CASE REPORTpublished: 18 August 2015

doi: 10.3389/fendo.2015.00123

Edited by:Jacqueline Jonklaas,

Georgetown University, USA

Reviewed by:Onyebuchi Okosieme,

Cwm Taf University Health Board, UKBijay Vaidya,

University of Exeter Medical School,UK

Yevgeniya Kushchayeva,National Institute of Health, USA

*Correspondence:Yasser Ali Hakami,

Obesity, Endocrine and MetabolismCenter, King Fahad Medical City,Aldabab Street, P.O. Box 59046,

Riyadh 11525, Saudi Arabiadr.yasser.ali@hotmail.com

Specialty section:This article was submitted to ThyroidEndocrinology, a section of the journal

Frontiers in Endocrinology

Received: 27 April 2015Accepted: 24 July 2015

Published: 18 August 2015

Citation:Hakami YA (2015) Transient thyroiditis

after surgery for tertiaryhyperparathyroidism: a case report.

Front. Endocrinol. 6:123.doi: 10.3389/fendo.2015.00123

Transient thyroiditis after surgeryfor tertiary hyperparathyroidism:a case reportYasser Ali Hakami*

Obesity, Endocrine and Metabolism Center, King Fahad Medical City, Riyadh, Saudi Arabia

Parathyroid (PTH) exploration surgery carries the risk of developing post-operativethyroiditis due to vigorous manual manipulation of the thyroid gland during surgery. Post-operative thyroiditis has a wide spectrum of clinical manifestations. However, it remainsunderreported. Here, we describe a case of post-operative transient thyroiditis in a 33-year-old male who developed 3days after parathyroidectomy for PTH hyperplasia. Wereview the limited literature regarding this interesting entity.

Keywords: thyroiditis, thyroid function tests, hyperparathyroidism, post-operative period, parathyroidectomy,adrenergic beta-antagonists

Introduction

Post-operative thyroiditis is one cause of iatrogenic thyrotoxicosis. It usually occurs after vigorousmanual manipulation of the thyroid gland during neck or parathyroid (PTH) exploratory surgery.It has a wide spectrum of clinical manifestations, varying from asymptomatic hyperthyroxinemia toa severe overt thyrotoxic state (1).

However, this disorder remains underestimated and only a few cases have been reported. Incurrent clinical practice, this condition is likely more common and important than previouslythought.

Case Report

A 33-year-old male came to the clinic complaining of generalized bone pain associated withprogressive weakness over the last year. The patient had been diagnosed with end-stage renal diseasesecondary to glomerulonephritis 11 years before his presentation and had been on hemodialysisthree times per week for the last 10 years. The patient had no past history of thyroid disorders. Therewas no goiter on physical examination.

The patient’s serum corrected-calcium level was 2.79mmol/L (normal range, 2.19–2.54mmol/L),his serum phosphate level was 1.29mmol/L (normal range, 0.7–1.5mmol/L), his vitamin D25-OHlevel was normal, his serum creatinine level was 756 μmol/L (normal range, 53–106.1 μmol/L),his serum urea was 17.2mmol/L (normal range, 2.9–8.2mmol/L), and his serum PTH level was489.5 pmol/L (normal range, 1.6–6.8 pmol/L).

At our clinic, the patient was diagnosed with tertiary hyperparathyroidism and renal osteodystro-phy as complications from his chronic kidney disease. His pre-operative serum thyroid-stimulatinghormone (TSH) level was within normal parameters (1.1mIU/L; normal range, 0.35–5.0mIU/L).A dual-phase PTH scan revealed two foci located below the lower poles of both thyroid lobes withintact thyroid uptake compatible with PTH adenomas (Figure 1). Diagnostic computed tomography(CT) or magnetic resonance imaging (MRI) scans were necessary for the final reading, whichinvolved fusion of the available axial cuts of the PTH scan with structural imaging data. Neck MRI

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Hakami Transient thyroiditis after surgery for tertiary hyperparathyroidism

FIGURE 1 | The patient’s FT4 levels peaked on post-operative day 3.Reference values are the following: free thyroxine (FT4): 9.1–23.8 pmol/L.

revealed four PTH masses posterior and inferior to the normalthyroid gland, with two masses on each side, suggesting PTHadenomas. Fine-needle aspiration (FNA) of the right PTH masseswas performed, and pathological examination revealed PTH cellsconsistent with hyperplastic proliferation. Therefore, the patientwas diagnosed with PTH hyperplasia.

