{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T14:21:49Z","timestamp":1777645309139,"version":"3.51.4"},"reference-count":15,"publisher":"The Endocrine Society","issue":"5","license":[{"start":{"date-parts":[[2026,4,21]],"date-time":"2026-04-21T00:00:00Z","timestamp":1776729600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,4,21]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>The habit of chewing betel leaf, or \u201cpaan\u201d, is prevalent in different parts of India. Betel leaves, areca nut, and lime are common ingredients of paan. Preclinical studies have demonstrated that betel leaf and areca nut affect thyroid function. Lime, due to its high calcium content, adsorbs levothyroxine (LT4) tablets. It is worthwhile to consider paan consumption as a possible etiology of \u201crefractory hypothyroidism\u201d in individuals being treated with a standard LT4 replacement dose in India. Chronic paan chewing causes reddish discoloration of the tongue. Encountering such a finding on examination in a patient with persistently elevated thyroid-stimulating hormone (TSH) should prompt the treating physician to meticulously inquire about dietary patterns and other habits. This is important when there is a consistent denial of noncompliance and an absence of clinical suggestions of malabsorptive and systemic diseases. We describe here a patient with primary autoimmune hypothyroidism with persistently elevated TSH, despite being on an unusually high dose of LT4, due to his habit of paan chewing. The red- colored tongue provided us a clue about the habit. TSH normalization was achieved with the standard replacement dose of LT4 following the cessation of paan consumption.<\/jats:p>","DOI":"10.1210\/jcemcr\/luag084","type":"journal-article","created":{"date-parts":[[2026,4,10]],"date-time":"2026-04-10T11:40:27Z","timestamp":1775821227000},"source":"Crossref","is-referenced-by-count":0,"title":["Betel leaf (paan) chewing: an unusual cause of refractory hypothyroidism in levothyroxine-treated patient"],"prefix":"10.1210","volume":"4","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-7682-4313","authenticated-orcid":false,"given":"Neeti","family":"Agrawal","sequence":"first","affiliation":[{"name":"Department of Endocrinology and Metabolism, AIIMS Nagpur , Nagpur, Maharashtra 441108 ,","place":["India"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ajitesh","family":"Roy","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Metabolism, Vivekananda Institute of Medical Sciences , Kolkata, West Bengal 700026 ,","place":["India"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3316-4525","authenticated-orcid":false,"given":"Partha Pratim","family":"Chakraborty","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Metabolism, Medical College and Hospital Kolkata , Kolkata, West Bengal 700073 ,","place":["India"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0362-5036","authenticated-orcid":false,"given":"Rana","family":"Bhattacharjee","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Metabolism, Medical College and Hospital Kolkata , Kolkata, West Bengal 700073 ,","place":["India"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"80","published-online":{"date-parts":[[2026,4,21]]},"reference":[{"issue":"2","key":"2026042902313496700_luag084-B1","first-page":"28","article-title":"A review: nutraceutical properties of Piper betel (paan)","volume":"4","author":"Chauhan","year":"2016","journal-title":"Am J Phytomed Clini Ther"},{"issue":"2","key":"2026042902313496700_luag084-B2","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1080\/09709274.2006.11905861","article-title":"Betel leaf: the neglected green gold of India","volume":"19","author":"Guha","year":"2006","journal-title":"J Hum Ecol"},{"issue":"1","key":"2026042902313496700_luag084-B3","first-page":"41","article-title":"Testing for betel nut alkaloids in hair of papuans abusers using UPLC-MS\/MS and UPLC-Q-Tof-MS","volume":"44","author":"Gheddar","year":"2020","journal-title":"J Anal Toxicol"},{"issue":"1","key":"2026042902313496700_luag084-B4","doi-asserted-by":"crossref","first-page":"83","DOI":"10.4103\/2230-8210.126582","article-title":"Are