Gender Disparities in Thyroid Cancer Diagnosis: Evaluating Detection Bias and Clinical Implications

Abstract

Background

Despite a female preponderance in clinical diagnoses, meta-analyses of autopsy studies demonstrate similar rates of subclinical thyroid cancer between sexes. This study examines granular demographic, clinical, and pathologic data to evaluate this discordance.

Methods

A single-center retrospective review (2015-2021) identified 195 thyroid cancer patients. Logistic regression models assessed demographics, presenting symptoms, pathology, recurrence, and mortality as factors in stage of presentation.

Results

Men presented with significantly larger nodules than women (median 4.45 cm vs 3.2 cm, P = 0.003), particularly when symptomatic (P = 0.011). However, nodule size did not differ in asymptomatic patients (P = 0.45). No significant differences were observed in BMI, age, prior radiation history, or ethnicity. Primary care status approached significance, with 42.5% of men lacking a documented primary care physician visit vs 24.5% of women (P = 0.067). Women were more likely to have small, localized tumors (P = 0.048), T1 disease (P = 0.035), and stage 1 disease (P < 0.001), while metastatic disease was more common in men (22.5% vs 5%, P < 0.001). Women were also more likely to be diagnosed with an incidental thyroid cancer when undergoing thyroidectomy for non-cancer indication. No differences in recurrence or mortality were found. Multivariate logistic regression revealed that visiting a PCP within 1 year of diagnosis was protective against advanced disease (OR:0.59, 95% CI:0.41-0.84, P = 0.003).

Conclusion

Women are more frequently diagnosed with subclinical and incidentally identified early-stage thyroid cancer and smaller thyroid nodules, whereas men present with larger nodules and more advanced disease. Men were also less likely to have had routine primary care visits. These findings suggest that diagnostic bias and healthcare access disparities may contribute to gender differences in thyroid cancer detection.

Keywords

endocrine general surgery socioeconomic surgical oncology

Key Takeaways

• Women are more likely to be diagnosed with subclinical and early-stage thyroid cancer; while men continue to present with larger nodules and advanced stage disease.

• Women may be disproportionately over-diagnosed with subclinical thyroid cancer as they undergo thyroid surgery for reasons other than a diagnosis of thyroid malignancy.

• Women continue to seek primary care at a higher rate than men and patients with a PCP visit within a year of diagnosis present with less advanced disease.

Introduction

Since the introduction of ultrasound for thyroid nodule evaluation, thyroid cancer has become the 9^th most common malignancy in women and the 10^th most common in men in the United States.¹ As ultrasonographic sensitivity has improved, the detection of early-stage thyroid cancer has markedly increased.² Clinically, thyroid cancer exhibits a well-documented female preponderance with a 4:1 diagnostic ratio; however, the underlying biological basis for this disparity remains unclear.²

A recent meta-analysis by LeClair et al demonstrated equivalent rates of subclinical thyroid cancer in autopsy studies of men and women, challenging the notion that intrinsic biological differences drive the observed gender discrepancy in clinical diagnosis.³ Instead, women are diagnosed and undergo thyroid surgery at 4 times the rate of men, despite comparable subclinical disease prevalence. Prior studies have shown that women have a higher healthcare utilization than men; this disparity raises critical questions regarding the influence of gender on healthcare utilization, thyroid screening practices, and diagnostic pathways.^4,5

In our own institutional experience, we observed a similar gender imbalance in thyroidectomies and sought to explore whether differences in symptomatology, clinical presentation, and pathologic findings contribute to this phenomenon. This study aims to systematically compare presenting symptoms, demographics, and pathologic characteristics to better understand the gender discordance in thyroid cancer diagnosis.

Methods

Study Design and Data Collection

The study was reviewed and approved by the Lundquist Institute Institutional Review Board at Harbor-UCLA. A single-center retrospective review was performed at a public hospital to identify adult patients (age >18) diagnosed with thyroid cancer from 2015-2021. Inclusion criteria included patients with a diagnosis of thyroid cancer (ICD10 codes: C73) who underwent a thyroidectomy, identified using CPT codes (60 240, 60 220, 60 225, 60 210, 60 212, 60 252, 60 254, 60 260). Data included in the analysis were patients’ demographics (age, sex, BMI, ethnicity, history of neck radiation, documented PCP visit within 1 year of diagnosis), presenting symptoms (incidental finding on imaging/diagnostic workup for unrelated symptoms including hyperthyroidism, hypothyroidism, and hyperparathyroidism), self-reported symptoms (pain, cough, globus, and neck mass), tumor characteristics (nodule size of US, presence of metastatic disease), pathology (tumor size, extrathyroidal extent, unifocal vs multifocal, histologic subtype, TNM staging), and oncologic outcomes (recurrence, mortality, need for adjuvant therapy). Laterality and recurrence were identified using chart review. Patients without a PCP visit within 1 year were referred to care through a combination of from Emergency Department, from an incidental finding, or from undocumented care from outside the system. Exclusion criteria included patients who chose to not undergo surgery and those with incomplete medical records. Nineteen patients did not undergo surgery and were excluded from analysis.

