Differentiated thyroid cancer in children and adolescents.

In this retrospective study we analyzed cancer characteristics and outcome in a consecutive series of 48 young patients (< or =20 yr of age) with a differentiated thyroid cancer (DTC), observed during the period 1977-1998. In none of them was thyroid cancer related to ionizing radiation. The median age was 18.1 yr, range 7-20, and the female/male ratio was 2.5/1. Papillary thyroid cancer (PTC) occurred in 83% and follicular thyroid cancer (FTC) in 17% of cases. All patients underwent total or near total thyroidectomy plus pre- and/or paratracheal lymphnode dissection. Surgery complication rate was low (4% permanent hypoparathyroidism; no permanent lesion of recurrent laryngeal nerve). Extrathyroid disease was present in 52% of patients with PTC and in 50% of patients with FTC, while nodal metastases were present in 62.5% of patients with PTC and in 12.5% of patients with FTC. Lung metastases occurred in 10 patients with PTC (25%) and in none with FTC. Twenty-one patients required radioiodine treatment for metastatic disease: 11 patients for relapsing lymph-node metastases, 4 patients for lung metastases, 6 patients for both lymph-node and lung metastases. After a mean follow-up of 85+/-12 months all patients followed regularly (no.=47) were alive; 37 patients (79%) were free of disease and 10 (21%) had residual disease. Our results indicate that non-radiation-related DTC occurring in young patients often presents at an advanced stage. For this reason, although the prognosis is usually good in these patients, we believe that total or near total thyroidectomy with lymphadenectomy is always the required initial surgical treatment.

[Differentiated carcinoma of the thyroid in the young. Clinical and histopathologic aspects]. / Carcinoma differenziato della tiroide in età giovanile. Aspetti clinici ed istopatologici.

BACKGROUND: The surgical approach to Differentiated Thyroid Carcinoma (DTC) is controversial. Aim of this study is to evaluate the opportunity of total thyroidectomy as treatment of choice for DTC in children. METHODS: We examined the tumor features at diagnosis, the complications of surgery and the clinical outcome in a consecutive series of 33 young patients, (age range 7-19 yrs), who underwent total thyroidectomy for DTC as compared to a consecutive series of 181 adult patients operated for DTC (age range 20-64 yrs). RESULTS: Histopathological examination has shown that bilateral foci of the tumor and extrathyroidal extension, were present with similar frequency in both groups of patients (15 vs 18% and 39 vs 48% respectively); node metastases and distant metastases were more frequent in young patients than in adult patients. Complications of total thyroidectomy were not frequent with 6% of permanent hypoparathyroidism. No case of laryngeal nerve damage was observed. In 7/8 patients with lung metastases the radioiodine treatment was effective: in four patients we observed a complete remission of disease, and in three patients a partial response with a decrease of Tg levels and a reduction of the radioiodine uptake areas. CONCLUSIONS: Thyroid carcinoma is not less aggressive in children than in adults. Total thyroidectomy plus lymph node dissections appears to be the treatment of choice as routine surgical treatment of DTC in children. Radioiodine therapy gives good results for the treatment of lung metastases.

Transition from cold to hot thyroid nodules.

We report three cases of autonomously functioning thyroid nodules (AFTNs) that appeared hypofunctioning at radioactive iodine (131I) thyroid scan carried out at initial observation. Since at that time thyroid hormones and thyrotropin (TSH) were also normal, they were initially classified as "cold" nodules and treated with levothyroxine (LT4). The correct diagnosis of AFTN was made years later when a thyroid scintigraphy was repeated. In two of these patients, re-evaluation of the nodule was done because of the development of LT4 intolerance. A possible explanation is that these AFTNs had undergone hemorrhagic/cystic degeneration when they were first studied, but in subsequent years, proliferation of residual AFTN tissue caused the recurrence of a typical functioning nodule.

[Echography at "high resolution" in the diagnosis of cervical lymphadenopathies in follow-up of thyroid carcinoma]. / Ecografia ad "alta risoluzione" nella diagnostica delle linfoadenopatie cervicali nel follow-up del carcinoma della tiroide.

BACKGROUND: In the diagnosis and follow-up of differentiated thyroid cancer (DTC) patients, a major clinical objective is to differentiate whether the cause of enlarged neck lymph nodes is either tumorous or inflammatory. High-frequency (7.5-10 MHz) ultrasound examination proved to be highly informative in this regard. An oval shape of the examined lymph node (longitudinal/anteroposterior diameter ratio, L/A > 1.5) and a central echogenic hilus indicate a benign lymphadenopathy. Roundness (L/A < or = 1.5), absence of the central echogenic hilus and a parenchymatous echogenicity are considered as signs of malignancy. METHODS: A series of 131 lymph nodes in DTC patients were examined at ultrasound and, on the basis of round shape (L/A < or = 1.5) in association with either one or both the other features (absence of central echogenic hilus, homogenous internal echo), 94 lymph nodes were classified a "malignant" and 37 "benign". The ultrasonographic diagnosis was evaluated with either cytologic or histologic diagnosis in all "malignant" nodes and in 7/30 "benign" nodes. In the other 30 "benign" nodes volume shrinkage or lymph node disappearance was observed during follow-up period. RESULTS: According to the results obtained, the ultrasound features utilized provided a good diagnostic accuracy (87%) with only 5 false positive case. CONCLUSIONS: High-frequency sonography, therefore, must be considered a useful and accurate method for evaluating suspected lymphadenopathy in DTC patients.

Adenylate-cyclase-dependent pituitary adrenocorticotropin secretion is defective in the inflammatory-disease-susceptible Lewis rat.

