ISSN: 2640-7582

International Journal of Clinical Endocrinology and Metabolism

Research Article       Open Access      Peer-Reviewed

Retrospective Study Evaluating Histopathological Thyroid Findings in an Iodine-Sufficient Area: Correlation with Anthropometric Characteristics and Thyroid Gland Morphological Parameters

Ioannis Legakis1*, Theodoros Bourchas2, Stylianos Archontakis2, Vasilis Psaltakos2 and GP Chrousos3

1Endocrinology Department, Henry Dunant Hospital, Greece
2Head & Neck Clinic, Henry Dunant Hospital, Greece
3Professor Emeritus of Pediatrics and Endocrinology, National and Kapodistrian University of Athens School of Medicine, Athens, Greece

Author and article information

*Corresponding author: Ioannis Legakis, Endocrinology Department, Henry Dunant Hospital, Greece, E-mail: [email protected]
doi : 10.17352/ijcem.000067
Submited: 02 March, 2026 | Accepted: 10 March, 2026 | Published: 11 March, 2026
Keywords: Nodular goiter; Thyroid; Follicular adenoma; Papillary carcinoma

Cite this as

Legakis I, et al. Retrospective Study Evaluating Histopathological Thyroid Findings in an Iodine-Sufficient Area: Correlation with Anthropometric Characteristics and Thyroid Gland Morphological Parameters. Int J Clin Endocrinol Metab. 2026; 12(1): 001-009. Available from: 10.17352/ijcem.000067

Copyright License

© 2026 Legakis I, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Objectives: To examine the association between thyroid nodular formation and histopathological outcomes in an iodine-sufficient region, we retrospectively reviewed histopathological findings from surgically excised thyroid specimens collected over three years (2021–2023) at Henry Dunant Hospital in the metropolitan area of Athens. Histological diagnoses, along with patient anthropometric characteristics and thyroid morphological parameters, were analysed to evaluate malignancy risk and enhance prognostic assessment.

Methods: Histopathological reports from 192 patients (138 men and 54 women) were retrospectively reviewed. Patients were categorised into three age groups: Group A (<40 years: 42 men, 14 women), Group B (40–69 years: 87 men, 35 women), and Group C (≥69 years: 9 men, 5 women). Correlations were performed between anthropometric characteristics and thyroid morphological parameters, including gland weight, gland dimensions, and the number of nodules per lobe.

Results: An age-related increase in thyroid gland weight was observed, which was more pronounced in the female population (p < 0.027). Multinodular goitre was present in more than 80% of patients across all age groups. In women aged 40–49 years, a significantly larger nodule diameter was observed in the right thyroid lobe. In contrast, an increase in the number of nodules was noted exclusively in the left lobe of men aged ≥69 years.

The prevalence of a solitary thyroid nodule was similar in men aged <40 and 40–69 years (23.8% and 24.1%, respectively), while women showed a higher prevalence in the <40-year age group (42.9%).

No statistically significant sex-related differences were observed in the incidence of papillary or follicular thyroid carcinoma. However, papillary carcinoma predominated over follicular carcinoma in both sexes within the <40 and 40–69 age groups. Metastatic disease was more frequently observed in men aged 40–69 years. Medullary carcinoma was identified exclusively in men, with a prevalence of 2.3% in the 40–69-year age group. Follicular adenoma was the most common histopathological diagnosis across all age groups.

Conclusions: Consistent with previous reports, follicular adenoma was the most frequent histopathological finding in patients with multinodular goitre, while papillary carcinoma represented the predominant thyroid cancer subtype. Thyroid gland weight increased with age, particularly among women, but this increase was not associated with a higher risk of malignancy. Further studies are required to confirm these findings and better define their implications for long-term clinical outcomes.

Indexing and Abstracting

Introduction

Epidemiological and clinical evidence indicate that the prevalence of thyroid nodules varies with anthropometric factors, including sex, body mass index, and age, as well as with the method of detection (self-detection, palpation, ultrasonography, or autopsy) and geographic region. In recent years, incidence rates have increased, particularly among asymptomatic individuals undergoing routine screening, contributing to overdiagnosis and, in many cases, subsequent medical overuse [1].

The clinical evaluation of thyroid nodules relies on established diagnostic tools and management algorithms supported by cost-effectiveness analyses. Despite advances in ultrasound-based risk stratification systems—including improvements in ultrasonographic technology, shear-wave elastography, three-dimensional (3D) ultrasound imaging, and modern surgical techniques—considerable variability persists in the diagnosis and management of thyroid nodules [2,3].

