Lingual Thyroid Presenting As Acquired Hypothyroidism in the Adulthood Katsuyoshi Tojo

CASE REPORT

Lingual Thyroid Presenting as Acquired Hypothyroidism in the Adulthood Katsuyoshi Tojo

There are numerous reported cases of lingual thyroid with an obvious prevalence in pediatric age. Such ectopic thyroid glands are probably quantitatively deficient and thyroid function may be low or at a low normal level. Apparently, most cases of ectopic thyroid tissue develop congenital hypothyroidism, the so-called cretinism. In this report, wedescribe a very rare adult malecase of lingual thyroid whodeveloped hypothyroidism in adulthood; the anomaly remained undiscovered, being without local commonsymptoms, and permitted a normal life. (Internal Medicine 37: 381-384, 1998) Key words: ectopic thyroid gland, thyroid function, cretinism

Introduction Methods Thyroid dysplasia (ectopy, hypoplasia, or aplasia) is a com- Thyroid function assessment moncause of congenital hypothyroidism. Essentially, all cases Commerciallyavailable kits were used to measureserum of thyroid aplasia and most cases of thyroid ectopy become concentrations of thyroid hormones as follows: For TSH, free clinically evident in infancy or childhood. A lingual thyroid, a triiodothyronine (FT3), free thyroxine (FT4), T3 and T4, an rare congenital anomaly first describedby Hickman in 1 869 ( 1), enzyme immunoassay (EIA) (E test [TOSOH] II (TSH), (FT3), is defined as the presence of thyroid tissue at the base of the (FT4), (TT3) and (TT4), TOSOH, Tokyo), respectively. Serum tongue. Actually, the thyroid gland develops as the thyroglossal thyroxine binding globulin (TBG) was determined by radioim- duct which grows at the base of the thyroid gland within the munoassay (RIA) (RIAgnost TBG kit, Hoechst Japan, Tokyo) foramen caecum and finally localizes in the lower neck inferior and thyroglobulin was determined by immuno-radiometric to the thyroid cartilage and anterior to the first few tracheal assay (IRMA) (Ab Bead Thyroglobulin 'EIKEN', EIKEN rings. These steps are usually completed by the 10th fetal week. Kagaku Tokyo). Anti-thyroglobulin antibody (TgAb) and anti- Anyarrest or irregularity in the normal descent of the thyroid thyroid microsomal antibody were determined by commer- gland will result in ectopy. Depending upon the anatomic cially available hemagglutination methods (TGHA:Thyroid location, an ectopic thyroid gland may be classified as lingual test and MCHA:Microsome test, Fuji Rebio, Tokyo). Titers of (at the base of the tongue), sublingual (below the tongue), TGHAand MCHA^1: 102 were defined as positive. TgAb was prelaryngeal (in front of the larynx) or substernal (in the also determined by RIA (TgAb Cosmic kit, Cosmic Co., To- mediastinum) (2). In the hypothyroid condition, oversecretion kyo). Anti-thyroid peroxidase antibody (TPOAb) was deter- of thyrotropin (TSH) causes hypertrophy of the lingual thyroid mined by RIA (TPOAb Cosmic kit, Cosmic Co., Tokyo). The producing local symptoms and in younger patients it may thyroid uptake of 123I was determined by the standard proce- induce dangerous airway obstruction. In some cases, however, dure. T3 uptake was measured by RIA (Spac T3 uptake kit, a lingual thyroid secretes adequate quantities of thyroid hor- Daiichi Radioisotope Lab., Tokyo). TSH-binding inhibitor mone during childhood but is associated with hypothyroidism immunoglobulins (TBII) were measured by the inhibition of in adolescence or adulthood. Wereport here a male adult case 125I-TSH binding to its receptor (TRAb kit, Baxter Travenol of lingual thyroid presenting as acquired hypothyroidism in Co., Tokyo) (normal range: <15%). Thyroid-stimulating anti- adulthood without any local symptoms. bodies (TSAb) were measured using cultured rat FRTL-5 cells. Bovine TSH (SigmaChemical Co., St. Louis, MO) was used as the standard for thyroid stimulation. TSAbactivity was ex-

From the Division of Endocrinology and Metabolism, the Second Department of Internal Medicine, The Jikei University School of Medicine, Tokyo Received for publication May 23, 1997; Accepted for publication December 22, 1997 Reprint requests should be addressed to Dr. Katsuyoshi Tojo, the Second Department of Internal Medicine, the Jikei University School of Medicine, 3-25-8 Nishi- Shinbashi, Minato-ku, Tokyo 105-8461

