Wolff–Chaikoff effect

{{Short description|Effect of iodine on the thyroid}}

File:Effekte der Jodblockade.png

The Wolff–Chaikoff effect{{cite book |author=Dorland |title=Dorland's Illustrated Medical Dictionary |url=https://books.google.com/books?id=nHKj1FyrSW4C&q=woolf+cha+kof&pg=PA2083 |year=2011 |publisher=Elsevier Health Sciences |isbn=9781416062578 |page=2083}} is a presumed reduction in thyroid hormone levels caused by ingestion of a large amount of iodine.{{cite book| title= Essentials of Human Physiology| first= Thomas M. |last= Nosek| chapter=Section 5/5ch5/s5ch5_6 |chapter-url=http://humanphysiology.tuars.com/program/section5/5ch5/s5ch5_6.htm |archive-url=https://web.archive.org/web/20160324124828/http://humanphysiology.tuars.com/program/section5/5ch5/s5ch5_6.htm|archive-date=2016-03-24}}

It was discovered by Drs. Jan Wolff and Israel Lyon Chaikoff at the University of California, Berkeley: in 1948, they reported that injection of iodine in rats almost completely inhibited organification (thyroglobulin iodination) in the thyroid gland.{{cite book |last1=Panneels|first1=V.|last2=Juvenal|first2=G.|last3=Boeynaems|first3=J.M.|last4=Durmont|first4=J.E.|last5=Sande|first5=J. Van|editor1-first=Victor R.|editor1-last=Preedy|editor2-first=Gerard N.|editor2-last=Burrow|editor3-first=Ronald Ross|editor3-last=Watson|title=Comprehensive Handbook of Iodine: Nutritional, Biochemical, Pathological and Therapeutic Aspects|publisher=Academic Press |year=2009 |page=304 |chapter=Iodide Effects on the Thyroid: Biochemical, Physiological, Pharmacological, and Clinical Effects of Iodide in the Thyroid|isbn=9780080920863|chapter-url=https://books.google.com/books?id=7v7g5XoCQQwC&q=Wolff-Chaikoff+effect&pg=PA304}}{{cite journal |vauthors=Wolff J, Chaikoff IL |title=Plasma inorganic iodide as a homeostatic regulator of thyroid function|journal=J Biol Chem|volume=174|issue=2|pages=555–564|year=1948|doi=10.1016/S0021-9258(18)57335-X|url=http://www.jbc.org/content/174/2/555.short|pmid=18865621|doi-access=free}} However, recent{{when|date=April 2022}} research into the study shows that the thyroid hormone levels of the rats were not checked prior to injections.{{citation needed|date=April 2022}}

Patients with Graves' disease are more sensitive than euthyroid patients,{{cite book|title=Pharmacology for Women's Health|last1=King|last2=Tekoa|first2=Mary Brucker|year=2010|publisher=Jones & Bartlett Learning|isbn=9780763753290|page= 549|url=https://books.google.com/books?id=u1wq63x4VsYC&q=Wolff-Chaikoff+effect+sensitive&pg=PA549}} and iodine has been used to manage Graves' disease.

The Wolff–Chaikoff effect is known as an autoregulatory phenomenon that inhibits organification in the thyroid gland, the formation of thyroid hormones inside the thyroid follicle, and the release of thyroid hormones into the bloodstream.{{cite book |title=Goodman and Gilman's the pharmacological basis of therapeutics |last1=Goodman |first1=Louis Sanford |last2=Gilman |first2=Alfred Goodman |edition=9th |year=1996 |publisher=McGraw-Hill |isbn= 978-0-07-026266-9 |page= 1402 |url=https://books.google.com/books?id=09h_hZiYXgUC&q=%22the+basal+metabolic+rate+may+fall+at+a+rate+comparable%22}} This becomes evident secondary to elevated levels of circulating iodide. The Wolff–Chaikoff effect is an effective means of rejecting a large quantity of imbibed iodide, and therefore preventing the thyroid from synthesizing large quantities of thyroid hormone.{{cite journal|last=Markou|first=K|title=Iodine induced hypothyroidism|date=May 2001|volume=11|issue=5|pages= 501–10|pmid= 11396709|doi=10.1089/105072501300176462|journal=Thyroid}} Excess iodide transiently inhibits thyroid iodide organification. In individuals with a normal thyroid, the gland eventually escapes from this inhibitory effect and iodide organification resumes; however, in patients with underlying autoimmune thyroid disease, the suppressive action of high iodide may persist.dennis L. Kasper, stephen L. Hauser, J. Larry Jameson, Anthony s. fauci, dan L. Longo, Joseph Loscalzo (2015). Harrison's Principles of Internal Medicine. 19th Edition. McGraw-Hill Education. P: 2285. {{ISBN|978-0-07-180216-1}}

The Wolff–Chaikoff effect lasts several days (around 10 days), after which it is followed by an "escape phenomenon,"{{cite journal |vauthors=Eng P, Cardona G, Fang S, Previti M, Alex S, Carrasco N, Chin W, Braverman L |title=Escape from the acute Wolff-Chaikoff effect is associated with a decrease in thyroid sodium/iodide symporter messenger ribonucleic acid and protein |journal=Endocrinology |volume=140 |issue=8 |pages=3404–10 |year=1999 |pmid=10433193 |doi=10.1210/endo.140.8.6893|doi-access=free }} which is described by resumption of normal organification of iodine and normal thyroid peroxidase function. "Escape phenomenon" is believed to occur because of decreased inorganic iodine concentration inside the thyroid follicle below a critical threshold secondary to down-regulation of sodium-iodide symporter (NIS) on the basolateral membrane of the thyroid follicular cell.