Outcome Measures

Primary outcome measures included identifying factors associated with a diagnosis of thyroid cancer. Secondary outcomes evaluated oncologic outcomes. Comparative analysis of gender-based differences were done using Chi-square and Fisher exact tests for categorical data and Mann-Whitney U test for continuous variables. Salient clinical and demographic variables based on prior literature were entered into logistic multivariate regression to identify the factors independently associated with method of presentation and clinical T stage (where T stage was split into stages 1 & 2 vs stages 3 & 4). Recurrence and mortality were calculated with multivariable Cox proportional hazards regression analysis. 2-sided P < .05 was considered statistically significant. Analyses were performed using R version 4.4.1.

Results

From 2015-2021, 195 patients diagnosed with thyroid cancer met inclusion criteria. Of 195 patients, 155 (79.5%) were female and 40 (20.5%) were male. There was no significant difference in the diagnosis of thyroid cancer between men and women when BMI (P = 0.78), age (P = 0.92), and prior radiation (P = 1.0) were compared (Table 1). There was no significant difference in the diagnosis of men and women when stratified by ethnicity including White (P = 0.96), Black (P = 0.41), and Hispanic patients (P = 1.0). Primary care status approached significance; 42.5% of men did not have a documented primary care physician within 1 year of diagnosis in comparison to 24.5% of women (P = 0.067). Multivariate logistic regression revealed that visiting a PCP within 1 year of diagnosis was protective against advanced disease (OR:0.59, 95% CI:0.41-0.84, P = 0.003) (Table 2).

Table 1.

Demographics

	Female (n = 155, 79.5%) (n%)	Male (n = 40, 20.5%) (n%)	Overall (n = 195, 100%) (n%)	P value
BMI				0.788
18.5 - 30	83 (53.6)	23 (57.5)	106 (54.5)
>30	72 (46.5)	17 (42.5)	89 (45.6)
Ethnicity
White	100 (64.5)	25 (62.5)	125 (64.1)	0.968
Black	14 (9.0)	6 (15)	20 (10.3)	0.414
Hispanic	17 (11.0)	4 (10)	21 (10.8)	1
Other	24 (15.5)	5 (12.5)	29 (14.9)	0.823
Age				0.9232
<55	88 (56.8)	22 (55.0)	110 (56.4)
≥55	66 (33.9)	18 (45.0)	84 (43.1)
Prior radiation				1
No	152 (98.1)	39 (97.5)	191 (97.9)
Yes	3 (1.9)	1 (2.5)	4 (2.1)
PCP visit <1 Year				0.067
No	38 (24.5)	17 (42.5)	55 (28.2)
Yes	117 (75.5)	23 (57.5)	140 (71.8)
Presentation
Self-reported symptoms	30 (19.4)	7 (17.5)	37 (19.0)	0.968
Neck mass	83 (53.5)	21 (52.5)	104 (53.3)	1
Incidental imaging finding	42 (27.1)	12 (30.0)	52 (26.7)	0.867

Table 2.

