Handbook of Clinical Anesthesia

Chapter 49

Endocrine Function

An understanding of the pathophysiology of endocrine function is important in the management of anesthesia for patients with disorders of the hormone-producing glands (Schwartz JJ, Akhtar S, Rosenbaum SH: Endocrine function. In Clinical Anesthesia. Edited by Barash PG, Cullen BF, Stoelting RK, Cahalan MK, Stock MC. Philadelphia: Lippincott Williams & Wilkins, 2009, pp 1279–1304).

  1. Thyroid Gland
  2. Thyroid Metabolism and Function.Thyroxine (T4) and triiodothyronine (T3) are the major regulators of cellular metabolic activity. The thyroid gland is solely responsible for the daily secretion of T4 (80–100 µg/day; elimination half-time, 6–7 days). About 80% of T3 is produced by extrathyroidal deiodination of T4 (elimination half-time, 24–30 hours). Thyroid hormone synthesis occurs in four stages (Fig. 49-1). Most of the excess effects of thyroid hormones (hyperadrenergic state) are mediated by T3 (Table 49-1).
  3. Tests of Thyroid Function(Table 49-2)
  4. Hyperthyroidism
  5. Treatment and Anesthetic Considerations(Table 49-3)
  6. A combination of propranolol (effective in attenuating the manifestations of excessive sympathetic nervous system activity, as evidenced by a heart rate <90 bpm) and potassium iodide (inhibits hormone release) is effective in rendering patients “euthyroid” before anesthesia and surgery. Esmolol may be administered as a continuous intravenous (IV) infusion to maintain the heart rate below 90 bpm.



Figure 49-1. Schematic depiction of the four stages of synthesis and release of thyroid hormone. T3 = triiodothyronine; T4 = thyroxine; TSH = thyroid-stimulating hormone.

Table 49-1 Effects of Triiodothyronine on Receptor Concentrations

Increased number of β-receptors
Decreased number of cardiac cholinergic receptors


Table 49-2 Tests of Thyroid Function


Serum Thyroxine

Serum Triiodo-thyronine

Thryoid Hormone Binding Rate

Thyroid Stimulating Hormone





Normal to low

Primary hypothy-roidism


Normal to low



Secondary hypothyroidism





Sick euthy-roidism










  1. The goal of intraoperative management is achievement of a depth of anesthesia (often with isoflurane or desflurane) that prevents an exaggerated sympathetic nervous system response to surgical stimulation. Drugs that activate the sympathetic nervous system (e.g., ketamine) or increase the heart rate (e.g., pancuronium) are not likely to be recommended.
  2. If a regional anesthetic is selected, epinephrine should not be added to the local anesthetic solution.

Table 49-3 Preparation of Hyperthyroid Patients

Propylthiouracil (inhibits synthesis and decreases peripheral conversion of T4 to T3)
Inorganic iodide (inhibits hormone release)
β-Adrenergic antagonists (propranolol administered over 12 to 24 hours decreases the heart rate to <90 bpm)
Iopanoic acid (radiographic contrast agent that decreases peripheral conversion of T4 to T3)
Glucocorticoids (decrease hormone release and peripheral conversion of T4 to T3)

T3 = triiodothyronine; T4 = thyroxine.

  1. P.785

Table 49-4 Possible Complications of Thyroid Surgery

Thyroid storm (should be distinguished from malignant hyperthermia, pheochromocytoma, and inadequate anesthesia; it most often develops in undiagnosed or untreated hyperthyroid patients because of the stress of surgery)
Airway obstruction (diagnosed with CT of the neck)
Recurrent laryngeal nerve damage (hoarseness may be present if the damage is unilateral, and aphonia may be present if the damage is bilateral)
Hypoparathyroidism (symptoms of hypocalcemia develop within 24 to 48 hours and include laryngospasm)

CT = computed tomography.

  1. Anesthesia for thyroid surgery(subtotal thyroidectomy) is an alternative to prolonged medical therapy. Complications associated with surgery occur more frequently when preoperative preparation is inadequate (Tables 49-4 and 49-5).
  2. It is useful to evaluate vocal cord function in the early postoperative period by asking patients to say the letter “e.”
  3. Unexpected difficult intubation is increased in the presence of goiter. (Inhalation induction or awake fiberoptic intubation should be considered if there is evidence of significant airway obstruction or tracheal deviation or narrowing.)

