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 Table of Contents  
Year : 2023  |  Volume : 2  |  Issue : 1  |  Page : 55-57

Coexistent papillary thyroid carcinoma in a patient with graves' disease

Department of Endocrinology, Mymensingh Medical College, Mymensingh, Bangladesh

Date of Submission18-Nov-2022
Date of Acceptance23-Nov-2022
Date of Web Publication05-Jan-2023

Correspondence Address:
A B. M. Kamrul-Hasan
Department of Endocrinology, Mymensingh Medical College, Mymensingh 2206
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/bjem.bjem_16_22

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A 21-year-old male presented with the features of thyrotoxicosis, and his thyroid function tests revealed primary hyperthyroidism. He also had mild bilateral exophthalmos with lid lag, lid retraction, and a clinical activity score of 1, suggestive of mild Graves' ophthalmopathy. Neck ultrasonography revealed mild diffuse goiter with bilateral fairly large nodules predominantly at the right lobe and bilateral multiple cervical lymphadenopathies. Tc-99m pertechnetate scan demonstrated diffuse goiter with homogeneously increased radiotracer concentration. He had an elevated titer of thyroid-stimulating hormone receptor autoantibody level. Fine-needle aspiration cytology from the largest nodule of the right lobe reported a Bethesda Category-VI lesion compatible with papillary thyroid carcinoma. Graves' disease and papillary thyroid cancer carcinoma might be present concomitantly in the same patient. Although links between these entities have long been investigated, a clear correlation is not established yet.

Keywords: Graves' disease, hyperthyroidism, papillary thyroid carcinoma, thyroid nodules

How to cite this article:
Kamrul-Hasan A B. Coexistent papillary thyroid carcinoma in a patient with graves' disease. Bangladesh J Endocrinol Metab 2023;2:55-7

How to cite this URL:
Kamrul-Hasan A B. Coexistent papillary thyroid carcinoma in a patient with graves' disease. Bangladesh J Endocrinol Metab [serial online] 2023 [cited 2023 Mar 28];2:55-7. Available from: https://www.bjem.org/text.asp?2023/2/1/55/367278

  Introduction Top

Graves' disease (GD) is the most common cause of hyperthyroidism accounting for 50%–80% of all hyperthyroid cases. In GD, hyperthyroidism is caused by autoantibodies to the thyroid-stimulating hormone receptor (TSHR) that act as agonists and induce hypertrophy and hyperplasia of the thyroid follicles and increasing the production of thyroid hormone, releasing the thyroid gland from the pituitary control. TSHR autoantibodies also underlie Graves' orbitopathy and pretibial myxedema.[1] The other common causes of hyperthyroidism are toxic multinodular goiter and toxic adenoma, in which multiple and single autonomously functioning thyroid nodules, respectively, secrete excess thyroid hormones. Thyroid carcinoma, a neoplasm of the thyroid epithelium, is the most common endocrine cancer.[2] Papillary thyroid carcinoma (PTC) is the most frequent (~80%) differentiated thyroid carcinoma arising from the follicular cells; follicular carcinomas and anaplastic or undifferentiated carcinomas are the other forms of follicular cell-derived thyroid carcinomas.[3]

Against the common belief of the rare occurrence of thyroid carcinoma in GD, evidence is emerging to support the concomitant event of these two grave conditions.[4] Although a pathogenic correlation is not established, a link between inflammation and carcinogenesis has been well known since 1863, when Virchow demonstrated leukocytes in cancer tissues and suggested a possible association with cancer development.[5]

Whether GD is a risk factor for PTC or patients with GD and PTC has a worse prognosis are still controversial issues. This study aimed to report a case of GD with multiple thyroid nodules, in which fine-needle aspiration cytology (FNAC) revealed PTC, and to perform a brief literature review of this interaction.

