Vol. 102 No. 2 August 2006

MEDICAL MANAGEMENT UPDATE Editors: F. John Firriolo, Craig S. Miller, and Nelson L. Rhodus Thyroid disorders. Part II: hypothyroidism and thyroiditis James W. Little, DMD, MS, Minneapolis, MN UNIVERSITY OF MINNESOTA

Part II of the series on thyroid disorders discusses hypothyroidism and thyroiditis that may be found in dental patients. An overview of the conditions is presented. Presenting signs and symptoms, laboratory tests used to diagnose hypothyroidism and thyroiditis, and their medical management is discussed. The dental management of patients with hypothyroidism is discussed in detail. The dentist by detecting the early signs and symptoms of hypothyroidism and thyroiditis can refer the patient for medical diagnosis and treatment and avoid potential complications of treating patients with uncontrolled disease. Patients with thyroiditis may have a short period of being hyperthyroid and it may be best to avoid routine dental treatment during that period. Patients with suppurative thyroiditis should not receive routine dental treatment during the acute stage of the disease. The end stage of Hashimoto’s thyroiditis results in hypothyroidism. Central nervous system depressants, sedatives, or narcotic analgesics must be avoided in patients with severe hypothyroidism because significant respiratory depression may occur. In addition, myxedematous coma, particularly in elderly hypothyroid patients, can be precipitated by central nervous system depressants, infection, and possibly stressful dental procedures. In medically well-controlled patients the dental treatment plan is not affected and most dental procedures can be offered to these patients. (Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2006;102:148-53)

The purpose of this paper (part II in the series on thyroid hypothyroidism.5,7Incontrast,patientswithsubacute disorders) is to discuss the dental management of patients thyroiditis may develop a transient period of hyperthy- with hypothyroidism and thyroiditis. The dentist may de- roidism(TableI).5,7,8Hypothyroidismcanoccurasa tect early signs and symptoms of these thyroid disorders congenitaloracquiredcondition.5,7Worldwide,the and refer the patient for medical evaluation and treatment. most common thyroid disorder is iodine deficiency In some cases, this may be lifesaving, whereas in others (diet-related) goiter. In some of these cases, hypothy- the quality of life can be improved and complications of roidism develops, and in some, hyperthyroidism re- certainthyroiddisordersavoided.1 sults. This type of goiter is called endemic if more than The dentist by history and clinical examination may 10%ofalocalpopulationisaffected.11-14Subclinical detect evidence that may be associated with one of hypothyroidism is a common, well-defined condition these disorders. Patients found to have signs and symp- thatoftenprogressestoovertdisease.15-17Inaddition, toms of thyroid enlargement or dysfunction should be concerns are evident that the subclinical states may referredfordiagnosisandpossibletreatment.1-5 contribute to hyperlipidemia and other complica- tions.6,18,19 HYPOTHYROIDISM Enlargements of the thyroid gland, termed a goiter, Incidence, Prevalence, and Demographics can be diffuse, nodular, singular, functional, or non- Hypothyroidism in Great Britain occurs at a rate of 3 functional.5,7Simplegoiteraccountsforabout75%of cases per 1000 women per year. The number of estab- allthyroidswellings.5Hashimoto’sthyroiditisleadsto lished cases was reported to be 14 per 1000 women. The number of established cases in men was 1 per 1000. The mean age at diagnosis was 57 years. About Professor emeritus, University of Minnesota, Minneapolis, MN. 1079-2104/$ - see front matter one third of all cases resulted from surgical or radiation 20 © 2006 Mosby, Inc. All rights reserved. treatmentforhyperthyroidism. doi:10.1016/j.tripleo.2005.05.070 In the United States hypothyroidism occurs in about

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Table I. Classification of hypothyroid disorders and thyroiditis8-10 Disorder Causes Hypothyroidism Primary (cretinism, Idiopathic (end-stage Hashimoto’s myxedema) disease) Iatrogenic (131I, surgery, radiation) Agenesis or dyplasia Goitrous Hashimoto’s thyroiditis Iodine deficiency Antithyroid agents Insufficient stimulation of the thyroid Secondary (pituitary) Isolated TSH deficiency TSH synthesis defect Defect in TSH receptor Thyroiditis Hashimoto’s Subacute Pyogenic Chronic fibrosing (Riedel’s) Chronic thyroiditis with transient thyrotoxicosis TSH, thyroid-stimulating hormone.

