Explore the vast range of titles available.

PurposeSurgical indications for pituitary tumors during pregnancy are rare, and are derived from a balance between expected benefits, particularly for maternal benefits, and anesthetic/surgical risks.MethodsA literature review was performed to define the optimal surgical indications for pituitary adenomas (PA) and other pituitary tumors during pregnancy.ResultsMain benefits are expected in case of critical visual impairment and/or life-threatening endocrine disturbances. Multidisciplinary patient management is systematically required although nonobstetric surgery presents a reasonable risk during pregnancy. The risks of congenital malformation during the first trimester and those of premature birth during the third trimester make the second trimester the optimal period for surgery. In prolactin-secreting, nonsecreting, GH- and TSH-secreting PAs, transsphenoidal surgery (TS) is recommended in cases involving severe visual impairment, characterized by severe visual field deficit, visual acuity impairment, and abnormal optical coherence tomography findings, and when no other medical alternatives are possible and/or sufficient. Uncontrolled and severe Cushing’s disease (CD) during pregnancy increases both maternal and fetal morbimortality, thus justifying TS or sometimes dopamine agonist therapy as a safer alternative. Finally, metyrapone, ketoconazole, or bilateral adrenalectomy could be recommended in certain cases after the failure of medical therapies and/or TS. Surgery is also required for suprasellar meningiomas, craniopharyngiomas, and pituitary cysts in the case of severe visual deficit.ConclusionSurgical indications for pituitary tumors are rare during pregnancy; therefore, surgery should be avoided when possible. Further, the second trimester should be considered as the optimal surgical period. Severe visual disturbance and uncontrolled CD are the main surgical indications during pregnancy.

Cushing’s disease, or pituitary ACTH dependent Cushing’s syndrome, is a rare disease responsible for increased morbidity and mortality. Signs and symptoms of hypercortisolism are usually non specific: obesity, signs of protein wasting, increased blood pressure, variable levels of hirsutism. Diagnosis is frequently difficult, and requires a strict algorithm. First-line treatment is based on transsphenoidal surgery, which cures 80% of ACTH-secreting microadenomas. The rate of remission is lower in macroadenomas. Other therapeutic modalities including anticortisolic drugs, radiation techniques or bilateral adrenalectomy will thus be necessary to avoid long-term risks (metabolic syndrome, osteoporosis, cardiovascular disease) of hypercortisolism. This review summarizes potential pathophysiological mechanisms, diagnostic approaches, and therapies.

PurposeTransient hypoparathyroidism is the most common complication after total thyroidectomy, and accidental parathyroidectomy (AP) may be a cause. The aim of this study was to investigate the incidence of AP and its impact on postoperative calcemia.Materials and methodsFrom February 2016 to May 2018, 766 patients undergoing total thyroidectomy were prospectively included. Surgical indications, hormonal status, definitive histology, and postoperative calcium and PTH levels were analyzed.Results578/(75.45%) were women and 188/(24.55%) men with mean age of 53.4 years. Parathyroid tissue on the thyroid specimen was observed in 40 (5.2%) patients: 30 APs and 10 parathyroid fragments. Among the 30 APs, 12 glands were intrathyroid and 18 (2.3%) in eutopic location. 97 (12.6%) patients were treated for postoperative hypocalcemia: 90 (11.7%) had transient and 5 (0.6%) definitive hypoparathyroidism; 2 were lost in follow-up. 13/30 (43.3%) with AP had transient hypoparathyroidism. A strong correlation was found (p < 0.0001) between AP and postoperative hypocalcemia. 1/30 (3.3%) patient with APs had definitive hypoparathyroidism. Transient and persistent nerve palsies were found in 10 (1.3%) and 3 (0.4%) patients, respectively.DiscussionA careful examination of the thyroid gland after resection help to identify an AP that could be autotransplanted. Surgeon and hospital activity volume per years seem to reduce the risk of hypoparathyroidism.ConclusionTotal thyroidectomy and intrathyroid localization of parathyroid glands are risk factors for the AP. The incidence of AP was 2.3%, and this remains low due to our longstanding experience in thyroid and parathyroid surgery.

