{"id":4422411,"date":"2025-01-11T17:52:50","date_gmt":"2025-01-11T23:52:50","guid":{"rendered":"https:\/\/myendoconsult.com\/learn\/topics\/pheochromocytoma\/"},"modified":"2025-01-12T16:20:34","modified_gmt":"2025-01-12T22:20:34","slug":"pheochromocytoma","status":"publish","type":"oen_topic","link":"https:\/\/myendoconsult.com\/learn\/topics\/pheochromocytoma\/","title":{"rendered":"Pheochromocytoma"},"content":{"rendered":"\n<h2 class=\"wp-block-heading\">PHEOCHROMOCYTOMA AND PARAGANGLIOMA <\/h2>\n\n\n\n<h3 class=\"wp-block-heading\">Typical Duration of Spell<\/h3>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Spell Duration<\/strong>: Commonly <strong>15\u201320 minutes<\/strong>, but may be much shorter or last several hours.<\/li>\n\n\n\n<li><strong>Important Note<\/strong>: Most patients with spells <strong>do not<\/strong> have a pheochromocytoma.<\/li>\n<\/ul>\n\n\n\n<figure class=\"wp-block-image size-full\"><img decoding=\"async\" src=\"https:\/\/myendoconsult.com\/learn\/wp-content\/uploads\/ppgl-chart.jpg\" alt=\"Paraganglioma anatomical positions\" class=\"wp-image-3959155\"\/><figcaption class=\"wp-element-caption\">Paraganglioma anatomical positions<\/figcaption><\/figure>\n\n\n\n<h3 class=\"wp-block-heading\">Additional Clinical Signs of Catecholamine-Secreting Tumors<\/h3>\n\n\n\n<ol class=\"wp-block-list\">\n<li><strong>Cardiovascular<\/strong>\n<ul class=\"wp-block-list\">\n<li><strong>Hypertensive retinopathy<\/strong>.<\/li>\n\n\n\n<li><strong>Orthostatic hypotension<\/strong> (possible paradoxical feature).<\/li>\n\n\n\n<li><strong>Angina<\/strong>.<\/li>\n<\/ul>\n<\/li>\n\n\n\n<li><strong>Gastrointestinal<\/strong>\n<ul class=\"wp-block-list\">\n<li><strong>Nausea<\/strong>, <strong>constipation<\/strong> (megacolon can be a presenting symptom).<\/li>\n<\/ul>\n<\/li>\n\n\n\n<li><strong>Metabolic<\/strong>\n<ul class=\"wp-block-list\">\n<li><strong>Hyperglycemia<\/strong>, <strong><a href=\"https:\/\/myendoconsult.com\/learn\/diabetes-mellitus\/\" data-wpil-monitor-id=\"192\">diabetes mellitus<\/a><\/strong> (\u03b1-adrenergic inhibition of insulin release).<\/li>\n\n\n\n<li><strong>Hypercalcemia<\/strong> (often resolves post-tumor removal, may be MEN 2\u2013related or due to PTHrP).<\/li>\n\n\n\n<li><strong>Raynaud phenomenon<\/strong>, <strong>livedo reticularis<\/strong>.<\/li>\n\n\n\n<li><strong>Erythrocytosis<\/strong> (secondary to increased catecholamine stimulation).<\/li>\n<\/ul>\n<\/li>\n\n\n\n<li><strong>Mass Effects<\/strong>\n<ul class=\"wp-block-list\">\n<li>Tumor size\/location effects.<\/li>\n\n\n\n<li><strong>Bladder paragangliomas<\/strong>: Painless hematuria, paroxysmal spells triggered by micturition or defecation.<\/li>\n<\/ul>\n<\/li>\n\n\n\n<li><strong>Cosecreted Hormones<\/strong>\n<ul class=\"wp-block-list\">\n<li><strong>ACTH<\/strong> \u2192 <a href=\"https:\/\/myendoconsult.com\/learn\/topics\/cushing-syndrome\/\" data-wpil-monitor-id=\"193\">Cushing syndrome<\/a>.<\/li>\n\n\n\n<li><strong>PTH-related peptide<\/strong> \u2192 hypercalcemia.