. Patients’ outcome was assessed after 7weeks of admission and labeled as the following: 1-death, 2-successfully treated and discharged. ResultsRespiratory failure patients showed evidence of euthyroid sick syndrome (ESS) at the 1st, 3rd and 10th days of admission with a frequency of 31.2%, 79.6% and 43.7% respectively while none of the control group showed evidence of (ESS) and the difference was statistically significant. There were highly significant negative correlation between serum levels of free T3 and TSH and each of the duration of mechanical ventilation and length of ICU stay. There was significant negative correlation between APACHE Π score and serum level of freeT3 in the respiratory failure group. There was non significant impact of thyroid hormone levels on patients’ outcome. There was non significant difference in the levels of thyroid hormones between replacement and non replacement groups at the 7th week of the study. ConclusionA state of hypothyroidism or euthyroid sick syndrome (ESS) is commonly found among patients with respiratory failure and this is related to the severity of the disease. ESS represents a risk factor for prolonged mechanical ventilation and length of ICU stay. l-thyroxin replacement therapy has no significant impact on patients’ outcome.

Sequential Thyroid Storm and Myxedema Coma: A Unique Case Report

Background and objective: Both thyroid storm and myxedema coma are rare life-threatening events and carry a high mortality rate. Our objective is to document a unique case of sequential thyroid storm and myxedema coma. Results: We report a very unusual case of a 46-year-old female patient who presented initially in 2002 with thyroid storm caused by a previously undiagnosed Graves’ disease. After two doses of radioactive iodine treatment, she developed hypothyroidism for which she was placed on l-thyroxine replacement therapy. She was lost to followup and, indeed, she failed to take her l-thyroxine medication and in the fall of 2010, she presented to our Emergency Department with myxedema coma, which was treated successfully. Conclusion: A careful and life-long follow-up is essential in patients who have received thyroid radioactive iodine ablation or total thyroidectomy to ensure that their thyroidal status remains stable. This constitutes the first step in the prevention of myxedema coma, a diagnosis which still carries an appreciable mortality rate.

Does Hypothyroidism Cause Hyponatremia?

Background: According to most clinical guidelines hypothyroidism should be excluded as a cause in the analysis of euvolemic hyponatremia. Although this axiom has been well established in clinical practice, relatively little evidence supports a relation between hypothyroidism and hyponatremia. The current study was conducted to prove an association between hypothyroidism and the occurrence of hyponatremia. In addition, we sought to determine the effect of L-thyroxine replacement therapy on plasma sodium levels. Methods: Data from 2009 to 2011 were retrospectively reviewed. The database included blood samples in which both thyroid function and plasma sodium were determined. Regression analysis and ANOVA were performed to reveal an association between hypothyroidism and hyponatremia. Results: Linear regression analysis of plasma sodium on plasma TSH revealed no relationship (R2 = 0.005). The corresponding gradient belonging to the regression line was ﹣0.427 mmol/log plasma TSH (p = 0.22). No significant relation between plasma sodium and TSH concentration could therefore be found. 32 hypothyroid patients who were treated with L-thyroxine, were identified. No clear change in plasma sodium could be discerned with regression analysis (0.707 mmol/L per year, p = 0.147). Conclusion: Hypothyroidism is not a common cause of hyponatremia. Screening for thyroid function does not seem warranted in the initial analysis of a hyponatremic patient.

Premature Menarche Associated with Hashimoto Thyroiditis at 2 years 9 months: Case Report

Primary hypothyroidism is frequently associated with delayed puberty. However, precocious puberty is known to occur in some rare cases of hypothyroidism untreated for a long time. A female patient with Down syndrome aged 2 years and 9 months was referred with the symptom of vaginal bleeding continuing for 1 week. In her history, there were no symptoms suggesting trauma, foreign body, urinary tract infection or intracranial mass. The patient exhibited the phenotypic features of Down syndrome and her height and weight were within 5%-25% percentiles and 25%-50% percentiles, respectively, regarding the growth curves generated for children with Down syndrome. Breast development was at Tanner stage 3 bilaterally, and she had no axillary or pubic hairs. Suprapubic ultrasonography revealed cystic lesions in the right lower quadrant and left adnexial region. She was diagnosed with Hashimoto thyroiditis as result of the tests and was started on Na lthyroxine replacement therapy, and all examination findings relevant to precocious puberty and laboratory parameters returned to normal in the 6th month of the treatment.

