Adrenal Medulla Physiology

1. Adrenal Medulla Physiology Bob Bing-You, MD, MEd, MBA Medical Director Maine Center for Endocrinology

2. A Case of the Sweats • 32 y.o. white male • 6 month h/o increased sweating; non-exertional, profuse • Occasional h/a’s, palpitations • Father had a “high calcium problem” and his paternal GGM had thyroid surgery for a tumor

3. Adrenal Over-production • Adrenal Medulla • Catecholamines, norepinephrine, epinephrine • Adrenal Cortex – surgical disease • Cushing’s syndrome • Hyperaldosteronism [Conn’s Syndrome] • Androgen-producing tumors

4. Adrenal medulla function • Stimulated by sympathetic nervous system to release epinephrine and norepinephrine • 80% epi and 20% norepi • Effects on tissues 10 x longer than direct sympathetic stimulation due to slow removal

5. Catecholamine effects • Norepinephrine • Vascular vasoconstriction • Increased heart rate • Inhibit GI tract • Pupil dilation • Epinephrine • Greater effect on cardiac activity • Weaker vasoconstriction [less effect on  BP]

6. Other effects • Epi >> norepi increasing metabolic rate • Support vascular “tone” • Catecholamines support direct stimulation of tissues activated by sympathetic system • Back-up system for each other

8. Tiger fight-or-flight •  arterial pressure •  blood flow to all active muscles •  rates cellular metabolism throughout body •  blood glucose concentration •  glycolysis in muscle •  mental activity •  rate of blood coagulation

9. Catecholamine biosynthesis • Tyrosine » dopamine » norepinenephrine » epinephrine • Degraded to vanillylmandelic acid [VMA] and metanephrines

12. Pheochromocytoma • Rare: 1/1000 HTN patients • Resistant HTN, secondary cause considered • Triad of symptoms • Multiple Endocrine Neoplasia [MEN] Type 2A and 2 B • “PAT”: parathyroid, adrenal pheo, medullary thyroid cancer • “MAT”: mucocutaneous neuromas

13. Case of the sweats • 32 y.o. white male • 6 month h/o increased sweating; non-exertional, profuse • Occasional h/a’s, palpitations • Father had a “high calcium problem” and his paternal GGM had thyroid surgery for a tumor

14. What MEN syndrome does he have? • A. MEN 1 • B. MEN 2a • C. MEN 3c • D. MEN 2b

15. Diagnosis • Plasma metanephrines • 24 hour urine catecholamines, sensitivity of metanephrines > VMA • Adrenal MRI, MIBG functional scan • MEN2A genetic testing

16. Alpha -vasoconstriction -iris dilation -bronchoconstriction -cardiac contractility -hepatic glucose production Beta -cardioacceleration -bronchodilation -lipolysis Catecholamine Receptors

17. Pre-op Rx • Block Adrenergic receptors • Alpha blockade before beta • Phenoxybenzamine, phentolamine • Beta blockade when orthostatic • Propanolol for non-selectivity, metoprolol or atenolol for β1 selection • ?labetolol

18. Other Rx • Hydration • Intra-cardiac monitoring • Severe HTN, arrhythmias • During induction, tumor manipulation, or anytime! • Nipride • Laparoscopic surgery

19. Surgical Outcome • 1% operative mortality • 5-10% recur, ?MEN syndrome • Catecholamine levels can remain elevated for several weeks • Persistent HTN suggests missed tissue • Malignant pheos 45% 5-year survival, ?I-131-meta-iodo-benzylguanidine

20. Take-home Points • Catecholamines needed for daily life and stress responses • Medulla and sympathetic system linked • Pheos rare but one of few chances to cure HTN • Pre-op medical Rx important • Operative events raises your own catecholamines!

21. Reference • Diagnostic and therapeutic strategies in pheochromocytoma, M.S. Golub, The Endocrinologist, 1992;2:101-6.

22. Questions?