Berit L. Fischer Crown Veterinary Specialists, Lebanon, NJ, 08833, USA Endocrine disease has largely been ignored in the veterinary literature up to this point regarding its impact on anesthesia. Many would argue that this is due to the uncommon development of severe complications and the fact that many of these patients perform well despite their disease(s). This chapter presents the pathophysiology associated with veterinary endocrinopathies and how it relates to patient management in the perianesthetic period. The thyroid gland in dogs and cats is bilobed and sits just lateral to the trachea and medial to the common carotid arteries at the level of the thyroid cartilage [1]. Synthesis and secretion of thyroid hormones are dictated by the hypothalamic–pituitary–thyroid axis. Thyrotropin‐releasing hormone (TRH) from the hypothalamus acts on the anterior pituitary to stimulate the release of thyrotropin‐stimulating hormone (TSH). This then acts on the thyroid follicular cells to stimulate triiodothyronine (T3) and thyroxine (T4) synthesis and release into the circulation where they act on organs throughout the body. Thyroid hormones autoregulate their release by providing negative feedback on the pituitary and hypothalamus, thereby decreasing TSH and TRH release, respectively [1]. Thyroid hormones, especially T3, work at the cellular level to elicit a broad range of biologic effects, which directly influence metabolic rate, protein synthesis, and normal fetal development [1, 2]. Of particular interest to the anesthesiologist are their chronotropic and inotropic effects on the heart, action on the respiratory centers of the brain to maintain sensitivity to hypercarbia and hypoxemia, and role in thermoregulation [1, 3]. Thyroid hormone deficiency, through disruption of the hypothalamic–pituitary–thyroid axis, results in hypothyroidism. It is a relatively common endocrinopathy in dogs with a prevalence similar to that of humans between 0.2% and 0.8% [2, 4]. The etiology is primary in origin 95% of the time with destruction via autoimmune lymphocytic thyroiditis and idiopathic atrophy being most common. It tends to affect middle‐aged to older dogs (mean approximately 7 years) with English Setters, Golden Retrievers, Giant Schnauzers, Dobermans, Boxers, Shetland Sheepdogs, and Cocker Spaniels being overrepresented [1, 4]. No gender predisposition has been identified. Spontaneously occurring hypothyroidism in cats is rare [3]. It is most often encountered in cats which have been previously treated via radioiodine therapy or thyroidectomy for hyperthyroidism [1, 5]. Cats develop similar clinical signs as their canine counterparts including lethargy, weight gain, decreased grooming, and poor coat quality [1, 3]. Because it is a rare condition, many of the complications reported in humans and dogs have not been reported in cats. However, cats which become hypothyroid iatrogenically have an increased risk of developing azotemia and chronic kidney disease (CKD) [5]. Those that develop azotemia also have significantly shorter survival times when compared to their euthyroid, azotemic counterparts (456 vs. 728 days, respectively) [5]. Clinical signs are varied with multiple organ systems being affected (Table 9.1). Dermatologic abnormalities and signs associated with decreased metabolic rate are most common, presenting in 60–80% and 50% of hypothyroid dogs, respectively [3]. Although uncommon, cardiovascular and neuromuscular signs can be significant and are a source of perianesthetic morbidity. Table 9.1 Clinical signs and physical exam findings of hypothyroidism in dogs and cats [1, 3, 4]. a Clinical signs reported in cats. Changes seen in the CBC and biochemical profile are not pathognomonic for the disease and may not always be present. In 28–44% of dogs with hypothyroidism, a mild normocytic, normochromic, nonregenerative anemia is present [1, 4, 6]. This represents decreased erythropoiesis and bone marrow response from thyroid hormone deficiency. This anemia is rarely of concern for anesthesia but may need to be addressed in patients where significant blood loss is expected. The most common abnormalities seen on the biochemical profile are hypercholesterolemia and hypertriglyceridemia [1, 3]. These result from impaired lipid metabolism and can be associated with atherosclerosis of blood vessels. There is a positive correlation with and increased prevalence of atherosclerosis in dogs diagnosed with hypothyroidism [7]. Although atherosclerosis is rare in dogs (0.5% prevalence), patients affected by it are 51 times more likely to be hypothyroid than not [7]. Other less common findings include mild to moderate increases in alkaline phosphatase (ALKP or ALP), alanine aminotransferase (ALT), aspartate aminotransferase (AST), and creatinine kinase, as well as mild hypercalcemia and hypoglycemia [1, 8, 9]. By contrast, cats may have a low ALKP, likely caused by decreased bone turnover [5]. Abnormalities are not typically found in the urinalysis of hypothyroid dogs. However, it is important to evaluate renal function in the hypothyroid patient undergoing anesthesia. Hypothyroidism is associated with decreased glomerular filtration rate (GFR) in both dogs and cats, attributed to both