Table 49-5 Management of Thyroid Storm

IV fluids
Sodium iodide (250 mg orally or IV every 6 hr)
Propylthiouracil (200–400 mg orally or via a nasogastric tube every 6 hr)
Hydrocortisone (50–100 mg IV every 6 hr)
Propranolol (10–40 mg orally every 4–6 hr) or esmolol (titrate)
Cooling blankets and acetaminophen (12.5 mg IV of meperidine every 4–6 hr may be used to treat or prevent shivering)
Digoxin (congestive heart failure with atrial fibrillation and rapid ventricular response)

IV = intravenous.

  1. P.786

Table 49-6 Manifestations of Hypothyroidism

Cold intolerance
Decreased cardiac output and heart rate
Peripheral vasoconstriction
Heart failure (unlikely unless coexisting cardiac disease is present)
Decreased platelet adhesiveness
Anemia (GI bleeding)
Impaired renal concentrating ability
Adrenal cortex suppression
Decreased GI motility (may compound the effects of postoperative ileus)

GI = gastrointestinal.

  1. Postoperative airway obstruction caused by hematoma or tracheomalacia may require urgent reintubation of the trachea.
  2. Operating on an acutely hyperthyroid patient may provoke thyroid storm.
  3. Hypothyroidism
  4. Hypothyroidism is a relatively common disease (0.5%–0.8% of the adult population) that results from inadequate circulating levels of T4, T3, or both (Table 49-6).
  5. Treatment and Anesthetic Considerations
  6. No evidence supports postponement of elective surgery (including coronary artery bypass graft surgery) in the presence of mild to moderate hypothyroidism.
  7. No evidence supports the choice of a specific anesthetic technique or selection of drugs for hypothyroid patients, although opioids and volatile anesthetics are often considered to have increased depressant effects in these patients. There appears to be little, if any, decrease in anesthetic requirements as reflected by the minimum alveolar concentration.
  8. Meticulous attention must be paid to maintaining body temperature.
  9. Myxedema coma is a medical emergency that requires aggressive therapy (Table 49-7).


Table 49-7 Management of Myxedema Coma

Tracheal intubation and controlled ventilation of the lungs as needed
Levothyroxine (200–300 mg IV over 5–10 min)
Cortisol (100 mg IV and then 25 mg IV every 6 hr)
Fluid and electrolyte therapy as guided by serum electrolyte measurements
Warm environment to conserve body heat

IV = intravenous.

  1. Parathyroid Glands
  2. Calcium Physiology.Parathyroid hormone secretion is regulated by the serum ionized calcium concentration (negative feedback mechanism) to maintain calcium levels in a normal range (8.8–10.4 mg/dL).
  3. Hyperparathyroidism
  4. Hypercalcemia is responsible for a broad spectrum of signs and symptoms (e.g., nephrolithiasis, confusion).
  5. Treatment and Anesthetic Considerations.Preoperative IV administration of normal saline and furosemide may lower serum calcium concentrations. There is no evidence that a specific anesthetic drug or technique is preferred. A cautious approach to the use of muscle relaxants is suggested by the unpredictable effect of hypercalcemia at the neuromuscular junction. Careful positioning of osteopenic patients during surgery is necessary to minimize the likelihood of pathologic bone fractures.
  6. Hypoparathyroidism.Clinical features are manifestations of hypocalcemia, and treatment is with calcium gluconate (10–20 mL of 10% solution IV) (Table 49-8).

Table 49-8 Manifestations of Hypocalcemia

Neuronal irritability
Skeletal muscle spasms
Congestive heart failure
Prolonged Q-T interval on the electrocardiogram


Table 49-9 Comparative Pharmacology of Corticosteroids*




Approximate Equivalent Dose (mg)

Short Acting

Cortisol (hydrocortisone)




















Intermediate Acting





Long Acting





*The glucocorticoid and mineralocorticoid properties of cortisol are considered to be equivalent to 1.

