Replacement Doses Of Levothyroxine Research Articles

SAT504 Thyroidal Pax de Deux: 2 Cases of Resistance to Thyroid Hormone and Coexisting Thyroid Disease

Abstract Disclosure: S.V. Ribeiro: None. T. Moreno: None. A. Varela: None. P. Freitas: None. D.M. Carvalho: None. Resistance to thyroid hormone (RTH) is a rare clinical syndrome defined by hyposensitivity to thyroid hormone (TH) and characterized by elevated TH levels in the absence of TSH suppression. In most subjects with RTH, treatment is not required as tissue resistance is adequately compensated for by an increase in the endogenous supply of TH. This is not the case in patients with limited thyroidal reserve. Here we describe the clinical features of two unrelated patients with RTH and coexisting thyroid disease. Patient 1 was an 18-year-old female medical student referred to our consultation from Pediatrics. She had been diagnosed with autoimmune thyroiditis at age of 7 following the development of an obvious goiter. By then her thyroid-function tests (TFT) showed elevated TSH (8.75 µIU/mL, NR 0.41-3.67) and a normal free T4 (1.3 ng/dL, NR 0.82-1.76). She tested positive for the presence of antibodies to thyroperoxidase and thyroglobulin. The cytological findings on aspiration biopsy were consistent with Hashimoto’s thyroiditis. Throughout the years, despite levothyroxine supplementation she displayed systematically elevated TSH and normal FT4. The results of a thyrotropin stimulation test were normal. The suspicious of erratic compliance to therapy was raised.Follow-up at our outpatient clinic confirmed requirement for unusually high replacement doses of levothyroxine in order to maintain TSH within normal limits at expense of elevated FT4 and FT3 levels, suggesting the possibility of RTH. She was found with a THRβ c.1292T>C p.(Iso431Thr) heterozygous mutation. She remains clinically euthyroid under supplementation. Patient 2 was an asymptomatic 54-year-old female who consulted us for further evaluation of a thyroid nodule. Thyroid-FT showed an elevated FT3, at 3.86 μg/dL (NR, 1.75 to 3.71), an elevated FT4 at 1.86 ng/dL (NR 0.70 to 1.48), and a normal TSH level at 1.55 µIU/mL (NR, 0.40 to 4.50). A diffuse goiter was revealed by scintigraphy and the ultrasound showed no relevant findings. A diagnosis of RTH was genetically confirmed (THRβ c.1707C>G p.(P453A)). After a 6-year follow-up, she was diagnosed with supraventricular tachyarrhythmia for which she was started on amiodarone. Shortly after, her TFT revealed elevated TSH that normalized a few months after amiodarone withdrawal. Three years later, she was admitted to the intensive care unit due to cardiogenic shock attributed to tachycardia-induced cardiomyopathy and restarted on amiodarone. Her subsequent TFT showed elevated TSH (42.07 µIU/mL), with decreasing levels of TH (FT3 2.02 μg/dL, FT4 1.06 ng/dL). A diagnosis of amiodarone-induced hypothyroidism was made and levothyroxine supplementation was initiated and adjusted considering the patient’s symptoms. These cases show that the coexistence of RTH with other thyroidal disease can make diagnosis and management challenging and requires awareness and long-term follow-up. Presentation Date: Saturday, June 17, 2023

Thyroid surgery in obese patients: A review of the literature.

The incidence of obesity in the general population has tripled in the past four decades. The number of bariatric surgeries performed annually has quadrupled in the past ten years due to this obesity epidemic. Concomitantly, the number of patients who are obese or who have undergone bariatric surgery and have become candidates for thyroid surgery has also increased considerably. Among patients undergoing thyroidectomy in the French population, the proportion of obese patients currently represents 10 to 20%. In addition, the frequency of benign and malignant thyroid pathologies seems to be increased by obesity, with a Hazard Ratio of around 1.8 for thyroid cancers in obese women. While obesity does not seem to influence the specific post-operative morbidity of thyroidectomy, a history of malabsorptive bariatric surgery should encourage the greatest caution in patients who need to undergo thyroid surgery since it is associated with a significant risk of severe hypocalcemia (>60% in some studies) requiring intravenous calcium supplementation in about 20% of cases. In the latter situation, peri-operative vitamin D-calcium supplementation is essential. In addition, the replacement dose of Levothyroxine (T4) intended for replacement must also be adapted in obese patients, calculated not from the actual weight but from the ideal weight. The objective of this review is to discuss the influence of obesity on the evolution of nodular and neoplastic thyroid pathologies, on the morbidity of thyroid surgery as well as on post-operative drug treatments. The impact of bariatric surgery on these different aspects is also discussed.

