The investigators will test the hypothesis that endogenous aldosterone impairs insulin
secretion and insulin sensitivity in subjects with primary aldosteronism.
The week of each study period, subjects will be provided a standard 160mmol/d sodium diet
for 6-8 days to control for inter-individual sodium intake.
In period 1, subjects will report after 5 days of controlled sodium diet for a hyperglycemic
clamp study (to measure insulin secretion). Subjects will continue the study diet, and then
return for a hyperinsulinemic-euglycemic clamp study (to measure insulin sensitivity).
After completion of period 1 assessment, subjects will undergo adrenalectomy by our
endocrine surgeons or initiate medical treatment, according to routine clinical care.
In period 2, the investigators will repeat the studies in the same manner as period 1, 3 to
12 months after adrenalectomy or initiation of medical treatment.
1. Ambulatory subjects, 18 to 70 years of age, inclusive
2. For female subjects, the following conditions must be met:
- postmenopausal status for at least 1 year, or
- status-post surgical sterilization, or
- if of childbearing potential, utilization of adequate birth control and
willingness to undergo urine beta-hcg testing on every study day.
3. Primary aldosteronism determined by both:
- Biochemical hyperaldosteronism defined as either:
1. Plasma aldosterone ≥15 ng/dL
2. or aldosterone-to-renin ratio of ≥30 if on ACE inhibitor
3. or aldosterone-to-renin ratio of ≥40 in absence of an ACE inhibitor
- Positive suppression test defined as either:
1. failure to suppress aldosterone to <7ng/dL after intravenous 0.9% saline
infusion over 2 hours
2. failure to suppress 24-hour urinary aldosterone excretion to <12 µcg with
simultaneously documented urine sodium excretion >200 mmol.
- Subjects presenting with any of the following will not be included in the study:
1. Previously diagnosed type 1 Diabetes
2. Type II Diabetes, as defined by ADA criteria:
- Hemoglobin A1C ≥6.5%
- Fasting plasma glucose ≥126mg/dl (7.0mmol/l)
- 2-hour 75g oral glucose tolerance test (OGTT) plasma glucose ≥200mg/dl (11.1
mmol/l) d. Current treatment with anti-diabetic medication(s)
3. Impaired renal function [estimated glomerular filtration rate (eGFR) of <30ml/min] as
determined by the four-variable Modification of Diet in Renal Disease (MDRD)
equation, where serum creatinine (Scr) is expressed in mg/dl and age in years.
4. Prior allergies to medications used in the study protocol (e.g. L-arginine, potassium
chloride, insulin), or to drugs within the same class.
5. Screening plasma potassium >5.5 mmol/L or sodium <135 mmol/L
6. Cardiovascular disease such as recent (<6 months) myocardial infarction, presence of
angina pectoris, significant arrhythmia, congestive heart failure (LV hypertrophy
acceptable), deep vein thrombosis, pulmonary embolism, second or third degree heart
block, mitral valve stenosis, aortic stenosis or hypertrophic cardiomyopathy
8. Treatment with anticoagulants
9. History of serious neurologic disease such as cerebral hemorrhage, stroke, seizure,
or transient ischemic attack
10. History or presence of immunological or hematological disorders
11. Diagnosis of asthma requiring use of inhaled beta agonist >1 time per week
12. Clinically significant gastrointestinal impairment that could interfere with drug
13. Impaired hepatic function [aspartate amino transaminase (AST) and/or alanine amino
transaminase (ALT) >2.0 x upper limit of normal range]
14. Hematocrit <35%
15. Any underlying or acute disease requiring regular medication which could possibly
pose a threat to the subject or make implementation of the protocol or interpretation
of the study results difficult, such as arthritis treated with non-steroidal
16. Treatment with chronic systemic glucocorticoid therapy (more than 7 consecutive days
in 1 month)
17. Treatment with lithium salts
18. History of alcohol or drug abuse
19. Treatment with any investigational drug in the 1 month preceding the study
20. Mental conditions rendering the subject unable to understand the nature, scope and
possible consequences of the study
21. Inability to comply with the protocol, e.g., uncooperative attitude, inability to
return for follow-up visits, and unlikelihood of completing the study