III. Adrenal Cortex

  1. The biologic effects of adrenal cortex dysfunction reflect cortisol or aldosterone excess or deficiency (Table 49-9).
  2. Glucocorticoid Excess (Cushing's Syndrome)(Table 49-10)
  3. The diagnosis of hyperadrenocorticism is established by failure of the exogenous administration of dex-amethasone to suppress endogenous cortisol secretion.
  4. Anesthetic Management(Table 49-11). Etomidate has been used for temporizing medical treatment of severe Cushing's disease because of its inhibition of steroid synthesis.

Table 49-10 Manifestations of Glucocorticoid Excess

Truncal obesity and thin extremities (reflects redistribution of fat and skeletal muscle wasting)
Hypertension (fluid retention)
Emotional changes
Susceptibility to infection

  1. P.789

Table 49-11 Management of Patients Undergoing Adrenalectomy

Regulate hypertension
Control diabetes
Normalize intravascular fluid volume (diuresis with spironolactone helps mobilize fluid and normalize the potassium concentration)
Glucocorticoid replacement (cortisol 100 mg IV every 8 hr)
Careful patient positioning on the operating table (osteopenic)
Decrease the initial dose of muscle relaxant if skeletal muscle weakness is present

IV = intravenous.

  1. Mineralocorticoid excessshould be considered in nonedematous hypertensive patients who have persistent hypokalemia and are not receiving potassium-wasting diuretics.
  2. Adrenal Insufficiency (Addison's Disease)
  3. Clinically, primary adrenal insufficiency is usually not apparent until at least 90% of the adrenal cortex has been destroyed.
  4. Clinical presentationalmost always includes hypotension. (A high degree of suspicion should be maintained for patients who demonstrate cardiovascular instability without a defined cause.)
  5. Treatment and Anesthetic Considerations.Immediate therapy consists of electrolyte resuscitation (glucose in normal saline) and steroid replacement (100 mg IV every 6 hours for 24 hours). Inotropic support is indicated if hemodynamic instability persists despite adequate fluid resuscitation.
  6. Steroid Replacement During the Perioperative Period
  7. Patients with adrenal insufficiency and those with hypothalamic–pituitary adrenal (HPA) axis suppression from chronic steroid use require additional corticosteroids to mimic the increased output of the normal adrenal gland during stress.
  8. Normal adrenal gland can secrete up to 200 mg/day of cortisol and may secrete between 200 and 500 mg/day during stress.
  9. The HPA axis is considered to be intact if plasma cortisol levels are greater than 22 µg/dL during acute stress.
  10. Regional anesthesia postpones the elevation in plasma cortisol levels evoked by surgery, and deep


general anesthesia suppresses the elevation of stress hormones.

  1. Despite symptoms of clinically significant adrenal insufficiency during the perioperative period, these findings have rarely been documented in direct association with glucocorticoid deficiency.
  2. Identifying patients who require steroid supplementation is not practical. (Provocative testing with adrenocorticotrophic hormone [ACTH] stimulation is too costly compared with the risk of brief steroid supplementation.)
  3. HPA axis suppression may occur after five daily doses of prednisone of 20 mg or more. Suppression may also occur with topical, regional, and inhaled steroids. (Alternate-day therapy decreases the risk of suppression.)
  4. Recovery of HPA axis function occurs gradually and can take up to 9 to 12 months.
  5. There is no proven optimal regimen for perioperative steroid replacement (low-dose vs high-dose replacement) (Table 49-12). Patients who are using steroids at the time of surgery should receive their usual dose on the morning of surgery and are supplemented at a level that is at least equivalent to the usual daily replacement. Cortisol coverage is rapidly tapered to the patient's normal maintenance dosage during the postoperative period.
  6. Although no conclusive evidence supports an increased incidence of infection or abnormal wound healing when supraphysiologic doses of supplemental steroids are used acutely, the goal of therapy is to use the minimal drug dosage necessary to adequately protect the patient.
  7. Exogenous Glucocorticoid Therapy(see Table 49-9)

Table 49-12 Supplemental Steroid Coverage Regimens

Physiologic (low-dose approach)
Cortisol 25 mg IV before induction of anesthesia followed by a continuous infusion (100 mg IV over 24 hr)
Cortisol 200–300 mg IV in divided doses on the day of surgery

IV = intravenous.


