Extraordinarily high aldosterone, 901.0 ng/dL, in a patient with primary aldosteronism: an insight into the underlying mechanism

Okubo, Yosuke; Sato, Yuka; Nakasone, Yasuto; Shirotori, Katsuko; Oguchi, Kazuhiro; Matsushita, Takehiko; Nishikawa, Tetsuo; Yamazaki, Yuto; Sasano, Hironobu; Komatsu, Mitsuhisa; Yamauchi, Kazuyo; Aizawa, Toru

doi:10.1507/endocrj.ej15-0398

Cited by 4 publications

(5 citation statements)

References 19 publications

(29 reference statements)

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“…In fact, the potassium-supplemented, hyperkalemic group had among the highest aldosterone levels reported in rodents, ranging 500-1000 ng/dl or higher. Values this high have been reported after dietary sodium deprivation in mice and in a human patient with an aldosterone-secreting tumor (Okubo et al, 1997(Okubo et al, , 2016, but probably lie at the upper extreme for adrenal production of this hormone, which normally circulates at levels well below 100 ng/ dl. The doubling of aldosterone in potassium-supplemented, sodium-deprived rats presumably reflects voltage-dependent mechanisms that increase aldosterone released by cells in the zona glomerulosa (ZG) of the adrenal glands (Aguilera & Catt, 1986;Lotshaw, 2001), plus hypovolemic RAS activation, by which angiotensin II helps promote aldosterone synthesis and release by these same cells (Lotshaw, 2001;Spielman & Davis, 1974).…”

Section: Potassium Is Important For Increasing Aldosterone But Is mentioning

confidence: 72%

Despite increasing aldosterone, elevated potassium is not necessary for activating aldosterone‐sensitive HSD2 neurons or sodium appetite

et al. 2021

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Sodium appetite is a complex, motivated behavioral state. It requires low-sodium status detection and a coordinated drive to seek and ingest salty foods. Interestingly, this elaborate behavior can be elicited by administering a singular hormone, aldosterone (Formenti et al., 2013; Gasparini et al., 2018; Geerling & Loewy, 2008). Aldosterone is a mineralocorticoid produced in the zona glomerulosa of the adrenal cortex. It affects cells that express the mineralocorticoid receptor (MR) by translocating this receptor into the cell nucleus to promote genomic activity (Robertson et al., 1993). Aldosterone-sensitive cells also require the enzyme 11-beta-hydroxysteroid dehydrogenase type 2 (HSD2), which protects the MR from glucocorticoids, leaving it more accessible to aldosterone (Funder et al., 1988; Naray-Fejes-Toth et al.,

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Section: Potassium Is Important For Increasing Aldosterone But Is mentioning

confidence: 72%

Despite increasing aldosterone, elevated potassium is not necessary for activating aldosterone‐sensitive HSD2 neurons or sodium appetite

et al. 2021

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“…We next characterized the effect of peripheral aldosterone infusion. We tested a range of infusion rates to reproduce plasma aldosterone levels spanning the full range of aldosterone levels reported after dietary sodium deprivation and across a variety of pathophysiologic states in humans, including dietary sodium deprivation, hyperkalemia, kidney disease, and aldosterone-secreting adenomas (34, 55, 61, 62). We again found dose-dependent effects on saline intake.…”

Section: Resultsmentioning

confidence: 99%

“…Like mice and rats, healthy human subjects generate circulating aldosterone levels upwards of 300 mg/dL if they are fed a low-sodium, high-potassium diet (55). Even higher aldosterone levels -more than three times this high -have been found in patients with aldosterone-secreting adenomas or chronic kidney disease (61,62). However, besides tribes outside contemporary civilization (78) and individuals who deliberately abstain from sodium (80), most people alive today consume more than enough sodium and probably will never generate such high aldosterone levels.…”

Section: Discussionmentioning

confidence: 99%

HSD2 neurons are evolutionarily conserved and required for aldosterone-induced salt appetite

