1 BACKGROUND

Thyroid gland enlargement also known as goiter, is a condition that occurs when each of the lateral lobes of the thyroid gland is larger than the person under examination's terminal phalanx of the thumb. In one of the guidelines of the World Health Organization in 2014, it was stated that the goiter prevalence goes up with the seriousness of iodine defect, and it is endemic in regions where the intake of iodine is less than 10 µg per day.¹ The prevalence of thyroid gland enlargement worldwide has been reported to be 15.8% and as high as 28.3% in Africa and 4.7% in America.²

The causes of thyroid gland enlargement include iodine deficiency, follicular adenoma, Hashimoto thyroiditis, familial or sporadic multinodular goiter, thyroid cancer, colloid nodules, cysts, and many others. Common clinical presentations of this condition comprise cough, dysphagia, difficulty in breathing, and hoarseness of voice.³ Magnetic resonance imaging, computed tomography scan, plain radiography, radioisotope scintigraphy, fludeoxyglucose positron emission tomography (FDG-PET), and ultrasonography (USG) are the imaging modalities for the examination and diagnosis of this condition.⁴ However, high-resolution USG scan is the recommended first-line imaging modality due to its high sensitivity in imaging of the thyroid gland and does not involve the use of ionizing radiation.⁵

Thyroid gland ultrasound helps in the characterization of nodules and detection of other non-palpable but clinically significant nodules, that may require fine needle aspiration.³ Based on their sonographic appearances, thyroid USG scan may also be used to distinguish between malignant and benign thyroid masses.⁵ Since ultrasound has been reported as the most readily available imaging modality in Ghana, its use in the examination of the thyroid gland for differentiating cystic from solid masses, and its availability will result in the diagnosis of large numbers of thyroid pathologies.⁶

A reporting system for thyroid nodules on ultrasound has been proposed by the American College of Radiology (ACR) called Thyroid Imaging Reporting and Data System (TI-RADS). This was proposed to deal with the dilemma of how to report the nodules, which are overwhelmingly benign, to ensure consistency across practices. The ACR TI-RADS points, from 0 to 3 are assigned to the ultrasound features from various categories; composition, margin, shape, echogenic foci, and echogenicity, to obtain TI-RADS scores. These assigned points to the features are; cystic (0), mixed cystic and solid (1), solid nodule (2), anechoic (0), isoechoic (1), hypoechoic (2), very hypoechoic (3), wider than tall (0), taller than wide (3), well-defined (0), ill-defined (0), irregular (2), and macrocalcifications (1).^{7, 8} The scores and their descriptions are shown in Table 1.

The prevalence of thyroid gland enlargement has been reported to be high in Africa and some other continents. A recent study by Vanderpump et al., disclosed that people who are at particular risk, tend to be remote and live in upland areas in Latin America, South-East Asia, and Central Africa. The thyroid gland enlargement prevalence is known to be as high as 80% in areas of severe iodine deficiency.^{2, 9}

2 METHODS

3 RESULTS

Of the 213 participants included in this study, females constituted the majority (82.16%). The overall mean age was 50.01 (SD = 17.27) years spanning from 16 to 92 years. The males with goiter were generally older (57.16 ± 16.76 years) than the females (48.46 ± 17.04 years). Most of the patients were within the 41−60 years age group (45.54%), followed by those who were more than 60 years (27.23%) and those within 21−40 years (22.07%). Only 5.16% of them were below 21 years, as shown in (Table 2).

The leading TI-RADS score in the study was TI-RADS 4 (36.62%, n = 78), followed by TI-RADS 1 (28.17%, n = 60) and TI-RADS 3 (25.82%, n = 55). The rarest TI-RADS scores were TI-RADS 2 (4.23%, n = 9) and TI-RADS 5 (5.16%, n = 11) as shown in Figure 1.

The mean size of cysts (diameter) for the females was 1.81 and 1.54 cm for the males, with a mean difference of 0.26 (CI: −0.14 to 0.67), but statistically, there was no difference between the mean sizes (p = 0.20). The average size of solid nodules (diameter) of females was 2.09 cm, and that of males was 1.97 cm with a mean difference of 0.12 (CI: −0.43 to 0.66). Statistically, there was also no difference between the mean sizes of solid nodules among the sexes (p = 0.67) (Table 3).

Both lobes, together with the isthmus, were the most affected area in the study, constituting 28.17% (n = 60), implying the majority of the patients presented with lesions in the entire thyroid (both lobes and isthmus), followed by both lobes only (24.41%, n = 52) and the right lobe only (20.19%, n = 43). The least affected areas were the isthmus only (10.33%, n = 22) and the left lobe only (16.90%, n = 36) (Figure 2).

The most common ultrasound features were well-defined solid nodules (38.68%, n = 94) (Figures 3 and 4), simple cysts (25.93%, n = 63) (Figure 5), solid nodules with cystic changes (20.99%, n = 51), and calcifications (6.17%, n = 15) (Figure 4). The least observed feature was complex cysts or cystic with solid components (2.88%, n = 7) (Figure 3). The remaining results on the proportions of the ultrasound features are shown in Table 4.