Table 49-13 Manifestations of Pheochromocytoma

Sustained (occasionally paroxysmal) hypertension (headaches)
Masquerade as malignant hyperthermia
Cardiac dysrhythmias
Orthostatic hypotension (decreased blood volume)
Congestive heart failure

  1. Adrenal Medulla

The adrenal medulla is analogous to a postganglionic neuron, although the catecholamines it secretes function as hormones, not as neurotransmitters.

  1. Pheochromocytoma.These tumors produce, store, and secrete catecholamines that may result in life-threatening cardiovascular effects (Table 49-13).
  2. Diagnosisof pheochromocytoma is based on measurement of catecholamines in the plasma and catecholamine metabolites (vanillylmandelic acid) in the urine. Excess production of catecholamines is diagnostic for pheochromocytoma. Computed tomography or magnetic resonance imaging may be used to localize these tumors.
  3. Anesthetic Considerations
  4. Preoperative preparationconsists of α blockade (phentolamine, prazosin) initiated before surgery, if possible, and restoration of intravascular fluid volume. β blockade is indicated only if cardiac dysrhythmias or tachycardia persists after institution of α blockade. The goals of medical therapy are to control heart rate, suppress cardiac dysrhythmias, and prevent paroxysmal increases in blood pressure.
  5. Perioperative Anesthetic Management(Table 49-14)
  6. Postoperatively, plasma catecholamine levels return to normal over several days, and about 75% of patients become normotensive within 10 days.
  7. Diabetes Mellitus

Diabetes mellitus is the most common endocrine disease present in surgical patients (25% to 50% of diabetics require surgery). It is a disease with a broad range of severity, and its manifestations can be altered (unmasked for the first time) in response to stress as produced by surgery.


Table 49-14 Anesthetic Management of Patients with Pheochromocytoma

Continue preoperative medical therapy.
Perform invasive monitoring (arterial and pulmonary artery catheters, TEE).
Ensure an adequate depth of anesthesia before initiating direct laryngoscopy for tracheal intubation.
Maintain anesthesia with opioids and a volatile anesthetic that does not sensitize the heart to catecholamines.
Select muscle relaxants with minimal cardiovascular effects.
Control systemic blood pressure with nitroprusside or phentolamine (magnesium, nitroglycerin, and calcium channel blockers may be alternative vasodilator drugs).
Control tachydysrhythmias with propranolol, esmolol, or labetalol.
Anticipate hypotension with ligation of the tumor's venous blood supply. (initially treat with IV fluids and vasopressors; continuous infusion of norepinephrine is an option if necessary).

IV = intravenous; TEE = transesophageal echocardiography.

  1. Classification(Table 49-15)
  2. Treatment(Table 49-16)
  3. Anesthetic Management
  4. Preoperative(Table 49-17). It is axiomatic that the patient should be in the best state of metabolic control that is possible preoperatively.
  5. Intraoperative.The details of the anesthetic plan depend ultimately on the presence of end-organ


disease. Invasive monitoring may be indicated for the patient with heart disease. Fluid management and drug selection may be influenced by renal function, and aspiration considerations may be affected by the presence of gastroparesis.

Table 49-15 Classification of Diabetes Mellitus

Type I (Insulin Dependent)
Childhood onset
Prone to ketoacidosis
Always requires exogenous insulin
Type II (Non–Insulin Dependent)
Maturity onset
Not prone to ketoacidosis
May be controlled by diet or oral hypoglycemic drugs
Gestational Diabetes
May presage future type II diabetes mellitus

Table 49-16 Treatment of Diabetes Mellitus






Diet and exercise
Sulfonylureas (enhances insulin secretion by β cells)
Metformin (enhances sensitivity of hepatic and peripheral tissues to insulin)
Thiazolidinediones (increase insulin sensitivity)
α-Glucosidase inhibitors (decrease postprandial glucose absorption)

  1. Blood glucose levels should be measured preoperatively and postoperatively. The need for additional measurements is determined by the duration and magnitude of surgery and the stability of the patient's diabetes.
  2. Dehydration may be present on the patient's arrival in the operating room based on osmotic diuresis.

