Rethinking Primary Aldosteronism: The 2025 John H. Laragh Research Award.

Dr John Laragh, a pioneer in the field of hypertension, held a fundamental belief in the need to challenge existing dogmas in medicine to enhance our scientific understanding of disease and advance patient care. Perhaps in no area of hypertension does this ring truer with than primary aldosteronism (PA). Following its initial description in the mid-1950s with an initial surge in diagnoses soon thereafter, PA was ultimately relegated to be considered a "zebra" of hypertension felt to be responsible for only a small percentage of cases.

Subclinical Primary Aldosteronism and Major Adverse Cardiovascular Events: A Longitudinal Population-Based Cohort Study.

Background: Primary aldosteronism (PA), an overt form of renin-independent aldosterone production, leads to a disproportionately high rate of major adverse cardiovascular events (MACEs). Mounting evidence suggests that milder forms of renin-independent aldosterone production (subclinical PA) are highly prevalent; however, the link between subclinical PA and MACE remains uncertain.

Methods: This prospective study included 2017 Canadian adults 40 to 69 years of age from the randomly sampled, population-based CARTaGENE cohort (Québec, Canada), in which aldosterone and renin concentrations at enrollment (2009-2010) were measured.

Barriers and facilitators to following dietary recommendations for bone health: a qualitative study.

Background: An estimated one in two women and one in five men will experience a low-trauma fracture after age 50. Diet is an important mediator of bone health but individuals with or at risk of osteoporosis do not always meet recommended intake of specific nutrients (protein, calcium, vitamin D) and whole foods. We aimed to identify barriers and facilitating factors to following dietary recommendations for bone health among adults with or at risk of osteoporosis.

Incidence of adrenal masses eventually discovered in patients screened for primary aldosteronism.

Context: Biochemical screening for endocrine hypertension may be complex; the known presence of an adrenal mass markedly increases the pre-test probability for adrenal hypertension and may inform diagnostic efforts.

Objective: Model the potential incidence of adrenal masses that may be detected by routine adrenal imaging in patients with suspected endocrine hypertension.

Design: Retrospective cohort study.

Spontaneous postpartum recovery of mild traumatic brain injury induced growth hormone deficiency.

A woman in her late 20s developed persistent post-concussion symptoms (PPCS) following a mild traumatic brain injury (mTBI) sustained in a motor vehicle collision. Symptoms included daily headaches, cognitive and physical fatigue and vision disturbances, which persisted despite extensive rehabilitation and medical interventions by multiple specialists. At 20 months post-mTBI, an endocrinological assessment confirmed post-traumatic growth hormone deficiency (GHD) through provocative glucagon stimulation testing (GST) revealing a peak GH level of 1.

Confirmatory Testing for Primary Aldosteronism : A Study of Diagnostic Test Accuracy.

Background: Confirmatory testing to verify the diagnosis of primary aldosteronism (PA) in patients who have an abnormal screening result is of uncertain benefit.

Objective: To perform a blinded assessment of the seated saline suppression test (SSST).

Design: Diagnostic test accuracy study.

Performance of the Siemens' thyroid stimulating immunoglobulin assay in the diagnosis of hyperthyroidism: Prospective cohort study.

Background: Auto-antibody testing is recommended for Graves' Disease (GD). The thyroid-stimulating-immunoglobulin (TSI) bridge method is designed to provide specificity for stimulatory antibodies to the TSH receptor which may translate to differences in performance in diagnosis of GD compared to TSH-receptor-antibody (TRAb) assays that don't distinguish between TSH-receptor antibody subclasses. The objective of this study was to prospectively compare the performance of a TSI assay to a TRAb assay for diagnosis of GD.

Big data determination and validation of reference range for 24-h urine cortisol by liquid chromatography-mass spectrometry.

Objective: Twenty-four-hour urine-free cortisol (UFC) is a first-line test for Cushing syndrome (CS). A new mass spectrometry assay for UFC requires a validated, relevant reference range appropriate to a screening population.

Design: Combined retrospective and prospective cohort study in a government health system and tertiary endocrinology clinic, Canada.

Discordance between adrenal vein sampling and imaging: the role of unilateral cortisol excess.

Objective: Adrenal vein sampling (AVS) is considered the gold-standard for identifying unilateral primary aldosteronism (PA), but is sensitive to any asymmetry in cortisol production. Subclinical autonomous cortisol production likely contributes to discordance between cross-sectional imaging and AVS.

Design And Methods: Retrospective chart review was performed of patients in Calgary, Alberta who (1) had a diagnosis of PA with clear adrenal mass, (2) had discordant AVS and cross-sectional imaging, and (3) underwent dexamethasone-suppressed NP59-iodocholesterol adrenal scintigraphy (n = 25).

Use of Albumin-Adjusted Calcium Measurements in Clinical Practice.

Importance: Using albumin-adjusted calcium is commonly recommended for for measuring calcium, but with little empirical evidence to support the practice.

