Transcript Endocrine hypertension

Endocrine Hypertension
Essential hypertension
92-94%
Secondary hypertension
Renal
Miscellaneous
6-8%
4-5%
~2%
Endocrine
Primary hyperaldosteronism
Cushing’s syndrome
Pheochromocytoma
1-2%
0.3-15%
<0.1%
<0.1%
Endocrine Hypertension
Mineralocorticoid excess
Cushing’s syn.
Pheochromocytoma
Sympathetic Nervous System
CA Synthesis & Metabolism
APUD cells
Epinephrine
Tyrosine Hydroxylase
AADC
Dopamine β Hydroxylase
Norepinephrine
COMT
Metanephrine
Normetanephrine
MAO
PNMT
Vanylmandelic Acid (VMA)
Pheochromocytoma
• ~ 0.1% or less of hypertension
• Extraadrenal- Paraganglioma
“10% Tumor”
Bilateral
Extra-adrenal
Familial(? ~20%)
Malignant
Pheochromocytoma
Symptoms
During paroxysm:
Headache
Sweating
Palpitations
Tremor
Chest pain
Abdominal pain
Nausea, vomiting
Between attacks:
Sweating
Cold hands & feet
Weight loss
Constipation
Pheochromocytoma
Signs:
 Increased blood pressure
 Orthostatic hypotension
 Tachycardia
Pheochromocytoma
Familial forms:
(germ-line mutations autosomal dominant)
SyndromicMultiple Endocrine Neoplasia Type 2 (A & B)
Multiple Endocrine Neoplasia Type 1 (rarely)
von Hippel-Lindau disease
Neurocutaneous syndromes (NF1)
Non- syndromic
SDHB, C, D;
TEM127
When to Suspect a
Pheochromocytoma?
 Episodic HTN accompanied by the
classical triad
 Refractory HTN
 Labile HTN
 Severe pressor response to surgery etc.
 Familial Hx associated with Pheo
 Incidental adrenal mass
 HTN at a young age
 Takotsubo cardiomyopathy
‫‪MEN2‬‬
‫קרצינומה מדולארית‬
‫של בלוטת התריס‬
‫‪90%‬‬
‫‪40-50%‬‬
‫‪100%‬‬
‫‪40-50%‬‬
‫‪90%‬‬
‫פאוכרומוציטומה‬
‫היפרפרהטירוידיזם‬
‫‪10-20%‬‬
‫‪ MEN 2A‬‬
‫‪ MEN 2B‬‬
‫‪ Familial Medullary Thyroid‬‬
‫)‪Carcinoma (FMTC‬‬
‫‪MEN2b‬‬
‫מראה מרפנואידי‬
‫נוירומות בריריות‬
Von-Hippel Lindau Disease
 Renal cell carcinoma
 Retinal angioma
 Cerebellar or spinal
hemangioblastoma
 Pheochromocytoma-7-19%.
PheochromocytomaBiochemical Diagnosis
 24 hour urine collection for free CATs
 epinephrine and norepinephrine
 Sensitivity ~70%
 24 hour urine collection for CAT metabolites (METS)
 metanephrine, normetanephrine and acid
 More specific, sensitivity >90%
 Urinary CATS + METS
 Sensitivity > 95%
 Plasma free metanephrines.
 Highest sensitivity > 95%
Pheochromocytoma imaging
Only after the Dx of pheo is biochemically
confirmed!!
 CT
 MRI
 I123MIBG
 PET-18FDG
 Octreoscan or 68Ga-DOTATATE-PET
Malignant pheo68Ga-DOTATATE
Scan
PheochromocytomaTherapy
Surgical resection of tumor If localized to adrenal- laparoscopic
adrenalectomy
Prior to surgery Hypertension: α-blockade
(phenoxybenzamine, doxasocin, phentolamine)
 Tachycardia- β-blockade (only after α
blockade)
Mineralocorticoid
excess
Biosynthesis and action of
Aldosterone
Glomerulosa
Kidney
11 β HSD type 2
cortisol
cortisone
ANDROSTENDIONE
Renin-Angiotensin- Aldosterone
Regulatory System
↑ACTH
Sympathetic stimulation
Mineralocorticoid Excess
Hyperaldosteronism
Primary
Secondary
Apparent MC excess
↓PRA and ↓ PAC
Hyperaldosteronism DD:
Primary- PRA
Secondary- PRA
1. Renal Artery Stenosis
(atherosclerosis, fibromuscular dysplasia).
2. Primary tumor of the JGA
Primary Aldosteronism
• Described by Conn in 1955.
• Hypertension, hypokalemia,
metabolic alkalosis.
• Prevalence: 5-15% of patients
with hypertension.
Causes of Primary
Aldosteronism
Aldosterone Producing
Adenoma (APA)
~30%
Idiopathic/hyperplasia (IHA)
~ 70%
Adrenocortical Carcinoma
rare
Clinical Presentation
Hypertension
Moderate to severe (APA>hyperplasia)
Refractory to medications
K on low dose diuretics
End-organ damage (aldosterone, HTN)
LVH
Micro and macro vascular disease
Clinical Presentation
 Laboratory
K, ↔K
Metabolic alkalosis
Mild Na
 Symptoms related to hypokalemia
Neuromuscular
Nephrogenic DI (polyuria & nocturia)
Screening for Primary
Hyperaldosteronism
 Hypertension and hypokalemia
(including patients treated with low dose
diuretics).
 Severe, resistant, or relatively acute
hypertension, age<30.
 An adrenal incidentaloma
Diagnosis:
• Screening test
• Confirmatory testing
• Determine the subtype
Screening Tests for Primary
Aldosteronism:
PAC/PRA
(PAC >20 ng/dl, PRA<1 ng/ml/h)
 >30 suggestive; >50 diagnostic
 Morning, ambulatory, paired, random PAC and
PRA.
 Serum K levels should be normalized
 Not under beta blockers and spironolactone
(preferably also w/o ACE inhibitors).
Diagnosis
 Confirmatory tests:
Saline infusion test- non suppressed aldo.
24 hour urinary aldosterone
 Determining subtype:
Posture testnormal response: elevation of Aldo
IHA- normal response
APA- no elevation
Imaging
• Only after biochemical Dx (2-10%
nonfunctioning adenomas on CT).
• Abdominal spiral CT
• In patients > 40 years of ageSelective adrenal venous sampling
Treatment
 APA- Unilateral total adrenalectomy
 IHA- Medical management
(aldactone, amiloride, aplerenone)
>30
Other Causes for
Endocrine HTN
 Hypothyroidism –diastolic HTN
 Hyperthyroidism- systolic HTN
 Acromegaly- salt retention
 Hyperparathyroidism