  Case Report Top

A 21-year-old male with an unremarkable medical history presented to the author's private practice with 10 kg weight loss in the previous 2 months, palpitations, sweating, restlessness, hyperdefecation, increasing thyroid swelling, proptosis of both eyes with eye-watering, and headache. Vital signs revealed blood pressure of 135/75 mmHg, pulse rate of 135 beats/min with a regular rhythm, respiratory rate of 20 breaths/min, and oxygen saturation of 97%. Physical examination revealed a body weight of 51 kg, a height of 164 cm, a body mass index of 19.0 kg/m2, and mild respiratory distress, and agitation. Head–neck examination revealed mild diffuse nontender goiter with two small firms to hard nontender, freely mobile nodules (one in the right lobe and another in the left lobe) with small lymph nodes in both submandibular regions. Eye examination revealed mild bilateral exophthalmos with lid lag, lid retraction, and a clinical activity score of 1. Other systemic examinations revealed no abnormality except exacerbation of deep tendon reflexes.

The laboratory results revealed a normal complete blood cell count and basic metabolic panel and a thyroid-stimulating hormone (TSH) of 0.11 μIU/mL (normal range 0.4–4.5 μIU/mL), total T4 314.57 nmol/L (normal range 61.8–133.8 nmol/L), and total T3 6.16 nmol/L (normal range 0.92–2.79 nmol/L). Neck ultrasonography (USG) revealed mild diffuse goiter with bilateral fairly large nodules predominantly at the right lobe [Figure 1]a, [Figure 1]b, [Figure 1]c. In the right lobe, the largest nodule measured about 2.9 cm × 2.1 cm, which was of mixed echo pattern; another larger one measured about 2.0 cm × 1.6 cm, which was hypoechoic. The left lobe also had a 2.0 cm × 1.3 cm mixed echogenic nodule; another 1.3 cm × 0.7 cm mixed echogenic nodule was found in the isthmus. Bilateral multiple cervical lymphadenopathies were also revealed by USG. Tc-99m pertechnetate scan demonstrated diffuse goiter with homogeneously increased radiotracer concentration. His TSH-receptor autoantibody level was 6.9 IU/L (normal range <1.5 IU/L). FNAC from the largest nodule of the right lobe reported a Bethesda Category-VI lesion compatible with PTC.
Figure 1: (a) Ultrasonography of thyroid. (b) Ultrasonography of thyroid. (c) Ultrasonography of thyroid

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  Discussion Top

GD and PTC have a controversial causal relationship. In our study, the patient was a young male. GD affects females more often than males by a ratio of 5-10: 1. The disorder usually develops during the middle age with a peak incidence of 40–60, but it can also affect children, adolescents, and the elderly.[6] Finding multiple thyroid nodules in GD is also not uncommon. Nodules associated with GD have been reported in various studies, with a prevalence rate ranging from 12.8% to 36.6%.[7],[8] These coexisting thyroid nodules in GD are usually nonfunctional (cold) and rarely functional (warm/hot), when they are referred to as Marine-Lenhart syndrome.[9]

Thyroid carcinoma in GD was initially thought to be a rare phenomenon, even an “insurance against cancer of the thyroid.” However, a several recent studies have indicated that the opposite may be true, reporting an increased prevalence of differentiated thyroid cancer compared to the normal population.[4],[5],[10] The current hypotheses of the mechanism of carcinogenesis center around pathways activated by the binding of thyroid-stimulating antibodies, which as well as stimulating growth, may promote invasion and angiogenesis and activate insulin-like growth factor pathways.[10] According to the American Thyroid Association, thyroid cancer occurs in GD with a frequency of 2% or less.[11] A recent meta-analysis reported that the incidence rate of thyroid carcinoma in GD is roughly 2.5 times the overall global figures.[12] 10%–15% of nodules associated with GD are reported to be thyroid cancers, with papillary thyroid cancer being the most common histopathology. The prevalence of medullary thyroid carcinoma in such nodules is rare.[8],[10] Thyroid USG has been widely used to stratify the risk of malignancy in thyroid nodules and aid decision making about whether FNAC is indicated. Ascertaining the pathological nature of these nodules by FNAC has an important bearing on the treatment choice. FNAC is the most cost-effective and accurate method for evaluating thyroid nodules. Lower rates of nondiagnostic and false-negative cytology from FNAC procedures performed using USG guidance compared to palpation have been reported. Diagnostic FNAC is recommended for nodules ≥1 cm in the greatest dimension with a high-suspicion and intermediate-suspicion sonographic pattern and nodules ≥1.5 cm in the greatest dimension with a low-suspicion sonographic pattern. Thyroid nodule diagnostic FNA may be considered for nodules ≥2 cm in the greatest dimension with a very low-suspicion sonographic pattern (e.g., spongiform).[11] Whether GD affects the prognosis of PTC is a controversial issue. Some studies have identified higher risks of associated multifocality/multicentricity and distant metastasis at the time of PTC diagnosis, high mortality, elevated rates of metastasis, and relapse in the presence of GD.[12],[13] Other studies showed that GD does not affect PTC prognosis and that thyroid cancer in patients with GD is not more aggressive.[14]