Purpose Pheochromocytomas/paragangliomas (PHEOs/PGLs) overexpress ă somatostatin receptors and recent studies have already shown excellent ă results in the localization of these tumors using Ga-68-labeled ă somatostatin analogs (Ga-68-DOTA-SSA), especially in patients with ă germline succinate dehydrogenase subunit B gene (SDHB) mutations and ă head and neck PGLs (HNPGLs). The value of Ga-68-DOTA-SSA has to be ă established in sporadic cases, including PHEOs. Thus, the aim of this ă study was to compare Ga-68-DOTATATE PET/CT, F-18-FDOPA PET/CT, and ă conventional imaging in patients with various PHEOs/PGLs with a special ă emphasis on sporadic cases, including those located in the adrenal ă gland. ă Design Ga-68-DOTATATE, F-18-FDOPA PET/CT, and conventional imaging ă (contrast-enhanced CT and MRI with MR angiography sequences) were ă prospectively performed in 30 patients (8 with SDHD mutations, 1 with a ă MAX mutation and 21 sporadic cases) with PHEO/PGL at initial diagnosis ă or relapse. ă Results The patient-based sensitivities were 93 % (28/30), 97 % ă (29/30), and 93 % (28/30) for Ga-68-DOTATATE PET/CT, F-18-FDOPA PET/CT, ă and conventional imaging, respectively. The lesion-based sensitivities ă were 93 % (43/46), 89 % (41/46), and 76 % (35/46) for Ga-68-DOTATATE ă PET/CT, F-18-FDOPA PET/CT, and conventional imaging respectively (p = ă 0.042). Ga-68-DOTATATE PET/CT detected a higher number of HNPGLs (30/30) ă than F-18-FDOPA PET/CT (26/30; p = 0.112) and conventional imaging ă (24/30; p = 0.024). Ga-68-DOTATATE PET/CT missed two PHEOs of a few ă millimeters in size and a large recurrent PHEO. One lesion was ă considered false-positive on Ga-68-DOTATATE PET/CT and corresponded to a ă typical focal lesion of fibrous dysplasia on MRI. Among the 11 lesions ă missed by conventional imaging, 7 were detected by conventional imaging ă with knowledge of the PET results (4 HNPGLs, 2 LNs, and 1 recurrent ă PHEO). ă Conclusion Ga-68-DOTATATE PET/CT is the most sensitive tool in the ă detection of HNPGLs, especially SDHD-related tumors, which may be very ă small and fail to concentrate sufficient F-18-FDOPA. The present study ă further expands the use of Ga-68-DOTATATE for all patients with HNPGLs, ă regardless of their genotype. Ga-68-DOTATATE PET/CT may be inferior to ă F-18-FDOPA PET/CT in the detection PHEOs.

Pheochromocytomas/paragangliomas (PHEOs/PGLs) overexpress somatostatin receptors and recent studies have already shown excellent results in the localization of these tumors using (68)Ga-labeled somatostatin analogs ((68)Ga-DOTA-SSA), especially in patients with germline succinate dehydrogenase subunit B gene (SDHB) mutations and head and neck PGLs (HNPGLs). The value of (68)Ga-DOTA-SSA has to be established in sporadic cases, including PHEOs. Thus, the aim of this study was to compare (68)Ga-DOTATATE PET/CT, (18)F-FDOPA PET/CT, and conventional imaging in patients with various PHEOs/PGLs with a special emphasis on sporadic cases, including those located in the adrenal gland. (68)Ga-DOTATATE, (18)F-FDOPA PET/CT, and conventional imaging (contrast-enhanced CT and MRI with MR angiography sequences) were prospectively performed in 30 patients (8 with SDHD mutations, 1 with a MAX mutation and 21 sporadic cases) with PHEO/PGL at initial diagnosis or relapse. The patient-based sensitivities were 93 % (28/30), 97 % (29/30), and 93 % (28/30) for (68)Ga-DOTATATE PET/CT, (18)F-FDOPA PET/CT, and conventional imaging, respectively. The lesion-based sensitivities were 93 % (43/46), 89 % (41/46), and 76 % (35/46) for (68)Ga-DOTATATE PET/CT, (18)F-FDOPA PET/CT, and conventional imaging respectively (p = 0.042). (68)Ga-DOTATATE PET/CT detected a higher number of HNPGLs (30/30) than (18)F-FDOPA PET/CT (26/30; p = 0.112) and conventional imaging (24/30; p = 0.024). (68)Ga-DOTATATE PET/CT missed two PHEOs of a few millimeters in size and a large recurrent PHEO. One lesion was considered false-positive on (68)Ga-DOTATATE PET/CT and corresponded to a typical focal lesion of fibrous dysplasia on MRI. Among the 11 lesions missed by conventional imaging, 7 were detected by conventional imaging with knowledge of the PET results (4 HNPGLs, 2 LNs, and 1 recurrent PHEO). (68)Ga-DOTATATE PET/CT is the most sensitive tool in the detection of HNPGLs, especially SDHD-related tumors, which may be very small and fail to concentrate sufficient (18)F-FDOPA. The present study further expands the use of (68)Ga-DOTATATE for all patients with HNPGLs, regardless of their genotype. (68)Ga-DOTATATE PET/CT may be inferior to (18)F-FDOPA PET/CT in the detection PHEOs.

