6 of SNS activation and the increased levels of aldosterone in patients with OSA, point towards potential advantages of drugs inhibiting these pathways on reducing blood pressure. Indeed, beta blockers were found to be more eﬀective than other antihypertensive drugs in OSA patients [119]; however, relevant data is still far from conclusive. Even more interestingly, however, spironolactone was shown not only to signiﬁcantly lower blood pressure in 12 patients with OSA and resistant hypertension, but to reduce the severity of OSA as well [120]. Further, larger studies are needed, however, to conﬁrm these beneﬁcial eﬀects of spironolactone in patients with OSA. 6. Primary Aldosteronism Primary aldosteronism (PA) was initially described by Conn in 1955 [121]. PA is characterized by autonomous produc- tion of aldosterone by adrenal glands and the subsequent decrease in renin levels though negative feedback. Aldos- terone excess leads to hypertension, metabolic alkalosis, hypernatremia, and potassium loss resulting in hypokalemia; the latter is currently considered a late manifestation of PA. PA can result from an aldosterone producing adenoma, bilat- eral adrenal hyperplasia, glucocorticoid-remediable aldos- teronism, or rare familial syndromes. Although the diagnosis of adrenal adenomas prevailed during the older times, recent reports reveal that hyperplasia is more frequent than adrenal adenomas. The prevalence of PA in the general hypertensive popu- lation remains an unresolved issue [122, 123]. Historically, PA has been considered a rare disease, aﬀecting about 1% of hypertensive patients [124–127]. However, several studies performed in the last decade report a much higher prevalence of PA (>10%), suggesting an “epidemic” of this condition [128–133]. These studies, however, were carried out in specialized referral centers, raising concerns of selection bias. Indeed, a study of more than 600 unselected patients with hypertension conducted in Chile, revealed a 6.1% prevalence of PA [134], suggesting that the true prevalence is somewhere in the middle. However, irrespective of its exact prevalence, PA has become fashionable again, with leading specialized centers appearing all over the world, from Alabama (D. Calhoun) to Italy (G. Rossi) and from Australia (M. Stowasser) to United Kingdom (M. Brown). The prevalence of hypertension relates to the severity of hypertension. In the study from Chile, PA was found in 1.99% of patients with Stage I hypertension and in 13.2% of patients with stage III hypertension [134]. In another study of more than 400 Czech patients with moderate- to-severe hypertension, the prevalence of PA was even higher (19%) [135]. Data from clinical practice indicates that resistant hypertension represents the condition with the highest probability of detecting PA [136, 137]. Indeed, the prevalence of PA ranged from 14–23% in 5 studies conducted in resistant hypertensives [138–142]. A study of 88 patients with resistant hypertension in Alabama showed that 18 patients (20%) suﬀered from PA; PA prevalence was race independent [138]. The prevalence of PA was quite International Journal of Hypertension Table 3: Endocrine causes of secondary hypertension. (i) Primary aldosteronism (ii) Pheochromocytoma (iii) Hyperthyroidism (iv) Hypothyroidism (v) Cushing’s syndrome (vi) Acromegaly (vii) Hyperparathyroidism (iix) Carcinoid tumor (ix) Congenital adrenal hyperplasia similar in two other studies, one from Seattle (17%) and one from Norway (23%) [139, 140]. A somehow lower prevalence was found in the remaining two studies. A study from Spain reported a 14% prevalence of primary hyperaldosteronism in patients with refractory hypertension; however, patients with hypokalemia were excluded from the study suggesting that the true prevalence of primary aldosteronism could be up to two times higher than the one reported [141]. Finally, a similar prevalence of 14% has been reported in diabetic subjects with resistant hypertension [142]. The above-mentioned studies have reported a PA preva- lence of 14–23% in patients with resistant hypertension, suggesting that the true prevalence would be around 20%. However, it has to be recognized that all these studies included a small number of patients. In total, only 418 patients participated in these studies, underlining the need for larger studies. A recent study from Greece evaluated 2,032 patients with resistant hypertension, with 1,616 of them having “true” resistant hypertension [143]. It was found that about 21% of studied patients had a high aldosterone to renin ratio combined with high aldosterone levels, which were suggestive of primary aldosteronism. However, only half of them (11.3%) were suﬀering for primary aldosteronism, conﬁrmed by salt suppression tests and response to spironolactone. Another very interesting ﬁnding is the coexistence of PA and OSA in patients with resistant hypertension. In one study of 109 patients with resistant hypertension, OSA was found in 84% of patients with PA [144]. However, in another study, PA was found in only 34% of patients with OSA [145]. The pathophysiologic mechanisms underlining the co-occurrence of these conditions need further elucida- tion. The other forms of endocrine hypertension, presented in Table 3, are less frequently encountered in hypertensive patients and, therefore, represent rare causes of resistant hypertension. In addition, the clinical presentation of these endocrine forms of secondary hypertension is usually so characteristic that is really hard to be missed. Since this paper addresses the most common secondary causes of resistant hypertension, readers interested in endocrine hy- pertension may refer to other recently published reviews [146, 147].