Endocrine and Metabolic Disorders

Endocrine and Metabolic Disorders

8.1 Diabetes Mellitus

Mark L. Stram

Micah T. Long

Douglas B. Coursin


Diabetes mellitus (DM) is categorized as type 1 or type 2 with additional subtypes. Type 1 patients do not produce endogenous insulin and have absolute insulin deficiency. Patients with type 1 DM have an obligatory need for exogenous insulin to maintain glycemic control and prevent diabetic ketoacidosis (DKA). Exercise- or acute illness-induced metabolic stress exacerbates insulin deficiency. Type 1 DM is generally a disease of childhood and adolescence. Some adults initially appear to have type 2 DM but have autoantibodies to pancreatic islet cells and subsequently become insulin dependent. They have latent autoimmune diabetes of adulthood. They may initially start on oral hypoglycemic agents, which become ineffective and ultimately require insulin.

Cellular insulin resistance and/or impaired insulin release characterize type 2 DM. Patients infrequently develop DKA. Its increased prevalence correlates directly with the obesity epidemic. Hypertension, insulin resistance, dyslipidemia, and truncal obesity comprise the metabolic syndrome and are often present.

Pregnancy results in insulin resistance and relative insufficiency of insulin production, which may result in gestational diabetes (GDM). GDM typically occurs during or after the second trimester and is associated with an increased incidence of preeclampsia, polyhydramnios, fetal macrosomia, neonatal hypoglycemia, and greater incidence of cesarean delivery. Women with GDM are 4.5 times more likely than normoglycemic women to develop type 2 DM within 5 years after delivery. Beyond 5 years, that relative risk jumps to 9.34 fold (1).


Chronic hyperglycemia causes dysfunction in multiple organ systems. Patients with poorly controlled DM have an increased risk of perioperative complications, including wound infections and even death in certain surgical populations. Complications of DM are a result of chronic hyperglycemia-induced tissue glycosylation, oxidative stress, protein kinase C activation, and other factors. Chronic hyperglycemia-induced
soft-tissue changes and cellular swelling affect airway anatomy, which may result in difficult glottic visualization due to stiff tissue and joints. Even accounting for equal degrees of obesity, the airway in patients with diabetes is more likely to be difficult compared to those without DM (2). Furthermore, diabetic autonomic neuropathy delays gastric emptying and can increase aspiration risk.

Individuals with DM have increased risk of cardiovascular morbidity and mortality (3). Vascular disease—microvascular, including nephropathy, retinopathy, and neuropathy; and macrovascular, including arterial atherosclerosis—increases perioperative morbidity. Poor glycemic control increases the risk of MACE and perioperative mortality (3,4). The revised cardiac risk index (RCRI) ranks insulin therapy as one of the six independent predictors for MACE (3). Diabetic autonomic neuropathy can result in blood pressure and heart rate lability and variability resulting in myocardial ischemia and increased risk of cardiopulmonary arrest (5). Signs include postural hypotension, resting tachycardia, peripheral sensory neuropathy, and lack of respiratory pulse variation.

Diabetes causes chronic kidney disease and is a predictor of perioperative AKI independent of pre-existing renal dysfunction (6). Hyperglycemia-induced impairment of autoregulation increases damage already caused by microvascular disease. Diabetes is associated with an increased risk of perioperative surgical site infection (SSI). Soft-tissue changes result in poor wound healing and limited wound tensile strength, and vascular disease diminishes perfusion to tissues. Hyperglycemia has detrimental effects on immune function, and patients may be at increased risk for peripheral nerve injury, soft-tissue compromise, and infection (7).


A systematic approach to preoperative evaluation of a patient with DM is reviewed in Table 8.1. The preoperative period is an opportunity to screen high-risk individuals for DM (Table 8.2) and identify patients with diabetes or prediabetes early in their disease process. Fasting plasma glucose testing is inexpensive and readily available. Values ≥126 mg/dL should be repeated or may be combined with a glycosylated hemoglobin (HbA1c) to confirm the diagnosis. A random sample >200 mg/dL, regardless of fasting state, is strongly suggestive of DM.

Preoperative testing is based on the type of surgery, comorbidities, and the likelihood that testing will change management. Patients having low-risk procedures—without planned use of intravenous iodinated radiocontrast—do not necessarily require preoperative testing beyond a morning blood glucose level. Patients having intermediate- to higher-risk procedures require an HbA1c before surgery as well as a recent assessment of renal function. A serum potassium measurement may be warranted in patients with pre-existing renal disease. Cardiac testing should be based upon the guidelines set forth by the American College of Cardiologists and American Heart Association (see Chapter 3.1).


The American Diabetes Association recommends a preoperative HbA1c goal of ≤7%, while the American College of Endocrinology recommends a level ≤6.5%. The Society

for Ambulatory Anesthesia (SAMBA) Consensus statement states that patients with preoperative hyperglycemia who have adequate long-term glycemic control may proceed to surgery. For patients with chronically poor glycemic control, SAMBA recommends a joint decision with the surgeon considering other comorbidities and risks of surgical complications. SAMBA also recommends postponing surgery if there are complications of hyperglycemia such as dehydration, diabetic ketoacidosis (DKA), or hyperosmolar nonketotic states (9). Some clinicians and institutions routinely specify that the HbA1c must be below a specific level (e.g., HbA1c <7 to 8) for some specific interventions (e.g., elective total joint replacement or spine surgery).