Solid nodules were more common for the 41−60 years age group (49.32%, n = 73), followed by those more than 60 years (31.08%, n = 46) and 21−40 years (16.89%, n = 25). The solid nodules were less frequent in those less than 21 years (2.70%, n = 4), with p = 0.001. The cysts were also more prevalent in the 41−60 years age category (35.71%, n = 25) and the 21−40 years age group (32.86%, n = 23). The rest are shown in Table 5.

The distribution of solid nodules and cysts among males and females is shown in (Table 6). The result showed that solid nodules were more common in females (83.11%, n = 123) than males (16.89%, n = 25), though the result was not statistically significant (p-value = 0.57). The cysts were also more frequent in females (81.43%, n = 57) than in males (18.57%, n = 13), with p = 0.85.

4 DISCUSSION

Thyroid gland enlargement has affected many people in the world, ranging from mild to severe conditions, which has reduced the quality of life, especially in women.^{13, 14} Epidemiological data have revealed that pregnancy poses a significant challenge to the maternal thyroid gland. This is due to the increase in hormone requirements during gestation, resulting from increased thyroid-binding globulin, and peripheral thyroid hormone requirements, as well as the stimulatory effect of human chorionic gonadotropin on thyroid-stimulating hormone receptors.^15-17 The direct actions of estrogen on the thyroid tissue also contribute to the development of thyroid gland enlargement, as reported by Li et al.¹⁸ In our study, we found that about 82.12% of the patients with thyroid gland enlargement were females. A similar result has been reported by Dauksiene et al., in Lithuania, who also found that thyroid gland enlargement is more prevalent in women than men, even though they reported a comparatively lower proportion (69.23% for women).¹⁹ This finding could also be due to the high consumption of cassava, which is a major staple in our setting among females, corroborated by other studies in Uganda, Nigeria, and Kenya.^20-22 The consumption of cassava induces the development of thyroid gland enlargement, due to the presence of goitrogenic compounds like methimazole, resorcinol, potassium perchlorate, phloroglucinol, ethylene thiourea, 6-propyl-2-thiouracil, and pyrazole.^22-24 This could further support the higher prevalence of thyroid gland enlargement in females.

In our study, we found that thyroid gland enlargement was more predominant in the 41−60 years age category, constituting 45.54%, which is in agreement with what was found by Saeed et al., in Saudi Arabia, who also reported a modal (43.93%) age group of 41−60 years.²⁵ These findings are contrary to what was reported by Zekarias et al., who indicated that thyroid gland enlargement is more common in those who are less than 35 years old (67.7%).²⁶ In assessing whether there is a difference in the sizes of solid nodules and cysts among the sexes, we found that the sizes of solid nodules and cysts in males were smaller than in females, but these differences in the sizes were not statistically significant, with p, 0.20 and 0.67 for males and females, respectively (Table 3). This is contrary to the findings of Germano et al., who found a significant difference in the sizes of thyroid nodules (solid and cystic) among the sexes.²⁷

TI-RADS 4 was the most frequent TI-RADS score (36.62%) in our study, indicating that the majority of the patients had moderately suspicious thyroid lesions, followed by TI-RADS 1 (28.17%) and TI-RADS 3 (25.82%) (Figure 1). In a study by Borlea et al., in Romania, TI-RADS 4 also constituted the majority of 48.12%, but contrary to what we found, their second and third commonest TI-RADS scores were TI-RADS 5 (29.32%) and TI-RADS 2 (18.80%), respectively. The authors recorded no TI-RADS 3 in their study.²⁸ In another study by Basha et al., their three most common TI-RADS scores were TI-RADS 2 (60.1%), TI-RADS 3 (18.0%), and TI-RADS 4 (12.7%).²⁹ These disparities could be due to the differences in the demographics. We also found that the three most frequent ultrasound features of thyroid gland enlargement in our setting were solid nodules (44.03%), simple cysts (25.93%), and solid nodules with cystic changes (20.99%) (Table 4). Studies by Girardi et al., and Xi et al., reported solid nodules as the leading feature, followed by mixed nodules (solid with cystic changes) and calcifications, constituting 46.97%, 24.85%, and 20.91%, respectively, for Girardi et al., and 44.13%, 32.39%, and 23.47%, respectively for Xi et al.^{30, 31}

The whole thyroid was most commonly affected (28.17%) in our study, followed by both lobes only (24.41%) and the right lobe only (20.19%) (Figure 2). Contrary to what we found, Saeed et al., reported that most patients presented with lesions in the right lobe only (41.60%), followed by both lobes only (37.00%) and the left lobe only (19.10%). The isthmus was the least affected area of the thyroid gland (1.20%) in their study, as also seen in ours (10.33%).²⁵ Other studies have also reported the right lobe as the most affected area of the thyroid and the isthmus as the least.^{32, 33} Even though the isthmus is the least affected site of the thyroid gland in the studies discussed above, it nonetheless could be an extra risk factor to examine for an accurate surgical approach in undetermined thyroid lesions or cancer at fine-needle aspiration.³⁴

