surgicaltreatmentforunexplainedseverepainof thethyroidgland...

Hindawi Publishing CorporationCase Reports in MedicineVolume 2011, Article ID 349756, 7 pagesdoi:10.1155/2011/349756

Case Report

Surgical Treatment for Unexplained Severe Pain ofthe Thyroid Gland: Report of Three Cases and ConciseReview of the Literature

Jan van Schaik,1 Olaf M. Dekkers,2 Eleonora P. M. van der Kleij-Corssmit,2

Johannes A. Romijn,2 Hans Morreau,3 and Cornelis J. H. van de Velde1

1 Department of Surgery, Leiden University Medical Center, P.O. Box 9600, 2300 RC Leiden, The Netherlands2 Department of Endocrinology, Leiden University Medical Center, P.O. Box 9600, 2300 RC Leiden, The Netherlands3 Department of Pathology, Leiden University Medical Center, P.O. Box 9600, 2300 RC Leiden, The Netherlands

Correspondence should be addressed to Cornelis J. H. van de Velde, c.j.h.van de [email protected]

Received 14 October 2010; Accepted 13 January 2011

Academic Editor: Nam Jong Paik

Copyright © 2011 Jan van Schaik et al. This is an open access article distributed under the Creative Commons Attribution License,which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Painful thyroid has a limited differential diagnosis. In rare cases, no clear cause can be found after careful clinical, biochemical,and radiological analysis. This may lead to extensive patient morbidity and frustration when symptomatic treatment provesinsufficient. Hemithyroidectomy or total thyroidectomy may then be the last resort for doctor and patient. Three cases ofunexplained painful thyroid which were successfully treated with hemi or total thyroidectomy are presented. In two cases extensivehistological evaluation did not yield a satisfactory explanation for the extreme thyroid pain. In one case histological evaluation ofthe thyroid revealed Hashimoto’s thyroiditis. Review of the literature does not mention surgical treatment for unexplained painfulthyroid, and only 15 cases of surgical treatment for painful Hashimoto’s thyroiditis are presented. Surgical therapy is a successfulfinal option in the treatment of unexplained painful thyroid and painful Hashimoto’s thyroiditis.

1. Introduction

Painful thyroid has a limited differential diagnosis. In addi-tion to trauma and nodular hemorrhages, subacute thy-roiditis, also known as de Quervain thyroiditis, is the mostcommon cause [1]. Subacute thyroiditis is a mostly bilateralinflammatory disorder causing a slightly swollen, tenderthyroid gland, frequently accompanied by thyrotoxicosis.Markedly elevated erythrocyte sedimentation rate and ele-vated C-reactive protein levels are hallmarks of this disorder.A viral cause has been proposed, as it is often preceded byan upper respiratory tract infection. The condition is self-limiting and symptomatic treatment with analgetics usuallysuffices. Sometimes corticosteroids are needed. Rare causesof a painful thyroid gland are infection, radiation induced-thyroiditis, malignancy, and neuralgia of the superior laryn-geal nerve [1–3]. In case of infection, surgical therapy canbe indicated when antibiotic therapy is inadequate ordrainage of an abscess is necessary. Nodular hemorrhages

and radiation-induced thyroiditis are usually self-limitingconditions [3]. Neuralgia of the superior laryngeal nerveis a complex pain disorder and may require high-doseanalgetics and peripheral blockade [2, 4, 5].

In rare cases, no clear cause for a painful thyroid glandcan be found after careful clinical, biochemical, and radio-logical analysis. This may lead to extensive patient morbidityand frustration when symptomatic treatment proves insuffi-cient. Hemithyroidectomy or total thyroidectomy may thenbe the last resort for doctor and patient. Three cases of unex-plained painful thyroid that were successfully treated withsurgical therapy are presented, and the differential diagnosisis discussed.

2. Case 1

A 41-year-old Caucasian woman with a history of a cesareansection and a diagnostic laparoscopy presented with anextremely painful right thyroid gland since four months.

2 Case Reports in Medicine

Figure 1: Diffuse hyperplasia with prominent uncomplicatedhyperplastic nodes and some lymphocytic thyroiditis (Hematoxy-lin-eosin, ×200).

