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Context: The international GENHYPOPIT network collects phenotypical data and screens genetic causes of non‐acquired hypopituitarism. Aims: To describe main phenotype patterns and their evolution through life. Design: Patients were screened according to their phenotype for coding sequence variations in 8 genes: HESX1, LHX3, LHX4, PROP1, POU1F1, TBX19, OTX2 and PROKR2. Results: Among 1213 patients (1143 index cases), the age of diagnosis of hypopituitarism was congenital (24%), in childhood (28%), at puberty (32%), in adulthood (7.2%) or not available (8.8%). Noteworthy, pituitary hormonal deficiencies kept on evolving during adulthood in 49 of patients. Growth Hormone deficiency (GHD) affected 85.8% of patients and was often the first diagnosed deficiency. AdrenoCorticoTropic Hormone deficiency rarely preceded GHD, but usually followed it by over 10 years. Pituitary Magnetic Resonance Imaging (MRI) abnormalities were common (79.7%), with 39.4% pituitary stalk interruption syndrome (PSIS). The most frequently associated extrapituitary malformations were ophthalmological abnormalities (16.1%). Prevalence of identified mutations was 7.3% of index cases (84/1143) and 29.5% in familial cases (n = 146). Genetic analysis in 449 patients without extrapituitary phenotype revealed 36 PROP1, 2 POU1F1 and 17 TBX19 mutations. Conclusion: This large international cohort highlights atypical phenotypic presentation of constitutional hypopituitarism, such as post pubertal presentation or adult progression of hormonal deficiencies. These results justify long‐term follow‐up, and the need for systematic evaluation of associated abnormalities. Genetic defects were rarely identified, mainly PROP1 mutations in pure endocrine phenotypes. [ABSTRACT FROM AUTHOR]

Aims and methods To evaluate the clinical value of 18 F-fluorodihydroxyphenylalanine (18 F- FDOPA) PET in relation to tumour localization and the patient's genetic status in a large series of pheochromocytoma/paraganglioma ( PHEO/ PGL) patients and to discuss in detail false-negative results. A retrospective study of PGL patients who were investigated with 18 F- FDOPA PET or PET/ CT imaging in two academic endocrine tumour centres was conducted ( La Timone University Hospital, Marseilles, France and National Institutes of Health ( NIH), Bethesda, MD, USA). Results One hundred sixteen patients (39·7% harbouring germline mutations in known disease susceptibility genes) were evaluated for a total of 195 PHEO/ PGL foci. 18 F- FDOPA PET correctly detected 179 lesions (91·8%) in 107 patients (92·2%). Lesion-based sensitivities for parasympathetic PGLs (head, neck, or anterior/middle thoracic ones), PHEOs, and extra-adrenal sympathetic (abdominal or posterior thoracic) PGLs were 98·2% [96·5% for Timone and 100% for NIH], 93·9% [93·8 and 93·9%] and 70·3% [47·1 and 90%] respectively ( P < 0·001). Sympathetic (adrenal and extra-adrenal) SDHx-related PGLs were at a higher risk for negative 18F- FDOPA PET than non- SDHx-related PGLs (14/24 vs 0/62, respectively, P < 0·001). In contrast, the risk of negative 18F- FDOPA PET was lower for parasympathetic PGLs regardless of the genetic background (1/90 in SDHx vs 1/19 in non- SDHx tumours, P = 0·32). 18F- FDOPA PET failed to detect two head and neck PGLs ( HNPGL), likely due to their small size, whereas most missed sympathetic PGL were larger and may have exhibited a specific 18F- FDOPA-negative imaging phenotype. 18F- FDG PET detected all the missed sympathetic lesions. Conclusions 18F- FDOPA PET appears to be a very sensitive functional imaging tool for HNPGL regardless of the genetic status of the tumours. Patients with false-negative tumours on 18F- FDOPA PET should be tested for SDHx mutations. [ABSTRACT FROM AUTHOR]