patients with primary hypothyroidism in India receiving appropriate thyroxine replacement? An observational study","volume":"18","author":"Mithal","year":"2014","journal-title":"Indian J Endocrinol Metab"},{"issue":"3","key":"2026042902313496700_luag084-B5","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1007\/s11154-021-09691-9","article-title":"Factors influencing the levothyroxine dose in the hormone replacement therapy of primary hypothyroidism in adults","volume":"23","author":"Caron","year":"2022","journal-title":"Rev Endocr Metab Disord"},{"key":"2026042902313496700_luag084-B6","first-page":"618","volume-title":"Werner & Ingbar's The Thyroid: A Fundamental and Clinical Text","author":"Jonklaas","year":"2021","edition":"11th ed"},{"issue":"1","key":"2026042902313496700_luag084-B7","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1210\/er.2018-00168","article-title":"Gastrointestinal malabsorption of thyroxine","volume":"40","author":"Virili","year":"2019","journal-title":"Endocr Rev"},{"key":"2026042902313496700_luag084-B8","first-page":"94","article-title":"Impact of taking thyroxine with herbal stews","volume":"4","author":"Thomas","year":"2018","journal-title":"J Curr Res Sci Med"},{"issue":"6","key":"2026042902313496700_luag084-B9","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1006\/phrs.1998.0398","article-title":"Dual role of betel leaf extract on thyroid function in male mice","volume":"36","author":"Panda","year":"1998","journal-title":"Pharmacol Res"},{"issue":"1","key":"2026042902313496700_luag084-B10","doi-asserted-by":"crossref","first-page":"12276","DOI":"10.1038\/s41598-019-48653-9","article-title":"Allylpyrocatechol, isolated from betel leaf ameliorates thyrotoxicosis in rats by altering thyroid peroxidase and thyrotropin receptors","volume":"9","author":"Panda","year":"2019","journal-title":"Sci Rep"},{"issue":"1-2","key":"2026042902313496700_luag084-B11","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.mce.2010.01.005","article-title":"Ultrastructural and hormonal modulations of the thyroid gland following arecoline treatment and albino mice","volume":"319","author":"Dasgupta","year":"2010","journal-title":"Mol Cell Endocrinol"},{"issue":"4","key":"2026042902313496700_luag084-B12","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1007\/s00240-006-0050-8","article-title":"The increased risk of urinary stone disease in betel quid chewers","volume":"34","author":"Allen","year":"2006","journal-title":"Urol Res"},{"issue":"10","key":"2026042902313496700_luag084-B13","doi-asserted-by":"crossref","first-page":"967","DOI":"10.1089\/105072501753211046","article-title":"The acute effect of calcium carbonate on the intestinal absorption of levothyroxine","volume":"11","author":"Singh","year":"2001","journal-title":"Thyroid"},{"issue":"5","key":"2026042902313496700_luag084-B14","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1089\/thy.2010.0296","article-title":"Absorption of levothyroxine when coadministered with various calcium formulations","volume":"21","author":"Zamfirescu","year":"2011","journal-title":"Thyroid"},{"issue":"2","key":"2026042902313496700_luag084-B15","first-page":"e172","article-title":"Betel nut chewing: an unrecognized cause of milk alkali syndrome","volume":"2","author":"Sendos","year":"2016","journal-title":"AACE Clin Case Rep"}],"container-title":["JCEM Case Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jcemcr\/article-pdf\/4\/5\/luag084\/68120425\/luag084.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jcemcr\/article-pdf\/4\/5\/luag084\/68120425\/luag084.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T06:31:55Z","timestamp":1777444315000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jcemcr\/article\/doi\/10.1210\/jcemcr\/luag084\/8659757"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,21]]},"references-count":15,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2026,4,21]]}},"URL":"https:\/\/doi.org\/10.1210\/jcemcr\/luag084","relation":{},"ISSN":["2755-1520"],"issn-type":[{"value":"2755-1520","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2026,5]]},"published":{"date-parts":[[2026,4,21]]},"article-number":"luag084"}}