Treatment Of Primary Hypothyroidism Research Articles

Actual practice vs guidelines in laboratory monitoring of older patients with primary hypothyroidism in primary care

Clinical guidelines are produced in order to achieve an acceptable standard of care, especially for patients with common diseases in primary care. The treatment of primary hypothyroidism serves as an example of the content of clinical guidelines and actual practice. The aim of this study was to compare the follow-up of primary hypothyroidism by thyroid function tests, serum TSH and serum-free T4, in older patients managed in primary care, with recommendations in treatment guidelines and textbooks. Participation rate 82% (n=1260), mean age 74 years, (range 64-100 yrs). Patients with primary hypothyroidism were identified by means of cross-sectional survey (Lieto Study 1998-1999) and 4-year retrospective collection of laboratory database medical records (1994-1998), performed in autumn 2003. In most stable (=treated for more than 14 months) thyroxine users, both serum TSH (mean 1.4 measurements/year) and serum-free T4 (mean 0.8 measurements/year) values were measured over the 4-year period of thyroxine treatment. 66.4% of serum TSH and 85.3% of serum-free T4 values were within normal range. 41.7% of serum-free T4 determinations had been performed without indication (=with TSH in normal range). Compared with the recommended testing frequency given in various guidelines, a considerable number of extra measurements, especially serum-free T4, were performed. However, some key issues in the recommendations were difficult to interpret, and the age or other main characteristics of the patient were not taken into consideration adequately.

Persistence of hyperprolactinemia after treatment of primary hypothyroidism and withdrawal of long term use of estrogen: are the tuberoinfundibular dopaminergic neurons permanently lesioned?

Long term use of high doses of estrogen and the presence of chronic hyperprolactinemia may, at least in the rat, provoke lesions in the tuberoinfundibular dopaminergic (TIDA) neurons responsible for the control of prolactin (Prl) secretion. This occurrence, which is not yet well documented in humans, may have taken place in a patient on chronic oral hormonal contraceptive (OC) treatment who was seen for primary hypothyroidism, hyperprolactinemia and a pituitary mass. After thyroid hormone replacement, OC withdrawn and bromocriptine treatment, this patient could not maintain normal Prl levels, unless continuously treated with a dopaminergic agonist even when MRI was indicative of a normal situation. Function of TIDA neurons was investigated by TRH test (200 microg IV) performed before and after treatment with 25 mg carbidopa plus 250 mg L-dopa every 4 hours for one day. Basal TSH was normal (3.9 microU/mL) whereas basal Prl was high (67.5 ng/mL); both TSH and Prl levels appropriately increased after TRH: peaks 31.8 microU/mL and 157.8 ng/mL, respectively. After treatment with carbidopa/L-dopa, basal TSH (1.6 microU/mL) and Prl (34 ng/mL) decreased and the response to TRH was partially blocked (10.3 microU/mL and 61 ng/mL, respectively). In spite of a normal response, we discuss the possibility that the persistence of hyperprolactinemia is due to lesion of the TIDA neurons produced by the long term use of high doses of estrogens and by the presence of chronic hyperprolactinemia.

Synthetic Thyroxine vs Dessicated Thyroid

To the Editor: Dr Clyde and colleagues concluded that treatment of primary hypothyroidism with combination levothyroxine plus liothyronine was not superior to levothyroxine alone in terms of body weight, serum lipid levels, hypothyroid symptoms, or cognitive performance. Although Clyde et al recommend that patients should be treated with synthetic thyroid on the basis of cost, natural desiccated thyroid is considerably less expensive. Thus, perhaps this would be the most rational treatment choice.

Treatment of primary hypothyroidism during pregnancy: Is there an increase in thyroxine dose requirement in pregnancy?

