**6.4 FNAC**

ATA recommends FNAC as the procedure of choice in evaluation of MNG, as it is the cost-effective and most accurate method for thyroid nodule evaluation. FNAC is very reliable and has a low false-negative (7%) and very low false-positive rate near to zero [33]. In one study negative predictive value of case classified as benign was 95% [34]. FNAC provides an algorithm for evaluation and management of patients with thyroid nodules based on sonographic pattern and FNA cytology. ATA recommends FNAC in nodule >1 cm with high or intermediate suspicion of malignancy, nodule >1.5 cm with low suspicion of malignancy, and nodule >2 cm

**105**

**7. Treatment**

**7.1 Surgical treatment**

*Multinodular Goiter*

significance

**Table 2.**

a follicular neoplasm

*DOI: http://dx.doi.org/10.5772/intechopen.90325*

Atypia of undetermined significance or follicular lesion of undetermined

Follicular neoplasm or suspicious for

*As reported in the Bethesda system by Cibas and Ali.*

**Diagnostic category Estimated/predicted risk of** 

with very low suspicion of malignancy. FNAC is not recommended for purely cystic nodule. To make a satisfactory FNAC, at least six to eight cell clusters are required in two slides. ATA recommends FNAC to be reported using diagnostic groups outlined in the Bethesda system for reporting thyroid cytopathology (**Table 2**). Based on literature review and expert opinion, the Bethesda system has six diagnostic categories and also provides an estimation of cancer risk within each category. These categories are (i) nondiagnostic/unsatisfactory; (ii) benign; (iii) atypia of undetermined significance/follicular lesion of undetermined significance (AUS/FLUS); (iv) follicular neoplasm/suspicious for follicular neoplasm (FN/SFN), a category that also encompasses the diagnosis of Hu¨rthle cell neoplasm/suspicious for Hürthle cell neoplasm; (v) suspicious for malignancy (susp); and (vi) malignant.

**malignancy by the Bethesda system, %a**

Nondiagnostic or unsatisfactory 1–4 20 (9–32) Benign 0–3 2.5 (1–10)

Suspicious for malignancy 60–75 70 (53–97) Malignant 97–99 99 (94–100)

*The Bethesda system for reporting thyroid cytopathology: Diagnostic categories and risk of malignancy.*

**Actual risk of malignancy in nodules surgically excised, % median (range)b**

5–15 14 (6–48)

15–30 25 (14–34)

Treatment of MNG is directed towards existing thyroid disease associated with MNG and etiology of the disease [35]. Management of toxic and nontoxic MNG is done separately and should be based on the type of MNG. Treatment selection is also based on overall health and comorbidities of the patient. Success of treatment depends on the patient selection and type of treatment. Treatment is broadly divided in surgical and nonsurgical modalities. Surgery is indicated in large MNG, retrosternal extension of MNG, compression of trachea or esophagus, rapid growth, suspicion of malignancy, and MNG associated with vocal cord palsy.

Definitive treatment of toxic MNG is done by surgery when goiter size is large. Two types of surgical procedures are performed: total thyroidectomy and subtotal thyroidectomy. In total thyroidectomy all thyroid tissue is surgically excised, whereas in subtotal thyroidectomy small amount of thyroid tissue 1 gm on each lobe of thyroid is left. Before doing surgical procedure, patient should be rendered euthyroid by antithyroid drugs, beta blockers, and potassium iodide or a combination of one or more of these. Preoperatively cardiac evaluation is mandatory, and patient should be stabilized with appropriate treatment. Surgical procedures are the


#### **Table 2.**

*Goiter - Causes and Treatment*

(toxic MNG) Plummer's disease.

*Nodule sonographic patterns and risk of malignancy.*

**6.3 CT/MRI**

**Figure 1.**

**6.4 FNAC**

i.e., tracer uptake is equal to the surrounding thyroid), or nonfunctioning ("cold," i.e., has uptake less than the surrounding thyroid tissue) [32]. Since hyperfunctioning nodules rarely harbor malignancy, so cytologic evaluation is not required in hyperfunctioning nodules. Scan is also useful in distinguishing Graves' disease from

CT/MRI is generally not recommended in evaluation of MNG. These modalities of imaging do not have any advantage over ultrasonography in description of intrathyroidal structure. These imaging modalities are useful only when malignancy is suspected or goiter is retrosternal in which MRI is more precise than CT. CT/MRI provides more information about the surrounding tissue in relation to the thyroid, i.e., trachea, esophagus, and neck vessels. So these imaging modalities are used when features of tracheal compression/deviation, dysphagia, vocal cord paralysis, and weight loss are present. CT/MRI provides additional anatomical information to

ATA recommends FNAC as the procedure of choice in evaluation of MNG, as it is the cost-effective and most accurate method for thyroid nodule evaluation. FNAC is very reliable and has a low false-negative (7%) and very low false-positive rate near to zero [33]. In one study negative predictive value of case classified as benign was 95% [34]. FNAC provides an algorithm for evaluation and management of patients with thyroid nodules based on sonographic pattern and FNA cytology. ATA recommends FNAC in nodule >1 cm with high or intermediate suspicion of malignancy, nodule >1.5 cm with low suspicion of malignancy, and nodule >2 cm

be helpful preoperatively for planning of surgical excision.

