Summary
Although anesthesiology and endocrinology are two distinct branches of medicine, some recent breakthrough treatments have brought together both medical specialties, particularly those concerned with surgical sciences and critical care. Related to the use of various traditional surgical techniques, the lack of newer and safer drugs, the lack of monitoring tools, and the scarcity of critical care services in the past, managing patients with various endocrine disorders has always been perceived as being more difficult by practicing anesthesiologists.
Introduction
Although anesthesiology and endocrinology are two distinct branches of medicine, some recent breakthrough treatments have brought together both medical specialties, particularly those concerned with surgical sciences and critical care. Related to the use of various traditional surgical techniques, the lack of newer and safer drugs, the lack of monitoring tools, and the scarcity of critical care services in the past, managing patients with various endocrine disorders has always been perceived as being more difficult by practicing anesthesiologists.
Patients with diverse endocrinopathies provide anesthesiologists with a variety of challenges during the perioperative phase. As such, a multidisciplinary strategy involving endocrinologists, anesthesiologists, intensivists, and surgeons is required today for a better perioperative patient outcome. The effect of endocrine abnormalities on perioperative outcome cannot be overstated, no matter how modest. Thus, it is critical to have a thorough understanding of the many anesthetic and nonanesthetic medicines that influence neurotransmitter and hormone production, to minimize perioperative morbidity and death. Among the primary endocrinologic illnesses, those affecting the thyroid, parathyroid, pancreatic, adrenal, and pituitary glands have a considerable impact on surgical results and anesthetic methods.
Hypothalamus/Posterior Pituitary
To understand these diseases, we must first remind ourselves of the role of antidiuretic hormone (ADH). ADH is produced in the hypothalamus and stored in the posterior pituitary where it is released in response to high plasma osmolality. Plasma osmolality is sensed in the hypothalamus by osmoreceptors. Once ADH is released, it has its primary effect in the distal convoluted tubule and collecting duct of the kidney by regulating the release of aquaporin channels, which allow the movement of water across cell membranes [Reference Palmer1].
Syndrome of Inappropriate Diuretic Hormone
SIADH occurs when the posterior pituitary continues to release ADH despite normal or low plasma osmolality. This high circulating level of ADH results in the production of concentrated urine due to water retention. Although ADH does cause water retention, SIADH results in a euvolemic, hyponatremic state. As the levels of ADH increase, the concentration of urine also increases. This results in high urine osmolality and high urine sodium concentration. Due to high water retention, patients will have decreasing sodium concentration, which is the ultimate cause of the symptoms seen with this disease. Early signs of SIADH are nonspecific such as fatigue, muscle weakness, nausea, confusion, and headaches. As sodium imbalance worsens, patients can experience life-threatening seizures and cerebral edema. SIADH has a large host of etiologies, including, but not limited to, central nervous system (CNS) disturbances, malignancy, pulmonary disease, drug toxicity, and surgery. To properly treat SIADH in the long term, healthcare workers must first localize the source of the syndrome and correct it. However, in the acute setting, first-line management is fluid restriction (<800 mL per day), unless the patient has subarachnoid hemorrhage as this can cause cerebral vasospasm. Intravenous (IV) hypertonic saline and salt tablets (salt tablets are known to cause nausea) can be used in severe cases of hyponatremia. Care must be taken not to correct faster than 8 mEq L−1 in a 24-hour period, as this can result in osmotic demyelination, a potentially lethal complication. A loop diuretic can be used in cases where urine osmolality is over twice the plasma osmolality. Vasopressin receptor antagonists, such as tolvaptan, are less commonly used due to their costs and side effect profile (e.g., hepatotoxicity and excessive thirst) [Reference Verbalis, Greenberg and Burst2].
