Thyroxine Requirements Research Articles

L-Thyroxine Requirement in Patients with Autoimmune Hypothyroidism and Parietal Cell Antibodies

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. We examined whether autoimmune gastritis might cause increased l-T(4) requirement in patients with autoimmune thyroiditis receiving l-T(4) replacement. 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. 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. 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).

Reversible hypothyroidism and Whipple's disease

BackgroundThe major cause of primary hypothyroidism is autoimmune mediated with progressive and permanent destruction of the thyroid gland resulting in life-long replacement therapy. Treatable and reversible hypothyroidism is unusual and here forth is such a case due to infection of the thyroid gland with Tropheryma whippleii, Whipple disease.Case presentationA 45 year-old female presented with symptoms and signs consistent with primary hypothyroidism, which was also confirmed biochemically. Her response to thyroxine replacement therapy was poor however, requiring a significantly elevated amount. Further investigation revealed the presence of Whipple's disease involving the gastrointestinal trace and possibly the thyroid gland. Her thyroxine requirement decreased drastically following appropriate antimicrobial therapy for Whipple's disease to the extent that it was ceased. Thyrotropin releasing hormone testing in the steady state suggested there was diminished thyroid reserve due to Whipple's disease.ConclusionThis is the first ante-mortem case report studying the possible involvement of the thyroid gland by Whipple's disease. Despite the normalization of her thyroid function test biochemically after antibiotic therapy, there is diminished thyroid reserve thus requiring close and regular monitoring.

Improvement of hypothyroidism after laparoscopic Roux-en-Y gastric bypass for morbid obesity.

Laparoscopic Roux-en-Y gastric bypass (LRYGBP) has been very effective in managing a broad range of morbid obesity-related co-morbidities. We report a beneficial effect of LRYGBP that has not been previously observed. Between December 1999 and September 2002, 224 patients underwent LRYGBP. Preoperative assessment for hypothyroidism and follow-up data were prospectively collected in our database. Improved thyroid function (ITF) or unchanged thyroid function (UTF) was determined by comparison of preoperative and postoperative thyroxine requirements. 23 of 224 patients (10.3%) were treated preoperatively for hypothyroidism. During a median follow-up of 17 months, hypothyroidism was improved in 10/23 patients (43.5%). 2 patients had complete resolution, and the remaining 8 had reduction (14%-50%) of their thyroxine requirements. ITF occurred at a mean follow-up of 8.9 months and at a mean excess weight loss (EWL) of 57%. 6 of the 8 patients (75%) with ITF >or= 25% had EWL >90% at last follow-up, compared to 1 out of 15 patients (6.6%) with UTF or <25% improvement (P =0.001). Comparison of patients with ITF and UTF over time during a 20-month follow-up, showed no significant difference in mean body mass index (BMI) and mean percentage of EWL. Improvement of hypothyroidism may be an additional benefit of bariatric surgery that has not been previously reported. Reduction of thyroxine requirements is most likely the result of the decrease in the BMI.

Estrogen increases thyroxine requirements in hypothyroidism

Estrogen increases thyroxine requirements in hypothyroidism

Estrogen increases thyroxine requirements in hypothyroidism

Estrogen increases thyroxine requirements in hypothyroidism

Management of hypothyroidism during pregnancy.

Hypothyroidism during pregnancy occurs in 1/1600-2000 deliveries, according to the most recent publications. The most common causes are chronic autoimmune thyroid disease, radiodine-131 treatment, or surgical removal. The diagnosis is difficult to make on clinical grounds alone, even in advanced cases, and a high index of suspicion is needed. Some women are at high risk of developing hypothyroidism, and they should be screened. These women may have had previous treatment for hyperthyroidism; high-dose neck irradiation, evidence of thyroid autoimmunity, amiodarone therapy, suspected hypopituitarism, and type I diabetics. The best laboratory test is the serum TSH, followed, if elevated, by a free T4 index and a TPO-ab titer. Thyroid antibodies have been associated with an increased (double) risk of miscarriage and postpartum thyroiditis. Frequent (22-44%) pregnancy-induced hypertension leading to preterm delivery, and prematurity is the main complication observed in those still hypothyroid near term. Proper therapy eliminates or reduces the risk. No congenital anomalies have been reported in the most recent studies, and the data available shows that both physical and mental development have been normal until children are 10 years old. However, one study reported lower IQs in children of euthyroid women with positive TPO-ab than in children of TPO-ab negative mothers. Levothyroxine is the treatment of choice. Euthyroidism must be reached and maintained in a timely fashion. Many women need more thyroxine during pregnancy, and surveillance of thyroid function is needed throughout gestation to make dose adjustments when needed. During the postpartum periods the thyroxine requirements decrease to preconception levels.