The Wolff–Chaikoff effect has been used as a treatment principle against hyperthyroidism (especially thyroid storm) by infusion of a large amount of iodine to suppress the thyroid gland. Iodide was used to treat hyperthyroidism before antithyroid drugs such as propylthiouracil and methimazole were developed. Hyperthyroid subjects given iodide may experience a decrease in basal metabolic rate that is comparable to that seen after thyroidectomy. The Wolff–Chaikoff effect also explains the hypothyroidism produced in some patients by several iodine-containing drugs, including amiodarone. The Wolff–Chaikoff effect is part of the mechanism for the use of potassium iodide in nuclear emergencies.{{cite journal |last1=Yoshida |first1=S |last2=Ojino |first2=M |last3=Ozaki |first3=T |last4=Hatanaka |first4=T |last5=Nomura |first5=K |last6=Ishii |first6=M |last7=Koriyama |first7=K |last8=Akashi |first8=M |title=Guidelines for iodine prophylaxis as a protective measure: information for physicians. |journal=Japan Medical Association Journal |date=1 May 2014 |volume=57 |issue=3 |pages=113–23 |pmid=25784824|pmc=4356652 }}{{cite journal |vauthors=Sternthal E, Lipworth L, Stanley B, Abreau C, Fang SL, Braverman LE |title=Suppression of thyroid radioiodine uptake by various doses of stable iodide|journal=N Engl J Med|volume=303|issue=19|pages=1083–8|year=1980|pmid=7421914|url=https://scholar.google.com/scholar?q=%22organification+of+iodide+%28acute+Wolff-Chaikoff%22&btnG=&hl=en&as_sdt=0%2C10|quote=The effect is rapid because of rapid inhibition of intrathyroid organification of iodide (acute Wolff–Chaikoff effect) and saturation of the iodide-transport mechanism.|doi=10.1056/nejm198011063031903|url-access=subscription}}{{cite journal |author=Becker DV|title=Physiological basis for the use of potassium iodide as a thyroid blocking agent logistic issues in its distribution|journal=Bull N Y Acad Med|volume=59|issue=10|pages=1003–8|year=1983|pmid=6582961|quote=In larger amounts [potassium iodide] acts immediately to block further uptake of iodide by several means, particularly by saturating the iodide transport mechanisms of the thyroid, by inhibiting the intrathyroidal organification of iodide, and by simple dilution.|pmc=1911930}}Adelstein SJ (1991). "[https://scholar.google.com/scholar?hl=en&q=%22by+saturating+the+iodide+transport+system%22&btnG=&as_sdt=1%2C10&as_sdtp= Intervention procedures for radionuclides]." Anticarcinogenesis and Radiation Protection 2. Springer US. pp. 227-8. "'Cold' iodide is effective in four ways: (a) by diluting the entering iodide pool; (b) by saturating

the iodide transport system; (c) by blocking organification of iodide and thus inhibiting thyroid hormone synthesis (the Wolff-Chaikoff effect); and (d) by promoting excretion and thus lowering the total body dose."

The Wolff–Chaikoff effect is subject to an escape phenomenon that limits its action after several days. It is to be distinguished from the Plummer effect, which inhibits the proteolysis of thyroglobulin and the release of pre-formed thyroid hormones from follicles.{{cite journal |last1=Saller |first1=B |last2=Fink |first2=H |last3=Mann |first3=K |title=Kinetics of acute and chronic iodine excess. |journal=Experimental and Clinical Endocrinology & Diabetes |date=1998 |volume=106 Suppl 3 |pages=S34-8 |doi=10.1055/s-0029-1212044 |pmid=9865552}} Both effects operate on different time scales. Only the Wolff–Chaikoff effect is helpful to prevent the thyroid from uptaking radioactive iodine in the case of nuclear emergencies. Therefore, "plummering" with high-dose iodine is only effective in a short time window after the release of radionuclides.{{cite journal |last1=Zanzonico |first1=PB |last2=Becker |first2=DV |title=Effects of time of administration and dietary iodine levels on potassium iodide (KI) blockade of thyroid irradiation by 131I from radioactive fallout. |journal=Health Physics |date=June 2000 |volume=78 |issue=6 |pages=660–7 |doi=10.1097/00004032-200006000-00008 |pmid=10832925|s2cid=30989865 }} Wrong timing of iodine use may even increase the risk by triggering the Plummer effect.{{cite journal |last1=Meristoudis |first1=G |last2=Ilias |first2=I |title=Caveats in the use of potassium iodide for thyroid blocking. |journal=European Journal of Nuclear Medicine and Molecular Imaging |date=June 2022 |volume=49 |issue=7 |pages=2120–2121 |doi=10.1007/s00259-022-05797-7 |pmid=35403862|s2cid=248071284 }}

The Plummer effect, the Wolff-Chaikoff inhibition effect, and the adaptive escape phenomenon, synergistically work together to fend off potentially harmful consequences of excess iodine load and ensure thyroid homeostasis.{{cite journal |last1=Jing |first1=Li |last2=Zhang |first2=Qiang |title=Intrathyroidal feedforward and feedback network regulating thyroid hormone synthesis and secretion |journal=Frontiers in Endocrinology |date=15 September 2022 |volume=13 |pages=992883 |doi=10.3389/fendo.2022.992883|doi-access=free |pmid=36187113 |pmc=9519864 }}