Some weeks before the onset of the pain she suffered froman upper respiratory tract infection. There was no fever. Thepain was constant and increased on swallowing. The patientwas initially treated by the family physician. Analgeticssuch as nonsteroidal anti-inflammatory drugs and mor-phinomimetics did not decrease the pain. On physical exam-ination the right thyroid lobe was not enlarged but extremelypainful on palpation. There were no obvious thyroid nodes.The left thyroid lobe was normal. There were no enlargedlymph nodes in the neck. Laboratory tests showed euthy-roidism: thyroid stimulating hormone (TSH) level was0.59 mU/L (normal value 0.4–4.4 mU/L), free thyroxine(T4) level was 19.4 pmol/L (normal value 10–24 pmol/L),and triiodothyronine (T3) level was 1.7 nmol/L (normalvalue 1.3–2.6 nmol/L). Thyroid peroxidase (TPO) antibodylevel was low (<10 ku/L). Leukocyte count (6,400/mm3),erythrocyte sedimentation rate (11 mm/h), and C-reactiveprotein level (7 mg/dL) were within normal limits. Ultra-sonography showed multiple nodes in the right thyroid lobewith a maximum diameter of 12 mm without any signs ofhaemorrhage or abscess. The dental surgeon and otolaryn-gologist excluded referred pain from dental or nasopharyn-geal pathology. The patient was treated with analgetics andsubsequently corticosteroids for several weeks based on thepresumed diagnosis of subacute thyroiditis. However, thisdid not resolve the symptoms. The pain was increasinglyinvalidating and led to absence of work. Finally, 6 monthsafter onset of symptoms, a right hemithyroidectomy wasperformed. The specimen measured 5×3×3 cm. Histologicalstudy revealed diffuse hyperplasia with prominent uncom-plicated hyperplastic nodes and some mild lymphocyticthyroiditis (Figure 1). Immediately after surgery the pain haddisappeared completely. Up to one year following surgery thepatient was free of pain and had a normal thyroid function.

3. Case 2

A 41-year-old Caucasian woman with a history of laparo-scopic gastric banding for morbid obesity and a laparoscopiccholecystectomy presented with an extremely painful rightthyroid lobe. Since several months she had experienced pal-pitations and heat intolerance, and since three weeks extreme

pain had developed in the right thyroid lobe during a periodof fever and malaise. She had not noticed any enlargementof the thyroid gland. There had been no weight loss or otherphysical changes. Analgesic therapy did not relieve the symp-toms. On physical examination there were no signs ofthyrotoxicosis. There was a slightly enlarged left thyroidlobe without any palpable nodes and a palpable node ofapproximately 2 cm in the right lobe, which was very painfulon examination. There were no enlarged lymph nodes inthe neck. Laboratory tests revealed thyrotoxicosis: TSH levelwas 0.02 mU/L (normal value 0.4–4.4 mU/L) and free thy-roxine (T4) level 60.7 pmol/L (normal value 10–24 pmol/L).There were no detectable thyroid-stimulating antibodies orTPO antibodies. There was no leukocytosis (4,400/mm3),erythrocyte sedimentation rate was 29 mm/h, and there wasa slight increase in C-reactive protein (23 mg/dL). A Tc-99Mscan showed a slightly enlarged thyroid with normal 24-hour uptake, and a cold node on the right side of 4 cm, aswell as a node on the left side (3 cm) with normal uptake.Fine-needle aspiration yielded no conclusive diagnosis. Theotolaryngologist excluded any pharyngeal or tracheal pathol-ogy. The following causes were considered in the differentialdiagnosis: subacute thyroiditis of de Quervain or an earlyhyperthyroid phase of Hashimoto’s thyroiditis (Hashitoxi-cosis). The thyroid function returned to normal within twomonths without any antithyroid therapy. However, the righthemithyroid remained extremely painful. The patient wastreated with nonsteroidal anti-inflammatory drugs and mor-phinomimetics for several weeks without any improvementof symptoms. Finally, four months after onset of pain, a righthemithyroidectomy was performed. The specimen measured4×4×2 cm. Histological study showed some nodular hyper-plasia with degenerative changes, a limited lymphocytic thy-roiditis, and a focal area with sclerosis. Elsewhere, bleedingand signs of previous bleeding were seen. Remarkable was thepresence of adipose metaplasia of thyroid stroma (Figure 2).Immediately after surgery the pain had disappeared com-pletely. Up to several months after surgery, the patient wasfree of pain and had a normal thyroid function.

