Evaluation of L-thyroxine replacement therapy in children with congenital hypothyroidism.

The outcome of L-thyroxine (L-T4) replacement therapy in children with congenital hypothyroidism (CH) remains to be completely evaluated. In this paper the overall pattern of response to L-T4 replacement therapy was studied in a group of 19 children with CH diagnosed by neonatal screening (10 with hypoplastic/aplastic thyroid disease, group H/A; 9 with gland ectopy, group E) who were followed-up for 60 +/- 27 months (mean +/- SD). With 1 exception serum T4 at diagnosis was greater than 2 micrograms/dl in children of group E and less than 2 micrograms/dl in those of group H/A. The initial dose of L-T4 (8-10 micrograms/kg BW/day) was modified in relation to age and weight in order to maintain serum TSH less than or equal to 5 microU/ml and FT3 in the normal range. A general inverse correlation between serum TSH and FT4 or FT3 concentrations was found, and the mean levels of serum FT4 and FT3 were significantly higher according to the following order of TSH results: low TSH (0-0.5 microU/ml) greater than normal (greater than 0.5-5 microU/ml) greater than elevated TSH (greater than 5 microU/ml). TSH levels less than or equal to 5 microU/ml were associated with FT4 values in the upper half of the normal range (54% of observations) or even higher (46%). Elevation of serum FT4 alone with FT3 values in the normal range did not result in clinical thyrotoxicosis, alteration of growth or premature craniosynostosis.(ABSTRACT TRUNCATED AT 250 WORDS)     

The efficacy of replacement therapy with L-thyroxine in manifest and latent forms of hypothyroidism

Individual sensitivity of the hypothalamo-hypophyseal-thyroid system was studied in 12 patients with various degrees of euthyroid hyperplasia in the first 2 days of thyroxine therapy and during prolonged therapy. The effectiveness of thyroxine substitution therapy was compared with that of therapy with thyroid drugs in 55 patients with hypothyroidism. Euthyroid hyperplasia of III degree was accompanied by a more marked decrease in the level of TSH than in II degree, however during 3 mos. of therapy the size of the gland did not change. L-thyroxine administration for substitution therapy for 3-5 mos. was accompanied by a stable decrease in the level of TSH and improvement of clinical indices in hypothyroidism.     

The effect of L-thyroxine replacement therapy on lipid based cardiovascular risk in subclinical hypothyroidism

The aim of our study was to assess the changes in serum lipid profiles after replacement therapy with L-T4 in patients with subclinical hypothyroidism (SCH), and to see whether there is an improvement in dyslipidemia based cardiovascular risk. Thirty non-smoker pre-menopausal women with newly diagnosed SCH (TSH between 4 and 10 microIU/ml) were involved in our study; twenty-six euthyroid healthy subjects were used as control group. TSH, free T3 (FT3), free T4 (FT4), total cholesterol (TC), triglyceride (TG), HDL cholesterol (HDL-C) and LDL cholesterol (LDL-C) levels were measured before and after 6 months of L-T4 (50-100 microg/ day) therapy. TSH levels were targeted as < 2.0 microIU/ml. LDL-C was calculated using the Friedewald formula, while the cardiovascular risk was assessed with the TC/HDL-C ratio. Pre-treatment serum TC and LDL-C concentrations in SCH patients were significantly higher than those of euthyroid subjects (199.8 +/- 22.2 vs 181.5 +/- 24.6 mg/dl, p < 0.01; 146.3 +/- 26.1 vs 124.8 +/- 12 mg/dl, p < 0.001, respectively). TC, LDL-C levels and the TC/HDL-C ratio were reduced significantly after 6-month replacement therapy (-21.1 +/- 34.4 mg/dl or -10.5%, p < 0.01; -21.5 +/- 30.3 mg/dl or -14.7%, p < 0.001, respectively; and TC/HDL-C from 4.8 +/- 0.6 to 4.1 +/- 0.5 mg/dl, p < 0.01), while body mass index (BMI) values did not change. In conclusion, even mild elevations of TSH are associated with changes in lipid profile significant enough to raise the cardiovascular risk ratio, and these changes are corrected once the patients have been rendered euthyroid.     

Normalization of hyperhomocysteinemia with L-thyroxine in hypothyroidism.