Thyroxine dosage during pregnancy in women with primary hypothyroidism.

To assess whether pregnancy changes the thyroxine requirements of hypothyroid women. A retrospective, longitudinal study. Queen Charlotte's and Chelsea Hospital for Women. 32 women referred for antenatal care during 35 pregnancies. Changes in thyroid stimulating hormone (TSH) and free thyroxine (fT4) levels as pregnancy progresses. In most of the pregnancies (80%), no change in thyroxine dose was required (mean dose 129 micrograms). The mean TSH levels in early (1.8 mU/l) and in late pregnancy (1.5 mU/l) were unchanged (P greater than 0.5). In the remaining pregnancies, thyroxine dose was increased after the first antenatal clinic appointment, on the basis of thyroid function test results, from a mean of 104 micrograms to a mean of 172 micrograms (P less than 0.01). These women had a mean early pregnancy TSH of 12.3 mU/l, which decreased by 95% to 1.3 mU/l (P less than 0.01). Most of the hypothyroid patients presenting to an antental booking clinic are well controlled in early pregnancy and will remain so throughout pregnancy. The dose of thyroxine does not need to be changed, and further assessments of thyroid function should not be necessary. It is unlikely that the patients were all 'overtreated' before conception, since they were referred to us by a large number of independent doctors. Women who are under-treated before the pregnancy are likely to require both increased thyroxine dose and further thyroid function assays. They can generally be easily detected, biochemically, at the first hospital visit.

Increased need for thyroxine during pregnancy in women with primary hypothyroidism

Abstract Background and Methods. Women with hypothyroidism have been thought not to require an increase in thyroxine replacement during pregnancy. To evaluate the effects of pregnancy on thyroxine requirements, we retrospectively reviewed the thyroid function of 12 women receiving treatment for primary hypothyroidism before, during, and after pregnancy. Results. In all patients, the serum thyrotropin level increased during pregnancy. The mean (±SE) serum freethyroxine index decreased from 111.0±5.8 before pregnancy to 86.5±5.2 during pregnancy (normal, 64 to 142; P<0.05), and the mean serum thyrotropin level increased from 2.0±0.5 mU per liter before pregnancy to 13.5±3.3 mU per liter during pregnancy (normal, 0.5 to 5.0 mU per liter; P<0.01). Because of high thyrotropin levels, the thyroxine dose was increased in 9 of the 12 patients. Among the three patients who did not require an increased thyroxine dose were two with low serum thyrotropin levels before pregnancy, suggesting excessive replacement at th...

Thyroxine requirement during pregnancy for replacement therapy of hypothyroidism

We examined the dose requirements of thyroxine (T4) and desiccated thyroid during eight pregnancies of six women who had undergone total thyroidectomy for thyroid carcinoma. In five pregnancies from four patients treated with T4, serum free T4, which was measured by a newly developed radioimmunoassay, decreased during pregnancy but increased above the normal range after delivery. Consistent with these changes in free T4, serum TSH (measured by a highly sensitive immunoradiometric assay) increased during pregnancy but returned to an undetectable level after delivery, with one exception. The serum triiodothyronine (T3)-to-T4 ratio, which is related to peripheral conversion of T4 to T3, was lower in patients treated with T4 than in normal controls, regardless of pregnancy. The ratio decreased further during pregnancy, and so relative deficiency of T3 during pregnancy was suspected, especially in T4-treated patients. On the other hand, in two pregnancies from two other patients treated with desiccated thyroid at a dose most equivalent to that of T4, serum free T4 decreased to a low-normal value during gestation but returned to the normal range after delivery, whereas serum TSH scarcely changed during pregnancy. These findings indicate that replacement therapy for pregnant patients with hypothyroidism after total thyroidectomy should include an increased dose of T4; in contrast, the dose of desiccated thyroid need not be changed.

