Common Endocrine Issues in the Hospitalized Patient

Jordan L. Geller, M.D.

Attending Physician Cedars-Sinai Medical Center

Division of EndocrinologyClinical Instructor of Medicine

UCLA Geffen School of Medicine

 

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?

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

Glycemic Control

What is the optimal blood glucose in an inpatient?

Rationale for Glycemic Control

Effects of hyperglycemia…

Fluid balance Immune function InflammationThrombosisVascular reactivity

Montori VM et al. JAMA. 2002;17:2167-2169

Hyperglycemia is associated with bad outcomes…

• Increased mortality and CHF in patients with acute MI

• Increased mortality, length of stay, prolongednursing home care, higher risk of infection in MICU/SICU

• Greater mortality, increased deep-wound infections, andmore overall infection in post-CABG

• Increased mortality, worse recovery in CVA

American Association of Clinical Endocrinologists, 2004

… insulin improves outcomes

Setting Intervention and Controls Outcome

MICU 80 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)

SICU IV 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)

CSICU IV 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)

Wards prospective observational studies Hyperglycemia associated with nosocomial infections and mortality

(Umpierrez GE et al 2004)

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

Thyroid

How can I distinguish euthyroid sick syndrome from hypothyroidism?

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

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

Distinction of Euthyroid Sick Syndrome from Hypothyroidism

TSH TT4 FT4 T3 RT3 T3RU

Euthyroid Sick ↓ ↓ ↔ ↓↓ ↑ ↑

Hypothyroid ↑ ↓ ↓ ↓ ↓ ↓

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)

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

Adrenal

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

Hypothalamic-Pituitary Adrenal Axis

• Secondary disorders more common in the hospital

Exogenous steroidsOpiatesPituitary adenomasPanhypopituitarismStalk disruptionSubarachnoid hemorrhage

Diagnosis of Adrenal Failure

RANDOM TESTINGRANDOM 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 TESTINGDYNAMIC 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

Algorithm for Suspected AI

Levy NT et al. (Mayo Clin Proc 1997;72:818-822)

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

Hypercalcemia

• How can I treat hypercalcemia without obscuring the diagnosis?

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

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

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

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

Thank You