Effect of Calcium Carbonate on the Absorption of Levothyroxine
TL;DR: This study of 20 patients receiving long-term levothyroxine replacement therapy indicates that calcium carbonate reduces T(4) absorption and increases serum thyrotropin levels.
Abstract: ContextThe effect of calcium carbonate on the absorption of levothyroxine has
not been studied systematically. Such a potential drug interaction merits
investigation because concurrent treatment with both drugs is common, particularly
in postmenopausal women.ObjectiveTo investigate the potential interference of calcium carbonate in the
absorption of levothyroxine.DesignProspective cohort study conducted from November 1998 to June 1999,
supplemented with an in vitro study of thyroxine (T4) binding to
calcium carbonate.SettingVeterans Affairs Medical Center in West Los Angeles, Calif.PatientsTwenty patients (age range, 27-78 years; n=11 men) with hypothyroidism
who were taking a stable long-term regimen of levothyroxine were included
in the study. All patients had serum free T4 and thyrotropin values
in the normal range before beginning the study.InterventionSubjects were instructed to take 1200 mg/d of elemental calcium as calcium
carbonate, ingested with their levothyroxine, for 3 months.Main Outcome MeasuresLevels of free T4, total T4, total triiodothyronine
(T3), and thyrotropin, measured in all subjects at baseline (while
taking levothyroxine alone), at 2 and 3 months (while taking calcium carbonate
and levothyroxine), and 2 months after calcium carbonate discontinuation (while
continuing to take levothyroxine).ResultsMean free T4 and total T4 levels were significantly
reduced during the calcium period and increased after calcium discontinuation.
Mean free T4 levels were 17 pmol/L (1.3 ng/dL) at baseline, 15
pmol/L (1.2 ng/dL) during the calcium period, and 18 pmol/L (1.4 ng/dL) after
calcium discontinuation (overall P<.001); mean
total T4 levels were 118 nmol/L (9.2 µg/dL) at baseline,
111 nmol/L (8.6 µg/dL) during the calcium period, and 120 nmol/L (9.3
µg/dL) after calcium discontinuation (overall P=.03).
Mean thyrotropin levels increased significantly, from 1.6 mIU/L at baseline
to 2.7 mIU/L during the calcium period, and decreased to 1.4 mIU/L after calcium
discontinuation (P=.008). Twenty percent of patients
had serum thyrotropin levels higher than the normal range during the calcium
period; the highest observed level was 7.8 mIU/L. Mean T3 levels
did not change during the calcium period. The in vitro study of T4
binding to calcium showed that adsorption of T4 to calcium carbonate
occurs at acidic pH levels.ConclusionsThis study of 20 patients receiving long-term levothyroxine replacement
therapy indicates that calcium carbonate reduces T4 absorption
and increases serum thyrotropin levels. Levothyroxine adsorbs to calcium carbonate
in an acidic environment, which may reduce its bioavailability.
Citations
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TL;DR: It is concluded that levothyroxine should remain the standard of care for treating hypothyroidism and no consistently strong evidence for the superiority of alternative preparations is found.
Abstract: Background: A number of recent advances in our understanding of thyroid physiology may shed light on why some patients feel unwell while taking levothyroxine monotherapy. The purpose of this task force was to review the goals of levothyroxine therapy, the optimal prescription of conventional levothyroxine therapy, the sources of dissatisfaction with levothyroxine therapy, the evidence on treatment alternatives, and the relevant knowledge gaps. We wished to determine whether there are sufficient new data generated by well-designed studies to provide reason to pursue such therapies and change the current standard of care. This document is intended to inform clinical decision-making on thyroid hormone replacement therapy; it is not a replacement for individualized clinical judgment. Methods: Task force members identified 24 questions relevant to the treatment of hypothyroidism. The clinical literature relating to each question was then reviewed. Clinical reviews were supplemented, when relevant, with related...
1,128 citations
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...Only two of these medications have been studied in a cross-over study design of chronic therapy (132,145), with two other studies also conducted prospectively (140,143)....
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...4 mIU/L after discontinuation of the calcium (132)....
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TL;DR: Patients with impaired acid secretion require an increased dose of thyroxine, suggesting that normal gastric acid secretion is necessary for effective absorption of oral thyrotropin.
Abstract: Background Malabsorption of thyroxine has been described in patients treated with drugs that modify an acidic environment. We determined whether there is an increased need for thyroxine in patients with euthyroid multinodular goiter and impaired secretion of gastric acid. Methods We assessed the dose of thyroxine required to obtain a low level of thyrotropin (0.05 to 0.20 mU per liter) in 248 patients with multinodular goiter. Of these 248 patients, 53 also had Helicobacter pylori–related gastritis and 60 had atrophic gastritis of the body of the stomach (31 with evidence of H. pylori infection and 29 without such evidence). The reference group comprised 135 patients with multinodular goiter and no gastric disorders. In addition, variation in the level of serum thyrotropin was prospectively studied in 11 patients treated with thyroxine before and after H. pylori infection and both before and during treatment with omeprazole in 10 patients treated with thyroxine who had gastroesophageal reflux. Results The...
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TL;DR: Effective management of mild to moderate potential or actual postoperative hypoPT can be achieved by administering either empiric/prophylactic oral calcium and vitamin D, selective oral calcium, and Vitamin D based on rapid postoperative PTH level(s), or serial serum calcium levels as a guide.
Abstract: Background: Hypoparathyroidism (hypoPT) is the most common complication following bilateral thyroid operations. Thyroid surgeons must employ strategies for minimizing and preventing post-thyroidect...