Evaluation of Treatment of Central Hypothyroidism Versus Primary Hypothyroidism in Relation to Levothyroxine Replacement Dose

Objective: The aim of this study was to evaluate levothyroxine (LT4) replacement daily doses in patients with central hypothyroidism (CeH) and compare them with those adequate for patients with primary hypothyroidism (P-HYPO). Methods: We included 53 patients with CeH and 57 with P-HYPO, matched by sex, age, weight, and body mass index, in the period of 1 year. At the time of inclusion, all presented a stable and adequate dose of LT4 for at least 3 months, considering as adequate the dose associated with normal thyroid-stimulating hormone (TSH) levels and free thyroxine (T4) in P-HYPO patients, and free T4 levels in CeH patients. Results: The absolute daily dose of LT4 differed significantly between the two groups, 103.0 ± 27.1 μg (CeH) and 89.3 ± 32.0 μg (P-HYPO) (P = .017), even after adjustment for age, gender, and free T4 (P = .04). The LT4 dose adjusted to weight was also higher after adjustment for age, gender and free T4 (P = .04), with an average of 1.3 ± 0.4 μg/kg (CeH) and 1.2 ± 0.4 μg/kg (P-HYPO). Sheehan syndrome patients had a lower absolute daily dose of LT4 (P = .001), and patients who underwent pituitary radiotherapy required higher doses (P = .008). There was no difference in the daily dose of LT4 according to other pituitary hormone deficiencies. Conclusion: The results reinforce the relevance of a careful individualization of LT4 replacement in CeH management and the need for new markers for proper LT4 replacement therapy in such cases. Abbreviations: BMI = body mass index; CeH = central hypothyroidism; GH = growth hormone; LT4 = levothyroxine; P-HYPO = primary hypothyroidism; T3 = triiodothyronine; T4 = thyroxine; TSH = thyroid-stimulating hormone.

SAT-596 Hypothyroidism with Recurrent Pericardial Effusion Due to Medication Noncompliance

Introduction: Pericardial effusions have been associated with primary hypothyroidism, but are clinically asymptomatic and difficult to detect. It is a very rare cause of cardiac tamponade. We describe a patient with primary hypothyroidism presenting with recurrent pericardial effusions due to medication non-compliance. Clinical Case: A 67-year-old male was admitted to the hospital on two occasions with large pericardial effusion related to severe hypothyroidism, that was incidentally discovered on CT scan. His initial presentation was at age 63; when he was worked up with a CT abdomen for abdominal pain and was diagnosed with primary hypothyroidism with a TSH of 46.88 uIU/ml (reference range 0.35-4.94) and FT4 <0.40 ng/dl (reference range 0.70-1.48). A large pericardial effusion was noted as an incidental finding on the CT scan. Subsequent cardiac echocardiography (ECHO) reported a large predominately posterior cardiac effusion with no evidence of cardiac dysfunction or hemodynamic compromise. He was started on levothyroxine which was titrated over three months to 175mcg daily. Repeat cardiac ECHO, done with TSH: 6.09 uIU/ml and FT4: 0.77 ng/dl showed resolution of the pericardial effusion. He was lost to follow-up till 2015, when he as readmitted for severe abdominal pain and underwent sigmoidocolectomy for a colonic mass that was diagnosed as adenocarcinoma of colon. He was followed by oncology till his cancer was in remission. He had no follow up thyroid tests and had stopped taking levothyroxine for two years. In 2018, he had a CT chest/abdomen/pelvis for cancer surveillance that showed an unusually large pericardial effusion that was not present on prior CT scan in 2016. He had a follow up cardiac ECHO with a large, generalized pericardial effusion without evidence of cardiac tamponade. He was asymptomatic with a TSH: 60.74 uIU/ml and FT4: <0.40 ng/dl. Levothyroxine replacement was restarted, and he was followed in endocrine clinic, and the dose of levothyroxine titrated over three months based on labs till TSH was 3.74 uIU/ml and FT4: 1.26 ng/dl on full replacement dose of levothyroxine at 200mcg daily. Repeat cardiac ECHO showed a small, generalized pericardial effusion with no evidence of tamponade Conclusions: In conclusion, this case demonstrates one of the many cardiovascular manifestations of hypothyroidism including pericardial effusion. It highlights the importance of recognizing and treating it appropriately with thyroid hormone replacement and not by needle or surgical decompression, thus resulting in near complete resolution of the pericardial effusion. It also illustrates the importance of monitoring compliance of levothyroxine therapy. The pericardial effusions secondary to hypothyroidism can present as a diagnostic challenge when seen incidentally during work up of other underlying disorders.