The aim of this prospective study was to compare the diagnostic value of [F]FDOPA-PET and [In]pentetreotide-SPECT somatostatin receptor scintigraphy (SRS) in patients with nonmetastatic extra-adrenal paragangliomas (PGLs). Twenty-five consecutive unrelated patients who were known or suspected of having nonmetastatic extra-adrenal PGLs were prospectively evaluated with SRS and [F]FDOPA-PET. I-MIBG and [F]FDG-PET were added to the work-up in patients with a personal or familial history of PGL, predisposing mutations, abdominal PGLs, metanephrine hypersecretion and abdominal foci on SRS and/or [F]FDOPA-PET. SRS correctly detected 23/45 lesions of which 20 were head or neck lesions (H&N) and 3 were abdominal lesions. [F]FDOPA-PET detected significantly more lesions than SRS (39/45, P < 0·001). Both SRS and F-DOPA-PET detected significantly more H&N than abdominal lesions (66·7% vs 20%, P = 0·003 and 96·7% vs 67%, P = 0·012, respectively). In two patients with the succinate dehydrogenase D (SDHD) mutation, [F]FDOPA-PET missed five abdominal PGLs which were detected by the combination of SRS, [I]MIBG and [F]FDG-PET. A lesion-based analysis using a forward stepwise logistic regression model demonstrates that size ≤ 10 mm ( P = 0·002) and abdominal lesions ( P = 0·031) were independently associated with '[F]FDOPA-PET diagnosis only'. In turn, a previous history of surgery and/or the presence of germline mutation was associated with lower lesion size ( P = 0·001). The sensitivity of SRS for localizing parasympathetic PGLs is lower than originally reported, and [F]FDOPA-PET is better than SRS for localizing small lesions. SRS should be replaced by [F]FDOPA-PET as the first-line imaging procedure in H&N PGL, especially in patients at risk of multifocal disease (predisposing mutations and or previous history of surgery). [ABSTRACT FROM AUTHOR]

Background 18F-DOPA has emerged as a promising tool in the localization of chromaffin-tissue-derived tumours. Interestingly, phaeochromocytomas (PHEO) are also FDG avid. Aim and methods The aim of this study was to retrospectively evaluate the results of 18F-FDOPA and/or 18F-FDG–PET in patients with PHEO and paragangliomas (PGLs) and to compare the outcome of this approach with the traditional therapeutic work-up. Nine patients with non-MEN2 related PHEO or PGL were evaluated. At the time of the PET studies, the patients were classified into three groups based on their clinical history, conventional and SPECT imaging. The groups were malignant disease ( n = 5, 1 VHL), apparently unique tumour site in patients with previous surgery ( n = 1, SDHB) and multifocal tumours ( n = 3, 1 VHL, 1 SDHD). 18F-FDOPA and 18F-FDG–PET PET/CT were then performed in all patients. Results PET successfully identified additional tumour sites in five out of five patients with metastatic disease that had not been identified with SPECT + CI. Whilst tumour tracer uptake varied between patients it exhibited a consistently favourable residence time for delayed acquisitions. 18F-FDOPA uptake (SUVmax) was superior to 18F-FDG uptake in cases of neck PGL (three patients, four tumours). If only metastatic forms and abdominal PGLs were considered, 18F-FDG provided additional information in three cases (two metastatic forms, one multifocal disease with SDHD mutation) compared to 18F-FDOPA. Conclusions Our results suggest that tumour staging can be improved by combining 18F-FDOPA and 18F-FDG in the preoperative work-up of patients with abdominal and malignant PHEOs. 18F-FDOPA is also an effective localization tool for neck PGLs. MIBG however, still has a role in these patients as MIBG and FDOPA images did not completely overlap. [ABSTRACT FROM AUTHOR]