vasoconstriction of the afferent and efferent arterioles via impaired nitric oxide release from endothelial cells, and decreased cardiac output from a lowered metabolic rate [5, 10]. The reduced GFR could be exacerbated in the perianesthetic period by hypotension and decreased renal perfusion resulting in additional postoperative morbidity. Diagnosis is based on the presence of clinical signs and appropriate biochemical testing. The gold standard includes determination of free thyroxine (FT4) serum levels via modified equilibrium dialysis [1, 3]. Without clinical evidence of hypothyroidism, a low serum level of T4 is not diagnostic. Breed, age, certain drugs including barbiturates and corticosteroids, and the presence of chronic disease or critical illness may falsely decrease serum T4 [1, 11]. Accurate diagnosis often requires a thyroid panel including baseline TSH concentration, free T4, and possible autoantibody tests [1]. Treatment consists of oral levothyroxine (T4) administration. Patients are often euthyroid within 4–6 weeks of treatment at an appropriate dose [1, 11]. Intravenous formulations of levothyroxine are available, but are only indicated in situations of myxedema coma, a rare manifestation of severe hypothyroidism characterized by obtundation, hypothermia, hypotension, hypoventilation, bradycardia, and nonpitting edema of the face [1, 2]. Because hypothyroidism is a common canine endocrinopathy, it is important for the anesthetist to be aware of the pathophysiology it causes and how it can be managed in the perianesthetic period. The presence of mild or subclinical hypothyroidism is not an absolute contraindication for anesthesia. However, it is ideal that patients be treated and rendered euthyroid prior to undergoing anesthesia for elective procedures [2]. Similar anesthetic practices should be utilized for the hypothyroid feline patient as well, taking care to recognize the increased risk of renal morbidity when untreated [5, 12]. Patients with a history of hypothyroidism or where there is a high index of suspicion based on clinical signs should have a thorough preanesthetic workup including physical exam, blood work (complete blood count [CBC], biochemical profile), urinalysis, and recent serum FT4 level. Numerous organ systems are affected by thyroid hormone deficiency making a systematic preanesthetic physical exam especially important. Overall body condition should be assessed, since many clinically hypothyroid patients are overweight resulting from lowered metabolic rate. Overweight or obese patients can be more difficult to manage under anesthesia [12]. Decreased thoracic compliance and compression atelectasis from increased organ weight can lead to hypoventilation and ventilation–perfusion mismatch [6, 12]. This could be exacerbated by decreased sensitivity and poor response to hypercarbia and hypoxemia, as well as altered diffusion of oxygen across the alveolar capillary membrane [2]. Careful cardiovascular evaluation should be performed because hypothyroidism leads to decreased numbers and affinity of beta‐adrenergic receptors and a decreased catecholaminergic response [1]. Hypothyroid patients can present with bradyarrhythmias, poor peripheral pulses, and a weak apex beat from impaired myocardial contractility, decreased cardiac output, and poor peripheral perfusion [1, 3]. Although this decrease in contractility may be mild in most situations, severe cases of systolic dysfunction resulting in congestive heart failure have been reported in the dog [13]. Thoracic radiographs with or without an echocardiogram should be strongly considered in patients where physical exam findings suggest reduced cardiac function, and are essential in patients where a murmur, arrhythmia, or evidence of congestive heart failure (i.e., jugular pulses, coughing, exercise intolerance) is present. In patients with arrhythmias, an electrocardiogram (ECG) should be evaluated. Sinus bradycardia with decreased QRS amplitude and inverted T waves is most common. However, first‐ and second‐degree atrioventricular blocks, ectopic beats, and, rarely, atrial fibrillation may be identified because of coronary artery atherosclerosis and subsequent myocardial hypoxia [1, 3, 7]. Blood pressure readings may reveal mild diastolic hypertension because of increased systemic vascular resistance (SVR) [2, 10, 14]. Hypertension does not usually require treatment, but the anesthetist should be aware that this could decrease circulating blood volume. When combined with the profound response hypothyroid patients often have to anesthetic drugs, significant hypovolemia and hypotension could result [2, 6]. An attempt to avoid this should be made by correcting any fluid deficits before anesthesia. Neuromuscular system evaluation is important because thyroid hormones play a vital role in axon growth and transport [3]. Peripheral neuropathies and myopathies causing generalized weakness, ataxia, and knuckling, progressing to paresis and paralysis, may develop in hypothyroid patients [3, 4]. Cranial nerves may also be affected, leading to decreased facial sensation, facial nerve paralysis, and vestibular disease. Despite being mentioned in concert with hypothyroidism, a causal relationship