To assess the malignant potential of thyroid nodules in an iodine-sufficient population, a retrospective study was conducted involving patients who underwent thyroidectomy at Henry Dunant Hospital over 3 years. Postoperative histopathological findings were correlated with patients’ anthropometric characteristics and thyroid morphological parameters.

Materials and methods

Histopathological reports from 192 patients (138 men and 54 women) were retrospectively reviewed. Patients were categorised into three age groups: Group A (<40 years: 42 men, 14 women), Group B (40–69 years: 87 men, 35 women), and Group C (≥69 years: 9 men, 5 women).

The anthropometric characteristics evaluated in this study included age and sex. Age was categorised into three groups (<40 years, 40–69 years, and ≥69 years), and sex was recorded as male or female. These variables were incorporated into the statistical analysis as grouping factors to examine their associations with thyroid morphological parameters, including gland weight, lobe volumes, and the number and diameter of nodules. Correlations were performed between anthropometric characteristics and thyroid morphological parameters, including gland weight, gland dimensions, and the number of nodules per lobe.

Statistical analysis

Quantitative variables are presented using measures of central tendency and dispersion (mean, median, standard deviation, minimum, and maximum), whereas categorical variables are summarised using absolute frequencies and percentages. The Mann–Whitney U test was used to compare continuous variables between groups, and the Kruskal–Wallis test was used to compare continuous variables across more than two groups when appropriate.

Associations between categorical variables were evaluated using the Pearson chi-square test. When contingency tables contained small expected cell counts, particularly in analyses involving the ≥69-year age group, chi-square tests with Monte Carlo simulation were applied to obtain reliable p-values.

All statistical tests were two-sided, and a p-value <0.05 was considered statistically significant. In addition to p-values, effect size measures (risk differences, odds ratios or Cohen’s d, where appropriate) were examined to facilitate clinical interpretation of observed group differences. Statistical analyses were performed using IBM SPSS Statistics for Windows, version 29.0 (IBM Corp., Armonk, NY, USA).

Results

Thyroid gland weight demonstrated a significant age-related increase, with a more pronounced effect observed in women (p < 0.027) (Table 1). Multinodular goitre was highly prevalent, occurring in more than 80% of cases across all age groups.

Table 1: Quantitative variables by age group and gender.
Variable Gender p-value (overall) p-value (groups 1-2) p-value (groups 1-3) p-value (groups 2-3)
Right lobe volume (RLV) Female 0.530      
Male 0.399      
Left lobe volume (LLV) Female 0.259      
Male 0.188      
Thyroid gland weight (gr) Female 0.049 0.198 0.027 0.051
Male 0.160      
Right lobe nodules (RLN) (cm) Female 0.149      
Male 0.078      
RLN diameter (cm) Female 0.311      
Male 0.647      
Left lobe nodules (LLN)(cm) Female 0.922      
Male 0.033 0.109 0.022 0.059
LLN diameter (cm) Female 0.519      
Male 0.373      
Isthmus Female 0.197      
Male 0.791      
Isthmus nodules diameter(IND) (cm) Female 0.516      
Male 0.791      
  • p-value (overall) compares if there is a difference between the 3 groups (Kruskal-Wallis’ test). Pairwise comparisons were performed with Mann-Whitney test.
  • Group 1: age<40years old
  • Group 2: 40≤age<69
  • Group 3: age≥69

Among women aged 40–49 years, nodule diameter was significantly greater in the right thyroid lobe (p < 0.038) (Tables 2a,b), and corresponded to a small-to-moderate effect size (Cohen’s d = 0.32). In contrast, in men, a significant increase in the number of nodules was observed exclusively in the left lobe in individuals older than 69 years (p < 0.022) (Table 1).