TABLE 8.1 History and Physical Examination


Procedural considerations

  • Type, length, and risks of surgery including blood loss, hypotension, and other specific risks

  • Fasting window and bowel prep (ideally, procedures are scheduled earlier in the day to avoid dysglycemia)

Type of diabetes

  • Type 1 DM = insulin deficiency, type 2 DM = insulin resistance

  • Type 1 DM must have basal insulin to prevent DKA

Duration of disease

  • The number and severity of complications increases over time

  • Fairly low incidence of nephropathy first 10 years of type 2 DM, then increases 2-3% per year for both type 1 and type 2 DM (8)

Glycemic control

  • HbA1c goal: 6.5-7%

  • Home glucose checks and logbook, if available

Hypoglycemic episodes

  • Severity, frequency, and symptoms or lack of hypoglycemia

Hyperglycemic syndromes

  • History of DKA or HHNS and precipitating factors

Cardiovascular disease

  • Evaluate shortness of breath or exercise intolerance

  • Review risk factors for cardiovascular disease

  • History of stroke or transient ischemic attacks

  • Note nephropathy, retinopathy, or neuropathy as indicators of likely significant vascular disease

Autonomic disease

  • History of orthostasis, presyncope, or gastroparesis

  • Other signs of neuropathy

Renal disease

  • Note existing history of nephropathy

  • Determine creatinine and estimated GFR

Home management

Diet and medications

  • Compliance with diet and medications


  • Type, dosage, interval, and dosing indication

  • Hyperglycemia correction ratio

  • Carbohydrate dosing ratio

Other medications

  • Note all diabetes medications, dose, and timing

  • Review other medications with perioperative implications (e.g., ACEIs, ARBs, NSAIDs, beta blockers, antiplatelet agents)

Physical examination


  • Airway assessment emphasizing mouth opening, upper lip bite test, jaw mobility, and neck range of motion

  • ‘Assess for loose teeth, periodontal disease, or odontogenic infections


  • Evaluate for weak or delayed pulses, edema, venous stasis, a gallop rhythm, or a lateral point of maximal impulse

  • Auscultate for carotid and other vascular bruits

  • Review ECG for Q waves indicating prior infarction

Autonomic disease

  • Examine for Charcot foot deformity, loss of vibratory or monofilament sensation (Fig. 8.1)

  • Assess for a loss of heart rate variation with deep breathing, Valsalva, or standing (parasympathetic dysfunction)

  • Assess for a significant blood pressure drop with standing (sympathetic dysfunction)

Skin changes

  • Heavy foot calluses, pretibial skin pigmentation (necrobiosis lipoidica diabeticorum), or chronic ulcerations


  • Note proliferative or nonproliferative diabetic retinopathy

DM, diabetes mellitus; DKA, diabetic ketoacidosis; HbA1c, glycosylated hemoglobin; HHNS, hyperosmotic hyperglycemic nonketotic syndrome; GFR, glomerular filtration rate; ACEIs, angiotensin-converting enzyme inhibitors; ARBs, angiotensin-receptor blockers; NSAIDs, nonsteroidal anti-inflammatory drugs; ECG, electrocardiogram

TABLE 8.2 Who Should Be Tested?

American Diabetes Association

  1. Testing should be considered in all adults who are overweight (BMI ≥25) and have additional risk factors:

    • Physical inactivity

    • First-degree relative with diabetes

    • Member of high-risk ethnic populations (African Americans, Asian Americans, Mexican Americans, Native American Indians, Native Hawaiians, and Pacific Islanders)

    • Women who delivered a newborn weighing >9 lb or more or were diagnosed with GDM

    • Hypertension

    • HDL-C level <35 mg/dL or triglyceride level >250 mg/dL

    • Women with PCOS

    • Impaired glucose tolerance or impaired fasting glucose on prior testing

    • Other clinical conditions associated with insulin resistance

    • History of cardiovascular disease

  2. In the absence of any of the above criteria, testing for diabetes and prediabetes should begin at age 45

  3. If results are normal, testing should be repeated at 3-year intervals, with consideration of more frequent testing depending on initial results and risk status

United States Preventative Service Task Force

  • Screening is recommended for asymptomatic adults with sustained blood pressure >135/80 mm Hg

  • No recommendation for asymptomatic adults with blood pressure ≤135/80 mm Hg

GDM, gestational diabetes mellitus; HDL-C, high density lipoprotein cholesterol; PCOS, polycystic ovarian syndrome


