6 - Endocrine Therapies

Editors: Susla, Gregory M.; Suffredini, Anthony F.; McAreavey, Dorothea; Solomon, Michael A.; Hoffman, William D.; Nyquist, Paul; Ognibene, Frederick P.; Shelhamer, James H.; Masur, Henry

Title: Handbook of Critical Care Drug Therapy, 3rd Edition

Copyright 2006 Lippincott Williams & Wilkins

> Table of Contents > Chapter 6 - Endocrine Therapies

Chapter 6

Endocrine Therapies

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TABLE 6.1. Corticosteroid Potencies

Agent	Equivalent Dose	Relative Mineralocorticoid Effecta	Biologic Half-Life
Short-Acting
Cortisone	25 mg	++	8 h
Hydrocortisone	20 mg	++	8 h
Intermediate-Acting
Prednisone	5 mg	+	18 h
Prednisolone	5 mg	+	18 h
Methylprednisolone	4 mg	0	18 h
Long-Acting
Dexamethasone	0.75 mg	0	36 h
aRange of mineralocorticoid effect is from ++ (highest) to 0 (none).

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TABLE 6.2. Thyroid, Pituitary, and Adrenal Hormonal Replacement

Agent	Indications	Dosage	Comments
Thyroid
Levothyroxine (T4, L-thyroxine)	Hypothyroidism, myxedema coma	Initial replacement: 25 50 g PO qd	Converted to T3 in periphery
		Maximum replacement: 200 g PO qd	Follow TSH for normalization and patient's clinical status
		In critically ill with myxedema coma: 200 500 g IV/day slowly	For stupor or coma, treat with 200 500 g IV bolus followed by 75 g/day; consider hydrocortisone 50 100 mg IV q8h 5 d as adjunctive therapy for hypocortisolism
			Half-life: euthyroid, 6 d; hypothyroid, 8 d; hyperthyroid, 3 d
			IV dose = 75% of PO dose (for replacement therapy)
			Preferred over T3 for critically ill patients
			Many experts prefer the lower doses initially for safety, especially in the elderly, comatose, and those with heart disease
			May precipitate angina or arrhythmias
Liothyronine (T3, triiodothyronine)	Hypothyroidism, myxedema coma	Replacement: 25 75 g PO qd	Assessment of therapy is more difficult; wait at least four hours after IV dose
		Myxedema coma: 12.5 25 g IV q6h	Half-life: euthyroid, 24 h; hypothyroid, 38 h; hyperthyroid, 17 h
Pituitary/Adrenal
Synthetic ACTH (cosyntropin)	Screening test for adrenal insufficiency	250 g (25 units) IV/IM	Some authors recommend using smaller doses such as 1 g for assessment of HPA axis
			Normal function is indicated by control cortisol level >5 g/dl and 30 min post level >18 g/dl with an increase of 7 g/dl above control
			Small doses of prednisone will not affect cortisol response
			Dexamethasone does not affect cortisol response
Fludrocortisone	Mineralo-corticoid replacement in primary adrenal insufficiency	50 200 g PO qd	Titrated to achieve normal serum potassium and blood pressure
			Not required in secondary adrenal insufficiency
Hydrocortisone	Replacement	25 mg IV/PO q AM and 12.5 mg IV/PO q PM	For equivalent corticosteroid dosages, see Table 6.1
	Stress	50 100 mg IV/PO q8h	For treatment of adrenal insufficiency complicating critical illness, maximum dose of glucocorticoid should be equivalent to hydrocortisone 300 mg/d
	Preoperative	1 d preoperatively: 25 mg IV/PO at 6 PM and midnight	For patients who may have adrenal insufficiency
		Day of operation: 50 mg IV during surgery
		Postoperative: 50 mg IV q8h 24 h, then 25 mg IV/PO q8h 24 48 h
Desmopressin	Diabetes insipidus	Intranasal: 10 40 g in 1 3 divided doses daily	May cause hypertension, water retention, headache, abdominal cramps; swelling and burning may occur at the injection site after SC administration
		SC/IV: 2 4 g in 2 divided doses daily
HPA, hypothalamic-pituitary-adrenal; IM, intramuscular; IV, intravenous; PO, by mouth; SC, subcutaneous; TSH, thyroid stimulating hormone

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TABLE 6.3. Therapy for Thyrotoxicosis

