Reassessment of Postural Stimulation Testing as a Simple Tool to Identify a Subgroup of Patients With Unilateral Primary Aldosteronism.

CONTEXT: Adrenal vein sampling (AVS) represents the current diagnostic gold standard for differentiation between unilateral and bilateral primary aldosteronism (PA). Postural stimulation testing (PST) has been used to provide additional diagnostic information. OBJECTIVE: This work aimed to evaluate the diagnostic utility of PST in the differential diagnosis of PA. METHODS: This cohort study was conducted at a single tertiary reference center. We analyzed 106 PST performed between 2008 and 2020. Diagnosis of PA and cause of PA were determined according to the Endocrine Society Clinical Practice Guideline, taking into account results of saline infusion testing, AVS, preoperative imaging, and outcome after medical or surgical treatment. The suggested cutoffs for the diagnosis of unilateral PA were revisited and optimized for high specificity using receiver operating characteristics (ROC) analysis. RESULTS: A total of 106 patients had confirmed PA (unilateral PA: n = 55, bilateral PA: n = 29, AVS unsuccessful/declined by patients: n = 22). Based on decreased aldosterone plasma concentration of 28% or more after 4 hours in the upright position, the PST showed a sensitivity of 36.4% at a specificity of 100% to identify unilateral disease (area under the curve [AUC] = 0.72; 95% CI, 0.62-0.83; P = .001). In patients with valid testing (drop of cortisol of 10% or more after 4 hours, n = 53) the sensitivity of PST rose to 51.4% at a specificity of 100% (AUC = 0.77; 95% CI, 0.65-0.90; P = .001). CONCLUSION: The high specificity of 100% for the detection of unilateral PA in patients with decreased aldosterone by at least 28% after 4 hours makes PST a simple, noninvasive contribution to subtype differentiation in PA.

Targeting 11-Beta Hydroxylase With [131I]IMAZA: A Novel Approach for the Treatment of Advanced Adrenocortical Carcinoma.

CONTEXT: Adrenocortical carcinoma (ACC) is a rare endocrine malignancy with limited treatment options. Theranostic approaches with adrenal specific radiotracers hold promise for improved diagnostics and treatment. OBJECTIVE: Here, we report a new theranostic approach to advanced ACC applying (R)-1-[1-(4-[123I]iodophenyl)ethyl]-1H-imidazole-5-carboxylic acid azetidinyl amide ([123I]IMAZA) for diagnostic imaging and [131I]IMAZA for radionuclide therapy. METHODS: Sixty-nine patients with nonresectable, metastatic ACCs were screened using a diagnostic [123I]IMAZA scan. Patients with significant uptake in all tumoral lesions were offered treatment with [131I]IMAZA. Tumor response was assessed according to Response Evaluation Criteria in Solid Tumors (RECIST version 1.1), and adverse effects were assessed by Common Toxicity Criteria (version 5.0). RESULTS: After screening, 13 patients were treated with a median of 25.7 GBq [131I]IMAZA (range 18.1-30.7 GBq). Five individuals received a second treatment course. Best response was a decrease in the RECIST target lesions of -26% in 2 patients. Five patients with disease stabilization experienced a median progression-free survival of 14.3 months (range 8.3-21.9). Median overall survival in all patients was 14.1 months (4.0-56.5) after therapy. Treatment was well tolerated, in other words no severe toxicities (CTCAE grade ≥3) were observed. CONCLUSION: In patients with advanced ACC refractory to standard therapeutic regimens, [131I]IMAZA treatment was associated with disease stabilization and nonsignificant tumor size reduction in a significant patient fraction and only limited toxicities. High [131I]IMAZA-uptake in tumor lesions was observed in 38.5% of patients with advanced ACC, rendering [131I] IMAZA a potential treatment option in a limited, well-defined patient fraction. Further clinical trials will be necessary to evaluate the full potential of this novel theranostic approach.