The patient underwent parathyroidectomy to remove his PTHglands. He was brought to the operating room under generalanesthesia. A transverse incision 6-cm long and 3-cm superiorto the sternal angle was made. The strap muscle was separated,and the dissection was continued until the surgeon reached thethyroid gland. Retraction of the thyroid gland on the right sidewas successful, and the recurrent laryngeal nerve was identified.The superior right PTH gland was anterior to the nerve and wasdissected successfully. The inferior right PTH gland was deep andnear the sternum. It was difficult to separate the inferior rightPTH gland from the thyroid gland surgically because they werefirmly attached, so the attached part of the thyroid glandwas takenas a resection margin along with the inferior right PTH gland.Subcapsular dissection of the thyroid gland was done on the leftside also, and the left recurrent laryngeal nerve was identified. Thesuperior left PTH gland, posterior to the nerve, was identified andseparated successfully. The left inferior PTH gland was located,dissected from around the gland, and extracted. All of the PTHglands were resected. The duration of the surgery was 78min.

The intra-operative serumPTH level was 414.2 pmol/L and haddeclined to 22.4 pmol/L 1 h after surgery. One day after surgery, itwas 4.2 pmol/L. The resected part of the thyroid gland was normalon pathological examination. The pathological examination ofthe resected PTH glands revealed nodular hyperplasia involvingall glands confirming the PTH hyperplasia diagnosis. There wereno complications during surgery. However, the patient developedhypocalcemia that was normalized with calcium replacementtherapy.

Three days after the surgery, the patient presented withnew symptoms of palpitation, anxiety, and hand tremors. Acomplete examination revealed mild, diffuse, non-tender goiter,

FIGURE 2 | The patient’s TSH levels following surgery. Reference valuesare the following: thyroid-stimulating hormone (TSH): 0.35–5.0mIU/L.

and fine tremor, with stable vital signs. Serum thyroid functiontests revealed that his TSH level was 0.171mIU/L and thathis free thyroxine (FT4) level was 97.6 pmol/L (normal range,9.1–23.8 pmol/L), consistent with primary hyperthyroidism(Figures 2 and 3). Technetium-99m (Tc-99m) pertechnetatescintigraphy revealed generalized reduced tracer uptake in thethyroid gland, a finding that is compatible with thyroiditis(Figure 4). Autoimmune markers were normal, includingthyroglobulin (Tg) antibodies (2.08 IU/mL; normal range,0–80 IU/mL), thyroid peroxidase (TPO) antibodies (0.3 IU/mL;normal range, 0–20 IU/mL), and TSH receptor antibodies(negative). However, inflammatory markers were elevatedincluding C-reactive protein (CRP) (8.8mg/L; normal range,1.0–3.0mg/L) and erythrocyte sedimentation rate (ESR)(78mm/H; normal range, 0.0–20.0mm/H). There was no clinicalevidence of sepsis. The patient did not receive iodinated contrastagents; he did not receive lithium or amidarone nor medicationthat might have affected his thyroid function tests. Otherpossible causes of thyroiditis have been ruled out, specifically,viral thyroiditis, bacterial thyroiditis, autoimmune thyroiditis,radiation thyroiditis, or drug-induced thyroiditis. Therefore, hewas diagnosed with post-operative thyroiditis and given oralBisoprolol. He did not receive an antithyroid agent.

His condition improved over the following weeks. After3weeks, he made a complete recovery and had no persistentclinical or biochemical manifestations of thyroid disease. Biso-prolol was withdrawn. The patient was examined in the clinicafter 6months. At this time, he was clinically and biochemicallyeuthyroid, with no indication of hypothyroidism.

A definitive diagnosis of post-operative transient thyroiditissecondary due to manual manipulation of the thyroid glandduring surgery was made.

Discussion

The incidence of post-operative thyroiditis is unknown as it isunderreported. There are no data in the literature pertaining to

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FIGURE 3 | 99m TcMIBI (sestamibi) dual-phase parathyroid scintigraphy revealed two foci located below the lower poles of both thyroid lobes withintact thyroid uptake compatible with parathyroid adenomas.

complications of parathyroidectomy on the prevalence of post-operative transient thyroiditis. This is likely because most patientsare asymptomatic or have mild non-specific symptoms.

