2023 AAHA Selected Endocrinopathies of Dogs and Cats Guidelines

VETERINARY PRACTICE GUIDELINES 2023 AAHA Selected Endocrinopathies of Dogs and Cats Guidelines Andrew Bugbee, DVM, DACVIM,† Renee Rucinsky, DVM, DABVP (Feline Practice),† Sarah Cazabon, DVM, Heather Kvitko-White, DVM, DACVIM, Patty Lathan, VMD, MS, DACVIM (Small Animal Internal Medicine), Amy Nichelason, DVM, DABVP (Canine and Feline), Liza Rudolph, BAS, RVT, VTS (Canine and Feline) (Small Animal Internal Medicine) ABSTRACT Canine and feline endocrinopathies reflect an endocrine gland disease or dysfunction with resulting hormonal abnormalities that can variably affect the patient’s wellbeing, quality of life, and life expectancy. These guidelines provide consensus recommendations for diagnosis and treatment of four canine and feline endocrinopathies commonly encountered in clinical practice: canine hypothyroidism, canine hypercortisolism (Cushing’s syndrome), canine hypoadrenocorticism (Addison’s disease), and feline hyperthyroidism. To aid the general practitioner in navigating these common diseases, a stepwise diagnosis and treatment algorithm and relevant background information is provided for managing each of these diseases. The guidelines also describe, in lesser detail, the diagnosis and treatment of three relatively less common endocrinopathies of cats: feline hyperaldosteronism, feline hypothyroidism, and feline hyperadrenocorticism. Additionally, the guidelines present tips on effective veterinary team utilization and client communication when discussing endocrine cases. (J Am Anim Hosp Assoc 2023; 59:䊏–䊏. DOI 10.5326/JAAHA-MS-7368) AFFILIATIONS Department of Small Animal Medicine and Surgery, University of Georgia, limitations unique to each individual practice setting. Evidence-guided Athens, Georgia (A.B.); Mid Atlantic Cat Hospital, Mid Atlantic Feline Thyroid and appropriate. Other recommendations are based on practical clinical Center, Queenstown, Maryland (R.R.); Boston Veterinary Clinic, Boston, Massachusetts (S.C.); KW Veterinary Consulting, LLC, Kansas City, Missouri experience and a consensus of expert opinion. Further research is (H.K.-W.); Mississippi State University, Mississippi State, Mississippi (P.L.); and labeling are current at the time of writing but may change over time. School of Veterinary Medicine, University of Wisconsin-Madison, Madison, Because each case is different, veterinarians must base their decisions Wisconsin (A.N.); Rowan College of South Jersey, Sewell, New Jersey (L.R.) on the best available scientific evidence in conjunction with their own knowledge and experience. CONTRIBUTING REVIEWERS support for specific recommendations has been cited whenever possible needed to document some of these recommendations. Drug approvals Audrey Cook, BVM&S, FRCVS, DACVIM-SAIM, DECVIM-CA, DABVP The 2023 AAHA Selected Endocrinopathies of Dogs and Cats Guide- (Feline), Texas A&M University Department of Small Animal Clinical Sciences lines are generously supported by Boehringer Ingelheim Animal Health, Daniel Langlois, DVM, DACVIM, Michigan State University College of Veteri- IDEXX, Merck, Zoetis, and Zomedica. nary Medicine Correspondence: [email protected] (A.B.); [email protected] (R.R.) † A. Bugbee and R. Rucinsky are the cochairs of the AAHA Selected Endocrinopathies of Dogs and Cats Guidelines Task Force. ACTH (adrenocorticotropic hormone); ACTHST (adrenocorticotropic hormone stimulation test); ADH (adrenal-dependent hyperadrenocortisolism); ALP (alkaline phosphatase); ALT (alanine aminotransferase); CKD (chronic kidney disease); CS (Cushing’s syndrome); DOCP (desoxycorticosterone pivalate); FHT (feline hyperthyroidism); fT4 (free thyroxine); fT4ed (free thyrox- These guidelines were prepared by a task force of experts convened by ine by equilibrium dialysis); HA (hypoadrenocorticism); HAC (hyperadreno- the American Animal Hospital Association. This document is intended as corticism); a guideline only, not an AAHA standard of care. These guidelines and suppression test); PDH (pituitary-dependent hyperadrenocortisolism); PHA recommendations should not be construed as dictating an exclusive pro- (primary hyperaldosteronism); SHT (systemic hypertension); T3 (triiodothyro- tocol, course of treatment, or procedure. Variations in practice may be nine); T4 (thyroxine); TSH (thyroid-stimulating hormone); TT4 (total thyroxine warranted based on the needs of the individual patient, resources, and concentration); UCCR (urine cortisol-to-creatinine ratio) © 2023 by American Animal Hospital Association 131 I (radioactive iodine); LDDST (low-dose dexamethasone JAAHA.ORG 1 Introduction to treatment recommendations and improved case outcomes is Veterinary clinicians routinely encounter and are expected to manage expected. various endocrinopathies in their canine and feline patients. Most commonly, these conditions include canine hypothyroidism, canine Canine Hypothyroidism hypercortisolism (Cushing’s syndrome), canine hypoadrenocorticism Overview (Addison’s disease), and feline hyperthyroidism (FHT). Canine and Hypothyroidism is most commonly an acquired condition of adult feline diabetes mellitus is not discussed in these guidelines but is dogs characterized by primary failure of the thyroid gland to produce 1 addressed in previously published guidelines. These endocrinopathies adequate amounts of thyroxine (T4) and triiodothyronine (T3). Path- can be overt or have minimal clinical impact, especially in early-stage ogenesis commonly involves immune-mediated destruction of func- disease. Diagnosis relies on a recognition of clinical signs or physical tional thyroid tissue (thyroiditis) or idiopathic thyroid atrophy, which examination abnormalities, careful compilation of the patient’s his- may represent end-stage thyroiditis.3 Well-documented breed associa- tory, interpretation of hormone concentration assays, and exclusion tions support a genetic susceptibility, with a selection of commonly of comorbidities that can complicate an accurate diagnosis. Early affected breeds including English setters, Doberman pinschers, Rho- intervention in endocrinopathy cases avoids the severe syndromes desian ridgebacks, and golden and Labrador retrievers.4–7 Disruption that can impact the patient’s quality of life and cause secondary organ of other portions of the thyroid axis are rarely reported as causes of damage and mortality. The guidelines are designed to provide practi- hypothyroidism, such as reduced secretion of pituitary thyroid- tioners with a practical, stepwise approach to the diagnosis and treat- stimulating hormone (TSH) or hypothalamic thyrotropin-releasing ment of the four most common canine and feline endocrinopathies. hormone.8 Congenital hypothyroidism resulting from inherited gen- The guidelines introduce each endocrinopathy by providing a definition and clinical profile of the disease. In addition to the four etic defects or abnormal thyroid gland development have been rarely reported in dogs.9–11 principal diseases described in the guidelines, three less common feline endocrinopathies are also discussed: feline hyperaldosteronism, feline hypothyroidism, and feline hyperadrenocorticism. The guidelines are not intended to cover all endocrinopathies that affect dogs and cats, but to provide a foundation for accurate recognition and diagnosis and effective clinical management of the most common endocrine-related morbidities. Practitioners will benefit from consulting the abundant literature to gain additional clinical perspectives on each disease. Diagnostic Testing and Monitoring Clinical signs of canine hypothyroidism often manifest in middle age, with a mean age at diagnosis reported to be 6.8 yr.12 Signs may be subtle and slowly progress over months to years. Dermatologic abnormalities occur frequently and often include truncal nonpruritic alopecia, “rat tail” appearance, poor coat quality, seborrhea, hyperpigmentation, and recurrent pyoderma.6 Other commonly reported The guidelines discuss the four principal endocrinopathies clinical signs include lethargy, mental dullness, exercise intolerance, using an innovative, categorical approach to diagnosis based on clin- obesity or unexplained weight gain, and heat-seeking behaviors. Less ical presentation, as previously described in the 2016 AAFP Guide- commonly reported associations include