Early evolutionary divergence between papillary and anaplastic thyroid cancers.

Background: Papillary thyroid cancer (PTC) is the most common thyroid carcinoma and exhibits an almost uniformly good prognosis, while anaplastic thyroid cancer (ATC) is less frequent and is one of the most aggressive cancers usually resistant to conventional treatment. Current hypothesis posits that ATC derives from PTC through the progressive acquisition of a discrete number of genomic alterations and implies that the mutational landscape of ATC resembles that of PTC. However, the clinical behaviour of ATC and PTC is radically different. We decided to address the disconnection between the clinical behaviour of ATC and PTC and the proposed model of the progressive development of ATC from PTC. Patients and methods: We carried out exome sequencing of DNA from 14 ATC specimens including three cases of concomitant ATC and PTC as well as their corresponding normal DNA from 14 patients. The sequencing results were validated using droplet digital PCR. We carried out immunohistochemistry and immunofluorescence studies of the concomitant ATC and PTC cases. In addition, we integrated our sequencing results with the existing TCGA data. Results: Most of the somatic mutations identified in the ATC component differed from the ones in PTC in the cases of concomitant ATC and PTC. The trunks of the phylogenetic trees representing the somatic mutations were short with long branches. In one case of concomitant PTC and ATC specimens, we observed an infiltration of PTC cells within the ATC component. Moreover, we integrated our results with data obtained from TCGA and observed that the most frequent mutations found in ATC presented high cancer cell fraction values and were significantly different from the PTC ones. Conclusion: ATC diverge from PTC early in tumour development and both tumour types evolve independently. Our work allows the understanding of the relationship between ATC and PTC facilitating the clinical management of these malignancies.

Inability of recombinant human thyrotropin to predict the evolution from subclinical hypothyroidism to overt disease. A pilot study.

BACKGROUND: The use of recombinant human TSH (rhTSH) is indicated to evaluate thyroid carcinoma patients. In recent years, some authors have reported that rhTSH could serve as a dynamic test of thyroid reserve. The aim of the present study was to determine whether or not rhTSH can predict the evolution from subclinical hypothyroidism (SH) to overt hypothyroidism. MATERIALS AND METHODS: Twenty-one women who met the diagnostic criteria of SH were enrolled. All patients received a single dose of rhTSH (0.1 mg). Basal blood samples for TSH, free T4 (fT4), thyroglobulin (Tg), and anti-thyoperoxidase and anti-Tg antibodies were obtained before and 1 day after rhTSH administration. All patients were followed for 2 yr, and blood samples were obtained every 6 months. RESULTS: Twenty-four hours after rhTSH administration, the TSH level increased to >20 mU/l in 14 patients; the serum peak TSH levels remained <10 mU/l in only 5 patients. On follow-up, 7 women (33%) required L-T4 replacement therapy for overt hypothyroidism or a persistent TSH level >10 mlU/l. None of the parameters analyzed differed significantly between patients who developed overt hypothyroidism from those who had persistent SH. CONCLUSIONS: The response of thyroid function tests to a single low dose of rhTSH is not useful in identifying those patients with SH who will develop overt hypothyroidism over a 2-yr period.

Oscillations in total body fat content through life: an evolutionary perspective.

Adipose tissue is considered an efficient system in which to store energy. Throughout life, the total amount of body fat exhibits some oscillations. Typically, there are three specific periods in which there are notable increases in fat mass, specifically early in life, during pregnancy and lactation, and with ageing. The existence of the first two peaks in fat mass has been interpreted, from an evolutionary point of view, as a beneficial manoeuvre to protect against the scarcity of energy to the offspring of the species. Nevertheless, the role of increasing body fat with ageing is more dubious. However, recent evidence suggests that the gain in adiposity in senescence may also be interpreted in the same evolutionary context. The aim of this review is to focus on the age-related changes in fat depots. In addition, an evolutionary explanation to the observed changes has been emphasized.

Communication between primary care and physician specialist: is it improving?