Objective: To assess the correlation between total calcium measurements (with or without adjustment) vs the ionized calcium level as a reference standard.

Design, Setting, And Participants: This was a population-based cross-sectional study in the province of Alberta, Canada, including adults tested for serum total calcium and ionized calcium simultaneously between January 1, 2013, and October 31, 2019.

Cushing syndrome from an ACTH-producing pheochromocytoma or paraganglioma: structured review of 94 cases.

Adrenocorticotropic hormone-producing pheochromocytomas/paragangliomas are rare neuroendocrine tumors that co-secrete excess catecholamines and adrenocorticotropic hormone, resulting in Cushing syndrome (CS). This review aims to summarize important patient characteristics, investigations, and outcomes in all cases reported in the English literature. A literature search was conducted to identify all English-language case reports and case series describing adrenocorticotropic hormone-producing pheochromocytomas/paragangliomas.

Sex-specific Associations of Aldosterone and Renin With Body Composition: A Population-based Cohort Study.

Context: Renin-angiotensin-aldosterone system (RAAS) activation is closely linked to obesity; however, the sex-specific associations between RAAS activity and body composition among individuals without obesity are not well understood.

Objective: To investigate the associations of aldosterone and renin with body composition according to sex in the general population.

Design: Population-based cohort study.

Multiple radiologist review of adrenal CT still frequently misses lateralized surgical primary aldosteronism.

Patients with primary aldosteronism (PA) have increased morbidity and mortality compared to those with essential hypertension. Accurate detection of lateralized PA is important so that affected patients can receive potentially curative adrenalectomy. However, around 40% of patients with lateralized PA have "normal" adrenal glands on computed tomography (CT).

Subclinical Primary Aldosteronism and Cardiovascular Health: A Population-Based Cohort Study.

Background: Primary aldosteronism, characterized by overt renin-independent aldosterone production, is a common but underrecognized form of hypertension and cardiovascular disease. Growing evidence suggests that milder and subclinical forms of primary aldosteronism are highly prevalent, yet their contribution to cardiovascular disease is not well characterized.

Methods: This prospective study included 1284 participants between the ages of 40 and 69 years from the randomly sampled population-based CARTaGENE cohort (Québec, Canada).

Biomarkers to Guide Medical Therapy in Primary Aldosteronism.

Primary aldosteronism (PA) is an endocrinopathy characterized by dysregulated aldosterone production that occurs despite suppression of renin and angiotensin II, and that is non-suppressible by volume and sodium loading. The effectiveness of surgical adrenalectomy for patients with lateralizing PA is characterized by the attenuation of excess aldosterone production leading to blood pressure reduction, correction of hypokalemia, and increases in renin-biomarkers that collectively indicate a reversal of PA pathophysiology and restoration of normal physiology. Even though the vast majority of patients with PA will ultimately be treated medically rather than surgically, there is a lack of guidance on how to optimize medical therapy and on key metrics of success.

Bone turnover markers for assessment of anti-resorptive effect in clinical practice: A good idea meets the problem of measurement uncertainty.

Objectives: Bone turnover markers (BTM) are measures for understanding the effect of anti-resorptives upon osteoclast activity. Post-hoc trial data suggests reduction in BTM of 40% may represent a target for defining appropriate response to therapy. We modeled clinical application of this target threshold in an individual patient setting where assay measurement uncertainty and biological variation are included.

Screening for Primary Aldosteronism Among Hypertensive Adults with Obstructive Sleep Apnea: A Retrospective Population-Based Study.

Background: Hypertension plus obstructive sleep apnea (OSA) is recommended in some guidelines as an indication to screen for primary aldosteronism (PA), yet prior data has brought the validity of this recommendation into question. Given this context, it remains unknown whether this screening recommendation is being implemented into clinical practice.

Methods: We conducted a population-based retrospective cohort study of all adult Ontario (Canada) residents with hypertension plus OSA from 2009 to 2020 with follow-up through 2021 utilizing provincial health administrative data.

General Comorbidity Indicators Contribute to Fracture Risk Independent of FRAX: Registry-Based Cohort Study.

Context: FRAX® estimates 10-year fracture probability from osteoporosis-specific risk factors. Medical comorbidity indicators are associated with fracture risk but whether these are independent from those in FRAX is uncertain.

Objective: We hypothesized Johns Hopkins Aggregated Diagnosis Groups (ADG®) score or recent hospitalization number may be independently associated with increased risk for fractures.

Fracture risk in Asian-Canadian women is significantly over-estimated by the Canadian Association of Radiologists-Osteoporosis Canada risk prediction tool: retrospective cohort study.

Unlabelled: Fracture risk calculators may not be accurate for all ethnicity groups. The Manitoba bone density registry was used to test the Canadian CAROC tool for predicting fracture risk in Asian-Canadian women. The tool significantly over-estimated fracture risk, suggesting that it may not be ideal for Asian-Canadian patients.