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

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Conflicts of interest

There are no conflicts of interest.

  References Top

Davies TF, Andersen S, Latif R, Nagayama Y, Barbesino G, Brito M, et al. Graves' disease. Nat Rev Dis Primers 2020;6:52.  Back to cited text no. 1
Ross DS, Burch HB, Cooper DS, Greenlee MC, Laurberg P, Maia AL, et al. 2016 American thyroid association guidelines for diagnosis and management of hyperthyroidism and other causes of thyrotoxicosis. Thyroid 2016;26:1343-421.  Back to cited text no. 2
Dralle H, Machens A, Basa J, Fatourechi V, Franceschi S, Hay ID, et al. Follicular cell-derived thyroid cancer. Nat Rev Dis Primers 2015;1:15077.  Back to cited text no. 3
Arosemena MA, Cipriani NA, Dumitrescu AM. Graves' disease and papillary thyroid carcinoma: Case report and literature review of a single academic center. BMC Endocr Disord 2022;22:199.  Back to cited text no. 4
Ferrari SM, Fallahi P, Elia G, Ragusa F, Ruffilli I, Paparo SR, et al. Thyroid autoimmune disorders and cancer. Semin Cancer Biol 2020;64:135-46.  Back to cited text no. 5
Hussain YS, Hookham JC, Allahabadia A, Balasubramanian SP. Epidemiology, management and outcomes of Graves' disease-real life data. Endocrine 2017;56:568-78.  Back to cited text no. 6
Mishra A, Mishra SK. Thyroid nodules in Graves' disease: Implications in an endemically iodine deficient area. J Postgrad Med 2001;47:244-7.  Back to cited text no. 7
[PUBMED]  [Full text]  
Khan SH, Rather TA, Makhdoomi R, Malik D. Nodular Graves' disease with medullary thyroid cancer. Indian J Nucl Med 2015;30:341-4.  Back to cited text no. 8
[PUBMED]  [Full text]  
Cakir M. Marine-Lenhart syndrome. J Natl Med Assoc 2005;97:1036-8.  Back to cited text no. 9
Staniforth JU, Erdirimanne S, Eslick GD. Thyroid carcinoma in Graves' disease: A meta-analysis. Int J Surg 2016;27:118-25.  Back to cited text no. 10
Haugen BR, Alexander EK, Bible KC, Doherty GM, Mandel SJ, Nikiforov YE, et al. 2015 American thyroid association management guidelines for adult patients with thyroid nodules and differentiated thyroid cancer: The American thyroid association guidelines task force on thyroid nodules and differentiated thyroid cancer. Thyroid 2016;26:1-133.  Back to cited text no. 11
Mekraksakit P, Rattanawong P, Karnchanasorn R, Kanitsoraphan C, Leelaviwat N, Poonsombudlert K, et al. Prognosis of differentiated thyroid carcinoma in patients with Graves disease: A systematic review and meta-analysis. Endocr Pract 2019;25:1323-37.  Back to cited text no. 12
Pellegriti G, Mannarino C, Russo M, Terranova R, Marturano I, Vigneri R, et al. Increased mortality in patients with differentiated thyroid cancer associated with Graves' disease. J Clin Endocrinol Metab 2013;98:1014-21.  Back to cited text no. 13
Kwon H, Moon BI. Prognosis of papillary thyroid cancer in patients with Graves' disease: A propensity score-matched analysis. World J Surg Oncol 2020;18:266.  Back to cited text no. 14


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