Table 49-17 Preoperative Evaluation of Patients with Diabetes Mellitus

History and physical examination (detect symptoms of cerebrovascular disease, coronary artery disease, peripheral neuropathy)
Laboratory tests (electrocardiography; blood glucose, creatinine, and potassium levels; urinalysis [glucose, ketones, albumin])
Evidence of stiff joint syndrome (difficult-to-perform laryngoscopy)
Evidence of cardiac autonomic nervous system neuropathy (resting tachycardia, orthostatic hypotension)
Evidence of vagal autonomic nervous system neuropathy (gastroparesis slows emptying of solids [metoclopramide may be useful] but probably not clear fluids)
Autonomic neuropathy predisposes the patient to intraoperative hypothermia


  1. It is important to note the amount of glucose administered IV to avoid an overdose. (The standard glucose dose for adults is 5–10 g/hr or 100–200 mL of 5% glucose/hr.)
  2. Another area of patient monitoring that is extremely important in patients with diabetes is positioning on the operating table. These patients' peripheral nerves may already be partly ischemic and are therefore uniquely susceptible to pressure or stretch injuries.
  3. Glycemic Goals(Table 49-18). Although the association between perioperative hyperglycemia and poor outcomes is strong, the value of controlling glucose levels tightly intraoperatively has not been proven conclusively. It may be prudent to maintain glucose levels at 180 mg/dL or below, especially in the perioperative period.
  4. Management of Perioperative Hyperglycemia.Many factors influence glucose levels in the perioperative period and the regimen selected to control hyperglycemia (Table 49-19). The goal of any regimen is to minimize metabolic derangements and avoid hypoglycemia (Table 49-20).
  5. Emergencies
  6. Hyperosmolar Nonketotic Coma(Table 49-21)
  7. Diabetic Ketoacidosis.Manifestations of diabetic ketoacidosis reflect insufficient insulin to block the


metabolism of fatty acids, resulting in the accumulation of acetoacetate and β-hydroxybutyrate (Table 49-22). Because leukocytosis, abdominal pain, ileus, and mildly elevated amylase levels are common in the presence of diabetic ketoacidosis, an occasional


patient is misdiagnosed as having an intra-abdominal surgical problem. Treatment of diabetic ketoacidosis includes insulin administration and fluid and electrolyte evaluation and management (Table 49-23).

Table 49-18 Current Recommendations for Glycemic Control


American College of Endocrinology (2004)

Canadian Diabetic Association (2003)

American Diabetic Association (2007)

AHA/ACC (2007)


Close to 110 mg/dL
Generally ≤180 mg/dL

≤110 mg/dL

≤100 mg/dL

110–180 mg/dL


≤150 mg/dL

90–190 mg/dL


110–180 mg/dL


Noncritically ill (90–130 mg/dL)

90–180 mg/dL


110–180 mg/dL

AHA = American Heart Association; ACC =American College of Cardiology; ICU = intensive care unit.

Table 49-19 Factors that Influence the Selection of Diabetic Management Regimen

Type of diabetes mellitus
How aggressively euglycemia will be sought
Whether the patient takes insulin
Whether surgery is minor and in an ambulatory unit
Whether surgery is elective or emergency
The ability of hospital resources to administer a complex regimen plan

Table 49-20 Intraoperative Management Regimens for Patients with Diabetes Mellitus

Type 1 Diabetes Mellitus
Administer two thirds of the patient's usual intermediate-acting insulin subcutaneously on the morning of surgery.
Titrate regular insulin (sliding scale) based on blood glucose measurement or infuse insulin (0.5–2.0 U/hr or 100 U of regular insulin in 1000 mL of normal saline at 5–20 mL/hr) adjusted to maintain blood glucose at the desired level.
Infuse glucose (5% at 75–125 mL/hr) to prevent hypoglycemia while fasting.
Type II Diabetes Mellitus
Hold sulfonylureas while the patient is NPO (this decreases the risk of hypoglycemia; these drugs interfere with the cardioprotective effect of ischemic preconditioning).
Hold metformin (especially if the patient is at risk for decreased renal function perioperatively and associated risk of lactic acidosis).
Continue thiazolidinediones (these do not predispose patients to hypoglycemia).
Hold α-glucosidase inhibitors (these only work with meals).
Treat patients receiving insulin as type I diabetics.
Transition the patient to a chronic regimen as he or she resumes oral intake.
Type II diabetics who undergo gastric bypass surgery may have rapid resolution of glucose intolerance (the need for oral agents or insulin is reduced).

