Ultrastructural Characteristics of the Thyroid Gland in Diffuse Toxic Goiter

The aim of the study was to study the ultrastructural characteristics of the thyroid gland (TG) in diffuse toxic goiter (DTG) in patients from a control group and in those with moderate and severe thyrotoxicosis.

Material and methods. Surgical specimens of the thyroid gland (TG) from 12 patients with diffuse toxic goiter (DTG) were examined. Control samples consisted of fragments of non-neoplastic tissue (n=12) taken from the resected thyroid lobe of patients with follicular neoplasms (Bethesda IV). The material was obtained by excising a tissue fragment of 2–3 mm³, which was then fixed in glutaraldehyde and osmium tetroxide. The ultrastructure of the thyroid epithelium within the follicles and in areas of proliferation, as well as the vascular bed, was studied using transmission electron microscopy. At the light-optical level, paraffin sections stained with hematoxylin and eosin, and semi-thin sections stained with toluidine blue, were examined.

Results. In DTG, changes were detected in the follicular epithelium and stroma of the thyroid gland. Heterogeneity of thyrocytes was noted: from columnar cells with smooth nuclear contours and minimal chromatin changes to thyrocytes with numerous protrusions of the nuclear membrane, chromatin hypercondensation, and dystrophic changes in the cytoplasm. The morphology of the granular endoplasmic reticulum varied from fragmentation and cisternal dilation to its destruction. In thyrocytes, degradation of mitochondrial cristae and clearing of the matrix were observed, especially in cells with hyperchromatic nuclei and signs of dystrophy. Thyrocytes were elongated in the basal-apical direction, characterized by lengthening of microvilli and the formation of long cytoplasmic processes of the apical membrane. Accumulations of phagosomes and colloid vesicles at the apical pole and throughout the cytoplasm reflect the high intensity of colloid uptake. The proliferating epithelium was represented by clusters of thyrocytes with signs of high synthetic activity. In the follicular epithelium, dissociation of tight junctions at the apical membranes was noted, leading to impaired follicle integrity. The basement membrane was thickened and folded. Vessels were grouped at the base of thyrocytes and between follicles, represented by fenestrated capillaries with stasis and sludging of erythrocytes. The endothelium was thinned, containing lysosomes, microvesicles, and secretory granules.

Conclusion. The morphological heterogeneity of the follicular epithelium in DTG is due to the different functional states of thyrocytes. The key changes affect the synthetic and energy-generating apparatus of the cells, which is caused by hyperfunction. Dystrophic changes in the cytoplasm of thyrocytes indicate an imbalance between the processes of colloid uptake and the hydrolysis of hormones dissolved within it. The enhancement of metabolic exchange between thyrocytes and capillaries, which mediates the toxic effect of hormones in DTG, is ensured by increased permeability of the basement membrane and endothelium, as well as the formation of new capillaries. The vascular component may represent a promising target for mitigating the toxic effects of thyroid hormones, alongside antithyroid therapy.

1. Botasheva VS, Lavrinenko AA, Bairamkulova AKh. Morfologicheskie parametry otsenki funktsional'nogo sostoyaniya shchitovidnoi zhelezy pri diffuznom toksicheskom zobe [Morphological parameters for assessing the functional state of the thyroid gland in diffuse toxic goiter]. Volgogradskii nauchno-meditsinskii zhurnal. 2021;1:21-24 (In Russ.).

2. Prikhodko VA, Selizarova NO, Okovityĭ SV. Molekulyarnye mekhanizmy razvitiya gipoksii i adaptatsii k nei. Chast' I [Molecular mechanisms for hypoxia development and adaptation to it. Part I]. Arkhiv patologii. 2021;83(2):52-61. (In Russ.).

3. Rakhmatullov RF, Mel'nikova LV, Rakhmatullov AF, Shchukin YuV. Vliyanie tirozola, bisoprolola i sotalola na strukturu i funktsiyu shchitovidnoi zhelezy, lipidy krovi pri sochetanii subklinicheskogo tireotoksikoza s fibrillyatsiei predserdii [The effect of tyrosol, bisoprolol and sotalol on the structure and function of the thyroid gland, blood lipids in a combination of subclinical thyrotoxicosis with atrial fibrillation]. Izvestiya vysshikh uchebnykh zavedenii. Povolzhskii region. Meditsinskie nauki. 2018;1(45):101-114. (In Russ.). doi: 10.21685/2072-3032-2018-1-11.

