Hahner, Stefanie

BACKGROUND: Primary aldosteronism (PA) is a common and treatable cause of hypertension, yet data on the durability of medical treatment response beyond the first year are limited. Using the PA medical treatment outcomes framework, we evaluated long-term biochemical and clinical outcomes and factors associated with treatment response. METHODS: We conducted an international, multicenter, observational cohort study across 27 centers on 4 continents. Adults with PA treated with mineralocorticoid receptor antagonists and/or epithelial sodium channel blockers between 2016 and 2021 were included if follow-up data were available at ≥12 months. Biochemical and clinical responses were classified as complete, partial, or absent using PA medical treatment outcomes criteria. Ordinal logistic regression identified determinants of a favorable treatment response. RESULTS: The cohort included 1292 patients (47.5% women, mean age 52 years) with a median follow-up of 34 months (interquartile range, 21–51). At ≥12 months, 58.3% achieved a complete biochemical response, and 20.8% achieved a complete clinical response, with only 5% showing no response. Determinants of a favorable biochemical response included lower aldosterone and lateralization index, and higher renin and potassium levels at baseline. In those taking spironolactone, a higher daily dose was also associated with a favorable biochemical response. Determinants of a favorable clinical response included female sex, lower body mass index, shorter duration of hypertension, and absence of hypertension-mediated organ damage. CONCLUSIONS: Targeted medical therapy for PA can deliver sustained biochemical and clinical benefits. Early disease detection and adequate dose titration are highly actionable determinants of long-term treatment success.

Abstract Disclosure: D.S. Ali: None. Z. Chung: None. L. Kamel: None. S. Björnsdottir: Shire. B.L. Clarke: Shire, Takeda, Ascendis, Calcilytix. S. Hahner: None. L.C. Hofbauer: Amgen Inc, Ascendis, UCB, Ascendis, Amolyte. P. Houillier: None. S.W. Ing: Amgen Inc, Radius Health, Inc, Takeda, AscendAlexion, Amolyt, Ascendis, Calcilytix, Kyowa Kirin. M.A. Levine: Takeda, Amolyt, Calcilytix. M. Mannstadt: Takeda, Amolyt, Calcilytix. L. Rejnmark: Takeda, Amolyt, Ascendis, Calcilytix. D.M. Shoback: Amolyt, Ascendis, member of the advisory board (PARADIGHM). M. Brandi: Takeda, Eli Lilly & Company, Calcilytix, Kyowa Kirin, UCB, Abiogen, Alexion, Amolyt, Amorphical, Bruno Farmaceutici, CoGeDi, Echolight. A.A. Khan: Takeda, Amgen Inc, Alexion, Ascendis, Amolyt, Calcilytix. Background: Hypoparathyroidism (HypoPT) is a rare endocrine disorder that requires close evaluation and follow up during pregnancy to minimize maternal and fetal complications. The primary objectives of this study are to evaluate the use of rhPTH (1-84) during pregnancy by analyzing data from the PARADIGHM disease registry, and to compare maternal and neonatal outcomes among patients who continued PTH therapy during pregnancy versus those on conventional therapy (CT). Methods: We performed a retrospective analysis of data in the PARADIGHM registry. Maternal and neonatal outcomes in women treated with rhPTH (1-84) were compared to women who received CT. Results: We analyzed 39 pregnancies of 32 women. Of those, 4 women (6 pregnancies) used rhPTH (1-84) either before or during pregnancy and 28 women (33 pregnancies) continued CT during pregnancy. The mean (SD) maternal age at enrollment was 31.7 (5.6) years. Postsurgical HypoPT was the most common etiology (68.8%). The mean gestational age at delivery was 36 (2.4) weeks (PTH-treated) vs 38.3 (3.3) weeks (CT) (p=0.162). Preterm delivery rates were higher in the PTH-treated group (50% vs. 27%, p=0.591), but this was not statistically significant. Two women had pre-eclampsia, one in each group (PTH-treated and CT). In the PTH-treated group, one pregnancy resulted in a stillbirth, and one infant was born with congenital anomalies (16.7% each). Conclusions: The safety of rhPTH (1-84) use in pregnancy cannot be determined at this time. The PTH-treated group exhibited trends towards higher rates of preterm delivery, but the rates of stillbirth, and congenital anomalies were low and comparable in both groups of women. Larger studies are necessary to determine the optimal approach to manage women with HypoPT during pregnancy. Presentation: Sunday, July 13, 2025

Abstract Glucocorticoids are widely prescribed as anti-inflammatory and immunosuppressive agents. This results in at least 1% of the population using chronic glucocorticoid therapy, being at risk for glucocorticoid-induced adrenal insufficiency. This risk is dependent on the dose, duration and potency of the glucocorticoid, route of administration, and individual susceptibility. Once glucocorticoid-induced adrenal insufficiency develops or is suspected, it necessitates careful education and management of affected patients. Tapering glucocorticoids can be challenging when symptoms of glucocorticoid withdrawal develop, which overlap with those of adrenal insufficiency. In general, tapering of glucocorticoids can be more rapidly within a supraphysiological range, followed by a slower taper when on physiological glucocorticoid dosing. The degree and persistence of HPA axis suppression after cessation of glucocorticoid therapy are dependent on overall exposure and recovery of adrenal function varies greatly amongst individuals. This first European Society of Endocrinology/Endocrine Society joint clinical practice guideline provides guidance on this clinically relevant condition to aid clinicians involved in the care of patients on chronic glucocorticoid therapy.