Thyroid Cancer Characteristics

	Female (n = 155, 79.5%) n (%)	Male (n = 40, 20.5%) n (%)	Overall (n = 195, 100%). n (%)	P value
Histologic Subtype
Classic PTC	72 (46.5)	14 (35.0)	86 (44.1)	0.262
Tall cell PTC	15 (9.7)	8 (20.0).	23 (11.7)	0.072
Hurthle cell PTC.	2 (1.3)	1 (2.5)	3 (1.5)	0.586
Follicular PTC	41 (26.5)	6 (15.0)	47 (24.1)	0.193
Medullary carcinoma	0 (0)	2 (5.0)	2 (1.0)	0.055
Follicular carcinoma	15 (9.7)	8 (20.0)	23 (11.7)	0.072
Hurthle cell Carcinoma	10(6.5)	3 (7.5)	13 (6.7)	0.816
Anaplastic	3 (1.9)	2 (5.0)	5 (2.6)	0.278
Other cancer	2 (1.3)	0 (0)	2 (1.0)	0.477
T stage
1	56 (36.1)	7 (17.5)	63 (32.3)	0.035
2	31 (20.0)	10 (25.0)	41 (21.0)	0.637
3	42 (27.1)	16 (40.0)	58 (29.7)	0.563
4	4 (2.6)	4 (10.0)	8 (4.1)	0.097
N Stage
0	112	27	139 (71.2)	0.5338
1-2	29	10	39 (20.0)
M stage
0	134 (86.5)	29 (72.5)	163 (83.6)	0.001
1	7 (4.5)	9 (22.5)	16 (8.2)
Overall stage
1	106 (68.4)	17 (42.5)	123 (63.1)	0.001
2	25 (16.1)	14 (35.0)	39 (20.0)	0.184
3	3 (1.9)	1 (2.5)	4 (2.1)	1
4	9 (5.8)	6 (15.0)	15 (7.7)	0.120
Extent
≤ 2 CM	47 (30.3)	6 (15.0)	53 (27.2)	0.048
> 2 CM	58 (37.4)	18 (30.0)	76 (39.0)	0.687
Locally/regionally advanced	26 (16.8)	5 (12.5)	31 (15.9)	0.566
Metastatic	7 (4.5)	9 (22.5)	16 (8.2)	0.001
Other^a	17 (11.0)	2 (5.0)	19 (9.7)	0.403
Lymphatic invasion
No	135 (87.1)	32 (80.0)	167 (85.6)	0.792
Yes	8 (5.2)	3 (7.5)	11 (5.6)
Extrathyroidal extension
No	109 (70.3)	25 (62.5)	134 (68.7)	0.533
Yes	34 (21.9)	11 (27.5)	45 (23.1)
Angioinvasion
No	120 (77.4)	22 (55.0)	142 (72.8)	0.008
Yes	22 (14.2)	13 (32.5)	35 (17.9)

^aIndicates patients who are missing partial data from their chart including M Stage, N Stage, pathologic tumor size, or T stage data.

Overall, men presented with significantly larger nodules (median 4.45 cm [IQR]:2.0-4.5 vs 3.2 cm, [IQR]:2.8-5.725, P = 0.003). When nodule size was stratified by presentation, men were more likely to have larger nodules than women when presenting with a neck mass (P = 0.011) or other self-reported symptoms (P = 0.05) (Figure 1, Table 3). There was no significant difference in average nodule size between men (2.95 cm, IQR:1.875-5.35) and women (2.35 cm, IQR:1.925-3.60) who presented as an incidental finding (P = 0.45).

Figure 1.

Nodule size by presenting symptoms

Table 3.

Multivariate Analysis of FACTORS Influencing Presentation to Care

	Odds ratio (OR)	95% confidence interval	P value
Sex
Female	1	**	NA
Male	1.858	1.260-2.740	0.003
PCP visit within one year of diagnosis
NO	1	**	NA
Yes	0.586	0.407-0.844	0.003
Presenting symptoms
Incidental finding	1	**	NA
Other symptoms	2.034	1.252-3.306	0.004
Palpable neck mass	1.650	1.028-2.649	0.036

Women were more likely to have small, localized thyroid cancers (defined as less than 2 cm without evidence of other metastatic disease) on surgical pathology (P = 0.048), T1 disease (P = 0.035), and overall TNM stage 1 disease (P < 0.001). Upon further investigation, 27 patients were noted to have a subclinical cancer incidentally found on final pathology for thyroidectomy performed for another indication; 26 of the 27 patients were women (P = 0.03). This phenomenon was driven primarily by multi-nodular goiter disease or hyperthyroidism with a toxic nodule. Metastatic disease was significantly more common in men (22.5% vs 5%, P < 0.001). Ultimately there was no significant difference between men and women in cancer recurrence (P = 0.56) or mortality during the study period.

Discussion

In this study of gender disparities in thyroid cancer presentation and treatment, we found that women were more likely to be diagnosed with early-stage, subclinical disease, whereas men more frequently presented with advanced, metastatic disease within our patient cohort. While no significant demographic or clinical differences were observed in the mode of presentation, men exhibited increased angioinvasion on final pathology and a larger tumor burden at diagnosis, and women were significantly more likely to be diagnosed with incidental thyroid cancer after undergoing surgery for other preoperative diagnoses including multi-nodular goiter and hyperthyroidism with a toxic nodule. These findings suggest that gender disparities in thyroid cancer diagnosis may be more strongly influenced by differences in healthcare access and diagnostic patterns rather than just intrinsic biological factors.

