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The neoplastic proliferation of parafollicular thyroid cells (C cells) may occur as either medullary thyroid carcinoma (MTC) or C cell hyperplasia (CCH) and is generically defined C cell disease. Since Calcitonin (CT) expression is fully maintained in neoplastic C cells, this hormone represents a sensitive marker for neoplasia of C cell derivation such as CCH and MTC. Serum CT levels display a high prognostic value and accurate estimation of tumor burden, allowing early detection of persistence/relapse and representing a reliable marker of response to treatment. Indeed, elevated CT levels can occur in other non-C cell-related conditions (i.e., other malignancies, systemic diseases, and pharmacological treatments). Moreover, some de-differentiated, more aggressive MTCs may present disproportionately low-circulating CT levels, as compared with tumor burden. During the postsurgical follow-up of MTC patients, CT levels usually parallel tumor progression and their increase unambiguously announces persistence/relapse. In this respect, CT Doubling Time (DT) has been proposed as prognostic factor of potential use for the identification of more aggressive MTCs. The present review will summarize the novel achievements on the clinical suitability of CT as a biomarker in clinical oncology and will point the attention to the most recent results concerning the usefulness and the possible drawbacks of circulating CT as a surrogate marker for the identification of rapidly progressing MTC patients, such as those candidate to targeted therapies. The emerging role of circulating CT as a parameter of response to local and systemic therapies will also be illustrated.

Corticosteroid agents (CA) are widely used in the treatment of metastatic castration-resistant prostate cancer (mCRPC) either as concomitant treatment with active agents such as docetaxel, cabazitaxel and abiraterone or in a palliative setting, predominantly due to their anti-inflammatory activity. However, the chronic use of CA has numerous side effects, especially in case of steroid-induced adrenal insufficiency. Furthermore, the latest clinical and preclinical data demonstrate that CA themselves are likely to promote tumour progression in certain populations of patients with mCRPC. Therefore, the role of CA in advanced disease should be carefully weighed for each patient and their withdrawal should be considered in some patients. This is necessary, especially in clinical trials that need good performance status patients to evaluate the activity and the safety of emerging drugs in mCRPC that do not require the concurrent use of CA. In oncology, there is no consensus on an algorithm of gradual steroid tapering and frequently the approach to this procedure is empirical. An algorithm is presented in this article based on clinical observations. Prospective studies are necessary to evaluate the efficacy and safety of the above-proposed algorithm in metastatic castration-resistant prostate cancer.

Thyroid hormone binding autoantibodies have been observed in serum from patients affected by either thyroid disorders or autoimmune nonthyroid diseases.ln most instances, no major involvement of thyroid status of these patients has been reported. However, some authors have attributed the occurrence of hypothyroidism to high capacity thyroid hormone binding autoantibodies.In order to verify such a hypothesis, the effect of these autoantibodies on serum TSH and liver mitochondrial alpha-glycerophosphate dehydrogenase has been investigated in rats, wherein circulating T3-binding antibodies (max cap10−12 10−8 to mol/l) were induced by active immunization.Starting from the 3rd week after antigen injection, the binding of 125I-T3 to serum immunoglobulins was progressively increased, with a peak at the 5th week. In immunized animals considered as a whole group, serum TSH levels were significantly higher and liver mitochondrial alpha-glycerophosphate dehydrogenase activity was significantly lower than in normal rats (m ± SE: 145 ± 15 vs 34 ± 2 ng/dl and 0.0450 ± 008 vs 0.0980 ± 005 ΔA. mg/prot/.min, respectively; p < 0.001) The pattern of both TSH increase and alpha-glycerophosphate dehydrogenase decrease were similar to the evolution of 125-I-T3 binding to serum immunoglobulins, the maximal TSH values and lowest enzyme levels being observed at the 5th week after the beginning of the experiment. These results indicate that high capacity thyroid hormone binding autoantibodies may actually reduce thyroid hormone disposal at cellular level, at least prior to the attainment of steady state T3- antibody hormone binding.

The rate of liver mitochondrial alpha-glycerophosphate dehydrogenase (GPD) induction was compared to the suppression of pituitary thyrotropin (TSH) secretion in thyroidectomized rats submitted to prolonged administration of small amounts of L-thyroxine (T4). With both 350 and 530 ng T4/100 g bw/day, liver alpha-GPD activity remained at post-thyroidectomy level (mean +/- SE: 0.030 +/- 0.002 and 0.034 +/- 0.001 delta A/mg prot/min, respectively) throughout all experiment. A sharp increase in enzyme activity was observed after 3 weeks of treatment in rats receiving 715 ng T4 / 100 g bw / day (mean +/- SE: 0.086 +/- 0.003 delta A/mg prot/min). In contrast, serum TSH levels were lower than pretreatment values (199 +/- 8ng/dI) in rats receiving 350 ng T4/100 g bw/day (mean +/- SE: 104 +/- 15 ng/dI; t = 7.48, p less than 0.001), decreased progressively with increasing T4 doses (m +/- SE:530 ng T4/100 g/day = 36 +/- 7 ng/dI); after only 48 h of treatment and were not significantly modified thereafter. The data are in agreement with the hypothesis of a nonlinear relationship between the degree of thyroid hormone receptor occupancy and the rate of liver mitochondrial alpha-GPD induction.