with laryngeal paralysis and megaesophagus has not been established [1, 3]. Although not common, seizures, disorientation, and circling can occur in hypothyroid dogs as a result of cerebral hypoxia originating from atherosclerosis of cerebral vessels [3, 7, 16, 17]. In such cases, further impairment could occur following anesthesia [17]. Thyroid neoplasia is an uncommon cause of hypothyroidism in dogs; however, examination of the cervical region should be performed. Thyroid carcinomas or squamous cell carcinomas can be large enough to cause upper airway obstruction. Affected dogs may drool, cough, have a history of voice change, or have respiratory distress [1, 12]. Preparation for a difficult airway intubation including tracheostomy setup should be performed. Hypothyroid patients may have altered anesthetic drug responses. Although a true sensitivity may not exist, the combination of lowered cardiac output, decreased circulating blood volume, hepatic metabolism, and renal excretion of drugs results in more profound changes in depth and hemodynamic parameters than expected in the euthyroid patient [2, 6]. Because inhalant anesthesia decreases metabolic rate, it is difficult to ascertain how hypothyroidism specifically influences minimum alveolar concentration (MAC) reduction. However, this is thought to be negligible [18]. Certainly, decreased thermoregulatory ability and cardiac output alone can significantly lower inhalant requirements in these patients [14, 18]. The untreated hypothyroid patient may respond to anesthesia with greater hemodynamic instability. It is advisable to choose anesthetic drugs that are relatively short‐acting and titratable to minimize negative cardiovascular effects. The phenothiazine tranquilizer, acepromazine, is long‐acting and causes vasodilation through antagonism of alpha‐1‐adrenergic receptors [19]. In hypothyroid patients who are volume‐contracted and have decreased metabolic capabilities, it is best avoided. Ketamine has been promoted in human literature because of its ability to increase cardiac output and blood pressure in patients with an intact sympathetic nervous system [2]. Caution is advised in those hypothyroid patients who have arrhythmias or suspected myocardial dysfunction, since increases in myocardial oxygen demand could result in greater hemodynamic instability [1]. Decreased gastric‐emptying time and ileus have been documented in humans with hypothyroidism and are suspected to occur in veterinary patients as well [1, 2, 6]. A full stomach could result in regurgitation and aspiration of gastric contents, as well as impair ventilation. Administration of gastroprotectants and prokinetics is recommended prior to anesthesia in humans and may be of use in veterinary patients as well [2, 6]. Hypothermia is a significant concern in the hypothyroid patient and results from impaired hypothalamic thermoregulation [2]. Hypothermia can be difficult to prevent and treat, and, when severe, can lead to impaired coagulation, decreased inhalant MAC, impaired response to adrenergic drugs, bradycardia, and refractory hypotension [2, 6]. Patient prewarming using a convective heat source for 20–30 min before anesthetic induction prevents hypothermia in healthy humans and dogs [6, 20]. Although it has not been evaluated in veterinary patients with hypothyroidism, prewarming is suggested to prevent hypothermia. Because they tend to have minimal effects on the cardiovascular and respiratory systems, a combination of an opioid and benzodiazepine is favorable for premedication in the hypothyroid patient. Induction using propofol or alfaxalone allows titration to effect; however, rapid administration may lead to apnea and profound hypotension from vasodilation. Ketamine, as stated earlier, may benefit the otherwise healthy, hypothyroid patient because it indirectly stimulates the sympathetic nervous system to help support cardiac output, heart rate, and blood pressure. Either isoflurane or sevoflurane can be used for maintaining anesthesia. Before anesthetic induction, the patient should be preoxygenated for 3–5 min, as reduced functional residual capacity (FRC) from increased body weight and possible airway obstruction from swollen pharyngeal tissues could lead to rapid desaturation [2, 12]. Induction and establishment of a patent airway should be rapid to avoid hypoxemia and hypoventilation, as well as aspiration of gastric contents. Standard monitoring including blood pressure, capnometry, pulse oximetry, ECG, and temperature should be used. Direct or indirect methods of blood pressure monitoring can be used depending on the invasiveness of the procedure and American Society of Anesthesiologists (ASA) physical status of the patient. In patients in whom cardiovascular dysfunction is suspected, direct blood pressure monitoring is indicated. If hypotension occurs, a systematic approach to treatment should be sought. Bolus administration of a crystalloid (5–10 ml kg−1) along with a reduction in inhalant anesthetic concentration can help to minimize vasodilation and maintain adequate venous return to the heart. Bradyarrhythmias can be treated through anticholinergic administration and decreased myocardial contractility may benefit from positive