Internal Medicine Vol. 37, No. 4 (April 1998) 381 Tojo pressed as the percent stimulation of bTSH(100 mU//)-stimu- In February 1 997, his home doctor checked his thyroid function lated CAMPincrease (normal range: <180%). because of the past history of lingual thyroid, and hypothyroidism was first pointed out. On physical examination, his general condition appeared almost normal. His height was 168 Case Report cm and weight was 67.8 kg. Bloodpressure was 1 16/72 mmHg A 32-year-old manwas referred to the endocrine clinic for and pulse rate was 64/min andregular. His skin was slightly dry. evaluation of thyroid function in February 1997. He showed His voice was normal. The thyroid gland was not palpable in the normal growth and development. His fertility is normal. He has normal pretracheal location. a son and a daughter. He had been in good health except for Since the past medical information including his laboratory, duodenal ulcer. There was no history of thyroid disease in his radiological and pathological data was not available unfortu- family. He had never taken any medication which would affect nately, a series of evaluation focused on thyroid function was thyroid function. He first noticed left otalgia in March 1994 and performed to confirm previous diagnosis. Laboratory data on consulted an otolaryngist of another hospital. During a series of admission revealed no particular abnormalities (Table 1 ). Thy- screening exploration for otalgia, a round reddish and rubbery roid function on admission is shown in Table 2. Serum levels of mass, approximately 2.5 cmin diameter was seen at the base of FT3, FT4, T3, T4 and TSH were 1.80 pg/ml, 0.41 ng/dl, 0.92 ng/ the tongue by laryngoscopy. A final diagnosis ofectopic thyroid ml, 3.9 [ig/dl and 379.6 plU/ml, respectively. TGHAand gland was obtained by incision biopsy. At that time his thyroid MCHAwere both weakly positive (1: 102 and l:102, respec- function was normal. Since that time, he was free from any tively. TBII and TSAb were negative (0.8 and 155%, respec- subjective complaints, and had not received any medications. tively). T3 uptake was low or low normal (T3-index: 0.84, T3-

Table 1. Laboratory Data on Admission Hematology Urea nitrogen 21 mg/dl White blood cells 5.5X10V Creatinine 1.1 mg/dl Red blood cells 4.53xl0V Na 142 mmol// Hemoglobin 13.7 g/dl K 4.4 mmol// Hematocrit 40.6% Ca 9.7 mg/dl Platelet 215x103/ll1 Pi 3.9 mg/dl Mg 2.0 mg/dl Chemistry Fe 107 jag/dl Asparate aminotransferase 18 IU/Z Unsaturated iron binding Alanine aminotransferase 16 iu// capacity 1 64 |ig/dl Lactic dehydrogenase 118 IU/Z Total cholesterol 202 mg/dl Cholinesterase 474 mU/ml Triglyceride 130 mg/dl Alkaline phosphatase 199 IU// High density lipoprotein Leucin aminopeptidase 65 IU// cholesterol 73 mg/dl y-Glutamyl transferase 18 mU/ml Creactive protein 0.0 mg/dl Creatine phosphokinase 104 IU// Aldolase 3.1 IU///37°C Urine 7.4 g/dl Protein (-) TotalAlbumin protein 4.6 g/dl Sugar (-) A/G 1.6 Occult blood (-)

Table 2. Thyroid Function

Thyrotropin379.6 (normal: 0.34-4.04 jilU/ml) Triiodothyronine (T3) Free triiodothyronine (Free T3) Thyroxine (T4) Free thyroxine (Free T4) T3 uptake: T3-index T3-percent 123I-uptake: 3 hour 6hour Thyroxine binding globulin

0.921.803.90.410.84 (normal:0.86-1.622.36-5.004.7-11.10.88-1.670.80-1.20)ng/ml)pg/ml)jug/dl)ng/dl)

23.217780 (normal:21.5-38.1%)6.5%8.1%12-30(Hg/dl)<30ng/ml)ThyroglobulinThyroidTSHreceptorantibodyperoxidasestimulatingantibody<0.3(normal:0.8155 <0.3(normal:<0.5%)U/ml)<0.3<180%) ThyroglobulinMicrosomehemagglutination1OOxlOOx (normal:<1OOx)<1 00x)