Selenoproteins in human body: focus on thyroid pathophysiology.

Selenium (Se) has a multilevel, complex and dynamic effect on the human body as a major component of selenocysteine, incorporated into selenoproteins, which include the selenocysteine-containing enzymes iodothyronine deiodinases. At the thyroid level, these proteins play an essential role in antioxidant protection and hormone metabolism. This is a narrative review based on PubMed/Medline database research regarding thyroid physiology and conditions with Se and Se-protein interferences. In humans, Se-dependent enzyme functions are best expressed through optimal Se intake, although there is gap in our knowledge concerning the precise mechanisms underlying the interrelation. There is a good level of evidence linking low serum Se to autoimmune thyroid diseases and, to a lesser extent, differentiated thyroid cancer. However, when it comes to routine supplementation, the results are heterogeneous, except in the case of mild Graves' orbitopathy. Autoimmune hypothyroidism is associated with a state of higher oxidative stress, but not all studies found an improvement of thyroid function after Se was introduced as antioxidant support. Meanwhile, no routine supplementation is recommended. Low Se intake is correlated with an increased risk of developing antithyroid antibodies, its supplementation decreasing their titres; there is also a potential reduction in levothyroxine replacement dose required for hypothyroidism and/or the possibility that it prevents progression of subclinical hypothyroidism, although not all studies agree. In thyroid-associated orbitopathy, euthyroidism is more rapidly achieved if the micronutrient is added to traditional drugs, while controls appear to benefit from the microelement only if they are deficient; thus, a basal assay of Se appears advisable to better select patients who need substitution. Clearly, further Se status biomarkers are required. Future introduction of individual supplementation algorithms based on baseline micronutrient levels, underlying or at-risk clinical conditions, and perhaps selenoprotein gene polymorphisms is envisaged.

Subhyoid ectopic thyroid with a solitary colloid nodule in a 10-year-old girl: a rare diagnostic entity

Ectopic thyroid is a rare clinical entity, of which its presence in a subhyoid location is uncommon. It is equally rare to find a solitary thyroid nodule in the paediatric age group. We report a case of subhyoid ectopic thyroid in a 10-year-old girl, and its course over a span of 3 years. It was associated with a solitary colloid nodule, which eventually became symptomatic and did not respond to suppressive levothyroxine therapy. Hence surgical excision was done, and the child was put on replacement doses of levothyroxine.

Does One Size Fit Everyone? Replacement Dose of Levothyroxine in Long-standing Primary Hypothyroidism in Adults.

Objectives:The recommended starting dose of levothyroxine (LT4) in primary hypothyroidism is 1.6 μg/kg body weight and is based on presumption of minimal residual thyroid function in autoimmune hypothyroidism. This study aimed at finding the range and determining factors for LT4 dose in long-standing hypothyroidism.Methods:A cross-sectional study of individuals with primary autoimmune hypothyroidism on LT4 replacement was done between March 2015 and January 2016. Individuals enrolled were euthyroid based on recent serum thyroid-stimulating hormone. The inclusion criteria included LT4 intake in the morning empty stomach, maintenance of at least 1-h food gap, not on medications known to hamper LT4 absorption within 4 h of dosing, diagnosis of hypothyroidism at least for 1 year, and on a minimum 25 μg LT4. P < 0.05 was considered statistically significant.Results:A total of 346 individuals (290 women and 56 men; 214 premenopausal and 76 postmenopausal women) were enrolled. The mean duration of hypothyroidism and age were 5.7 years and 42.1 years, respectively. The range and mean of absolute LT4 daily dose (ADD), LT4 dose based on body weight (D/W), and LT4 dose based on ideal body weight (D/IBW) were 25–200 μg daily and 77.1 μg, 0.3–2.82 μg/kg and 1.21 μg/kg, and 0.42–3.5 μg/kg and 1.58 μg/kg, respectively. Duration of hypothyroidism was significant predictors of ADD, D/W, and D/IBW. Gender-based difference in ADD and D/IBW was explained by gender difference in anthropometry.Conclusion:Long-standing primary autoimmune hypothyroidism has variable dose requirement of LT4 for achieving euthyroidism and may be dependent on the degree of residual functional thyroid. Duration of hypothyroidism was significant positive predictor for either ADD, D/W, or D/IBW.