For the age distribution of solid nodules and cysts, we found that solid nodules and cysts were more predominant in those 41–60 years, constituting 49.32% and 35.71%, respectively, and less common in those less than 21 years, which also constituted 2.70% and 10.00%, respectively. Similar findings have been reported by Lin et al., who also found solid nodules and cysts to be more common in the 41–60 years age category.³⁵ Our study also revealed that solid nodules and cysts are more prevalent in females than males, even though these results were not statistically significant, with p = 0.57 and p = 0.85, respectively (Table 6). This could be due to the high incidence of thyroid diseases in females, as also seen in our study (Table 2).³⁶ In Japan, similar findings have also been corroborated by Uchino et al. In their study, cysts and solid nodules constituted the majority of 70.83% and 71.43%, respectively in females.³⁷

5 LIMITATION

The relatively small sample size used in this retrospective study was a limitation, hence the findings for this study cannot be generalized. Future multicenter prospective studies with larger sample sizes may be required. Histopathology findings and the thyroid function test were not included in the study since the focus of this was mainly on ultrasonographic features.

6 CONCLUSION

Well-defined solid nodules, simple cysts, and solid nodules with cystic changes were the most common ultrasound features of enlarged thyroid gland in our study. The diameters of solid nodules and cysts were higher for females than for males, but these findings were not statistically significant. TI-RADS 4 was the most predominant TI-RADS score, and TI-RADS 2 was the least. This indicates that the majority of the patients had moderately suspicious thyroid lesions, which is an issue of public health concern. Few patients presented with lesions in the isthmus only, and the majority in the entire thyroid gland. Cysts and solid nodules were mostly seen in those aged 41−60 years and least in those aged <21 years.

AUTHOR CONTRIBUTIONS

Emmanuel Kobina Mesi Edzie: Conceptualization; methodology; investigation; writing—original draft; writing—review and editing; validation; formal analysis; project administration. Klenam Dzefi-Tettey: Conceptualization; methodology; investigation; validation; writing—original draft; writing—review and editing; formal analysis. Edmund Kwakye Brakohiapa: Conceptualization; methodology; validation; writing—original draft; writing—review and editing; formal analysis; supervision. Obed Nimo: Writing—original draft; writing—review and editing; methodology; investigation; formal analysis; supervision; validation. Peter Appiah-Thompson: Writing—original draft; writing—review and editing; methodology; validation; formal analysis; supervision; conceptualization. Michael Kofi Amedi: Writing—original draft; writing—review and editing; methodology; investigation; validation; conceptualization. Ansumana Bockarie: Writing—original draft; writing—review and editing; validation; conceptualization; investigation. Frank Quarshie: Writing—review and editing; writing—original draft; methodology; investigation; validation; data curation; formal analysis; software. Emmanuel Onimole: Methodology; writing—original draft; writing—review and editing; visualization; formal analysis; resources. Emmanuel Akorli: Writing—original draft; writing—review and editing; investigation; methodology; formal analysis; validation. Richard Anthony: Writing—original draft; writing—review and editing; methodology; investigation; formal analysis; supervision. Richard Ato Edzie: Writing—original draft; writing—review and editing; methodology; investigation; data curation; formal analysis. Nana Ama Amankwa: Writing—original draft; writing—review and editing; investigation; methodology; validation; formal analysis. Aaron Amartey: Writing—original draft; writing—review and editing; methodology; validation; supervision; formal analysis; software. Bernard Osei: Writing—original draft; writing—review and editing; investigation; methodology; validation; formal analysis; data curation. Bright Oppong: Writing—original draft; writing—review and editing; validation; formal analysis; methodology; investigation; supervision. Abdul R. Asemah: Writing—original draft; writing—review and editing; methodology; investigation; validation; formal analysis; data curation; project administration. Philip Narteh Gorleku: Writing—original draft; writing—review and editing; conceptualization; methodology; investigation; supervision; validation.

CONFLICT OF INTEREST STATEMENT

The authors declare no conflict of interest.

ETHICS STATEMENT

The committee for ethical review, Cape Coast Teaching Hospital, gave approval for this research to be carried out, with clearance number CCTHERC/EC/2020/096. Anonymity and confidentiality were ensured throughout the study. This study conformed to the 1975 Declaration of Helsinki. Informed consent was not obtained for this large number of retrospective patients as we could not have contacted all the patients because patients might have changed contacts, dead at the time of data collection, or been long discharged. These were made known to the CCTHERC, and no concerns were raised.

TRANSPARENCY STATEMENT

The lead author, Emmanuel Kobina Mesi Edzie, affirms that this manuscript is an honest, accurate, and transparent account of the study being reported, that no important aspects of the study have been omitted, and that any discrepancies from the study as planned (and if relevant, registered) have been explained.