We studied the dose requirements of thyroxine (T4) and serum concentrations of thyrotropin-stimulating hormone (TSH) and free T4 in 16 pregnant women with primary hypothyroidism due to autoimmune thyroid disease (ATD, n = 11) or thyroidectomy (n = 5). All patients had been advised by their obstetricians to take prenatal vitamins enriched with iron (~90mg/tablet) and calcium (~200 mg/tablet), known to inhibit absorption of T4. We asked patients to take their vitamins 4 hours after ingesting T4 in the morning. The mean T4 dose of 0.10 ± 0.01 (mean ± SEM, mg/d) during pregnancy did not differ significantly from that (0.09 ± 0.005) before or after (0.10 ± 0.01) pregnancy. Similarly, mean serum TSH of 2.7 ± 0.28 mIU/L during pregnancy did not differ significantly from that before (2.2 ± 0.47) or after (3.2 ± 1.31) pregnancy. The mean serum free T4 concentration during pregnancy (16 ± 0.97 pmol/L) was significantly (P <.05) lower than that (22 ± 1.5) before or after (23 ± 2.2) pregnancy and similar to that observed with our free T4 measurement technique in normal (healthy) pregnant women. We next examined the data separately in patients with ATD and thyroidectomy. The mean T4 dose (0.08 ± 0.009) and TSH (2.4 ± 0.29) during pregnancy in 11 ATD patients did not differ appreciably from those before (T4 dose, 0.08 ± 0.0006; TSH, 2.7 ± 0.54) or after (T4 dose 0.09 ± 0.0063; TSH, 4.1 ± 1.91) pregnancy. Similarly, the mean T4 dose (0.12 ± 0.022, n = 5) during pregnancy in thyroidectomized patients was similar to that before (0.12 ± 0.017, n = 3) or after (0.12 ± 0.022) pregnancy. However, serum TSH increased significantly, albeit within the normal range, during pregnancy in thyroidectomized patients (3.2 ± 0.62, n = 5 v 0.41 ± 0.017, n = 3, P <.05) and it (1.3 ± 0.60) decreased significantly (P <.05) after pregnancy. Our data suggest that (1) the dose requirement of T4 does not change systematically in pregnancy in most hypothyroid women. There may occur a modest increase in T4 dose requirement during pregnancy in some thyroidectomized patients; (2) diminished absorption of T4, possibly related to ingestion of exogenous agents (eg, iron, calcium, vitamins), may have contributed to previous suggestions of substantial increased T4 requirement in pregnancy; (3) ingestion of T4 dose absorption-inhibiting agents some 4 hours away from T4 markedly diminishes or obviates their effect in many patients. Although many hypothyroid patients may not require an adjustment in their T4 dose during pregnancy, it is prudent to monitor all such patients carefully as the consequences of inadequate therapy may be very important. Copyright 2003, Elsevier Science (USA). All rights reserved.

Monitoring of treatment in thyroid diseases

The effectiveness of antithyroid drug treatment of Graves' hyperthyroidism is documented by measuring initially free T4 and free T3 and later free T4, free T3 and TSH. An elevated titer of the Graves'-specific thyroid stimulating antibodies is not usually rechecked before the end of the antithyroid drug therapy. Thyroxine treatment of primary hypothyroidism is controlled by TSH measurements. In patients in whom TSH levels might be affected by drugs or nonthyroid diseases, free T4 is measured in addition to TSH. The assessment of the treatment of Hashimoto's chronic thyroiditis consists of the control of the therapy of its associated hypothyroidism. In subacute thyroiditis de Quervain control of the effectiveness of the analgesic therapy is most important. To check the effect of thyroid hormone treatment given with the intent to reduce goiter size, serial sonographies are of great value. In the follow-up of patients with thyroid carcinomas, measurements of thyroglobulin (for papillary and follicular thyroid cancers) and of calcitonin (for medullary thyroid cancers) in the serum as well as thyroid scans and other imaging procedures play an important role.

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...

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

Transient growth hormone deficiency after treatment of primary hypothyroidism

In primary hypothyroidism, enlargement of the pituitary sella can mimic a primary pituitary tumor on computed tomography) Enlargement of the sella, thought to represent pituitary hyperplasia and hypertrophy in response to lack of feedback inhibition of thyroid hormone, has been demonstrated in 81% of adults with primary hypothyroidism. 2 The magnitude of the sellar enlargement is proportional to thyrotropin levels, and thyroid hormone replacement therapy can produce reduction of the enlarged pituitary gland to normal size. Rarely, treatment of primary hypothyroidism has resulted in hypopituitarism? A recent report documents by CT the development of an empty sella and hypopituitarism in a child after thyroid hormone replacement because of primary hypothyroidism. 4 Hypopituitarism in the absence of empty sella syndrome has also been described after thyroid hormone replacement. In only one reported patient, an adult with primary hypothyroidism, this hypopituitarism (gonadotropin deficiency) was thought to be transient? We report two children with longstanding primary hypothyroidism who grew poorly despite adequate hormone replacement and were found to have growth hormone deficiency. Subsequently, under androgen influence and without GH therapy, growth was good and testing showed adequacy of endogenous growth hormone secretion.

Calcitonin deficiency in primary hypothyroidism.