9 Fig 1. Gross clinical hypothyroidism showing nonpitting 1%to2%ofthegeneralpopulaton. Itoccursin3%to edema in the skin of the face. Note the dry, puffy facial 4% of ill older patients admitted to the hospital. It is 5 appearance and the course hair. The patient had hypothermia, to 6 times more common than hyperthyroidism. It is the skin was cold, and she showed mental apathy. (With estimated that 10% of the women older than the age of permission from Forbes CD, Jackson WF. Color atlas and text 40 years have a thyroid hormone deficiency caused by of clinical medicine. 3rd ed. St Louis: Mosby; 2003. p. 311.) autoimmunethyroiddisease.14Bothhypothyroidism and hyperthyroidism are 5 or more times common in womenthaninmenintheUnitedStates.20,21 Acquired impairment of thyroid function affects and (3) insufficient stimulation of a normal gland (hy- about 2% of adult women and about 0.1% to 0.2% of pothalamic or pituitary disease or defects in the throid- adult men in North America. Neonatal screening pro- stimulatinghormone[TSH]molecule).5,7,22Primary grams in many areas of the world show that hypothy- and goitrous hypothyroidism account for 95% of all roidismispresentin1ofevery4000newborns.7,9 cases.9 Permanent hypothyroidism also occurs about once in Most infants with permanent congenital hypothy- every3500to4000livebirthsintheUnitedStates.5,7,22 roidism have thyroid dysgenesis: ectopic, hypoplastic, Transient hypothyroidism occurs in 1% to 2% of new- or thyroid agenesis. The acquired form may follow borns.7,9 thyroid gland or pituitary gland failure. Radiation of the The incidence of hypothyroidism is 10 times higher thyroid gland (radioactive iodine), surgical removal, thanaverageiniodine-deficientareas.9Theincidence and excessive antithyroid drug therapy are responsible also is increased in areas exposed to waterborne goitro- for the majority of these cases of hypothyroidism; how- gens or where there is excessive consumption of goitro- ever,somecasesappearwithnoidentifiablecause.5,7 genssuchascassava.9Theincidenceisincreasedin areasexposedtoexcessiveradiation.9 Clinical Presentation Neonatal cretinism is characterized by dwarfism; Etiology and Pathogenesis overweight; a broad, flat nose; wide-set eyes; thick lips; Thecausesofhypothyroidism(TableI)canbedi- a large, protruding tongue; poor muscle tone; pale skin; vided into 3 main categories: (1) primary, or permanent stubby hands; retarded bone age; delayed eruption of loss or atrophy of thyroid tissue; (2) goitrous hypothy- teeth; malocclusions; a hoarse cry; an umbilical hernia; roidism (hypothyroidism with compensatory thyroid andmentalretardation.5,7Allofthesecharacteristics enlargement due to impairment of hormone synthesis); canbeavoidedwithearlydetectionandtreatment.5,7 OOOOE 150 Little August 2006

Table II. Clinical findings and treatment of thyroiditis Condition Type Functional status Treatment

Thyroiditis Hashimoto’s – rubbery firm goiter, Later in disease T4,T3, and TBG Thyroid hormone, surgery in hypothyroidism develops later are decreased, TSH becomes rare cases (compression of elevated vital tissues) Subacute – enlarged, firm, tender Hyperthyroid returning to Aspirin, prednisone, gland, pain that may radiate to euthyroid status propranolol for symptoms ear or jaw of thyrotoxicosis Pyogenic – pain, tenderness in Euthyroid Incision and drainage, gland, fever, malaise appropriate antibiotics Chronic fibrosing – hard, fixed, Usually remains euthyroid, Usually none, surgery if enlarged gland hypothyroid status can occur vital tissues compressed, thyroid hormone Chronic with thyrotoxicosis – firm, Hyperthyroid for 5 to 6 months Propranolol for symptoms of nontender, enlarged gland returning to euthyroid status thyrotoxicosis TBG, thyroid-binding globulin; TSH, thyroid-stimulating hormone.