Effects ofl-Thyroxine on Gastric Motility and Ghrelin in Subclinical Hypothyroidism: A Prospective Study

Overt hypothyroidism affects the gastrointestinal system. Limited data are available regarding gastric motility in subclinical hypothyroidism (SCH). The aim of this study was to assess gastric motility-related gastric symptoms and levels of ghrelin in patients with SCH compared with those in healthy control subjects and to evaluate the potential effects of l-thyroxine replacement therapy. Twenty premenopausal women with SCH and 20 age- and body mass index-matched healthy control women were enrolled in the study. The gastroparesis cardinal severity index questionnaire was used to reveal gastrointestinal motility changes, and electrogastrographic activities were measured. Fasting and postprandial ghrelin levels at 30, 60, and 120 minutes were determined during a mixed meal test. All tests were repeated after 6 months when patients were in the euthyroid state. The gastroparesis cardinal severity index score, fasting tachygastria ratio, and postprandial/fasting bradygastria ratio in electrogastrography were higher in patients with SCH compared with control subjects (P = .03, P = .04, and P = .04, respectively). All 3 parameters significantly improved after l-thyroxine replacement therapy (P < .001, P = .005, and P =.02 respectively) reaching levels similar to those of control subjects. Baseline and area under the curve for ghrelin during mixed meal tests did not show a difference between patients with SCH and control subjects and before and after l-thyroxine replacement in SCH. Gastric dysmotility and the resultant upper gastrointestinal symptoms can be observed in SCH, and symptomatology related to dysmotility and parameters appear to be improved with thyroid hormone replacement. Our results also suggest that ghrelin levels in response to a meal are similar between women with SCH and healthy women and that normalization of thyroid function by l-thyroxine does not modulate these levels.

Combined l-thyroxine and l-triiodothyronine replacement therapy in congenital hypothyroidism

L-thyroxine replacement therapy is the treatment of choice for hypothyroidism. Recently, several studies suggested to complete it with l-triiodothyronine in acquired hypothyroidism. To study the role of combined l-thyroxine and l-triiodothyronine therapy in special cases with congenital hypothyroidism. Data of 16 patients (age: 11.9 ± 6.3 years; mean ± SD) are presented who had high serum free thyroxine values or even above the upper limit of reference range (21.16 ± 2.5 pmol/l) together with nonsuppressed TSH levels (15.7 ± 5.7 mIU/l), and therefore received l-triiodothyronine in completion (0.18 ± 0.09 μg/kg) once a day. The combined replacement therapy resulted in a rapid improvement of the hormone parameters (TSH: 4.2 ± 3.15 mIU/l; free thyroxine: 16.55 ± 2.4 and free triiodothyronine: 7.4 ± 1.8 pmol/l). The efficiency of this combined therapy proved to be more evident (TSH: 4.33 ± 3.2 mIU/l; free thyroxine: 16.85 ± 3.1 and free triiodothyronine: 6.4 ± 0.85 pmol/l) in 10 patients treated for a longer period of time (duration of treatment: 2.9 ± 2.0 years). The dose of thyroxine substitution decreased from 2.6 ± 0.9 to 2.18 ± 0.6 μg/kg/day), the ratio of these hormones was between 5:1 and 19:1 and the quotient of free fractions was normalized (3.8 ± 0.4→2.6 ± 0.3) during the replacement therapy. According to the observation of the authors a serious disturbance of feed-back mechanism may develop in some (>5%) children with congenital hypothyroidism (increased TSH release despite elevated free thyroxine level) after normal function of the feed-back system for years. Hormone parameters of these patients improve, then become normal on combined therapy supporting the rationale for this treatment method.

Diagnostic Significance of Subclinical Hypothyroidism in Health Check-ups

Subclinical hypothyroidism (SHT) is defined as an asymptomatic state associated with normal serum FT4 and a slightly elevated serum TSH concentration. Patients with SHT have a high rate of progression to clinically overt hypothyroidism (OHT), and in addition, SHT is thought to be a risk factor for atherosclerosis and coronary heart disease. The aim of this study was to identify SHT patients and refer them to a thyroid specialist for treatment and management. We retrospectively studied 1168 subjects (324 males and 844 females) who received health check-ups including thyroid function tests in our Health Service Association Clinic over a period of three years and eleven months. Sixty subjects (5.1%) were diagnosed as SHT. The TSH/FT4 ratio (SHT index) was found to be helpful for diagnosing SHT. The main causes of SHT were Hashimoto's thyroiditis, excess dietary iodine intake. L-thyroxine replacement therapy was recommended for patients with a TSH greater than 10 μU/mL. For patients with very mild SHT who are pregnant or anticipate becoming pregnant, L-thyroxine therapy should be started. We devised a flowchart for the diagnosis and management of SHT.