<\/li>\n\n\n\n<li><strong>Vasopressin<\/strong> \u2192 SIADH.<\/li>\n\n\n\n<li><strong>VIP<\/strong> \u2192 watery diarrhea.<\/li>\n\n\n\n<li><strong>GHRH<\/strong> \u2192 <a href=\"https:\/\/myendoconsult.com\/learn\/topics\/acromegaly-notes\/\" data-wpil-monitor-id=\"194\">acromegaly<\/a>.<\/li>\n<\/ul>\n<\/li>\n\n\n\n<li><strong>Cardiomyopathy and Heart Failure<\/strong>\n<ul class=\"wp-block-list\">\n<li>Possibly <strong>unrecognized<\/strong> as pheochromocytoma cause.<\/li>\n\n\n\n<li>May be <strong>dilated or hypertrophic<\/strong>, often <strong>reversible<\/strong> post-resection.<\/li>\n\n\n\n<li>Myocarditis, myocardial infarction with normal coronaries also possible.<\/li>\n<\/ul>\n<\/li>\n<\/ol>\n\n\n\n<h3 class=\"wp-block-heading\">Physical Exam and Genetic Syndromes<\/h3>\n\n\n\n<ul class=\"wp-block-list\">\n<li>Possible findings from hereditary predispositions:\n<ul class=\"wp-block-list\">\n<li><strong>Retinal angiomas<\/strong>, <strong>marfanoid habitus<\/strong>, <strong>caf\u00e9-au-lait spots<\/strong>, <strong>axillary freckling<\/strong>, <strong>subcutaneous neurofibromas<\/strong>, <strong>mucosal neuromas<\/strong> (e.g., MEN 2B).<\/li>\n<\/ul>\n<\/li>\n\n\n\n<li>Some patients may be <strong>asymptomatic<\/strong> despite high catecholamine levels (receptor desensitization from chronic stimulation).<\/li>\n<\/ul>\n\n\n\n<h3 class=\"wp-block-heading\">The \u201cRule of 10\u201d (Historically)<\/h3>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>10%<\/strong> are extra-adrenal.<\/li>\n\n\n\n<li><strong>10%<\/strong> occur in children.<\/li>\n\n\n\n<li><strong>10%<\/strong> are multiple\/bilateral.<\/li>\n\n\n\n<li><strong>10%<\/strong> recur post-surgery.<\/li>\n\n\n\n<li><strong>10%<\/strong> are malignant.<\/li>\n\n\n\n<li><strong>10%<\/strong> are familial.<\/li>\n\n\n\n<li><strong>10%<\/strong> of benign sporadic pheos found incidentally.<\/li>\n<\/ul>\n\n\n\n<p><em>(Modern data suggests up to 20% familial, and about 50% discovered incidentally in some series.)<\/em><\/p>\n\n\n\n<h3 class=\"wp-block-heading\">Increasing Incidental Detection<\/h3>\n\n\n\n<ul class=\"wp-block-list\">\n<li>Widespread use of <strong>CT imaging<\/strong> and familial testing \u2192 up to <strong>50%<\/strong> discovered before symptoms.<\/li>\n\n\n\n<li>Tumors found incidentally may be small (&lt;3 cm) but can be large (\u226510 cm).<\/li>\n<\/ul>\n\n\n\n<h3 class=\"wp-block-heading\">Diagnosis<\/h3>\n\n\n\n<ol class=\"wp-block-list\">\n<li><strong>Biochemical Confirmation<\/strong>\n<ul class=\"wp-block-list\">\n<li><strong>Fractionated catecholamines and <a href=\"https:\/\/myendoconsult.com\/learn\/metanephrines\/\" data-wpil-monitor-id=\"195\">metanephrines<\/a><\/strong> (plasma or 24-hour urine).<\/li>\n<\/ul>\n<\/li>\n\n\n\n<li><strong>Imaging<\/strong> only <strong>after<\/strong> biochemical confirmation:\n<ul class=\"wp-block-list\">\n<li><strong>Pheochromocytomas<\/strong>: Typically adrenal; average ~4.5 cm.