Thyroxine replacement in post‐radioiodine hypothyroidism

Thyroxine replacement dose in 70 patients with post-radioiodine (for Graves' thyrotoxicosis) hypothyroidism was compared with that in 34 patients with autoimmune hypothyroidism matched for age and sex and diagnosed during the same period. Median replacement dose in the post-radioiodine group (100 micrograms daily) was significantly lower (P = 0.006) than in the autoimmune hypothyroid group (137.5 micrograms daily). Furthermore there was marked variation in the time elapsing from onset of post-radioiodine hypothyroidism to achievement of a given maintenance dose. These findings may be explained by persistence of non-TSH mediated thyroid function, after radioiodine therapy for Graves' thyrotoxicosis. The observations indicate the potential risk of overtreatment with thyroxine in post-radioiodine hypothyroidism unless the dose is carefully titrated against serum TSH levels. Final thyroxine requirements may not be evident in the initial phase of treatment and patients with apparently low maintenance thyroxine requirements require long-term follow up.

Increased Need for Thyroxine During Pregnancy in Women With Primary Hypothyroidism

Thywid Diagnostic Center and Endocrine-Hypertension Division, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts

Increased Need for Thyroxine during Pregnancy in Women with Primary Hypothyroidism

Women with hypothyroidism have been thought not to require an increase in thyroxine replacement during pregnancy. To evaluate the effects of pregnancy on thyroxine requirements, we retrospectively reviewed the thyroid function of 12 women receiving treatment for primary hypothyroidism before, during, and after pregnancy. In all patients, the serum thyrotropin level increased during pregnancy. The mean (+/- SE) serum free-thyroxine index decreased from 111.0 +/- 5.8 before pregnancy to 86.5 +/- 5.2 during pregnancy (normal, 64 to 142; P less than 0.05), and the mean serum thyrotropin level increased from 2.0 +/- 0.5 mU per liter before pregnancy to 13.5 +/- 3.3 mU per liter during pregnancy (normal, 0.5 to 5.0 mU per liter; P less than 0.01). Because of high thyrotropin levels, the thyroxine dose was increased in 9 of the 12 patients. Among the three patients who did not require an increased thyroxine dose were two with low serum thyrotropin levels before pregnancy, suggesting excessive replacement at that time. The mean thyroxine dose before pregnancy was 0.102 +/- 0.009 mg per day; it was increased to 0.148 +/- 0.015 mg per day during pregnancy (P less than 0.01). The mean postpartum serum free-thyroxine index was 136.6 +/- 11.4 (P less than 0.05 as compared with values before and during pregnancy), and the mean postpartum serum thyrotropin level was 1.4 +/- 0.4 mU per liter (P less than 0.01 as compared with levels during pregnancy), demonstrating a decrease in the thyroxine requirement. The mean postpartum thyroxine dose was decreased to 0.117 +/- 0.011 mg per day (P less than 0.01 as compared with the dose during pregnancy). Our results indicate that the need for thyroxine increases in many women with primary hypothyroidism when they are pregnant, as reflected by an increase in serum thyrotropin concentrations. Although the effects of this modest level of hypothyroidism are not known, we think it prudent to monitor thyroid function throughout gestation and after delivery and to adjust the thyroxine dose to maintain a normal serum thyrotropin level.

Levothyroxine replacement dose for primary hypothyroidism decreases with age.

We studied 23 elderly (other than 65) and 44 younger ambulatory adult patients with primary hypothyroidism to ascertain the dose of levothyroxine needed for complete replacement in relation to age. The elderly patients (average age, 75.7 years) needed an average 118 microgram/d whereas the younger patients (average age, 48.1 years) needed 158 microgram/d. The data indicate that thyroxine requirement may decrease continuously with age. This decrease probably reflects the progressive decrease in thyroxine degradation rate that occurs with age.

Critical studies on determination of thyroid secretion rate in cold-adapted animals.

