Medullary thyroid cancer, papillary thyroid microcarcinoma and Graves' disease: an unusual clinical coexistence.

We describe the unusual case of a Caucasian woman who had a diagnosis of medullary thyroid cancer and papillary microcarcinoma 5 years after a diagnosis of Graves' disease. The patient came to our observation for recurrence of hyperthyroidism. An ultrasound scan revealed diffuse thyroid enlargement with a nodule, recently increased in size. The serum CT and carcinoembrional antigen were elevated, and the fine-needle aspiration cytology with immunocytochemical analysis for CT was suggestive for medullary thyroid carcinoma. The nodular lesion showed intense 111In-pentetreotide uptake, whereas total body scintigraphy with the same tracer and with Thallium-201, 99mTc (V) dimercaptosuccinic acid was negative for lymph node and distant metastasis. The histological examination of thyroidectomy specimens confirmed the diagnosis of medullary thyroid cancer, showing a lymphocytic intratumoral infiltration. The histological analysis of the controlateral lobe showed an occult papillary microcarcinoma. Medullary thyroid carcinoma and papillary microcarcinoma showed intense staining with policlonal anti-RET antibodies, although genetic analysis was negative for RET mutations most frequently involved in familial and sporadic medullary thyroid carcinomas. Possible implications about the coexistence of the 3 thyroid diseases are discussed.

Postintervention serum TSH levels may be useful to differentiate patients who should undergo levothyroxine suppressive therapy after thyroid surgery for multinodular goiter in a region with moderate iodine deficiency.

Recent studies have raised doubts about the efficacy of the postoperative use of levothyroxine (LT4) suppressive doses in patients who underwent thyroid surgery for multinodular goiter. The purpose of this retrospective study was to examine the efficacy of different doses of LT4 in preventing postsurgical recurrences of simple multinodular goiter and to identify a marker that could be useful in discriminating patients with a higher risk of developing recurrence. Two hundred thirty-two patients (57 male, 175 female) operated for nontoxic multinodular goiter were divided into two groups: (I) patients with normal postsurgery thyrotropin (TSH) levels (0.25 to 4.5 mU/L) and (II) patients with elevated postsurgery TSH levels (>4.5 mU/L). All patients were subjected to replacement (1.3 microg LT4/kg/day) or suppressive (1.7 microg LT4/kg/day) doses of LT4, and they were followed for a median period of 6 years (range 2 to 12). No statistical difference was found for sex, age, and postsurgery serum TSH between patients submitted to suppressive and replacement therapy. The ultrasound (US) detection of new postsurgery nodules of at least 0.5 cm maximum diameter was considered a recurrence of disease and was found in 10% of the cases studied. Patients with normal postsurgery serum TSH showed a high recurrence rate (30.4%) when submitted to lower daily doses of LT4. In patients with elevated postsurgery serum TSH, the rate of nodular goiter recurrence did not vary with different types of LT4 therapy. In conclusion, our results suggest that the postsurgical serum TSH is useful for prediction of nodular goiter recurrence, as it reflects the amount of residual functioning thyroid tissue in the cervical area. It may also be indicative of patients who might benefit from LT4 suppressive therapy.

Differential diagnosis between undifferentiated tumor and thymoma by electron microscopy and immunohistochemical labelling.

This study of a particular case of tumor posed and resolved problems of differential diagnosis between an undifferentiated tumor and a thymoma by using electron microscopy in association with immunocytochemical methods. The first step was the distinction between an epithelial and a mesenchymal tumor, which was done by electron microscopy and immunofluorescence observation with anti-keratin antibody. The second step, a new approach to this problem, was the distinction between an epithelial tumor of thymic origin and another tumor located in the mediastinal lodge. A clear distinction was made by observation in immunofluorescence using anti-thymulin monoclonal antibody. This double approach permits differential diagnosis, excludes neoplasms of germ-cell origin, malignant lymphomas and leukemias, as well as mesenchymal tumors, and affirms the thymic origin of the tumor observed. A second type of cell observed in this tumor with a peculiar aspect, different from all types of epithelial cells observed in normal thymus, is discussed.

Hypocalcaemic effect of WR-2721, S-2 (3-aminopropylamino) ethyl-phosphorothioic acid in an anuric haemodialysis patient.

The radio- and chemoprotective agent, S-2 (3-aminopropylamino) ethyl-phosphorothioic acid (WR-2721) has been reported to lower hypercalcaemia in patients with cancer, probably by increased renal calcium excretion and decreased parathyroid hormone (PTH) secretion and bone calcium resorption. The present study reports the first clinical use of WR-2721 in an anuric haemodialysis patient with severe secondary hyperparathyroidism. The drug was administered intravenously at different doses, i.e. 150, 300, and 500 mg/m2. The infusion was followed by a striking decrease of plasma immunoreactive (i) PTH within 30 min. The nadir of the iPTH decrease was reached at 60 min and was followed by a steady return to previous values. Serum ionised calcium decreased more progressively from 1.55 mmol/l initially to 1.30 mmol/l at 4 h after the 300-mg dose, remained at that level at 24 h, but rose again to pre-infusion values after 48 h. The extent and duration of the decrease in plasma iPTH and ionised calcium were dose-dependent. The circulating iPTH at 24 h was inversely related to the corresponding plasma ionised calcium concentration and had risen above preinfusion values at that time. Plasma concentrations of three other hormones, i.e. renin, insulin, and prolactin, were not affected by the administration of WR-2721. In conclusion, WR-2721 can induce a decrease in serum ionised calcium in the absence of any excretory kidney function. The rapid effect of the drug on circulating iPTH supports the notion of an interference with PTH secretion or catabolism.

Thymoma epithelial cells secrete thymic hormone but do not express class II antigens of the major histocompatibility complex.

17 thymomas were studied by indirect immunofluorescence for the presence of thymic hormones and antigens of the major histocompatibility complex (MHC). The thymoma epithelial cells (specifically identified by their keratin content) contained thymic hormones (thymulin and thymosin alpha 1), a finding corroborated by the observation of elevated thymulin serum levels. In contrast with normal or hyperplastic thymuses, thymoma epithelial cells did not express HLA-DR and HLA-DC antigens as assessed by immunofluorescence as well as immunoblot analyses. Conversely, MHC class I antigens (HLA-ABC) were normally expressed. Thus, we conclude that thymoma epithelial cells are endocrinologically active but are defective for the expression of some MHC products (class II molecules) known to play an essential role in intrathymic T cell differentiation.