<\/li>\n\n\n\n<li><strong>Paragangliomas<\/strong>: Extra-adrenal chromaffin tissue (para-aortic, organ of Zuckerkandl, bladder wall, sympathetic chain in neck\/mediastinum).<\/li>\n<\/ul>\n<\/li>\n\n\n\n<li><strong>Head\/Neck Paragangliomas<\/strong>:\n<ul class=\"wp-block-list\">\n<li>Usually <strong>parasympathetic<\/strong> origin, <strong>nonsecretory<\/strong>.<\/li>\n<\/ul>\n<\/li>\n\n\n\n<li><strong>Thoracic\/Abdominal\/Pelvic Paragangliomas<\/strong>:\n<ul class=\"wp-block-list\">\n<li><strong>Sympathetic<\/strong> origin, typically <strong>catecholamine-secreting<\/strong>.<\/li>\n<\/ul>\n<\/li>\n<\/ol>\n\n\n\n<figure class=\"wp-block-image size-full\"><img loading=\"lazy\" decoding=\"async\" width=\"3091\" height=\"2100\" src=\"https:\/\/myendoconsult.com\/learn\/wp-content\/uploads\/clonidine-suppression-test-1.png\" alt=\"\" class=\"wp-image-4422790\" srcset=\"https:\/\/myendoconsult.com\/learn\/wp-content\/uploads\/clonidine-suppression-test-1.png 3091w, https:\/\/myendoconsult.com\/learn\/wp-content\/uploads\/clonidine-suppression-test-1-300x204.png 300w, https:\/\/myendoconsult.com\/learn\/wp-content\/uploads\/clonidine-suppression-test-1-768x522.png 768w, https:\/\/myendoconsult.com\/learn\/wp-content\/uploads\/clonidine-suppression-test-1-1536x1044.png 1536w, https:\/\/myendoconsult.com\/learn\/wp-content\/uploads\/clonidine-suppression-test-1-2048x1391.png 2048w\" sizes=\"auto, (max-width: 3091px) 100vw, 3091px\" \/><figcaption class=\"wp-element-caption\">The Clonidine Suppression Test<\/figcaption><\/figure>\n\n\n\n<p><\/p>\n\n\n\n<hr class=\"wp-block-separator has-alpha-channel-opacity\"\/>\n\n\n\n<h2 class=\"wp-block-heading\">ADRENAL MEDULLA AND CATECHOLAMINES<\/h2>\n\n\n\n<h3 class=\"wp-block-heading\">Anatomy and Cells<\/h3>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Adrenal Medulla<\/strong>: Central 10% of the adrenal gland volume.<\/li>\n\n\n\n<li><strong>Chromaffin Cells (Pheochromocytes)<\/strong>: Stain brown with chromium salts (due to oxidation of epinephrine\/norepinephrine).<\/li>\n\n\n\n<li><strong>Sympathetic Input<\/strong>: Preganglionic fibers from T10\u2013L1 splanchnic nerves.<\/li>\n\n\n\n<li><strong>Stressful Stimuli<\/strong>: Trigger catecholamine release (MI, anesthesia, hypoglycemia).<\/li>\n<\/ul>\n\n\n\n<h3 class=\"wp-block-heading\">Catecholamine Basics<\/h3>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Catechol Nucleus<\/strong>: ortho-dihydroxybenzene ring + amino side chain.\n<ul class=\"wp-block-list\">\n<li><strong>Epinephrine<\/strong>: Principal adrenal medulla hormone (80% of normal output).<\/li>\n\n\n\n<li><strong>Norepinephrine<\/strong>: Also in adrenal medulla &amp; peripheral sympathetic nerves.<\/li>\n\n\n\n<li><strong>Dopamine<\/strong>: Precursor, main CNS transmitter.<\/li>\n<\/ul>\n<\/li>\n<\/ul>\n\n\n\n<h3 class=\"wp-block-heading\">Physiologic Effects<\/h3>\n\n\n\n<ol class=\"wp-block-list\">\n<li><strong>Cardiovascular<\/strong>: \u2191HR, BP, myocardial contractility, conduction velocity.