Insulin therapy for diabetes is discussed in Chapter 18.4. Oral medications commonly used to treat type 2 DM are described in Table 8.3. Sulfonylureas are prototypical secretagogues, and the resultant insulin release can result in hypoglycemia. Metformin is one of the most widely used agents and has several benefits over other agents: weight loss, favorable effects on lipids, improvement of insulin resistance, and reduction in all-cause mortality (10). Notably, metformin does not cause significant hypoglycemia and, despite common misconceptions, rarely causes lactic acidosis—even for renal-impaired patients (11). Perioperative metformin recommendations from the UK National Health Service call for its continuation on the day of surgery if the fasting period is brief (i.e., only one meal missed) (12). The exceptions to this
practice are renal impairment (defined as eGFR <60 mL/min/1.73 m2) and the anticipated use of IV iodinated radiographic contrast. Recently, in two important trials, the GLP-1 agonist liraglutide and the SGLT-2 inhibitor empagliflozin have been shown to reduce MACE, cardiovascular death, and all-cause mortality (13,14). These can also be given perioperatively provided the fasting period is brief (i.e., only one meal missed) (12).

Figure 8.1 Rapid screening for diabetic neuropathy.

The decision to give or hold oral medications for diabetes is based on the type of DM, pharmacology of chronic medications, type and duration of surgery, and the risk of hypo- and hyperglycemia. Oral hypoglycemics are generally continued until

the commencement of fasting with some specific exceptions (see Table 8.3). For insulin instructions, see Chapter 18.3, noting that patients with type 1 DM require constant exogenous insulin to prevent ketoacidosis.

Diabetes Medications


Mechanism of Action

Major Side Effects

Special Considerations

Perioperative Management



Chlorpropamide (Diabinase®)

Stimulate pancreatic islet cells to release insulin

Prolonged hypoglycemia

Stevens-Johnson syndrome

Rare cause of SIADH

  • Long half-life (36 hours)

  • Use no longer recommended

Stop 3 days before surgery

Tolazamide (Tolinase®)

Tolbutamide (Orinase®)

Stimulate islet cells to release insulin


Hold on day of surgery


Glipizide (Glucotrol®)

Glyburide (Diabeta®, Micronase®)

Glimepiride (Amaryl®)

Stimulate islet cells to release insulin


Hold on day of surgery


Metformin (Glucophage®)

Suppresses hepatic gluconeogenesis

Lactic acidosis, especially with kidney or heart failure

  • May help with weight loss

  • May lower mortality

May be given on day of surgery if brief fasting perioda

Hold on day of surgery if IV contrast is planned, if the eGFR <60 mL/min/1.73 m2, or if anticipating prolonged fasting postoperatively

Check serum creatinine post procedure if IV contrast given


Rosiglitazone (Avandia®)

Pioglitazone (Actos®)

Increase insulin sensitivity

Weight gain

Risk of heart failure


  • May increase fracture risk in women

Hold on day of surgery

Alpha-glucosidase Inhibitors

Acarbose (Precose®)

Miglitol (Glyset®)

Inhibit conversion of complex polysaccharides to monosaccharides

Flatulence which decreases compliance

  • Slows rise in postprandial glucose

  • Acarbose may also benefit type 1 diabetes

  • Hold day of surgery

DPP-4 Inhibitors (“gliptins”)

Alogliptin (Nesina®)

Linagliptin (Tradjenta®)

Saxagliptin (Onglyza®)

Sitagliptin (Januvia®)

Inhibit dipeptidyl peptidase-4

Possibly pancreatitis



Stevens-Johnson syndrome

Arthralgias and myalgias

  • Not first-line therapy for most type 2 diabetes patients

  • Alogliptin and saxagliptin should be stopped with heart failure

  • Linagliptin does not require dose adjustment in CKD

Hold the day of surgery

SGLT-2 Inhibitors (“flozins”)

Canagliflozin (Invokana®)

Dapagliflozin (Farxiga®)

Empagliflozin (Jardiance®)

Inhibit sodium-glucose cotransporter-2 in proximal tubule in kidneys promoting glucose excretion

Vulvovaginal candidiasis

Urinary tract infections

Osmotic diuresis leading to hypotension

“Euglycemic” ketoacidosis

Acute kidney injury

  • Weight loss

  • Avoid in stage 3-5 CKD

  • Empagliflozin may reduce MACE (14)

  • Canagliflozin increases risk of toe, foot, or leg amputation in patients with PAD, neuropathy, or foot ulcers

May take morning of surgery if brief fasting perioda

Meglitinide Analog

Nateglinide (Starlix®)

Repaglinide (Prandin®)

Stimulate islet cell insulin release via regulation of ATP-dependent K+ channels


  • Caution with nateglinide and renal impairment

Hold day of surgery

GLP-1 Agonists (“tides”)

Albiglutide (Tanzeum®)

Dulaglutide (Trulicity®)

Exenatide (Byetta®, Bydureon®)

Liraglutide (Victoza®, Saxenda®)

Enhance glucosemediated insulin secretion

Reduce postprandial glucagon

Nausea and vomiting Pancreatitis

  • Reduce gastric emptying

  • Decrease appetite and promote weight loss

  • Caution in renal impairment (exenatide contraindicated in severe CKD)

  • Albiglutide, exenatide, and liraglutide not recommended with a history or family history of MEN 2A or 2B or medullary thyroid carcinoma

  • Liraglutide may reduce MACE (13)

May take morning of surgery if brief fasting perioda

a Brief fasting defined as missing one meal preoperatively and anticipating normal oral intake postoperatively. SIADH, syndrome of inappropriate antidiuretic hormone; eGFR, estimated glomerular filtration rate; CKD, chronic kidney disease; IV, intravenous; MACE, major adverse cardiovascular event; MEN, multiple endocrine neoplasia (syndrome).