The increased detection and treatment of early-stage thyroid cancer in women is consistent with prior literature.² We saw no difference in gender diagnostic prevalence based on race, age, or history of radiation; however, there was a significant female predominance in the proportion of incidental micro-papillary thyroid cancer found on final pathology due to multi-nodular goiters and toxic nodules. This could have contributed to the high proportion of early-stage thyroid cancer in our data and resulted in a four-to-one difference in female-to-male cancer diagnoses. LeClair et al demonstrated in their meta-analysis that increased incidence of thyroid cancer in women is driven by the detection of small PTCs, despite comparable subclinical disease prevalence between sexes in autopsy studies.² Although some studies have suggested a potential role of estrogen receptor expression in thyroid cancer, a systematic review in 2012 found no conclusive evidence supporting hormonal influences as a significant risk factor for disease development.⁶ In our study, men and women presented at similar rates across each of the presentation categories: incidental finding, palpable neck mass, or symptomatic tumor burden. However, women were diagnosed with tumors that were, on average, 1.2 cm smaller, which may be correlated to a lower likelihood of advanced or metastatic disease. This size discrepancy was not seen in the incidental asymptomatic cohort, showing that although women present with symptomatic and palpable neck masses at a smaller size, incidental imaging and diagnostic findings provide a snapshot of disease prevalence similar to LeClair et al.’s autopsy study.²

This size discrepancy in the symptomatic and palpable neck mass cohorts raises the question of whether disparities in thyroid cancer diagnosis could stem from masculine sociocultural factors influencing healthcare seeking behavior, barriers to healthcare access, or anatomical differences. Prior studies have shown that women have a higher healthcare utilization than men, which may contribute to increased thyroid cancer detection.^4,5 Since the introduction of routine ultrasound screening, the incidence of thyroid cancer nearly tripled from 4.9 per 100 000 in 1975 to 14.3 per 100 000 in 2009 with a majority of the diagnoses being PTC.⁷ As a result, clinical guidelines now recommend limiting evaluation of subclinical thyroid nodules to those greater than 1 centimeter, except in individuals with genetic or environmental risk factors.⁸ Another potential contributor to gender disparity is provider bias, as thyroid cancer is often perceived as a predominantly female disease. This could skew the number of screening neck ultrasounds in women and decrease the likelihood of ultrasound in men due to it being perceived as lower on the differential diagnosis. Additionally, women were also found to undergo thyroid ultrasound for atypical symptoms such as fatigue, potentially leading to incidental identification of subclinical nodules.⁹ Anatomical differences, such as decreased neck subcutaneous fat distribution, may contribute to greater symptomatology in women, leading to earlier detection of smaller tumors. However, BMI was not found to be a significant factor in our analysis of gender discordance of presentation factors.

The over-identification of small, subclinical thyroid cancer in women carries its own risks. Many of these patients undergo aggressive treatment, including total thyroidectomy, rather than hemithyroidectomy, despite the latter being an acceptable alternative.^7,8,10 Total thyroidectomy is associated with significant perioperative risks, including hematoma and recurrent laryngeal nerve injury, with unclear survival benefits given that the natural history of early-stage PTC, particularly in elderly patients, rarely leads to mortality. Furthermore, total thyroidectomy necessitates lifelong thyroid hormone replacement therapy, increasing the burden of polypharmacy. Conversely, the perceived gender disparity of thyroid cancer could be contributing to the lack of evaluation in men leading to their more advanced presentations. In prior literature non-PTC cancers, such as medullary and anaplastic thyroid cancers, were also diagnosed with near equivalent proportions and with a near equivalent mortality ratio.^11,12 This was also seen in our study with no significant difference between genders. Public awareness of the equal predisposition of thyroid cancer amongst both genders is critical for appropriate and timely evaluation and intervention.

This study has several limitations. It was a single-center retrospective design in a very diverse county hospital with poor health care access which may limit its generalizability. Additionally, there could be possible selection bias due to inclusion of only surgically treated patients within the cohort. While we stratified patients by documented PCP visit within a year of diagnosis, it is entirely possible that patients were seeking primary care outside of our system, which may bias our results. Given the relatively small number of male patients in our cohort, the observed sex-based differences in presentation, particularly among men, should be interpreted as hypothesis-generating rather than definitive and warrant validation in larger, prospective studies. However, this is one of the largest single-institution analyses of gender disparities in thyroid cancer. Further studies should focus on evaluation of long-term outcomes of thyroid cancer by gender or identifying differences in a multi-institutional cohort.

Conclusion

In summary, women are more likely to be diagnosed with early-staged thyroid cancers, while men present with larger, more advanced disease. Our study suggests that this gender disparity in clinical diagnosis may be driven by incidental diagnoses in women undergoing surgery for multi-nodular goiters or autoimmune disease, improved primary care access, and earlier presentation for evaluation of symptoms. These findings highlight the need for a more balanced diagnostic approach to prevent overdiagnosis in women and delayed detection in men.

Footnotes

ORCID iD

Paul Brosnihan

Funding

The authors received no financial support for the research, authorship, and/or publication of this article.

Declaration of Conflicting Interests

The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

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