Is the Replacement Dose of Levothyroxine Affected By the Presence of the Thyroid Gland?

Is the Replacement Dose of Levothyroxine Affected By the Presence of the Thyroid Gland?

Influence of prior carbimazole on the outcome of radioiodine therapy in pediatric and adolescent Graves' disease.

Therapeutic options for pediatric Graves' disease (PGD) include antithyroid drug therapy (ATD) as the first line and radioiodine (I-131) therapy as the second line of treatment. To date, controversies persist regarding the true effect of prior ATD in the outcome of I-131 therapy in PGD. This study evaluated the effect of prior carbimazole treatment on the outcome of I-131 therapy in PGD. This is a retrospective study covering the years 1995-2012, with a median follow-up of 75 months. Records of 114 children (84 girls and 30 boys, age range: 5-20 years, mean 24-h radioiodine uptake, 58%) who had clinically and biochemically proven Graves' disease irrespective of prior ATD therapy were included. All patients were treated with fixed doses of 5 mCi (185 MBq) I-131 for Graves' disease; 74 had undergone prior carbimazole treatment (group 1) and 40 were drug naive (group 2). The endpoint of follow-up was stable euthyroid or hypothyroid in patients. The effect of prior carbimazole treatment on the outcome of I-131 therapy in PGD patients was evaluated. The success of radioiodine therapy was defined as the cure of hyperthyroidism. Variables were analyzed to identify the potential predictive factors for euthyroidism/hypothyroidism after treatment. The cure rate was 70% in group 1 and 83% in group 2 with a single dose of radioiodine (P=0.299). The success rate achieved at the end of 1-year follow-up in group 1 and group 2 was 81 and 87%, respectively (P=0.401). No independent predictor was associated with success or failure of treatment. At the median follow-up of 75 months (range: 12-216 months), 76% of patients were hypothyroid on replacement doses of levothyroxine and 24% still continued to be euthyroid. Prior carbimazole treatment does not alter the outcome of radioiodine therapy in PGD.

Do Patients Gain Weight After Thyroidectomy for Thyroid Cancer?

Patients who undergo thyroidectomy often complain of weight gain, which they frequently attribute to inadequate thyroid hormone replacement. To assess the weight changes associated with thyroid hormone replacement or suppressive therapy after thyroidectomy, we measured the weights of patients before and after thyroidectomy and compared them to the weights of euthyroid patients with thyroid nodules who were being followed for many years. The weights and heights of 67 women and 35 men who underwent total thyroidectomy for thyroid cancer were recorded before and for a mean of 8.3 years after thyroidectomy. All patients received either suppressive or replacement doses of levothyroxine. As a comparison group, 70 women and 22 men with goiter or thyroid nodules and were euthyroid had serial measurements of height and weight. They were followed for a mean of 7.6 years. The body mass index (BMI) and age-adjusted BMI percentiles were calculated. The weight, BMI, and BMI percentile changes were compared both unadjusted and adjusted for age, gender, thyrotropin (TSH) level, and duration between measurements. At baseline, patients with thyroid nodules were older (mean 50.4 years) than those with thyroid cancer (mean 45.8 years). There were no significant differences in baseline weight, BMI, or BMI percentile. The baseline TSH levels were lower for patients with thyroid cancer (mean 0.8 mIU/L) than for those with nodules (mean 1.8 mIU/L) (p=0.002). There were no significant differences between the changes in weight, BMI, or BMI percentile from the start to the completion of the study whether unadjusted or after adjustment for age, gender, TSH, and duration of follow-up. Despite the perception of many patients that their thyroidectomy and thyroid hormone replacement or suppressive therapy is responsible for their subsequent weight gain, there were no significant differences in weight gain over time in comparison to a control group of euthyroid patients with thyroid nodules or goiter.

