Water and Electrolytes Content in HYpertension (WHYSKI) in the SKIn

Inclusion Criteria:

PA Group

* Age: 18-75-year-old.
* Signed informed consent form.
* A diagnosis of PA defined as

  o Plasma aldosterone concentration \> 15 ng/dL and aldosterone/renin ratio greater than 20.6 ng/mIU, measured after washout of interfering drugs or after changes of the drug treatment as previously detailed.
* Unilateral or bilateral evidence of PA at adrenal vein sampling

PH Group

* Age: from 18 to 75 years old
* Signed and dated informed consent form
* Diagnosis of essential hypertension defined either as:

  * Use of antihypertensive drug (s)
  * Arterial hypertension: in untreated patients this must be confirmed by daytime ambulatory blood pressure monitoring (ABPM), or home blood pressure monitoring, with blood pressure higher or equal to 135 mmHg for systolic blood pressure and/or higher or equal to 85 mmHg for diastolic blood pressure.
  * Exclusion of secondary hypertension by hormonal biochemical screening (aldosterone, renin, ARR\<2.06 ng/dL:mIU/L, ACTH, 24h urine cortisol, morning plasma cortisol level, 24h urine metanephrines and catecholamines).

Control Group

* Age: from 18 to 75 years old
* Signed and dated informed consent form
* Normal arterial blood pressure defined either as:

  * None anti-hypertensive drug (s)
  * Normal arterial hypertension confirmed by daytime ambulatory blood pressure monitoring (ABPM), or home blood pressure monitoring, with blood pressure lower or equal to 135 mmHg for systolic blood pressure and/or lower or equal to 85 mmHg for diastolic blood pressure.
  * Exclusion of secondary hypertension by hormonal biochemical screening (aldosterone, renin, ACTH, 24h urine cortisol, morning plasma cortisol level, 24h urine metanephrines and catecholamines).

Exclusion Criteria:

PA Group

* history of allergy/intolerance to local anesthesia;
* refusal of the patient to undergo skin biopsy;
* refusal of the patient to undergo AVS, and/or contraindications to the general anesthesia that is required for laparoscopic adrenalectomy and/or to undergo adrenalectomy if indicated;
* cortisol-aldosterone co-secreting adenoma or pheochromocytoma. PH Group and Control Group
* Concurrent skin diseases, for example psoriasis, and any pathological conditions that, in the judgement of the investigators, could affect skin electrolyte and water content.
* Subjects with diabetes mellitus type 1 and 2, as drugs affecting the renin-angiotensin-aldosterone system and/or renal Na+ handling as, for example, SGLT-2 inhibitors (gliflozins) 16 were considered to potentially bias results.
* Other conditions characterized by possible lymphatic disruption such as lipedema, cyclic idiopathic edema, lymphedema, and malignancies were also exclusion criteria.