More recently, insulin pump therapy is becoming more common for diabetes management. Continuous subcutaneous insulin infusion pumps provide a continuous rate of a short-acting insulin, with prandial and correction insulin delivered with patient involvement. If the decision is made in consultation with the endocrinologist to continue the pump periprocedurally, the patient is instructed to place the infusion pump and catheter away from the surgical site. If there will be radiation exposure, lead should cover the pump or it should be removed based on manufacturer’s recommendations, as some manufacturers state that x-ray and electromagnetic radiation may damage their pumps. Intra- and postoperatively, glucose is checked hourly, with insulin supplementation as needed. The catheter location, connection, and pump function (infusing or not) should be confirmed on an hourly basis. With well-established safety protocols, continuing basal insulin via pump has been found to be safe and benefit perioperative glycemic control (15).


1. Bellamy L, Casas JP, Hingorani AD, et al. Type 2 diabetes mellitus after gestational diabetes: a systematic review and meta-analysis. Lancet. 2009;373(9677):1773-1779.

2. Reissell E, Orko R, Maunuksela EL, et al. Predictability of difficult laryngoscopy in patients with long-term diabetes mellitus. Anaesthesia. 1990;45(12):1024-1027.

3. Grasso AW, Jaber WA. Cardiac risk stratification for noncardiac surgery. June 2014. Available at http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/cardiology/cardiac-risk-stratification-for-noncardiac-surgery/Accessed on September 23, 2016.

4. The Diabetes Control and Complications Trial Research Group. Effect of intensive diabetes management on macrovascular events and risk factors in the diabetes control and complications trial. Am J Cardiol. 1995;75(14):894-903.

5. Burgos LG, Ebert TJ, Asiddao C, et al. Increased intraoperative cardiovascular morbidity in diabetics with autonomic neuropathy. Anesthesiology. 1989;70(4):591-597.

6. Biteker M, Dayan A, Tekkeşin A, et al. Incidence, risk factors, and outcomes of perioperative acute kidney injury in noncardiac and nonvascular surgery. Am J Surg. 2014;207(1): 53-59.

7. Martin ET, Kaye KS, Knott C, et al. Diabetes and risk of surgical site infection: a systematic review and meta-analysis. Infect Control Hosp Epidemiol. 2016;37(1):88-99.

8. Adler AI, Stevens RJ, Manley SE, et al. UKPDS GROUP Development and progression of nephropathy in type 2 diabetes: the United Kingdom Prospective Diabetes Study (UKPDS 64). Kidney Int. 2003;63(1):225-232.

9. Joshi GP, Chung F, Vann MA, et al. Society for Ambulatory Anesthesia consensus statement on perioperative blood glucose management in diabetic patients undergoing ambulatory surgery. Anesth Analg. 2010;111(6):1378-1387.

10. Bannister CA, Holden SE, Jenkins-Jones S, et al. Can people with type 2 diabetes live longer than those without? A comparison of mortality in people initiated with metformin or sulphonylurea monotherapy and matched nondiabetic controls. Diabetes Obes Metab. 2014;16(11):1165-1173.

11. DeFronzo R, Fleming A, Chen K, et al. Metformin-associated lactic acidosis: current perspectives on causes and risk. Metabolism. 2016;65(2):20-29.

12. Membership of the Working Party: Barker P, Creasey PE, Dhatariya K, et al. Perioperative management of the surgical patient with diabetes 2015: Association of Anaesthetists of Great Britain and Ireland. Anaesthesia. 2015;70(12): 1427-1440.

13. Marso SP, Daniels GH, Brown-Frandsen K, et al. for the LEADER Steering Committee on behalf of the LEADER trial investigators. Liraglutide and cardiovascular outcomes in type 2 diabetes. N Engl J Med. 2016;375(4):311-322.

14. Zinman B, Wanner C, Lachin JM, et al. for the EMPA-REG OUTCOME Investigators. Empagliflozin, cardiovascular outcomes, and mortality in type 2 diabetes. N Engl J Med. 2015;373(22):2117-2128.

15. Corney SM, Dukatz T, Rosenblatt S, et al. Comparison of insulin pump therapy (continuous subcutaneous insulin infusion) to alternative methods for perioperative glycemic management in patients with planned postoperative admissions. J Diab Sci Tech. 2012;6(5):1003-1015.

8.2 Hyperthyroidism

Nicolette A. Schlichting

Muoi Trinh

The thyroid gland is a butterfly-shaped endocrine structure located in the anterior aspect of the neck that secretes hormones critical for development and metabolic processes. The gland consists of follicles containing thyroglobulin, a large glycoprotein that is the precursor and predominant storage form of thyroid hormones. Thyroid hormone is regulated by the hypothalamic-pituitary-thyroid axis. Dysfunction in any of the three components results in clinical or subclinical disease. Over or underactivity of thyroid hormone may have broad-reaching systemic effects (1,2,3).