Abstract Context Germline CDKN1B variants predispose patients to multiple endocrine neoplasia type 4 (MEN4), a rare MEN1-like syndrome, with <100 reported cases since its discovery in 2006. Although CDKN1B mutations are frequently suggested to explain cases of genetically negative MEN1, the prevalence and phenotype of MEN4 patients is poorly known, and genetic counseling is unclear. Objective To evaluate the prevalence of MEN4 in MEN1-suspected patients and characterize the phenotype of MEN4 patients. Design Retrospective observational nationwide study. Narrative review of literature and variant class reassessment. Patients We included all adult patients with class 3/4/5 CDKN1B variants identified by the laboratories from the French Oncogenetic Network on Neuroendocrine Tumors network between 2015 and 2022 through germline genetic testing for MEN1 suspicion. After class reassessment, we compared the phenotype of symptomatic patients with class 4/5 CDKN1B variants (ie, with genetically confirmed MEN4 diagnosis) in our series and in literature with 66 matched MEN1 patients from the UMD-MEN1 database. Results From 5600 MEN1-suspected patients analyzed, 4 with class 4/5 CDKN1B variant were found (0.07%). They presented with multiple duodenal NET, primary hyperparathyroidism (PHPT) and adrenal nodule, isolated PHPT, PHPT, and pancreatic neuroendocrine tumor. We listed 29 patients with CDKN1B class 4/5 variants from the literature. Compared with matched MEN1 patients, MEN4 patients presented lower NET incidence and older age at PHPT diagnosis. Conclusion The prevalence of MEN4 is low. PHPT and pituitary adenoma represent the main associated lesions, NETs are rare. Our results suggest a milder and later phenotype than in MEN1. Our observations will help to improve genetic counseling and management of MEN4 families.

PurposeWith increasing economic pressures to shorten the length of hospital stay, there has been much recent interest in studying risk factors for the development of postoperative hypocalcemia after total thyroidectomy.The aim of this study was to investigate whether serum calcium and/or PTH levels can predict post-thyroidectomy hypoparathyroidism.MethodsFrom January to December 2014, 477 consecutive patients undergoing total thyroidectomy were included. Corrected calcemia and PTH were systematically performed on postoperative day 1/(POD1). Symptomatic patients were treated on POD1 or POD2 with calcium and vitamin D.ResultsSixty-eight patients (14.25%) were treated for postoperative hypocalcemia. No patients with calcemia ≥ 2.16 mmol/l and PTH ≥ 1.9 pmol/l were supplemented and therefore were safely discharged on POD1 (specificity = 100%). All patients with calcemia ≤ 1.89 mmol/l were treated regardless the PTH values (n = 10) (specificity = 100%). For calcium value between 1.9 and 2.16 mmol/l with a PTH > 4.7 pmol/l, nobody was treated. With a calcemia between 1.9 and 2.16 mmol/l and a PTH > 1.9 pmol/l, 44 patients did not develop any symptom. ROC curve analysis showed that combination of Cac = 2.16 mmol/l and iPTH = 4.7 pmol/l provided a sensitivity of 97.06% and a specificity of 76.53% (p < 0.0001). We therefore propose an algorithm that would allow to 70% of patients could have been discharged on POD1 without risk of hypocalcemia or overtreatment.ConclusionCombination of corrected calcemia and PTH on POD1 can efficiently predict hypocalcemia and be integrated into clinical practice for personalizing lengths of hospitalization and appropriate treatment.Trial registrationClinicalTrials.gov PRS. Unique Identifying number or registration ID: NCT04372225