BACKGROUND AND OBJECTIVE: Efforts have recently been made in Spain to improve the communication model between primary care and specialized care. The aim of our study was to analyze the impact of a change in the communication model between the two areas when comparing a traditional system to a consulting system in terms of satisfaction of general practitioners and the number of patient referrals. METHODS: A questionnaire was used to assess the point of view on the relations with the endocrinologist team of 20 general practitioners from one primary care center at baseline and 18 months after the implementation of the new method of communication. In addition, we counted the number of referrals during the two periods. RESULTS: We analyzed 30 questionnaires; 13 before and 17 after the consulting system was established. Consulting system was preferred to other alternatives as a way of communication with endocrinologists. After the consulting system was implemented, general practitioners were more confident in treating hypothyroidism and diabetes. There was a decrease in the number of patient referrals to specialized care from 93.8 to 34.6 per month after implementation of the consultant system. CONCLUSIONS: The consultant system was more efficient in resolving problems and responding to general practitioners than the traditional system. General practitioners were more confident in self-management of hypothyroidism and diabetes. A very large decrease in the number of patient referrals was observed after implementation of the consultant system.

nm23-H1 immunoreactivity as a prognostic factor in differentiated thyroid carcinoma.

Several prognostic factors have been proposed to identify the patients at risk to develop metastases in differentiated thyroid carcinoma. Reduced nm23-H1 expression (a metastatic suppressor gene) has been correlated with high tumor metastatic potential in various human carcinomas, but the results obtained in differentiated thyroid carcinoma remain controversial. To elucidate the usefulness of nm23-H1 as a differentiated thyroid carcinoma prognosis factor, we evaluate the relationship between nm23-H1 immunoreactivity as well as both clinical status and patient outcome. For this purpose, thyroid resected specimens obtained from 94 differentiated thyroid carcinoma consecutive patients (64 papillary and 30 follicular) with at least 5 yr of follow-up were stained using monoclonal antibody to nm23-H1. We did not observe any relationship between nm23-H1 immunoreactivity and age, gender, initial differentiated thyroid carcinoma stage, local recurrence, or distant metastases in patients with papillary carcinoma. However, in patients with follicular carcinoma, a significant inverse association between metastatic disease and the expression of nm23-H1 product was obtained (P < 0.05). In addition, significant differences were found in the survival curves according to nm23-H1 immunoreactivity (log-rank P < 0.01). Finally, nm-23-H1 immunoreactivity was more specific but less sensitive than AMES score to predict metastases. In conclusion, our results suggest that nm23-H1 immunostaining could be added to the classic prognostic factors currently used to predict the outcome of patients with follicular thyroid carcinoma.

Ageing purpose: another thrifty genotype.

For evolutionary biology, ageing is a non-adaptive process. The 'disposable soma' theory proposes that senescence is the consequence of a reduction in the energy invested in the processes of cell maintenance and repair due to the fact that it is more beneficial to invest it in reproduction. Recently, various genes have been identified whose mutations modify the life span of certain animals. Most of these genes are related to energy metabolism, especially insulin, IGF-1 and their receptors. Furthermore, it has also been demonstrated that there is a modification in metabolic pathways during ageing. As a result, the energy-storing pathways are strengthened and there is a reduction in the pathways that use energy. All these findings suggest that ageing is a strategy designed by natural selection to save energy, in accordance with other saving strategies. This way the energy that is not used can be dedicated to offspring to improve their pre-reproductive survival.

[Diagnostic performance of serum thyroglobin and iodide-131 Na scan according to the type of recurrence in differentiated thyroid carcinoma]. / Rendimiento diagnóstico de la determinación plasmática de tiroglobulina y del rastreo corporal con 131INa según el tipo de recurrencia en el carcinoma diferenciado de tiroides.

BACKGROUND: There is no consensus about the best follow-up protocol in differentiated thyroid carcinoma (DTC). The aim of this study is to evaluate the usefulness and prognostic value of serum thyroglobulin (Tg) and the iodide-131 whole body scan (WBS) in DTC recurrences as a whole and according to the type of recurrence (local recurrence or distant metastases). PATIENTS AND METHODS: Thirty-four patients with recurrent DTC recruited in our institution over 15 years, with a minimum 5 years of follow-up and without either distant metastases at time of diagnosis nor detectable anti-Tg antibodies were included in the study. All patients were submitted to total or near-total thyroidectomy and 131INa ablation of postsurgical thyroid remnants. The follow-up included Tg measurement and WBS performed in hypothyroid state. RESULTS: Serum Tg was increased in the 67.4% of the patients and the WBS was positive in the 82.3%. In the isolated local recurrences the sensitivity of WBS was higher than Tg measurement (93.7 vs 43.7%; p < 0.05), but patients with positive Tg had a worse prognostic. By contrast, in patients with distant metastases the sensitivity of Tg was higher than WBS (83.3 vs 58.3%; p = NS). In 14 patients (41.2%) the results of WBS and Tg were in disagreement. In these cases a worse prognosis was observed when Tg was positive and WBS negative. CONCLUSIONS: The sensitivity of Tg and WBS is different depending on the type of recurrence. Therefore, both tests complement each other and it is not recommended to omit one of them in the follow-up of DTC.

