JESFC 2016 FLASH ACTUALITÉ HTA Bilan étiologique de l'hta : dosages hormonaux toujours avant l'imagerie?

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1 JESFC 2016 FLASH ACTUALITÉ HTA Bilan étiologique de l'hta : dosages hormonaux toujours avant l'imagerie? Etiology of hypertension : hormonal assays always before imaging? 16 JANVIER 2016 Bernard CHAMONTIN Service de Médecine Interne et Hypertension Artérielle Pole Cardiovasculaire et Metabolique CHU Rangueil TOULOUSE

2 Bernard CHAMONTIN Service de Médecine Interne et Hypertension Artérielle Pole Cardiovasculaire et Métabolique CHU Rangueil TOULOUSE - F L auteur déclare n avoir aucun conflit d intérêt concernant les données de sa communication

3 Which patients? Uncontrolled, complicated or resistant Hypertension Different causes of secondary hypertension Primary hyperaldosteronism 5.6%, Renal artery stenosis i2.4% 3%, Renal parenchymal disease 1.6%-2 % Obstructive sleep apnea % Pedrosa, Hypertension 2011 Renal and renovascular hypertension Endocrine hypertension : adrenal forms of hypertension Hormonal assays or Imaging?

4 Les raisons pour disposer d une imagerie préalable Reasons for imaging as first line Renal artery CT scan confirm or rule out renal artery stenoses due to atheroma or fibromuscular dysplasia (FMD) unifocal or multifocal. Hypertensive patient with coronary artery disease,+/- CKD, 55 years RAS evaluation : reluctance for «drug wash out» (stop beta blockers, RAS inhibitors, diuretics.) Hypertension in young adult, woman < 40 years, +/- contraceptive pill Avoid X rays? Contrasting clinical situations

5 Justifications des dosages hormonaux Arguments for hormonal assays CT scan : uni-bilateral adrenal morphological abnormalities How to demonstrate the responsability in hypertension? Normal adrenal CT scan

6 LE BILAN ETIOLOGIQUE DE L HTA- ETIOLOGICAL WORK UP Prevalence of incidentaloma Prevalence of incidentaloma : 3 to 7% of general population, increasing with age Kloos RT et al, Endocrine Rev 1995;16: Inappropriate adrenalectomy would have occurred in 14.6% of patients, inappropriate exclusion from adrenalectomy would have occurred in 19.1% (where AVS showed unilateral secretion), and adrenalectomy on the wrong side would have occurred in 3.9% In 37.8% of patients (359 of 950), CT/MRI results did not agree with AVS results Kempers MJE et al, Ann Intern Med 2009;151:329 (metaanalysis 38 studies)

7 La découverte d anomalies morphologiques TDM surrénaliennes Abdominal CT scan : adrenal morphological abnormalities Which patients? Hypertensive patient stage 3, spontaneous hypokaliemia, drug resistant hypertension, left ventricular hypertrophy HAP FA IDM AVC HVG Insuffisan ce cardiaque Milliez, JACC ,1 6,5 4,2 2,9 NA Savard*, Hypertens 2013 Mulatero*, JCEM ,6 NA NA 2,9 1,9 NA 2,2 10,3 NA Case control study CV events 12 y FU, 22.6 vs 12.7 % : 14.1 vs 8.4 % at diagnosis / 8.5 vs 4.3 % at FU

8 La découverte d anomalies morphologiques TDM surrénaliennes Abdominal CT scan : adrenal morphological abnormalities Adrenocortical adenoma Solitary hypodense nodule (WO). with normal contraleral adrenal «smooth and thin» Conn APA or Cushing adenoma?

9 La découverte d anomalies morphologiques TDM surrénaliennes Abdominal CT scan : adrenal morphological abnormalities Which patients? Hypertensive patient with metabolic syndrome and dyslipidemia, osteopeny particularly in women CUSHING NSA: incidentalome Imp IMP: cushing clinique SCS: cushing infra clinique (le Cushing du cardiologue) Di Dalmazi EJE 2012

10 La découverte d anomalies morphologiques TDM surrénaliennes Abdominal CT scan : adrenal morphological abnormalities Aldosterone Renin Ratio «ARR», as screening test for Primary Aldosteronism ARR is currently the most reliable available means of screening for primary aldosteronism. ARR is more constant with respect to age and positional variation compared to Aldosterone and Renin alone Se 68 to 96%, Testing conditions : kaliemia, sodium diet, postural influence,age Tiu SC et al, JCEM 2005, 90 (72-78) Rossi GP at al, Hypertension 2009, 55 : 83-9 Tanabe A et al, JCEM 2003, 88:

11 Medications may affect «ARR» : false-positive or false negative Factors affecting ARR : potassium status, dietary sodium advancing age, and above all medications