Table 2a: Quantitative variables by gender and age group.
Variable Age groups Gender N Mean Median SD Min Max p-value
Right lobe volume Age<40 Male 42 36.85 18.00 41.97 0.00 216.00    0.150  
Female 14 53.96 40.35 52.12 8.75 200.00
Total 56 41.12 23.20 44.85 0.00 216.00
40≤Age<69 Male 87 42.94 22.50 53.95 0.00 356.25    0.775  
Female 35 57.80 30.00 139.03 0.00 840.00
Total 122 47.20 23.44 86.86 0.00 840.00
Age≥69 Male 9 81.26 70.00 91.77 0.00 250.00    1.000  
Female 5 52.20 66.00 28.83 15.00 80.00
Total 14 70.88 68.00 75.15 0.00 250.00
Total Male 138 43.58 21.63 54.35 0.00 356.25    0.206
Female 54 56.29 31.19 114.60 0.00 840.00
Total 192 47.16 24.60 76.13 0.00 840.00
Left lobe volume Age<40 Male 42 37.23 19.00 50.24 0.00 270.00    0.374  
Female 14 27.81 13.56 37.92 0.00 133.00
Total 56 34.88 17.25 47.31 0.00 270.00
40≤Age<69 Male 87 35.06 24.00 36.72 0.00 200.00    0.318  
Female 35 50.34 16.20 126.78 0.00 756.00
Total 122 39.44 23.50 74.31 0.00 756.00
Age≥69 Male 9 57.51 42.00 57.38 4.60 189.00    0.898  
Female 5 73.52 48.00 86.96 12.35 225.00
Total 14 63.23 45.00 66.46 4.60 225.00
Total Male 138 37.19 24.00 42.71 0.00 270.00    0.309
Female 54 46.64 16.10 106.79 0.00 756.00
Total 192 39.85 22.50 67.02 0.00 756.00
Thyroid gland weight (gr) Age<40 Male 42 28.54 19.25 28.40 0.50 174.00    0.188  
Female 14 37.47 24.50 31.02 10.70 108.00
Total 56 30.77 20.00 29.05 0.50 174.00
40≤Age<69 Male 87 34.70 23.00 34.64 7.00 200.00    0.755  
Female 35 31.23 26.00 20.61 8.00 100.00
Total 122 33.70 24.00 31.22 7.00 200.00
Age≥69 Male 9 68.69 49.00 56.07 8.20 160.00    1.000  
Female 5 56.54 52.00 35.12 20.70 113.00
Total 14 64.35 50.50 48.48 8.20 160.00
Total Male 138 35.04 23.00 35.58 0.50 200.00    0.274  
Female 54 35.19 27.00 25.62 8.00 113.00
Total 192 35.08 24.00 33.02 0.50 200.00
Right lobe nodules (RLN)(cm) Age<40 Male 42 1.62 1.00 1.25 0.00 5.00    0.456  
Female 14 1.36 1.00 1.22 0.00 4.00
Total 56 1.55 1.00 1.23 0.00 5.00
40≤Age<69 Male 87 1.44 1.00 1.06 0.00 4.00    0.022  
Female 35 1.91 2.00 1.12 0.00 4.00
Total 122 1.57 1.00 1.10 0.00 4.00
Age≥69 Male 9 2.11 2.00 0.93 1.00 3.00    0.438  
Female 5 2.60 3.00 1.14 1.00 4.00
Total 14 2.29 2.50 0.99 1.00 4.00
Total Male 138 1.54 1.00 1.12 0.00 5.00    0.097  
Female 54 1.83 2.00 1.18 0.00 4.00
Total 192 1.62 1.00 1.14 0.00 5.00
RLN diameter (cm) Age<40 Male 42 1.25 1.00 1.13 0.00 5.50    0.231  
Female 14 1.59 1.50 1.24 0.00 4.00
Total 56 1.33 1.00 1.16 0.00 5.50
40≤Age<69 Male 87 1.44 1.40 1.14 0.00 4.60    0.065  
Female 35 1.87 1.70 1.18 0.00 4.30
Total 122 1.56 1.50 1.16 0.00 4.60
Age≥69 Male 9 1.66 1.50 0.94 0.50 3.00    0.699  
Female 5 1.44 0.80 0.92 0.80 2.80
Total 14 1.58 1.30 0.90 0.50 3.00
Total Male 138 1.40 1.25 1.12 0.00 5.50    0.038  
Female 54 1.76 1.50 1.17 0.00 4.30
Total 192 1.50 1.40 1.14 0.00 5.50
Left lobe nodules (LLN) (cm) Age<40 Male 42 1.67 1.00 1.41 0.00 4.00 0.190
Female 14 1.14 1.00 1.35 0.00 4.00
Total 56 1.54 1.00 1.40 0.00 4.00
40≤Age<69 Male 87 1.62 1.00 1.40 0.00 5.00 0.438
Female 35 1.80 2.00 1.35 0.00 5.00
Total 122 1.67 1.00 1.38 0.00 5.00
Age≥69 Male 9 1.78 2.00 1.39 0.00 4.00 0.147