237 citations
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...Levothyroxine should be taken 1 hour before or 3 hours after calcium salts are taken (100)....
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TL;DR: Many commonly used drugs, such as bile acid sequestrants, ferrous sulphate, sucralfate, calcium carbonate, aluminium-containing antacids, phosphate binders, raloxifene and proton-pump inhibitors, have also been shown to interfere with the absorption of levothyroxine.
198 citations
References
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TL;DR: Therapy for milder forms of hypothyroidism is controversial and the controversy surrounding therapy will not be resolved until more randomized studies are available for the subgroup of patients with TSH <10 mIU/L, and until the question of cardiovascular risk factors is further clarified.
Abstract: The term 'subclinical hypothyroidism' applies to patients who have mildly increased levels of serum thyrotropin hormone (TSH) and normal levels of thyroxine and liothyronine (triiodiothyronine). This very common condition, also called 'mild thyroid failure', accounts for 75% of patients who have increased serum TSH. For patients with sustained increases above 10 mIU/L, there is uniform agreement that thyroxine therapy is indicated. Therapy for milder forms of hypothyroidism is controversial. Some randomized clinical trials favor therapy for mild thyroid failure, but they are inconclusive because they lack stratification for the subgroup of patients with TSH levels below 10 mIU/L. For this subgroup, we recommend individualized management. The presence of goiter, positive thyroperoxidase (TPO) antibodies, manic-depressive disorder, fertility problems, or pregnancy or the anticipation of pregnancy favors the initiation of therapy. Positive TPO antibodies are a strong indication for therapy because of the high likelihood in these patients of progression to overt hypothyroidism; patients who are already receiving thyroxine should have adjustments of their dosage. Children and adolescents with mild thyroid failure should also be treated because of possible adverse effects on growth and development. It has been suggested that subclinical hypothyroidism is a cardiovascular risk factor, however further investigation is needed. The controversy surrounding therapy will not be resolved until more randomized studies are available for the subgroup of patients with TSH <10 mIU/L, and until the question of cardiovascular risk factors is further clarified.
387 citations
TL;DR: For some patients with nodular thyroid disease, conflicting or insufficient data may not allow an unequivocal consensus recommendation, and in such circumstances, the existing evidence is reviewed and a rational strategy for treatment is provided.
Abstract: Purpose: To review the indications for and the proper monitoring of levothyroxine therapy in patients with thyroid disease. Data Sources: Relevant English language articles published from 1966 to 1...
306 citations
TL;DR: Simultaneous ingestion of ferrous sulfate and thyroxine causes a variable reduction in thyroxin efficacy that is clinically significant in some patients.
Abstract: ▪Objective:To determine whether simultaneous ingestion of ferrous sulfate and thyroxine reduces the efficacy of thyroid hormone in patients with primary hypothyroidism. ▪Design:Uncontrolle...
203 citations
TL;DR: The association between hypercholesterolaemia and subclinical hypothyroidism is described and the effect of thyroid substitution therapy is quantified by an analysis of previously published intervention studies.
Abstract: OBJECTIVE The significance of mild hypercholesterolaemia in subclinical hypothyroidism and whether there is beneficial reduction after thyroxine replacement, remain controversial. We aimed to describe the association between hypercholesterolaemia and subclinical hypothyroidism, and to quantify the effect of thyroid substitution therapy by an analysis of previously published intervention studies. DATA SOURCES Intervention studies cited in the Medline database from January 1976 until January 1995, with index terms cholesterol, hypercholesterolaemia, hyperlipidaemia, thyrotrophin (TSH), hypothyroidism, thyroid and human. A total of 148 studies were reviewed. DATA EXTRACTION We recorded the year of publication, study design, number of patients enrolled, mean age, duration of thyroid substitution, normal range of TSH levels, TSH levels pre and post-substitution treatment and total cholesterol in plasma before and after treatment. DATA ANALYSIS (1) Qualitative description of studies on the relationship between hypercholesterolaemia and hypothyroidism, both subclinical and clinical. (2) Precision weighted pooled estimates of the effect of thyroid substitution therapy on the plasma levels of total cholesterol, in patients with subclinical and overt hypothyroidism. RESULTS Subclinical hypothyroidism was two to three times more frequent in people with an elevated total plasma cholesterol. In addition, the total plasma cholesterol levels were slightly elevated in patients with subclinical dysfunction of the thyroid. Thyroid substitution therapy in patients with subclinical hypothyroidism, restoring the TSH levels to normal, decreased total cholesterol by 0.4 mmol/l (95% confidence interval (CI) 0.2-0.6 mmol/l) independently of the initial plasma level. The effect of thyroid substitution therapy on HDL-cholesterol in patients with subclinical hypothyroidism was not consistent. The effect of thyroid substitution in patients with overt hypothyroidism was highly dependent on the pretreatment levels of total cholesterol. In these patients substitution therapy decreased total cholesterol by 1.2 mmol/l (95% CI 0.9-1.5 mmol/l) when the plasma levels were elevated up to 8 mmol/l, and by 3.4 mmol/l (95% CI 3.0-3.7) when plasma levels were higher than 8 mmol/l. The high density lipoprotein (HDL)-cholesterol level decreased and amounted to 0.16 mmol/l (95% CI 0.07-0.24). CONCLUSIONS Thyroid substitution treatment in patients with hypercholesterolaemia and subclinical hypothyroidism decreases total plasma cholesterol by 0.4 mmol/l, but plasma levels remain elevated in most patients. Further treatment with dietary restriction and cholesterol synthesis inhibitors should then be considered.
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170 citations