Levothyroxine Replacement Doses Are Affected by Gender and Weight, But Not Age

Body weight (BW) and age have been shown to affect the dose of levothyroxine (LT(4)) that results in normalization of serum thyroid-stimulating hormone (TSH) in hypothyroid patients. Our objective was to determine whether gender, menstrual status, and ideal BW (IBW) also affect the LT(4) dose required to achieve a serum TSH within the normal range. We retrospectively reviewed the charts of patients being treated for primary hypothyroidism who had TSH values within a normal range. We selected patients aged 18-85 years who were taking LT(4) without any confounding medications, and who had no serious chronic conditions. Their LT(4) doses, referred to here as LT(4) dose requirements, based on both BW and IBW were documented. The relationship between gender, menstrual status, age, serum TSH concentrations, and the degree of overweight on LT(4) dose requirements were determined using multivariate analyses. Women were significantly more overweight than men (ratio of BW/IBW was 1.35 for women vs. 1.17 for men, p <0.0001). LT(4) requirements based on BW did not differ by gender when age was included in the model. However, when degree of overweight was also included, men required lower LT(4) doses than both premenopausal women (1.34 μg/kg vs. 1.51 μg/kg, p = 0.038) and menopausal women (1.34 μg/kg vs. 1.49 μg/kg, p = 0.023). When examining IBW using a model incorporating age, men also required lower LT(4) doses than both premenopausal women (1.64 μg/kg vs. 1.92 μg/kg, p = 0.0033) and menopausal women (1.64 μg/kg vs. 1.90 μg/kg, p = 0.0024). Serum TSH concentrations were not significantly different in any of the gender groups. There was no relationship between serum TSH and either age or BW. The initial serum TSH concentration was by design with the normal range, but the concentration within that range was not a significant predictor of the LT(4) replacement dose in any of the models. In contrast to previous studies suggesting that age affects LT(4) replacement requirements, we found that age-based differences in doses are secondary to differences in BW and gender. In addition, in contrast to prior studies showing that lean body mass, but not gender, affected LT(4) dose, we instead found a significant impact of gender. Gender-based differences in dose requirement only became apparent either when IBW was used to correct for the dose or when degree of overweight was included in the model. Gender differences in LT(4) dose requirement exist, but are masked unless gender-based differences in degree of overweight are also considered.

Impaired Pharmacokinetics of Levothyroxine in Severely Obese Volunteers

Suppressive or replacement doses of levothyroxine (LT4) are affected by the rate and extent of the active ingredient absorbed, as well as by the lean body mass. Obesity has reached epidemic proportions worldwide and is related with many comorbidities. The aim of this study was to determine the pharmacokinetic parameters of LT4 in severely obese individuals and compared them with similar data in lean control subjects. We studied 62 euthyroid subjects who had negative tests for anti-thyroid peroxidise antibodies (Ab-TPO). Thirty eight of these subjects were severely obese but otherwise healthy (severe obese subjects [SOS] group). Twenty-four were healthy control subjects (control group), with a body mass index of 23.3 ± 1.7 kg/m(2). Subjects received 600 μg oral sodium LT4 after an overnight fast. Serum triiodothyronine (T3), T4, and thyroid-stimulating hormone were measured at baseline. Serum T4 and T3 was measured 0.5, 1, 1.5, 2, 2.5, 3, and 4 hours after LT4 administration. Baseline serum T4 and thyroid-stimulating hormone concentrations were higher in the SOS group than in the control group; serum T3 was similar in the two groups. The corrected area under the curve and the maximum T4 concentration after LT4 administration were lower, whereas the time to maximum concentration from the baseline was higher in SOS than in the control group. The estimated plasma volume was higher in the SOS than in the control group. Mean serum T3 levels increased gradually during the four hours after LT4 administration in the control group. In contrast, they decreased gradually in the SOS group. Severely obese individuals may need higher LT4 suppressive or replacement doses than normal-weight individuals due, among other factors, to impaired LT4 pharmacokinetic parameters. The latter could be attributed to their higher plasma volume and/or to delayed gastrointestinal LT4 absorption. T4 conversion to T3 might be defective in severe obesity.

