The thyroid gland is a highly vascular, butterfly-shaped endocrine organ located in the anterior neck, extending from the sixth cervical to the first thoracic vertebra (C6–T1). It consists of two lobes joined by a thin isthmus overlying the second to fourth tracheal rings and is responsible for producing hormones essential for metabolic regulation. Enlargement of the thyroid gland is one of the most common endocrine presentations in clinical practice and may manifest as diffuse, nodular, toxic, or non-toxic goiter. Multinodular goiter (MNG) represents a late stage in the evolution of diffuse goiter and remains one of the most prevalent thyroid disorders globally. It is characterized by an irregularly enlarged gland containing multiple nodules, resulting from recurrent episodes of hyperplasia and involution of thyroid follicles. The etiopathogenesis of MNG is multifactorial and includes iodine deficiency, genetic predisposition, exposure to goitrogens, dyshormonogenesis, and environmental factors. Iodine deficiency remains the best-established risk factor, and the prevalence of goiter is inversely related to iodine intake. In iodine-deficient regions, endemic goiter affects more than 10% of the population, while in iodine-sufficient areas, sporadic goiter persists, often due to autoimmune thyroiditis or other intrinsic thyroid disorders.[1] Epidemiologically, MNG affects 500–600 million individuals worldwide, with a female predominance (3:1) and peak incidence between the third and fifth decades of life. In India, around 54 million people have goiter, with another 167 million at risk, particularly in sub-Himalayan regions and pockets of endemicity across various states. Even after universal salt iodization, persistence of MNG in certain areas indicates additional factors such as dietary goitrogens (cabbage, cassava, soybeans), chronic infections, or environmental pollutants. Genetic susceptibility, including polymorphisms in the TSH receptor and thyroglobulin genes, may also predispose individuals to nodular goiter formation.[2] The pathophysiological progression of MNG involves focal hyperplasia of follicular cells leading to nodule formation. Selwyn Taylor described five stages in its natural history, beginning with diffuse hyperplasia, followed by focal hyperfunction, hemorrhage and necrosis within lobules, and culminating in nodular transformation. Repeated cycles of hyperplasia and involution result in a heterogeneous gland with varying nodule sizes, fibrosis, hemorrhage, and cystic degeneration. Over time, some nodules may develop autonomous function, giving rise to toxic multinodular goiter, while others remain non-toxic but cause compressive symptoms due to enlargement.[3] Clinically, MNG may remain asymptomatic for years before presenting as a gradually enlarging neck mass. Symptoms result from pressure on adjacent structures—tracheal deviation causing dyspnea, esophageal compression leading to dysphagia, or retrosternal extension producing mediastinal compression. Hyperthyroid features may appear in toxic variants.[4] Fine Needle Aspiration Cytology (FNAC) is the gold-standard preoperative diagnostic tool for thyroid nodules. It provides a minimally invasive, reliable, and cost-effective means for differentiating benign from malignant lesions, especially when categorized according to the Bethesda System for Reporting Thyroid Cytopathology. However, its diagnostic accuracy may be limited in follicular neoplasms, which require histopathological evaluation to confirm capsular or vascular invasion. Hence, correlation of cytology with histopathology remains crucial for final diagnosis and management decisions.[5] Aim To study the clinical spectrum and cytological-histopathological correlation among patients with multinodular goiter undergoing total thyroidectomy. Objectives 1. To evaluate the demographic profile and clinical presentation of patients with multinodular goiter. 2. To correlate preoperative cytological findings with final histopathological diagnosis.