Abstract Glucocorticoids are widely prescribed as anti-inflammatory and immunosuppressive agents. This results in at least 1% of the population using chronic glucocorticoid therapy, being at risk for glucocorticoid-induced adrenal insufficiency. This risk is dependent on the dose, duration and potency of the glucocorticoid, route of administration, and individual susceptibility. Once glucocorticoid-induced adrenal insufficiency develops or is suspected, it necessitates careful education and management of affected patients. Tapering glucocorticoids can be challenging when symptoms of glucocorticoid withdrawal develop, which overlap with those of adrenal insufficiency. In general, tapering of glucocorticoids can be more rapidly within a supraphysiological range, followed by a slower taper when on physiological glucocorticoid dosing. The degree and persistence of HPA axis suppression after cessation of glucocorticoid therapy are dependent on overall exposure and recovery of adrenal function varies greatly amongst individuals. This first European Society of Endocrinology/Endocrine Society joint clinical practice guideline provides guidance on this clinically relevant condition to aid clinicians involved in the care of patients on chronic glucocorticoid therapy.

Abstract Context Appropriate management of adrenal insufficiency (AI) in pregnancy can be challenging due to the rarity of the disease and lack of evidence-based recommendations to guide glucocorticoid and mineralocorticoid dosage adjustment. Objective Multicenter survey on current clinical approaches in managing AI during pregnancy. Design Retrospective anonymized data collection from 19 international centers from 2013 to 2019. Setting and Patients 128 pregnancies in 113 women with different causes of AI: Addison disease (44%), secondary AI (25%), congenital adrenal hyperplasia (25%), and acquired AI due to bilateral adrenalectomy (6%). Results Hydrocortisone (HC) was the most commonly used glucocorticoid in 83% (97/117) of pregnancies. Glucocorticoid dosage was increased at any time during pregnancy in 73/128 (57%) of cases. In these cases, the difference in the daily dose of HC equivalent between baseline and the third trimester was 8.6 ± 5.4 (range 1-30) mg. Fludrocortisone dosage was increased in fewer cases (7/54 during the first trimester, 9/64 during the second trimester, and 9/62 cases during the third trimester). Overall, an adrenal crisis was reported in 9/128 (7%) pregnancies. Cesarean section was the most frequent mode of delivery at 58% (69/118). Fetal complications were reported in 3/120 (3%) and minor maternal complications in 15/120 (13%) pregnancies without fatal outcomes. Conclusions This survey confirms good maternal and fetal outcome in women with AI managed in specialized endocrine centers. An emphasis on careful endocrine follow-up and repeated patient education is likely to have reduced the risk of adrenal crisis and resulted in positive outcomes.

BACKGROUND. Adrenal aldosterone excess is the most common cause of secondary hypertension and is associated with increased cardiovascular morbidity. However, adverse metabolic risk in primary aldosteronism extends beyond hypertension, with increased rates of insulin resistance, type 2 diabetes, and osteoporosis, which cannot be easily explained by aldosterone excess. METHODS. We performed mass spectrometry–based analysis of a 24-hour urine steroid metabolome in 174 newly diagnosed patients with primary aldosteronism (103 unilateral adenomas, 71 bilateral adrenal hyperplasias) in comparison to 162 healthy controls, 56 patients with endocrine inactive adrenal adenoma, 104 patients with mild subclinical, and 47 with clinically overt adrenal cortisol excess. We also analyzed the expression of cortisol-producing CYP11B1 and aldosterone-producing CYP11B2 enzymes in adenoma tissue from 57 patients with aldosterone-producing adenoma, employing immunohistochemistry with digital image analysis. RESULTS. Primary aldosteronism patients had significantly increased cortisol and total glucocorticoid metabolite excretion (all P < 0.001), only exceeded by glucocorticoid output in patients with clinically overt adrenal Cushing syndrome. Several surrogate parameters of metabolic risk correlated significantly with glucocorticoid but not mineralocorticoid output. Intratumoral CYP11B1 expression was significantly associated with the corresponding in vivo glucocorticoid excretion. Unilateral adrenalectomy resolved both mineralocorticoid and glucocorticoid excess. Postoperative evidence of adrenal insufficiency was found in 13 (29%) of 45 consecutively tested patients. CONCLUSION. Our data indicate that glucocorticoid cosecretion is frequently found in primary aldosteronism and contributes to associated metabolic risk. Mineralocorticoid receptor antagonist therapy alone may not be sufficient to counteract adverse metabolic risk in medically treated patients with primary aldosteronism. FUNDING. Medical Research Council UK, Wellcome Trust, European Commission.