Value of 123I/99mTc-sestamibi parathyroid scintigraphy with subtraction SPECT/CT in primary hyperparathyroidism for directing minimally invasive parathyroidectomy.

BACKGROUND: Primary hyperparathyroidism/(PHPT) is one of the most common endocrinological conditions. Surgery remains the only curative option. We have evaluated the performance of double isotope 123I/99mTc-sestamibi parathyroid scintigraphy/(PS) with subtraction SPECT/CT in PHP for identifying uniglandular disease. METHODS: Ninety PHPT patients undergoing parathyroidectomy (December 2015-August 2016) were included. All patients were evaluated with neck ultrasound/(US), PS and SPECT/CT with a new protocol. Outcomes from imaging modalities were reported as: uniglandular disease/(UGD), multiglandular disease/(MGD), or negative, and were compared to post-operative diagnoses. RESULTS: Post-operatively, 72 and 18 patients had true UGD and MGD, respectively. Sensitivities and specificities of US, pinhole scintigraphy with subtraction, pinhole and SPECT/CT with subtraction, and all modalities combined were 91.7%/38.9%, 88.9%/72.2%, 93%/66.7% and 84.72%/77.78%, respectively: specificity of US + PS superior to US alone, p = 0.074. SPECT/CT enables reclassification of doubtful uptake foci. CONCLUSIONS: Combination of neck US and PS with subtraction SPECT/CT offers a higher specificity for guiding towards minimally invasive parathyroidectomy.

Psychological impact of von Hippel-Lindau genetic screening in patients with a previous history of hemangioblastoma of the central nervous system.

Von Hippel-Lindau (VHL) syndrome is a hereditary cancer syndrome characterized by a high risk of developing benign and malignant tumors, including central nervous system hemangioblastomas (CNS HBs). For an early diagnosis of VHL, before the occurrence of cancers (especially renal cell carcinoma), it is of huge importance to initiate VHL genetic testing in at-risk patients. The aim of the study was to assess the psychological impact of VHL genetic testing in patients previously diagnosed with a CNS HB. From 1999 until 2015, 55 patients underwent surgery for CNS HBs. Eleven patients were already screened for VHL mutations and 3 patients deceased before the start of the study. From the remaining 42 patients, 24 were accepted to be enrolled in the study. Assessment of psychological impact of VHL genetic testing was performed by measuring anxiety levels, mood disorders, quality of life, and psychological consequences of genetic screening. Twenty-one of the enrolled 24 patients underwent VHL genetic testing and 12 patients came back for the communication of positive genetic results. The baseline psychological status did not differ between these 2 groups. Patients who attended the visit of communication of genetic results had similar anxiety levels compared to those who had not. Furthermore, they also experienced an improvement in the level of anxiety and two QoL dimension scores compared to their baseline status. In summary, there is no evidence of a negative psychosocial impact of VHL genetic testing in patients with a previous history of CNS HB. We, therefore, recommend the recall of patients who have not been previously screened.

Paraganglioma of the organ of Zuckerkandl associated with a somatic HIF2α mutation: A case report.

Paragangliomas of the organ of Zuckerkandl (OZ-PGL) are rare tumors that, in >70% of cases, occur in association with succinate dehydrogenase complex iron sulfur subunit B (SDHB) or SDHD gene mutations. The aim of the current study was to determine whether a somatic genetic defect in the hypoxia-inducible factor 2α (HIF2α) gene was present in a case of sporadic OZ-PGL. A 32-year-old African female presented with uncontrolled hypertension during the first trimester of pregnancy. A diagnostic hysteroscopy was performed 3 months after delivery, precipitating a hypertensive crisis. Thereafter, the patient was diagnosed with noradrenaline-secreting OZ-PGL. A complete blood count identified mild normocytic anemia of an inflammatory origin. Surgical removal of the tumor resulted in normalization of plasma and urinary normetanephrine levels. Genetic testing for germline mutations (including large deletions) in the von Hippel-Lindau tumor suppressor, SDHB, SDHC and SDHD genes was normal. However, a heterozygous missense mutation (c.1589Cys>Tyr) was detected in exon 12 of HIF2α, which results in a substitution of alanine 530 with valine (Ala530Val) in the HIF2α protein. A germline mutation was excluded based on the negative results of blood DNA testing. A three-dimensional homology model of Ala530Val was constructed, which showed impaired HIF2α/VHL interaction and decreased HIF2α ubiquitination. 1H-high-resolution magic-angle-spinning nuclear magnetic resonance spectroscopy detected low succinate levels and high α and ß glucose levels. To the best of our knowledge, the present case represents the first of its kind to associate a somatic HIF2α gain-of-function mutation with OZ-PGL. It is therefore recommended that patients without germline SDHx mutations should be tested for HIF2α mutations.

