1. Common Endocrine Issues in the Hospitalized Patient Jordan L. Geller, M.D. Attending Physician Cedars-Sinai Medical Center Division of Endocrinology Clinical Instructor of Medicine UCLA Geffen School of Medicine

2. Evidence Based Questions Diabetes -What is the optimal blood sugar in a inpatient? Thyroid -How can I distinguish euthyroid sick syndrome from hypothyroidism? Adrenal -Who is at risk for adrenal failure and what is the proper way to distinguish primary from secondary causes? Calcium -How can I urgently treat hypercalcemia without obscuring the diagnosis?

3. Learning Objectives Become aware of common endocrine issues in the hospitalized patient Review the evidence for treatment of four key endocrine topics Know what pertinent data to gather for the consultant to use later on

4. Glycemic Control What is the optimal blood glucose in an inpatient?

5. Rationale for Glycemic Control Effects of hyperglycemia… Fluid balance Immune function Inflammation Thrombosis Vascular reactivity Montori VM et al. JAMA. 2002;17:2167-2169

6. Hyperglycemia is associated with bad outcomes… Increased mortality and CHF in patients with acute MI Increased mortality, length of stay, prolonged nursing home care, higher risk of infection in MICU/SICU Greater mortality, increased deep-wound infections, and more overall infection in post-CABG Increased mortality, worse recovery in CVA American Association of Clinical Endocrinologists, 2004

7. … insulin improves outcomes SettingIntervention and ControlsOutcome MICU80 to 110 mg/dL w/ IV insulin vs conventional (insulin if BG> 215) Benefit in pts in ICU >3 days. RR of death declined 18.1%; Total cohort improved renal function and vent time (Van Den Berghe et al, 2006) SICUIV insulin to goal 80-110 mg/dL vs. 180-200 in controls Mortality reduction 34%, sepsis 46%, ARF 41%, transfusions 50%, neuropathy 44% (Van Den Berghe et al, 2001) CSICUIV insulin to goal <200 mg/dL x 3 postop days vs. sliding scale 57% reduction in sternal infection; 66% mortality reduction, lowest w/ glucose <150 (Furnary AP et al. 1999) Diabetics with AMI IV insulin for 24 hrs then daily MDI x 3 months (126-180 mg/dL) vs. “conventional treatment” Long-term survival improved 28% (Malmberg K et al. 1999) Wardsprospective observational studiesHyperglycemia associated with nosocomial infections and mortality (Umpierrez GE et al 2004)

8. Hyperglycemia Key Points Diabetes is a Vascular Disease Regardless of a prior history of DM, keeping glucose 80-110 mg/dl leads to better outcomes Standardized protocols improve glycemic control and lower rates of hypoglycemia Follow-up is essential

9. Thyroid How can I distinguish euthyroid sick syndrome from hypothyroidism?

10. The euthyroid sick syndrome is an adaptive response to illness Not a primary thyroid disorder Results from changes in peripheral thyroid hormone metabolism and transport Causes include infection, malignancy, inflammation, MI, surgery, trauma, starvation

11. Thyroid Functions in Acute Illness TSH levels normal or slightly low Total T4 decreases, and T3 resin uptake increases from reduced protein binding Free T4 usually normal Low total & free T3 from impaired conversion of T4 to T3 in liver Elevated rT3 De Groot LJ et al, 2006

12. Distinction of Euthyroid Sick Syndrome from Hypothyroidism TSHTT4FT4T3RT3T3RU Euthyroid Sick↓↓↔↓↓↑↑ Hypothyroid↑↓↓↓↓↓

13. Treat Euthyroid Sick Syndrome? No consistent or convincing data demonstrating a recovery or survival benefit from treating euthyroid sick syndrome patients with either levothyroxine (LT4) or liothyronine (LT3)

14. THYROID KEY POINTS Only check TSH if high likelihood of thyroid disease Euthyroid sick syndrome is an adaptive response to illness Do not treat euthyroid sick syndrome

15. Adrenal What is the proper way to distinguish primary from secondary adrenal failure?

16. Hypothalamic-Pituitary Adrenal Axis Secondary disorders more common in the hospital Exogenous steroids Opiates Pituitary adenomas Panhypopituitarism Stalk disruption Subarachnoid hemorrhage

17. Diagnosis of Adrenal Failure RANDOM TESTING Diagnose with a cortisol <5 μg/dL during severe physiologic stress Rule-out with a random cortisol >20 ug/dL Simultaneous measurement of ACTH is helpful DYNAMIC TESTING 250 mcg IV Cosyntropin Cortisol level >20ug/dL after 30-60 minutes excludes diagnosis Does not rule out a subtle or recent ACTH deficiency Additional testing (insulin-induced hypoglycemia, low dose-ACTH) may be necessary to demonstrate appropriate response to stress Wiebke A et al. Lancet 2003; 361: 1881-93

18. Algorithm for Suspected AI Levy NT et al. (Mayo Clin Proc 1997;72:818-822)

19. ADRENAL KEY POINTS Think about adrenal failure Empiric dexamethasone will not interfere with the measurement of cortisol but will suppress ACTH When in doubt, give empiric steroids and reassess later on

20. Hypercalcemia How can I treat hypercalcemia without obscuring the diagnosis?

21. PTH or non-PTH-Mediated? If PTH is upper-normal or high then it’s likely primary hyperparathyroidism If PTH is suppressed than it’s likely malignancy or extra-renal vitamin D production Ca ++, urine Ca/cr, 25 and 1,25 vitamin D Empirically treat once labs are drawn Al Zahrani et al. Lancet 1997;352:306-311

22. Volume Replacement Calcium >12 mg/dL requires urgent treatment First administer normal saline to enhance delivery of calcium to loop of Henle Once euvolemic, give loop diuretic to enhance calciuresis If still hypercalcemic, give loading dose of vitamin D along with IV bisphosphonate

23. Bisphosphonates for Hypercalcemia Zolendronic acid 4 mg or 8 mg IV are superior to Pamidronate in hypercalcemia of malignancy If given to patients with vitamin D insufficiency (50% of the population), profound hypocalcemia may occur Give loading dose of vitamin D 50,000 units PO Major P et al., J Clin Onc 2001; 19:558-567

24. CALCIUM KEY POINTS Primary hyperparathyroidism and malignancy account for >90% of causes of hypercalcemia 10-20% pts with primary hyperparathyroidism have iPTH in upper normal range Most patients are volume depleted Indiscriminate use of bisphosphonates may lead to profound hypocalcemia

25. Thank You