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OR34-03 Variable and Pulsatile Circulating Aldosterone Levels in Primary Aldosteronism: Implications for Diagnosis and Sub-Type Differentiation

Abstract Introduction: Considerable intra-individual variability in circulating aldosterone levels has been observed in patients with primary aldosteronism (PA). The magnitude and implications of this phenomenon are not well characterized. Objective: To evaluate the acute variability in aldosterone in patients with confirmed PA. Methods: 373 patients with confirmed PA underwent adrenal venous sampling (AVS) after appropriate catheterization of bilateral adrenal veins. Peripheral venous aldosterone levels were measured 2 hours prior to AVS while in supine posture. After anesthesia induction with fentanyl and midazolam, AVS was performed while in the same supine posture, and aldosterone levels were drawn from the inferior vena cava (IVC) and in triplicate from the bilateral adrenal veins over 10 minutes. Differences between the pre-AVS and intra-AVS IVC aldosterone levels were analyzed, and regression models used to identify independent predictors of change. Coefficients of variation (COV) between triplicate aldosterone levels in each adrenal vein were calculated. Results: 81% of patients demonstrated a decrease in aldosterone concentration from pre-AVS to the intra-AVS IVC measurement. The mean decrease in aldosterone was 10.5 ng/dL (95% CI: 7.6–13.3) and the mean relative decrease in aldosterone was 39% (95% CI: 27–51%, P<0.0001). The absolute decrease in aldosterone was striking, with 48% of patients who had a decrease in aldosterone exhibiting an IVC aldosterone of less than or equal to 5 ng/dL. The absolute decrease in aldosterone was significantly associated with a higher aldosterone level (p<0.001) and lower systolic blood pressure at diagnosis (p=0.02). A wide variation in triplicate aldosterone values was seen in the span of 10-minute sampling, ranging from 1–300%, with COV of 21.0% in the left adrenal vein and 25.0% in the right adrenal vein. If the lowest of three aldosterone-to-cortisol (A/C) ratios on the dominant side and highest of three A/C ratios on the contralateral side were used instead of the average of the three values, the interpretation of the AVS would have changed from unilateral PA to bilateral PA in 15.9% of cases. Conclusions: These findings underscore the pulsatile and variable nature of circulating aldosterone levels in patients with bona fide PA. Aldosterone levels substantially declined in 81% of patients within a period of 2 hours while maintaining a fixed and supine posture. In half of these patients, aldosterone levels declined to 5 ng/dL or below, a threshold typically considered incompatible with PA. Further, adrenal venous aldosterone levels exhibited large variations on repeated sampling within a 10-minute span that could have influenced the interpretation of sub-type differentiation in nearly 16% of cases. Single circulating aldosterone values lack precision and reproducibility and may result in incorrect diagnosis and sub-type differentiation.


SUN-173 Introduction
Patients with untreated congenital adrenal hyperplasia (CAH) can present early with severe symptoms of salt wasting, adrenal insufficiency and hyperandrogenism. Late consequences as a result of long term untreated CAH are rarely seen nowadays. We present a patient who presented with a massive uterine leiomyoma and bilateral adrenal myelolipomas due to longstanding treatment noncompliance.

Discussion
Glucocorticoids and mineralocorticoids are the mainstays of treatment in CAH, with the goal of providing adequate replacement while reducing levels of ACTH and adrenal androgens. Persistently elevated levels of ACTH and androgens can lead to many serious sequela, even outside of adrenal insufficiency and virilization. Due to the conversion of androgens to estrogens, untreated females with CAH have significantly elevated levels of both hormones. These high levels of androgens and estrogen can then stimulate growth of estrogen-dependent organs as exemplified by our patient. Chronic ACTH stimulation can cause adrenal hyperplasia, but has also been associated with the development of other adrenal masses including adrenal myelolipomas. Adrenal myelolipomas can become hormonally functional or cause mass effect, hemorrhage, necrosis when reaching a large enough size.

Conclusion
This case demonstrates the importance of CAH treatment compliance as there are many serious sequela outside of the expected adrenal insufficiency and virilization. Even when the desired effect is virilization with physical male features, other means of hormonal therapy should be considered as there remains the risks of abnormal growth of certain organs sensitive to the excessive hormones.