In 2005, Stang et al. examined pre- and post-operative thyroidfunction and outcomes in 199 patients who had PTH exploratorysurgery for primary sporadic hyperparathyroidism. They foundthat the incidence of TSH suppression below the lower limits ofnormal levels was 29% (58/199) (1). Akira et al. reported a typeof thyrotoxicosis that occurred after needle aspiration of thyroidcysts. The incidence of post-aspiration thyrotoxicosis was 0.9% (1of 115) (2). In two small studies, the rate of post-operative hyper-thyroidism after parathyroidectomy was 20% (3, 4). Reportedcauses of iatrogenic thyrotoxicosis include use of medication thatcan affect the thyroid gland, such as lithium and amiodarone,recent radioiodine ablation, thyroid hormone replacement ther-apy, iodine excess, immunotherapy, external irradiation, andmanipulation of the thyroid gland during surgery.

The exact mechanism of post-operative thyroiditis is unclear.In the past, hyperthyroidism arising after PTH surgery has beenthought to be transient and relate to retraction of the thyroid glandfor exposure during surgery.

In 1975, Carney et al. described an association between vigor-ous thyroid lobe palpations under pentobarbital anesthesia with

the histological finding of granulomatous thyroid folliculitis inmassaged thyroid lobes in dogs. Noting that similar multifocalinflammatory changes usually were present in resected humanthyroid lobes. It is suggested that manipulation of the thyroidgland was sufficient to cause transient inflammatory reactions inboth humans and dogs, which they termed as palpation thyroiditisand multifocal granulomatous folliculitis (5).

In 1992, Walfish et al. reported on three patients who hadundergone resection of PTH adenoma, which occurred after rou-tine transection of the superior thyroid pole and vessels and devel-oped thyrotoxicosis post-operatively. They concluded that thethyroid disruption caused post-operative hyperthyroidism. Theywere the first to suggest evidence of a clinical syndrome of trauma-induced thyroiditis in those patients (6). On the contrary, in Stanget al. study, they treat the thyroid gland as gently as possible, butthere data supported a causative role of operative trauma to thethyroid lobe, since bilateral exploration was associated with thedevelopment of post-operative hyperthyroidism (1).

In Akira et al. study, the mechanism of post-aspiration thy-rotoxicosis is unknown; however, they speculated that the com-bination of thyroiditis and leakage of thyroid contents into thecystmight have triggered thyroid hormone release into circulationafter needle aspiration of thyroid cysts (2). In Bergenfelz et al.

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FIGURE 4 | Technetium-99m (Tc-99m) pertechnetate scintigraphy ofthe patient’s thyroid gland is faintly observed with generalized reducedtracer uptake in the thyroid gland. There is increased background traceractivity in the salivary glands. These findings are compatible with thyroiditis.

prospective study of 20 patients undergoing operation for pri-mary hyperparathyroidism, compared with 6 patients undergo-ing laparoscopic cholecystectomy. Four patients (20%) developedbiochemical hyperthyroidism, but serum antithyroid antibodylevels did not increase. Control patients experienced a slightincrease in mean TSH post-operatively, and the authors con-cluded that post-parathyroidectomy hyperthyroidism was relatedto metabolic derangement intrinsic to the primary hyperparathy-roidism itself (3).

In Lindblom et al. report, they examined post-parathyroidectomy hyperthyroidism in 26 patients undergoingoperation for primary hyperparathyroidism, but with moredetail about anesthetic and operative factors and with a differentcontrol group of 11 patients undergoing breast cancer surgery.Post-operative levels of T4 and T3 were higher after PTHoperation than after breast operation. The investigator concludedthat manipulation of the thyroid gland was most likely the majorcontributing factor to post-operative hyperthyroidism. However,it may not be the sole explanation, since there data suggest a moremultifactorial scenario (4).

Rudofsky et al. reported a case of transient symptomatic thyro-toxicosis following PTH surgery for tertiary hyperparathyroidismin a 33-year-old woman; they presumed that it was caused by atraumatic thyroiditis as a result of manipulation of the thyroidgland during surgery (7).

Calle and Cohen reported on a patient who developed transientthyroiditis following total laryngopharyngoesophagectomy withgastric pull-up for a right hypopharynx tumor with preservationof the thyroid gland (8).

In the Stang et al. study cited above, the incidence ofpost-operative hyperthyroidism was independent of age, gender,

the pre-operative and intra-operative PTH levels, and adenomaweight. There was no relationship between the type of PTHpathology, that is, multi-glandular disease versus solitary ade-noma, the presence of goiter, or prior thyroiditis. None of thefollowing indicators of operative trauma were predictive of post-operative thyroiditis: time that the operation took, incision length,difficulty in making the dissection, thyroid nodulectomy, thy-roidectomy for intrathyroidal PTH adenoma, retropharyngealadenoma, concurrent cervical thymectomy, the degree of perithy-roidal inflammation, or whether or not a drain was placed (1).