The thyroid hormones with biologic activity are thyroxine (T4) and triiodothyronine (T3). About 90% of the hormones released from the thyroid gland are in the less active T4 prohormone state, which is converted by deiodinases to the T3 form that has a much higher affinity for receptors. T4 can also be converted to reverse T3 (rT3), which is inactive. The vast majority of circulating thyroid hormone is bound to carrier proteins, primarily thyroid-binding globulin (TBG), transthyretin, albumin, and lipoproteins. The remaining unbound (free) hormone is metabolically active (1,2,3).


Thyrotropin-releasing hormone (TRH) is a peptide hormone produced by the hypothalamus that stimulates thyrotropin (or thyroid-stimulating hormone [TSH]) release from the anterior pituitary. TSH, in turn, stimulates the release of T4 and T3 from the thyroid. Minute increases in T3 and T4, via a very sensitive feedback mechanism, inhibit both the production and secretion of TSH and TRH. Miniscule decreases in T3 and T4 stimulate TRH synthesis, thereby increasing TSH release, which increases levels of circulating thyroid hormone (1,2,3).


The prevalence of hyperthyroidism is 1.2% in the United States with 0.5% being clinically apparent and 0.7% being subclinical (2). Incidence increases with age, and it is more common in women and in areas with iodine deficiency (4,5).


Thyrotoxicosis refers to the clinical manifestations from abnormally high thyroid hormone action in the peripheral tissues. Hyperthyroidism refers specifically to thyrotoxicosis from overactive synthesis and release of T3 and T4 from the thyroid gland (2,4). The causes of thyrotoxicosis can be split into two groups, true hyperthyroidism (thyroid gland has increased metabolic activity) and thyrotoxicosis without hyperthyroidism (metabolic activity of the thyroid is decreased) (4,5). In the latter group, the thyrotoxic manifestations are caused by extrathyroidal sources of thyroid hormone or by a release of preformed hormones from the thyroid itself (5).

Common causes of true hyperthyroidism include Graves disease, toxic multinodular goiter (TMNG), and toxic adenoma (TA). In Graves disease, activating autoantibodies stimulate the TSH receptor, whereas with TMNG and TA, thyroid nodules develop autonomy via genetic mutations (4). Causes of thyrotoxicosis without hyperthyroidism are less common and include subacute painful thyroiditis and lymphocytic (silent or postpartum) thyroiditis, whereby thyroid follicles damaged by inflammation release stored T3 and T4, and drug-induced thyrotoxicosis from drugs containing iodine (such as amiodarone and contrast dyes), lithium, interferon alpha, interleukin 2, and several tyrosine kinase inhibitors (e.g., sunitinib) (2,4,5). These types are often short-lived with periods of thyrotoxicosis, followed by a hypothyroid stage, and an eventual return to a euthyroid state (4,5). Exogenous thyrotoxicosis may be iatrogenic or the result of thyroid hormone ingestion to promote weight loss or increase energy (4,5).


Symptoms of hyperthyroidism are primarily related to increased metabolic and sympathetic activity, most commonly weight loss, heat intolerance, tremor, palpitations, and anxiety (see Table 8.4) (4,5,6). Elderly patients may present with apathetic hyperthyroidism with weight loss, listlessness, and tachycardia (6). Thyrotoxicosis can cause tachyarrhythmias, most commonly sinus tachycardia, in the adult patient but predisposes the elderly to atrial fibrillation because of coexisting cardiac disease (6). Thyroid storm, a severe thyrotoxicosis, may have significant cardiovascular implications, including the development of heart failure or myocardial ischemia from increased cardiac oxygen requirements (7).


The U.S. Preventive Services Task Force does not recommend screening for thyroid disease in asymptomatic patients. In symptomatic patients, TSH level is the most sensitive and specific test when evaluating for thyroid dysfunction. Obtaining free T4 and total T3 improves diagnostic accuracy and distinguishes between overt and subclinical hyperthyroidism (1,2,4,5). Serum TSH is low in patients with primary hyperthyroidism (<0.01 mU/L when measured by third-generation assays) and T3 and T4 levels are elevated (2,8). Patients with subclinical hyperthyroidism have a low serum TSH (however, often >0.05 mU/L) with normal levels of T3 and T4 (2,8). Medications can cause thyroid dysfunction and/or affect the interpretation of thyroid assays. Glucocorticoids and dopamine decrease TSH secretion; iodide and amiodarone can increase or decrease T3 and T4 secretion (9). The clinical picture must be evaluated when interpreting the results of a thyroid function panel.