Malignant thyroid teratoma: report of an aggressive tumor in a 64-year-old man.

Malignant teratoma of the thyroid is a rare and aggressive tumor, frequent in children than in adults. Histologically, thyroid teratomas usually show a predominance of a neuroectodermal component. Mature cartilage and bone may be present. We present the case of primary malignant teratoma of the thyroid in a 64-year-old man. Histologically, the tumor displayed a predominant neuroectodermal component. The diagnosis was confirmed by immunohistochemistry. The patient underwent a radical thyroidectomy with central neck dissection as primary treatment and radioiodine treatment afterwards. The patient had local and distant recurrence. A second surgery was performed with poor results and the patient died 3 months afterwards.

Iron in obesity. An ancient micronutrient for a modern disease.

Iron is a necessary constituent of several macromolecules involved in cell metabolism, but, at the same time, it could be a potentially dangerous element. For this reason iron balance must be finely regulated. At present, obesity has been recognized as a worldwide public health problem. Excess body fat is associated with increased all-cause mortality and increased risk for several medical morbidities. Many studies have shown that obesity might increase the risk of iron deficiency but, at the same time, obese subjects exhibit high serum ferritin levels. Recent studies seem to indicate that obesity is associated with iron deficiency although the aetiology appears to be multifactorial and includes (i) A decrease in iron food intake; (ii) An impairment of intestinal iron uptake and iron release from stores because of an overexpression of hepcidin and (iii) Inadequate iron bioavailability because of inflammation. In addition, abnormal ferritin concentrations can be explained by chronic inflammation rather than by iron overload. The aim of the present article is to review current knowledge of iron and obesity.

Clinical significance of RET/PTC and p53 protein expression in sporadic papillary thyroid carcinoma.

AIMS: Rearranged during Transfection (RET)/papillary thyroid carcinoma (PTC) and p53 are two genes involved in the pathogenesis of PTC. It has been suggested that RET/PTC expression is associated with higher rates of local extension and lymph node involvement, whereas p53 mutations are more frequent in poorly differentiated and anaplastic carcinomas. In addition, experimental studies have shown that p53 activity can modify the behaviour of PTC carrying RET/PTC. The aim of this study was to investigate the expression of both RET/PTC and p53 in order to evaluate their usefulness as prognostic factors. METHODS AND RESULTS: Resected specimens of 61 cases of PTC were studied immunohistochemically using a polyclonal antibody to RET and a monoclonal antibody to p53 protein. RET/PTC expression was associated with extrathyroid extension of PTC, at diagnosis (P < 0.05). In contrast, no relationship between p53 immunoreactivity and clinical status was found. In addition, p53 expression was more prevalent among RET/PTC+ patients, and significantly influenced the relationship observed between RET/PTC and extrathyroid extension of the disease. CONCLUSION: Our results suggest that immunohistochemistry for both PTC/RET and p53 could be useful in the clinical evaluation of patients with PTC.

Short-term hypothyroidism has no effect on serum leptin concentrations.

The aim of the study is to determine the effect of short-term hypothyroidism on serum leptin levels. For this purpose 30 patients with past medical history of thyroidectomy for differentiated thyroid carcinoma were included. Serum leptin concentrations were similar when patients were on thyrotrophin-suppressive thyroxine therapy than when were admitted 4 weeks after stopping thyroxine treatment to perform a routine 131I scan in hypothyroid status (17.0 +/- s.e.m. 2.14 vs. 17.6 +/- s.e.m. 2.41 ng/ml; p = n.s.). Moreover, no differences were obtained when the analysis was performed separately in men and in women. We conclude that short-term hypothyroidism does not alter serum leptin concentrations. Furthermore, our results suggest that thyroid hormones do not operate through changes in serum leptin levels to regulate energy expenditure.