<\/li>\n\n\n\n<li><strong>Receptor Subtypes<\/strong>\n<ul class=\"wp-block-list\">\n<li><strong>\u03b11<\/strong>: Vascular smooth muscle contraction \u2192 \u2191BP.<\/li>\n\n\n\n<li><strong>\u03b12<\/strong>: Presynaptic inhibition of NE release; central anti-hypertensive effect.<\/li>\n\n\n\n<li><strong>\u03b21<\/strong>: Cardiac inotropy, chronotropy; renin release, lipolysis.<\/li>\n\n\n\n<li><strong>\u03b22<\/strong>: Bronchodilation, vasodilation in skeletal muscle, glycogenolysis.<\/li>\n\n\n\n<li><strong>\u03b23<\/strong>: Lipolysis, energy expenditure.<\/li>\n\n\n\n<li><strong>DA1<\/strong> (renal vasculature dilation), <strong>DA2<\/strong> (presynaptic inhibition of NE release).<\/li>\n<\/ul>\n<\/li>\n<\/ol>\n\n\n\n<h3 class=\"wp-block-heading\">Pharmacologic Implications<\/h3>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Selective \u03b1\/\u03b2 agonists\/antagonists<\/strong> treat various conditions (e.g., \u03b21-blockers for HTN, \u03b12-agonists for HTN, \u03b22-agonists for asthma).<\/li>\n<\/ul>\n\n\n\n<hr class=\"wp-block-separator has-alpha-channel-opacity\"\/>\n\n\n\n<h2 class=\"wp-block-heading\">CATECHOLAMINE SYNTHESIS, STORAGE, SECRETION, METABOLISM, INACTIVATION<\/h2>\n\n\n\n<h3 class=\"wp-block-heading\">Synthesis<\/h3>\n\n\n\n<ol class=\"wp-block-list\">\n<li><strong>Tyrosine<\/strong> \u2192 DOPA via <strong>tyrosine hydroxylase<\/strong> (rate-limiting).\n<ul class=\"wp-block-list\">\n<li>Inhibited by cytoplasmic catecholamines; relieved by secretory depletion.<\/li>\n\n\n\n<li>\u03b1-Methylparatyrosine (metyrosine) inhibits tyrosine hydroxylase.<\/li>\n<\/ul>\n<\/li>\n\n\n\n<li><strong>DOPA<\/strong> \u2192 <strong>Dopamine<\/strong> via aromatic L-amino acid decarboxylase.<\/li>\n\n\n\n<li><strong>Dopamine<\/strong> \u2192 <strong>Norepinephrine<\/strong> via dopamine \u03b2-hydroxylase (DBH) in storage vesicles.<\/li>\n\n\n\n<li><strong>Norepinephrine<\/strong> \u2192 <strong>Epinephrine<\/strong> via phenylethanolamine N-methyltransferase (PNMT) in cytosol.\n<ul class=\"wp-block-list\">\n<li>PNMT requires glucocorticoids and S-adenosylmethionine.<\/li>\n<\/ul>\n<\/li>\n<\/ol>\n\n\n\n<figure class=\"wp-block-image size-full\"><img loading=\"lazy\" decoding=\"async\" width=\"3000\" height=\"2100\" src=\"https:\/\/myendoconsult.com\/learn\/wp-content\/uploads\/synthesis-of-catecholamines.png\" alt=\"\" class=\"wp-image-4422794\" srcset=\"https:\/\/myendoconsult.com\/learn\/wp-content\/uploads\/synthesis-of-catecholamines.png 3000w, https:\/\/myendoconsult.com\/learn\/wp-content\/uploads\/synthesis-of-catecholamines-300x210.png 300w, https:\/\/myendoconsult.com\/learn\/wp-content\/uploads\/synthesis-of-catecholamines-768x538.png 768w, https:\/\/myendoconsult.com\/learn\/wp-content\/uploads\/synthesis-of-catecholamines-1536x1075.png 1536w, https:\/\/myendoconsult.com\/learn\/wp-content\/uploads\/synthesis-of-catecholamines-2048x1434.png 2048w\" sizes=\"auto, (max-width: 3000px) 100vw, 3000px\" \/><figcaption class=\"wp-element-caption\">Synthesis of catecholamines<\/figcaption><\/figure>\n\n\n\n<h3 class=\"wp-block-heading\">Storage and Secretion<\/h3>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Vesicular Monoamine Transporters (VMAT)<\/strong>: Pump catechols into secretory vesicles.