Thyroid peroxidase antibodies are positively associated with trait markers of depression. The presence of TPOAb may be a vulnerability marker for depression.

Introduction Multiple Endocrine Neoplasia type 1 (MEN1)-related neuroendocrine tumors (NETs) of the lung are mostly indolent with a good prognosis. Nevertheless, cases of aggressive lung NET do occur, and therefore the management of individual patients is challenging. Aim To assess tumor growth and survival of patients with MEN1-related lung NETs at long-term follow-up. Methods The population based Dutch MEN1 Study Group (DMSG) database (n = 446) was used to identify lung NETs by histopathological and radiological examinations. Tumor diameter was assessed. Linear mixed models and the Kaplan-Meier method were used for analyzing tumor growth and survival. Molecular analyses were performed on a lung NET showing particularly aggressive behavior. Results In 102 patients (22.9% of the total MEN1 cohort), 164 lesions suspect of lung NETs were identified and followed for a median of 6.6 years. Tumor diameter increased 6.0% per year. The overall 15-yr survival was 78.0% (95% confidence interval (CI): 64.6% - 94.2%) without lung NET-related death. No prognostic factors for tumor growth or survival could be identified. A somatic c.3127A>G (p.Met1043Val) PIK3CA driver mutation was found in a case of rapid growing lung NET after six years of indolent disease, presumably explaining the sudden change in course. Conclusion MEN1-related lung NETs are slow-growing and have a good prognosis. No accurate risk factors for tumor growth could be identified. Lung NET screening should therefore be based on well-informed shared decision-making, balancing between the low absolute risk of an aggressive tumor in individuals and the potential harms of frequent thoracic imaging.

Objective: The aim of this study was to investigate the influence of age on the association between thyroid function and mortality. Design: The Nijmegen Biomedical Study is a population-based study, comprising 5816 randomly selected adults of all age groups without previously known thyroid disease. years).Results: Subclinical thyrotoxicosis was associated with mortality in subjects aged !65 years (hazard ratio (HR) 2.5, 95% CI 1.1-5.7), but not in subjects aged O65 years. As for thyroid function within the normal range: in the 493 participants aged 80 years or older, an FT 4 level in the high-normal range (18.5-22 pmol/l) was associated with a higher mortality in comparison with FT 4 levels in the middle range (11.5-15.0 pmol/l): HR 1.7 (95% CI 1.0-2.9). In these elderly, TSH levels within the highnormal range (3.0-4.0 mIU/l) were also associated with a higher mortality in comparison with TSH levels within the middle range (1.0-2.0 mIU/l): HR 1.8 (95% CI 1.0-3.1). Conclusions:The relationship between thyroid function and mortality differs according to age. This finding might (partially) explain the discrepant results of previous studies examining the relationship between thyroid function and mortality in different age groups.

The relationship between thyroid function and disease rates is underestimated by studies using only one measurement of TSH and FT(4). The true association will be about 33% (1/0.75) higher for studies with a follow-up time of 2-4 yr.

Denosumab (Dmab) treatment can benefit patients with fibrous dysplasia/McCune-Albright syndrome (FD/MAS) by suppressing the receptor activator of nuclear factor κB ligand (RANKL)-mediated increased bone resorption. However, limited data of two pediatric cases indicate that a rebound phenomenon may occur after withdrawal. Therefore we studied the safety of Dmab discontinuation in FD/MAS. Thirty-seven patients using Dmab, mostly after unsuccessful bisphosphonate (BP) treatment, were included. Health records were screened for pain scores, side effects, and bone turnover markers (BTMs) (calcium, alkaline phosphatase [ALP], procollagen 1 N-terminal propeptide [P1NP], and β-crosslaps [B-CTX, also termed β-C-terminal telopeptide]) during treatment, and for BTMs and clinical rebound effects after withdrawal. BTM levels after withdrawal were compared to pretreatment values. Data were calculated as median (interquartile range [IQR]). BTMs normalized in two-thirds of patients and pain scores decreased significantly during treatment (p = 0.002). One patient (2.7%) developed osteonecrosis of the jaw. Sixteen patients discontinued Dmab treatment after a median of 1.6 years (IQR 1.0 years) because of insufficient effect on pain (n = 10, 63%), side effects (n = 4, 25%), or other reasons (n = 4, 25%). Follow-up posttreatment was 3.2 (2.8) years, wherein no fractures, pain flares, or lesion progression occurred. Calcium remained normal in all but one patient, who had a mild asymptomatic hypercalcemia (2.73 mmol/L) 5 months after discontinuation. ALP passed pretreatment levels in five of 11 patients (46%), increased most after 6 months by 18 (43) U/L, and returned to baseline levels thereafter. P1NP exceeded pretreatment levels in four of nine patients (44%), CTX in eight of nine patients (89%). P1NP rose most after 3 months and stabilized thereafter. CTX showed the highest relative elevation. Patients with high pretreatment levels responding well to Dmab seemed to have the highest rebound. These results suggest beneficial effects of Dmab on pain and BTMs, and show a biochemical but asymptomatic rebound phenomenon after withdrawal in adults with FD/MAS, mainly in case of high pretreatment levels, good response, and multiple injections. Further studies on the safety of Dmab and withdrawal are needed and ongoing.