facial nerve paralysis, vestib- 2 lines for the Management of Feline Hyperthyroidism. This approach ular disease, and polyneuropathy.13 evaluates the patient’s clinical presentation as determined by the Abnormalities on initial biochemical screening are nonspecific, attending veterinarian, combined with the patient’s medical history with a fasted hypercholesterolemia, hypertriglyceridemia, and mild as reported by the client. The clinical presentation of each disease is nonregenerative anemia most commonly found.14 Hypothyroid dogs summarized in a table, which also includes the next steps for diag- are expected to have a total thyroxine concentration (TT4) below the nosis and treatment. Accompanying the table is a more detailed, laboratory reference range; a result in the upper half of the reference referenced narrative specific to each disease. The table is a prescrip- range generally excludes the condition. If clinical suspicion of hypo- tive, quick-reference tool, whereas the narrative provides useful con- thyroidism is high in a patient with a TT4 below or in the lower end textual background for making informed clinical decisions. of the reference interval, evaluation of free T4 (fT4) and TSH con- The most successful veterinary practices recognize the impor- centrations is warranted. Although equilibrium dialysis is preferred tance of engaging the owner in the management of a pet’s health. for fT4 testing (fT4ed), it is not essential, and assay availability The dialog with the client should involve the entire practice should be confirmed with the laboratory. Definitive hypothyroidism team. Accordingly, these guidelines also include a section on practice diagnosis is characterized by TT4 and fT4 concentrations below the team and client considerations. When all those involved in the reference interval with a TSH concentration above the reference patient’s wellbeing are well informed and engaged, better adherence interval; however, 20–40% of dogs with overt hypothyroidism will 2 JAAHA | 59:3 May/Jun 2023 2023 AAHA Selected Endocrinopathies of Dogs and Cats Guidelines—Final TABLE 1 Summary of Categorical Approach to Diagnosing Suspected Canine Hypothyroidism have TSH concentrations within the reference range.15,16 Therefore, improve rapidly once therapy is started; however, dermatologic having two of the three hormone concentrations indicative of hypo- abnormalities may be slower to resolve. thyroidism is enough to support the diagnosis in a patient with com- Treatment monitoring is initiated 4 wk after starting supplemen- patible clinical or biochemical abnormalities. An isolated TT4 below tation unless signs persist in the face of therapy or signs of iatrogenic the reference interval should not be the only criteria used to diagnose hyperthyroidism develop. Monitoring includes TT4 assessment, with hypothyroidism. Practitioners must consider that reduction of TT4 the blood sample obtained 4–6 hr after medication administration concentrations can occur secondary to patient breed, advancing age, (“post-pill”) to check the peak serum concentration. Dose adjustments and administration of certain medications, such as prednisone, as are performed as needed monthly until the post-pill serum TT4 con- well as during periods of illness or stress.17,18 Severe illness can also centration is in the upper half or slightly above the laboratory’s refer- suppress fT4 concentrations, further mimicking a hypothyroid state; ence range, or within the range for dogs receiving supplementation if therefore, thyroid testing should ideally be performed following clini- provided by the laboratory. If an elevated TSH concentration was pre- cal stabilization or disease recovery when possible, to maximize the sent at diagnosis, it should return to the reference range following 19 diagnostic accuracy of results. treatment; however, confirming TSH normalization is not required and adds additional cost to monitoring. Once control is achieved, twice-daily dosing can be continued indefinitely with TT4 monitoring Therapy performed every 6–12 mo. Alternatively, after several months of Treatment involves oral hormone replacement using levothyroxine twice-daily