inotropic support [2, 12]. Commonly used positive inotropes in veterinary medicine include dopamine (3–10 μg kg−1 min−1) or dobutamine (1–10 μg kg−1 min−1). In humans, hypothyroidism can lead to a concomitant decrease in adrenal cortical function and decreased circulating cortisol levels. If hypotension is refractory to treatment using the abovementioned methods, a physiologic dose of corticosteroids could be considered [2]. Prevention and aggressive treatment of hypothermia with active methods for warming including intravenous fluid warmers, circulating warm water blankets, and convective air warmers should be used. Assisted ventilation is often required because of decreased thoracic compliance and decreased sensitivity to hypercarbia and hypoxemia [12]. Locoregional anesthetic techniques are an important component of balanced anesthesia when indicated. In patients in whom a peripheral neuropathy is present, caution should be used because neurologic deficits may be exacerbated after regional anesthesia [21]. If additional hair clipping is required for locoregional anesthesia, it is advisable to inform the owner that hair regrowth may be slow or not occur [1]. Monitoring should continue into the postanesthetic period. Recovery is often prolonged because of decreased hepatic metabolism and renal excretion of anesthetic drugs [2, 12]. Esophageal suctioning prior to recovery may prevent aspiration of gastric contents if silent regurgitation occurred during anesthesia. Respiratory depression may lead to postoperative hypoventilation with subsequent hypoxemia. Administration of supplemental oxygen via mask, prongs, or nasal catheter should occur after extubation if hemoglobin oxygen saturation decreases below 94%. Just as thyroid hormone deficiency results in multisystem dysfunction, excessive thyroid hormone also creates a montage of effects throughout the body. Hyperthyroidism is the most common endocrinopathy in cats older than 8 years with a mean age of 13 years [22]. The etiology is primary in origin and typically caused by multinodular adenomatous goiter or adenomatous hyperplasia like humans. No secondary or tertiary causes have been identified in cats, nor has a breed or gender predisposition been found [22]. Hyperthyroidism in dogs is uncommon. It is often the result of a functional thyroid carcinoma which occurs only in approximately 10% of dogs with thyroid neoplasia [23]. Affected dogs are typically older than 8 years and more than half have distant metastases to the lung, regional lymph nodes, or liver at the time of diagnosis [23]. Another cause of canine hyperthyroidism includes excessive levothyroxine administration to dogs being treated for hypothyroidism. In dogs identified with hyperthyroidism, anesthetic precautions and preparation are like that of cats. Thyroid hormones influence all tissues throughout the body by increasing gene transcription [22, 24, 25]. Excess thyroid hormone results in an overall increase in basal metabolic rate, which increases energy needs and oxygen consumption [22, 24]. The most common clinical signs in cats are weight loss and polyphagia (Figure 9.1) [22]. Affected cats also exhibit hyperactivity and aggression and may be difficult to restrain for physical exam and blood sampling. Gastrointestinal signs of vomiting and diarrhea may be present. Diarrhea likely results from decreased ororectal transit time and malabsorption. The cause of vomiting has not been fully elucidated but may result from thyroid hormone activity on the chemoreceptor trigger zone and altered motility of the esophagus, stomach, and duodenum [22]. Because hyperthyroidism is one of many causes of “endocrine hypertension,” signs associated with high blood pressure including blindness or seizures could be present [24–27]. Panting, tachypnea, and dyspnea may occur from hyperthermia, respiratory muscle weakness, increased metabolic oxygen requirements, and cardiac failure [22, 26].. Thyroid neoplasia in the dog can have signs attributable to a cervical space‐occupying mass including dysphagia, drooling, voice change, and varying amounts of respiratory distress [23]. Proper preparation for emergency airway management is imperative in these cases. Figure 9.1 A hyperthyroid cat. Note the thin body condition and unkempt appearance. Like hypothyroidism, there are no pathognomonic hematologic or biochemical changes associated with hyperthyroidism. The most common hematologic finding in cats is a mild increase in packed cell volume (PCV) reflective of the stimulatory effects thyroid hormones have on erythropoiesis [22]. Moderate increases in ALT and ALKP from a combination of increased bone turnover and decreased hepatic perfusion are seen in approximately 75% of hyperthyroid cats [22]. The presence or absence of azotemia should be interpreted with caution. Both increases in GFR from the high cardiac output state and decreased muscle mass result in lower serum concentrations of creatinine potentially masking CKD. Additional testing utilizing the renal biomarker, symmetric dimethylarginine (SDMA), and urine specific gravity (USG) may be more useful to the anesthetist when evaluating for underlying renal disease. Suggested cutoffs of >10 μg dl−1 and <1.030 for SDMA