|Year : 2018 | Volume
| Issue : 2 | Page : 42-47
Management of thyroid nodules in adults
Dukhabandhu Naik, K Felix Jebasingh, Nihal Thomas
Department of Endocrinology, Diabetes and Metabolism, Christian Medical College, Vellore, Tamil Nadu, India
|Date of Web Publication||20-Jun-2018|
Dr. Dukhabandhu Naik
Department of Endocrinology, Diabetes and Metabolism, Christian Medical College, Vellore - 632 004, Tamil Nadu
Source of Support: None, Conflict of Interest: None
Thyroid nodule is an abnormal growth of thyroid cells that form a lump in the thyroid gland. The prevalence rate is dependent on the mode of diagnosis and increases with use of ultrasound. A thyroid nodule may be either single or multiple and the majority are asymptomatic and benign in nature. The clinical features of thyrotoxicosis are seen in those with a toxic thyroid nodule. Thyroid ultrasound is the imaging of choice for assessing the location, numbers, and size of the thyroid nodules and also the background of thyroid parenchyma. Ultrasound elastography, fine needle aspiration biopsy and molecular tests further aid in diagnosis and planning of treatment. Surgical excision is the therapeutic intervention of choice.
Keywords: Fine-needle aspiration biopsy, thyroid imaging reporting and data system, thyroid nodules, thyroid ultrasound, ultrasound elastography
|How to cite this article:|
Naik D, Jebasingh K F, Thomas N. Management of thyroid nodules in adults. Curr Med Issues 2018;16:42-7
| Introduction|| |
Thyroid nodule is commonly encountered in general and surgical practice. The prevalence of palpable thyroid nodules in adults ranges between 1% and 5%. Ultrasonography (USG) screening increases the prevalence rate almost ten times and increases the rate of detection of clinically nonsignificant nodules. Most thyroid nodules are benign in nature. Thyroid malignancy is relatively rare and is present approximately in 5%–15% of patients with thyroid nodules. The primary goal of evaluating thyroid nodules is to rule out any malignancy.
| Epidemiology|| |
Thyroid nodule is an abnormal growth of thyroid cells that form a lump in the thyroid gland. In a population-based study, the prevalence of thyroid nodule is <5% on palpation and is around 65% by ultrasound. Approximately 20%–48% of patients have additional thyroid nodules on ultrasound screening., Thyroid nodules are more common in iodine-deficient regions, among females, and with advancing age. The prevalence of thyroid nodule increases with age. The prevalence rate is 2%–2.7% in patients with age <30 years and 14.5%–18% in patients above 60 years of age. In Framingham survey, the prevalence of thyroid nodule in nonpregnant adult population was 6.4% in women and 1.5% in men. Studies from India showed a prevalence of 18.9% in iodine-sufficient areas and 80% in areas with iodine deficiency., Currently, there is an increasing evidence in diagnosis of asymptomatic small nodule <10 mm due to increased use of imaging modalities such as positron emission tomography scan, Carotid Doppler, magnetic resonance imaging, or computed tomography of head-and-neck region for the purpose other than thyroid disorders. These nodules are otherwise known as thyroid incidentaloma. More than half of these thyroid nodules are solitary in nature, and the overall risk of malignancy in these thyroid nodules is 8%–15%. However, the malignancy rate increases with the presence of various risk factors such as younger age group, male sex, past history of irradiation to head-and-neck region, and family history of thyroid cancer.
| Etiology of Thyroid Nodules|| |
A thyroid nodule may be either single or multiple. They are largely asymptomatic and benign in nature. The clinical features of thyrotoxicosis are seen in those with a toxic thyroid nodule. Mild toxic features are seen in medullary and follicular carcinoma of the thyroid. Thyroid nodules can be either benign or malignant with the benign variety forming the majority. The nodules with benign etiology included colloid nodules, hyperplastic nodules, cystic nodules, Hashimoto's thyroiditis, follicular adenoma, and Hurthle cell adenoma. Malignant causes of thyroid nodules include differentiated thyroid cancer, anaplastic thyroid cancer, lymphoma, and metastatic cancer. Multinodular goiters also have a similar risk of malignancy as a solitary nodule. [Table 1] etiology of thyroid nodule.
