Age, Sex and C Cells: What About the Human Thyroid Follicle with Acid Mucin and Solid Cell Nests?a

H. Ruben Harach

St.Bartholomew’s Hospital London, United Kingdom, ECIA 7BE

I read with interest the recent article about C-cell hyperplasia occurring more commonly in adult males than in females at autopsy by Guyetant and colleagues (1). The evidence of an increased thyroid C cell population in such individuals is strongly supported by the use of image analysis in their study. Although much has been written and referred to in the English literature about sporadic C cell hyperplasia in various conditions, including chronic hypercalcemia, lymphocytic thyroiditis, thyroid follicular cell tumors, and as an autopsy finding in normal situations (1, 2), not much attention has been paid to gender in these settings (1), and obviously no comments or analyses were made of other normal situations where C cells are one of the main components.

A distinct second kind of thyroid follicle has been recognized in man (3). These follicles contain intraluminal acid mucin, are anatomically related to the ultimobranchial thyroid solid cell nests, and are light microscopically lined only by C cells, or more frequently by abundant C cells together with follicular cells (3, 4). Prominent C cell "conglomerates" are often found close to or around follicles with acid mucin. Interestingly, thyroid follicles with acid mucin occur more frequently in males (30%) than in females (5%) (P < 0.01), their prevalence not differing with age in males (3).

Another normal component of the thyroid gland is the ultimobranchial solid cell nests (5). Occasional C cells can be found within solid cell nests proper, and C cells in background thyroid tissue are more frequent the closer they are to solid cell nests, anatomical observation that cannot be ignored when sampling the thyroid for investigation of C cell hyperplasia (5, 6, 7). Concerning gender, it is interesting to note that C cells within solid cell nests, again, occur more frequently in males (60%) than in females (32%) (P < 0.05). The presence of C cells in solid cell nests was similar in both sexes under the age of 30 (males: 33%, females: 44%), but increased in males and decreased in females with rising age, to a difference that was significant in individuals after the age of 60 (males: 70%, females: 14%; P < 0.01) (7).

The pathogenetic mechanisms influencing the volume of the thyroid C cell population in normal situations remain obscure (1, 3), as do the factors that influence the prevalence of C cells within solid cell nests (7). Whether the increase in C cell number in normal circumstances has to be considered as truly hyperplastic remains unclear (2). One possibility suggested by Guyetant and colleagues (1) is that an increase in the C cell population "may only reflect C cell number heterogeneity among normal individuals." Most (if not all) observations from the literature involving C cell counting in man were based on the presence of the hormone calcitonin in the thyroid C cells. In this case a negatively stained C cell population could not be excluded. Undetectable calcitonin product in tissue sections may be caused by tissue autolysis, rapid release of calcitonin into the circulation, or mechanisms that may interfere with calcitonin synthesis (8). Up- and down-regulating mechanisms that control C cell growth in relation to aging and sex hormones could not be excluded either. A further step for interpreting, at least in part, C cell growth in human thyroid tissue sections could be approached by colocalization studies involving cell proliferation markers, calcitonin product (storage), and the calcium ion sensing receptor (9) by immunocytochemistry, and calcitonin-mRNA (synthesis) by in situ hybridization. Also serum calcitonin levels would be essential in this approach (2), but may be difficult to obtain in autopsy studies.

Footnotes

Received March 3, 1997. Address correspondence to: H. Ruben Harach, Department of Histopathology, St. Bartholomew’s Hospital, London, United Kingdom, ECIA 7BE.

References

  1. Guyetant S, Rousselet MC, Durigon M, et al. 1997 Sex-related C cell hyperplasia in the normal human thyroid: a quantitative autopsy study. J Clin Endocrinol Metab. 82:42–47.[Abstract/Free Full Text]
  2. LiVolsi VA. 1997 Editorial: C cell hyperplasia/neoplasia. J Clin Endocrinol Metab. 82:39–41.[Free Full Text]
  3. Harach HR. 1985 Thyroid follicles with acid mucins in man: a second kind of follicles? Cell Tissue Res. 242:211–215.[Medline]
  4. Harach HR. 1991 Thyroglobulin in human thyroid follicles with acid mucin. J Pathol. 164:261–263.[Medline]
  5. Harach HR. 1988 Solid cell nests of the thyroid. J Pathol. 155:191–200.[Medline]
  6. Janzer RC, Weber E, Hedinger C. 1979 The relation between solid cell nests and C cells of the thyroid gland. Cell Tissue Res. 197:295–312.[Medline]
  7. Harach HR. 1985 Histological markers of solid cell nests of the thyroid: with some emphasis on their expression in thyroid ultimobranchial-related tumors. Acta Anat. 124:111–116.[Medline]
  8. Nadig J, Weber E, Hedinger C. 1978 Morphologic and morphometric studies on human C cells in disorders of calcium metabolism. Virchows Arch. B 29:151–165.
  9. Garret JE, Tamir H, Kifor O, et al. 1995 Calcitonin-secreting cells of the thyroid express an extracellular calcium receptor gene. Endocrinology. 136:5202–5211.[Abstract]