382 Internal Medicine Vol. 37, No. 4 (April 1998) Lingual Thyroid and Hypothyroidism percent: 23.2%). Serum thyroglobulin level was extremely high thyroid with homogeneous uptake of radiolabeled iodine (Fig. (780 ng/ml), and remained at a high level during hospitalization 2). The uptake was 6.5% at 3 hours and 8.1% at 6 hours. (between 400 and 600 ng/ml). Basal metabolic rate (BMR) was -13%. Computed tomography (CT) of the pharynx revealed a Discussion round mass with high intensity in the mid region at the base of the tongue (Fig. 1). Ultrasonography of the neck revealed a Lingual thyroid is a relatively rare developmental anomaly. mass with echogenicity similar to that of thyroid tissue. No Montgomery (3) first suggested the basic diagnostic criteria thyroid tissue was found in the typical location in the lower for establishing the diagnosis: (i) a lingual mass between the neck. Diagnosis of ectopic thyroid was confirmed by 123I epiglottis and circumvallate papillae, (ii) identification of thy- scanning. 123I thyroid scintigraphy demonstrated a lingual roid tissue by biopsy, and (iii) hypothyroidism after surgical removal. Wardet al (4) later amendedthis to include uptake of radioactive iodine at the base of the tongue. It has a prevalence of approximately 1 per 100,000 to 300,000 patients (5, 6) and 1 in 4,000 cases of thyroid disease (7). Buckman and Pa (8) reported that of 140 female patients with lingual thyroid, 55% became symptomatic between the ages of 18 and 40 years, and commonpresenting symptoms are dysphagia, dyspnea, and dysphonia (9-12). Occasionally respiratory difficulty or hemorrhage can occur (13). Female patients predominated in all reported series, ranging from 75% to 89% of the cases (3, 6, 9, 14). Although there may be other thyroid tissue present, in approximately 70% of cases, the lingual thyroid is the only functioning thyroid tissue (3, 15-17). Ectopic thyroid tissue may be the site of development of a colloid goiter, hypo or hyperthyroidism, adenoma, or even carcinoma. An ectopic thyroid tissue not clinically apparent maybecomeevident when such a pathological condition develops in it. The overall prevalence of hypothyroidism in lingual thyroid varies in different series, between 14.5% and 33% (3, 6). Adult patients with lingual thyroid may present with hypothyroidism. However,features of cretinism are then usually absent imply- Figure 1. Unenhanced computed tomographic scan showing ing that the ectopic tissue has secreted adequate thyroid hor- lingual thyroid. mone during childhood, thus preventing the development of cretinism and leading to the diagnosis of hypothyroidism later in life. McGirr and Hutchison (18) postulated that the age of onset of thyroid insufficiency depended upon the amount of thyroid tissue present. The exact relationship between ectopic thyroid and hypothyroidism remains to be elucidated. Blizzard et al (19) have suggested that antibodies directed towards the thyroid cause arrest of descent during early fetal life and poor function. Gabr (20) proposed that a metabolic defect in thyroid hormonesynthesis might be in somewayrelated to the failure of descent. Alternatively, Kaplan et al (21) suggested that since the ectopic tissue is frequently hypoplastic, the maldescent may be secondary to the maldevelopmentof the gland. Thepresent case is unusual in that there wasno clinical feature due to hypothyroidism and that commonlocal symp- tomsdue to ectopic thyroid tissue wereabsent. In the literature, cases with ectopic thyroid gland developing hypothyroidism in the adulthood are quite rare (22-24). Even in such cases, most of them had features to suggest that hypothyroidism had been present from birth. The exact cause of hypothyroidism in the present case remains obscure. The development of hypothyroidism following partial surgical removal has been reported Figure 2. 123I thyroid scan showing lingual thyroid. No thy- (14, 25, 26). But this is not true of the present case. Shakir (22) roid tissue is seen in normal thyroid bed. reported a 43-year-old white female with lingual thyroid asso-