Gasparini,

Peltekian,

McDonough

et al. 2024

Preprint

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Excessive aldosterone production increases the risk of heart disease, stroke, dementia, and death. Aldosterone increases both sodium retention and sodium consumption, and increased sodium consumption predicts end-organ damage in patients with aldosteronism. Preventing this increase may improve outcomes, but the behavioral mechanisms of aldosterone-induced sodium appetite remain unclear. In rodents, we identified aldosterone-sensitive neurons, which express the mineralocorticoid receptor and its pre-receptor regulator, 11-beta-hydroxysteroid dehydrogenase 2 (HSD2). Here, we identify HSD2 neurons in the human brain and use a mouse model to evaluate their role in aldosterone-induced salt intake. First, we confirm that dietary sodium deprivation increases aldosterone production, HSD2 neuron activity, and salt intake. Next, we show that activating HSD2 neurons causes a large and specific increase in salt intake. Finally, we use dose-response studies and genetically targeted ablation of HSD2 neurons to show that aldosterone-induced salt intake requires these neurons. Identifying HSD2 neurons in the human brain and their necessity for aldosterone-induced salt intake in mice improves our understanding of appetitive circuits and highlights this small cell population as a therapeutic target for moderating dietary sodium.

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“…Although there are a few case reports of patients who have PA with unsuppressed PRA [ 5 – 7 ] due to renal artery stenosis [ 6 ] or the development of hypertensive nephrosclerosis [ 7 ], information regarding the characteristics of such patients remains unclear. In such cases, deviating from the guidelines, screening tests and confirmatory tests using ARR are thought to be relatively negative because of elevated PRA.…”

Section: Introductionmentioning

confidence: 99%

Characteristics of aldosterone-producing adenomas in patients without plasma renin activity suppression

et al. 2022

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Primary aldosteronism (PA) usually accompanies suppressed plasma renin activity (PRA) through a negative feedback mechanism. While some cases of PA with unsuppressed PRA were reported, there have been no studies about the characteristics of PA with unsuppressed PRA; thus, these characteristics were examined herein. Nine patients with unsuppressed PRA and 86 patients with suppressed PRA were examined. All patients underwent segmental adrenal venous sampling (sAVS) and adrenalectomy, and were pathologically confirmed to have cytochrome P450 11B2 (CYP11B2)-positive aldosterone-producing adenoma according to international histopathology consensus criteria. Unsuppressed and suppressed PRA were defined as PRA levels of > 1.0 and ≤ 1.0 ng/mL/hr, respectively, in multiple blood samples obtained in the resting position. The unsuppressed PRA group had higher morning cortisol levels (12.6 [8.5, 13.5] vs. 8.5 [7.1, 11.0] μg/dL, P = 0.03) and higher cortisol levels after a 1 mg dexamethasone suppression test (DST) (2.2 [1.6, 2.5] vs. 1.3 [1.0, 1.9] μ g/dL, P = 0.004) than the suppressed PRA group. The unsuppressed PRA group also showed higher aldosterone levels on the non-surgical side during sAVS (P = 0.02 before adrenocorticotropic hormone (ACTH) stimulation, P = 0.002 after ACTH stimulation), a higher intensity of CYP17 expression in the resected adrenal gland (P = 0.02), and a lower clinical complete success rate 1 year after surgery (P = 0.04) compared with those in the suppressed PRA group. These findings suggest that PA should not be ruled out by unsuppressed PRA among patients with hypertension, particularly when their cortisol levels remain unsuppressed in the 1 mg DST. Meanwhile, it should be acknowledged that patients with unsuppressed PRA have higher aldosterone levels on the non-surgical side, and a lower likelihood of postoperative complete clinical success is to be expected.

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Extraordinarily high aldosterone, 901.0 ng/dL, in a patient with primary aldosteronism: an insight into the underlying mechanism

Cited by 4 publications

References 19 publications

Despite increasing aldosterone, elevated potassium is not necessary for activating aldosterone‐sensitive HSD2 neurons or sodium appetite

Despite increasing aldosterone, elevated potassium is not necessary for activating aldosterone‐sensitive HSD2 neurons or sodium appetite

HSD2 neurons are evolutionarily conserved and required for aldosterone-induced salt appetite

Characteristics of aldosterone-producing adenomas in patients without plasma renin activity suppression

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