Cerebral Salt Wasting
Cerebral salt wasting (CSW) is a somewhat controversial distinction from SIADH in which severe CNS injuries result in inability of the body to retain salt, leading to a hypovolemic, hyponatremic state. One possible mechanism is loss of sympathetic regulation, and therefore decreased release of aldosterone and renin. Another source is decreased B-type natriuretic peptide (BNP), which impairs sodium reabsorption in the renal tubules. The resulting sodium loss will lead to increased ADH circulation, increased urinary sodium concentration, increased urine osmolality, and decreased plasma sodium concentration. Signs and symptoms of CSW include hypotension, decreased skin turgor, elevated hematocrit, and eventually more life-threatening outcomes such as seizures and cerebral edema. The difficulty in distinguishing SIADH from CSW lies in the difficulty in truly measuring body volume. CSW would theoretically respond to isotonic saline by releasing more dilute urine; however, this is generally not recommended, as patients can have concurrent SIADH, which will cause worsening of hyponatremia and possible fatal outcomes. As CSW is associated with CNS injuries, the first-line therapy is usually hypertonic saline until a safe plasma sodium concentration is reached [Reference Sterns and Silver3].
Diabetes Insipidus
Two forms of diabetes insipidus (DI) exist: central and nephrogenic. Central DI occurs when the body is unable to produce ADH, resulting in polyuria, polydipsia, and nocturia. Nephrogenic DI occurs when the kidney fails to respond to ADH, with similarly resulting symptoms. The key difference is that central DI will have low ADH levels, whereas nephrogenic DI will have high ADH levels. You can tell the difference clinically using a water deprivation test. Urine osmolality will increase in response to an ADH analog in central DI. The mainstay of treatment in central DI is desmopressin. In nephrogenic DI, the mainstay of treatment is hydrochlorothiazide (HCTZ). In both forms of DI, it is important for the patient to remain hydrated at all times and not ignore their thirst mechanism [Reference Gubbi, Hannah-Shmouni, Koch, Verbalis, Feingold, Anawalt and Boyce4].
Thyroid: Pathophysiology, Differential Diagnosis, Treatment, and Perioperative Management
Hypothyroidism
Etiology
Primary – ↑ thyroid-stimulating hormone (TSH) and ↓ free thyroxine (T4); >90% of hypothyroidism cases: Hashimoto thyroiditis (+ antithyroid peroxidase (TPO), antithyroglobulin (Tg)), iatrogenic (thyroidectomy, radioactive iodine, amiodarone, lithium), iodine deficiency.
Secondary (↓ free T4 and ↑, ↓, or normal TSH): central, due to hypothalamic or pituitary failure.
Subclinical hypothyroidism.
Clinical Manifestations
See references [Reference McDermott5] and [Reference Ono, Ono, Yasunaga, Matsui, Fushimi and Tanaka6].
Early: fatigue, weakness, depression, weight gain, headache, myalgia, arthralgia, cold intolerance, dry skin, coarse and brittle hair, brittle nails, delayed deep tendon reflexes, carpal tunnel syndrome, constipation, menorrhagia, hyperlipidemia, diastolic hypertension.
Late: slow speech, hoarseness, periorbital puffiness, myxedema (nonpitting edema), bradycardia, atherosclerosis, pleural, pericardial and peritoneal effusions.
Myxedema crisis and coma: profound hypothyroidism, with high mortality rate (50–75%), even with treatment. Often precipitated by trauma, infection, illness, or narcotics. Hallmark – hypothermia and change of mental status (confusion, lethargy, obtundation, psychotic features, and coma). Hypotension, hypoventilation, hyponatremia, and hypoglycemia frequently present.
Management
See reference [Reference Bigos, Ridgway, Kourides and Maloof7].
Levothyroxine 1.5–1.7 μg kg−1 per day → titrate until euthyroid, rechecking TSH every 5–6 weeks.
Decreased starting dose 0.3–0.5 μg kg−1 per day if elderly or risk of ischemic heart disease.
Increased dose if poor gastrointestinal (GI) absorption (celiac, inflammatory bowel disease), pregnancy, drugs (proton pump inhibitor (PPI), iron, calcium, colestyramine, phenytoin, phenobarbital).
Myxedema coma: load with 5–8 μg kg−1 T4 intravenously (IV), then 50–100 μg IV once daily. May give 5–10 μg T3 IV every 8 hours if unstable with bradycardia and/or hypothermia (peripheral conversion T4 → T3 impaired). Must give empiric glucocorticoid replacement (e.g., IV hydrocortisone 100 mg every 8 hours). Correction takes time – supportive care to maintain blood pressure and respiration, electrolytes and glucose correction, and passive rewarming.
Myxedema Coma and Glucocorticoid Replacement
See reference [Reference Bigos, Ridgway, Kourides and Maloof7].
