Dr. Ron’s Research Review – June 3, 2020

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This week’s research review focuses on levothyroxine malabsorption

Some patients remain hypothyroid on LT4 (Levothyroxine, Synthroid) doses in excess of weight-based calculations, a condition known as refractory hypothyroidism. The LT4 absorption test (LT4AT) has been proposed to have utility in these patients by enabling distinction of LT4 malabsorption from pseudo-malabsorption, a condition of intentional non-adherence. (Ghosh et al., 2020)

Vitamin C

A study examined the effect of vitamin C on the absorption of l-T4 in patients with hypothyroidism and gastritis. 
Thirty-one patients with hypothyroidism, 28 females age 47.5 ± 13.5 (mean ± SD) years and 3 males age 55.7 ± 11.2 years ingested the dose of l-T4 in 120 mL water containing or not containing 500 mg vitamin C in a solution of pH 2.9 ± 0.1 (mean ± SD).
Serum concentrations of free T4 and TSH were measured at the end of 3 periods of 2 months each, 2 controls and 1 vitamin C. Serum total T3 was measured in 16 of the patients, before and at the end of the vitamin C period. Serum TSH and free T4 and T3 were measured by a solid-phase, enzyme-labeled chemiluminescent competitive immunoassay All patients had gastrointestinal pathology and were not in good control when taking l-T4 before the study, and 23 had autoimmune thyroiditis or idiopathic hypothyroidism. The median l-T4 dose was 100 μg with an interquartile range of 50 μg.
Serum concentrations of TSH, free T4, and T3 improved while on vitamin C. Serum TSH decreased in all patients (control, 11.1 [10.5] μIU/mL, median [interquartile range]), vitamin C 4.2 (3.7) μIU/mL, P = .0001), and it was normalized in 17 patients (54.8%). The average decrease was 69.2%. Serum T4 was higher with vitamin C in 30 of the 31 patients (control, 1.1 [0.3] ng/dL; vitamin C, 1.3 [0.3] ng/dL; P < .0001), and serum T3 increased as well in all 16 patients in whom it was measured (control, 60.5 [16.5] ng/dL; vitamin C, 70 [21] ng/dL; P < .005). 
In patients with hypothyroidism and gastrointestinal pathology, vitamin C improves the abnormalities in serum free T4, T3, and TSH concentrations. (Jubiz and Ramirez, 2014)

Dr. Ron


Articles

 

Levothyroxine Absorption Test to Differentiate Pseudomalabsorption from True Malabsorption.
            (Ghosh et al., 2020)  Download
Background:  The levothyroxine absorption test for evaluation of pseudomalabsorption in patients with primary hypothyroid is not standardised. An individual in whom a workup for malabsorption is warranted remains undefined. Methods:  Twenty-five euthyroid, 25 newly diagnosed hypothyroid, 25 treated hypothyroid with normalised TSH, and 25 hypothyroid subjects with elevated TSH despite adequate dose of levothyroxine for more than 6 months, and 10 euthyroid subjects with true malabsorption were administered levothyroxine (10 μg/kg or maximum 600 μg) to study its absorption profile by measuring free T4 level at hourly intervals for 5 h. <b>Results</b> : Free T4 peaked at 3 h with marginal insignificant decline at 4 h in all groups. The increments of free T4 (between baseline and 3 h) of the four groups (except malabsorption) were not statistically different. The mean increment of free T4 in true malabsorption was 0.39 ng/dL (95% CI: 0.29-0.52) and it was 0.78 ng/dL (95% CI: 0.73-0.85) (10.4 pmol/L) for other groups combined together. The cut off of free T4 increment at 3 h from baseline above 0.40 ng/dL had a sensitivity of 97% and specificity of 80% (AUC 0.904, p < 0.001) to exclude true malabsorption. Conclusion:  Subjects with elevated TSH on adequate dose of LT4 can be reliably diagnosed to be non-adherent to treatment with levothyroxine absorption test. The incremental value above 0.40 ng/dL (5.14 pmol/L) at 3 h may be useful to identify individuals where workup of malabsorption is unwarranted.

Effect of vitamin C on the absorption of levothyroxine in patients with hypothyroidism and gastritis.
            (Jubiz and Ramirez, 2014)  Download
BACKGROUND:  Malabsorption of l-T4 is a major clinical problem. Changes in gastric pH caused by several medical illnesses are associated with difficulties in the control of patients with hypothyroidism receiving the hormone. Means to correct these alterations would be of clinical value. OBJECTIVES:  Our objective was to study the effect of vitamin C on the absorption of l-T4 in patients with hypothyroidism and gastritis. DESIGN:  Thirty-one patients with hypothyroidism, 28 females age 47.5 ± 13.5 (mean ± SD) years and 3 males age 55.7 ± 11.2 years ingested the dose of l-T4 in 120 mL water containing or not containing 500 mg vitamin C in a solution of pH 2.9 ± 0.1 (mean ± SD). Serum concentrations of free T4 and TSH were measured at the end of 3 periods of 2 months each, 2 controls and 1 vitamin C. Serum total T3 was measured in 16 of the patients, before and at the end of the vitamin C period. Serum TSH and free T4 and T3 were measured by a solid-phase, enzyme-labeled chemiluminescent competitive immunoassay All patients had gastrointestinal pathology and were not in good control when taking l-T4 before the study, and 23 had autoimmune thyroiditis or idiopathic hypothyroidism. The median l-T4 dose was 100 μg with an interquartile range of 50 μg. The protocol was reviewed and approved by our institution's ethics committee. Patients were asked to sign a written consent to participate in the study. RESULTS:  Serum concentrations of TSH, free T4, and T3 improved while on vitamin C. Serum TSH decreased in all patients (control, 11.1 [10.5] μIU/mL, median [interquartile range]), vitamin C 4.2 (3.7) μIU/mL, P = .0001), and it was normalized in 17 patients (54.8%). The average decrease was 69.2%. Serum T4 was higher with vitamin C in 30 of the 31 patients (control, 1.1 [0.3] ng/dL; vitamin C, 1.3 [0.3] ng/dL; P < .0001), and serum T3 increased as well in all 16 patients in whom it was measured (control, 60.5 [16.5] ng/dL; vitamin C, 70 [21] ng/dL; P < .005). CONCLUSIONS:  In patients with hypothyroidism and gastrointestinal pathology, vitamin C improves the abnormalities in serum free T4, T3, and TSH concentrations. This approach is helpful in the management of these patients.

 

References

Ghosh, S, et al. (2020), ‘Levothyroxine Absorption Test to Differentiate Pseudomalabsorption from True Malabsorption.’, Eur Thyroid J, 9 (1), 19-24. PubMed: 32071898
Jubiz, W and M Ramirez (2014), ‘Effect of vitamin C on the absorption of levothyroxine in patients with hypothyroidism and gastritis.’, J Clin Endocrinol Metab, 99 (6), E1031-4. PubMed: 24601693