12 La découverte d anomalies morphologiques TDM surrénaliennes Abdominal CT scan : adrenal morphological abnormalities How to interprete «ARR», which thresholds? 64 (plasma aldosterone pmol/l, active renin mu/l) 23 (plasma aldosterone pg/ml, active renin pg/ml) 300 (plasma aldosterone pg/ml, PRA ng/ml/h) 750 (plasma aldosterone pmol/l, PRA ng/ml/h) 60 (plasma aldosterone pmol/l, PRA pmol/l/min) Le facteur de conversion pour l aldostérone est : 1 pmol/l = 1 pg/ml x 2,77 Le facteur de conversion pour la rénine active est: 1 mui/l = 1 pg/ml x 1 Attention : le facteur de conversion pour la rénine active peut être : 1 mui/l = 1 pg/ml x 1,6 à 1,8 (trousse de dosage) Le facteur de conversion pour l ARP est : 1 ng/ml/h = 12,8 x pmol/l/min Propositions du groupe de travail SFHTA/SFE 2013

13 Nieman, L. K. et al. J Clin Endocrinol Metab 2008;93: La découverte d anomalies morphologiques TDM surrénaliennes Abdominal CT scan : adrenal morphological abnormalities Cushing récusé si cortisolémie <1.8µg/dl

14 La découverte d anomalies morphologiques TDM surrénaliennes Abdominal CT scan : adrenal morphological abnormalities PHEOCHROMOCYTOMA? «Triad» Resistant HT Paroxysmal HT orthostatic hypotension Prévalence 1/ Chez l hypertendu <1/1000 Référé en milieu spécialisé << Adrenal masses Genetic forms NEM 2a,VHL,NF, SDHB Dilated Cardiomyopathy Tako Tsubo Heart failure..

15 La découverte d anomalies morphologiques TDM surrénaliennes Abdominal CT scan : adrenal morphological abnormalities PHEOCHROMOCYTOMA? Urinary Metanephrines, normetanephrines Plasma Metanephrines, normetanephrines Sensitivity Specificity Méta P*/ Normeta P Meta U/ Normeta U hereditary sporadic hereditary sporadic Nécessité de test diagnostique de grande sensibilité et spécificité 1 phéo pour 1000 HT, test de spécificité 95% = 50 faux positifs *chromatography

16 La découverte d anomalies morphologiques TDM surrénaliennes Abdominal CT scan : adrenal morphological abnormalities Recommendation : We suggest CT rather than MRI as the - first choice imaging modality because of its excellent spatial resolution Pheochromocytoma and paraganglioma : endocrine society clinical practice guideline Lenders J. et al JCEM 2014; 99 :

17 La découverte d anomalies morphologiques TDM surrénaliennes Abdominal CT scan : adrenal morphological abnormalities PHEOCHROMOCYTOMA / PARAGANGLIOMA - Computed tomography is suggested for initial imaging, but magnetic resonance is a better option in patients with metastatic disease or when radiation exposure must be limited. (123)I-metaiodobenzylguanidine scintigraphy is a useful imaging modality for metastatic PPGLs (PET scan)- - Plasma free metanephrines : specificity equivalent, sensitivity superior - Patients with paraganglioma should be tested for SDHx mutations, and those with metastatic disease for SDHB mutations. JCEM guidelines Lenders 2014, 99,1915

18 La poursuite du bilan étiologique en présence d une imagerie surrénalienne normale Normal abdominal CT scan Can we exclude endocrine hypertension? No significant CT adrenal abnormalities normal adrenal CT scan «smooth and thin» adrenal glands No, in case of resistant hypertension, hypokaliemia, suggested situations Low renin hypertension? Primary aldosteronism? Spironolactone cf recommendations of French Society of Hypertension SFHTA 2015, Pathway 2 trial

19 La poursuite du bilan étiologique en présence d une imagerie surrénalienne normale Normal abdominal CT scan SPIRONOLACTONE RESPONDERS : PATHWAY 2 Trial BP vs Renin Savoir renouveler l exploration d un HAP et recourir au Kt surrénalien Bryan Williams et al, Lancet 18 septembre 2015

20 La poursuite du bilan étiologique en présence d une imagerie surrénalienne normale Normal abdominal CT scan Be aware of drug interactions and hormonal assays : Medications that may cause falsely elevated test results for plasma and urinary metanephrines Tricyclic antidepressants, MAO inhibitors, antiparkinsonian drugs etc Paracetamol (plasma metanephrines) «False pheochromocytoma»

21 La poursuite du bilan étiologique en présence d une imagerie surrénalienne normale Normal abdominal CT scan Be aware of drug interactions and hormonal assays + antiviraux «False Cushing»

22 LE BILAN ETIOLOGIQUE DE L HTA ETIOLOGICAL WORK UP Rare forms of endocrine hypertension with normal abdominal CT scan Primary Hyperparathyroïdism (screening for hypercalcemia) MEN 2a Pheochromocytoma Cushing s syndrome, pituitary adenoma No significant CT adrenal abnormalities (or bilateral adrenal hyperplasia) Refer to endocrinologist : pituitary adenoma

23 Conclusions The easy "access", difficulties to meet the requirements to have reliable hormone levels explain the first line use of imaging in daily practice. The CT angiography / CT allows the working diagnosis: confirmed or eliminates renovascular, identify adrenal morphological abnormalities but without allowing formal diagnostic conclusion There is a place for imaging in the screening with a need for diagnostic confirmation. The absence of morphological abnormality does not allow to reject endocrine causes. The efficiency of imaging as a first line in the screening of secondary hypertension is relative, and confrontation with hormone assays will be critical to the diagnostic and therapeutic management If endocrine hypertension is suspected in young women the hormone assays may precede imaging.