Anesthetic Considerations in Hypothyroidism
Preoperative
Confirm euthyroid status in patients with known hypothyroidism.
Thyroid replacement therapy should be continued in the perioperative period.
Subclinical and mild disease: not at increased risk of complications.
Moderate to severe disease: consider delaying elective surgery. If emergent, consider pretreatment with IV thyroxine ± T3 and corticosteroids.
Airway evaluation: enlarged tongue, mucinous edema of the pharynx and larynx (myxedema).
Intraoperative
↑ sensitivity and exaggerated response to anesthetics, sedatives, and opioids. Consider etomidate and ketamine for induction.
↓ myocardial function → ↑ risk of hemodynamic instability or myocardial ischemia.
↓ response to α- and β-adrenergic agents → larger doses of vasopressors may be needed.
Hypoventilation (↓ respiratory drive and ↓ respiratory muscle strength).
↓ Red blood cell (RBC) mass and anemia.
Hypothermia (↓ metabolic rate, ↓ Na+/K+ ATPase pumps).
Myxedema coma (see above).
Postoperative
Pathophysiology
Cardiovascular
See references [Reference Klein and Danzi8] and [Reference Sachdev and Hall9].
↓ Myocardial function (↓ cardiac output, ↑ systemic vascular resistance, ↓ or normal systolic blood pressure, ↑ diastolic blood pressure, ↓ contractility, ↓ heart rate) → ↑ risk of hemodynamic instability or myocardial ischemia.
Diminished response to α- and β-adrenergic agents → larger doses of vasopressors needed.
Can induce or worsen arrhythmias.
Pericardial effusion.
Respiratory
See references [Reference Wilson and Bedell10] and [Reference Sadek, Khalifa and Azoz11].
↓ Hypoxic respiratory drive and ↓ hypercapnic respiratory drive (severe diagnosis), and ↓ respiratory muscle strength → alveolar hypoventilation.
↑ Obstructive sleep apnea (OSA) (2/2 to ↓ respiratory drive or airway narrowing due to enlarged tongue and mucinous edema of the pharynx and larynx).
Exudative pleural effusions.
Minimum alveolar concentration (MAC) not affected by hypothyroidism.
↑ risk of delayed emergence and prolonged ventilatory support.
Consider hypothyroidism in respiratory failure with difficulty to wean off ventilator → weaning aided by treatment.
Metabolic
↓ Renal and hepatic clearance of medications (antiepileptics, anticoagulants, opioids, and hypnotics).
Hypothermia: ↓ metabolism and thermogenesis; associated with mortality.
Hyponatremia: ↓ free water clearance (excess ADH, renal impairment, adrenal insufficiency).
Hypoglycemia: ↓ gluconeogenesis and glycogenolysis; adrenal insufficiency can contribute.
↓ RBC mass → normochromic, normocytic anemia.
↓ clearance of vitamin K-dependent factors – coumadin dose adjustment.
Hyperthyroidism
Clinical Manifestations
See reference [Reference Angell, Lechner, Nguyen, Salvato, Nicoloff and LoPresti13].
Restlessness, sweating, tremor, hyperreflexia, most warm skin, heat intolerance, fine hair, tachycardia, palpitations, atrial fibrillation, weight loss, ↑ bowel movement frequency, menstrual irregularities, osteoporosis, stare, and lid lag. Graves’ disease-specific: ophthalmopathy and infiltrative dermopathy (myxedema). Elderly patients can present with lethargy only.
Thyroid storm (20–30% mortality): massive release of T4. Presents with fever, delirium, tachycardia, systolic hypertension with wide pulse pressure and ↓ mean arterial pressure (MAP), and GI symptoms. Unlike malignant hyperthermia, there is no increase in CO2 that is unresponsive to increased minute ventilation, no ↑ in creatine kinase (CK), and no muscle rigidity or acidosis.
Management of Thyroid Storm
See reference [Reference Akamizu, Satoh and Isozaki14].
Beta-blocker (↓ adrenergic tone) – propranolol 60–80 mg every 4–6 hours; adjust for heart rate and blood pressure control.
Propylthiouracil (PTU) 200 mg every 4 hours or methimazole 20 mg every 4–6 hours (to block new hormone synthesis). PTU > methimazole due to its inhibition of peripheral T4 → T3 conversion.oPropranolol, PTU, and methimazole can be given through a nasogastric tube.