BACKGROUND: Hyperhomocysteinemia is an independent risk factor for coronary, peripheral, and cerebrovascular disease. Elevated plasma homocysteine levels were described in a preliminary report on primary hypothyroidism. OBJECTIVE: To determine whether restoration of euthyroidism by L-thyroxine replacement therapy would reduce or normalize plasma homocysteine levels. DESIGN: Prospective cohort study. SETTING: Outpatient endocrinology department of a tertiary center. PATIENTS: 14 patients (10 women and 4 men; 25 to 77 years of age): 4 with newly diagnosed chronic (Hashimoto) hypothyroidism and 10 who had been rendered acutely hypothyroid (thyroid-stimulating hormone level > 25 mU/L) by total thyroidectomy for thyroid carcinoma. MEASUREMENTS: Total plasma homocysteine levels were measured at baseline and 3 to 9 months later, after euthyroidism had been attained by L-thyroxine replacement therapy. RESULTS: Median baseline plasma homocysteine levels in both sexes (women, 11.65 micromol/L [range, 7.2 to 26.5 micromol/L]; men, 15.1 micromol/L [range, 14.1 to 16.3 micromol/L]) were higher (P = 0.002) than those in healthy female (n = 35) and male (n = 36) volunteers (women, 7.52 micromol/L [range, 4.3 to 14.0 micromol/L]; men, 8.72 micromol/L [range, 5.94 to 14.98 micromol/L]). Eight patients (57%) had baseline plasma homocysteine levels that exceeded the upper limit of sex-specific reference ranges. Upon attainment of euthyroidism, all patients had a diminution in plasma homocysteine levels. The median overall change of -5.5 micromol/L (range, -15.4 to -1.8 micromol/L) corresponds to a difference of -44% (range, -58% to -13%) (P < 0.001). Homocysteine levels returned to normal in 7 of the 8 patients with elevated pretreatment values. CONCLUSIONS: Hypothyroidism may be a treatable cause of hyperhomocysteinemia, and elevated plasma homocysteine levels may be an independent risk factor for the accelerated atherosclerosis seen in primary hypothyroidism.     

Remission of Raynaud's phenomenon after L-thyroxine therapy in a patient with hypothyroidism.

A 50-year-old man is described who had a 15-year history of Raynaud's phenomenon with severe and frequent vasospastic attacks in his fingers and toes during the past years. Exacerbation of his digital symptoms, which started about 4 years ago, was accompanied by signs of thyroid deficiency, such as tiredness, memory impairment, decreased libido, constipation, dryness of skin and bradycardia. Hormonal evaluation revealed primary hypothyroidism and the patient began substitution therapy with L-thyroxine. After 2 months of treatment not only did he become euthyroid but the digital symptoms also disappeared. The patient may thus represent one of the very few cases whose thyroid replacement therapy proved to be highly effective in treating both hypothyroidism and Raynaud's phenomenon.     

Effects of thyroid replacement therapy on arterial blood pressure in patients with hypertension and hypothyroidism

Background Hypothyroidism is frequently accompanied by cardiac dysfunction, increased vascular resistance, and a greater prevalence of hypertension. Treatment of hypothyroidism may lead to normalization of blood pressure, although some patients may exhibit sustained hypertension. The mechanism of this condition may be the alterations in aortic stiffness. Methods Aortic stiffness was studied in 30 patients who never received treatment for hypertension or hypothyroidism, 15 patients with normal blood pressure and hypothyroidism, and 15 patients with hypertension and normal thyroid function. Thirty healthy age- and sex-matched subjects with normal thyroid function served as control subjects. Aortic diameter evaluated by M-mode echocardiography and blood pressure measured by a sphygmomanometer were used to calculate aortic stiffness index. Results Patients with high blood pressure and hypothyroidism, those with normal blood pressure and hypothyroidism, and those with hypertension and normal thyroid function showed increased aortic stiffness index (18.8 ± 6.4, 11.7 ± 3.5, and 19.2 ± 5.3 vs 9.5 ± 2.7; P < .001) compared with control subjects. In 15 patients with hypertension and hypothyroidism, levothyroxine therapy showed only a small decrease in blood pressure (151/105 ± 9/9 mm Hg, group A). The remaining 15 patients showed complete normalization of blood pressure (118/83 ± 8/3 mm Hg, group B). Aortic stiffness index was increased in group A compared with group B both before and after treatment (before, 24.0 ± 4.1 vs 13.7 ± 3.2; and after, 22.3 ± 4.2 vs 11.1 ± 2.9; P < .001 for both comparisons). Felodipine was given to patients in group A after levothyroxine was administered, resulting in normalization of blood pressure and a significant decrease of aortic stiffness index (P < .001). Aortic stiffness index was decreased in patients with hypothyroidism and hypertension after administration of levothyroxine (9.5 ± 2.2; P < .001) and felodipine (14.5 ± 7.5; P < .001) therapy, respectively. Percent changes in systolic blood pressure showed a significant correlation with percent changes in aortic stiffness index in all patients (r = 0.65, P < .001). After multivariate adjustment, aortic stiffness index (odds ratio = 1.9932; confidence interval = 1.1481 to 3.4605) was significantly associated with incomplete normalization of blood pressure. Conclusions Patients with hypertension and hypothyroidism have increased aortic stiffness. Aortic stiffness is decreased in all patients, whereas hypertension is completely reversible in 50% of patients by hormone replacement therapy. Sustained hypertension may be due to increased aortic stiffness. (Am Heart J 2002;143:718-24.)     