| History and Clinical Evaluation|| |
The primary objective in evaluating thyroid nodules is to differentiate the malignant from benign conditions. The majority of thyroid nodules are asymptomatic. In patients with thyroid nodules, the symptoms of a lump or foreign body sensation, dysphagia, cough in the supine position, breathing difficulty, and pain (due to hemorrhage) should be elicited. A history of rapid increase in the size of the swelling, hoarseness of voice, and dysphagia needs urgent evaluation for malignancy. The clinical examination should include inspection of the thyroid swelling for mobility and palpation for consistency, retrosternal extension, and cervical lymph node enlargement [Figure 1]. A firm-to-hard swelling with fixity to the surrounding structures and associated lymphadenopathy requires prompt evaluation. A thyroid nodule is often missed on clinical examination because of its posterior location within the gland, smaller size, or of similar consistency as a thyroid. Some patients can present with features of distant metastasis which include milliary infiltrations in the lungs or nodules in the chest X-ray, lower back pain, and bony swellings with skeletal metastasis [Figure 2] and [Figure 3]. The typical features of thyroid malignancy are usually absent in many patients, and in such cases, the presence of the following factors can predict malignancy. The details of clinical risk factors which can predict malignancy are shown in [Table 2]. Sometimes, thyroid cancer can be familial in nature. There are several syndromes associated with thyroid cancer which include multiple endocrine neoplasia (MEN-1), MEN-2, familial non-MEN medullary carcinomas, Cowden's syndrome, Gardner's syndrome, familial adenomatous polyposis, and Carney's complex. History of tumors in the other parts of the body in Cowden's syndrome (multiple hamartomas, fibrocystic breast disease, and breast cancer), Gardner's syndrome (multiple soft tissue and bone tumors and intestinal polyposis), and Carney's complex (spotty skin pigmentation and cardiac myxoma) suggests tumor syndrome and raises the possibility of thyroid neoplasm.
|Figure 1: A 56-year-old female presented with a history of thyroid swelling since 10 years and rapidly increasing size of the swelling for 6 months. Clinical features showing retrosternal extension of the thyroid swelling (Pemberton sign).|
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|Figure 2: (a) Multinodular goiter. (b) A 16-year-old boy presented with multinodular goiter. He underwent total thyroidectomy and gross specimen is shown in Figure 2b. The histology showed papillary structures and Psammoma bodies which were suggestive of papillary thyroid carcinoma.|
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|Figure 3: A 55-year-old male presented with a history of low back for 3 months. The X-ray spine followed by MRI showed a soft-tissue lesion. A computed tomography-guided biopsy of the soft-tissue lesion was suggestive of follicular carcinoma thyroid.|
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| Laboratory Evaluation|| |
Serum thyroid-stimulating hormone (TSH) should be measured during initial evaluation in all the patients. The goal is to exclude patients with thyrotoxicosis which is seen in <5% of cases. If TSH is suppressed, then T4 and FT4 should be measured. If T4 and FT4 levels are also elevated, then radionucleotide (I-131) scan should be performed which shows a focal increase in uptake. If TSH level is higher than the reference range, then T4, FT4, and thyroid antibodies should be measured to rule out Hashimoto's thyroiditis. Routine estimation of serum thyroglobulin and calcitonin is not recommended since it is not found to be cost-effective.
| Thyroid Ultrasound|| |
Thyroid ultrasound is the imaging of choice for assessing the location, numbers, and size of the thyroid nodules and also the background of thyroid parenchyma. It is a portable, economical, and universally acceptable tool for the evaluation of thyroid nodules. A high frequency (>12 Hz) transducer is required to obtain excellent image definition. Thyroid ultrasound is indicated when a thyroid gland is palpable or when a nodule is incidentally detected in another imaging study. The other important indications of thyroid ultrasound are shown in [Table 3]. Thyroid ultrasound is also helpful in differentiating thyroid nodule from other anterior neck masses. [Table 4] has shown the differential diagnosis of anterior neck masses. The sonographic features are very useful in cancer risk stratification of thyroid nodules. The combination of Doppler along with ultrasound is helpful in differentiating central vascular pattern from perinodular vascular pattern. The ultrasound features which are associated with increased risk of malignancy are solid lesion, irregular shape, ill-defined border, microcalcification, hypoechogenicity, heterogeneous internal echoes, absence of halo, taller than wider, extrathyroidal extension, and pathological lymphadenopathy., The differences between the features of benign and malignant nodules are shown in [Table 5] and [Figure 4] and [Figure 5]. The ultrasound features also helps guide the decision whether to perform a fine-needle biopsy or not.