Iopanoic acid or iodine >1 hour after PTU (Wolff–Chaikoff effect).
Iodinated radiocontrast (inhibits peripheral T4 → T3 conversion).
Glucocorticoid (↓ peripheral T4 → T3 conversion, ↑ vasomotor stability, ↓ autoimmune process in Graves’ disease or treatment-associated adrenal insufficiency) – IV hydrocortisone 100 mg every 8 hours.
Bile acid sequestrants (severe cases; ↓ enterohepatic recycling of thyroid hormones – cholestyramine 4 g orally four times daily).
Aggressive management of hyperpyrexia with cooling blankets and acetaminophen.
Anesthetic Considerations in Hyperthyroidism
Preoperative
Intraoperative
↑ Sensitivity to catecholamines → consider direct-acting vasoconstrictors (phenylephrine).
↑ Risk of hemodynamic instability and myocardial ischemia.
Slower induction and ↑ concentrations of inhaled anesthetics may be needed due to ↑ cardiac output (effects on uptake and redistribution) and rate of drug metabolism.
No change in MAC requirement.
Thyroid storm: intraoperatively or in first 18 hours postsurgery. Watch for hyperthermia, tachycardia, and changes in blood pressure (see above for more details).
Normochromic, normocytic anemia (↑ in plasma volume > ↑ in RBC mass).
Pathophysiology
Cardiovascular
See reference [Reference Osuna, Udovcic and Sharma15].
↑ Cardiac output, ↑ contractility, ↑ peripheral oxygen consumption, ↑ heart rate, ↑ pulse pressure, ↓ systemic vascular resistance, ↑ systolic blood pressure → ↑ risk of hemodynamic instability or myocardial ischemia.
Prone to sinus tachycardia and atrial fibrillation, coronary spasms, and development of cardiomyopathy.
Complications of Thyroid Surgery
Hypocalcemia (most common complication): 24–72 hours postoperatively. Symptoms range from mild (paresthesia) to moderate (muscle twitching and cramping) and severe (trismus or tetany). Management: calcium carbonate 1250–2500 mg daily in 2–4 doses. If on PPI, give calcium citrate. If persistent hypocalcemia and symptoms despite oral calcium, consider IV calcium and magnesium. Calcitriol if very low parathyroid hormone (PTH) [Reference Lopes, Kliemann and Bini17].
Hypoparathyroidism: parathyroid gland damage or accidental removal. Can be transient (days, weeks, or months) or permanent.
Hoarseness (common): transient (24–48 hours) due to vocal cord edema caused by endotracheal tube; resolves spontaneously. Persistent or severe hoarseness is rare and can be due to arytenoid dislocation or nerve injury causing cord dysfunction → laryngoscopy and neurolaryngeal evaluation [Reference Cooper and Gittoes18].
Nerve injury and vocal cord paresis or paralysis: nerves affected include superior laryngeal (voice changes), recurrent laryngeal (difficulty swallowing and ↑ risk of aspiration) and vagus (sensory and motor deficits of larynx; ↑↑ risk of aspiration) [Reference Dralle, Sekulla, Lorenz, Brauckhoff and Machens19].
Dysphagia: uncertain etiology; may be related to postoperative adhesions, decreased laryngeal elevation, cricothyroid trauma/inflammation, or nerve damage [Reference Lombardi, Raffaelli and De Crea20].
Horner syndrome: associated with lateral neck dissection, ischemic nerve damage, or stretching of cervical sympathetic chain.
Cervical hematoma: immediate or delayed (days). Cessation of anticoagulation prior to surgery can prevent hematoma formation. If it occurs, manage with evacuation in the operating room. Hematoma must be evacuated prior to intubation, as the mass can compress the larynx, complicating intubation.
Seroma: resolves without intervention.
Chyle leak or fistula: injury to the thoracic duct most common during lateral node dissection. It can lead to severe fluid loss and electrolyte imbalance → <500 mL per day; manage with fasting, and high-output leaks require surgical repair.
Tracheal injury: necrosis due to cautery damage to small branches of the inferior thyroid artery. Can result in air leak or subcutaneous emphysema. Requires surgical repair or tracheostomy.
