Thyroidectomy without Radioiodine in Patients with Low-Risk Thyroid Cancer.

BACKGROUND: In patients with low-risk differentiated thyroid cancer undergoing thyroidectomy, the postoperative administration of radioiodine (iodine-131) is controversial in the absence of demonstrated benefits. METHODS: In this prospective, randomized, phase 3 trial, we assigned patients with low-risk differentiated thyroid cancer who were undergoing thyroidectomy to receive ablation with postoperative administration of radioiodine (1.1 GBq) after injections of recombinant human thyrotropin (radioiodine group) or to receive no postoperative radioiodine (no-radioiodine group). The primary objective was to assess whether no radioiodine therapy was noninferior to radioiodine therapy with respect to the absence of a composite end point that included functional, structural, and biologic abnormalities at 3 years. Noninferiority was defined as a between-group difference of less than 5 percentage points in the percentage of patients who did not have events that included the presence of abnormal foci of radioiodine uptake on whole-body scanning that required subsequent treatment (in the radioiodine group only), abnormal findings on neck ultrasonography, or elevated levels of thyroglobulin or thyroglobulin antibodies. Secondary end points included prognostic factors for events and molecular characterization. RESULTS: Among 730 patients who could be evaluated 3 years after randomization, the percentage of patients without an event was 95.6% (95% confidence interval [CI], 93.0 to 97.5) in the no-radioiodine group and 95.9% (95% CI, 93.3 to 97.7) in the radioiodine group, a difference of -0.3 percentage points (two-sided 90% CI, -2.7 to 2.2), a result that met the noninferiority criteria. Events consisted of structural or functional abnormalities in 8 patients and biologic abnormalities in 23 patients with 25 events. Events were more frequent in patients with a postoperative serum thyroglobulin level of more than 1 ng per milliliter during thyroid hormone treatment. Molecular alterations were similar in patients with or without an event. No treatment-related adverse events were reported. CONCLUSIONS: In patients with low-risk thyroid cancer undergoing thyroidectomy, a follow-up strategy that did not involve the use of radioiodine was noninferior to an ablation strategy with radioiodine regarding the occurrence of functional, structural, and biologic events at 3 years. (Funded by the French National Cancer Institute; ESTIMABL2 ClinicalTrials.gov number, NCT01837745.).

In silico development of new PET radiopharmaceuticals from mTOR inhibitors.

Rapamycin (or sirolimus) is a macrolide that has shown to be useful as an immunosuppressant and that was studied in metabolic, neurological, or genetic disorders. Rapamycin is a specific natural inhibitor of the mechanistic target of rapamycin (mTOR) that is a kinase protein playing a pivotal role in cell growth and proliferation by activation of several metabolic processes. This work aimed to evaluate the utility of several compounds obtained from rapamycin and its semi-synthetic analogs everolimus and temsirolimus as possible radiopharmaceuticals oriented to this protein. Density Functional Theory calculations of these molecules were made and further analysis of the dual descriptor, charges populations, and of the electrostatic potential surfaces were performed. Molecular docking simulations were used to evaluate the interactions of the rapamycin with the studied candidates. They allowed us to propose two strategies for the synthesis of novel compounds based on electrophilic reactions. Molecular docking results also helped us to eliminate molecules that did not interact correctly with the target. Finally, we found for the first time, that the novel compounds synthesized through the electrophilic addition reaction that employed 18F-selectfluor, should maintain the biological activity of original compounds and could be suitable as Positron Emission Tomography radiopharmaceuticals targeting mTOR Complex1 system.

Triglycerides as a Metabolic Target in Afrocaribbean Infertile Women with Polycystic Ovary Syndrome.

Background: Polycystic ovary syndrome (PCOS) is classically associated with insulin resistance, metabolic syndrome, or type 2 diabetes. Infertile Afrocaribbean (AC) women with PCOS may have metabolic features that could help to better target their management. Objective: To evaluate the characteristics of PCOS in this population and their metabolic profile to target the worst metabolic parameter. Methods: A retrospective study including infertile AC women for 4 years. PCOS was diagnosed using Rotterdam criteria and compared with non-PCOS women referred consecutively for infertility during the same period. Results: Among 981 AC women evaluated for infertility, PCOS was found in 17%. PCOS women were younger than non-PCOS women. After age and body mass index (BMI) matching, only fasting blood glucose and triglyceride levels were higher in PCOS women compared with non-PCOS women. PCOS was positively correlated with triglyceride levels and negatively with vitamin D levels. PCOS women with obesity had low high-density lipoprotein-cholesterol and increased triglyceride levels compared with those without obesity. No correlation was found between lipids or glucose levels and androgen levels. Multivariate analysis showed that only triglycerides were independently related to PCOS after adjustment for age and BMI. Conclusions: In the AC population where the prevalence of obesity and diabetes is increased, the metabolic profile of infertile women with PCOS is mainly characterized by hypertriglyceridemia, with a higher risk of visceral obesity and nonalcoholic fatty liver disease. Interventional studies would be useful to evaluate the predictive value of hypertriglyceridemia on diabetes and cardiovascular diseases in this population.

A Hungry Bone Syndrome Predicted by 18F-Fluorocholine PET/CT.

Predicting hungry bone syndrome (HBS) after surgical cure of primary hyperparathyroidism (PHPT) can be challenging. A 57-year-old man diagnosed with PHPT was assessed preoperatively by F-fluorocholine PET/CT. An intense and diffuse tracer uptake of the axial and peripheral skeleton was visualized, in addition to a pathologic uptake suggestive of hyperfunctioning parathyroid gland. After the removal of a parathyroid adenoma, a severe and prolonged HBS requiring high doses of calcium and active metabolites of vitamin D was observed. This observation suggests that intense and diffuse bone uptake on F-fluorocholine PET/CT could be a predictive factor for HBS in patients with PHPT.

A PRKAR1A mutation associated with primary pigmented nodular adrenocortical disease in 12 kindreds.

CONTEXT: Primary pigmented nodular adrenocortical disease (PPNAD), a rare cause of corticotropin-independent Cushing syndrome, can be part of Carney complex (CNC), an autosomal dominant multiple neoplasia syndrome characterized by spotty skin pigmentation, cardiac myxomas, and endocrine tumors or be isolated (i). Germline PRKAR1A-inactivating mutations have been observed in both CNC and iPPNAD, but with no apparent genotype-phenotype correlation. OBJECTIVE: The objectives of the study were a detailed phenotyping for CNC manifestations in 12 kindreds bearing the same PRKAR1A mutation and a study of the consequences of the mutation and a potential founder effect. DESIGN: The study consisted of descriptive case reports. SETTING: The study was conducted at two referral centers. PATIENTS: The patients described in this study were referred for PRKAR1A gene mutation analysis because of a diagnosis of apparently iPPNAD. RESULTS: We describe a 6-bp polypyrimidine tract deletion [exon 7 IVS del (-7-->-2)] in 12 unrelated kindreds that were referred for Cushing syndrome due to PPNAD. Nine of the patients had no family history; in two, there was a family history of iPPNAD. Only one patient met the criteria for CNC. Relatives carrying the same mutation had no manifestations of CNC or PPNAD, suggesting a low penetrance of this PRKAR1A defect. A founder effect was excluded by extensive genotyping of chromosome 17 markers. CONCLUSIONS: In conclusion, a small intronic deletion of the PRKAR1A gene is a low-penetrance cause of mainly iPPNAD; it is the first PRKAR1A genetic defect to have an association with a specific phenotype.