4. Case 3

A 17-year-old Caucasian woman with no prior medicalhistory presented with an extremely painful thyroid. She hadnoticed gradual enlargement of the thyroid gland since fiveyears, but more rapid growth during the last six months,accompanied by pain on the right side. Moreover, she haddifficulty swallowing because of pain, resulting in decreasedfood intake and 10 kg weight loss during the last six months.In addition, she complained of a coarse voice since severalmonths. There was no fever. Analgetic therapy did not relievethe symptoms. On physical examination there were no signsof hypo- or hyperthyroid function. There was a WHO gradeII goiter without palpable nodules which was extremelypainful on examination. There were no enlarged lymphnodes in the neck, and there were no signs of respiratorydistress. Laboratory tests showed biochemical euthyroidism:TSH level was 3.77 mU/L (normal value 0.4–4.4 mU/L), free

Case Reports in Medicine 3

Figure 2: Nodular hyperplasia with degenerative changes, a lim-ited lymphocytic thyroiditis and adipose metaplasia of thyroidstroma. Some signs of bleeding and previous bleeding are seen(Hematoxylin-eosin, ×40).

Figure 3: Severe lymphocytic infiltration with formation of lym-phatic follicles and Hurthle cells (Hematoxylin-eosin, ×100).

thyroxine (T4) level was 13.4 pmol/L (normal value 10–24 pmol/L), and triiodothyronine (T3) level was 2.1 nmol/L(normal value 1.3–2.6 nmol/L). TPO antibody level was in-creased (459 ku/L). There was no increased leukocyte count(3,400/mm3) or increased erythrocyte sedimentation rate(5 mm/h). An I-123 scan showed a homogenously enlargedthyroid (slightly more increased on the right side) witha 24-hour uptake of 42%. The otolaryngologist excludedany pharyngeal or tracheal pathology. Esophagogastroscopyrevealed no pathology explaining difficulty swallowing orweight loss. Fine-needle aspiration of the thyroid revealedlymphocytic thyroiditis, in accordance with the diagnosis ofHashimoto’s thyroiditis. The patient was treated with nons-teroidal anti-inflammatory drugs and corticosteroids for sev-eral months without any improvement of symptoms. Finally,eight months following onset of pain, a total thyroidectomywas conducted. Histological study indeed showed a verysevere lymphocytic thyroiditis with formation of lymphaticfollicles (Figure 3). Immediately after surgery the pain haddisappeared completely. Up to several years following surgerythe patient was free of pain.

5. Discussion

This case series describes three patients with extreme, inval-idating pain located within the thyroid gland, which could

not adequately be managed by symptomatic treatment.The complaints resolved completely and immediately uponsurgical removal of the painful thyroid tissue.

The clinical presentation in the first case is reminiscent ofsubacute thyroiditis which is sometimes preceded by a viralupper respiratory tract infection. However, unilateral pain,normal levels of C-reactive protein, and a normal erythrocytesedimentation rate are not in agreement with this diagnosis.Moreover, subacute thyroiditis is often characterized by thy-rotoxicosis followed by hypothyroidism. The symptoms usu-ally improve dramatically following the administration ofnonsteroidal anti-inflammatory drugs. Finally, the histolog-ical specimens did not show the typical changes expectedin subacute thyroiditis nor yielded any other cause for thepatient’s complaints.