Predicting thyroxine requirements following total thyroidectomy

Optimal thyroxine replacement following total thyroidectomy is critical to avoid symptoms of hypothyroidism. The aim of this study was to determine the best formula to determine the initiated replacement dose of levothyroxine immediately following total thyroidectomy. Prospective study. All patients were initiated on 100 μg levothyroxine and titrated to within the reference range for TSH and free T4. Correlations to height, weight, age, lean body mass (LBM), body surface area (BSA) and body mass index (BMI) were calculated. One hundred consecutive adult patients underwent total thyroidectomy for non-malignant disease. Comparison between three methods of levothyroxine dose prediction, aiming for a levothyroxine dose correct to within 25 μg of actual dose required. Correlations were seen between levothyroxine dose and patient age (r=-0.346, P<0.01), bodyweight (r=0.296, P<0.01), LBM (r=0.312, P<0.01), BSA (r=0.319, P<0.01) and BMI (r=0.172, P<0.05). A regression equation was calculated (predicted levothyroxine dose=[0·943 × bodyweight] + [-1.165 × age] + 125.8), simplified to (levothyroxine dose= bodyweight - age + 125) pragmatically. Initiating patients empirically on 100 μg post-operatively showed that 40% of patients achieved target within 25 μg of their required dose; this increased to 59% when using a weight-only dose calculation (1.6 μg/kg) and to 72% using the simplified regression equation. A simple calculated regression equation gives a more accurate prediction of initiated levothyroxine dose following total thyroidectomy, reducing the need for outpatient attendance for dose titration.

Enlarged Thyroid Gland with Normal Thyroid Function Tests

A 41-year-old woman had a 1-to 2-cm asymptomatic thyroid mass, which had been monitored by an endocrinologist for several years with serial sonography. Noting that it had enlarged in the face of normal thyroid function tests, the endocrinologist ordered a fine-needle aspiration biopsy, which showed a cellular follicular lesion. Although some of the nuclear changes seen in papillary carcinoma were present, the cells did not fulfill all of the cytologic criteria for that diagnosis. The patient was referred to Baylor University Medical Center for surgery; she brought with her two ultrasound images (Figure ​(Figure11) and a chest x-ray that showed a minimal leftward deviation of the trachea. Figure 1 The two preoperative thyroid ultrasound images showing a well-cir-cumscribed, solid lesion with heterogeneous echotexture. The mass was 2.4 cm (longitudinal) × 1.9 cm (anteroposterior) × 1.9 cm (transverse). A thyroidectomy was performed in the patient, and 15 lymph nodes in her neck were dissected from the central compartment of the neck. The excised mass was like a small rock (Figure ​(Figure22). The patient's surgery was uneventful, and she was discharged home. She had no postoperative complications and has been started on a replacement dose of levothyroxine. She has resumed all normal activities. Figure 2 Gross features of a hyalinizing trabecular tumor of the thyroid. It has a delicately lobulated cut surface, with a yellow cast and gaping vessels. Pathological evaluation showed a 2.0 cm encapsulated nodule in the right lobe with a distinctly trabecular pattern, elongated tumor cells with enlarged nuclei with longitudinal grooves, occasional intranuclear cytoplasmic intrusions, and eosinophilic hyalin stroma. The features were strongly in favor of a hyalinizing trabecular tumor (HTT). There was advanced lymphocytic thyroiditis in the nonneoplastic right lobe parenchyma and in the left lobe (Figure ​(Figure33). The resected lymph nodes revealed no metastatic disease. The differential diagnosis of HTT is chiefly medullary thyroid carcinoma and papillary thyroid carcinoma, since several histologic features are shared with these two entities. Immunohistochemical studies were positive for thyroglobulin and thyroid transcription factor-1 and negative for calcitonin, confirming the follicular cell origin of the tumor and excluding medullary thyroid carcinoma. An immunostain for the tumor proliferation marker MIB-1 demonstrated a distinctive cell membrane pattern that has been described in HTT but not in papillary carcinoma (Figure ​(Figure44). A test for the mesothelial cell surface protein recognized by monoclonal antibody HBME-1 was invalid, as it demonstrated patchy staining of the tumor and the nonneoplastic thyroid tissue in this case. Cytokeratin 19 was negative in the tumor cells. Figure 3 Hyalinizing trabecular tumor (“adenoma”). (a) A distinctive trabecular pattern is seen from low power in this encapsulated tumor. (b) Eosinophilic hyaline material is seen surrounding the tumor cells in many areas. (c) The nuclei are enlarged ... Figure 4 MIB-1 staining in the specimen demonstrates a very low proliferative index; the rare positive nuclei in this field are endothelial cell nuclei—no tumor cells are staining. DIAGNOSIS: Hyalinizing trabecular tumor.