Source of Data: Data were obtained retrospectively from hospital records of patients who underwent total thyroidectomy for multinodular goiter at Kovai Medical Center and Hospital, Coimbatore, Tamil Nadu. Study Design: Retrospective observational study. Study Location: Department of General Surgery, Kovai Medical Center and Hospital, Coimbatore. Study Duration: Two years - September 2014 to September 2016. Sample Size: A total of 45 patients were included. Inclusion Criteria: • All clinically and radiologically diagnosed cases of multinodular goiter undergoing total thyroidectomy. Exclusion Criteria: • Patients undergoing surgery for solitary thyroid nodules. • Patients who had only hemithyroidectomy or near-total thyroidectomy. • Patients who refused surgery. Procedure and Methodology: Each patient’s demographic data, medical history, and clinical findings were recorded using a structured proforma. Preoperative investigations included Complete Blood Count, Random Blood Sugar, Serum Creatinine, Serum Calcium, Serum Albumin, Thyroid Profile (T3, T4, TSH), Fine-Needle Aspiration Cytology (FNAC), and imaging (Ultrasound neck ± X-ray neck). All patients underwent total thyroidectomy under general anesthesia following standard surgical protocol. The recurrent laryngeal nerve was identified and preserved bilaterally, and parathyroid glands were carefully dissected to prevent devascularization. The specimen was sent for histopathological examination. Postoperative monitoring included assessment of vocal cord function during extubation and serial serum calcium measurements on postoperative days 0, 1, 2, 3, and 15. Patients were evaluated clinically for hypocalcemia (tingling, paresthesia, carpopedal spasm, or positive Chvostek’s/Trousseau’s sign). Sample Processing: FNAC smears were prepared and stained with May-Grünwald-Giemsa and Papanicolaou stains, classified as per the Bethesda system. Surgical specimens were fixed in 10% formalin, sectioned, processed, and stained with hematoxylin and eosin. Histopathological diagnosis was recorded as benign (colloid goiter, adenoma, thyroiditis) or malignant (papillary, follicular, Hurthle-cell carcinoma). Statistical Methods: Data were entered in Microsoft Excel and analyzed using SPSS version 20. Descriptive statistics (mean, standard deviation, proportions) were used to summarize demographic and clinical data. Associations between FNAC and histopathology were evaluated using chi-square tests. A p-value < 0.05 was considered statistically significant. Data Collection: Patient demographics (age, sex), duration of symptoms, family history, compressive features, preoperative thyroid function, FNAC results, intra- and postoperative findings, were extracted from case sheets and operative notes. All patient identifiers were anonymized to ensure confidentiality.

Table 1: Demographic profile & clinical presentation (N=45) Variable Category / Metric n (%) or Mean(SD) 95% CI Age (years) Mean (reported) 45.47 (-) - Mean (approx. from grouped data)† 43.89 (15.26) 40.9-50.1 Age groups 10-20 1 (2.2) 0.4-11.4% 20-29 9 (20.0) 10.9-33.8% 30-39 10 (22.2) 12.5-36.3% 40-49 8 (17.8) 9.2-31.4% 50-59 10 (22.2) 12.5-36.3% 60-69 5 (11.1) 4.9-23.5% 70-79 2 (4.4) 1.2-14.8% Sex Female 37 (82.2) 68.7-90.7% Male 8 (17.8) 9.3-31.3% Compressive symptoms Any present 6 (13.3) 6.2-26.6% Asymptomatic 39 (86.7) 73.4-93.8% Duration of swelling <1 mo 7 (15.6) 7.8-28.7% 1-6 mo 11 (24.4) 14.1-38.9% 6-12 mo 7 (15.6) 7.8-28.7% 12-60 mo 10 (22.2) 12.5-36.3% >60 mo 9 (20.0) 10.9-33.8% Family history Present 1 (2.2) 0.4-11.4% Absent 44 (97.8) 88.6-99.6% IDL scopy Normal 45 (100) - Table 2 outlines the demographic characteristics and presenting features of the study cohort. The mean age of patients was approximately 45 years (mean ± SD = 43.9 ± 15.3 years), with a 95% CI ranging from 40.9 to 50.1 years, indicating predominance in the middle-aged group. The age distribution showed the highest frequency in the 30-39 and 50-59 year groups (each 22.2%), followed by the 20-29 year (20%) and 40-49 year (17.8%) ranges. A marked female preponderance was noted, with 37 women (82.2%) and only 8 men (17.8%), which was statistically significant (p = 1.5 × 10⁻⁵). Most patients (86.7%) were asymptomatic, whereas only 6 (13.3%) reported compressive symptoms such as dysphagia or dyspnoea. The mean duration of swelling varied widely, with 24.4% presenting within 1-6 months, 22.2% with 12-60 months, and 20% with > 5 years of symptoms, reflecting the chronic nature of multinodular goiter. Family history was positive in only 1 patient (2.2%), and indirect laryngoscopic examination showed normal vocal cord mobility in all cases (100%). Altogether, the demographic profile supports that MNG predominantly affects middle-aged females and usually presents as a long-standing, asymptomatic neck swelling. Table 2: Cytology-histopathology correlation (N=45) FNAC category HPE benign HPE malignant Malignancy risk % (95% CI) Key test Colloid nodule 24 2 7.7% (2.1-24.1) Ref. Follicular neoplasm 8 6 42.9% (21.4-67.4) vs Colloid nodule → Fisher exact OR 9.00 (1.50-53.86), p=0.014 Lymphocytic thyroiditis 2 0 0.0% (0.0-65.8) Descriptive Suspicious for malignancy 1 0 0.0% (0.0-79.3) Descriptive Inconclusive 0 2 - Descriptive Overall 35 10 22.2% (12.5-36.3) - Fisher exact p=0.003; OR 11.56 (95% CI 2.06-64.86). Table 3 compares preoperative FNAC diagnoses with final histopathological findings, illustrating the diagnostic accuracy and predictive value of cytology. Out of 26 patients cytologically diagnosed with colloid nodule, 24 (92.3%) were histologically benign, while 2 (7.7%) turned out malignant. In contrast, among 14 cases labeled follicular neoplasm, 6 (42.9%, 95% CI 21.4-67.4) were malignant on HPE, showing a significant correlation (Fisher’s exact p = 0.014; OR = 9.00, 95% CI 1.50-53.86) compared to colloid nodules. Lymphocytic thyroiditis (n = 2) and suspicious cytology (n = 1) showed no malignancy, while 2 inconclusive cases proved malignant on final histology. Overall, 10 out of 45 patients (22.2%, 95% CI 12.5-36.3) harbored carcinoma-predominantly papillary type. When FNAC results were dichotomized into benign vs non-benign, malignancy occurred in 8/17 non-benign versus 2/28 benign cytologies, yielding a highly significant association (Fisher’s p = 0.003; OR = 11.56, 95% CI 2.06-64.86). These findings affirm that preoperative FNAC provides a reliable screening tool, with high specificity but occasional under-detection of follicular malignancies requiring histological confirmation.

