Thyroid nodules: pathogenesis, diagnosis and treatment.

Serum thyroglobulin levels were serially measured in 25 normal pregnant women to evaluate thyroidal activity during normal pregnancy. Measurements included serum T3, T4, free T4, TBG, and TSH. Tg and FT4 levels were found to be decreased in the third trimester when compared with those of the first trimester and with those of normal non-pregnant individuals (P less than 0.01). TSH levels were higher than normal in pregnant women at all stages of pregnancy, with a significant rise at the third trimester. These findings suggest the presence of a subclinical hypothyroid state in the late stage of normal pregnancy.

Decreased serum thyroglobulin levels in the late stage of pregnancy

Adenomatous goiter with hyperthyroidism is a rare disease entity in Japan. Over a five-year period, we operated on 20 patients with this disease. Pre-operatively, basal thyrotropin was not necessarily suppressed and the thyrotropin-binding inhibiting immunoglobulin activity, which had been recently measured in five patients, showed normal values. Uneven patches of cold areas were noted on131I thyroidal scintigrams. Thyroid function tests carried out three years after surgery in one lobectomy case and in eleven subtotal thyroidectomy cases revealed hypothyroidism in seven, hyperthyroidism in two and euthyroidism in only three cases. These results suggest that the pathogenesis and clinical features of adenomatous goiter with hyperthyroidism are quite different from those of Graves’ disease, and that routinely performing near-total thyroidectomy may be considered as the treatment of choice.

Adenomatous goiter with hyperthyroidism

Thyroid nodules are very frequent findings, and their prevalence steadily increases with age. However, clinically significant thyroid cancer is a rare malignancy, and death from thyroid cancer is even less common with an estimated annual death rate of 0.25 per 100,000 in the US population. Moreover, the ever-increasing discovery of thyroid nodules by high-resolution radiological imaging procedures performed for other indications raises the problem of how incidentally discovered lesions should be investigated in a cost-effective and safe manner to identify the rare patient with a clinically significant malignancy.

Evaluation of Thyroid Nodules

Measurements of serum thyroglobulin (hTg) were performed using a specific radioimmunoassay. Sera with detectable anti-thyroglobulin (anti-Tg) antibody titers (>1∶10) as assessed by passive hemagglutination were discarded. Assays were carried out under conditions in which anti-Tg titers less than 1:10 produced no interference. The assay sensitivity was 1.25 ng/ml and the mean ± SE concentration of serum hTg in 58 control subjects was 9.5 ± 0.9 ng/ml (range< 1.25–27 ng/ml). A slight but significant (p<0.025) increase in the mean hTg level was observed in 12 pregnaint women at delivery (25.7 ± 5.2 ng/ml). Moderate to marked elevations of serum hTg were observed in patients with nontoxic goiter (61.4 ± 15 ng/ml; n = 23), subacute thyroiditis (138 ± 67 ng/ml; n =5), toxic adenoma (129 ±47 ng/ml; n =13), untreated (424 ± 101 ng/ml; n = 35) or treated (328 + 222 ng/ml; n =14) toxic diffuse goiter. 88 patients with thyroid carcinoma and 10 with nonthyroidal malignancies were studied. The mean level of serum hTg was increased in untreated differentiated thyroid carcinoma (89.5 ± 19 ng/ml; n = 13) but not in undifferentiated (10 ±2.9 ng/ml; n =6) or medullary (0.8 ±0.2 ng/ml; =3) carcinoma. In treated differentiated thyroid carcinoma the mean hTg levels were normal (8.2 ± 2.2 ng/ml) in patients (n = 24) with no evidence of either a thyroid residue or metastatic disease, moderately increased (56.6 ± 16 ng/ml) in patients (n =27) with residual thyroid tissue, markedly elevated in patients with lymph node metastases (199 ± 50 ng/ml; n = 15) and extremely elevated in those with bone (4004 ± 982 ng/ml; n = 8) or lung (2520 ± 620 ng/ml; n = 5) metastases. There was no significant difference in serum hTg between functioning (n =23) and nonfunctioning (n =5) metastases as assessed by 131| whole body scan. A slight but significant (p < 0.0005) increase in the mean concentration of hTg was observed in nonthyroidal malignancies (21.7 ±4.5 ng/ml; n = 10). Serial measurements showed a transient increase of serum hTg after131| therapy of differentiated thyroid carcinoma, toxic diffuse goiter or toxic adenoma, with peak values usually occurring within the first three days. A fall of serum hTg after administration of suppressive doses of thyroid hormone to patients with nontoxic goiter and a rise after discontinuation of thyroid suppressive therapy in patients with metastatic differentiated thyroid carcinoma was observed. The present data confirm and extend previous data indicating that serum hTg is frequently elevated in thyroid disease, and that the release of hTg from malignant and nonmalignant thyroid tissue is at least in part thyrotropin (TSH) dependent and it is enhanced by radioiodine therapy. Measurements of serum hTg do not differentiate from benign and malignant thyroid disease, but may be usefullly employed in the follow up of differentiated thyroid carcinoma. Of particular interest was the finding that nonfunctioning metastases may be detected by measurement of serum hTg and that bone or lung metastases are associated with much higher levels of serum hTg than lymph node metastases.

Serum thyroglobulin in thyroid carcinoma and other thyroid desorders

To investigate further the relationship between thyroid hormones and thyroglobulin (TG) secretion, total and free thyroid hormone levels, TSH and its response to TRH and serum TG concentrations were determined in 61 patients with solitary autonomous thyroid nodules. Thyroid function varied widely from euthyroidism to clearcut thyrotoxicosis. Serum TG levels were significantly higher in patients than in normal controls. Individually they were above the normal range (greater than 50 ng/ml) in 95% of the patients, as well as in those with normal total and/or free thyroid hormone levels. Patients with high total and/or free thyroid hormone levels had higher TG concentrations than euthyroid patients. TG concentrations were significantly correlated with FT3 values. They were higher in patients in whom TSH was unresponsive to TRH than in the responsive groups. TG was also slightly higher in patients with hot nodules than in those with warm nodules. These data seem to indicate that TG is secreted along with thyroid hormones in the absence of any stimulatory action. It also is a sensitive index of thyroid hyperfunction. Twenty patients were controlled 6 months after nodulectomy. TG levels, though significantly lower than in the preoperative state, were still higher than in normal subjects. This increase was attributed to persistent hyperthyroidism in two patients only. The observation that the increase in TSH after TRH stimulation in post-operative patients was greater than that found in normal controls led us to believe that in most cases the high TG levels after surgery are due to stimulation of the normal thyroid tissue by rebound TSH secretion.

Serum thyroglobulin in patients with autonomous thyroid nodules.

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Serum thyroglobulin in patients with autonomous thyroid nodules.