Thyroxine replacement therapy enhances clearance of chylomicron remnants in patients with hypothyroidism.

To further confirm the benefit of replacement therapy in terms of risk for coronary artery disease, we evaluated the effect of T4 on postprandial lipoproteins in patients with hypothyroidism. Nine normolipidemic patients (aged 62.75+/-7.6 yr) with TSH of 32.2+/-13.2 mU/L and free T4 of 0.66+/-0.17 ng/mL were treated with T4 (50-100 microg/day) for at least 4 months. The behavior of postprandial lipoproteins was assessed before and during treatment by determining retinyl palmitate levels in the total plasma, chylomicrons (Sf >1000) and chylomicron remnants (Sf <1000) fractions for 8 h after a mixed meal plus vitamin A. During T4 treatment, serum levels of TSH and FT4 were 4.4+/-4.9 mU/L and 1.2+/-0.34 ng/mL (P = 0.001 and P = 0.002), respectively. Fasting low density lipoprotein cholesterol decreased from 166+/-35 to 135+/-23 mg/dL (P = 0.035). Retinyl palmitate (RP) levels in the chylomicron remnant fraction was reduced significantly during therapy from 6948+/-2790 to 5174+/-2401 microg/L x h (area under the curve +/-SD; P = 0.014). Total plasma RP and chylomicron RP remained unchanged. We conclude that T4 enhances the clearance of chylomicron remnants in normolipidemic patients with hypothyroidism.     

Coronary flow reserve after L-thyroxine therapy in Hashimoto's thyroiditis patients with subclinical and overt hypothyroidism

Backgound/Aims Overt and subclinical hypothyroidism are reported to be associated with increased cardiovascular disease risk. We have used coronary flow reserve (CFR) measurement by trans-thoracic Doppler echocardiography (TTDE) to determine coronary microvascular function in Hashimoto’s thyroiditis patients with overt and subclinical hypothyroidism and to evaluate effects of l-thyroxine replacement on coronary endothelial function. Methods In total, 10 overt hypothyroid patients, 10 subclinical hypothyroid patients, and 10 controls were enrolled. FT4, TSH, anti-thyroid antibodies, lipid profile, insulin, glucose, HOMA-IR, physical parameters, and CFR measured by TTDE were recorded before and after 6 months of l-thyroxine replacement in all groups. Results CFR values of all hypothyroid patients at baseline were significantly lower than those in controls. After l-thyroxine, CFR increased significantly in overt and subclinical hypothyroidism with respect to the baseline measurements (P < 0.05). When baseline and second measurements were evaluated collectively for patients and controls, CFR was positively correlated with FT4 levels (r = 0.31, P = 0.01) and negatively correlated with TSH and HOMA-IR (r = −0.38, P = 0.002 and r = −0.42, P < 0.001, respectively). Conclusion Subclinical as well as overt hypothyroid patients have impaired coronary microvascular function which improved after l-thyroxine therapy. Treatment of Hashimoto’s thyroiditis patients with subclinical hypothyroidism should be considered to improve cardiovascular disease risk.     