The relative lack of sensitivity and specificity of current assays for plasma calcitonin (CT) have made it difficult to study possible CT deficiency conditions. Using a new extraction method that considerably improves the sensitivity of the assay for CT monomer, CT levels were measured before and after a short calcium (Ca) stimulation test (2 mg Ca/kg over 5 min) to determine C-cell secretory reserve in women with autoimmune primary hypothyroidism and normal women. Mean basal plasma CT concentrations were lower in the hypothyroid women [0.9 +/- 0.1 (+/- SEM) pg/ml] than in the normal women (1.5 +/- 0.2 pg/ml; P less than 0.01). Serum Ca increased similarly in both groups, but postinfusion CT levels were lower in the women with primary hypothyroidism (3.8 +/- 1.3 pg/ml) than in normal women (15.9 +/- 3.0 pg/ml; P less than 0.001). The functional thyroid status at the time of the study did not influence CT levels; both hypothyroid patients (n = 10) and patients who were euthyroid during T4 treatment (n = 11) were CT deficient to the same extent. Unlike that in primary hypothyroidism, CT secretion was normal in four patients with hypothyroidism of pituitary origin. We conclude that the process that causes hypothyroidism in patients with autoimmune thyroid disease can also cause marked CT deficiency. This first demonstration of spontaneous CT deficiency in adults should contribute to the understanding of CT physiology; it also suggests that bone metabolism should be closely monitored during the treatment of primary hypothyroidism.

Seasonal variation of serum thyrotropin concentration and thyrotropin response to thyrotropin-releasing hormone in patients with primary hypothyroidism on constant replacement dosage of thyroxine.

Ten patients with primary hypothyroidism (aged 32--66 yr), replaced on constant daily doses of L-T4 (mean +/- SD, 1.90 +/- 0.22 micrograms/kg BW), were used to examine seasonal variations in serum levels of thyroid-related hormones for a period of 14 months. Basal and peak TSH concentrations after TRH (500 micrograms) were higher in winter than in summer. Summer values for basal TSH were all normal (normal range, less than 4.8 microU/ml), while winter values were supranormal in 5 of 10 patients. Summer values for peak TSH were subnormal or normal (normal range, 5.0--40.0 microU/ml), while winter values were supranormal in 3 patients, with the remaining values being normal [log basal TSH, 0.511 +/- 0.438 vs. 0.084 +/- 0.244 (P less than 0.05); log peak TSH, 1.394 +/- 0.410 vs. 1.017 +/- 0.423 (P less than 0.05)]. Serum resin T3 uptake, T4, free T4 index(FT4I), T3, free T3 index, and rT3 levels did not vary seasonally, although T4 and FT4I tended to fall in the winter. The summer and winter QKd interval (the interval from the onset of a QRS complex in the electrocardiogram to the appearance of the Korotkoff sound at diastolic pressure), basal metabolic rate, and serum cholesterol concentrations were all within the normal range. Basal and peak TSH after TRH were inversely correlated with serum T4 and FT4I levels. The basal TSH concentration was further inversely correlated with the seasonally altering ambient temperature. These results indicate that during the treatment of primary hypothyroidism with constant doses of T4, 1) serum TSH and its response to TRH show seasonal variation, 2) the hypersecretion TSH in the winter is related to small changes in serum T4 and FT4I levels, and 3) the seasonal variation in the serum TSH concentration may need to be taken into consideration when evaluating the adequacy of a T4 replacement dose.

Thyrotrophin estimation in diagnosis and treatment of childhood thyroid disorders.

Serum thyrotrophin (TSH) was estimated by double-antibody radioimmunoassay in 200 children aged 2 months to 16 years with normal thyroid function. There was no apparent variation in TSH with age or sex and only 4 children had TSH levels greater than 5 muU/ml. High TSH values were obtained in 9 children with primary hypothyroidism, in 3 children with thyroiditis, and in one girl with a lingual thyroid. Moderately raised TSH was found in 3 girls with thyroiditis, 2 brothers with goitres due to enzyme defect, and a girl with an ectopic thyroid. In one girl with a defect of iodine organification and in 3 boys with thyroxine binding globulin deficiency the TSH levels were normal despite very low serum thyroxine values. Serum TSH was also estimated in 20 children during treatment for primary hypothyroidism. 3 of these children showed slightly raised TSH levels despite apparently adequate replacement therapy with L-thyroxine. One girl showed a very high TSH level 3 weeks after treatment had been temporarily withdrawn.

Effect on the plasma citrate of treatment of primary hypothyroidism with triiodothyronine.

DURING the course of metabolic studies on myxœdematous subjects it was noted that the plasma citrate-level was in some cases raised. In the hope that useful information might be obtained on the mode of action of thyroid hormones on tissue metabolism, the plasma citrate-level was followed during the treatment of four female patients suffering from primary myxœdema, using ordinary replacement doses of triiodothyronine. Triiodothyronine was also administered to four normal medical students, two male and two female, and their plasma citrate-levels were followed.