Stang et al. identified three surgical variables associated withpost-parathyroidectomy hyperthyroidism. These were bilateralexploration, the absence of concurrent thyroid lobectomy, andperformance of the operation at community hospitals. Whenpatients were cared for at the community hospitals, explorationhad to be done bilaterally because the intra-operative PTH couldnot be monitored. The use of lithium was observed to be anindependent risk factor for post-operative hyperthyroidism. Thismay be because lithiumprovides a persistent toxic insult to thyroidtissue, rendering it more sensitive to manipulation during necksurgery. Patients who underwent complete thyroid lobectomywere less likely to have post-operative thyroiditis (1).

Post-operative thyroiditis has a wide clinical presentation spec-trum, ranging from asymptomatic hyperthyroxinemia to severehyperthyroidism. In addition, a few cases of thyroiditis followingneck surgery that caused the onset of atrial fibrillation have beenreported (9, 10). McDermott et al. reported a case of transient thy-roiditis secondary to surgical manipulation of the thyroid in a 76-year-old man, which caused significant tachyarrhythmia follow-ing total laryngectomy for a subglottic tumor with preservation ofthyroid gland (11).

In the Stang et al. study, hyperthyroidism symptoms werereported in 19 of 125 (15%) patents with pre-operatively nor-mal serum TSH levels. Of these, five patients (4%) were foundto be overtly thyrotoxic. The duration for complete biochem-ical resolution ranged from 12 days to 90 days post-operation,whether or not there was medical management (1). The findingthat there was spontaneous resolution of the condition within6weeks in the majority of the patients supports the hypothesisthat manipulation of the gland during parathyroidectomy is amajor contributing factor in its development. Development ofthyrotoxicosis withmore prolonged hyperthyroxinemia later than6weeks after surgery may be caused by other factors, includ-ing lithium therapy or a predisposition to Grave’s disease (12).It is not clear that permanent hypothyroidism is common inthese cases, as there are few data on this question. There isalso little information on how an abnormal thyroid status willaffect the development of post-operative thyroiditis comparedto patients with a normal thyroid. Nonetheless, it would appearto be prudent to follow up patients who suffered post-operativethyroiditis for permanent hypothyroidism. In all cases, symp-tomatic treatment should be applied until spontaneous resolutionof symptoms.

We speculate that there is an association between vigorousmanual manipulation of the thyroid gland during PTH explo-ration surgery and the incidence of post-operative transient thy-roiditis.

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Further retrospective and prospective studies should beconducted to confirm the association between vigorous manualmanipulation of the thyroid gland during PTH explorationsurgery and the incidence of post-operative thyroiditis. Theyshould also address identification of the risk factors and thepatients who should undergo additional testing. This would beimportant to enhance our understanding of the disease process,and establish the clinical criteria for accurate diagnosis and earlytreatment.

Post-operative thyroiditis can cause significant clinical prob-lems that can be easilymissed. Clinicians should have an increasedawareness of the clinical consequences and complications.

Establishing the risks inherent to PTH exploration surgeryshould enable clinicians to develop strategies for effective riskreduction, such as minimizing the extent of surgery.

Based on the current literature data, the authors recom-mend pre-operative counseling as well as routine biochemi-cal and clinical surveillance for hyperthyroidism during thepost-operative period. Although diagnosis should be early andexpectant, treatment should be symptomatic as allowed byspontaneous resolution of symptoms. Continued efforts tominimize the extent of PTH exploration surgery, if possi-ble, may reduce the potential morbidity of thyrotoxicosis aftersurgery.

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3. Bergenfelz A, Ahren B. Hyperthyroxinemia after surgery for primary hyper-parathyroidism. Langenbecks Arch Chir (1994) 379:178–81. doi:10.1007/BF00680115

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Conflict of Interest Statement: The author declares that the research was con-ducted in the absence of any commercial or financial relationships that could beconstrued as a potential conflict of interest.

Copyright © 2015 Hakami. This is an open-access article distributed under the termsof the Creative Commons Attribution License (CC BY). The use, distribution orreproduction in other forums is permitted, provided the original author(s) or licensorare credited and that the original publication in this journal is cited, in accordancewithaccepted academic practice. No use, distribution or reproduction is permitted whichdoes not comply with these terms.

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