and USG, respectively, may improve sensitivity in detecting masked CKD in hyperthyroid cats [28]. Hypernatremia, hypokalemia, and hypercalcemia can also occur [22]. Potassium should be monitored carefully, as hypokalemia can be severe and cause muscle weakness. Hypercalcemia can be paraneoplastic in the dog or reflective of increased bone turnover [23]. Elevated serum calcium when combined with a heart that is already sensitized to catecholamines can result in myocardial irritability and arrhythmia formation [22, 29]. Hypercoagulability occurs in hyperthyroid humans and cats and could contribute to significant morbidity in the perianesthetic period [22, 29, 30]. Proposed mechanisms include increases in Factor VIII, Factor IX, fibrinogen, and altered metabolism of vitamin K. Although anticoagulant therapy has been used in preparation for human surgery, its use is controversial [22, 26, 29, 30]. Consideration for postoperative antithrombotic treatment may be advisable, particularly in cats already at risk for thrombosis from concurrent cardiac dysfunction. Diagnosis is usually straightforward in the face of appropriate clinical signs and an elevated T4 level. Additional diagnostics including cervical ultrasonography and scintigraphy can be used to confirm diagnosis should the T4 concentration not be supportive or where concurrent disease may falsely decrease thyroid hormone levels [22]. There are multiple treatment options for hyperthyroidism in cats. Definitive treatments, such as thyroidectomy or radioiodine therapy, require the patient to be anesthetized or heavily sedated. Patients should be medically managed and euthyroid prior to anesthesia for elective procedures to avoid significant complications that can accompany uncontrolled hyperthyroidism [2, 31, 32]. This is done through the administration of methimazole, or, in Europe, carbimazole [22, 25, 32, 33]. Both are thioureylenes, which inhibit the synthesis of thyroid hormones, but do not influence thyroid hormones already in circulation. It is expected that cats treated via oral or transdermal routes are euthyroid with a decrease in clinical signs after 2–4 weeks of therapy [33]. T4 levels may respond within 1 week, so cases where there is a greater sense of urgency should be checked at that time [22, 25]. In patients where treatment with thioureylenes or other definitive means is not possible, the use of a commercial low iodine diet has also been used successfully to treat hyperthyroidism with normalization of total T4 concentrations being observed as early as 4 weeks of exclusive feeding [34]. Definitive treatment for functional thyroid carcinomas in dogs is thyroidectomy and requires similar medical management prior to anesthesia [23]. Anesthetic management of the hyperthyroid patient can present a myriad of complications. While mild hypothyroidism may not overtly affect anesthesia, even mild hyperthyroidism can be of concern to the anesthetist. As with hypothyroidism, a thorough preanesthetic physical exam, considering the pathophysiology of hyperthyroidism, should be performed along with appropriate imaging and clinicopathologic testing. Weight loss can be dramatic, and many patients present with cachexia. Although hyperthermia may be present in the awake state, the absence of body fat and the peripheral vasodilation from T3‐induced relaxation of vascular smooth muscle can lead to rapid loss of core body heat in the anesthetized patient [1, 29]. Similarly, there is equal risk of hyperthermia, as patients may respond rapidly to warming measures or could potentially develop a thyrotoxic crisis caused by excessive release of thyroid hormones [2, 26, 31, 35]. The cardiovascular system is greatly affected by excess thyroid hormone necessitating a full cardiac workup before anesthesia. T3 acts directly on myocardial sodium, potassium, and calcium channels, as well as on α‐myosin chains to increase contractility [36]. It also directly relaxes vascular smooth muscle causing peripheral vasodilation. The resulting decrease in SVR causes activation of the renin–angiotensin–aldosterone system (RAAS) leading to increased plasma volume and a 50–400% increase in cardiac output [22, 32, 36]. In addition, the number and affinity of beta‐adrenergic receptors increase leading to increased myocardial sensitivity to catecholamines. These cardiovascular changes increase the work and oxygen demand of the heart causing progressive left ventricular hypertrophy and subsequent cardiac failure [22, 36]. Thus, patients often present with tachyarrhythmias and bounding peripheral pulses. Auscultation may reveal a systolic murmur, gallop rhythm, and adventitious pulmonary sounds consistent with cardiac failure [22, 26]. Systolic hypertension is present in approximately 17–87% of hyperthyroid cats and can also be found in dogs, necessitating blood pressure measurements in the preanesthetic evaluation [22, 24, 37]. Its presence can be associated with retinopathies or encephalopathies resulting in blindness, seizures, ataxia, and altered mental status. Hypertension may require treatment prior to anesthesia with antihypertensive drugs, such as amlodipine. Beta‐adrenergic antagonists can be effective for decreasing heart rate but are only