4. Fadeev VV. Po materialam klinicheskikh rekomendatsii Evropeiskoi tireoidnoi assotsiatsii po diagnostike i lecheniyu tireotoksikoza pri bolezni Greivsa 2018 goda [Review of European thyroid association guideline (2018) for the management of Graves’ hyperthyroidism]. Klinicheskaya i eksperimental'naya tireoidologiya. 2020;16 (1):4-20. (In Russ.).

5. Egamberdiev AA, Zhumanov UU Diffuznyi toksicheskii zob (obzor literatury). Dostizheniya nauki i obrazovaniya [Diffuse toxic goiter (literature review)]. Availble at: https://cyberleninka.ru/article/n/diffuznyytoksicheskiy-zob-obzor-literatury (accessed: 27.05.2025) (In Russ.).

6. Abbasalizad Farhangi M, Tajmiri S. The correlation between inflammatory and metabolic parameters with thyroid function in patients with hashimoto's thyroiditis: the potential role of interleukin 23 (IL-23) and vascular endothelial growth factor (VEGF) - 1. Acta Endocrinol. 2018;14(2):163-168. doi: 10.4183/aeb.2018.163.

7. Antonelli A, Fallahi P, Elia G, Ragusa F, Paparo SR, Ruffilli I, et al. Graves' disease: Clinical manifestations, immune pathogenesis (cytokines and chemokines) and therapy. Best Pract Res Clin Endocrinol Metab. 2020 Jan;34(1):101388. doi: 10.1016/j.beem.2020.101388.

8. Liu K, Fu Y, Li T, Liu S, Chen D, Zhao C, et al. Clinical efficacy of thyroid-stimulating immunoglobulin detection for diagnosing Graves' disease and predictors of responsiveness to methimazole. Clin Biochem. 2021 Nov;97:34-40. doi: 10.1016/j.clinbiochem.2021.07.014.

9. ilva de Morais N, Angell TE, Ahmadi S, Alexander EK, Dos Santos Teixeira PF, Marqusee E. Performance of Thyroid-Stimulating Immunoglobulin Bioassay and Thyrotropin-Binding Inhibitory Immunoglobulin Assay for the Diagnosis of Graves' Disease in Patients With Active Thyrotoxicosis. Endocr Pract. 2022 May;28(5):502-508. doi: 10.1016/j.eprac.2022.01.007.

10. Nishino M. Thyroid pathology: Controversies and best practices. Semin Diagn Pathol. 2020;37(5):211-212. doi: 10.1053/j.semdp.2020.07.004.

11. Pokhrel B, Bhusal K. Graves Disease. 2023 Jun 20. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan–.

12. Struja T, Fehlberg H, Kutz A, Guebelin L, Degen C, Mueller B, Schuetz P. Can we predict relapse in Graves' disease? Results from a systematic review and meta-analysis. Eur J Endocrinol. 2017 Jan;176(1):87-97. doi: 10.1530/EJE-16-0725.

13. Trzos S, Link-Lenczowski P, Sokołowski G, Pocheć E. Changes of IgG N-Glycosylation in Thyroid Autoimmunity: The Modulatory Effect of Methimazole in Graves' Disease and the Association With the Severity of Inflammation in Hashimoto's Thyroiditis. Front Immunol. 2022 Mar 15;13:841710. doi: 10.3389/fimmu.2022.841710.

14. Zhang QY, Liu W, Li L, Du WH, Zuo CL, Ye XP, et al. Genetic Study in a Large Cohort Supported Different Pathogenesis of Graves' Disease and Hashimoto's Hypothyroidism. J Clin Endocrinol Metab. 2020 Jul 1;105(7):dgaa170. doi: 10.1210/clinem/dgaa170.