Iodide Transport Defect and Breast Milk Iodine

What Is Known about This Topic?

• Iodide transport defect (ITD) is a dyshormonogenetic congenital hypothyroidism caused by sodium/iodide symporter (NIS) gene mutations. In the lactating mammary gland, iodide is concentrated by NIS.

What Does This Case Report Add?

• The iodine concentration in an ITD patient's breast milk is low. Possible iodine deficiency in the infant breast-fed by an ITD patient should be kept in mind.

Introduction

Iodide transport defect (ITD) is a dyshormonogenetic congenital hypothyroidism caused by sodium/iodide symporter (NIS) gene mutations [1]. NIS mediates active iodide transportation, and plays an important role in concentrating iodide in the thyroid. NIS is also expressed in several other tissues, including the salivary glands, placenta, and lactating mammary gland [1]. In the lactating mammary gland, NIS concentrates iodide, and the infant is thereby supplied with iodine in the breast milk. We herein report on a pregnant ITD patient homozygous for an NIS mutation. She took potassium iodide tablets after delivery to supply iodine to her baby in the breast milk. This is the first report, to our knowledge, to focus on measurement of the breast milk iodine concentration (BMIC) in a patient with ITD.

Materials and Methods

Breast milk samples of 13 lactating Japanese women served as controls, with their consent. Three women had hypothyroidism treated with levothyroxine (LT₄) (2 due to post ¹³¹I therapy of Graves' hyperthyroidism, and one due to postsurgical treatment of Graves' hyperthyroidism). One patient had euthyroid Hashimoto's thyroiditis and one had no thyroidal abnormalities. Eight patients with Graves' hyperthyroidism were treated with potassium iodide (5 at 50 mg per day, and 3 at 50 mg every other day).

BMIC was determined by Hitachi Chemical Clinical Laboratory (Tokyo, Japan). Breast milk was ultracentrifuged with a molecular weight cutoff of 50,000 Da. The iodine concentration in the clear fluid of the whey layer was measured employing a commercial iodine measurement kit (Hitachi Chemical Co., Ltd., Tokyo, Japan) [2]. This kit has adopted an ammonium persulfate digestion microplate method using the Sandell-Kolthoff reaction in a sealing cassette [3]. The coefficient of variation was less than 15%, the detection limit 25 μg/l, and the range of measurement 25-500 μg/l [2]. The accuracy of the kit was 80-120% of the value determined by inductively coupled plasma mass spectrometry [2]. Samples showing values over the measurement range were remeasured after dilution to obtain quantitative results.

BMIC in the Present Patient and Control Subjects

Figure 1 shows the BMIC of our present patient and the control subjects (n = 13). The BMIC in the lactating Japanese women (n = 5) ranged from 166 to 2,560 µg/l (median 214). The BMIC ranged from 3,150 to 47,000 µg/l (median 28,350) in the patients with Graves' disease treated with 50-mg potassium iodide tablets every 1 or 2 days (n = 8).

View Full Size

BMICs of control subjects (n = 13) and the present patient. KI^-: group without intake of potassium iodide (n = 5) and the present patient. KI⁺: group with Graves' disease treated with potassium iodide (n = 8) and the present patient during intake of potassium iodide. Circles: the present patient; dots: controls.

Citation: European Thyroid Journal 5, 2; 10.1159/000446496

• Download Figure
• Download figure as PowerPoint slide

Discussion

Our patient had the T354P NIS mutation, which is the most common mutation in Japan. Although this patient did not begin treatment with LT₄ during the neonatal period, she had no apparent neurodevelopmental deficits. The clinical features of ITD patients with NIS mutations are heterogeneous, and their broad spectrum of manifestations range from extremely small goiters to huge goiters, and from euthyroidism to overt hypothyroidism [5]. The Japanese people generally consume rather large amounts of iodine in traditional foods. Substantial iodine intake may have compensated for impaired active iodide transport due to the mutated NIS in our present patient. Moreover, there might be partial compensation for the functions of the mutated NIS due to iodide transport through nonspecific channels or carriers, or even via diffusion [6].

The baby is probably heterozygous for the NIS mutation. No patients were reported in her husband's pedigree. Since NIS is located at the apical membrane (maternal side) of placental syncytiotrophoblasts, the efficacy of iodide transport across the placenta is assumed to be decreased in ITD patients with NIS mutations. However, in this case, the baby's thyroid function was normal at birth. Substantial maternal iodine supplementation and the following placental characteristics may have compensated for impaired iodide transport due to the mutated NIS. Although its capacity is much lower than that of the thyroid, the placenta stores iodine to be supplied to the fetus [7]. Additionally, type 3 iodothyronine deiodinase, which is present in the placenta, plays a role in supplying iodine to the fetus [8]. While autoregulation of NIS in the lactating mammary gland seems minimal or absent [9], it is suggested that NIS in the placenta is autoregulated to keep iodide transport unaltered [10]. Finally, several iodide transporters are presumed to be involved in placental transport [10].

The reported median BMIC in lactating women ranges from 35 to 155 μg/l in the United States [11]. BMIC less than 50 μg/l is considered to indicate iodine deficiency [12], and BMIC exceeding 80 μg/l is required for an infant before the commencement of weaning foods [13]. Since the lactating mammary gland with the inactivating NIS mutation is not able to effectively concentrate iodide in breast milk, the BMIC of ITD patients would presumably be low. In fact, our patient's BMIC was 54 µg/l, clearly lower than that of lactating Japanese women in general. Our patient's BMIC increased modestly to 90 μg/l after taking a daily 50-mg potassium iodide tablet, a level just above the minimum iodine requirement. Although NIS is not regulated by TSH in the breast [1], the BMIC in patients with Graves' hyperthyroidism may differ from that in euthyroid or hypothyroid patients. Nevertheless, the BMIC during potassium iodide intake was much lower in this patient than in control subjects with Graves' hyperthyroidism. Infants breast-fed by ITD patients are at risk for developing severe iodine deficiency, especially in iodine-deficient geographic areas. Prophylactic iodine supplementation is essential for such infants in order to prevent severe iodine deficiency. In spite of NIS mutation, the BMIC of ITD patients can be increased above the minimum requirement level by supplying high doses of iodine.

Commercial infant formulas generally contain much lower amounts of iodine than breast milk. The iodine contents of commercial formulas vary considerably among manufacturers as well as among branded product lots. Japanese commercial formulas are not iodized by law. The iodine content in these formulas also warrants attention as some infants are fed only such formulas.

In conclusion, clinicians need to be aware of possible iodine deficiency in the infant breast-fed by an ITD patient.

Disclosure Statement

The authors have no conflicts of interest to disclose.