Correction of Hypothyroidism Seems to Have No Effect on Body Fat

Aim. We aimed to observe the effects of L-thyroxine replacement therapy on body fat content determined with various anthropometric methods and a bioelectrical impedance analysis method in patients with hypothyroidism. Methods. Forty-two women with naive autoimmune hypothyroidism were included. Also, 40 healthy participants were enrolled as a control group. Weight, body mass index, waist circumference, and subscapulary, suprailiac, femur, biceps, and triceps skin fold thicknesses were measured. Body fat percentages were calculated and body fat measurements were performed. Euthyroidism was maintained with L-thyroxine. At the 6th and 18th month, of therapy, measurements were reperformed. Results. Mean TSH levels were 57.49 ± 36.46 mIU/L in hypothyroid group and 1.94 ± 1.12 mIU/L in control subjects at admission. In hypothyroid patients, calculated body fat percentages were greater than those of the control subjects during follow-up. Body fat percentage of each hypothyroid case decreased at 6- and 18-month controls, but the decrements were statistically insignificant. Although skin fold thicknesses measured from all sites were observed to decline, only those obtained from femur and biceps showed a significant decrease (P = 0.03 and P = 0.01, resp.). Discussion. Correction of hypothyroidism did not cause any improvement in body weight and body fat percentage. The decrease in skin fold thicknesses might probably result from the reduction in subcutaneous mucopolysaccharide deposits.

Clinical Significance of TSH Circadian Variability in Patients with Hypothyroidism

Objective. To investigate the clinical significance of thyroid-stimulating hormone (TSH) circadian variability in patients with hypothyroidism. Design. A total of 20 women with subclinical hypothyroidism and 22 patients taking l-thyroxine replacement therapy for hypothyroidism were enrolled in the study. Measurements of serum TSH levels were done twice a day from 08.00 to 09.00 a.m. and from 2.00 to 4.00 p.m. Results. The morning median TSH value in the patients with subclinical hypothyroidism was 5.83 mU/L; in the afternoon, it was 3.79 mU/L. The range of TSH circadian variability reached the level of 73%. According to the current TSH reference interval, hypothyroidism was not diagnosed in about 50% of the cases in the afternoon. The morning median TSH value in the patients taking l-thyroxine was 3.27 mU/L; it decreased to the value of 2.18 mU/L in the afternoon. The range of TSH circadian variability reached the level of 64.7%. Further analysis demonstrated inadequate compensation of hypothyroidism, which was defined in 45.5% of the morning samples and in 9% of the afternoon samples (p < 0.05). Conclusion. The time of blood sampling has an important role in the interpretation of TSH levels. Moreover, the high TSH circadian variability should be considered in discussions about the narrowing of its reference range.

Metabolic and Cardiovascular Aspects of Subclinical Hypothyroidism: Effects of L-Thyroxin Replacement Therapy

Abstract Background: Subclinical hypothyroidism (SH) is a common clinical issue, presented with high serum TSH and normal T4, T3 levels. Various clinical and metabolic derangements were reported related to SH. L-T4-replacement is a challenge in daily practice. We investigated the efficacy of L-T4-replacement on certain metabolic and cardiovascular parameters in subjects with SH. Methods: Fifty-three (40 female; 13 male) subjects were included. Of the 53 subjects, 29 were randomly given L-T4 replacement, 24 were followed as control group through 6-months. Before L-T4 replacement (basal) and at the end of the study; symptoms, physical examination, serum metabolic parameters, Holter ECG and trans-thoracic echocardiography were performed. Two groups were compared. Results: Mean age of the patients was 44.02 ± 13.9; body mass index 29.4 ± 6.4 kg/m2. In the T4-replacement group, there was a significant difference between serum TSH and FT3 levels compared to the basal measurements (p = 0.005 and p = 0.017). LDL-cholesterol levels of the replacement group were not changed significantly, but of the control group significantly increased (p=0.01). Mean ejection fraction (EF) did not show significant change at both basal and 6-month. Peak transmitral early diastolic flow speed (E) decreased in the control group (p = 0.013). Peak transmitral late diastolic flow speeds (Em/Am) of the controls were found to be decreased compared to the basal ratio (p = 0.005). Isovolumetric relaxation times (IVRT) of both groups were prolonged at the time of basal measurements (123 ± 45.8 msc). Long IVRT persisted in the control group through the study (p=0.012). Conclusion: Symptoms of hypothyroidism are common in subjects with SH, and L-T4 replacement can improve the Cand metabolic derangements.

Difficult treatment of consumptive hypothyroidism in a child with massive parotid hemangioma

Consumptive hypothyroidism is a rare condition related to massive infantile hemangiomas producing an excess of the thyroid-hormone-inactivating enzyme type 3 iodothyronine deiodinase. We report the first case of consumptive hypothyroidism secondary to a large parotid hemangioma, highlighting the difficulties in selecting an adequate therapeutic strategy. The affected child was initially referred to our center for congenital hypothyroidism with a hypoplastic thyroid gland. L-Thyroxine (L-T4) replacement therapy was started at seven days of life. In the following weeks, the hemangioma rapidly increased in volume and the child developed severe hypothyroidism refractory to high doses of L-T4 therapy. The concentration of reverse triiodothyronine was elevated, suggesting that the underlying cause was an excessive conversion of thyroid hormones by high type 3 iodothyronine deiodinase levels in the tumor. Corticosteroid treatment showed only partial benefit. Introduction of propranolol instead led to normalization of thyroid hormones along with a dramatic involution of the hemangioma.