Table 49-21 Manifestations of Hyperosmolar Nonketotic Coma

Elderly patients with impaired thirst mechanism
Minimal or mild diabetes
Profound hyperglycemia (>600 mg/dL)
Absence of ketoacidosis
Hyperosmolarity (seizures, coma, venous thrombosis)

  1. Hypoglycemiaproduces signs of sympathetic nervous systemic stimulation (tachycardia, hypertension, diaphoresis), which may be masked or misdiagnosed in an anesthetized patient as an inadequate level of anesthesia relative to surgical stimulation.
  2. Diabetic surgical patients are more likely to de-velop hypoglycemia if insulin or sulfonylureas are given without supplemental glucose.
  3. Renal insufficiency prolongs the action of insulin and oral hypoglycemic drugs.
  4. Pituitary Gland

The pituitary gland is divided into the anterior pituitary (thyroid-stimulating hormone, ACTH, gonadotropins, growth hormone) and posterior pituitary (vasopressin, oxytocin). Both are under the control of the hypothalamus.

  1. Anterior Pituitary.Acromegaly poses several problems for anesthesiologists (Table 49-24).
  2. Diabetes insipidusreflects a relative or absolute deficiency of antidiuretic hormone (ADH), resulting in


hypovolemia (inability to concentrate urine) and hypernatremia. ADH is also used in vasodilatory shock as an adjuvant to other pressors.

Table 49-22 Manifestations of Diabetic Ketoacidosis

Metabolic acidosis
Hyperglycemia (300–500 mg/dL)
Dehydration (osmotic diuresis and vomiting)
Hypokalemia (manifests when acidosis is corrected)
Skeletal muscle weakness (hypophosphatemia with correction of acidosis)

Table 49-23 Management of Diabetic Ketoacidosis

10 U IV of regular insulin followed by a continuous IV infusion (insulin in U/hr = blood glucose/150)
IV fluids (isotonic) as guided by vital signs and urine output (anticipate a 4- to 10-L deficit)
10–40 mEq/hr IV of potassium chloride when urine output exceeds 0.5 mL/kg/hr
Glucose 5% 100 mL/hr when serum glucose concentration decreases below 250 mg/dL
Consider IV sodium bicarbonate to correct pH below 6.9

IV = intravenous.

  1. Inappropriate secretion of antidiuretic hormonemanifests as dilutional hyponatremia and decreased serum osmolarity. These changes typically occur in the presence of head injury or an intracranial tumor. Initial treatment is restriction of daily fluid intake to 800 mL.

VII. Endocrine Responses to Surgical Stress

Anesthesia, surgery, and trauma elicit a generalized endocrine metabolic response (increased plasma levels of cortisol, ADH, renin, catecholamines, endorphins) and metabolic changes (hyperglycemia, negative nitrogen balance). Regional anesthesia may block part of the metabolic stress response during surgery (blockade of neural communications from the surgical area).

Table 49-24 Anesthetic Problems Associated with Acromegaly

Hypertrophy of skeletal, connective, and soft tissues
Enlarged tongue and epiglottis (upper airway obstruction)
Increased incidence of difficult intubation
Thickening of the vocal cords (hoarseness; consider awake tracheal intubation)
Paralysis of the recurrent laryngeal nerve (stretching)
Dyspnea or stridor (subglottic narrowing)
Peripheral nerve or artery entrapment
Diabetes mellitus

Editors: Barash, Paul G.; Cullen, Bruce F.; Stoelting, Robert K.; Cahalan, Michael K.; Stock, M. Christine

Title: Handbook of Clinical Anesthesia, 6th Edition

Copyright ©2009 Lippincott Williams & Wilkins

> Table of Contents > Section VII - Anesthesia for Surgical Subspecialties > Chapter 50 - Anesthesia for Otolaryngologic Surgery