L-thyroxine requirement in patients with autoimmune hypothyroidism and parietal cell antibodies

BACKGROUND: Hypothyroid patients on l-T(4) therapy may require replacement doses exceeding the theoretical needs to normalize serum TSH due to low patient compliance, drugs interference, and malabsorption. OBJECTIVE: We examined whether autoimmune gastritis might cause increased l-T(4) requirement in patients with autoimmune thyroiditis receiving l-T(4) replacement. PATIENTS: We studied 391 patients with clinical or subclinical hypothyroidism from autoimmune thyroiditis who had achieved normal serum TSH concentration (0.3-3.0 microU/ml) under l-T(4) for at least 6 months. Patients were screened for serum parietal cell antibodies (PCA) as a marker of autoimmune gastritis, and the PCA status was correlated with the l-T(4) dose. We also studied a group of 60 patients receiving l-T(4) replacement after total thyroidectomy. RESULTS: PCA-positive (155 of 391) and PCA-negative (236 of 391) patients did not differ for pretherapy serum TSH levels and thyroid volume. The l-T(4) requirement was significantly (P = 0.002) higher in PCA-positive (1.24 +/- 0.40 microg/kg x d) than in PCA-negative patients (1.06 +/- 0.36 microg/kg x d), and a significant positive correlation was found between l-T(4) requirement and serum PCA levels. Among PCA-positive patients, l-T(4) requirement was even higher in those with proven gastritis (1.52 +/- 0.40 microg/kg x d) compared with those without gastric damage (1.15 +/- 0.33 microg/kg x d) (P < 0.0001). The increased l-T(4) requirement was confirmed also in PCA-positive thyroidectomized patients (1.81 +/- 0.27 microg/kg x d) compared with PCA-negative thyroidectomized patients (1.52 +/- 0.24 microg/kg x d). Independent variables affecting l-T(4) requirement were PCA and serum TSH at diagnosis. CONCLUSIONS: Autoimmune gastritis is an additional factor affecting l-T(4) requirement in patients with autoimmune thyroiditis. Serum PCA measurement should be considered in patients with an unexplained high requirement of l-T(4).     

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

<正>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 were     

Changes in serum apolipoprotein concentrations after L-thyroxine therapy in infants with congenital hypothyroidism

To further characterize the impact of thyroid hormones on the serum lipid profile, we studied serum apolipoproteins in infants with congenital hypothyroidism before and after L-thyroxine (L-T4) replacement therapy. Serum high-density lipoprotein cholesterol (HDLC) decreased after L-T4 therapy. Total cholesterol (TC) and low-density lipoprotein cholesterol (LDLC) levels did not change significantly after therapy. Two months after L-T4 replacement therapy, serum apolipoprotein A-I (apo A-I), C-III, and E declined and apo B increased significantly. No significant changes were observed for serum concentrations of apo A-II and C-II after L-T4 substitution. We conclude that in infants, thyroid hormone reduces serum levels of apo A-I, the principal protein component of HDLC, and this may contribute to the decline of serum HDLC concentrations after L-T4 replacement therapy.     

Unusual neurotoxicity associated with amiodarone therapy

One hundred two patients with recurrent, drug-refractory tachyarrhythmias were treated with amiodarone for nine +/- eight months (mean +/- SD) (range, one to 50 months). Forty-five patients exhibited some form of neurotoxic reaction that was severe enough in nine patients to require discontinuation of treatment or reduction in dosage of the drug. The most frequent neurotoxic findings were tremor (44 patients), peripheral neuropathy (ten patients), and ataxia (seven patients). Five patients developed unusual neurotoxic manifestations: brainstem dysfunction characterized by downbeat nystagmus, hemisensory loss and ataxia, severe dyskinesia, jaw tremor, and proximal myopathy. Neurophysiologic studies revealed varying degrees of predominantly demyelinating peripheral neuropathy. Neurotoxic symptoms improved after discontinuing treatment or decreasing the dosage of the drug. Age of the patient and total cumulative dose did not seem to be risk factors for development of neurotoxicity. These neurotoxic findings suggest that amiodarone-induced neurotoxic reactions are not only confined to the peripheral nervous system, but also that parts of the central nervous system (eg, basal ganglia, brain stem, or their connections) may also be involved.     