If the patient is found to have a new diagnosis of thyrotoxicosis, additional tests are needed and are best guided by an endocrinologist. Tests may include a radioactive iodine (RAI) uptake test, thyroid ultrasonography, or laboratory tests for thyroid receptor antibodies (2,4,5). Assessment of a patient with diagnosed thyrotoxicosis includes a thyroid function panel to assess adequacy of treatment. In patients with Graves disease, both T3 and T4 levels are monitored, as there may be a lag in normalization of TSH despite achieving a euthyroid state. An electrocardiogram to evaluate for the presence of tachyarrhythmias, such as atrial fibrillation, or ischemia may be indicated. An echocardiogram may be considered to evaluate ventricular function (4). If the patient has a large goiter or compressive symptoms, imaging is ordered to assess airway abnormalities (see Table 8.5).

TABLE 8.5 Systemic Manifestation of Hypothyroidism and Myxedema Coma


Weight gain, dry skin, myxedema, brittle hair and nails


Fatigue, somnolence, poor concentration, poor memory, hyporeflexia, ataxia


Periorbitial edema, laryngeal edema, goiter


Bradycardia, diastolic and systolic dysfunction, prolonged QT, abnormal T wave, torsades de pointes


Hypoventilation, hypercapnia, sleep apnea, pleural effusion


Decreased appetite, delayed gastric emptying, constipation


Cold intolerance, irregular menses, osteoporosis


Thrombosis (mild hypothyroidism); coagulopathy from acquired von Willebrand syndrome or DIC (myxedema coma)


Depression, paranoia, hallucinations

HEENT, head, eyes, ears, neck, throat; DIC, disseminated intravascular coagulopathy


All nonemergency procedures are delayed until a euthyroid state is reached. The three main options for definitive therapy are antithyroid drugs (ATDs), radioactive iodine, or thyroidectomy depending on the underlying cause (2,4,5). Side effects of ATDs, like granulocytosis and hepatotoxicity, warrant further testing, including hematologic and comprehensive metabolic panels (2). Sympathetic outflow and cardiovascular disease are managed with beta-adrenergic blockers, and pain (e.g., from subacute thyroiditis) is controlled with NSAIDs or corticosteroids (4).


1. Stathatos N. Thyroid physiology. Med Clin North Am. 2012;96:165-173.

2. Ross D, Burch H, Cooper S, et al. 2016 American Thyroid Association Guidelines for diagnosis and management of hyperthyroidism and other causes of thyrotoxicosis. Thyroid. 2016;26:1343-1421.

3. Ross D. Thyroid hormone synthesis and physiology. In: Post TW, ed. UpToDate. Waltham, MA; 2016.

4. Stuart C, Seigel M, Hodak S. Thyrotoxicosis. Med Clinics N Am. 2012;96:175-201.

5. De Leo S, Lee S, Braverman L. Hyperthyroidism. Lancet. 2016;388:906-918.

6. Palaleontiou M, Haymart M. Approach to and treatment of thyroid disorders in the elderly. Med Clin N Am. 2012;96:297-310.

7. Klubo-Gwiezdzinska J, Wartofsky L. Thyroid emergencies. Med Clin N Am. 2012;96: 385-403.

8. Ross D. Diagnosis of hyperthyroidism. In: Post TW, ed. UpToDate. Waltham, MA; 2016.

9. Kundra P, Burman KD. The effect of medications on thyroid function tests. Med Clin North Am. 2012;96:283-295.

8.3 Hypothyroidism

Muoi Trinh


See Chapter 8.2 Hyperthyroidism for a review of the physiology of thyroid hormone secretion.


In the United States, the prevalence of overt hypothyroidism is 0.3% to 0.4% and subclinical hypothyroidism is 4% to 8.5%, with higher rates in women and the elderly (1,2,3). Other risk factors for hypothyroidism include personal or family history of autoimmune disease, prior radiation to the head and neck, history of thyroidectomy, and taking specific medications such as: amiodarone, tyrosine kinase inhibitors, interferon-alpha, or lithium (2,3,4).


Hypothyroidism is caused by either an inadequate production of thyroid hormone or an inappropriate response at the targeted tissue. Primary hypothyroidism results from a deficiency in endogenous production of hormones, whereas secondary hypothyroidism results from dysfunction in the hypothalamic-pituitary axis. The most common cause of hypothyroidism in iodine-sufficient areas is Hashimoto thyroiditis, an autoimmune disease resulting in lymphocytic infiltration and destruction of the thyroid gland. Destruction of the gland from radiation, viral thyroiditis, or surgery can result in insufficient glandular tissue for adequate production of hormone. Hypothyroidism can be caused by medications, most commonly amiodarone, an antiarrhythmic drug that can inhibit normal T3 formation. Up to 50% of patients taking amiodarone have abnormal TSH levels, warranting frequent monitoring of thyroid function (5,6). Other medications associated with hypothyroidism are lithium, interferon alpha, and interleukin-2. Damage to the pituitary gland from radiation, surgery, or hypertension can lead to secondary hypothyroidism.


