Front Endocrinol (Lausanne). 2021;12:664839.

Decreased Expression of Ileal Thyroid Hormone Transporters in a Hypothyroid Patient: A Case Report.

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제1저자 정재원 · 교신저자 박영주, 배정모

PMID 34122338 PMC8187942 DOI 10.3389/fendo.2021.664839 IF 5.7 내분비대사내과

소속 (5)

Department of Internal Medicine, Seoul National University Hospital, Seoul, South Korea.
Department of Internal Medicine, The Catholic University of Korea Incheon St. Mary's Hospital, Incheon, South Korea.
Department of Internal Medicine, Seoul National University College of Medicine, Seoul, South Korea.
Department of Pathology, Seoul National University Hospital, Seoul, South Korea.
Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, Seoul National University, Seoul, South Korea.

Abstract

BACKGROUND Malabsorption of levothyroxine (LT4) is a common problem faced in clinical practice. It is usually solved, if there are no complexities including gastrointestinal absorption disorder, by taking medicines on an empty stomach and avoiding foods interfering with LT4. Herein we present a rare case of a patient exhibiting malabsorption of LT4 with decreased membranous expression of ileal transporters.

CASE The 22-Year-old female presented with sustained hypothyroid status despite medication of 7.8 μg/kg LT4. Medical history and LT4 absorption test (the absorption rate 8.4%) excluded pseudomalabsorption. No organic gastrointestinal disorder was found in the patient by blood chemistry, endoscopies, and abdominal computed tomography scan. The immunohistochemical analysis showed decreased membranous expression of LAT1 and LAT2 in distal ileum and ascending colon in the patient compared to 20 controls who have no thyroid disease. The expression of MCT8 in colon appeared at both nucleus and brush border in the patient, while it was limited to brush border in controls. The expression of other transporters was similar between the patient and controls.

CONCLUSION The changes of the expression of LAT1 and LAT2 in this patient showing LT4 malabsorption might help to understand the role of intestinal transporters in the absorption of LT4 in humans. The functional relevance of the decrement of LAT1 and LAT2 in this patient remains to be elucidated.

Keywords

hypothyroidismimmunohistochemistrylevothyroxine absorption testmalabsorption of levothyroxinethyroid hormone transporter

Figures

**Figure 1** Medical history, log TSH, and LT4 dose per bodyweight of the case patient. The dose of sertraline and ethynyl estradiol were 50 mg per day and 0.03 mg per day, respectively. The beginning dates of each medication were May 2015, September 2015, and September 2016. There was fluctuation of serum TSH level in spite of increasing LT4 dose over bodyweight. LT4, levothyroxine; Bwt, bodyweight.

**Figure 2** LT4 absorption test. The serum total T4 level increased and TSH level decreased in response to high dose of LT4 ingestion. Absorption rate of LT4 was 8.4%.

**Figure 3** **(A–K)** Immunohistochemistry result of ileal LT4 transporters in distal ileum. The panels were taken at × 20 magnification, and inset represents × 40 magnification. OATP1C1 was expressed in both nucleus and brush border in control **(A)** and the patient **(B)**. OATP2B1 and MCT10 were mainly expressed in brush border in control **(C, E)** and the patient **(D, F)**, respectively. LAT1 was mainly expressed in brush border in control **(G)**, whereas there was perinuclear staining in the patient **(H)**. LAT2 was detected at both perinuclear area and brush border in control **(I)**, but was stained at only perinuclear area in the patient **(J)**. The expression of MCT8 was not able to check in the patient due to lack of remnant ileal tissue. It was mainly expressed in brush border in control **(K)**.

**Figure 4** **(A–L)** Immunohistochemistry result of ileal LT4 transporters in ascending colon. The panels were taken at × 20 magnification, and inset represents × 40 magnification. OATP1C1 was expressed in both nucleus and brush border in control **(A)** and the patient **(B)**. OATP2B1 was expressed in brush border in control **(C)** and the patient **(D)**. MCT10 staining was weak and limited to brush border in control **(E)** and the patient **(F)**. LAT1 was mainly stained at brush border in control **(G)**, but was mainly stained at nucleus in the patient **(H)**. While LAT2 was stained at both nucleus and brush border in control **(I)**, it was stained at only perinuclear area in the patient **(J)**. MCT8 was expressed in brush border in control **(K)**, but was expressed in both nucleus and brush border in the patient **(L)**.

**Figure 5** Expression of SLCO1C1 (OATP1C1), SLCO2B1 (OATP2B1), SLC16A10 (MCT10), SLC7A5 (LAT1), SLC7A8 (LAT2), and SLC16A2 (MCT8) in gastrointestinal tract. Violin plots were used to express the TPM data of transporters in each tissue. The colors indicate the different tissues. TPM, transcripts per million.

그림 출처: PubMed Central 공개 논문 (PMC8187942)

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

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