|Figure 4: Features of a being thyroid nodule (a) presence of halo sign (white arrow), (b) cystic lesion, (c) spongiform lesion, and (d) macro calcification.|
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|Figure 5: Features of malignant thyroid nodule (a) hypoechogenicity (arrows) (b) microcalcification (c) nodular vascularity (d) irregular margin or no halo (arrows) (e) taller than wider (f) suspicious lymph nodes.|
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| Thyroid Imaging Reporting and Data System|| |
Thyroid imaging reporting and data system (TIRADS) was first reported by Horvath et al. This is similar to the concept of breast imaging reporting and data system. The American College of Radiology has recommended TIRADS, the point system for systematic assessment of imaging of thyroid nodules. The initial TIRADS had 10-point system; the modified version TIRDAS has a 5-point system which includes points for solid lesion, hypoechoic, ill-defined margins, taller than wide lesions, and microcalcification. [Table 6] shows the six types of TIRADS grades and types of thyroid nodules. The risk for cancer in each group according to TIRADS types is as follows: 0% in TIRADS 1 and 2, 2%–2.8% in TIRADS 3, 3.6%–12.7% in TIRADS 4A, 6.8%–37.8% in TIRADS 4B, 21%–91.9% in TIRADS 4c, and 88.7%–97.9% in TIRADS 5 lesions.
| Ultrasound Elastography|| |
It is used to measure the stiffness of the tissues or its displacement in response to an applied force by an ultrasound probe. A benign nodule deforms easily as it is softer, whereas a malignant nodule is harder and hence deforms less. Differences in tissue displacement are calculated and presented as color maps, also known as an elastogram. Each elasticity score is coded by different colors [Figure 6]. The range of colors from red to blue corresponds to increasing stiffness of the tissue of interest. Red color represents soft tissues, green those of intermediate stiffness, and blue the “hard” ones. Ultrasound elastography is useful in characterizing an indeterminate nodule as malignant with its effectiveness almost comparable to fine-needle aspiration cytology (FNAC).
| When to Do Fine-Needle Aspiration Biopsy|| |
Fine-needle aspiration biopsy (FNAB) is one of an important reliable and cost-effective investigation for evaluation of thyroid nodules. FNAB is indicated when there is a clinical or sonographical evidence of a nodule >1 cm. An USG-guided FNAB is considered superior to the palpatory method; however, it is not indicated in all patients. The main indications for USG-guided FNAB are (a) in a dominantly cystic nodule from solid components, (b) if a nodule is not easily palpable clinically, (c) in multiple nodules, where an FNAC should be done from a suspicious nodule after ultrasound screening, and (d) in the case of a failed or nondiagnostic FNAC by a palpatory method in a suspicious nodule., Worldwide, the thyroid cytology reports are reported according to the Bethesda classification system. The thyroid reporting is classified into six different categories [Table 7].
|Table 7: The Bethesda system for reporting thyroid cytopathology: Implied risk of malignancy and recommended clinical management|
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Category 1 is defined as nondiagnostic or insufficient. Category 2 is defined as benign. Category 3 is defined as atypia of undetermined significance or a follicular lesion of undetermined significance. Category 4 is defined as a follicular neoplasm or suspicious for a follicular neoplasm. Category 5 and 6 are defined as suspicious for malignancy. Category 3 and 4 are also classified as indeterminate type which constitutes about 20%–30% of all biopsies. This category rarely includes aggressive variants of papillary thyroid carcinoma and the rate of follicular carcinoma is also low. This category is recently recognized as noninvasive follicular thyroid neoplasm with papillary nuclear features.
| Molecular Testing|| |
Molecular testing in a FNAC samples is increasing popular and their acceptance in many developed countries play a role in the interpretation of the indeterminate thyroid nodule. Testing FNAC samples “for a panel of mutations which includes BRAF (V 600E), RAS, RET/PTC, and PAX8/PPARγ” can help in improving the diagnostic accuracy of FNAC. These mutations are associated with malignancy in thyroid nodules and might help in refining clinical management for a significant proportion of patients with indeterminate cytology. ATA recommends “the use of molecular markers, as BRAF, RAS, RET/PTC, and PAX8/PPARγ for patients with indeterminate FNAC to help guide management.” The knowledge of these molecular pathways has permitted the development of newer targeted therapies for aggressive thyroid cancer.