The onset of hypothyroidism in older children and count with indices is obtained to detect anemia that may adults(Fig1)ischaracterizedbyadullexpression; beassociatedwithhypothyroidism.9 puffyeyelids;alopeciaoftheouterthirdoftheeye- brows; palmar yellowing; dry, rough skin; dry, brittle, Treatment and coarse hair; increased size of the tongue; slowing of Patients with hypothyroidism are treated with syn- physical and mental activity; slurred, hoarse speech; thetic preparations containing sodium levothyroxin anemia; constipation; increased sensitivity to cold; in- (Synthyroid) (LT4) or sodium liothyronine (Leotrix) 5,7 creased capillary fragility; weight gain; muscle weak- (LT3). Theusualprescriptionforidealbodyweight 5,7 ␮ ␮ ness;anddeafness. for LT4 is 75 gto112 g per day for women and 125 The accumulation of subcutaneous fluid (intracellu- ␮gto200␮gperdayformen.5,7Areductionofabout larly and extracellularly) is usually not as pronounced 20% for thyroid hormone replacement is seen in hypo- in patients with pituitary myxedema (suprathyroid hy- thyroidpatients70yearsofageorolder.7Hypothyroid pothyroidism) as it is in those with primary (thyroid) patients receiving warfarin or other related oral antico- 5,7 myxedema. Theserumcholesterollevelsareelevated agulants when treated with T4 may have further pro- in thyroid myxedema and are closer to normal values in longing of the prothrombin time and could be at risk for thepatientswithpituitarymyxedema.5,7Untreatedpa- hemorrhage.5,7Inaddition,hypothyroidpatientswith tients with severe myxedema may develop hypothermic diabetes have a decreased need for insulin or sulfonyl- comathatmaybefatal.5,7 ureas and may become hyperglycemic when treated 5,7,23 with T4. Women with hypothyroidism need to Diagnosis increasetheirthyroidhormonereplacementdosagedur- The diagnosis of hypothyroidism is based on history, ingpregnancy.24 clinical findings, and laboratory investigation. The pri- mary laboratory test used for the diagnosis is the TSH Prognosis assay.9Theserumlevelsareraisedifthepatienthas If treatment is started early and is maintained, a overtormildprimaryhypothyroidism.9TheTSHmay complete return to normal thyroid state occurs after be normal or low in cases of suprathyroid (pituitary severalmonths.9Interruptionoftreatmentwillresultin dysfunction) hypothyroidism. Free T4 assay reveals the return of symptoms. Untreated hypothyroidism may reduced free T4levelsinovertdiseasebutnormallevels lead to myxedema coma, particually in the elderly. are found in patients with subclinical hypothyroidism. Myxedema coma even when treated aggressively has a Only about one third of the patients with overt hypo- mortalityrateof0%to50%.9 9 thyroidism show reduced levels of free T3. Thyroid autoantibody assay (preoxidase antibodies [TPOAb], Complications and thyroglobulin antibodies [TgAb]) shows a positive Patients with untreated hypothyroidism are sensitive result in more than 95% of patients with autoimmune to the actions of narcotics, barbiturates, and tranquiliz- thyroiditis.9Serumlipidlevelsareusuallymeasuredto ers,sothesedrugsmustbeusedwithcaution.5,7Smok- detect dyslipidemia that often is associated with pri- ingcanworsenthedisease.25Thereisanincreased mary hypothyroidism. In addition, complete blood susceptibility to infection in patients with severe hypo- OOOOE Volume 102, Number 2 Little 151

dilutional hyponatremia and the occasional hypoglyce- mia.5,7

THYROIDITIS Thyroiditis is inflammation of the thyroid gland and may arise due to a variety of causes. There are 5 types of thyroiditis: Hashimoto’s, subacute, Riedel’s chronic fibrosing, chronic with thyrotoxicos pyogenic, (Table II).5,8Radiationtherapyanddrugssuchaslithiumand amiodaronealsomaycausethyroiditisiatrogenically.5,8 In some cases (subacute thyroiditis) the inflammation can result in transient hyperthyroidism due to follicle damageandreleaseofpreformedthyroidhormone.8In contrast, Hashimoto’s thyroiditis (chronic autoimmune thyroiditis) results in progressive hypothyroidism. Sup- purative thyroiditis requires urgent antibiotic therapy andevaluationbyaspecialist.5,8