Estimation of thyroid secretion rate by determining the amount of l-thyroxine required to block the thyroidal I131 release, confirmed that the thyroxine requirement of 6 C-acclimated rats is twice as high as that of 23 C-acclimated controls (5.5 ± 0.7 μg/100 g per day against 2.73 ± 0.3 μg/100 g per day). In white rats acclimatized to cold by outdoor exposure during the winter on the other hand, it was only 1.8 ± 0.38 μg/100 g per day. Larger amounts of thyroxine were found in the feces of the 6 C-acclimated rats (1.66 ± 0.66 μg/100 g body wt per day) as compared to 0.69 ± 0.07 μg/100 g body wt per day for controls. Urinary elimination rates of I131 were more rapid in “6 C rats” than in controls. These observations indicate that the greater requirement for thyroxine in cold-adapted rats is at least partly due to greater fecal loss of the hormone. It seems plausible to seek an explanation for the lesser thyroxine requirement of the outdoor winter rats in their fecal elimination rate of that hormone. cold acclimation; fecal excretion of thyroxine Submitted on June 18, 1964

Fetal hypothyroidism: I. Effects of thyroxine on neural development II. Fetal versus maternal contributions to fetal thyroxine requirements III. Clinical implications

Fetal hypothyroidism: I. Effects of thyroxine on neural development II. Fetal versus maternal contributions to fetal thyroxine requirements III. Clinical implications

Mucopolysaccharides in relation to growth and thyroid hormones

It may be stated that homeostasis of acid mucopolysaccharides occurs if the requirements of the connective tissues for the hormones are supplied. The participation of insulin in the maintenance of normal levels and normal turnover of acid mucopolysaccharides in skin has been described in a previous publication [28]. The requirement for thyroxine was documented in the present communication by demonstrating that its administration restored the defects in mucopolysaccharide metabolism observed in the hypothyroid animal. The decreased turnover of chondroitinsulfuric acid in hypophysectomized rats was effectively reversed by injection of growth hormone. However, the abnormally high concentration of hyaluronic acid was increased further by this treatment. Evidently, administration of growth hormone alone did not create a favorable endocrine environment in the hypophysectomized animal for the restoration of hyaluronic acid metabolism to normal. Although no direct experimental evidence has been presented, it is suggested that maintenance of normal concentrations of hyaluronic acid depends upon an adequate supply of both growth hormone and thyroxine. Taurog et al. [42] have demonstrated that secretion of thyroid hormones is reduced by more than 90 per cent in the hypophysectomized rat. Since hypothyroidism is a conspicuous manifestation of pituitary deficiency, it was not unexpected to find that the alterations in mucopolysaccharide metabolism were similar in both conditions. These studies demonstrate undeniably an influence of hormones on acid mucopolysaccharide metabolism. However, they reveal no unanimity of hormone-enzyme relationships on the biosynthetic or degradative processes involved. In the diabetic rat and in the animal receiving cortisone, the metabolism of both mucopolysaccharides is depressed suggesting a common fundamental defect in the early stages of synthesis. On the other hand, the differential effects of growth hormone and thyroxine on hyaluronic acid and chondroitinsulfuric acid metabolism leads one to conclude that these hormones exert their effects on later stages of synthesis or on degradative pathways.

STUDIES ON THE PERIPHERAL DISAPPEARANCE OF THYROID HORMONE

Among the different factors which may influence the peripheral needs for thyroid hormone, changes in environmental temperature seem to have been most extensively studied. Different workers in this field (Bondy et al., 1952, Leblond et al., 1952, Rand et al., 1952, Kassenaar et al., 1956) were able to show by different types of experiments, that prolonged exposure to low temperatures is accompanied by an increase in peripheral thyroxine requirement. Kassenaar et al. (1956) clearly showed that these experiments have preferably to be done on thyroidectomized, thyroxine maintained animals as compensatory action may mask the results when intact animals are used.

Relative Activities of l- and dl-Thyroxine

We have compared the biological activities of l- and dl-thyroxine in rats receiving 4-methyl-2-thiouracil by determining the ‘thyroxine requirement’ as defined by Griesbach and Purves1. This method consists of finding the amount of thyroxine which will prevent the pituitary basophil changes, resulting from the thyroxine deficiency produced by the blockage of thyroxine synthesis by the methyl thiouracil. The thyroxine samples used were: (1) l-thyroxine presented by Dr. C. R. Harington, and prepared by the iodination of l-di-iodothyronine2; (2) l-thyroxine presented by Dr. E. P. Reineke, and prepared by, acid hydrolysis of iodinated casein3; (3) l-thyroxine prepared in this laboratory from l-di-iodotyrosine by the method of Harington and Pitt Rivers4; (4) dl-thyroxine presented by Burroughs Wellcome and Co., and prepared by alkaline hydrolysis of thyroid substance.