Evaluation of the adequacy of levothyroxine replacement therapy in patients with central hypothyroidism

As there are few data on the evaluation of the adequacy of levothyroxine (L-T4) therapy in patients with central hypothyroidism (CH), a prospective study was performed to assess the accuracy of various parameters in the follow-up of 37 CH patients. Total and free thyroid hormones, TSH, and a series of clinical and biochemical indexes of peripheral thyroid hormone action have been evaluated off and on L-T4 therapy. Samples were taken before the daily administration of L-T4. In all patients off therapy, clinical hypothyroidism and low levels of free T4 (FT4) were observed, whereas values of FT3, total T4, and total T3 were below the normal range in 73%, 57%, and 19% of cases, respectively. Most of the indexes of thyroid hormone action were significantly modified after L-T4 withdrawal and exhibited significant correlation with free thyroid hormone levels. During L-T4 replacement therapy, 32 patients had circulating levels of FT4 and FT3 and indexes within the normal range with a mean L-T4 daily dose of 1.5 +/- 0.3 microg/kg BW. Despite normal serum FT4, 3 patients had borderline high values of FT3 and a clear elevation of serum-soluble interleukin-2 receptor concentrations, suggesting overtreatment. Low or borderline low FT4/FT3 levels indicated undertreatment in 2 patients. The clinical parameters lack the required specificity for the diagnosis or follow-up of CH patients. The L-T4 daily dose should be established, taking into account the weight, the age, and the presence of other hormone deficiencies or pharmacological treatment of CH patients. In conclusion, our results indicate that the diagnosis of CH is reached at best by measuring TSH and FT4 concentrations. In the evaluation of the adequacy of L-T4 replacement therapy, both FT4 and FT3 serum levels together with some biochemical indexes of thyroid hormone action are all necessary to a more accurate disclosure of over- or undertreated patients.     

Two cases of hypothyroidism associated with alpha-interferon therapy.

Alpha-interferon was used for anti-cancer or anti-viral therapy in two patients with preexisting autoimmune thyroid disease and in seven patients with chronic viral hepatitis who had no history of thyroid dysfunction. Primary hypothyroidism developed in the two patients who had a history of autoimmune thyroid disease, while no changes in thyroid function were observed in the other seven patients. Modulation of the immune system by alpha-interferon may have been responsible for the development of hypothyroidism in these two patients. Therefore, autoantibodies to the thyroid and the thyroid function should be assessed in patients undergoing alpha-interferon therapy.     

Decreased HDL cholesterol in subclinical hypothyroidism: the effect of L-thyroxine therapy

Thyroid function and lipid tests were measured in 29 premenopausal women with subclinical hypothyroidism. This group was compared with 41 euthyroid women matched for age and metabolic parameters. In basal condition there was no difference in thyroid hormone levels between the two groups except for TSH concentration (P less than 0.01). Total cholesterol, triglycerides and apolipoprotein (apo A1, A2, B) of women with subclinical hypothyroidism were not different from controls. HDL cholesterol was significantly decreased in subclinical hypothyroidism compared to the controls (P less than 0.01). With thyroxine therapy, normalization of serum TSH was associated with (1) no significant change in total cholesterol and triglycerides, (2) an increase of HDL cholesterol (P less than 0.01) and apoprotein A1 (P less than 0.05) levels. Total cholesterol/HDL cholesterol ratio was increased in subclinical hypothyroidism (P less than 0.01). During L-thyroxine therapy this ratio returned to normal value. Decreased HDL cholesterol concentration might cause coronary heart disease reported in women with subclinical hypothyroidism.     

Effect of prophylactic amiodarone in patients with rheumatic valve disease undergoing valve replacement surgery

The study was carried out to evaluate the effect of prophylactic single-dose intravenous amiodarone in patients undergoing valve replacement surgery. Maintenance of sinus rhythm is better than maintenance of fixed ventricular rate in atrial fibrillation (AF) especially in the presence of irritable left or right atrium because of enlargement. Fifty-six patients with valvular heart disease with or without AF were randomly divided into two groups. Group I or the amiodarone group (n=28) received amiodarone (3 mg/kg in 100 ml normal saline) and group II or the control group received same volume of normal saline. The standardized protocol for cardiopulmonary bypass was maintained for all the patients. AF occurred in 7.14% patients in group I, and in group II, 28.57% (P=0.035); ventricular tachycardia/fibrillation was observed in 21.43% patients in group I and 46.43% patients in group II (P=0.089) after release of aortic clamp. Most of the patients in group I (92.86%) maintained sinus rhythm without cardioversion or defibrillation after release of aortic cross clamp (P=0.002). Defibrillation or cardio version was needed in 7.14% patients in group I and 28.57% patients in group II (P=0.078). A single prophylactic intraoperative dose of intravenous amiodarone decreased post bypass arrhythmia in this study in comparison to the control group. Single dose of intraoperative amiodarone may be used to decrease postoperative arrhythmia in open heart surgery.