Drug	Indication	Dosage/Route	Comment
Thiourea Agents	Used when radioisotopes are NOT indicated: e.g., children, young adults, pregnancy, mild thyrotoxicosis, small goiters Preparing hyperthyroid patients for surgery and elderly patients for radioactive iodide treatment		Inhibit thyroid hormone synthesis Low incidence of posttreatment hypothyroidism Complications: agranulocytosis (0.1% to 0.4% of patients) Definitive therapy required; relapses after these agents discontinued
Propylthiouracil		100 300 mg PO q6 8h (<200 mg/d during pregnancy)	Drug of choice during pregnancy Complication (rare): hepatic necrosis
Methimazole		80 120 mg PO qd	Less frequent dosing than propylthiouracil Lower incidence of hepatitis
Iodide	Thyroid storm		Inhibits thyroid hormone release
Lugol's solution (7 mg l/drop)		3 10 gtts PO tid	Cannot be used as sole therapy
SSKI (35 mg I/drop)		5 gtts PO qid
Other Agents
Radioactive iodine (l131)	Generally used in older patients (>25 years) because of theoretical risk of carcinogenesis		Destroys cells that concentrate iodine Never used in pregnant patients
Propranolol	Antagonism of peripheral effects of hormone Symptomatic relief of tremor, tachycardia, etc. Initial treatment of choice for thyroid storm	10 40 mg PO q6 8h 1 mg IV aliquots up to 0.15 mg/kg 3 5 mg/h infusion	Dose adjusted to response in heart rate (goal is 100 beats/min) Other -blockers may be equally effective
Dexamethasone	Thyroid storm	2 mg IV q6h	Inhibits thyroid hormone release
IV, intravenous; PO, by mouth

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TABLE 6.4. Ketoacidosis and Hyperosmolar Coma

Syndrome	Situation	Therapy	Comments
Diabetic ketoacidosis	Fluid deficit	Initially isotonic fluids, 1 L rapidly, then 1 L/h after clinical response of patient	Rate and type of fluid is adjusted according to laboratory results and patient response 0.45% NaCl can be alternated with 0.9% NaCl Dextrose may be added to the IV fluids when the blood glucose falls below 300 mg/dl
	Hyperglycemia	Regular insulin 6 10 U/h IV infusion	Blood glucose must be monitored every 2 h Insulin infusion rate should be titrated to reduce blood glucose by 60 100 mg/dl/h to glucose of 300 mg/dl
	Hypokalemia	Potassium 10 40 mEq/h	Serum potassium may be elevated acutely in the presence of acidosis, but total body potassium is reduced
			Correction of acidosis and insulin administration will reduce serum potassium levels
			Administration should begin when the measured potassium level is in the normal range
			Administer with caution to patients with renal insufficiency
			Administer as the chloride or phosphate salt
	Acidosis	Bicarbonate	Usually unnecessary unless pH <6.9 or arrhythmias are present
	Hypophosphatemia	Potassium phosphate or sodium phosphate	Guide by serum phosphate level
Hyperosmolar nonketotic coma	Dehydration	1 L 0.45% NaCl rapidly, then 1 L/h for several h	A major free water deficit is usually present Rehydration is the major therapy Neurologic status should be monitored frequently because of the possibility of cerebral edema from too rapid a fall in serum osmolality
	Hyperglycemia	Regular insulin 3 5 U/h IV infusion	Goal of insulin therapy is to achieve a blood glucose of 250 300 mg/dl
			Patients are quite sensitive to the effects of insulin; blood glucose should be lowered at a rate of 60 100 mg/dl/h
			Because blood glucose can fall precipitously, insulin infusion rates should be more conservative than in patients with diabetic ketoacidosis
Alcoholic Ketoacidosis			Usually when PO intake stopped Management is correction of fluid, electrolyte, and acid-base abnormalities that affect the chronic alcoholic Blood glucose usually is <200 mg/dl
IV, intravenous; PO, by mouth

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TABLE 6.5. Insulin Preparations

Preparation	Onset	Peak	Duration	Comments
Short-Acting
Regular	IV: 10 30 min SC: 30 60 min	IV: 30 min SC: 2 3 h	IV: 1 h SC: 5 7 h	Preferred for ketoacidosis and other conditions with rapidly changing requirements Only form of insulin that can be given IV
Semilente	SC: 30 90 min	SC: 4 10 h	SC: 12 16 h	Not for IV administration
Lispro	SC: 0.25 h	SC: 0.5 1.5 h	SC: 2.5 5 h	Not for IV administration
Insulin aspart	SC: 0.25 h	SC: 1 3 h	SC: 3 5 h	Not for IV administration
Insulin glulisine		SC: 0.5 1.5 h	SC: 1 2.5 h	Not for IV administration
Intermediate-Acting
NPH	SC: 1 2 h	SC: 4 12 h	SC: 18 24 h	Not for IV administration
Lente	SC: 1 2.5 h	SC: 7 15 h	SC: 18 24 h	Not for IV administration
Long-Acting
Protamine zinc	SC: 6 8 h	SC: 18 24 h	SC: 36 h	Not for IV administration
Ultralente	SC: 4 8 h	SC: 10 30 h	SC: 36 h	Not for IV administration
IV, intravenous; SC, subcutaneous

