Clinical Use of Laboratory Tests for the Identification of Secondary Forms of Arterial Hypertension

Abstract

The prevalence of secondary hypertension can be underestimated if appropriate tests are not performed. The importance of selecting patients with a high pre-test probability of secondary forms of hypertension is first discussed. The laboratory tests currently used for seeking a cause of hypertension are critically reviewed, with emphasis on their operative features and limitations. Strategies to identify primary aldosteronism, the most frequent form of secondary hypertension, and to determine its unilateral or bilateral causes are described. Treatment entails adrenalectomy in unilateral forms, and mineralocorticoid receptor blockade in bilateral forms. Renovascular hypertension is also a common, curable form of hypertension, that should be identified as early as possible to avoid the onset of cardiovascular target organ damage. The tests for its confirmation or exclusion are discussed. The various tests available for the diagnosis of pheochromocytoma, which is much rarer than the above but extremely important to identify, are also described, with emphasis on recent developments in genetic testing. Finally, the tests for diagnosing some rarer monogenic forms and other renal and endocrine causes of arterial hypertension are explored.

Key words :

• Hypertension
• renin
• aldosterone
• angiotensin
• renovascular
• Cushing's syndrome

Abbreviations
11β HSD2,	=	11 β-hydroxysteroid dehydrogenase type 2;
2K1C, 2-kidney,	=	1 clip;
ACE,	=	angiotensin-converting enzyme;
ACTH,	=	adrenocorticotropic hormone;
AME,	=	apparent mineralocorticoid excess;
APA,	=	aldosterone-producing adenoma;
ARR,	=	aldosterone/renin ratio;
AVS,	=	adrenal venous sampling;
CRH,	=	corticotropin-releasing hormone;
CT,	=	computed tomography;
CV,	=	coefficient of variation;
DOPA,	=	[L]-dihydroxyphenylalanine;
E,	=	epinephrine;
EIA,	=	enzyme immunoassay;
FH-I,	=	familial hyperaldosteronism type I;
FH-II,	=	familial hyperaldosteronism type II;
GFR,	=	glomerular filtration rate;
GH,	=	growth hormone;
GRA,	=	glucocorticoid-remediable aldosteronism;
HPLC,	=	high-performance liquid chromatography;
HPLC-ESI-MS/MS,	=	HPLC-electrospray-tandem mass spectrometry;
HT,	=	arterial hypertension;
ICMA,	=	immunochemiluminometric assay;
IHA,	=	idiopathic hyperaldosteronism;
123 I-MIBG,	=	123Iodinated metaiodobenzylguanidine;
IRMA,	=	immunoradiometric assay;
LV,	=	left ventricular;
MDRD Study,	=	Modification on Diet in Renal Disease Study;
MEN,	=	multiple endocrine neoplasia;
MR,	=	magnetic resonance;
NE,	=	norepinephrine;
NPY,	=	neuropeptide Y;
PA,	=	primary aldosteronism;
PAPY,	=	Primary Aldosteronism Prevalence in Italy;
PHA type II,	=	pseudohypoaldosteronism type II;
PRA,	=	plasma renin activity;
PRC,	=	plasma renin concentration;
PTRA,	=	percutaneous transluminal renal angioplasty;
RAAS,	=	renin-angiotensin-aldosterone system;
RAS,	=	renal artery stenosis;
RIA,	=	radioimmunoassay;
ROC,	=	receiver operating characteristic;
RVH,	=	renovascular hypertension;
RVRR,	=	renal vein renin ratio;
SDHB,	=	succinate dehydrogenase subunit B;
SDHC,	=	succinate dehydrogenase subunit C;
SDHD,	=	succinate dehydrogenase subunit D;
T3,	=	tri-iodothyronine;
T4,	=	tetra-iodothyronine;
THF:THE,	=	tetrahydrocortisol and allotetrahydrocortisol (THF) to tetrahydrocortisone (THE) ratio;
TPOAb,	=	thyroid peroxidase antibodies;
TSH,	=	thyroid-stimulating hormone;
VHL,	=	Von Hippel Lindau;
VMA,	=	vanillylmandelic acid;
ZG,	=	zona glomerulosa;
ZF,	=	zona fasciculata.

Abbreviations
11β HSD2,	=	11 β-hydroxysteroid dehydrogenase type 2;
2K1C, 2-kidney,	=	1 clip;
ACE,	=	angiotensin-converting enzyme;
ACTH,	=	adrenocorticotropic hormone;
AME,	=	apparent mineralocorticoid excess;
APA,	=	aldosterone-producing adenoma;
ARR,	=	aldosterone/renin ratio;
AVS,	=	adrenal venous sampling;
CRH,	=	corticotropin-releasing hormone;
CT,	=	computed tomography;
CV,	=	coefficient of variation;
DOPA,	=	[L]-dihydroxyphenylalanine;
E,	=	epinephrine;
EIA,	=	enzyme immunoassay;
FH-I,	=	familial hyperaldosteronism type I;
FH-II,	=	familial hyperaldosteronism type II;
GFR,	=	glomerular filtration rate;
GH,	=	growth hormone;
GRA,	=	glucocorticoid-remediable aldosteronism;
HPLC,	=	high-performance liquid chromatography;
HPLC-ESI-MS/MS,	=	HPLC-electrospray-tandem mass spectrometry;
HT,	=	arterial hypertension;
ICMA,	=	immunochemiluminometric assay;
IHA,	=	idiopathic hyperaldosteronism;
123 I-MIBG,	=	123Iodinated metaiodobenzylguanidine;
IRMA,	=	immunoradiometric assay;
LV,	=	left ventricular;
MDRD Study,	=	Modification on Diet in Renal Disease Study;
MEN,	=	multiple endocrine neoplasia;
MR,	=	magnetic resonance;
NE,	=	norepinephrine;
NPY,	=	neuropeptide Y;
PA,	=	primary aldosteronism;
PAPY,	=	Primary Aldosteronism Prevalence in Italy;
PHA type II,	=	pseudohypoaldosteronism type II;
PRA,	=	plasma renin activity;
PRC,	=	plasma renin concentration;
PTRA,	=	percutaneous transluminal renal angioplasty;
RAAS,	=	renin-angiotensin-aldosterone system;
RAS,	=	renal artery stenosis;
RIA,	=	radioimmunoassay;
ROC,	=	receiver operating characteristic;
RVH,	=	renovascular hypertension;
RVRR,	=	renal vein renin ratio;
SDHB,	=	succinate dehydrogenase subunit B;
SDHC,	=	succinate dehydrogenase subunit C;
SDHD,	=	succinate dehydrogenase subunit D;
T3,	=	tri-iodothyronine;
T4,	=	tetra-iodothyronine;
THF:THE,	=	tetrahydrocortisol and allotetrahydrocortisol (THF) to tetrahydrocortisone (THE) ratio;
TPOAb,	=	thyroid peroxidase antibodies;
TSH,	=	thyroid-stimulating hormone;
VHL,	=	Von Hippel Lindau;
VMA,	=	vanillylmandelic acid;
ZG,	=	zona glomerulosa;
ZF,	=	zona fasciculata.