effective in decreasing blood pressure in approximately 30% of affected cats [24]. Cardiomegaly may not be seen on thoracic radiographs. Pleural effusion or pulmonary edema may be present if heart failure has occurred or in the rare situation of pulmonary hypertension. In dogs, radiographs may reveal metastasis that could impair oxygenation and ventilation under anesthesia [23]. Thyrotoxic cardiomyopathy is present in many affected cats but may vary in severity. Therefore, even if cardiomegaly is not present, echocardiography is recommended if a murmur is auscultated. Plasma levels of the N‐terminal prohormone of brain natriuretic peptide (proBNP), a biomarker upregulated in the presence of myocardial stretch, can be used to help identify cats with potentially moderate to severe cardiac dysfunction when echocardiography is unavailable [38]. The anesthetist should be aware, however, that proBNP can be falsely elevated in the presence of azotemia. Common ECG findings in hyperthyroidism include increased R‐wave amplitude, sinus tachycardia, atrial fibrillation, supraventricular tachycardia, and atrial or ventricular premature contractions, all reflective of increased catecholamine sensitivity and/or myocardial hypoxia [22, 26]. Before surgery, a minimum database of PCV, total solids, electrolytes, and acid–base status should be performed with any aberrations identified and treated. Owners should be instructed to continue antithyroid medications the day of anesthesia because all have relatively short half‐lives like that of humans [6, 31]. Increased metabolic rate, cardiac output, and hyperthermia caused by untreated hyperthyroidism lead to altered pharmacokinetics and pharmacodynamics of numerous anesthetic drugs. For example, in humans, hyperthyroid patients require increased fentanyl and propofol doses, and propofol clearance and volume of distribution are significantly increased [39]. Pharmacokinetics of the benzodiazepine, oxazepam, in rodents with hyperthyroidism also show increased dosing requirements to achieve effects similar to those in euthyroid rats [40]. Because of the variable drug responses and dramatic hemodynamic changes, it is best to use short‐acting and reversible agents such as opioids and benzodiazepines at standard doses, administering additional drug only if adequate sedation is not achieved. Drugs that promote activation of the sympathetic nervous system should be avoided, including ketamine at large induction doses [2, 6, 12]. Indirect catecholamine release could further increase oxygen demands of the heart, leading to myocardial hypoxia and malignant arrhythmias. Likewise, anticholinergics should be used with discretion [2, 6, 12]. Acepromazine has been advocated in the past because it desensitizes the myocardium to catecholamines [12]. However, with the advent of short‐acting, antihypertensive agents, and concerns over rapid drops in preload associated with acepromazine, it should be used cautiously. Thiopental was also long advocated for use in hyperthyroidism due to its ability to block peripheral conversion of T4 to T3 [6, 12]. However, it is not available in the United States, making propofol or alfaxalone acceptable alternatives. Preoxygenation should be performed before anesthetic induction because of increased oxygen demand of the tissues and the increased likelihood of developing hypoxemia [12]. This allows increased time for an airway to be established before hemoglobin desaturation. Anesthesia can be maintained safely in the hyperthyroid patient with inhalant or injectable anesthetics (total intravenous anesthesia [TIVA]) [12, 39]. Although the MAC of inhalants does not increase, the required doses of injectable drugs needed to maintain an adequate anesthetic plane may be higher than expected [12, 39]. Stress minimization during anesthesia avoids excessive catecholamine release and associated cardiovascular responses [6]. A constant rate infusion (CRI) of fentanyl (5–42 μg kg−1 h−1) or locoregional block, if necessary, may assist in reducing the stress response and provides analgesia during anesthesia. In hyperthyroid patients who require anesthesia, extensive hemodynamic monitoring should be used including invasive blood pressure monitoring, ECG, capnometry, and pulse oximetry. Temperature monitoring is vital to monitor for hypothermia or hyperthermia. Because CO2 production can be increased from the elevated basal metabolic rate, a rebreathing circuit is advised to ensure adequate CO2 removal [12]. Intermittent positive pressure ventilation (IPPV) may also benefit the patient, since muscle weakness can predispose them to hypoventilation, hypercapnia, and subsequent indirect stimulation of the sympathetic nervous system [41]. Cautious fluid use is advised in the face of cardiac dysfunction and objective means of monitoring volume status should be used whenever possible. Sudden upward trends in central venous pressure may also help identify the onset of cardiac failure and volume overload. However, it is less useful in identifying low volume states and in guiding intraoperative fluid therapy. The use of dynamic fluid indices such as pulse pressure variation or plethysmography variance index, while still in their infancy in veterinary