Anticancer Activity and Mechanisms of Action of MAPK pathway inhibitors

WHO have defined the epidemiological criterion for iodine deficiency as a UIC of less than 100 g/l (Table 4)

WHO have defined the epidemiological criterion for iodine deficiency as a UIC of less than 100 g/l (Table 4). Table 4 ? Epidemiological criteria for assessing iodine nutrition based on Median urinary concentration of school-age children (6 yr1)) thead Median urinary Iodine (g/l)Iodine intakeIodine status /thead 20InsufficientSevere deficiency20C49InsufficientModerate deficiency50C99InsufficientMild deficiency100C199AdequateAdequate iodine nutrition200C299Above requirementsLikely to provide adequate intake for Pregnant/lactating women, but may pose a slight risk of more than adequate intake in the overall populace 300ExcessiveRisk of adverse health consequence (iodine-induced hyperthyroidism, autoimmune thyroid disease) Open in a separate window Two following clinical issues remain to be elucidated. HID in patient receiving long term TEN. strong class=”kwd-title” Keywords: hypothyroidism due to iodine deficiency, enteral nutrition, urinary iodine concentration, severe motor intellectual disabilities Introduction Iodine is an essential trace element for synthesis of thyroid hormones and normal brain development requires thyroxine BIIE 0246 (T4). Iodine deficiency (ID) may cause hypothyroidism which results in severe developmental delay in infants BIIE 0246 and stillbirth in pregnant women (1). In iodine deficient areas, which are distributed in fifty-four countries of the world, iodine supplementation programs using iodized salt have been implemented (2,3,4,5). Patients on long term enteral nutrition (EN) develop ID because of the low iodine content of EN formula. A few domestic reports describing ID in subjects on long term total EN (TEN) have been published since early 1990s (6, 7). In this report, we present seven patients who developed hypothyroidism due to iodine deficiency (HID) during long-term TEN. We also discuss the efficacy of treatment using powdered kelp. Patients Seven patients (five male, two female) were studied, including four outpatients living with their families who provided their daily care and three inpatients living in a nursing home (Table 1). They were all diagnosed as having severe motor and intellectual disabilities (SMID) and RPB8 all seven were on medication for epilepsy. There was no specific choice of antiepileptics. All seven had received TEN for more than three years because of their swallowing disorders with an average duration of TEN was BIIE 0246 7.1 (3C16) yr. Hypothyroidism was diagnosed at 16.7 (2C41) yr of age. Labels of EN formula used were the following: Ensure? (Abbott) in 2, Ensure High? (Abbott) in 1, Racol? (Otsuka) in 2, Enterud? (Terumo) in 1, Elental? (Ajinomoto) was changed to E-3? (Clinico) in 1 case. Their daily iodine intake was calculated to be less than 20 g per day. In three cases, goiter (III/IV: Shichijos classification) was found and two of them also had constipation. In four cases without goiter, two had other clinical manifestations of hypothyroidism, specifically, bradycardia with low body heat in one, and extension of sleeping time in the other. No significant BIIE 0246 symptoms were present in the remaining two cases. Table 1 ?Seven cases thead CaseOnset age/SexDiagnosisEN formulaDuration of TEN (yr)Iodine intake (g /d)Clinical manifestation /thead 115/MSequela of encepalitisRacol519.2constipation, goiter217/MSequela of HIE*Ensure1612.0constipation, goiter326/MSpasistic quadriplegiaEnsure79.6C413/MSequela of HIERacol818.4C541/MSequela of HIEEnsure H412.0extension of sleeping time63/FSequela of HIEEnterud3Very lowgoiter72/FToluene embryopathyElental-P/E-32/549.6/21.0bradycardia, low body heat Open in a separate window *HIE: hypoxic ischemic encephalopathy. Methods TSH and freeT4 (FT4) were measured by CLIA. Anti-thyroglobulin (Tg) – antibody and anti-thyroid peroxidase (TPO) – antibody were measured by EIA. Urinary iodine concentration (UIC) was measured using the morning spot urine sample by the Sandell-Kolthoff reaction using 96-well micro plates (HITACHI) (8). When a patient had goiter, we investigated the thyroid gland to detect tumors or nodules by ultrasound scanning. Hypothyroidism in patients with TSH 4.0 IU/ml or FT4 0.8 ng/dl without elevation of anti-Tg/TPO-antibody and low level of UIC (less than 100 g/l), was attributed to ID. We provided 1C2 g/d (200C400 g/d iodine) of powdered kelp dissolved in EN formula or a small amount of water and fed through their nutritional tubes. After starting powdered kelp, TSH and FT4 were measured 1C2 mo later. UIC was also measured 3C11 mo later. Before the investigation, informed consent for thyroid function test and UIC measurement was obtained from all family members of the seven patients, according to Helsinki declaration. We provided the results if requested by the family. Results The patients thyroid function and UICs before and after treatment by powdered kelp are presented in Table 2. Before treatment, TSH was 7.6C82.3 (median 9.2) BIIE 0246 IU/ml and FT4 was 0.4C1.5 (median 0.66) ng/dl. Anti-Tg/TPO-antibody was negative in all cases. In five cases (Case 1C5), UICs were measured before treatment and extremely low (less than 25 g /l in 4, 58 g/l in one case). Thyroid function TSH: 0.7C4.7 IU/ml (median 3.52), FT4: 0.8C1.5 ng/dl (median 1.05) and UIC 180C648 g/l (median 282) (N=7) were normalized after treatment. No thyroid tumors or nodules were detected by ultrasound carried out in 3 cases.