Subclinical and manifested hypothyroidism as a consequence of thyroid autoimmune disease

Chronic thyroiditis (Hashimoto's disease) is a slowly developing persistent inflamation of the thyroid gland, which frequently leads to hypothyroidism. Some of the up-to-date knowledge about hypothyroidism, both subclinical and manifested, caused by autoimmune disease, was presented. Autoimmune thyroid gland disease can occur at any age, but predominantly affects women after periods of high emotional and physical stress or accidents, as well as during periods of hormonal changes. It can also develop in families, and having an autoimmune disease slightly increases the risk of developing another. This paper showed an increasing incidence of subclinical hypothyroidism (4.17%) in elderly, and, at the same time, the incidence of primary hypothyroidism accounting for 1%. It is very usefull to estimate the stimulated thyrotropin (TSH) response, as well as the value of fast, short time thyroid gland reserves, analyzed by T3 and T4 serum level at 60th minute after TRH stimulation. Treatment of choice for HT (hypothyroidism of any cause) is thyroid hormone replacement. Drug of choice is orally administered levothyroxine sodium, usually for life-time. The standard dose is 1.6-1.8 mcg/kg body weight per day, but is in most cases patient dependent. Elderly patients usually require smaller replacement dose of levothyroxine, sometimes less than 1 mcg/kg body weight per day with coronary dilatator at the same time.

Hypothyroidism in patients older than 55 years: an analysis of the etiology and assessment of the effectiveness of therapy.

Several epidemiological studies on the prevalence of hypothyroidism in the elderly have been reported; however, extensive series of elderly patients with thyroid dysfunction have not been studied. Our aim has been to assess the relative frequency of the diverse causes of hypothyroidism in a group of patients older than 55 years and the adequacy of control of thyroid function attained by levothyroxine therapy. We performed a descriptive, observational, cross-sectional study in the setting of a hospital endocrinology clinic. From a total of 1581 patients older than 55 who were complaining of a thyroid disorder, we studied a group of 655 patients with hypothyroidism. There were 559 women (85.3%, age 65.01 +/- 7.90 years) and 96 men (14.7%, 65.36 +/- 8.39 years). In every patient, we collected etiology, presence of goiter, time of evolution from diagnosis and from therapy prescription, previous and present treatments, current thyroid functional status (free thyroxine and thyrotropin concentration), adequacy of disease control, and thyroid autoimmune status. The causes of hypothyroidism were as follows: autoimmune thyroiditis, 308 (47.0%); postoperative hypothyroidism, 175 (26.7%); therapy for previous thyrotoxicosis, 63 (9.6%); thyrotropin deficiency, 15 (2.3%); iodine excess, 6 (0.9%); subacute thyroiditis, 2 (0.3%); and unknown etiology, 86 (13.1%) patients. Most patients with autoimmune thyroiditis were positive for thyroid peroxidase antibodies at the time of the study (94.4%). Mean (+/- SD) age at diagnosis was 61.8 +/- 9.4 years in men and 59.8 +/- 9.7 years in women. Median (range) duration of hypothyroidism was 1.4 (0-18) years in men and 3 (0-45) years in women ( p <.05). Adequacy of therapy was studied in 385 patients treated with replacement doses of levothyroxine. Two hundred and sixty (67.5%) of these subjects attained good control, whereas 125 (32.5%) showed inadequate control of the disease at the time of the study. A model of logistic regression showed that adequacy of therapy was dependent on the duration of therapy, but independent of age, gender, degree of hypothyroidism, etiology, autoimmune status, age at diagnosis, and dose of levothyroxine. A 2-year follow-up study performed in 56 newly diagnosed patients showed that an adequate control of hypothyroidism was attained in 35 (62.5%) patients at 6 months, in 46 (82.1%) patients at 1 year, and in 49 (87.5%) at 2 years of therapy with levothyroxine. Autoimmune thyroiditis and postoperative hypothyroidism are the main causes of thyroid hypofunction in patients older than 55 years. The time from starting therapy is the main determinant of the adequacy of control of thyroid hypofunction in this population. With effective therapy and appropriate monitoring, more than 80% of the patients showed adequate control within 1 year of follow-up.