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*The Bethesda system for reporting thyroid cytopathology: Diagnostic categories and risk of malignancy.*

with very low suspicion of malignancy. FNAC is not recommended for purely cystic nodule. To make a satisfactory FNAC, at least six to eight cell clusters are required in two slides. ATA recommends FNAC to be reported using diagnostic groups outlined in the Bethesda system for reporting thyroid cytopathology (**Table 2**). Based on literature review and expert opinion, the Bethesda system has six diagnostic categories and also provides an estimation of cancer risk within each category. These categories are (i) nondiagnostic/unsatisfactory; (ii) benign; (iii) atypia of undetermined significance/follicular lesion of undetermined significance (AUS/FLUS); (iv) follicular neoplasm/suspicious for follicular neoplasm (FN/SFN), a category that also encompasses the diagnosis of Hu¨rthle cell neoplasm/suspicious for Hürthle cell neoplasm; (v) suspicious for malignancy (susp); and (vi) malignant.

## **7. Treatment**

Treatment of MNG is directed towards existing thyroid disease associated with MNG and etiology of the disease [35]. Management of toxic and nontoxic MNG is done separately and should be based on the type of MNG. Treatment selection is also based on overall health and comorbidities of the patient. Success of treatment depends on the patient selection and type of treatment. Treatment is broadly divided in surgical and nonsurgical modalities. Surgery is indicated in large MNG, retrosternal extension of MNG, compression of trachea or esophagus, rapid growth, suspicion of malignancy, and MNG associated with vocal cord palsy.

#### **7.1 Surgical treatment**

Definitive treatment of toxic MNG is done by surgery when goiter size is large. Two types of surgical procedures are performed: total thyroidectomy and subtotal thyroidectomy. In total thyroidectomy all thyroid tissue is surgically excised, whereas in subtotal thyroidectomy small amount of thyroid tissue 1 gm on each lobe of thyroid is left. Before doing surgical procedure, patient should be rendered euthyroid by antithyroid drugs, beta blockers, and potassium iodide or a combination of one or more of these. Preoperatively cardiac evaluation is mandatory, and patient should be stabilized with appropriate treatment. Surgical procedures are the same for toxic and nontoxic MNG. In nontoxic MNG preoperative treatment with antithyroid drugs, beta blockers, or potassium iodide is not required.

Although most surgeons prefer to do total thyroidectomy, still controversy exists regarding the removal of thyroid tissue in between total and subtotal thyroidectomy for surgical treatment of MNG. In study temporary or permanent recurrent laryngeal nerve palsy, temporary or permanent hypoparathyroidism, hemorrhage, and wound complications were not significantly different in total thyroidectomy versus subtotal thyroidectomy [36]. In an analysis, goiter recurrence was significantly more in subtotal thyroidectomy than total thyroidectomy, but reintervention due to goiter was not significantly higher. Incidence of permanent recurrent laryngeal nerve palsy and permanent hypoparathyroidism was more in the total thyroidectomy group, but it was statistically nonsignificant [37]. Postoperatively serum TSH level should be monitored, many physicians prefer to start thyroid hormone as theoretically this may prevent recurrence of goiter, but studies have not shown this kind of benefit from thyroid hormone suppressive therapy [38–39].

#### **7.2 Medical treatment**

Levothyroxine (LT4) is used as TSH suppression therapy with variable success for nontoxic goiter. But suppressive therapy with LT4 is associated with thyrotoxicosis particularly in elderly patients. In this subset of patients, it is associated with osteopenia and cardiac arrhythmia and is inversely related to TSH concentration. Very rarely thyroid nodules can become functionally autonomous [40–41]. The goal is to keep TSH in between 0.1 mIU/L and 0.4 mIU/L. However the suppressive therapy is still a matter of debate. A meta-analysis of 11 studies has shown a twofold increase of chance in reduction in nodule size with LT4 suppressive therapy with proper selection of patient [42]. In another study with 54 patients 12 months after starting suppressive therapy, 37.1% of patients with single, solid nodules are found to regress more than 50% in nodule volume, and 20.3% of patients had reduction in nodule volume more than 20% but less than 49.9%. One-third of subjects with MNG had 50% or more regression of the glandular volume, whereas 46.8% were considered as nonresponsive. During suppressive therapy with LT4, the mean serum Tg level was also decreased significantly in these patients [43]. Because of lifelong therapy is required for prevention of goiter recurrence and is associated with risk of autonomous functioning of nodules, so in many patients, TSH suppression with LT4 is not feasible.