OR34-03
Introduction: Considerable intra-individual variability in circulating aldosterone levels has been observed in patients with primary aldosteronism (PA). The magnitude and implications of this phenomenon are not well characterized. Objective: To evaluate the acute variability in aldosterone in patients with confirmed PA. Methods: 373 patients with confirmed PA underwent adrenal venous sampling (AVS) after appropriate catheterization of bilateral adrenal veins. Peripheral venous aldosterone levels were measured 2 hours prior to AVS while in supine posture. After anesthesia induction with fentanyl and midazolam, AVS was performed while in the same supine posture, and aldosterone levels were drawn from the inferior vena cava (IVC) and in triplicate from the bilateral adrenal veins over 10 minutes. Differences between the pre-AVS and intra-AVS IVC aldosterone levels were analyzed, and regression models used to identify independent predictors of change. Coefficients of variation (COV) between triplicate aldosterone levels in each adrenal vein were calculated. Results: 81% of patients demonstrated a decrease in aldosterone concentration from pre-AVS to the intra-AVS IVC measurement. The mean decrease in aldosterone was 10.5 ng/dL (95% CI: 7.6-13.3) and the mean relative decrease in aldosterone was 39% (95% CI: 27-51%, P<0.0001). The absolute decrease in aldosterone was striking, with 48% of patients who had a decrease in aldosterone exhibiting an IVC aldosterone of less than or equal to 5 ng/dL. The absolute decrease in aldosterone was significantly associated with a higher aldosterone level (p<0.001) and lower systolic blood pressure at diagnosis (p=0.02). A wide variation in triplicate aldosterone values was seen in the span of 10-minute sampling, ranging from 1-300%, with COV of 21.0% in the left adrenal vein and 25.0% in the right adrenal vein. If the lowest of three aldosterone-to-cortisol (A/C) ratios on the dominant side and highest of three A/C ratios on the contralateral side were used instead of the average of the three values, the interpretation of the AVS would have changed from unilateral PA to bilateral PA in 15.9% of cases. Conclusions: These findings underscore the pulsatile and variable nature of circulating aldosterone levels in patients with bona fide PA. Aldosterone levels substantially declined in 81% of patients within a period of 2 hours while maintaining a fixed and supine posture. In half of these patients, aldosterone levels declined to 5 ng/dL or below, a threshold typically considered incompatible with PA. Further, adrenal venous aldosterone levels exhibited large variations on repeated sampling within a 10-minute span that could have influenced the interpretation of sub-type differentiation in nearly 16% of cases. Single circulating aldosterone values lack precision and reproducibility and may result in incorrect diagnosis and sub-type differentiation.

MON-029
There is no approved treatment for adolescent girls with PCOS. The vast majority of these patients are guided into a trajectory that starts with oral contraceptive (OC) treatment, leads into oligo-anovulatory subfertility, then into the use of assisted reproductive techniques, and ultimately into pregnancies with a double-to-triple risk for complications (such as gestational diabetes, preeclampsia and preterm birth) potentially with lifelong sequelae in the offspring. Evidence is converging into the insight that adolescent PCOS is frequently driven by hepato-visceral fat excess ("central obesity") ensuing from a mismatch between (rather restrictive) prenatal and (rather abundant) postnatal nutrition, on a background of genetic susceptibility (Trends Endocrinol Metab 2018;29:815). This insight has prompted the exploration of an alternative PCOS treatment that aims at reducing the central-fat excess (without causing weight loss in non-obese girls) in order to normalize the entire phenotype, including ovulation rate. So far, this alternative approach has been tested in two randomized controlled pilot studies that were performed in non-obese girls with PCOS and with no need for contraception (total N=62; age 16 yr; BMI 24 Kg/m 2 ; treatment for 1 year; ovulation assessment during the post-treatment year). In these studies, the effects of an OC were compared to those of SPIOMET, which is a low-dose combination of spironolactone (= a mixed anti-androgen and -mineralocorticoid, also activating brown adipose tissue; Diab Ob Metab 2019;21:509), pioglitazone and metformin (= two insulin sensitizers acting through different mechanisms). Pooled results of the pilot studies confirm the first report (J Adolesc Health 2017;61:446) that SPIOMET has more normalizing effects than OC; there were approximately 3-fold more ovulations post-SPIOMET than post-OC; normovulation occurred only post-SPIOMET; anovulation was >10-fold more frequent post-OC. Pooled results also disclosed two new features of adolescent PCOS: low concentrations of circulating CXCL14 (= a brown adipokine, signaling activity in brown adipose tissue; Cell Metab 2018;28:750) and miR-451a (= an inhibitor of THRSP-mediated hepatic lipogenesis; Mol Cell