A 62-year-old woman presented abdominal pain and a rightsided pelvic mass. Ultrasonography showed a large, thickwalled, cystic ovarian mass with solid components. The patient underwent laparotomic monolateral annessectomy. Histology showed an endometriosic cyst, with a 17-cm struma ovarii containing a 3-mm single papillary thyroid carcinoma. Pelvic ultrasonography showed a normal left ovary, abdomino-pelvic CT scan showed only two renal cysts. The patient had no previous history of thyroid disease. Thyroid evaluation showed a 12 9 17 mm hypoechoic nodule with benign

Clinical investigation of enlarged, local lymph nodes after surgery for papillary thyroid carcinoma is problematic. Use of the fine-needle aspiration thyroglobulin assay could help to identify patients whose disease has progressed to lymph-node metastasis.

Thyroid hormones (TH) have been shown to exert a direct stimulatory effect on the Ca++-dependent ATPase from human and other mammalian erythrdcytes. In this in vitro system, T4 has been shown to be more effective than T3. In the present study, TH effects on Ca++-dependent ATPase were investigated, using rabbit and human erythrocyte membranes, after preincubation with 10−10M T4, in the presence or in the absence of exogenous calmodulin (CaM) (5.10−12M to 5.10−9 M). Ca++-dependent ATPase activity was measured as inorganic phosphate (Pi) release from 1 mM ATP. The results showed that basal Ca++-dependent ATPase activity in rabbits was moderately increased by T4 (1.44 ± 0.05 vs 1.32 ± 0.04 μmol Pi/mg protein/90 min, mean ± SE; p

Serum concentrations of T4, T3, reverse T3 (rT3), TSH, Thyroxine binding globulin (TBG) and Thyroxine binding prealbumin (TBPA) were measured and a TRH-stimulation test was performed in 10 iodide untreated children affected by cystic fibrosis (CF) and in 84 controls. As compared to the controls, CF patients had lower T4 and rT3, similar T3 and TBG and increased T3:T4 ratios. They also had lower TBPA, but this could not account for the low T4. Finally they had higher basal and TRH-stimulated TSH. Our results indicate subclinical hypothyroidism in CF. The mechanisms responsible for this situation are not elucidated by our data.

This paper describes the identification of circulating autoantibodies to thyroid hormones in 5 patients with Graves’ disease (n = 2), Hashimoto’s thyroiditis (n = 1), primary myxedema (n = 1) and Sjogren syndrome (n = 1) out of 351 individuals. The 351 patients suffered from different autoimmune thyroid disorders, thyroid cancer or lymphoreticular system disorders as well as autoimmune non thyroid illnesses. Immunoglobulin G (IgG) binding of one or both tracer thyroid hormones and in one case also of reverse triiodothyronine, was demonstrated by radioimmunoprecipitation experiments and by reverse flow zone electrophoresis or cellulose acetate electrophoresis and autoradiography. In all cases the binding of radiolabeled thyroid hormones to IgG was displaced by an excess of the respective non radioactive thyroid hormone. Thyroglobulin displaced the binding in 2 cases but preadsorption with human thyroglobulin was ineffective in other 2 cases. Radioimmunoelectrophoresis and autoradiography of the Immunoelectrophoresis plates indicated that in 2 cases the light chains involved in the binding were k chains of the G3 subclass and to a lesser extent of the G1 subclass, in another case they were λ chains and therefore of restricted heterogeneity. In a case of myxedema coma IgG were polyclonal (k and λ chains of the G1 > G2 > G3 subclasses). The thyroxine (T4) or triiodothyronine (T3) antibodies interfere with the hormone measurement in unextracted serum by falsely lowering their concentrations when non specific separation methods are used and raising their concentrations when double antibody radioimmunoassays are used.In one serum containing anti-T4 antibodies, the association constant (Ka) was 0.63 × 106 l/M and absolute binding (Ab0) was1.54 x10-7 l/M. In another serum with anti-T3 IgG, Ka was 4.44 × 107 l/M and Abo 6.22 × 10-9 l/M. In the case of myxedema coma Ka ranged between 3.1 and 4.3 × 108 l/M.