medicine, may prove to be better determinants of volume responsiveness [42]. Because hyperthyroid patients have higher metabolic oxygen requirements, tissue oxygen delivery is important to assess intraoperatively. In addition to monitoring hemodynamics and arterial oxygen partial pressure (PaO2), the anesthetist may also consider the use of serial lactate concentrations, base deficits, and venous–arterial PCO2 differences to further identify poor oxygen delivery and track response to therapy [43]. Thyroid storm is a rare, life‐threatening manifestation of uncontrolled hyperthyroidism well‐described in humans [26, 29, 35]. It results from the sudden release of thyroid hormones into the circulation caused by a precipitating event such as stress, anesthesia, infection, trauma, or illness [26, 35]. Since there is no correlation between circulating hormone levels and the development of thyroid storm, it is difficult to ascertain which patients are at risk [26, 39]. Acute thyrotoxicosis, which presents similarly, can occur in veterinary species [26]. Clinical signs include exacerbation of those associated with hyperthyroidism, including tachyarrhythmias, hypertension, hyperthermia, congestive heart failure, and cardiac arrest (Table 9.2) [26]. Treatment targets decreasing thyroid hormone synthesis and secretion, blocking thyroid hormone actions at their effector sites, providing supportive care, and eliminating the precipitating cause [26, 29, 35]. Methimazole is the drug of choice to decrease synthesis of thyroid hormones. However, in situations of thyroid storm, methimazole is administered in combination with an iodine compound, such as potassium iodate, to prevent preformed thyroid hormone secretion [26]. While the immediate preanesthetic administration of methimazole to untreated hyperthyroid cats has not been investigated in terms of its effects on a thyrotoxic crisis, it appears reasonable that pretreatment may minimize severity when combined with other systemic treatments and is the current recommendation in thyrotoxic humans faced with emergent anesthesia [2]. Tachyarrhythmias and hypertension are in part caused by increased sensitivity to catecholamines and can be combated by administration of a beta‐adrenergic antagonist. Under anesthesia, the most rapid‐acting, titratable agent available is the selective beta‐1‐antagonist, esmolol (0.05–0.15 mg kg−1 slow IV bolus followed by a CRI of 10–200 μg kg−1 min−1) [19, 26]. Severe hypertension can also be treated with sodium nitroprusside or magnesium sulfate similar to patients with pheochromocytoma [19, 44]. Caution should be used with antihypertensive drugs, as patients with acute thyrotoxicosis are already maximally vasodilated and volume depleted. Indiscriminate use could lead to rapid cardiovascular collapse [24]. Table 9.2 Clinical manifestations of thyrotoxicosis [26, 27, 34]. Source: Adapted with permission from reference [26]. a Manifestations observed under anesthesia. Supporting therapy should include goal‐directed replacement of circulating volume with crystalloids and colloids, as well as treatment of hyperthermia with active cooling methods such as ice packs [26, 29]. Dextrose and potassium supplementation may be needed because of increased energy requirements [2]. Mechanical ventilation should be instituted to help eliminate excessive carbon dioxide produced in the pyrexic state. Cardiac failure and pulmonary edema may necessitate administration of diuretics to improve oxygenation and ventilation [26]. Monitoring should continue during recovery because thyroid storm in humans can occur up to 48 h after anesthesia [29]. Supplemental oxygen should be available to fulfill elevated metabolic oxygen requirements and prevent hypoxemia. Frequent blood pressure monitoring and telemetry can help identify the development of hypertension and arrhythmias in the immediate postoperative period. Patients undergoing surgery should receive appropriate multimodal analgesia to minimize pain and stress, as well as continued antithyroid drug administration. Adrenal glands represent another integral component of the endocrine system, playing a vital role in fluid balance, the stress response, and sympathetic nervous system activation [6, 45]. They are paired, ovoid structures lying near the cranial pole of the kidneys and are composed of a cortex and medulla. The cortex has three layers: the zona glomerulosa secretes aldosterone to stimulate sodium and water retention, and the zona fasciculata and zona reticularis function together to produce cortisol and androgens. The medulla is functionally separate, producing catecholamines [45]. Cortisol is normally secreted from the adrenal cortex under the regulation of the hypothalamic–anterior pituitary–adrenal axis [45]. The hypothalamus secretes corticotropin‐releasing hormone (CRH) to act on the anterior pituitary. It subsequently releases adrenocorticotropic hormone (ACTH) to stimulate secretion of cortisol from the adrenal cortex [45]. Other than hypothyroidism, HAC is the most common endocrinopathy seen in middle‐aged to older dogs [45]. Hyperadrenocorticism is caused by excessive circulating glucocorticoids, namely, cortisol, and can be caused by a primary functional