Finn Noe Bennedbæk

A Prospective Comparative Study of Parathyroid Dual-Phase Scintigraphy, Dual-Isotope Subtraction Scintigraphy, 4D-CT, and Ultrasonography in Primary Hyperparathyroidism.

Purpose Preoperative localization of the diseased parathyroid gland(s) in primary hyperparathyroidism allows for minimally invasive surgery. This study was designed to establish the optimal first-line preoperative imaging modality. Patients and Methods Ninety-one patients were studied consecutively in a prospective head-to-head comparison of dual isotope (99mTc-MIBI vs 123I) subtraction parathyroid scintigraphy (PS), dual-phase PS, 4-dimensional (4D) CT, and ultrasonography (US). Surgery, histological confirmation, and postoperative normalization of Ca++ and parathyroid hormone were the reference standard. Results Ninety-seven hyperfunctioning parathyroid glands (HPGs) were identified by the reference standard. Sensitivity and specificity for subtraction PS, dual-phase PS, 4D-CT, and US were 93%, 65%, 58%, and 57% as well as 99%, 99.6%, 86%, and 95%, respectively. Interrater agreement was excellent for subtraction PS (&kgr; = 0.96) while only fair for 4D-CT (&kgr; = 0.34). Pinhole imaging and subtraction of delayed images (the latter especially in case of a nodular thyroid gland) increased the sensitivity of subtraction PS. SPECT/low-dose CT did not increase sensitivity but aided in the exact localization of the HPGs. Of 7 negative subtraction PS studies, 4D-CT and US were able to locate 3 and 1 additional HPGs, respectively. Conclusions Dual isotope pinhole subtraction PS has higher diagnostic accuracy compared with dual-phase PS, 4D-CT, and US as a first-line imaging study in primary hyperparathyroidism. In case of a negative scintigraphy or suspicion of multiglandular disease, 4D-CT and/or US is recommended as a second-line modality. However, diagnostic algorithms should be adapted in accordance with local availability and expertise.

The use of exercise interventions to overcome adverse effects of androgen deprivation therapy

Androgen deprivation therapy (ADT) induces severe hypogonadism and is associated with several adverse effects that negatively affect health and quality of life in patients with prostate cancer. ADT changes body composition characterized by an increase in fat mass and a reduction in muscle mass and strength. Insulin sensitivity is also diminished and population-based studies indicate an increased risk of diabetes mellitus and cardiovascular disease in men receiving ADT. Particularly the first 6 months of treatment seem to hold an additional risk of new cardiovascular events for patients with already existing cardiovascular disease. In this initial phase of ADT, metabolic changes are also most prominent. In addition, ADT increases the rate of bone loss and fracture risk. Currently available evidence supports the use of exercise interventions to improve physical function and mitigate ADT-induced fatigue. Some studies also indicate that exercise might moderate ADT-related changes in body composition. However, beneficial effects of exercise interventions on other ADT-related conditions have not been conclusively proven. Trials investigating the effects of ADT on fracture risk and development of diabetes mellitus and cardiovascular disease are still warranted. Furthermore, studies investigating safety and effects of physical activity in men with bone metastases are lacking.

Luteinizing Hormone-Releasing Hormone Agonists are Superior to Subcapsular Orchiectomy in Lowering Testosterone Levels of Men with Prostate Cancer: Results from a Randomized Clinical Trial

Purpose: Recent evidence suggests that reaching the lowest achievable levels of testosterone with androgen deprivation therapy delays disease progression and increases overall survival in men with advanced prostate cancer. The aim of this analysis was to compare posttreatment serum testosterone levels between patients undergoing subcapsular orchiectomy and patients treated with the luteinizing hormone‐releasing hormone agonist triptorelin. Materials and Methods: In this randomized clinical trial we included 58 consecutive hormone naïve men diagnosed with advanced prostate cancer at Herlev and Gentofte University Hospital, Herlev, Denmark from September 2013 to March 2015. Followup was 48 weeks. Participants were randomly assigned 1:1 to subcapsular orchiectomy or triptorelin 22.5 mg given as 24‐week depot injections. Androgen status was measured by liquid chromatography‐tandem mass spectrometry prior to treatment and after 12, 24 and 48 weeks. Between group differences in achieved hormone levels were analyzed by longitudinal Tobit regression. Results: Triptorelin injections resulted in 29% lower testosterone levels (95% CI 17.2–41.7) compared to subcapsular orchiectomy (p <0.001). A significantly higher proportion of men receiving triptorelin had testosterone levels less than 20 ng/dl at 12 and 48 weeks compared to men undergoing orchiectomy (97% vs 79% and 100% vs 87%, respectively, p <0.05). There was no detectable difference in the adrenal androgen reduction between the treatment groups. Conclusions: The use of 24‐week depot triptorelin injections results in significantly lower testosterone levels compared to subcapsular orchiectomy. To our knowledge this is the first randomized study to demonstrate a difference in treatment effect between surgical and medical castration on testosterone levels.

A Placebo-Controlled, Blinded and Randomised Study on the Effects of Recombinant Human Thyrotropin on Quality of Life in the Treatment of Thyroid Cancer

Background: It is well known that thyroid hormone withdrawal (THW) in thyroid cancer patients can induce a decrease in quality of life (QOL). Recombinant human thyrotropin (rh-TSH) has been used to avoid this; however, no blinded studies have ever documented the effect. Objective: To compare QOL in patients with differentiated thyroid cancer (DTC) treated with either rh-TSH or liothyronine (L-T3) THW for 10 days. Study Design: Double-blind, randomised cross-over. Patients: Fifty-six patients with DTC treated by total thyroidectomy and indication for postsurgery radioiodine (RI) ablation therapy. Intervention: Randomisation to either L-T3 and rh-TSH prior to the first RI course and following this to ingest placebo tablets and receive placebo injections before a second RI uptake measurement 4-6 months later, or to receive placebo before the primary RI ablation and active therapy 4-6 months later. Main Outcome Measures: QOL was measured by SF-36 and 2 visual analogue scale (VAS) scores at baseline and during RI therapy or RI uptake. Results: A significant difference in QOL was seen in 2 of 4 predefined SF-36 domains (7.2 and 6.6%) and 2 VAS scales (10 and 14%), favouring rh-TSH therapy. Conclusion: This is the first blinded randomised clinical trial describing the effect of rh-TSH compared to L-T3 THW on QOL in DTC patients. A significant difference was demonstrated, though smaller than described in previous non-blinded studies.

18F-FET-PET in Primary Hyperparathyroidism: A Pilot Study

Preoperative localisation of the diseased parathyroid gland(s) in primary hyperparathyroidism (PHP) is a prerequisite for subsequent minimally invasive surgery. Recently, as alternatives to conventional sestamibi parathyroid scintigraphy, the 11C-based positron emission tomography (PET) tracers methionine and choline have shown promise for this purpose. We evaluated the feasibility of using the 18F-based PET tracer fluoroethyl-l-tyrosine (FET), as the longer half-life of 18F makes it logistically more favourable. As a proof-of-concept study, we included two patients with PHP in which dual-isotope parathyroid subtraction single photon emission computed tomography had determined the exact location of the parathyroid adenoma. A dynamic FET PET/CT scan was performed with subsequent visual evaluation and calculation of target-to-background (TBR; parathyroid vs. thyroid). The maximum TBR in the two patients under study was achieved approximately 30 min after the injection of the tracer and was 1.5 and 1.7, respectively. This ratio was too small to allow for confident visualisation of the adenomas. FET PET/CT seems not feasible as a preoperative imaging modality in PHP.