Internal Medicine Vol. 37, No. 4 (April 1998) 383 Tojo ciated with hypothyroidism and lymphomatous thyroiditis. In Weider DJ, Parker W. Lingual thyroid: review, case reports, and thera- this case, lymphomatous thyroiditis was confirmed by high peutic guidelines. Ann Oto Rhinol Laryngol 86: 841, 1977. titers of anti-microsomal and anti-thyroglobulin antibodies, Neinas FW, Gorman CA, Devine KD, Woolner LB. Lingual thyroid: clinical characteristics of 15 cases. Ann Intern Med 79: 205, 1973. along with characteristic histologic findings. Wecould not Orti E, Castells S, Qazi QH, Inamdar S. Familial thyroid disease: lingual obtain previous histological confirmation, but high serum thy- thyroid in two siblings and hypoplasia ofathyroid lobe in a third. J Pediatr roglobulin levels may lead to the hypothesis that hypothyroid 78: 675, 1971. Buckman LT, Pa W-B. Lingual thyroid. Laryngoscope 46: 765, 1936. function followed thyroiditis transforming lingual thyroid into Katz AD, Zager WJ. The lingual thyroid: its diagnosis and treatment. a fibrous tissue not sensitive to the trophic action of TSH, Arch Surg 102: 582, 1971. although thyroid autoantibodies were negative except for low Cheah JS, Tan BY, Coh EH, Chew CH. Lingual thyroid: report of a case positive titers of TGHAand MCHA.Treatment of the lingual and review of the literature. Med J Aust 2: 403, 1969. thyroid depends on its size, the presence or absence of symp- Elprana D, Manni JJ, Smals AG. Lingual thyroid. Case report and review of the literature. ORLJ Otorhinolaryngol Relat Spec 46: 147, 1984. toms, and complicating factors such as ulceration, hemorrhage, Gallo WJ, Ellis E. Management of a large lingual thyroid in the orthognathic or malignancy. It could be recommendedto use thyroid hor- surgery patient. Oral Surg Oral Med Oral Pathol 59: 344, 1985. mone in a sufficient dosage to suppress TSHstimulation and to Baker RJ, Pzanto PB. Lingual thyroid. Ann Surg 153: 310, 1960. minimize goitrous enlargement. Surgery mayonly be indicated Kamat MR, Kulkarni JN, Desai PB, Jussawalla DJ. Lingual thyroid: a if there are complications such as hemorrhage, cystic degenera- review of 12 cases. BrJ Surg 66: 537, 1979. tion, or suspected malignancy. Kansal et al (27) suggested that Fish J, Moore RM.Ectopic thyroid tissue and ectopic thyroid carcinoma: a review of the literature and report ofa case. Ann Surg 157: 212, 1963. all patients have lifelong thyroxine suppression, even those Pitchenik AE. Lingual thyroid. South Med J 71: 1 179, 1978. who are asymptomatic and who have an initially small lingual Al-Samarrai AY, Crankson SJ, Al-Jobori A. Autotransplantation of thyroid, as it will prevent its subsequent enlargement, diminish lingual thyroid into the neck. Br J Surg 75: 287, 1988. the risk of malignancy, and prevent the onset of hypothy- McGirr EM,Hutchison JH. Dysgenesis of the thyroid gland as a cause of cretinism and juvenile myxedema. J Clin Endocrinol Metab 15: 668, roidism. Ablation of the thyroid tissue with radioactive iodine 1955. is an alternative approach (28). Patients with obstructive symp- Blizzard RM, Chandler RW, Landing BH, Pettit MD, West CD. Maternal toms, suspected malignancy, ulceration, and hemorrhage, or autoimmunization to thyroid as a probable cause of athyrotic cretinism. who will fail to respond to thyroid hormone suppression should N Engl J Med263: 327, 1962. undergo iodine 131 ablation or surgical excision of thyroid Gabr M. The role of thyroid dysgenesis and maldescent in the etiology of sporadic cretinism. J Pediatr 60: 830, 1962. tissue (4) with or without autotransplantation (29, 30). In the Kaplan M, Kauli R, Lubin E, Grunebaum M, Laron Z. Ectopic thyroid present case local complications wereabsent and replacement gland: A clinical study of30 children and review. J Pediatr92: 205, 1976. with thyroxine was the only treatment required. Finally, it may Shakir KM. Lingual thyroid associated with hypothyroidism and lym- be emphasized that in any primary adult hypothyroidism, phomatous thyroiditis: a case report. Mil Med 147: 591, 1982. careful examination not only of the neck but also of the base Yeung VTF, Loong EPL, Cockram CS. Cretinism and lingual thyroid of tongue is necessary even if oropharyngeal symptomsare presenting in an adult. Postgrad Med J 63: 881, 1987. lacking. Borgoni F, Liberatori E, Giambagli M, et al. Lingual thyroid and hypothyroidism: report of a case in a middle aged woman.Panminerva Med36: 95,1994. References Sauk JJ Jr. Ectopic lingual thyroid. J Pathol 102: 239, 1970. Strickland AL, Mac fie JA, Van Wyk JJ, French FS. Ectopic thyroid gland 1 ) Hickman W. Congenital tumor of the tongue pressing down the epiglottis simulating thyroglossal duct cysts. Hypothyroidism following surgical on the larynx and causing death by suffocation sixteen hours after birth. excision. JAMA 208: 307, 1969. Trans Path Soc London 20: 160, 1869. Kansal P, Sakati N, Rifai A, Woodhouse N. Lingual thyroid: diagnosis 2) Krishnamurthy GT, BlahdWH. Lingual thyroid associated withZenker's and treatment. Arch Intern Med147: 2046, 1987. and vallecular diverticula. Report of a case and review of the literature. Schilling JA, Karr JW, Hursh JB. The treatment ofa lingual thyroid with Arch Otolaryngol 96: 171, 1972. radioactive iodine. Surgery 27: 130, 1950. 3) Montgomery ML. Lingual thyroid: acomprehensive review. WestJ Surg 43: 661, 1935; 44: 54, 122, 189, 237, 303, 373, 442, 1936. Hilless AD, Black JE. Lingual ectopia of the thyroid gland and autotransplantation. Br J Surg 63: 924, 1976. 4) Ward GE, Cantrell JR, Allan WB. The surgical treatment of lingual Wertz ML. Management of underscended lingual and subhyoid thyroid thyroid. Ann Surg 139: 536, 1954. glands. Laryngoscope 84: 507, 1974.

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