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In most patients with suspected or confirmed pituitary adenomas (PAs), MRI, performed using T1- (with or without gadolinium enhancement) and T2-weighted sequences, provides sufficient information to guide effective clinical decision making. In other patients, additional MR sequences (e.g., gradient recalled echo, fluid-attenuation inversion recovery, MR elastography, or MR angiography) may be deployed to improve adenoma detection, assess tumoral consistency, or aid distinction from other sellar/parasellar lesions (e.g., aneurysm, meningioma). However, there remains a small but important subgroup of patients in whom primary or secondary intervention (e.g., first or redo transsphenoidal surgery, stereotactic radiosurgery) is limited by the inability of MRI to accurately localize the site(s) of de novo, persistent, or recurrent PA. Emerging evidence indicates that hybrid imaging, which combines molecular (e.g. 11C-methionine PET) and cross-sectional (MRI) modalities, can enable the detection and precise localization of sites of active tumor to guide targeted intervention. This not only increases the likelihood of achieving complete remission with preservation of remaining normal pituitary function but may mitigate the need for long-term (even lifelong) high-cost medical therapies. Here, we review published evidence supporting the use of molecular imaging in the management of PAs, including our own 10-y experience with 11C-methionine PET.

Primary aldosteronism (PA) due to a unilateral aldosterone-producing adenoma (APA) is a common, curable cause of hypertension, but invasive methods of diagnosis and treatment contribute to -17%, the pre-specified margin of non-inferiority. The best univariate predictors of complete clinical cure were home systolic blood pressure (SBP)

Thyroid-stimulating hormone (TSH)-secreting pituitary adenomas (thyrotropinomas) are a rare but important cause of hyperthyroidism. Recent studies point to a higher incidence than previously suspected, with a greater proportion of microadenomas. This is likely to reflect, at least in part, the increased use of combined free hormone and TSH measurements to screen for thyroid dysfunction, coupled with improvements in modern magnetic resonance (MR) imaging. The latter has allowed the detection of smaller tumours, but at the same time carries the risk of identifying pituitary incidentalomas that are then falsely identified as the cause of hyperthyroxinaemia with non-suppressed TSH. Accordingly, a systematic approach (combining clinical, biochemical, radiological, and genetic investigations) is required to ensure a robust diagnosis. For most patients transsphenoidal surgery remains the preferred treatment, with somatostatin analogues (SSAs) used to facilitate safe surgery (by normalizing thyroid hormone levels) and as adjunctive therapy when complete surgical resection is not possible. However, emerging data suggests that primary SSA therapy alone is a reasonable option for some patients. Radiotherapy is generally reserved for aggressive (especially SSA resistant) tumours.

Objective To describe clinical practice experience of 11 C-Metomidate PET/CT as an adjunct to adrenal vein sampling (AVS) in the lateralization of aldosterone-producing adenomas (APA) in primary aldosteronism (PA). Context Accurate lateralization of APA in the setting of PA offers the potential for surgical cure and improved long-term cardiovascular outcomes. Challenges associated with AVS, the current gold standard lateralization modality, mean that only a small proportion of potentially eligible patients currently make it through to surgery. This has prompted consideration of alternative strategies for lateralization, including the application of novel molecular PET tracers such as 11 C-Metomidate. Design Clinical Service Evaluation/Retrospective audit. Patients Fifteen individuals with a confirmed diagnosis of PA, undergoing lateralization with 11 C-Metomidate PET/CT prior to final clinical decision on surgical vs medical management. Measurements All patients underwent screening aldosterone renin ratio (ARR), followed by confirmatory testing with the seated saline infusion test, according to Endocrine Society Clinical Practice Guidelines. Adrenal glands were imaged using dedicated adrenal CT. 11 C-Metomidate PET/CT was undertaken due to equivocal or failed AVS. Management outcomes were assessed by longitudinal measurement of blood pressure, ARR, number of hypertensive medications following adrenalectomy or institution of medical therapy. Results We describe the individual lateralization and clinical outcomes for 15 patients with PA. Conclusion 11 C-Metomidate PET/CT in conjunction with adrenal CT and AVS provided useful information which aided clinical decision-making for PA within a multidisciplinary hypertension clinic.

© 2020 Elsevier Inc. In most patients with pituitary adenomas magnetic resonance imaging (MRI) is essential to guide effective decision-making. T1- and T2-weighted sequences allow the majority of adenomas to be readily identified. Supplementary MR sequences (e.g. FLAIR; MR angiography) may also help inform surgery. However, in some patients MRI findings are ‘negative’ or equivocal (e.g. with failure to reliably identify a microadenoma or to distinguish postoperative change from residual/recurrent disease). Molecular imaging [e.g. 11C-methionine PET/CT coregistered with volumetric MRI (Met-PET/MRCR)] may allow accurate localisation of the site of de novo or persistent disease to guide definitive treatment (e.g. surgery or radiosurgery).