In the second case, the differential diagnosis includedearly hyperthyroid phase of Hashimoto’s thyroiditis (HT)and subacute thyroiditis. Unilateral pain, however, is not typ-ical for either condition. The absence of thyroid antibodieswould support subacute thyroiditis. However, a normal 24-hour I-123 uptake or Tc-99M scan and the only slightly ele-vated erythrocyte sedimentation rate and C-reactive proteinlevels are more in favour of HT. We could not documenthistological changes confirming HT nor subacute thyroiditis.

Histological evaluation of the thyroid gland of the thirdcase clearly identified HT. This autoimmune disease is char-acterized by painless goiter, and hypothyroidism is some-times preceded by a hyperthyroid phase [1]. TPO antibodiesare usually elevated, but they may be low or even absent inHT. Rarely, it may present as a painful goiter and sometimesclinically resembles subacute thyroiditis. Although painfulHT often presents with fever, transient thyrotoxicosis, ele-vated erythrocyte sedimentation rate, and elevated levelsof C-reactive protein, patients may also be euthyroid orhypothyroid, and infection parameters may be normal [10].The diagnosis of HT in the case of an extremely painfulthyroid is therefore typically based on histological studies.Although painful HT has been previously described, theliterature is limited to case series [6–12]. Initial treatment forpainful HT is typically symptomatic with nonsteroidal anti-inflammatory drugs and corticosteroids or may be focusedon hormone replacement therapy. Quite often this might notbe sufficient. In these cases surgical treatment has provena successful option, in accordance with our observation [6–9]. Clinical features and pain relief following surgery ofall patients presented in the literature that were surgicallytreated for painful HT are summarized in Tables 1 and 2.

Speculation on the cause of pain in the first two casesincludes atypical viral infection since both patients had expe-rienced a prodromal period of fever and malaise. Anotherspeculation is that even uncomplicated thyroid nodes mightcause severe pain in exceptional cases.

The differential diagnosis of unilateral thyroid painincludes superior laryngeal neuralgia, a complex pain dis-order which is thought to represent a “referred pain” fromthe pharyngeal and laryngeal regions. A viral infection hasalso been proposed. A substrate for superior laryngeal neu-ralgia is seldom found. The pain is typically located betweenthe thyroid and the ear and is described as paroxysmal and


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Table 2: Pain relief to treatment and surgical pathology in fifteen cases of painful Hashimoto’s thyroiditis.

Authors No.Pain relief toT4

Pain relief tosteroids

Pain relief toaspirin orNSAIDS

Time frompain onset tosurgery(years)

Pain relief afterthyroidectomy

Type ofsurgery

Pathology

Kon andDeGroot [6]

1 No No Not given 2Total,permanent

NTTFocal lymphocyticthyroiditis

2 No No Not given 2Total, butrecurrence after1 year

NTTHashimoto’sthyroiditis, incidentalpappilary cancer

3 NoRapid butrelapsing

Not given 3.1Total,permanent

NTTNear end stagethyroiditis


No to NSAID 1.1Total,permanent

STTFocal lymphoidinfiltrates, sparseHurthle cells

5 Partial Not givenUnable totolerate NSAID

6.2Total,permanent

STTFibrosis, large reactivelymphocyte follicles,Hurthle cell clusters

6 No Not given No 0.5 Partial STTDiffuse lymphocyticthyroiditis


Partial 0.6 Total, relapsed STTHashimoto’sthyroiditis

Ohyeet al. [7]

1Yes butrelapsing

Rapid butrelapsing

NM 2.7Total,permanent

TTSevere fibrosis,lymphocyticinfiltration







4 Not givenRapid butrelapsing


TTGiant cells, mildfibrosis, remainingfollicular structure

Gourgiotiset al. [8]

1 No Yes, relapsing NM >10Total,permanent

TT

Severe fibrosis,lymphocyticinfiltration, Hurthlecells

2 No NM NM 2.1Total,permanent

TTLymphocyticthyroiditis, focalHurthle cells

Zimmermanet al. [9]

1 No No Yes, relapsing >5Total,permanent

TTLymphocyticinfiltration

2 No Yes, relapsing Not given 0.5Total,permanent

TTLymphocyticthyroiditis

NTT: near total thyroidectomy; STT: subtotal thyroidectomy; TT: total thyroidectomy.