Female 5 3.00 3.00 1.22 1.00 4.00
Total 14 2.21 2.50 1.42 0.00 4.00
Total Male 138 1.64 1.00 1.39 0.00 5.00 0.674
Female 54 1.74 1.50 1.40 0.00 5.00
Total 192 1.67 1.00 1.39 0.00 5.00
LLN diameter (cm) Age<40 Male 42 0.98 0.70 1.05 0.00 3.60 0.515
Female 14 0.87 0.40 1.20 0.00 4.30
Total 56 0.95 0.65 1.08 0.00 4.30
40≤Age<69 Male 87 1.19 1.00 1.24 0.00 7.00 0.745
Female 35 1.28 0.90 1.27 0.00 5.00
Total 122 1.22 1.00 1.24 0.00 7.00
Age≥69 Male 9 1.37 1.20 1.32 0.00 3.60 0.797
Female 5 1.66 0.50 2.34 0.40 5.80
Total 14 1.47 0.90 1.67 0.00 5.80
Total Male 138 1.14 0.80 1.19 0.00 7.00 0.981
Female 54 1.21 0.80 1.36 0.00 5.80
Total 192 1.16 0.80 1.24 0.00 7.00
Isthmus Age<40 Male 41 0.20 0.00 0.60 0.00 3.00    0.580  
Female 14 0.07 0.00 0.27 0.00 1.00
Total 55 0.16 0.00 0.54 0.00 3.00
40≤Age<69 Male 87 0.13 0.00 0.37 0.00 2.00    0.664  
Female 35 0.11 0.00 0.40 0.00 2.00
Total 122 0.12 0.00 0.38 0.00 2.00
Age≥69 Male 9 0.367 0.000 0.6964 0.0 2.0    0.364  
Female 5 0.000 0.000 0.0000 0.0 0.0
Total 14 0.236 0.000 0.5759 0.0 2.0
Total Male 137 0.163 0.000 0.4733 0.0 3.0    0.270  
Female 54 0.093 0.000 0.3512 0.0 2.0
Total 191 0.143 0.000 0.4424 0.0 3.0
Isthmus nodules diameter (IND) (cm) Age<40 Male 42 0.12 0.00 0.36 0.00 1.80    0.561  
Female 14 0.03 0.00 0.11 0.00 0.40
Total 56 0.09 0.00 0.31 0.00 1.80
40≤Age<69 Male 87 0.09 0.00 0.29 0.00 1.50    0.563  
Female 35 0.12 0.00 0.48 0.00 2.50
Total 122 0.10 0.00 0.35 0.00 2.50
Age≥69 Male 8 0.26 0.00 0.49 0.00 1.10    0.524  
Female 5 0.00 0.00 0.00 0.00 0.00
Total 13 0.16 0.00 0.39 0.00 1.10
Total Male 137 0.11 0.00 0.32 0.00 1.80    0.267  
Female 54 0.09 0.00 0.39 0.00 2.50
Total 191 0.10 0.00 0.34 0.00 2.50
  • Mann-Whitney test was implemented
Table 2b: Quantitative variables by gender.
Variable Gender N Mean Median SD Min Max p-value
Right lobe volume Male 138 43.58 21.63 54.35 0.00 356.25 0.206
Female 54 56.29 31.19 114.60 0.00 840.00
Total 192 47.16 24.60 76.13 0.00 840.00
Left lobe volume Male 138 37.19 24.00 42.71 0.00 270.00 0.309
Female 54 46.64 16.10 106.79 0.00 756.00
Total 192 39.85 22.50 67.02 0.00 756.00
Thyroid gland weight (gr) Male 138 35.04 23.00 35.58 0.50 200.00 0.274
Female 54 35.19 27.00 25.62 8.00 113.00
Total 192 35.08 24.00 33.02 0.50 200.00
Right lobe nodules (RLN) (cm) Male 138 1.54 1.00 1.12 0.00 5.00 0.097
Female 54 1.83 2.00 1.18 0.00 4.00
Total 192 1.62 1.00 1.14 0.00 5.00
RLN diameter (cm) Male 138 1.40 1.25 1.12 0.00 5.50 0.038
Female 54 1.76 1.50 1.17 0.00 4.30
Total 192 1.50 1.40 1.14 0.00 5.50
Left lobe nodules (LLN) (cm) Male 138 1.64 1.00 1.39 0.00 5.00 0.674
Female 54 1.74 1.50 1.40 0.00 5.00
Total 192 1.67 1.00 1.39 0.00 5.00
LLN diameter (cm) Male 138 1.14 0.80 1.19 0.00 7.00 0.981
Female 54 1.21 0.80 1.36 0.00 5.80
Total 192 1.16 0.80 1.24 0.00 7.00
Isthmus Male 137 0.16 0.00 0.47 0.00 3.00 0,270
Female 54 0.09 0.00 0.35 0.00 2.00
Total 191 0.14 0.00 0.44 0.00 3.00
Isthmus nodules diameter (IND)(cm) Male 137 0.11 0.00 0.32 0.00 1.80 0.267
Female 54 0.09 0.00 0.39 0.00 2.50
Total 191 0.10 0.00 0.34 0.00 2.50
  • Mann-Whitney test was implemented

