11C-Metomidate PET/CT for Endocrine Hypertension and Characterisation of Adrenal Tumours

Overview

• 10% of patients with hypertension potentially have the treatable condition - primary aldosteronism (PA). This is caused by either bilateral adrenal disease (~40%), managed with lifelong medications; or unilateral disease (~60%), cured with laparoscopic surgery (adrenalectomy). Current diagnosis of PA includes a screening test with aldosterone-renin ratio, followed by a confirmatory salt loading test (in most patients) to demonstrate unsuppressed aldosterone levels. Of note, some patients with suppressed aldosterone after confirmatory tests (also termed low-renin hypertension) may also have unilateral adrenal tumors.
  • The difficulty with identifying curable unilateral disease is due to adrenal vein sampling (AVS): an invasive, and technically-difficult procedure. An alternative novel imaging, 11C-Metomidate Positron emission tomography-computed tomography (PET-CT), can detect adrenal tumors which are over-producing aldosterone. It is non-invasive, non-operator-dependent, and potentially may identify more patients with curable unilateral disease. The results from our pilot study in 25 patients with confirmed PA (ClinicalTrials.gov NCT03990701, PA_CURE) showed that 11C-Metomidate PET-CT exhibited comparable performance to AVS in subtyping PA, and this should be validated in a larger study.
  • In addition, 11C-Metomidate is also able to differentiate adrenocortical lesions in the adrenal gland from other lesions found in adrenal tissue, such as adrenomedullary lesions (e.g. pheochromocytoma).
  • Hence, the investigators hypothesize that 11C-metomidate PET-CT can accurately (1) identify patients with surgically curable unilateral adrenal disease among hypertensive Asians with primary aldosteronism (PA_CURE 2 / PA_MTO EH study) and (2) differentiate adrenocortical lesions from other lesions in patients with adrenal tumors (PA_MTO AT study)

Description

• The investigators aim to recruit 100 patients with confirmed, or likely, primary aldosteronism to undergo conventional tests, CT, AVS, and 11C-metomidate PET-CT.
  • Results will be reviewed and discussed at a multidisciplinary meeting, and patients with unilateral PA or adrenal tumor will be offered surgery. Patients will be reviewed 6 months post-surgery.
  • In a separate study, the investigators will recruit 10 patients with adrenal tumors to differentiate adrenocortical lesions from other lesions in patients with adrenal tumors

Eligibility

Inclusion Criteria:

• For patients with primary aldosteronism (PA_CURE 2 / PA_MTO EH):
  1. Confirmed diagnosis of primary aldosteronism, as defined in Endocrine Society Guidelines 2016, with positive confirmatory test (post-salt loading aldosterone >140pmol/L); or hypokalemia with undetectable renin levels and aldosterone >550pmol/L; or likely primary aldosteronism / low-renin hypertension (inappropriate aldosterone levels and suppressed renin levels)
  2. Keen for surgical treatment if shown to have unilateral adrenal disease.
• For patients with suspected adrenal tumors (PA_MTO AT)
  1. All patients with suspected adrenal tumors based on imaging and clinical suspicion.

Exclusion Criteria:

• Inability to provide written informed consent.
• Chronic renal failure of Stage 3b or greater severity, estimated glomerular filtration rate (eGFR) < 45ml/min/1.73m2 using Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula. (only applicable for PA_CURE 2 / PA_MTO EH)
• Severe or terminal medical condition(s) that in the view of the investigator prohibits participation in the study or interferes with possible treatment or health-related quality of life, e.g. cancer, end-stage liver disease, end stage renal failure (only applicable for PA_CURE 2 / PA_MTO EH)
• Contraindications to isotope scanning (e.g. Female patients who are pregnant (self-declared or via positive pregnancy test), intending to become pregnant (within 3 months of scan) or breastfeeding) or CT Scan, which includes but not limited to waist circumference >140cm, morbid obesity or claustrophobia (limiting entry in CT scanner)
• Contraindication to ingestion of corticosteroids (e.g. poorly controlled diabetes, HbA1C >13%)