Variations In Adequate Levothyroxine Replacement Therapy In Patients With Different Causes Of Hypothyroidism

To compare the levothyroxine replacement dose in 181 patients with various causes of hypothyroidism. We analyzed the dose of levothyroxine used in the following five patient groups: (1) 37 patients with hypothyroidism after radioiodine therapy for Graves' thyrotoxicosis who were receiving a stable (for at least 4 years) replacement dose (mean time after 131 I therapy, 11.3 years); (2) 36 patients with Hashimoto's hypothyroidism (chronic autoimmune thyroiditis with a goiter or positive test results for antithyroid antibodies); (3) 36 patients with central hypothyroidism; (4) 36 patients with hypothyroidism after near-total thyroidectomy and 131 I therapy for thyroid carcinoma with negative total-body 131 I scans who were euthyroid when receiving levothyroxine; and (5) 36 patients with atrophic thyroiditis (no goiter and negative test results for antithyroid antibodies). Adequacy of levothyroxine replacement dose was defined as a normal thyrotropin level and clinical euthyroidism in patients with primary hypothyroidism and a serum free thyroxine index in the upper half of the normal range in conjunction with clinical euthyroidism in patients with central hypothyroidism. The mean (+/- standard error of the mean) replacement dosage of levothyroxine (mg/kg per day) in patients with atrophic thyroiditis (1.26 +/- 0.07) was lower (P<0.05) than in patients with Hashimoto's hypothyroidism (1.59 +/- 0.07) and those with hypothyroidism after radioiodine therapy (1.56 +/- 0.05). These doses, in turn, were lower (P<0.01) than those in patients with central hypothyroidism (1.88 +/- 0.10) or euthyroid thyroid carcinoma (2.08 +/- 0.07). In a separate analysis, the levothyroxine dose in 43 patients with hypothyroidism after 131 I treatment was evaluated serially over time. The mean levothyroxine dosage increased from 0.87 +/- 0.12 at 6 months after 131 I therapy to 1.57 +/- 0.09 at 7 years (P<0.001). The serum thyrotropin concentration (in mU/mL) during levothyroxine therapy in patients with central hypothyroidism (0.31 +/- 0.08) was lower (P<0.01) than in patients with hypothyroidism after 131 I therapy (1.69 +/- 0.37), Hashimoto's hypothyroidism (1.39 +/- 0.20), atrophic thyroiditis (1.86 +/- 0.22), and euthyroid thyroid carcinoma (1.48 +/- 0.26). The levothyroxine replacement dose varies with the cause of the hypothyroidism.

Plasma von Willebrand factor antigen concentration in dogs with hypothyroidism

Summary Plasma von Willebrand factor antigen concentration was measured in 10 dogs with hypothyroidism, before and after administration of a replacement dose of levothyroxine for 67 ± 12 days. Results were reported as a percentage of normal activity, with plasma pooled from clinically normal dogs given a value of 100%. Plasma von Willebrand factor antigen concentration was within reference limits in dogs with hypothyroidism (126 ± 41%) and was significantly (P &lt; 0.01) decreased (94 ± 39%) after treatment with levothyroxine. Contrary to findings in some other studies, a deficiency of plasma von Willebrand factor did not appear to result from hypothyroidism.

Administration of levothyroxine to euthyroid dogs does not affect echocardiographic and electrocardiographic measurements

The effects of a replacement dose of levothyroxine on electrocardiographic and echocardiographic parameters in euthyroid dogs were examined. Two-dimensional guided M-mode echocardiograms and electrocardiograms were obtained before and after administration of levothyroxine (0·5 mg m −2 twice a day) to 10 euthyroid dogs for a period of eight weeks; four untreated dogs acted as controls. The resting serum total thyroxine concentration was significantly increased in treated dogs during weeks 4 to 8. There were no significant differences in any of the echocardiographic or electrocardiographic measurements resulting from treatment.

Subclinical Hyperthyroidism: Possible Danger of Overzealous Thyroxine Replacement Therapy

Many patients taking customary doses of levothyroxine have slightly elevated serum thyroxine (T4), apparently normal serum triiodothyronine, suppressed serum thyrotropin (thyroid-stimulating hormone; TSH) concentrations, and no clinical symptoms of hyperthyroidism. Recent reports suggest that these patients may have adverse effects from subclinical hyperthyroidism, including abnormally short systolic time intervals, elevations in liver enzymes, and reductions in bone density. Controversy exists about which thyroid function tests should be used to monitor patients taking levothyroxine. A review of currently available data suggests that replacement doses of levothyroxine given to hypothyroid patients should be adjusted so that serum TSH measured by the new sensitive assays is within the normal range. Patients requiring suppressive doses of levothyroxine to shrink goitrous thyroid tissue or to prevent growth of abnormal tissue should be given the minimal dose needed to accomplish the desired clinical or biochemical response.