Thyroid Hypoplasia as a Cause of Congenital Hypothyroidism in Monozygotic Twins Concordant for Rubinstein-Taybi Syndrome

Rubinstein-Taybi syndrome (RSTS), a genetic disorder characterized by growth retardation, mental deficiency, dysmorphic face, broad thumbs and large toes, generally affects monozygotic twins concordantly. Thyroid hypoplasia (TH) is a common cause of congenital hypothyroidism (CH) and often accompanies dysmorphic syndromes. A pair of female twins were admitted to our neonatology unit 16 hours after delivery. They were born at 35 weeks of gestation. Both twins had an unusual dysmorphic facial appearance with microcephaly, as well as broad short thumbs and large toes. Based on the presence of characteristic dysmorphic features, the twins were diagnosed as RSTS. Thyroid function tests in the first twin revealed the following results: free thyroxine (T4) 8.4 pg/mL, thyrotropin (TSH) 4.62 mIU/L, thyroglobulin (TG) 213.24 ng/mL and a normal level of urinary iodine excretion (UIE). Thyroid function test results in the second twin in the second week were: free T4 5.9 pg/mL, TSH 9.02 mIU/L, TG 204.87 ng/mL, and normal UIE levels. Thyroid volumes were 0.36 mL and 0.31 mL in the first and second twin, respectively. TH was confirmed by technetium 99 m pertechnetate thyroid scans in both infants. Thyroid function tests normalized with L-thyroxine replacement therapy (10 μg/kg/day) around the end of the 3rd week of life. The infants were discharged planning their follow-up by both endocrinology and cardiology units. The rarity of cases of twins with RSTS (concordant) co-existing with CH led us to present this report. Conflict of interest:None declared.

Deteriorated Executive Functions in Patients with Successful Surgery for Pituitary Adenomas Compared with Other Chronically Ill Patients

Pituitary adenomas, even after successful treatment, are associated with cognitive impairments. It is unclear whether these deficits are a consequence of unspecific factors associated with having a chronic illness and whether the cognitive dysfunctions exceed those of other chronically ill patients. Thirty-eight patients with transsphenoidal surgery for pituitary adenomas and 38 patients undergoing L-thyroxine replacement therapy after thyroid surgery were studied neuropsychologically with established tests. Executive function was examined with the Trail-Making Test A and B, working memory with the digit span test, attention with the digit symbol test, verbal memory with the German version of the Auditory Verbal Learning and Memory Test, and general verbal intelligence by a vocabulary test. Attention (p = .007), attentional speed (p = .0004), executive control (p = .04), and working memory (p = .01), were significantly reduced in patients with pituitary adenomas compared with other chronically ill patients. In contrast, no differences were found between the groups for verbal memory (all subtests: p ≥ .06). Patients with successful surgery for pituitary adenomas show also in comparison with other chronically ill patients an increased risk for deficits in certain aspects of cognitive function, including attention and working memory, supporting the relevance of the brain lesion and its treatment for these dysfunctions.

The impact of sunitinib-induced hypothyroidism on progression-free survival of metastatic renal cancer patients: A prospective single-center study

BackgroundSeveral studies have reported unexpected rates of hypothyroidism in patients treated with sunitinib. The biochemical basis of this impairment is unknown. A relationship between hypothyroidism and improved outcome has been suggested in some cancer patients. Here we describe the incidence of newly onset hypothyroidism and its relationship with progression-free survival in metastatic renal cell carcinoma patients undergoing sunitinib treatment at our institution. Patients and methodsBetween July 2007 and June 2009, 22 patients received a first line sunitinib for metastatic renal cell carcinoma. Thyroid function tests were prospectively evaluated as routine laboratory assessment in every patient, at baseline and on the first and last day of every ON and OFF sunitinib period. ResultsThe median duration of treatment was 39.5 weeks. During sunitinib therapy, 13 patients (59.1%) showed at least one elevated TSH level. No reductions of TSH below normal ranges were observed. L-thyroxine replacement therapy was required in 2 patients. Based on thyroid function, median progression-free survival was 8.55 months for hypothyroid compared with 7.03 months for euthyroid patients (P < 0.05). ConclusionPatients administered sunitinib have an high incidence of hypothyroidism. The improved outcome of hypothyroid patients suggests an important relationship between sunitinib and this uncommon side effect.