Abstract
Congenital hypothyroidism (CH), if not correctly treated with levothyroxine (L-T4), may cause permanent intellectual disability. If patients treated with L-T4 do not achieve good thyroid stimulating hormone (TSH) control, the possibility of poor compliance and/or poor absorption of L-T4 should be investigated. We describe an infant with CH whose thyroid hormone levels worsened after she started a carob-bean gum thickened formula. A baby girl was diagnosed with CH by newborn screening [confirmatory venous blood TSH was 496.0 µIU/mL and free thyroxine (fT4) was 0.13 ng/dL]. Five weeks after beginning replacement L-T4 treatment (10.6 µg/kg per day), thyroid function normalized (TSH 2.72 µIU/mL, fT4 2.08 ng/dL). However, five weeks later, thyroid function test results had worsened (TSH 31.1 µIU/mL, fT4 1.27 ng/dl), which worsened further (TSH 44.8 µIU/mL, fT4 1.16 ng/dL) even after L-T4 dose was increased (10.9 µg/kg per day). Anamnesis disclosed that she had started a carob-bean gum thickened formula to combat gastroesophageal reflux disease rather than regular type 1 formula milk. The anti-reflux milk formula was discontinued. Fourteen days later her TSH level dropped to 0.38 µIU/mL and fT4 increased to 2.68 ng/dL, allowing the L-T4 dose to be reduced (from 10.9 µg/kg per day to 8.0 µg/kg per day). These findings suggest that carob-bean gum thickened formula may affect absorption of L-T4. If such formulas are used, we recommend a more frequent evaluation of thyroid function. In CH infants, inexplicably high TSH levels may be caused by gastrointestinal disorders or the interference from drugs or other substances, including some types of milk formula, which impair L-T4 absorption.
Keywords: Congenital hypothyroidism, L-thyroxine, treatment, carob-bean gum thickened formula, gastro-intestinal absorption, gastroesophageal reflux, case report
Read the full text
4 sections · 2 figures · PDF
Create your free account to read the full text.
- Full text with figures and tables
- PDF and supplementary files
- Access on every Galenos journal
One Galenos account works on every Galenos journal site.
References
Rastogi MV, LaFranchi SH. Congenital hypothyroidism. Orphanet J Rare Dis. 2010;5:17.
Stagi S, Municchi G, Ferrari M, Wasniewska MG. An Overview on different L-thyroxine (l-T4) formulations and factors potentially influencing the treatment of congenital hypothyroidism during the first 3 years of life. Front Endocrinol (Lausanne). 2022;13:859487.
Salerno M, Micillo M, Di Maio S, Capalbo D, Ferri P, Lettiero T, Tenore A. Longitudinal growth, sexual maturation and final height in patients with congenital hypothyroidism detected by neonatal screening. Eur J Endocrinol. 2001;145:377-383.
Aleksander PE, Brückner-Spieler M, Stoehr AM, Lankes E, Kühnen P, Schnabel D, Ernert A, Stäblein W, Craig ME, Blankenstein O, Grüters A, Krude H. Mean high-dose l-thyroxine treatment is efficient and safe to achieve a normal IQ in young adult patients with congenital hypothyroidism. J Clin Endocrinol Metab. 2018;103:1459-1469.
van Trotsenburg P, Stoupa A, Léger J, Rohrer T, Peters C, Fugazzola L, Cassio A, Heinrichs C, Beauloye V, Pohlenz J, Rodien P, Coutant R, Szinnai G, Murray P, Bartés B, Luton D, Salerno M, de Sanctis L, Vigone M, Krude H, Persani L, Polak M. Congenital hypothyroidism: a 2020-2021 Consensus Guidelines Update-An ENDO-European Reference Network Initiative Endorsed by the European Society for Pediatric Endocrinology and the European Society for Endocrinology. Thyroid. 2021;31:387-419.
Brito LNS, Andrade CLO, Alves CAD. Adhesion to treatment by children with congenital hypothyroidism: knowledge of caregivers in Bahia state, Brazil. Rev Paul Pediatr. 2021;39:e2020074.
Centanni M, Benvenga S, Sachmechi I. Diagnosis and management of treatment-refractory hypothyroidism: an expert consensus report. J Endocrinol Invest. 2017;40:1289-1301. Epub 2017 Jul 10.
Skelin M, Lucijanić T, Amidžić Klarić D, Rešić A, Bakula M, Liberati-Čizmek AM, Gharib H, Rahelić D. Factors affecting gastrointestinal absorption of levothyroxine: a review. Clin Ther. 2017;39:378-403. Epub 2017 Jan 30.
Wiesner A, Gajewska D, Paśko P. Levothyroxine interactions with food and dietary supplements-a systematic review. Pharmaceuticals (Basel). 2021;14:206.