“electrical”. There is usually a trigger point, and episodes maybe accompanied by nausea or excessive lacrimation. Treat-ment is symptomatic and may require high-dose analgeticsand peripheral blockade [2, 4, 5]. However, none of theabove-mentioned clinical presentations resembled superiorlaryngeal neuralgia.

In conclusion, we describe three patients with extremeinvalidating pain which severely interfered with daily activ-ities and work. In all cases symptomatic treatment was notsuccessful. The pain was immediately relieved by hemithy-roidectomy or total thyroidectomy. Remarkably, extensive

histological evaluation did not yield a satisfactory explana-tion for the extreme thyroid pain in two cases, and in onecase, HT was found. This indicates that surgical therapy isa successful final option in the treatment of unexplainedpainful thyroid and painful HT.

Conflict of Interest

There is no conflict of interests that could be perceived asprejudicing the impartiality of the research reported.


Funding

This research did not receive any specific grant from anyfunding agency in the public, commercial, or not-for-profitsector.

References

[1] E. N. Pearce, A. P. Farwell, and L. E. Braverman, “Thyroiditis,”New England Journal of Medicine, vol. 348, no. 26, pp. 2646–2655, 2003.

[2] O. Aydin, M. Ozturk, and Y. Anik, “Superior laryngeal neural-gia after acute laryngitis and treatment with a single injectionof a local anesthetic,” Archives of Otolaryngology, vol. 133, no.9, pp. 934–935, 2007.

[3] A. S. Fauci, E. Braunwald, K. J. Isselbacher et al., Eds., Harri-son’s Principles of Internal Medicine, McGraw-Hill, Singapore,14th edition, 1998.

[4] D. Schmidt and I. Strutz, “Superior laryngeal neuralgia,”Journal of Neurology, vol. 225, no. 3, pp. 223–225, 1981.

[5] K. T. Sato, M. Suzuki, A. Izuha, S. Hayashi, T. Isosu, andM. Murakawa, “Two cases of idiopathic superior laryngealneuralgia treated by superior laryngeal nerve block with a highconcentration of lidocaine,” Journal of Clinical Anesthesia, vol.19, no. 3, pp. 237–238, 2007.

[6] Y. C. Kon and L. J. DeGroot, “Painful Hashimoto’s thyroiditisas an indication for thyroidectomy: clinical characteristics andoutcome in seven patients,” Journal of Clinical Endocrinologyand Metabolism, vol. 88, no. 6, pp. 2667–2672, 2003.

[7] H. Ohye, S. Fukata, S. Kubota et al., “Successful treatment forrecurrent painful Hashimoto’s thyroiditis by total thyroidec-tomy,” Thyroid, vol. 15, no. 4, pp. 340–345, 2005.

[8] L. Gourgiotis, N. Al-Zubaidi, M. C. Skarulis et al., “Suc-cessful outcome after surgical management in two cases ofthe “painful variant” of Hashimoto’s thyroiditis,” EndocrinePractice, vol. 8, no. 4, pp. 259–265, 2002.

[9] R. S. Zimmerman, M. D. Brennan, and W. M. McConahey,“Hashimoto’s thyroiditis. An uncommon cause of painfulthyroid unresponsive to corticosteroid therapy,” Annals ofInternal Medicine, vol. 104, no. 3, pp. 355–357, 1986.

[10] H. Ohye, E. Nishihara, I. Sasaki et al., “Four cases ofGraves’ disease which developed after painful Hashimoto’sthyroiditis,” Internal Medicine, vol. 45, no. 6, pp. 385–389,2006.

[11] A. K. C. Leung and K. Hegde, “Hashimoto’s thryroiditissimulating De Quervain’s thyroiditis,” Journal of AdolescentHealth Care, vol. 9, no. 5, pp. 434–435, 1988.

[12] C. Shigemasa, Y. Ueta, Y. Mitani et al., “Chronic thyroiditiswith painful tender thyroid enlargement and transient thyro-toxicosis,” Journal of Clinical Endocrinology and Metabolism,vol. 70, no. 2, pp. 385–390, 1990.

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