The prevalence of solitary thyroid nodules in men was comparable between the <40 and 40–69 age groups (23.8% and 24.1%, respectively). In women, solitary nodules were most frequently observed in the <40 age group (42.9%) (Table 3). Hence, the absolute risk difference between genders for the solitary nodules in the <40-year age group was 19.1%.

Table 3: Qualitative variables by gender and age group.
Variable   Ν %   Ν %   % difference p-value
Age group: Age < 40
Gender   Males   Females      
    42 100.0   14 100.0      
Subtotal thyroidectomy left lobe                  
  No 40 97.6   14 100.0   -2.4 0.555
  Yes 1 2.4   0 0.0   2.4
Subtotal thyroidectomy right lobe                  
  No 40 97.6   14 100.0   -2.4 0.555
  Yes 1 2.4   0 0.0   2.4
Total Thyroidectomy                  
  No 3 7.1   0 0.0   7.1 0.304
  Yes 39 92.9   14 100.0   -7.1
Multi-nodular Goitre (MNG)                  
  No 8 19.0   4 28.6   -9.5 0.452
  Yes 34 81.0   10 71.4   9.5
Single nodule                  
  No 32 76.2   8 57.1   19.0 0.172
  Yes 10 23.8   6 42.9   -19.0
In situ_ca                  
  No 33 78.6   14 100.0   -21.4 0.059
  Yes 9 21.4   0 0.0   21.4
Papillary_ca                  
  No 29 69.0   11 78.6   -9.5 0.495
  Yes 13 31.0   3 21.4   9.5
Follicular ca                  
  No 36 85.7   12 85.7   0.0 1.000
  Yes 6 14.3   2 14.3   0.0
Mixed_ca                  
  No 36 85.7   12 85.7   0.0 1.000
  Yes 6 14.3   2 14.3   0.0
Follicular adenoma                  
  No 20 47.6   6 42.9   4.8 0.757
  Yes 22 52.4   8 57.1   -4.8
Metastases lymph                  
  No 40 95.2   14 100.0   -4.8 0.406
  Yes 2 4.8   0 0.0   4.8
Hyperplastic_MNG                  
  No 11 26.2   5 35.7   -9.5 0.495
  Yes 31 73.8   9 64.3   9.5
Hurth cell adenoma                  
  No 41 97.6   12 85.7   11.9 0.087
  Yes 1 2.4   2 14.3   -11.9
Acidophilic adenoma                  
  No 40 95.2   12 85.7   9.5 0.231
  Yes 2 4.8   2 14.3   -9.5
Medullary_ca                  
  No 42 100.0   13 92.9   7.1 0.081
  Yes 0 0.0   1 7.1   -7.1
Pyramoid lobe                  
  No 41 97.6   13 92.9   4.8 0.406
  Yes 1 2.4   1 7.1   -4.8
Age group: 40 ≤ Age < 69
Gender   Males   Females      
    87 100.0   35 100.0      
Subtotal thyroidectomy left lobe                  
  No 84 96.6   35 100.0   -3.4 0.266
  Yes 3 3.4   0 0.0   3.4
Subtotal thyroidectomy right lobe                  
  No 86 98.9   33 94.3   4.6 0.141
  Yes 1 1.1   2 5.7   -4.6
Total Thyroidectomy                  
  No 4 4.6   2 5.7   -1.1 0.796
  Yes 83 95.4   33 94.3   1.1
Multi-nodular Goitre (MNG)                  
  No 16 18.4   3 8.6   9.8 0.176
  Yes 71 81.6   32 91.4   -9.8
Single nodule                  
  No 65 74.7   29 82.9   -8.1 0.557
  Yes 21 24.1   6 17.1   7.0
In situ_ca                  
  No 77 88.5   30 85.7   2.8 0.671
  Yes 10 11.5   5 14.3   -2.8
Papillary_ca                  
  No 63 72.4   25 71.4   1.0 0.913
  Yes 24 27.6   10 28.6   -1.0
Folliccular_ca                  
  No 71 81.6   28 80.0   1.6 0.837
  Yes 16 18.4   7 20.0   -1.6
Mixed_ca                  
  No 73 83.9   29 82.9   1.1 0.785
  Yes 14 16.1   6 17.1   -1.1
Follicular adenoma                  
  No 46 52.9   14 40.0   12.9 0.198
  Yes 41 47.1   21 60.0   -12.9
Metastases lymph                  
  No 81 93.1   31 88.6   4.5 0.145
  Yes 5 5.7   0 0.0   5.7
Hyperplastic_MNG                  
  No 22 25.3   4 11.4   13.9 0.091
  Yes 65 74.7   31 88.6   -13.9
Hurth cell adenoma                  
  No 80 92.0   31 88.6   3.4 0.555
  Yes 7 8.0   4 11.4   -3.4
Acidophilic adenoma                  
  No 84 96.6   31 88.6   8.0 0.086
  Yes 3 3.4   4 11.4   -8.0
Medullary_ca                  
  No 85 97.7   35 100.0   -2.3 0.366
  Yes 2 2.3   0 0.0   2.3
Pyramoid lobe                  
  No 83 95.4   33 94.3   1.1 0.796
  Yes 4 4.6   2 5.7   -1.1
Age group: Age≥69
Gender   Males   Females      
    9 100.0   5 100.0      
                   