Context: Germline CDKN1B variants predispose patients to multiple endocrine neoplasia type 4 (MEN4), a rare MEN1-like syndrome, with <100 reported cases since its discovery in 2006. Although CDKN1B mutations are frequently suggested to explain cases of genetically negative MEN1, the prevalence and phenotype of MEN4 patients is poorly known, and genetic counseling is unclear. Objective: To evaluate the prevalence of MEN4 in MEN1-suspected patients and characterize the phenotype of MEN4 patients. Design: Retrospective observational nationwide study. Narrative review of literature and variant class reassessment. Patients: We included all adult patients with class 3/4/5 CDKN1B variants identified by the laboratories from the French Oncogenetic Network on Neuroendocrine Tumors network between 2015 and 2022 through germline genetic testing for MEN1 suspicion. After class reassessment, we compared the phenotype of symptomatic patients with class 4/5 CDKN1B variants (ie, with genetically confirmed MEN4 diagnosis) in our series and in literature with 66 matched MEN1 patients from the UMD-MEN1 database. Results: From 5600 MEN1-suspected patients analyzed, 4 with class 4/5 CDKN1B variant were found (0.07%). They presented with multiple duodenal NET, primary hyperparathyroidism (PHPT) and adrenal nodule, isolated PHPT, PHPT, and pancreatic neuroendocrine tumor. We listed 29 patients with CDKN1B class 4/5 variants from the literature. Compared with matched MEN1 patients, MEN4 patients presented lower NET incidence and older age at PHPT diagnosis. Conclusion: The prevalence of MEN4 is low. PHPT and pituitary adenoma represent the main associated lesions, NETs are rare. Our results suggest a milder and later phenotype than in MEN1. Our observations will help to improve genetic counseling and management of MEN4 families. Key Words: CDKN1B, MEN4, MEN1, multiple endocrine neoplasia, pituitary, parathyroid, neuroendocrine tumor

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. 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. (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. (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.

Our objective was to evaluate (18)F-FDG PET uptake in patients with nonmetastatic and metastatic chromaffin-derived tumors. Twenty-eight consecutive unrelated patients with chromaffin tumors, including 9 patients with genetically determined disease, were studied. A combination of preoperative imaging work-up, surgical findings, and pathologic analyses was used to classify the patients into 2 groups: those with nonmetastatic disease (presumed benign, n = 18) and those with metastatic tumors (n = 10). (18)F-FDG PET was performed in all cases. Visual and quantitative analyses were individually graded for each tumor. Somatic mutations of the succinate dehydrogenase subunits B and D and Von-Hippel Lindau genes were also evaluated in 6 benign sporadic tumor samples. All but 2 patients showed significantly increased (18)F-FDG uptake on visual analysis. The maximum standardized uptake value (SUVmax) ranged from 1.9 to 42 (mean +/- SD, 8.2 +/- 9.7; median, 4.6) in nonmetastatic tumors and 2.3 to 29.3 (mean +/- SD, 9.7 +/- 8.4; median, 7.4) in metastatic tumors. No statistical difference was observed between the groups (P = 0.44), but succinate dehydrogenase-related tumors were notable in being the most (18)F-FDG-avid tumors (SUVmax, 42, 29.3, 21, 17, and 5.3). Succinate dehydrogenase and Von-Hippel Lindau-related tumors had a significantly higher SUVmax than did neurofibromatosis type 1 and multiple endocrine neoplasia type 2A syndrome-related tumors (P = 0.02). (18)F-FDG PET was superior to (131)I-metaiodobenzylguanidine in all metastatic patients but one. By contrast, (18)F-FDG PET underestimated the extent of the disease, compared with 6-(18)F-fluorodopa PET, in 5 patients with metastatic pheochromocytoma. However, succinate dehydrogenase mutations (germline and somatic) and functional dedifferentiation do not adequately explain (18)F-FDG uptake since most tumors were highly avid for (18)F-FDG. (18)F-FDG PET positivity is almost a constant feature of pheochromocytomas and paragangliomas. It may be considered a molecular signature of such tumors, although which aspect of the plethora of molecular changes associated with dedifferentiation, germline genetic defects, or the adaptive response to hypoxia is responsible for this characteristic requires further elucidation.