monocentric study, randomised double blinded (healthy subjects, or transversal (patients with gitelman syndrome)

Conditions: Gitelman Syndrome; Potassium Depletion

Summary: progesterone is needed to permit adaptation of the kidney to limit potassium loss in the urines. the investigators wonder whether progesterone or other adrenal hormon play the same role. the investigators will investigate surrenal hormone production in healthy subjects under a 7-day potassium depleted diet and in patients chronically hypokalaemic due to a renal loss of potassium.

the investigators will study the adaptation of steroidogenesis to potassium depletion in healthy volunteer, and the role of progesterone in renal adaptation to potassium depletion. practically, healthy volunteers will be submitted twice to two periods of normal na+/ high k+ diet (control period) followed by a normal na+/ low k+ diet sustained by a pharmacological treatment with kayexalate (k+-depleted condition). the subjects will be treated with either ru486 or a placebo, according to a randomization. the adrenal response will be evaluated after stimulation by synacthen at baseline and at the end of each experimental period. a synacthen test will be also done in 10 patients suffering of chronic hypokalemia linked to a hereditary tubulopathy inducing renal k+ leak called gitelman syndrome and their plasma steroid profile will be established.

Eligibility criteria:
inclusion criteria for healthy subjects: * caucasian male subject * 18-35 yrs-old * bmi between 18 and 30 kg/m2 * normal biological pattern (sodium, potassium, egfr \>60ml/min/1.73 m2, sgot and sgpt \< 2.5 normal value) * non smoker subjects or less than 5 cigarettes a day * no drug abuse * no active viral b or c hepatitis, no positive hiv serology * no treatment except paracetamol * normal ekg * inform consent given * affiliation to french medicare assurance inclusion criteria for patients : * 18-75 years old subjects * genetically proven gitelman syndrome * normal ekg * inform consent given * affiliation to french medicare assurance non inclusion criteria for healthy subjects: * history of cardiac arrythmia or abnormal ekg * recent or chronic diarrhea * spontaneous low potassium intakes * biological abnormality : sgot or sgpt \> 2.5 n, fasting hyperglycemia (\> 6.5 mmol/l, anemia (hemoglobin\< 12g/dl) * single or functionally solitary kidney * any severe allergies, or allergic history to any drug. * predicted difficulty monitoring and compliance. * blood donation for less than 2 months. * persons directly involved in the implementation of the protocol. * person in exclusion period in biomedical research. * protected person (person under guardianship, deprived of liberty, ...). * taking medication in the previous 7 days (except paracetamol). * chronic adrenal insufficiency. * known allergy to any of the excipients of the ru 486 (colloidal anhydrous silica, maize starch, povidone, microcrystalline cellulose, magnesium stearate). * severe asthma not controlled by treatment. * porphyria hereditary. non inclusion criteria for gitelman patients: * people that did not give their consent or unable to understand the protocol. * anemia (hg \<10 g / dl). * clinically significant abnormality on the ekg. * any severe allergies, or allergic history to any drug. * treatment with corticosteroids. * patient in exclusion period in biomedical research. * protected person (patient trust, deprived of liberty, ...)

Keywords: potassium intake progesterone steroidogenesis ru486 synachtene test