Morphological and Functional Changes in the Thyroid Follicles of the Aged Murine and Humans

Abstract

Background: Although both thyroid histology and serum concentrations of hormones are known to change with age, only a few reports exist on the relationship between the age-related structural and functional changes of the thyroid follicles in both mice and humans. Our objectives were to investigate age-related histological changes of the thyroid follicles and to determine whether these morphological changes were associated with the functional activity of the follicles.

Methods: The thyroid glands of mice at 18 weeks and at 6, 15, and 30 months of age were histologically examined, and the serum levels of thyroid hormones were measured in 11-week-old and 20-month-old mice. Samples of human thyroid tissue from 10 women over 70 years old and 10 women between 30 and 50 years of age were analyzed in conjunction with serum thyroid hormone level.

Results: The histological and functional changes observed in the thyroid follicles of aged mice and women were as follows: variable sizing and enlargement of the follicles; increased irregularity of follicles; Sanderson's polsters in the wall of large follicles; a large thyroglobulin (Tg) globule or numerous small fragmented Tg globules in follicular lumens; oncocytic change in follicular cells; and markedly dilated follicles empty of colloid. Serum T3 levels in 20-month-old mice and humans were unremarkable.

Conclusions: Thyroid follicles of aged mice and women show characteristic morphological changes, such as cystic atrophy, empty colloid, and Tg globules.

Keywords: Aged; Elderly; Thyroid gland; Thyroid hormones.

Fig. 1.

The 18-week-old control thyroid gland. (A) Description of the central and peripheral zones of the thyroid gland in the longitudinal and transverse planes. (B, C) Conserved zonal variation in the thyroids of 18-week-old control mice. (B) Hematoxylin and eosin–stained sections of thyroid from an 18-week-old control mouse in the central and peripheral zones. (C) Mean area (±standard deviation, n=2) of follicles in the central and peripheral (pph) zones of an 18-week-old mouse thyroid.

Fig. 2.

Adult and aged mouse thyroid gland. (A–F) Markedly enlarged follicles and loss of zonal variation in follicle size in aged mice. (A, C, E) Hematoxylin and eosin–stained sections of thyroid from 6-month-old (A), 15-month-old (C), and 30-month-old (E) mice in the central and peripheral zones. (B, D, F) Mean area (±standard deviation; n=2) of follicles in the central and peripheral (pph) zones. Tg, thyroglobulin.

Fig. 3.

Increased irregularity of follicles in the aged mouse thyroid. Hematoxylin and eosin (H&E)–stained sections of thyroid from 15-month-old (A) and 30-month-old (B) mice. (C) Oncocytic change in the follicular cells of aged mouse thyroid stained with H&E. (D) Sections of 30-month-old mouse thyroid stained with anti–translocase of the outer mitochondrial membrane (TOM20) antibody visualized by 3,3'-diaminobenzidine. Non-oncocytic follicular cells are weak for TOM20 (left panels), while oncocytic follicular cells are strongly TOM20-positive (right panels). Tg, thyroglobulin.

Fig. 4.

Colloid density in thyroid follicular lumens. (A–C) The density of periodic-acid-Schiff (PAS)–positive intrafollicular colloid in each age group. Sections of 6-month-old (A), 15-month-old (B), and 30-month-old (C) mice thyroids stained with hematoxylin and eosin (H&E) (top row) and PAS at the indicated magnifications. The markedly enlarged follicles in the aged thyroids (B, C) exhibit increased PAS-positive colloid density. The PAS-positive density of the colloid in irregularly-shaped and empty follicles is significantly decreased compared to the adult group (A). Follicles in the peripheral zones of 15-month-old mice are empty with clear cytoplasm and a centrally located shrunken nucleus (B, inset).

Fig. 5.

Sections of thyroid from elderly females highlighting various morphological changes. (A) Size variation and enlargement of the follicles. (B) Increased irregularity of follicles and Sanderson’s polsters in the wall of large follicles. (C) A large thyroglobulin (Tg) globule (right upper image) and numerous small fragmented Tg globules (right lower image) in the follicular lumen. (D) Oncocytic change in the follicular cells and in those with Sanderson’s polsters. (E) Irregularly dilated follicles lacking colloid. (F) Fibrosis of the extracellular matrix. (G) Fatty infiltration in the extracellular matrix.