There is no evidence to support screening for thyroid disease in asymptomatic patients. When hypothyroidism is suspected, the most sensitive test is a serum TSH level. A normal TSH rules out primary hypothyroidism. Laboratory values consistent with primary hypothyroidism are elevated TSH and low T3 or free T4. Subclinical hypothyroidism is an asymptomatic individual with an elevated TSH and normal T3 or free T4 in the setting of an intact hypothalamic-pituitary axis and the absence of systemic illness. For patients who exhibit severe symptoms and confirmatory laboratory values of hypothyroidism, an endocrinologist should be consulted for further workup and management. Elective surgery is delayed if the patient is symptomatic until the patient has returned to a euthyroid state. However, it should be noted that symptoms may resolve prior to normalization of laboratory values. No additional testing is necessary in patients with well-compensated thyroid disease on a stable dose of medication and documentation of euthyroid state within 3 to 6 months prior to surgery date (7,8).

Hypothyroidism can affect many organ systems and the following tests may be useful: a transthoracic echocardiogram to detect decreased cardiac function, diastolic heart failure, or large pericardial effusions; electrocardiogram to detect bradycardia or low voltage, electrical alternans; chest radiograph which may demonstrate goiter and airway deviation allowing anticipation of a difficult airway; and a basic metabolic panel to evaluate hyponatremia, metabolic acidosis, and hypoglycemia associated with inadequacy of hormone (2,5,7,8) (see Table 8.6).

TABLE 8.6 Preoperative Testing



Chest radiograph

Evaluate airway abnormalities, goiter, tracheal deviation


Evaluate systolic and diastolic function


Bradycardia, prolonged QT, atrial fibrillation


Evaluate electrolytes, hyponatremia, acidosis

Thyroid function test

Assess thyroid dysfunction and adequacy of treatment


Levothyroxine, the mainstay therapy for hypothyroidism is effective, has a long halflife and favorable side-effect profile. The prohormone levothyroxine is converted to the active hormone T3. Levels are monitored once treatment is started, as iatrogenic thyrotoxicosis carries its own risk (see Chapter 8.2 Hyperthyroidism) (2,3).

The management of patients with recently diagnosed hypothyroid disease is based on limited studies and complicated by varying definitions of severity for hypothyroidism. For the purposes of our discussion, the following definitions will be used. Severe hypothyroidism is a disease state characterized by chronic clinical symptoms such as seen in myxedema coma, including altered mental status, large pericardial effusion, heart failure, or laboratory values showing low T4 (<1 mcg/dL) or free T4 (<0.5 ng/dL). Moderate hypothyroidism is overt hypothyroidism and high TSH with low free T4. Mild hypothyroidism is subclinical disease and elevated TSH with normal free T4 (7,8).

Elective surgery is postponed in patients with moderate and severe hypothyroidism until a euthyroid state is achieved. Urgent surgery in a patient with moderate hypothyroidism should not be delayed; however, these patients may experience more hemodynamic perturbations intraoperatively. Patients with severe thyroid dysfunction undergoing urgent surgery benefit from endocrinology consult to guide dosing of intravenous T3 and T4 for rapid replacement (7,8). Intraoperatively, patients with moderate or severe hypothyroidism depending on the patient’s comorbidities may benefit from arterial line, transesophageal echocardiography, or pulmonary artery catheter for hemodynamic monitoring. Surgery should not be postponed in patients with mild hypothyroidism (7,8). Thyroid replacement medications have a half-life 7 to 10 days, though a common cause of hypothyroidism is failure to take replacement as indicated. General anesthesia and surgery can precipitate myxedema coma (2,3,9).


1. Almandoz J, Gharib H. Hypothyroidism: etiology, diagnosis, and management. Med Clin North Am. 2012;96:203-221.

2. Jonklass J, Bianoc A, Bauer A, et al. Guidelines for the treatment of hypothyroidism. Thyroid. 2014;12:1670-1751.

3. Palaleontiou M, Haymart M. Approach to and treatment of thyroid disorders in the elderly. Med Clin North Am. 2012;96:297-310.

4. Lele A, Clutter S, Price E, et al. Severe hypothyroidism presenting as myxedema coma in the postoperative period in a patient taking sunitinib: case report and review of literature. J Clin Anesth. 2013;25:47-51.

5. Danzi S, Klein I. Thyroid hormone and the cardiovascular system. Med Clin N Am. 2012;96:257-268.

6. Cohen-Lehman J, Dahl P, Danzi S, et al. Effects of amiodarone on thyroid function. Nat Rev Endocrinol. 2010;6:34-41.

7. Manzullo E, Cooper D, Mulder J. Nonthyroid surgery in the patient with thyroid disease. In: Post TW, ed. UpToDate. Waltham, MA; 2017.