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TABLE 6.6. Hyperglycemia: Regular Insulin Sliding Scales

Subcutaneous (SC) Dosing
Blood glucose concentration (mg/dL)	SC regular insulin (units)
<180
180 240	2
240 300	4
300 360	6
360 400	8
>400	10 12
IV Continuous Dosing
Blood glucose concentration (mg/dL)	IV infusion rate (U/h)
<120
120 179	0.5 1
180 240	1 2
241 300	2
301 360	3
361 400	4
>400	6 8
Administer insulin not more than every 4 hours. Not for patients with shock or other hypoperfusion states. Monitor serum glucose every 2 to 4 hours; may alternate with finger stick glucose measurements.

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TABLE 6.7. Amylin Analog

Conversion of Pramlintide to Insulin Unit Equivalents
Prescribed Pramlintide Dose ( g)	Insulin Unit Equivalents Using U-100 Syringe (Units)	Corresponding Volume (ml)
15	2.5	0.025
30	5	0.05
45	7.5	0.075
60	10	0.1
120	20	0.2
Pramlintide is an adjunct treatment in patients who use mealtime insulin therapy and who have failed to achieve desired glucose control despite optimal insulin therapy. Pramlintide is not indicated for acute glucose management in critically ill patients and should be discontinued in this setting. Pramlintide therapy should only be restarted after the patient's critical illness has resolved, and the patient is consuming a stable caloric intake. Titration of the patients's insulin dose, oral hypoglycemic dose, and pramlintide may be required in this setting. Patients should be monitored at regular intervals to assess the effect on blood glucose. Pramlintide Dosage and Administration Pramlintide should be administered using a 0.3 ml, U-100 insulin syringe. The pramlintide dose may be prescribed in micrograms, but it will be administered in Units indicated on the U-100 insulin syringe. Table 6.7 outlines the conversion of the pramlintide dose prescribed in micrograms to the administration dose in Units.

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TABLE 6.8. Oral Hypoglycemic Agents

Agent	Starting Dosage	Onset/Duration	Comments
Sulfonylurea
Glimepiride	1 2 mg PO qd	Onset: 2 3 h Duration: 24 h	Lower dosage in elderly and those with hepatic or renal disease because of risk of hypoglycemia
Glipizide	5 mg PO qd	Onset: 1 h Duration: 10 24 h	As potent as glyburide Contraindicated in patients with renal or hepatic impairment
Glyburide	2.5 mg PO qd	Onset: 1.5 h Duration: 18 24 h	Prolonged biologic effect despite short half-life (1 2 h)
-Glucosidase Inhibitor
Acarbose	25 mg PO tid	Onset: unknown Duration: unknown	Delays glucose absorption from GI tract Not recommended in patients with renal impairment GI side effects
Miglitol	25 100 mg PO tid	Onset: unknown Duration: unknown	Delays glucose absorption from GI tract Not recommended in patients with renal impairment GI side effects
Bioguanide
Metformin	500 mg PO bid	Onset: 1 3 h Duration: 24 h	May increase serum levels of cimetidine May decrease absorption of vitamin B12 and folic acid causing deficiencies May cause lactic acidosis, especially in patients with renal impairment; stop drug in setting of excessive ethanol ingestion, hypoxemia, shock, hepatic failure or surgery
			GI side effects
Meglitinides
Repaglinide	0.5 4 mg PO tid before meals	Onset: unknown Duration: unknown	Take 15 30 min before meals Starting dose in patients with severe renal function is 0.5 mg
Nateglinide	60 120 mg PO tid before meals	Onset: unknown Duration: unknown	Take 15 30 min before meals Use with caution in patients with chronic liver disease
Thiazolidinedione
Pioglitazone	15 45 mg PO qd	Onset: unknown Duration: unknown	Usually used in combination with sulfonylureas, metformin, or insulin Check LFT before beginning therapy
			Contraindicated in liver disease when ALT >2.5 ULN
			Can cause fluid retention and may exacerbate HF
			Drug interactions with CYP450 3A4 substrates
Rosiglitazone	2 8 mg PO qd	Onset: unknown Duration: unknown	Usually used in combination with sulfonylureas, metformin, or insulin Check LFT before beginning therapy
			Contraindicated in liver disease when ALT >2.5 ULN
			Contraindicated in renal impairment
			Can cause fluid retention and may exacerbate HF
ALT, aminotransferase; GI, gastrointestinal; HF, heart failure; LFT, liver function tests; PO, by mouth; ULN, upper limit of normal