Parathyroid: Hyperparathyroidism versus Hypoparathyroidism – Pathophysiology, Signs and Symptoms, Differential Diagnosis, and Management
Hyperparathyroidism
The parathyroid gland is essential in maintaining proper calcium homeostasis. It secretes PTH, which acts on receptors in osteoclast cells in bone to increase bone resorption and subsequently calcium and PTH levels. Calcium-sensing receptors in the parathyroid gland regulate the amount of PTH secretion in response to calcium levels [Reference Walker and Silverberg21].
Ninety years ago, primary hyperparathyroidism (PHPT) was first discovered simultaneously in the United States and Europe. Since that time, the medical understanding of this disease process has drastically changed – initially, it was seen as being only characterized by severe symptoms of “bones, stones, groans” (e.g., osteoporosis, osteitis fibrosa cystica, nephrolithiasis, abdominal pain, and other GI symptoms); PHPT is now understood to encompass also characteristic biochemical changes of hypercalcemia and increased or inappropriately normal PTH levels, even when patients are asymptomatic [Reference Walker and Silverberg21]. Subclinical skeletal disease and osteoporosis have been observed through dual-energy X-ray absorptiometry (DEXA).
PHPT results from increased PTH secretion by abnormal parathyroid glands. The causes and respective incidences of PHPT are as follows: parathyroid adenoma (approximately 80%); parathyroid hyperplasia (10–15%); multiple adenomas (5%); and parathyroid carcinoma (<1%) [Reference Walker and Silverberg21]. It can also be seen in familial syndromes such as multiple endocrine neoplasia type 1 (MEN 1) and 2a (MEN 2a). PHPT is more commonly seen in postmenopausal women (nearly half of all patients) and African Americans.
Secondary hyperparathyroidism (SHPT) is associated with hypocalcemia and elevated PTH. Common etiologies include vitamin D deficiency, chronic kidney disease (CKD), and malabsorption. Parathyroid hyperplasia occurs in response to the hypocalcemic stimulus [Reference Muppidi, Meegada and Rehman22]. In CKD, the kidneys cannot convert vitamin D to its active form and thus have reduced absorption of calcium from the GI tract; increased phosphate levels are due to inadequate excretion by the kidneys.
Tertiary hyperparathyroidism (THPT) occurs as a sequela of protracted, severe SHPT; the parathyroid gland becomes autonomous and secrete excessively high levels of PTH, resulting in hypercalcemia and hypophosphatemia. THPT is often seen in renal transplant patients with SHPT after they continue to have high PTH levels.
Management and Treatment
Parathyroidectomy is the only definitive therapy for PHPT. It is pursued in symptomatic cases (including those with cognitive or psychiatric symptoms) and in asymptomatic cases where subclinical end-organ renal or skeletal effects have been confirmed. Medical management includes HCTZ (decreased urinary calcium excretion), estrogen replacement therapy, bisphosphonates, and cinacalcet.
Management of SHPT is typically medical and involves maintenance of normal serum calcium levels, normal phosphate levels, and control of PTH and vitamin D levels. Phosphate binders (aluminum hydroxide, sevalamer, lanthanum carbonate) and dietary restriction of phosphate-rich foods (meat, cheese, certain beverages) are used to maintain normophosphatemia. Calcimimetics such as cinacalcet or etelcalcetide improve the sensitivity of calcium-sensing receptors in the parathyroid gland and decrease PTH production. Cinacalcet is frequently used in dialysis patients [Reference Cozzolino, Galassi, Conte, Mangano, Di Lullo and Bellasi23]. Vitamin D analogs are used to decrease PTH levels and have multiple benefits in CKD patients, including improved mortality, reduced hospitalizations, and reduced inflammation [Reference Gravellone, Rizzo, Martina, Mezzina, Regalia and Gallieni24]. Surgical treatment with subtotal or total parathyroidectomy is used in cases where medical therapy has been unsuccessful or in those with severe features such as severe hypercalcemia (>10.2 mg dL−1), calciphylaxis, osteoporosis, fractures, or recalcitrant pruritus [Reference Pitt, Sippel and Chen25]. Subtotal parathyroidectomy has been associated with less postoperative hypocalcemia. Parathyroidectomy is also the cornerstone of treatment for THPT.
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