Primary aldosteronism (PA) is now considered the sole, often curable, cause of hypertension in 5-10% of patients. Yet there has been only one RCT, and practice has changed little since the advent of CT scanning. Adrenal vein sampling (AVS) and adrenalectomy remain the standard, invasive interventions, leading to a 50% reduction in pill count as the average clinical improvement. Study Design In MATCH (Is Metomidate PET-CT superior to Adrenal vein sampling in predicting ouTCome from adrenalectomy in patients with primary Hyperaldosteronism), 142 patients, mean age 52, 32% female, 32% of African ancestry, 46% hypokalemic, had both AVS and 11C-metomidate PET CT (MTO) in random order, and were referred for surgery if aldosterone/cortisol ratio differed >4-fold between adequately cannulated adrenal veins, and/or SUVmax on MTO was >1.25 higher, in a definite tumour, than the opposite adrenal. The primary outcome is the proportion of patients in whom adrenalectomy achieved complete or partial biochemical or clinical cure, analysed hierarchically using PASO criteria.1 Anticipating ~50% incidence of unilateral PA, MATCH is powered to detect 25% superiority of MTO vs AVS, or non-inferiority at a lower-bound CI of -17%. Secondary outcomes include non-randomised comparison of outcomes between unilateral and bilateral PA; prediction of clinical outcome from the home BP (12 readings over 3 days) before and after starting spironolactone 100 mg od for 4 weeks; quality-of-life assessments; and analyses, by RNAseq, of genotype and transcriptomes of 56 of the CYP11B2-positive tumors, correlated with ethnicity and outcomes. Results: The analysis set is 75 patients who, on 31 Dec 2020, had undergone adrenalectomy with > 6 months follow-up. 67 patients (89%) had complete biochemical cure following PASO criteria,1 and 63 (84%) had complete or partial clinical cure. In 39 of the surgical patients, only one of MTO or AVS was scored as high-probability using criteria above. This score was confirmed at the multi-centre, Multi-Disciplinary Team (MDT) meeting which reviewed all MTO scans without knowledge of AVS. In the primary analysis, comparing accuracy of MTO and AVS by McNemar test, the 39 discordant results were allocated as a win to the positive investigation, if the patient was cured, or to the negative investigation, if not cured. 50/56 CYP11B2-positive tumors had a known mutation; the frequency was CACNA1D>KCNJ5>ATP1A1>ATP2B3>CTNNB1>GNAQ>CLCN2, differing between patients whose hypertension was completely or partially cured. Two other tumors had novel gene mutations. Several RNAseq transcripts varied with genotype and outcome, including some encoding measurable, secreted proteins. Full primary and secondary outcomes will be presented. 1. Williams TA, et al. Lancet Diabetes Endocrinol. 2017;5:689-699

The management of endogenous Cushing's syndrome (CS) typically involves two key steps: (i) confirmation of autonomous hypercortisolism and (ii) localization of the cause to guide treatment. Adrenocorticotropic hormone (ACTH)-dependent CS is most commonly due to a pituitary corticotrope tumor which may be so small as to evade detection on conventional magnetic resonance imaging (MRI). Although biochemical testing (e.g., corticotropin stimulation; dexamethasone suppression) can provide an indication of the likely origin of ACTH excess, bilateral inferior petrosal sinus catheterization offers greater accuracy to distinguish pituitary-driven CS [Cushing's Disease (CD)] from the ectopic ACTH syndrome [EAS, e.g., due to a bronchial or pancreatic neuroendocrine tumor (NET)]. In patients with CD, 40-50% may not have a pituitary adenoma (PA) readily visualized on standard clinical MRI. In these subjects, alternative MR sequences (e.g., dynamic, volumetric, fluid attenuation inversion recovery) and higher magnetic field strength (7T > 3T > 1.5T) may aid tumor localization but carry a risk of identifying coincidental (non-causative) pituitary lesions. Molecular imaging is therefore increasingly being deployed to detect small ACTH-secreting PA, with hybrid imaging [e.g., positron emission tomography (PET) combined with MRI] allowing precise anatomical localization of sites of radiotracer (e.g., 11C-methionine) uptake. Similarly, small ACTH-secreting NETs, missed on initial cross-sectional imaging, may be detected using PET tracers targeting abnormal glucose metabolism (e.g., 18F-fluorodeoxyglucose), somatostatin receptor (SSTR) expression (e.g., 68Ga-DOTATATE), amine precursor (e.g., 18F-DOPA) or amino acid (e.g., 11C-methionine) uptake. Therefore, modern management of ACTH-dependent CS should ideally be undertaken in specialist centers which have an array of cross-sectional and functional imaging techniques at their disposal.

Decision-making in pituitary disease is critically dependent on high quality imaging of the sella and parasellar region. Magnetic resonance imaging (MRI) is the investigation of choice and, for the majority of patients, combined T1 and T2 weighted sequences provide the information required to allow surgery, radiotherapy (RT) and/or medical therapy to be planned and long-term outcomes to be monitored. However, in some cases standard clinical MR sequences are indeterminate and additional information is needed to help inform the choice of therapy for a pituitary adenoma (PA). This article reviews current recommendations for imaging of PA, examines the potential added value that alternative MR sequences and/or CT can offer, and considers how the use of functional/molecular imaging might allow definitive treatment to be recommended for a subset of patients who would otherwise be deemed unsuitable for (further) surgery and/or RT.