Clinical Findings Hashimoto’s thyroiditis is the most common cause of primaryhypothyroidismintheUnitedStates.8Itisan autoimmune disorder presenting most often as an asymptomaticdiffusegoiter(Fig2).Hightitersof circulating thyroid autoantibodies and thyroid antigen- specific T cells are found. It usually affects young and middle-aged women. However, it can occur in men (20 timesmorecommoninwomen)andatanyage.8Bythe time the diagnosis is established, most patients are Fig 2. Goiter associated with Hashimoto’s thyroiditis. This hypothyroid. There is often a family history of Hashi- patient has severe hypothyroidism. (With permission from moto’s thyroiditis or other autoimmune thyroid disor- Forbes CD, Jackson WF. Color atlas and text of clinical 5,8 medicine. 3rd ed. St Louis: Mosby; 2003. p. 312.) ders. Itmaybeassociatedwithotherautoimmune diseases such as pernicious anemia and type 1 diabetes mellitus. Early in the disease the thyroid is enlarged and firm and may have a nodular consistency. Late in the thyroidism. Megacolon, psychosis with paranoia, and diseasetheglandmaybeatrophiedandnotpalpable.5,8 infertility are complications that may occur in patients Subacute thyroiditis is uncommon and often follows withseveredisease.9 upperrespiratorytractviralinfection.8Patientsoften Myxedema heart disease may occur in patients with present with an enlarged, painful, tender gland with severe primary hypothyroidism. The heart becomes en- signsandsymptomsofhyperthyroidism.5,8Thereisa larged due to dilation and pericardial effusion. It is marked increase in the erythrocyte sedimentation rate usually asymptomatic and is usually not associated with (ESR) a low radioactive iodine uptake. There may be a an additional risk of morbidity. It regresses after several brief phase of hypothyroidism. Recovery of normal monthsofthyroidhormonetherapy.9 thyroid function can be expected. Subacute thyroiditis Stressful situations such as cold, operations, infec- has a peak incidence in the third through fifth decades. tions, or trauma may precipitate a hypothyroid (myx- It is about 4 times more common in women than edema)comainuntreatedhypothyroidpatients.5,7The men.5,8 external manifestations of severe myxedema, bradycar- Painlessthyroiditisalsoisanautoimmunedisorder.8 dia, and severe hypotension are just about always Patients usually present with signs and symptoms of present.5,7Myxedematouscomaoccursmostoftenin hyperthyroidism without thyroid pain or tenderness or severely hypothyroid elderly patients. It is more com- fever. The ESR is normal and the radioactive iodine mon during the winter months, and has a high mortality uptake is abnormally low. Transient hypothyroidism rate.5,7Hypothyroidcomaistreatedbyparenterallevo- may occur before normal thyroid function returns. It thyroxin (T4), steroids, and artificial respiration. Hyper- occurs in up to 10% of postpartum females and is more tonic saline and glucose may be required to alleviate commoninfemalesthanmales.5,8 OOOOE 152 Little August 2006