Aims and Methods: To evaluate the clinical value of (18) F-fluorodihydroxyphenylalanine ((18) F-FDOPA) PET in relation to tumour localization and the patient's genetic status in a large series of pheochromocytoma/paraganglioma (PHEO/PGL) patients and to discuss in detail false-negative results. A retrospective study of PGL patients who were investigated with (18) F-FDOPA PET or PET/CT imaging in two academic endocrine tumour centres was conducted (La Timone University Hospital, Marseilles, France and National Institutes of Health (NIH), Bethesda, MD, USA)., Results: One hundred sixteen patients (39·7% harbouring germline mutations in known disease susceptibility genes) were evaluated for a total of 195 PHEO/PGL foci. (18) F-FDOPA PET correctly detected 179 lesions (91·8%) in 107 patients (92·2%). Lesion-based sensitivities for parasympathetic PGLs (head, neck, or anterior/middle thoracic ones), PHEOs, and extra-adrenal sympathetic (abdominal or posterior thoracic) PGLs were 98·2% [96·5% for Timone and 100% for NIH], 93·9% [93·8 and 93·9%] and 70·3% [47·1 and 90%] respectively (P < 0·001). Sympathetic (adrenal and extra-adrenal) SDHx-related PGLs were at a higher risk for negative (18) F-FDOPA PET than non-SDHx-related PGLs (14/24 vs 0/62, respectively, P < 0·001). In contrast, the risk of negative (18) F-FDOPA PET was lower for parasympathetic PGLs regardless of the genetic background (1/90 in SDHx vs 1/19 in non-SDHx tumours, P = 0·32). (18) F-FDOPA PET failed to detect two head and neck PGLs (HNPGL), likely due to their small size, whereas most missed sympathetic PGL were larger and may have exhibited a specific (18) F-FDOPA-negative imaging phenotype. (18) F-FDG PET detected all the missed sympathetic lesions., Conclusions: (18) F-FDOPA PET appears to be a very sensitive functional imaging tool for HNPGL regardless of the genetic status of the tumours. Patients with false-negative tumours on (18) F-FDOPA PET should be tested for SDHx mutations., (© 2012 John Wiley & Sons Ltd.)

Aims and Methods: The aim of this prospective study was to compare the diagnostic value of [¹⁸F]FDOPA-PET and [¹¹¹In]pentetreotide-SPECT somatostatin receptor scintigraphy (SRS) in patients with nonmetastatic extra-adrenal paragangliomas (PGLs). Twenty-five consecutive unrelated patients who were known or suspected of having nonmetastatic extra-adrenal PGLs were prospectively evaluated with SRS and [¹⁸F]FDOPA-PET. ¹³¹I-MIBG and [¹⁸F]FDG-PET were added to the work-up in patients with a personal or familial history of PGL, predisposing mutations, abdominal PGLs, metanephrine hypersecretion and abdominal foci on SRS and/or [¹⁸F]FDOPA-PET., Results: SRS correctly detected 23/45 lesions of which 20 were head or neck lesions (H&N) and 3 were abdominal lesions. [¹⁸F]FDOPA-PET detected significantly more lesions than SRS (39/45, P < 0·001). Both SRS and ¹⁸F-DOPA-PET detected significantly more H&N than abdominal lesions (66·7% vs 20%, P = 0·003 and 96·7% vs 67%, P = 0·012, respectively). In two patients with the succinate dehydrogenase D (SDHD) mutation, [¹⁸F]FDOPA-PET missed five abdominal PGLs which were detected by the combination of SRS, [¹³¹I]MIBG and [¹⁸F]FDG-PET. A lesion-based analysis using a forward stepwise logistic regression model demonstrates that size ≤ 10 mm (P = 0·002) and abdominal lesions (P = 0·031) were independently associated with "[¹⁸F]FDOPA-PET diagnosis only". In turn, a previous history of surgery and/or the presence of germline mutation was associated with lower lesion size (P = 0·001)., Conclusions: The sensitivity of SRS for localizing parasympathetic PGLs is lower than originally reported, and [¹⁸F]FDOPA-PET is better than SRS for localizing small lesions. SRS should be replaced by [¹⁸F]FDOPA-PET as the first-line imaging procedure in H&N PGL, especially in patients at risk of multifocal disease (predisposing mutations and or previous history of surgery)., (© 2010 Blackwell Publishing Ltd.)