8. Surks M, Ross D, Mulder J. Clinical manifestations of hypothyroidism. In: Post TW, ed. UpToDate. Waltham, MA; 2017.

9. Klubo-Gwiezdzinska J, Wartofsky L. Thyroid emergencies. Med Clin North Am. 2012;96:385-403.

8.4 Adrenal Insufficiency

Martin Chen

Adrenal insufficiency can be the consequence of inadequate production or action of glucocorticoids. It can be accompanied by a deficiency of other adrenal steroid hormones (aldosterone, adrenal estrogens). The average basal adrenal cortisol secretion is 30 mg/day. The stress of surgery, trauma, and infection can increase adrenal output of glucocorticoids up to 10-fold to 300 mg/day. Glucocorticoids modify the effect of catecholamines on vascular tone, and one consequence of adrenal insufficiency is hypotension refractory to vasopressor therapy and fluid resuscitation during periods of physiologic stress (1). There are three broad classes of adrenal insufficiency. Primary and secondary adrenal insufficiency, resulting from destruction of the adrenal or pituitary glands respectively, are less common and can be caused by conditions such as autoimmune adrenalitis, tuberculosis, tumors, infiltrative processes, surgery, human immunodeficiency virus (adrenal), and radiation (pituitary). Tertiary adrenal insufficiency is much more commonly encountered in clinical practice and results from processes that interfere with release of hypothalamic hormones that stimulate adrenal cortisol synthesis. This most often is due to suppression of hypothalamic-releasing hormone secretion by high-dose glucocorticoid therapy, which leads to reduced adrenal cortisol synthesis in response to stress (2). Many patients chronically take high doses of glucocorticoids for allergic and inflammatory diseases, or as part of their immunosuppressive regimen after transplantation, and are at risk for tertiary adrenal insufficiency. Tertiary adrenal insufficiency is almost always present in patients on chronic high-dose steroid therapy (>20 mg prednisone/day or equivalent for more than 4 weeks) (3). However, suppression can occur with doses as low as 5 mg (3). There is almost no administration form, dose, or treatment duration for which adrenal insufficiency can be excluded with certainty, so identification requires a high degree of clinical suspicion (4). Adrenal insufficiency can persist for 6 to 12 months after discontinuation of steroids (1,3).


Measurements of complete blood count, electrolyte and glucose levels are indicated because hyponatremia, hyperkalemia, hypoglycemia, and normochromic anemia can be present with adrenal insufficiency. In elective situations where there is a high degree of suspicion for adrenal insufficiency, an ACTH stimulation test should be done to assess the ability of the adrenal glands to respond to stress and determine if hydrocortisone supplementation is indicated. In emergency cases where there is a similar degree of suspicion for adrenal insufficiency, presumptive therapy with hydrocortisone is appropriate (1). In newly diagnosed primary adrenal insufficiency, recommendations for diagnostic testing include titers of adrenal antibodies (to exclude autoimmune adrenal insufficiency), serum 17-hydroxyprogesterone levels (to rule out congenital adrenal hyperplasia), and imaging of the adrenal glands (to evaluate for infiltrative processes or hemorrhage) (3). Newly diagnosed secondary adrenal insufficiency should be evaluated with an MRI of the pituitary gland (3).


  • Patients continue their glucocorticoid or mineralocorticoid replacement therapy on the day of surgery.

  • Steroid supplementation is advisable for major procedures in patients taking >20 mg/day of prednisone or its equivalent. See Chapter 18.6.

  • The risk of adrenal insufficiency remains for up to 1 year after the cessation of highdose steroid therapy.


1. Kohl B, Schwartz S. Surgery in the patient with endocrine dysfunction. Anesthesiol Clin. 2009;27:687-703.

2. Charmandari E, Nicolaides N, Chrousos G. Adrenal insufficiency. Lancet. 2014;383:2152-2167.

3. Bancos I, Hahner S, Tomlinson J, et al. Diagnosis and management of adrenal insufficiency. Lancet Diabetes Endocrinol. 2015;3:216-226.

4. Broersen L, Pereira A, Jørgensen J, et al. Adrenal insufficiency in corticosteroids use: systematic review and meta-analysis. J Clin Endocrinol Metab. 2015;100:2171-2180.

8.5 Cushing Syndrome

Janet van Vlymen

Dana Zoratto

Cushing syndrome manifests after prolonged exposure to excessive levels of circulating cortisol. Most commonly, this elevation results from an exogenous source; however, pituitary adenomas, ectopic ACTH-secreting tumors, adrenal adenomas,
and adrenal carcinomas can lead to inappropriately high plasma levels of glucocorticoids (1). Cushing disease refers specifically to Cushing syndrome caused by pituitary secretion of excessive ACTH.

Cortisol promotes protein catabolism and liver gluconeogenesis ensuring adequate blood glucose concentrations during fasting and is important for the appropriate cardiovascular response to stress (2). The normal daily amount of endogenous cortisol production is 10 to 20 mg, which increases during times of stress to values between 150 and 300 mg. Exogenous glucocorticoid doses of greater than the equivalent of 20 mg of cortisol per day for more than 3 weeks can lead to iatrogenic Cushing syndrome.


Clinical features of Cushing syndrome result from the systemic effects of cortisol on the body (Table 8.7). Many manifestations are nonspecific, and there is a wide variation in clinical phenotype leading to difficulty in diagnosis (3). Obesity, hypertension, volume overload, electrolyte imbalances, myopathy, and metabolic derangements such as glucose intolerance are important considerations for the anesthesiologist. In addition, these patients have increased susceptibility to infection and impaired wound healing.

Nov 14, 2018 | Posted by in ANESTHESIA | Comments Off on Endocrine and Metabolic Disorders

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