Studies examining the weight of normal thyroid glands, either by direct measurement or by extrapolation from volume measurement, have yielded variable means and ranges, particularly the latter.⁴,⁵,⁶,⁷,⁸ Distillation of these findings yields an average weight of about 18 g for adult men and 15 g for adult women. The reported distributions of thyroid weights tend to show a positive skew, with a broader range of weights above the mean than below. Most of the reported weights of normal adults lie within a range from 8 to 30 g. Glands with weights in excess of 50 g have also been reported, but these outliers raise questions regarding their normal status. The glands of adult women tend to be smaller than that of adult men, but the differences are modest and the ranges mostly overlap. Some studies have shown a positive correlation between thyroid weight and body weight, body mass index, or age.⁴,⁵,⁶,⁷,⁸,⁹ Body weight or body mass index tends to show stronger correlation than age, but overall these correlations are weak. Thyroid weight tends to show a progressive increase in childhood and adolescence, stability in early to midadulthood, and gradual decline in older age.⁷,⁸ An increase in thyroid size has been reported in pregnant women.¹⁰,¹¹ However, most cases of enlargement may reflect iodine deficiency as opposed to an invariable physiologic response to pregnancy.

The colloid within the central follicular space contains thyroglobulin, an iodinated glycoprotein that is the precursor of triiodothyronine (T₃) and thyroxine (T₄). Colloid has an amorphous eosinophilic appearance and is highlighted by periodic acid-Schiff and thyroglobulin stains. The intensity of staining with hematoxylin and eosin can vary. The colloid in follicles with low activity usually shows more intense eosinophilia compared with the colloid in follicles with a high level of hormone synthesis and release. Colloid in these latter follicles may also show scalloping or small vacuoles at the interface with follicular cells, a sign of endocytotic resorption. Larger, round to oval clear spaces are common within colloid, and some of these spaces may contain calcium oxalate crystals. Colloid generally has a homogeneous appearance. However, it can contain particulate-like clumps of material that are more intensely eosinophilic or slightly basophilic (Fig. 1.6). This histologic finding seems more common in active follicles, but it is unclear whether this is a manifestation of increased synthetic activity or a nonspecific artifact.¹⁴

The presence of calcium oxalate crystals within colloid is a common finding.¹⁵,¹⁶ Crystals appear as small clear refractile foci and are birefringent when viewed with polarizing filters (Fig. 1.7). These crystals begin to appear during childhood and adolescence and become more prevalent as adults age. Calcium oxalate crystals have potential utility in distinguishing thyroid from parathyroid tissue.¹⁷

Ultrastructural examination of follicular cells reveals junctional complexes of desmosomes and terminal bars linking cells along their lateral borders near the apices. The bases of the cells abut a basal lamina that separates them from the interstitial stroma and fenestrated capillary network (Fig. 1.9). The nuclei are basally located. Granular endoplasmic reticulum and mitochondria are readily identifiable components of the cytoplasm. The supranuclear region contains a Golgi complex that increases in prominence with increased activity. The apical region contains Golgi-derived dense secretory vacuoles, which transport glycoproteins to the plasmalemma for exocytosis into the follicular lumen. Lysosomes are prominent cytoplasmic components. This includes both primary and secondary lysosomes. The latter, also known as phagolysosomes, represents the fusion of primary lysosomes with colloid taken into the cytoplasm by endocytosis. Numerous apical microvilli are present, and their length increases when hormonal synthesis is stimulated.

Follicular cells exhibit cytoplasmic positivity in sections immunohistochemically stained for thyroglobulin and low molecular weight cytokeratins (Fig. 1.10).¹⁸,¹⁹,²⁰,²¹ Coexpression of vimentin has also been noted.¹⁸,¹⁹,²⁰ Normal follicular cells express transcription factors including thyroid transcription factor-1 (TTF1), TTF2, and paired box gene 8 (PAX8).²²,²³ Thyroid stimulating hormone (TSH) receptor and thyroid peroxidase (TPO) can also be demonstrated immunohistochemically in normal follicular cells.²²,²⁴,²⁵ Growth factors and their receptors are also expressed, including epidermal growth factor (EGF), transforming growth factor (TGF(α)), and epidermal growth factor receptor (EGFR) (Table 1.1).²⁶,²⁷