adrenocortical tumor (AT) or be secondary to an ACTH‐secreting pituitary adenoma (pituitary‐dependent hyperadrenocorticism; PDH). Iatrogenic HAC from overzealous administration of glucocorticoids is also reported [45]. PDH is cited as the cause of HAC in approximately 80–85% of dogs [27, 45, 46]. Mean age of affected dogs is approximately 11 years with very little difference between PDH and AT. Common breeds include Poodles, Terriers, Beagles, and Dachshunds with females being overrepresented [45, 46]. Hypoadrenocorticism is rare in cats and the etiology is most commonly pituitary in origin [47, 48]. Middle‐aged to older cats are primarily affected with a median age of 10 years. No sex or breed predilection has been identified [47, 48]. Cortisol, like other endocrine hormones, has a wide scope of target organs and effects, including stimulation of hepatic gluconeogenesis, lipolysis, and protein catabolism. It can also impact erythropoiesis, vascular tone, kidney function, and acts as a “safety net” in times of stress to maintain homeostasis [45]. Compared to other endocrinopathies, the clinical presentation of HAC can be strikingly different between dogs and cats, since cats are considerably less responsive to the effects of glucocorticoids [48]. Dogs commonly present with polyuria/polydipsia from cortisol inhibition of antidiuretic hormone (ADH) release, and polyphagia, a presenting complaint not witnessed in other species [45]. Panting, pendulous abdomen, muscle weakness, and endocrine alopecia can help diagnose canine Cushing’s disease (Figure 9.2) [12, 45, 46]. Clinical signs of HAC in cats tend to be more elusive and may not occur until other concurrent disease, such as diabetes mellitus, manifests [47, 48]. Cats demonstrate muscle weakness, poor haircoat, tachypnea, and thin, fragile skin [47, 48]. Rarely, both species may present with encephalopathies or retinopathies from atherosclerosis, pituitary tumor impingement, or secondary hypertension [45,47–50]. Cortisol causes neutrophilia, monocytosis, lymphopenia, and eosinopenia [45]. This “stress leukogram” is seen commonly in dogs, whereas cats may show few hematologic changes [48]. Polycythemia can be caused by cortisol‐induced erythropoiesis, increased circulating half‐lives of red blood cells, or may signal the presence of a chronic hypoxic state from alveolar hypoventilation [45]. Changes in the biochemical profile can differ between dogs and cats, but increased ALT from hepatocyte damage and impaired hepatic perfusion as well as hypercholesterolemia from increased lipolysis are seen in both species [45]. Both may also demonstrate mild to moderate hyperglycemia from increased gluconeogenesis and impaired insulin sensitivity [45, 48]. Dogs alone see dramatic elevations in ALKP from induction of a steroid‐responsive ALKP isozyme not present in other species [45, 48]. Cortisol prevents ADH from binding to receptors on the renal tubules causing diuresis and a subsequent decrease in blood urea nitrogen (BUN) in dogs [45]. This is not observed in cats due to decreased renal glucocorticoid receptors [48]. Figure 9.2 A dog diagnosed with hyperadrenocorticism caused by a functional adrenocortical tumor after presenting for polyuria, polydipsia, and muscle weakness. Note the thin, patchy haircoat.
9
Endocrine Disease
Introduction
Thyroid Disease
Thyroid Gland Anatomy and Physiology
Thyroid Hormone Effects
Hypothyroidism
Canine Hypothyroidism
Feline Hypothyroidism
Clinical Signs and Symptoms
Decreased metabolic rate
Lethargya
Weakness
Weight gaina
Exercise intolerance
Hypothermiaa
Mental dullness
Decreased appetitea
Dermatologic
Endocrine alopecia
Dull, brittle haircoata
Poor regrowth of haira
Hyperpigmentation
Poor wound healing
Bruising
Myxedema (puffy face)a
Decreased groominga
Recurrent bacterial infections
Cardiovascular
Sinus bradycardiaa
Weak apex beat
Decreased peripheral pulses
Diastolic hypertension
Decreased left ventricular pump function
Low QRS voltage
Inverted T waves
Cardiac arrhythmias
Gastrointestinal
Constipation
Diarrhea
Delayed gastric emptying
Neuromuscular
CNS
Seizures
Ataxia
Head tilt
Positional nystagmus
Strabismus
Decreased facial sensation
PNS
Generalized weakness
Knuckling
Dragging of limbs
Paraparesis
Quadriparesis
Paralysis
Lameness
Exercise intolerance
Muscle atrophy
Myopathy
+/– Larngeal paralys
+/– Megaesophagus
Clinicopathologic Findings
Diagnosis
Treatment
Anesthetic Management
Preanesthetic Physical Exam
Preanesthetic Period
Intraoperative Period
Monitoring
Locoregional Anesthesia and Analgesia
Anesthetic Recovery
Hyperthyroidism
Feline Hyperthyroidism
Canine Hyperthyroidism
Clinical Signs and Symptoms
Clinicopathologic Findings
Diagnosis
Treatment
Anesthetic Management
Preanesthetic Period
Intraoperative Period
Monitoring
Thyroid Storm
Cardiac arrhythmiasa
Hypertensiona
Tachypnea
Hyperthermiaa
Panting
Dyspnea
Pulmonary edema
Muscle weakness
Congestive heart failure
Cardiac arresta
Postanesthetic Management
Adrenal Disease
Adrenal Gland Anatomy and Physiology
Hyperadrenocorticism (HAC; Cushing’s Disease)
Canine Hyperadrenocorticism
Feline Hyperadrenocorticism
Clinical Signs
Clinicopathologic Changes
Stay updated, free articles. Join our Telegram channel
Full access? Get Clinical Tree