| Management|| |
The management of thyroid nodules depends on biopsy reports. In patients with Bethesda (class 5 and 6), surgery is the therapy of choice. The extent of surgery depends on the size of the tumors and also includes the clinical and radiological presence of lymph nodes or distant metastasis. In patients with small intrathyroidal tumor of size <1 cm and without local invasion, lobectomy or active annual ultrasound surveillance is required. In patients with a size >1 cm, total thyroidectomy is the preferred approach. In indeterminate nodules (Bethesda Class – 3 and 4), lobectomy is preferred and if the biopsy is suggestive of malignancy, completion thyroidectomy is recommended. The category 3 and 4 is also defined as follicular lesion, Hurthle cell neoplasm. In these cases, differentiating malignant from benign lesions requires histological evidence of capsular or vascular invasion. Patients with nondiagnostic FNAB are required to be followed up at regular intervals with repeat USG and FNAB. In benign nodules, follow-up is a preferred option and surgery should be considered if nodule size are >4 cm, in the presence of compressive symptoms, and retrosternal extension or if the chance of malignancy is still high, based on radiological and clinical features. In patients with discordant cytological, radiological, and clinical finding, a multidisciplinary team approach is recommended. [Figure 7] shows the management algorithm for a thyroid nodule.
| Conclusion|| |
Majority of thyroid nodules are benign in nature. A diagnostic approach that uses the clinical presentation, radiological features, and FNAB finding are helpful in identifying nodules with malignant potential. The use of a current molecular multigene profile may improve the diagnostic and treatment approach in indeterminate nodules.
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.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
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;26:1-33.
Mazzaferri EL. Management of a solitary thyroid nodule. N
Engl J Med 1993;328:553-9.
Guth S, Theune U, Aberle J, Galach A, Bamberger CM. Very high prevalence of thyroid nodules detected by high frequency (13 MHz) ultrasound examination. Eur J Clin Invest 2009;39:699-706.
Vander JB, Gaston EA, Dawber TR. The significance of nontoxic thyroid nodules. Final report of a 15-year study of the incidence of thyroid malignancy. Ann Intern Med 1968;69:537-40.
Marwaha RK, Tandon N, Ganie MA, Kanwar R, Sastry A, Garg MK, et al.
Status of thyroid function in Indian adults: Two decades after universal salt iodization. J Assoc Physicians India 2012;60:32-6.
Unnikrishnan AG, Menon UV. Thyroid disorders in India: An epidemiological perspective. Indian J Endocrinol Metab 2011;15:S78-81.
Russ G, Leboulleux S, Leenhardt L, Hegedüs L. Thyroid incidentalomas: Epidemiology, risk stratification with ultrasound and workup. Eur Thyroid J 2014;3:154-63.
Aldrink JH, Adler B, Haines J, Watkins D, Matthews M, Lubeley L, et al.
Patients exposed to diagnostic head and neck radiation for the management of shunted hydrocephalus have a significant risk of developing thyroid nodules. Pediatr Surg Int 2016;32:565-9.
Richards ML. Familial syndromes associated with thyroid cancer in the era of personalized medicine. Thyroid 2010;20:707-13.
Papini E, Guglielmi R, Bianchini A, Crescenzi A, Taccogna S, Nardi F, et al.
Risk of malignancy in nonpalpable thyroid nodules: Predictive value of ultrasound and color-Doppler features. J Clin Endocrinol Metab 2002;87:1941-6.
Jeh SK, Jung SL, Kim BS, Lee YS. Evaluating the degree of conformity of papillary carcinoma and follicular carcinoma to the reported ultrasonographic findings of malignant thyroid tumor. Korean J Radiol 2007;8:192-7.
Tessler FN, Middleton WD, Grant EG, Hoang JK, Berland LL, Teefey SA, et al.
ACR thyroid imaging, reporting and data system (TI-RADS): White paper of the ACR TI-RADS committee. J Am Coll Radiol 2017;14:587-95.
Rago T, Santini F, Scutari M, Pinchera A, Vitti P. Elastography: New developments in ultrasound for predicting malignancy in thyroid nodules. J Clin Endocrinol Metab 2007;92:2917-22.
Durante C, Grani G, Lamartina L, Filetti S, Mandel SJ, Cooper DS, et al.
The diagnosis and management of thyroid nodules: A review. JAMA 2018;319:914-24.
Baskin HJ. Ultrasound-guided fine-needle aspiration biopsy of thyroid nodules and multinodular goiters. Endocr Pract 2004;10:242-5.
Bongiovanni M, Spitale A, Faquin WC, Mazzucchelli L, Baloch ZW. The Bethesda system for reporting thyroid cytopathology: A meta-analysis. Acta Cytol 2012;56:333-9.
Nikiforov YE. Role of molecular markers in thyroid nodule management: Then and now. Endocr Pract 2017;23:979-88.
[Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6], [Figure 7]
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6], [Table 7]