Antithyroid drugs propylthiouracil and thionamides (carbimazole and methimazole) are used to restore euthyroidism in toxic MNG. They can be used for a long time in patients whom surgery and radioiodine (I-131) treatment are contraindicated. But risk of agranulocytosis remains a major concern. In a recent study, methimazole was used for 8 years in 53 patients for treatment of toxic MNG without any serious adverse effect [44].

#### **7.3 Radioiodine (I-131)**

Radioiodine (I-131) is in use for management of thyroid disorder for more than 50 years. Radioiodine (I-131) is used particularly for thyrotoxic disorder mainly in Graves' disease. Radioiodine (I-131) also causes a significant reduction of thyroid gland volume. Due to its effect on reduction of thyroid gland volume, it has been used in management of nontoxic nodular thyroid disease also. In one study, 35 patients with nontoxic large MNG were treated with mean 1806 mbq (range 800–4000) of I-131. The mean reduction in thyroid volume was 43.18% (range −17.23–89.66%) seen after 3 months of treatment with I-131 [45]. In another

**107**

**Author details**

Hospitals, Jaipur, Rajasthan, India

provided the original work is properly cited.

Department of Endocrinology, SMS Medical College and Associated Group of

© 2020 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/ by/3.0), which permits unrestricted use, distribution, and reproduction in any medium,

\*Address all correspondence to: drsanjaysaran@gmail.com

Sanjay Saran

*Multinodular Goiter*

offspring remains in mind.

**8. Conclusion**

*DOI: http://dx.doi.org/10.5772/intechopen.90325*

study 63.4 ± 3.6% reduction in volume was seen with I-131 in rhTSH-treated nontoxic MNG patients [46]. Treatment with radioiodine (I-131) also relieves symptoms of tracheal and esophagus compression in large MNG. In toxic MNG radioiodine (I-131), euthyroid state is restored in addition to decrease of nodule size in MNG. Pretreatment with rhTSH increases the uptake of radioiodine (I-131) by thyroid tissue in a homogenous manner so that cold areas also take up radioiodine (I-131). In a small study, pretreatment with rhTSH is associated with greater reduction of thyroid volume in radioiodine (I-131)-treated patient [47]. Treatment with radioiodine (I-131) is also associated with adverse effects in a few cases, i.e., hypothyroidism, radiation thyroiditis, and autoimmune hyperthyroidism. Although long-term studies have not demonstrated carcinogenic effect of radioiodine (I-131), still concern regarding thyroid cancer, leukemia, and congenital abnormalities in

MNG is the most common thyroid disorder, but usually it is asymptomatic. When large enough it can cause compression to the trachea, esophagus, and neck veins. Other complications of MNG are autonomous functioning nodules, and very rarely it may progress to malignancy. Diagnostic evaluation includes clinical evaluation, thyroid function, and imaging study. Additional testing with FNAC may be required. Treatment modalities include drugs, surgery, and radioiodine (I-131), depending on results of diagnostic evaluation and associated complications.

### *Multinodular Goiter DOI: http://dx.doi.org/10.5772/intechopen.90325*

study 63.4 ± 3.6% reduction in volume was seen with I-131 in rhTSH-treated nontoxic MNG patients [46]. Treatment with radioiodine (I-131) also relieves symptoms of tracheal and esophagus compression in large MNG. In toxic MNG radioiodine (I-131), euthyroid state is restored in addition to decrease of nodule size in MNG. Pretreatment with rhTSH increases the uptake of radioiodine (I-131) by thyroid tissue in a homogenous manner so that cold areas also take up radioiodine (I-131). In a small study, pretreatment with rhTSH is associated with greater reduction of thyroid volume in radioiodine (I-131)-treated patient [47]. Treatment with radioiodine (I-131) is also associated with adverse effects in a few cases, i.e., hypothyroidism, radiation thyroiditis, and autoimmune hyperthyroidism. Although long-term studies have not demonstrated carcinogenic effect of radioiodine (I-131), still concern regarding thyroid cancer, leukemia, and congenital abnormalities in offspring remains in mind.