Subtotal thyroidectomy left lobe                  
  No 9 100.0   5 100.0   0.0 1.000
  Yes 0 0.0   0 0.0   0.0
Subtotal thyroidectomy right lobe                  
  No 9 100.0   5 100.0   0.0 1.000
  Yes 0 0.0   0 0.0   0.0
Total Thyroidectomy                  
  No 0 0.0   0 0.0   0.0 1.000
  Yes 9 100.0   5 100.0   0.0
Multi-nodular Goitre                  
  No 0 0.0   0 0.0   0.0 1.000
  Yes 9 100.0   5 100.0   0.0
Single nodule                  
  No 8 88.9   5 100.0   -11.1 0.439
  Yes 1 11.1   0 0.0   11.1
In situ_ca                  
  No 9 100.0   3 60.0   40.0 0.040
  Yes 0 0.0   2 40.0   -40.0
Papillary_ca                  
  No 8 88.9   3 60.0   28.9 0.052
  Yes 0 0.0   2 40.0   -40.0
Follicular_ca                  
  No 9 100.0   3 60.0   40.0 0.040
  Yes 0 0.0   2 40.0   -40.0
Mixed_ca                  
  No 9 100.0   3 60.0   40.0 0.040
  Yes 0 0.0   2 40.0   -40.0
Follicular adenoma                  
  No 3 33.3   1 20.0   13.3 0.597
  Yes 6 66.7   4 80.0   -13.3
Metastases lymph                  
  No 9 100.0   5 100.0   0.0 1.000
  Yes 0 0.0   0 0.0   0.0
Hyperplastic_MNG                  
  No 1 11.1   1 20.0   -8.9 0.649
  Yes 8 88.9   4 80.0   8.9
Hurth cell adenoma                  
  No 7 77.8   4 80.0   -2.2 0.923
  Yes 2 22.2   1 20.0   2.2
Acidophilic adenoma                  
  No 7 77.8   4 80.0   -2.2 0.923
  Yes 2 22.2   1 20.0   2.2
Medullary_ca                  
  No 9 100.0   5 100.0   0.0 1.000
  Yes 0 0.0   0 0.0   0.0
Pyramoid lobe                  
  No 9 100.0   5 100.0   0.0 1.000
  Yes 0 0.0   0 0.0   0.0
The chi-square test was implemented; when expected cell counts were small, Monte Carlo-simulated p-values were used.

