Secondary Endocrine Hypertension

Non-endocrine origin of hypertension

• renovascular

• renoparenchymal

• exogen

• cardiac or artery anomaly

Endocrine origin of hypertension

• primary hyperaldosteronism

• phaechromocytoma

• acromegalia, Cushing

• thyrotoxicosis

• hypothyroidism, hyperparathyroidism

Who should be examined?

• hypertension in youth < 40yrs

• malignant hypertension > 180/120 mmHg

• sudden onset with high blood pressure value

• patient with hypertension and adrenal tumor

• patient with hypertension and OSAS

• therapy-refractory hypertension

Definition of primary hyperaldosteronism

primary adrenal over expression of aldosterone

• suppressed renin value

• hypertension and hypokalemia

Classification of Conn syndrome

• 35-50% aldosterone producing adenoma

• 50-65% bilateral adrenal hyperplasia

• < 1% familial hyperaldosteronism

• < 1% aldosterone-producing adrenal cancer

Clinical signs of Conn

• hypertension

• hypokalemia (50% of cases)

• hypertension complications

  • stroke, HF, MI, AF

  • kidney failure - proteinuria

  • metabolic syndrome/(pre)DM

Characteristic of Conn hypokalemia

• spontaneous

• diuretics induced

• fatigue, weakness, muscle cramp, arrhythmia

Screening of Conn

• ratio of plasma aldosterone concentration and plasma renin activity

  • fasting, morning sample min 20-30 min in rest (sitting, lying)

• normokalemia is essential

• some medications should be temporarily left out

Why is normokalemia essential in screening of Conn?

low serum K+ will decrease aldosterone and increase renin

• false negative result

ARR cannot be calculated if

• aldosterone receptor antagonists

  • spironolactone, eplerone

• K+ sparing diuretic

  • amilorid

ARR false positive result

ARR false negative result

Screening is positive if

• ARR > 30

• plasma aldosterone concentration → 15ng/dl (416 pmol/L)

At what concentration is PRA considered suppressed?

< 0.2 ng/ml/h

Confirmatory testing of Conn

• intravenous Na+ loading test

• oral sodium loading test

• fludrocortison suppression test

• captopril test

What is the intravenous Na+ loading test?

• 0 min → blood sample: plasma aldosterone, Na, K

• 4 hours 2000 ml 0,9% NaCl infusion

• 240 min → repeat same blood test

Evaluation of intravenous Na+ loading test

• after Na+ infusion the concentration of plasma aldosterone < 5ng/dl - unlikely disease

• after Na+ infusion the concentration > 5ng/dl - diagnosis confirmed

• 5-10ng/dl might refer to bilateral hyperplasia

• > 10ng/dl might refer to aldosterone producing adrenal adenoma

What should be done before localisation scan?

confirmation of overproduction of aldosterone with hormone test

What’s the first choice of localisation?

adrenal CT (MRI) → adenoma < 1cm

Gold standard of localisation

adrenal vein sampling

Three localisations of catheters in adrenal vein sampling

• IVC

• right/left adrenal vein

What do we calculate in adrenal vein sampling?

aldosterone/cortisol ratio

Confirmation of correct catheter localisation

adrenal vein cortisol 2-3x higher than cortisol in VC

When can we confirm aldosterone producing adenoma with adrenal vein sampling?

one side blood sample has 3-4x higher aldosterone ratio than the other side

When can we confirm a bilateral hyperplasia with adrenal vein sampling?

less or no difference in ratio between the sides

Treatment of one-sided APA

adrenalectomy

What can we see postoperatively?

temporarily hypoaldosteronism, hyperkalemia

Bilateral hyperplasia/APA in case of no operation

• mineralocorticoid receptor antagonists

  • spironolactone, eplerenone

• normalisation of serum K+, tension control

• amilorid can be add on medication

Definition of phaechromocytoma

Catecholamine producing neuroendocrine adrenal tumor

Forms of phaechromocytoma

• extra adrenal - paraganglioma

• pediatric

• genetic involvement

• uni/bilateral adrenal

• benign/malignant

Hereditary phaechromocytoma

• MEN2 A/B (RET protooncogene)

• von Hippel-Lindau syndrome (VHL tumorsuppressor gene)

• neurofibromatosis1 (NF1 neurofibromin gene)

Catecholamins produced in phaechormocytoma

• epinephrine - only adrenal phaechromocytoma

• norepinephrine, dopamine - every phaechromocytoma

Why epinephrine is only secreted in adrenal phaechromocytoma?

high glucocorticoid concentration is needed for PNMT enzyme function

Signs of phaechromocytoma

• headache, palpitations

• perspiration, fix hypertension

• pallor, fatigue, weight loss

• panic attack, anxiety

• paroxysmal/orthostatic hypertension

Catecholamin overproduction is high risk factor for

• angina pectoris

• malignant arrhythmia

• cardiac failure, aorta dissection, sudden death

Catecholamine crisis situation

• mechanical irritation of the tumor (operation, intraabdominal pressure elevation)

• thyramine, BBL

Screening is recommended if

• unusual presence of hypertension

• hypertension in youth or in young adults

• therapy-resistant hypertension

• blood pressure lability

• paroxysmal hypertension

• adrenal incidentaloma + hypertension

• unknown cause of DCM

• unknown of shock

• paradox blood pressure elevation after BB initiation

Confirmation of catecholamine overproduction

• (nor)metanephrine excretion (plasma/24h urine)

• in low pH, dark bowel

• positive if 3x > ULN

• vanilin mandolin acid

• 3-metoxithyramine

What’s chromogranine A?

• common neuroendocrine tumor marker

• serum level is proportional with tumor size

Should we perform biopsy in phaechromocytoma?

NO biopsy !!!

DD of phaechromocytoma

• thyrotoxicosis

• carcinoid syndrome

• MTC - high calcitonin

• perimenopausal syndrome

• migraine, epilepsy

• panic attack, anxiety disorders

• drugs, mastocytosis, porphyria

Treatment of phaechromocytoma

surgical resection

Preoperative pretreatment of phaechromocytoma

• α-blocker at first at least for 2 weeks

  • doxazosine, urapidil, prazosine

  • phenoxybenzamine

When is BBL allowed?

only after a-blocker therapy

Operation of phaechromocytoma

• adrenal vein ligature

• avoid mechanical irritation