Medullary thyroid carcinoma with double negative calcitonin and CEA: a case report and update of literature review.

BACKGROUND: Medullary thyroid carcinoma is a malignant uncommon and aggressive tumour of the parafollicular C cells. In about 75% of cases it is sporadic while, in case of RET mutation, it is associated to multiple endocrine neoplasia type 2 (25% of cases). The biochemical features of medullary thyroid carcinoma include the production of calcitonin and carcinoembryogenic antigen. The above-mentioned features are useful in the diagnostic process as well as in the follow up and in the prognostication of the disease. Even if calcitonin elevation is strongly associated to MTC, it can also be found increased in many pathological different conditions as pregnancy, lactation, C-cells hyperplasia, autoimmune thyroiditis, end stage renal disease, lung and prostate cancer and several neuroendocrine tumours. Major medullary thyroid tumours are usually connected to high doses of circulating calcitonin, in fact non-secretory variants have hardly been described. CASE PRESENTATION: We herein report the case of a 59 years old male, who had undergone total thyroidectomy for multinodular goiter with negative preoperative calcitonin, showing medullary thyroid carcinoma at definitive pathology. To the best of our knowledge, this is the first case documenting a non-secretory medullary thyroid carcinoma, with double negative markers at the time of diagnosis and at the relapse. CONCLUSION: A Literature review underlining pathological hypothesis, differential diagnosis and alternative and innovative biomarkers to identify non-secretory medullary thyroid carcinoma was carried out.

On-street parking availaibilty data in San Francisco, from stationary sensors and high-mileage probe vehicles.

This dataset contains records of the measured on-street parking availability in San Francisco, obtained from the public API of the SFpark project. In 2011, the San Francisco Municipal Transportation Agency (SFMTA) started a project on smart parking, called SFpark, whose goal was the improvement of on-street parking management in San Francisco, mostly by means of demand-responsive price adjustments [1]. One of the key points of the project was the collection of information about on-street parking availability. To this aim, about 8,000 parking spaces were equipped with specific sensors in the asphalt, periodically broadcasting availability information. The SFpark project made available a public REST API, returning the number of free parking spaces and total number of provided parking spaces per road segment, for 5,314 parking spaces on 579 road segments in the pilot area. We collected parking availability data from 2013/06/13 until 2013/07/24, by querying this API at approximately 5-min intervals. As a result, we obtained in total about 7 million observations of parking availability on the road segments. These observations represent the first dataset we are providing. In addition, we simulated the achievable sensing coverage of on-street parking availability that could be achieved by a fleet of taxis, if they were equipped with sensors able to detect free parking spaces, like side-scanning ultrasonic sensors [3], or windshield-mounted cameras [4]. In particular, by exploiting real taxi trajectories in San Francisco from the Cabspotting project [5], we first computed the frequencies of taxi visits for each road segment covered by the SFpark sensors. Then, we downsampled the first dataset, in order to have a parking availability information for a road segment at a given time only in presence of a transit of a taxi on that segment at that time. This step was replicated for 5 different sizes of taxi fleets, namely 100, 200, 300, 400, and 486. Consequently, in total six datasets are available for further research in the field of on-street parking dynamics. All these datasets can be downloaded at: https://dataverse.harvard.edu/dataset.xhtml?persistentId=doi:10.7910/DVN/YLWCSU.

Calcitonin negative Medullary Thyroid Carcinoma: a challenging diagnosis or a medical dilemma?

BACKGROUND: Medullary thyroid carcinoma is a neuroendocrine tumor belonging form a malignant growth of the thyroid parafollicular C-cells, representing from 1 to 10% of all thyroid cancer. The biochemical activity of medullary thyroid carcinoma includes the production of calcitonin and carcinoembryogenic antigen, which are sensitive tumor markers, facilitating the diagnosis, follow-up and prognostication. The diagnosis is reached through the identification of high basal calcitonin serum level or after pentagastrin stimulation test. Medullary thyroid carcinoma is able to produce other relevant biomarkers as procalcitonin, carcinoembryionic antigen and chromogranin A. In Literature are described few cases of medullary thyroid carcinoma without elevation of serum calcitonin, an extremely rare event. The aim of this study was to analyse the presentation, the main features and therapeutic management of medullary thyroid carcinoma associated with negative serum calcitonin levels. METHODS: Using the PubMed database, a systematic review of the current Literature was carried out, up to February 2018. Finally, nineteen articles met our inclusion criteria and were selected according to the modified Newcastle-Ottawa scale. RESULTS: Fourty-nine patients with definitive pathology confirming medullary thyroid carcinoma and with calcitonin serum level in the normal range were identified (24 female, 24 male and not reported gender in 1 case). Mean age was 51.7 years. Serum calcitonin levels were reported for 20 patients with a mean value of 8.66 pg/mL and a range of 0.8-38 pg/mL. Despite the low or undetectable calcitonin serum level, at immunochemistry in almost the half of the cases reported by the Authors, the tumors presented diffuse or focal positivity for calcitonin and carcinoembryionic antigen, while was reported a chromogranin A positivity in 41 of the 43 tested patients. CONCLUSIONS: Calcitonin negative medullary thyroid carcinoma is an extremely rare pathology. The diagnosis and the surveillance is often challenging and delayed, due to the lack of elevation of serum markers as calcitonin and carcinoembryionic antigen. Further studies are needed, to better define options for management of non secretory medullary thyroid carcinoma and to identify new and reliable biomarkers associated to diagnosis and relapse of this medical dilemma.

Pregnancy may favour the development of severe autoimmune central diabetes insipidus in women with vasopressin cell antibodies: description of two cases.

Recently, an increased incidence of central diabetes insipidus (CDI) in pregnancy, and less frequently in the post partum period, has been reported, most probably favoured by some conditions occurring in pregnancy. This study was aimed at investigating the influence of pregnancy on a pre-existing potential/subclinical hypothalamic autoimmunity. We studied the longitudinal behaviour of arginine-vasopressin cell antibodies (AVPcAbs) and post-pituitary function in two young women with a positive history of autoimmune disease and presence of AVPcAbs, but without clinical CDI, and who became pregnant 5 and 7 months after our first observation. The behaviour of post-pituitary function and AVPcAbs (by immunofluorescence) was evaluated at baseline, during pregnancy and for 2 years after delivery. AVPcAbs, present at low/middle titres at baseline in both patients, showed a titre increase during pregnancy in one patient and after delivery in the other patient, with development of clinically overt CDI. Therapy with 1-deamino-8-d-arginine vasopressin (DDAVP) caused a prompt clinical remission. After a first unsuccessful attempt of withdrawal, the therapy was definitively stopped at the 6th and the 7th month of post partum period respectively, when AVPcAbs disappeared, accompanied by post-pituitary function recovery, persisting until the end of the follow-up. The determination of AVPcAbs is advisable in patients with autoimmune diseases planning their pregnancy, because they could be considered good predictive markers of gestational or post partum autoimmune CDI. The monitoring of AVPcAb titres and post-pituitary function during pregnancy in these patients may allow for an early diagnosis and an early replacement therapy, which could induce the disappearance of these antibodies with consequent complete remission of CDI.