No statistically significant sex-based differences were identified in the incidence of papillary or follicular thyroid carcinoma (Table 4). Papillary carcinoma appeared more frequent than follicular carcinoma in both sexes within the <40 and 40–69 age groups (Table 3); however, these observations should be interpreted descriptively unless supported by statistically significant differences. Metastatic disease was more frequently observed in men aged 40–69 years, although this difference did not reach statistical significance.

Medullary thyroid carcinoma was identified exclusively in men, with a prevalence of 2.3% in the 40–69 age group (Table 3). However, the number of cases was small, and no statistical inference can be drawn for the general population. Metastatic lymph node involvement was observed only among men in the 40–69-year age group (5.7%), corresponding to an absolute risk difference of 5.7% (OR ≈ 4.5); however, the small number of cases limits definitive inference.

Across all age groups, follicular adenoma was the most common histopathological diagnosis among resected thyroid specimens (Table 4).

Table 4: Quantitative variables by age group and gender.
Variable Gender p-value (overall)
Subtotal thyroidectomy left lobe Female 0.823
Male -
Subtotal thyroidectomy right lobe Female 0.793
Male 0.569
Total thyroidectomy Female 0.639
Male 0.569
Multi-nodular Goitre Female 0.361
Male 0.113
Single nodule Female 0.843
Male 0.067
In situ_ca Female 0.143
Male 0.068
Papillary_ca Female 0.191
Male 0.717
Folliccular_ca Female 0.336
Male 0.470
Mixed_ca Female 0.705
Male 0.419
Follicular adenoma Female 0.501
Male 0.650
Metastases lymph Female 0.747
Male -
Hyperplastic_MNG Female 0.618
Male 0.141
Hurth cell adenoma Female 0.102
Male 0.855
Acidophilic adenoma Female 0.050
Male 0.855
Medullary_ca Female 0.552
Male 0.233
Pyramoid lobe Female 0.684
Male 0.834
  • p-value (overall) tests for a difference among the 3 groups (Chi-square test was implemented; when expected cell counts were small, Monte Carlo-simulated p-values were used). Pairwise comparisons were also performed using the Chi-square test.
  • Group 1: age < 40 years old
  • Group 2: 40 ≤ age < 69
  • Group 3: age ≥ 69

Discussion

Recent progress in the diagnosis and treatment of thyroid cancer has substantially transformed current management paradigms. Ultrasound-based risk stratification systems for thyroid nodules, together with minimally invasive therapeutic approaches for low-risk thyroid malignancies, have become integral components of routine clinical practice. Consequently, there is an increasing demand for well-designed randomised controlled trials and large-scale population-based observational studies to strengthen evidence-based decision-making and inform the development of clinical management guidelines for thyroid cancer [4-6].

Thyroid nodules are a common finding in the general population and are most frequently assessed using ultrasonography (US). Previous studies comparing solitary thyroid nodules (STNs) and multinodular goitre (MNG) have yielded heterogeneous results, particularly regarding patient age and sex [7].

Epidemiological evidence suggests that the prevalence of thyroid nodules may exceed 67%, depending on the diagnostic approach used (palpation, ultrasonography, or autopsy), with marked variation across geographic regions [8,9]. Estimates based on ultrasound screening and autopsy studies report prevalence rates ranging from 34% to 66% [10]. Several determinants, including female sex, higher body mass index (BMI), and increasing age, have consistently been associated with a greater likelihood of thyroid nodule development [11]. Moreover, women tend to develop thyroid nodules at an earlier age than men, while multinodular goitre has been more frequently linked to multicentric malignancy, particularly in papillary thyroid carcinoma [12].

Marked geographic differences have been reported, with Denmark and South Africa documenting nodular presentation rates of 54% and 79%, respectively, whereas substantially lower rates of approximately 30% have been observed in Canada and the United States [13].

Despite the high prevalence of thyroid nodules, the majority are benign or lack ultrasonographic features indicative of malignancy and therefore have limited clinical relevance [14].

In agreement with previously published data, our findings showed that multinodular goitre was present in more than 80% of patients, irrespective of sex or age group. Thyroid gland weight increased progressively with age (with mean values rising from 30.8 g in individuals younger than 40 years to 64.4 g in those aged ≥69 years, representing a moderate-to-large standardised difference (Cohen’s d ≈ 0.8)), a trend that was more pronounced among female patients.