Virili C, Antonelli A, Santaguida MG, Benvenga S, Centanni M. Gastrointestinal malabsorption of thyroxine. Endocr Rev. 2019;40:118-136.
Van Wyk JJ, Arnold MB, Wynn J, Pepper F. The effects of a soybean product on thyroid function in humans. Pediatrics. 1959;24:752-760.
Vigone MC, Ortolano R, Vincenzi G, Pozzi C, Ratti M, Assirelli V, Vissani S, Cavarzere P, Mussa A, Gastaldi R, Di Mase R, Salerno M, Street ME, Trombatore J, Weber G, Cassio A. Treatment of congenital hypothyroidism: comparison between L-thyroxine oral solution and tablet formulations up to 3 years of age. Eur J Endocrinol. 2021;186:45-52.
Akcay T, Turan S, Guran T, Unluguzel G, Haklar G, Bereket A. T4 plus T3 treatment in children with hypothyroidism and inappropriately elevated thyroid-stimulating hormone despite euthyroidism on T4 treatment. Horm Res Paediatr. 2010;73:108-114. Epub 2010 Feb 9.
Bosscher D, Van Caillie-Bertrand M, Van Dyck K, Robberecht H, Van Cauwenbergh R, Deelstra H. Thickening infant formula with digestible and indigestible carbohydrate: availability of calcium, iron, and zinc in vitro. J Pediatr Gastroenterol Nutr. 2000;30:373-378.
Ianiro G, Mangiola F, Di Rienzo TA, Bibbò S, Franceschi F, Greco AV, Gasbarrini A. Levothyroxine absorption in health and disease, and new therapeutic perspectives. Eur Rev Med Pharmacol Sci. 2014;18:451-456.
Balapatabendi M, Harris D, Shenoy SD. Drug interaction of levothyroxine with infant colic drops. Arch Dis Child. 2011;96:888-889. Epub 2011 Jul 23.
Vivatvakin B, Buachum V. Effect of carob bean on gastric emptying time in Thai infants. Asia Pac J Clin Nutr. 2003;12:193-197.
Papaefstathiou E, Agapiou A, Giannopoulos S, Kokkinofta R. Nutritional characterization of carobs and traditional carob products. Food Sci Nutr. 2018;6:2151-2161.
Vandenplas Y, Sacré L. Milk-thickening agents as a treatment for gastroesophageal reflux. Clin Pediatr (Phila). 1987;26:66-68.
Tsai AC, Peng B. Effects of locust bean gum on glucose tolerance, sugar digestion, and gastric motility in rats. J Nutr. 1981;111:2152-2156.
Miyazawa R, Tomomasa T, Kaneko H, Morikawa A. Effect of formula thickened with locust bean gum on gastric emptying in infants. J Paediatr Child Health. 2006;42:808-812.
Marciani L, Gowland PA, Spiller RC, Manoj P, Moore RJ, Young P, Al-Sahab S, Bush D, Wright J, Fillery-Travis AJ. Gastric response to increased meal viscosity assessed by echo-planar magnetic resonance imaging in humans. J Nutr. 2000;130:122-127.
Darwiche G, Björgell O, Almér LO. The addition of locust bean gum but not water delayed the gastric emptying rate of a nutrient semisolid meal in healthy subjects. BMC Gastroenterol. 2003;3:12.
Chon DA, Reisman T, Weinreb JE, Hershman JM, Leung AM. Concurrent milk ingestion decreases absorption of levothyroxine. Thyroid. 2018;28:454-457. Epub 2018 Mar 28.
Roberts GW. Taking care of thyroxine. Aust Prescr. 2004;27:75-76.
Bhatia J, Greer F; American Academy of Pediatrics Committee on Nutrition. Use of soy protein-based formulas in infant feeding. Pediatrics. 2008;121:1062-1068.
Hydovitz JD. Occurrence of goiter in an infant on a soy diet. N Engl J Med. 1960;262:351-353.
Pinchera A, Macgillivray MH, Crawford JD, Freeman AG. Thyroid refractoriness in an athyreotic cretin fed soybean formula. N Engl J Med. 1965;273:83-87.
Chorazy PA, Himelhoch S, Hopwood NJ, Greger NG, Postellon DC. Persistent hypothyroidism in an infant receiving a soy formula: case report and review of the literature. Pediatrics. 1995;96:148-150.
Fruzza AG, Demeterco-Berggren C, Jones KL. Unawareness of the effects of soy intake on the management of congenital hypothyroidism. Pediatrics. 2012;130:e699-702. Epub 2012 Aug 20.
Conrad SC, Chiu H, Silverman BL. Soy formula complicates management of congenital hypothyroidism. Arch Dis Child. 2004;89:37-40.