Table 1 (Demography & presentation) The cohort demonstrates the usual MNG demography: mid-life predominance (mean 44-45 y) and marked female preponderance (82.2%). This aligns with endocrine epidemiology data in both iodine-deficient and -replete settings Ríos-Zambudio A et al.(2004)[4] and with Indian data showing substantial goiter burden and female skew Hanumanthappa MB et al.(2015)[5] & Shaikh IA et al.(2012)[6]. Clinically, 86.7% were asymptomatic at presentation-again in line with the long, indolent evolution of MNG-with only 13.3% reporting compressive symptoms. The broad spread in duration (including 20% > 5 years) reinforces the chronicity of nodular disease and the need for longitudinal surveillance to detect interval growth or evolving toxicity. Efremidou EI et al.(2009)[7] & Thomusch O et al.(2003)[8] Table 2 (FNAC ↔ HPE correlation) Cytology-histology pairing shows a low malignancy rate for FNAC-labelled colloid nodules (7.7%) but a high conversion for follicular neoplasm (42.9%), producing a strong association versus colloid (OR 9.0; p = 0.014) and an even more pronounced signal when “non-benign” FNAC is contrasted with benign categories (OR 11.56; p = 0.003). This pattern is biologically and methodologically coherent: follicular-patterned lesions require capsular/vascular invasion on histology for a definitive diagnosis, so Bethesda IV categories naturally carry higher malignancy risk on excision than Bethesda II/thyroiditis Padur AA et al.(2016)[9] & Cibas ES et al.(2017)[10]. Overall malignancy proportion (22.2%) is compatible with the Bethesda-anchored ROM ranges for mixed surgical series and with Indian surgical cohorts where case-mix often enriches for higher-risk nodules Bongiovanni M et al.(2012)[11].

The present retrospective observational study highlights that multinodular goiter (MNG) predominantly affects middle-aged females and usually presents as a long-standing, asymptomatic thyroid enlargement. The cytological-histopathological correlation revealed an overall malignancy rate of 22.2%, emphasizing that MNG carries a significant risk of occult carcinoma, particularly in cases reported as follicular neoplasm on FNAC. Total thyroidectomy was found to be a safe and effective treatment modality, with transient hypocalcaemia (22.2%). These were comparable with global literature benchmarks and were self-limiting in most cases. Thus, thorough preoperative evaluation, meticulous intraoperative nerve and parathyroid identification, and vigilant postoperative monitoring are crucial to achieving optimal outcomes in MNG surgery.

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