<\/li>\n\n\n\n<li><strong>Secretory Granules<\/strong>: Contain catecholamines, ATP, calcium, neuropeptides, chromogranins.<\/li>\n\n\n\n<li><strong>Exocytosis<\/strong> Trigger: Acetylcholine (via nicotinic receptors) \u2192 depolarization \u2192 voltage-gated Ca\u00b2\u207a channels \u2192 vesicle fusion and release.<\/li>\n\n\n\n<li><strong>Short Plasma Half-Life<\/strong>: 10\u2013100 seconds. About half loosely bound to albumin.<\/li>\n<\/ul>\n\n\n\n<h3 class=\"wp-block-heading\">Metabolism and Inactivation<\/h3>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Reuptake<\/strong>: ~90% of synaptic NE taken up by presynaptic nerve (uptake-1); inhibited by cocaine, TCAs.<\/li>\n\n\n\n<li><strong>Enzymatic<\/strong>: Catechol-O-methyltransferase (COMT) and monoamine oxidase (MAO) degrade catechols.\n<ul class=\"wp-block-list\">\n<li><strong>Metanephrine\/normetanephrine<\/strong> formed by COMT.<\/li>\n\n\n\n<li>Final major metabolite: <strong>vanillylmandelic acid (VMA)<\/strong>.<\/li>\n<\/ul>\n<\/li>\n\n\n\n<li><strong>Dopamine<\/strong>: Metabolized to homovanillic acid (HVA).<\/li>\n<\/ul>\n","protected":false},"excerpt":{"rendered":"<p>PHEOCHROMOCYTOMA AND PARAGANGLIOMA Typical Duration of Spell Additional Clinical Signs of Catecholamine-Secreting Tumors Physical Exam and Genetic Syndromes The \u201cRule of 10\u201d (Historically) (Modern data suggests up to 20% familial, and about 50% discovered incidentally in some series.) Increasing Incidental Detection Diagnosis ADRENAL MEDULLA AND CATECHOLAMINES Anatomy and Cells Catecholamine Basics Physiologic Effects Pharmacologic Implications [&hellip;]<\/p>\n","protected":false},"featured_media":0,"template":"","oen_topic_chapter":[684],"class_list":["post-4422411","oen_topic","type-oen_topic","status-publish","hentry","oen_topic_chapter-adrenal-gland","post-wrapper","thrv_wrapper"],"_links":{"self":[{"href":"https:\/\/myendoconsult.com\/learn\/wp-json\/wp\/v2\/oen_topic\/4422411","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/myendoconsult.com\/learn\/wp-json\/wp\/v2\/oen_topic"}],"about":[{"href":"https:\/\/myendoconsult.com\/learn\/wp-json\/wp\/v2\/types\/oen_topic"}],"version-history":[{"count":8,"href":"https:\/\/myendoconsult.com\/learn\/wp-json\/wp\/v2\/oen_topic\/4422411\/revisions"}],"predecessor-version":[{"id":4422796,"href":"https:\/\/myendoconsult.com\/learn\/wp-json\/wp\/v2\/oen_topic\/4422411\/revisions\/4422796"}],"wp:attachment":[{"href":"https:\/\/myendoconsult.com\/learn\/wp-json\/wp\/v2\/media?parent=4422411"}],"wp:term":[{"taxonomy":"oen_topic_chapter","embeddable":true,"href":"https:\/\/myendoconsult.com\/learn\/wp-json\/wp\/v2\/oen_topic_chapter?post=4422411"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}