Table III. Dental management of the hypothyroid pated for the presence of a pyramidal lobe. Although patient difficult to detect, the normal thyroid gland can be 2,5 Clinical setting Hypothyroid palpatedinmanypatients. Itmayfeelrubberyand Detection of Symptoms may be more easily identified by having the patient undiagnosed Signs swallowduringtheexamination.1Asthepatientswal- disease Refer for medical Dx and Rx lows, the thyroid rises; lumps in the neck that may be Diagnosed disease Original diagnosis and Rx associated with it also rise (move superiorly). Nodules Past treatment Current treatment in the midline area of the thyroglossal duct move up- 1 Lack of signs and symptoms wardwithprotrusionofthepatient’stongue. Presence of any complications An enlarged thyroid gland caused by hyperplasia Untreated or poorly Avoid surgical procedures (goiter) feels softer than the normal gland. Adenomas controlled Treat oral infection and carcinomas involving the gland are firmer on pal- Avoid CNS depressants such as narcotics, 2,5 barbiturates pationandareusuallyseenasisolatedswellings. Well controlled Avoid oral infections Patients with Hashimoto’s disease or Riedel’s thyroid- Implementation of normal procedures and itis have a much firmer gland on palpation than the management normalgland.8Patientswithsuppurativethyroiditis Medical crisis Recognition and initial management of may have fever, a tender gland, erythema of the skin (rare) myxedematous coma Seek medical aid over the thyroid, and tender cervical lymphadenopathy. Hydrocortisone (100 to 300 mg) In general, the patient with mild symptoms of un- Cardiopulmonary resuscitation treated hypothyroidism is not in danger when receiving CNS, central nervous system; Dx, diagnosis; Rx, treatment. dental therapy. Central nervous system (CNS) depres- sants, sedatives, or narcotic analgesics may cause an exaggerated response in patients with mild to severe hypothyroidism. These drugs must be avoided in all Suppurative thyroiditis is caused by microbial infec- patients with severe hypothyroidism and used with care tionofthethyroid.8Patientspresentwithsevereneck (reduced dosage) in patients with mild hypothyroidism; pain, fever, focal thyroid tenderness, and erythema of however, patients with untreated severe symptoms of the overlying skin. It is an acute infection that may hypothyroidism may be in danger if dental treatment is 1 require fine-needle aspiration and culture to determine rendered. Thisisparticularlytrueofelderlypatients theappropriateantibiotictherapy.5,8Itmayalsorequire with myxedema. A myxedematous coma can be pre- surgical incision and drainage if an abscess is present. cipitated by CNS depressants, surgical procedures, and It is rare and when found is seen in immunocompro- infections; thus, once again, the major goal of the mised individuals and those with penetrating neck dentist is to detect these patients and refer them for wounds.8 medical management before any dental treatment is Riedel’s thyroiditis is a fibrous infiltration of the rendered(TableIII).1 thyroidglandofunknownetiology.8Itmayrepresenta Patients with less severe forms of hypothyroidism variant of Hashimoto’s thyroiditis. It presents as a also should be identified when possible, because the slowly enlarging stony neck mass, which may extend quality of their life can be greatly improved with med- beyond the thyroid gland. As it gets larger it may cause ical treatment. In young individuals, permanent mental compressive symptoms such as dyspnea, dysphagia, retardation can be avoided with early medical manage- hoarseness,andthesensationofchoking.5,8Theclini- ment. In addition, oral complications of delayed erup- cal course is unpredictable and may require surgery. It tion of teeth, malocclusion, enlargement of the tongue, occurs predominantly in females. Riedel’s thyroiditis and skeletal retardation can be prevented with early may eventually lead to clinically significant hypothy- detectionandmedicaltreatment.1 roidism.8 Once the hypothyroid patient is under good medical care, no special problems are presented in terms of Dental Management dental management, except for dealing with the maloc- Examination of the thyroid gland should be part of a clusionandenlargedtongueifpresent.1 head and neck examination performed by the dentist. Patients with subacute thyroiditis and painless thy- The anterior neck region can be scanned for indications roiditis may present with symptoms of hyperthroidism of old surgical scars; the posterior dorsal region of the (see part I for discussion of hyperthyroidism) and tongue should be examined for a nodule that could should be referred for medical evaluation and treat- represent lingual thyroid tissue; and the area just supe- ment. Once the hyperthyroidism has been managed the rior and lateral to the thyroid cartilage should be pal- patient can return for dental treatment. Patients with OOOOE Volume 102, Number 2 Little 153 signs and symptoms suggesting suppurative thyroiditis Williams textbook of endocrinology. 9 ed. Philadelphia: W. B. should be referred immediately for medical evaluation Saunders Company; 1998. p. 389-515. and treatment. After treatment of the acute symptoms 12. Wartofsky L. Diseases of the thyroid. In: Fauci AS, Braunwald E, Isselbacher KJ, Wilson JD, Martin JB, Kasper DL, et al., the patient can return for continuation of dental treat- editors. Harrison’s principles of internal medicine. 14 ed. New ment. York: McGraw-Hill; 1998. p. 2012-35. 13. Gharib H. Diffuse nontoxic and multinodular goiter. In: Bardin Oral Findings CW, editor. Current therapy in endocrinology and metabolism. Infants with cretinism may demonstrate thick lips, 5th edition ed. St. Louis: Mosby; 1994. p. 99-102. 14. Carnell NE, Wilber JF. Primary hypothyroidism. In: Bardin CW, enlarged tongue, delayed eruption of teeth, and result- editor. Current therapy in endocrinology and metabolism. 5th ing malocclusion. The only specific oral change mani- edition ed. St. Louis: Mosby; 1994. p. 82-86. fested by adults with acquired hypothyroidism is an 15. Hoogendoorn EH, Den Heijer M, Van Dijk AP, Hermus AR. enlargedtongue.1Patientswithsubacutethyroiditis Subclinical hyperthyroidism: to treat or not to treat? Postgrad may complain of oral pain that is referred from the Med J 2004;80(945):394-8. 10 16. Lock RJ, Marden NA, Kemp HJ, Thomas PH, Goldie DJ, thyroidgland. Gompels MM. Subclinical hypothyroidism: a comparison of strategies to achieve adherence to treatment guidelines. Ann Clin REFERENCES Biochem 2004;41(Pt 3):197-200. 1. Little JW. Thyroid disease. In: Little JW, Falace DA, Miller CS, 17. Imaizumi M, Akahoshi M, Ichimaru S, Nakashima E, Hida A, Rhodus NL, editors. Dental management of the medically com- Soda M, et al. Risk for ischemic heart disease and all-cause promised patient. 6 ed. St. Louis: Mosby; 2002. p. 283-303. mortality in subclinical hypothyroidism. J Clin Endocrinol 2. Schlurnberger M-J, Filetti S, Hay ID. Benign and malignant Metab 2004;89(7):3365-70. nodular thyroid disease. In: Larsen PR, Kronenberg HM, 18. Biondi B, Klein I. Hypothyroidism as a risk factor for cardio- Melmed D, Polonsky KS, editors. Williams Textbook of Endo- vascular disease. 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