Quality of life, clinical outcomes and safety of early prophylactic levothyroxine administration in patients with Graves' hyperthyroidism undergoing radioiodine therapy: a randomized controlled study.

OBJECTIVE: While radioiodine therapy is commonly used for treating Graves' disease, a prolonged and clinical hypothyroidism may result in disabling symptoms leading to deterioration of quality of life (QoL) of patients. Introducing levothyroxine (LT4) treatment in the early post-therapeutic period may be an interesting approach to limit this phenomenon. METHODS: A multicenter, prospective, open-label randomized controlled trial enrolled 94 patients with Graves' hyperthyroidism randomly assigned to the experimental group (n=46) (group A: early prophylactic LT4 treatment) or the control group (n=48) (group B: standard follow-up). The primary endpoint was the 6-month QoL. The secondary endpoints were other QoL scores such as Graves' ophthalmopathy (GO) outcomes, thyroid function tests and safety. RESULTS: The primary endpoint at 6 months was achieved: the mental composite score (MCS) of Short Form 36 (SF-36) was significantly higher in group A compared to group B (P=0.009). Four other dimension scores of the SF-36 and four dimension scores of the thyroid-specific patient-reported outcome (ThyPRO) significantly differed between the two groups, indicating better QoL in group A. After adjustment for variables, the early LT4 administration strategy was found as an independent factor for only two scores of SF-36: the MCS and the general health (GH) score. There were no differences in GO, final thyroid status and changes in the anti-TSH receptor antibodies (TRAbs) levels between the two groups. No adverse cardiovascular event was reported. CONCLUSION: Early LT4 administration post-radioactive iodine (RAI) could represent a safe potential benefit for patients with regard to QoL. The optimal strategy taking into account administered RAI activities and LT4 treatment dosage and timing remains to be determined.

(18)F-DOPA PET/CT in the diagnosis and localization of persistent medullary thyroid carcinoma.

PURPOSE: To evaluate the performance of (18)F-L-dihydroxyphenylalanine ((18)F-DOPA) PET/CT in the detection of locoregional and distant medullary thyroid carcinoma (MTC) metastases and to compare imaging findings with histological data. METHODS: We retrospectively evaluated 86 MTC patients with persistently high serum calcitonin levels after initial surgery who had undergone (18)F-DOPA PET/CT between January 2007 and December 2014 in two referral centres. They were followed up for at least 6 months after the PET/CT assessment. The results were compared with histological data or with the findings obtained during follow-up using a complementary imaging modality. RESULTS: (18)F-DOPA PET/CT was positive in 65 of the 86 patients, corresponding to a patient-based sensitivity of 75.6 %. Distant metastatic disease (M1) was seen in 29 patients including 11 with previously unknown metastases revealed only by PET/CT. Among the 36 patients without distant metastatic spread, 25 had nodal involvement limited to the neck, and 10 of these 25 patients underwent reoperation. The lymph node compartment-based sensitivity of (18)F-DOPA PET/CT was 100 % in the two institutions but lesion-based sensitivity was only 24 %. Preoperative and postoperative median calcitonin levels were 405 pg/mL (range 128 - 1,960 pg/mL) and 259 pg/mL (range 33 - 1,516 pg/mL), respectively. None of the patients achieved normalization of serum calcitonin after reoperation. CONCLUSION: (18)F-DOPA PET/CT enables early diagnosis of a significant number of patients with distant metastasis. It has a limited sensitivity in the detection of residual disease but provides high performance for regional analysis. A surgical compartment-oriented approach could be the approach of choice whatever the number of nodes revealed by (18)F-DOPA PET/CT.

Application and Dosimetric Requirements for Gallium-68-labeled Somatostatin Analogues in Targeted Radionuclide Therapy for Gastroenteropancreatic Neuroendocrine Tumors.

Neuroendocrine tumors (NETs) are associated with variable prognosis, with grade 1 and 2 NETs having more favorable outcomes than grade 3. Patients with gastroenteropancreatic (GEP)-NET need individualized interdisciplinary evaluations and treatment. New treatment options have become available with significant improvements in progression-free survival. Peptide receptor radionuclide therapy (PRRT) using (90)Y or (177)Lu-labeled somatostatin analogues (SSTa) has also shown promise in the treatment of advanced progressive NETs. (68)Ga-1,4,7,10-tetraazacyclodecane-1,4,7,10-tetraacetic acid (DOTA)-SSTa can be used as companion imaging agents to assist in radionuclide therapy selection. (68)Ga-DOTA-SSTa PET/computed tomography might also provide information for prognosis, tumor response assessment to PRRT, and internal dosimetry.