Sex-related differences in nodule characteristics were also identified. Women aged 40–49 years exhibited a significant increase in nodule diameter in the right thyroid lobe (p < 0.038). In contrast, men showed an age-related increase in the number of nodules confined to the left thyroid lobe after age 69 years.

Age-dependent variation was also evident in the prevalence of solitary thyroid nodules. Among women, the highest frequency was observed in those younger than 40 years (42.9%), whereas men showed comparable prevalence rates in the <40-year (23.8%) and 40–69-year (24.1%) age categories. Some of our findings, though, are derived from small age strata, particularly the ≥69-year group, and should be interpreted cautiously and viewed as exploratory observations that require confirmation in larger cohorts.

The incidence of malignancy among thyroid nodules reported in the literature has risen substantially following the widespread implementation of thyroid ultrasonography. Reported malignancy rates range from 4% to 42%. They are influenced by regional cancer prevalence, incidental detection, environmental and endemic factors, inequalities in healthcare access, radiation exposure, and iodine deficiency, particularly in low- and middle-income countries [16,17]. Despite these regional disparities, the female-to-male ratio of thyroid cancer remains relatively stable worldwide at approximately 3:1 [18].

A retrospective analysis conducted at the Ankara Oncology Training and Research Hospital assessed thyroid nodularity and malignancy in a high-risk population. Clinically significant nodules were detected in 6.4% of female and 1.5% of male patients, while malignant lesions accounted for approximately 4% - 6% of all thyroid nodules [19].

Global incidence data from the Cancer Incidence in Five Continents database, spanning 1973 to 2007 and including 24 populations from the Americas, Asia, Europe, Africa, and Oceania, revealed a worldwide increase in thyroid cancer incidence. The highest rates were observed among women, particularly in Israel and within the United States Surveillance, Epidemiology, and End Results (SEER) registry [20].

A prospective cohort study conducted at the Brigham & Women’s Hospital Thyroid Nodule Clinic between 1995 and 2011 further examined the relationship between age, thyroid nodularity, and cancer risk. The investigators reported that while the prevalence of thyroid nodules increased with age, well-differentiated thyroid cancers were more likely to develop earlier in life. Conversely, older individuals more frequently presented with aggressive histological subtypes, including variants of papillary thyroid carcinoma, poorly differentiated carcinoma, and anaplastic carcinoma [21].

In China, thyroid cancer has become the fastest-growing malignancy, with an estimated annual increase in incidence of approximately 20% between 2003 and 2011 [22]. Subsequent analyses of temporal trends from 1990 to 2021 demonstrated a pronounced rise in incidence accompanied by a plateau in mortality reduction. This divergence from global trends is thought to reflect intensified diagnostic activity aimed at expanding screening coverage, as well as persistent concerns related to overdiagnosis [23]. Observational cross-sectional analyses based on Global Burden of Disease data further indicate that the overall burden of thyroid cancer across EU15+ countries is declining [24,25]. In contrast, the United States and Australia have shown increasing trends in age-standardised mortality rates (ASMR) and disability-adjusted life years (DALYs) over 30 years [26].

In line with the existing literature, our study demonstrated a modest female predominance, with women accounting for 79.7% of overall thyroid cancer cases compared with 70.3% in men. Nevertheless, no statistically significant sex-based differences were observed in the distribution of cancer subtypes. Specifically, ocular cancer accounted for 13.8% of cases in men and 13.0% in women; papillary carcinoma for 26.8% in men versus 27.8% in women; follicular carcinoma for 15.9% in men versus 20.4% in women; and mixed carcinoma for 13.8% in men versus 18.5% in women. Papillary carcinoma predominated over follicular carcinoma in both sexes within the <40 and 40–69-year age groups. An increased frequency of metastatic disease was observed exclusively among men aged 40–69 years.

Recent developments in molecular diagnostics have markedly improved both preoperative and postoperative accuracy in thyroid tumour characterisation and risk stratification, enabling more personalised clinical management [27,28]. However, conventional morphological assessment continues to face limitations related to reproducibility and quantitative evaluation in routine practice. With ongoing advances in artificial intelligence, the integration of morphological, clinical, molecular, and epigenetic data at the individual patient level may further enhance prognostic precision and optimise therapeutic decision-making [29].

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