Susceptibility to arthritis in the Lewis rat is associated with a defect of the hypothalamic-pituitary-adrenal axis. We examined the pituitary corticotropes of both intact and dexamethasone-treated male and female inflammatory-disease-susceptible Lewis and inflammatory-disease-resistant Fischer rats. We determined adrenocorticotropin levels in the media from primary cultures of anterior pituitary cells of both strains. In other experiments we have measured intracellular cyclic adenosine monophosphate and inositol monophosphate accumulation. Cells were incubated with corticotropin-releasing hormone, arginine vasopressin, forskolin, phorbol myristate acetate, or thyrotropin-releasing hormone. Corticotropin-releasing hormone stimulated adrenocorticotropin secretion from both male and female Lewis rat pituitary cells in a concentration-dependent manner. Basal and stimulated adrenocorticotropin levels in cells from Lewis rats were lower than those measured in the incubation media of Fischer rat dispersed pituitary cells. Arginine vasopressin, as well as forskolin and phorbol myristate acetate, induced a significant release of adrenocorticotropin from pituitary cells of both strains. Incubation with corticotropin-releasing hormone did not produce a significant accumulation of intracellular cyclic adenosine monophosphate in Lewis rat dispersed pituicytes of both sexes. On the other hand, forskolin induced a significant increase of intracellular cyclic adenosine monophosphate in the same cultures. Finally, inositol monophosphate accumulation was comparable in pituitary cells from both Lewis and Fischer rats of both sexes incubated with thyrotropin-releasing hormone. Adrenocorticotropin secretion from pituitary cells of male Lewis rats treated in vivo with dexamethasone was either reduced or abolished following incubation with different secretagogues. A defect in pituitary adrenocorticotropin secretion could be among the causes of the hyporesponsiveness of the hypothalamic-pituitary-adrenal axis in the Lewis rat. Such a defect appears to be associated with dysfunction of receptor-coupled events related to adenylate cyclase.

Effects of pidotimod on the immune and the neuroendocrine system in the aging rat.

The effects of pidotimod ((R)-3-[(S)-(5-oxo-2-pyrrolidinyl)carbonyl]-thiazolidine-4-carboxylic acid, PGT/1A, CAS 121808-62-6), a synthetic thymic dipeptide, on immune response in 2 and 24 month-old rats were investigated. Peripheral blood lymphocytes and splenocytes of aging rats treated for 1 week with different doses of pidotimod showed increased rates of mitogen-stimulated proliferation. Also, interleukin-2 production by 24 month-old rat lymphocytes was significantly increased after treatment with the drug. In addition, the response of the hypothalamic-pituitary-adrenal (HPA) axis to interleukin-1 in 2 and 24 month-old Sprague-Dawley rats previously treated with pidotimod was studies. Blood samples were withdrawn--30, 0, 30, 60, 90 and 120 min after interleukin-1 injection. Interleukin-1 injection stimulated ACTH secretion in a dose-related manner, in both 2 and 24 month-old rats. Peak of the effect was 60 min after the injection. ACTH levels returned to baseline within 120 min in 2 month-old rats, whereas they were still high in untreated 24 month-old rats. However, plasma ACTH levels at 120 min were significantly lower in 24 month-old rats treated with pidotimod. Results suggest that pidotimod possesses immunomodulating properties, such as enhancement of splenocyte and peripheral blood lymphocyte proliferation, and improvement of the deficitary feedback mechanism between the hypothalamic-pituitary-adrenal axis and cytokines and, namely, interleukin-1 in the aging rat.

Modulating effects of the synthetic thymic dipeptide pidotimod on the immune system in the aging rat.

We have investigated the in vivo and in vitro effect of pidotimod, a synthetic thymic-derived drug, on the immune response in young (2 month-old), and aging (24 month-old) Sprague-Dawley rats. We studied the effect of different doses of pidotimod on the responsiveness of both cultured peripheral blood lymphocytes and splenocytes to mitogenic stimuli, as well as on interleukin-2 production by peripheral blood lymphocytes after stimulation with interleukin-1 and phytohemagglutinin. Treatment with pidotimod in vivo as well as in vitro resulted in an increase of tritiated thymidine incorporation in both mitogen-stimulated lymphocytes and splenocytes from 24 month-old rats. Production of IL-2 from lymphocytes of 24 month-old rats was significantly increased in groups of animals treated with pidotimod. On the other hand, treatment with pidotimod did not influence the responsiveness of 2 month-old rat lymphocytes to mitogens, nor affected IL-2 production. Our results suggest a possible specific modulatory activity of pidotimod on the aging immune system.

Thymic factors influence on behavior in rodents.

We studied the effect of thymopentin, a synthetic thymic peptide, on spontaneous behavior and stress models in BALB/c mice in which a WEHI 164 clone 13 murine fibrosarcoma had been implanted, as well as in the intact Sprague-Dawley rat. In untreated animals with tumors, spontaneous behavior was significantly inhibited. Resistance to swimming in cold water was also decreased in untreated animals. Thymopentin (10, 100, 1,000, and 5,000 micrograms/kg body weight, IP, 20 min before the test) enhanced spontaneous behavior in tumor-implanted mice. In addition, thymopentin partially restored floating capability of tumor bearers in either freely moving or animals on which an additional weight had been applied. In the latter test, plasma corticotropin and corticosterone levels were relatedly modified according to treatment. Rats treated with thymopentin showed a decreased sensitivity to painful stimuli. The effect of thymopentin was comparable to acetylsalicylate. Finally, thymic factors appeared capable of restoring the diminished behavioral activity of animals bearing tumors, as well as of increasing resistance to stressful stimuli and pain.