dosing, patients can possibly be transitioned to once-daily sodium at a starting dosage of 0.02 mg/kg twice daily. In obese medication administration. A serum sample is obtained at the time patients, dose calculations should be based on estimated lean body the medication is due (“pre-pill”). A trough TT4 concentration weight. Veterinary approved medications should be used and given .1.5 mcg/dL suggests the dose is likely adequate for once-daily on an empty stomach. If given with food, higher doses of supple- administration. Pre-pill TT4 concentrations ,1.5 mcg/dL warrant mentation may be needed to overcome reductions in bioavailability either continuation of twice-daily dosing or increasing the once-daily and dose monitoring should be performed in a nonfasted state so dose by at least 50% and assessing a month later. Both pre- and results accurately reflect the patient’s response. Clinical signs typically 4–6 hr post-pill monitoring would be necessary at this visit to ensure JAAHA.ORG 3 the dose increase avoids iatrogenic hyperthyroidism and provides sufficient 24 hr hormone replacement. Megaesophagus has been diagnosed in dogs with hypothyroidism, but there is little evidence of a causative linkage.13  Assess for consistent laboratory abnormalities such as hypercholesterolemia and hypertriglyceridemia (ideally on a fasted sample). A mild nonregenerative anemia may also be present. Clinical Tips • Certain breeds and active working dogs are known to Next Steps have thyroid hormone concentrations that are below standard laboratory reference ranges in the absence of thyroid disease. Therefore, it is essential to consider the patient’s breed and purpose when presented with abnormal thyroid hormone concentration results. This is especially important in sighthounds, such as greyhounds or salukis.20–22 • Although uncommon, circulating autoantibodies against thyroxine (T4) can cross-react with the TT4 assay, causing an artificially high reported result. A free T4 by equilibrium dialysis (fT4ed) or quantification of circulating autoantibodies may be warranted any time a normal dog is found to have an elevated TT4 concentration or in patients with clinical or biochemical abnormalities suggesting hypothyroidism but a TT4 concentration within reference range.5,23  Submit additional thyroid testing to document a subnormal fT4 and/or an elevated TSH concentration to confirm diagnosis.  Approximately 20–40% of dogs with hypothyroidism have a low TT4 and low fT4 but a normal TSH concentration.15,16 However, this scenario could also indicate nonthyroidal illness, so additional testing such as assessing for the presence of antithyroid autoantibodies or a TSH response test can be run to help confirm diagnosis, although these tests may be cost-prohibitive for some clients.24  Initiate treatment with twice-daily levothyroxine supplementation (ideally on an empty stomach to maximize absorption).  Monitor therapy based on clinical improvement and serial TT4 testing. Assess a TT4 level 4–6 hr post morning pill 4 wk after starting medication or after dose adjustments until control is achieved, then every 6–12 mo as indicated.  Consider monitoring TSH level until normalized if it was elevated at initial diagnosis (refer to treatment and monitoring section above). GROUP 2: DOGS WITH NO CLINICAL SIGNS OF HYPOTHYROIDISM AND A LOW TT4 Clinical Presentation Categorical Approach to Diagnosis Based on Clinical Presentation Hypothyroidism is one of the most common endocrinopathies of the Group 2 dogs have no symptoms of hypothyroidism and a decreased TT4 on routine laboratory screening. Next Steps dog, and a clear-cut diagnosis can be made when the signalment and presentation of symptoms are classic and are supported by appropriate endocrine test results. However, the guidelines authors acknowledge that hypothyroidism is commonly overdiagnosed owing to the nonspecific nature of the signs, as well as the challenges that arise with the interpretation of thyroid function testing. GROUP 1: DOGS WITH CLASSICAL SIGNS OF HYPOTHYROIDISM AND A LOW TT4 Clinical Presentation  Signalment: middle-aged dogs and breed predisposition (beagles, golden retrievers, Doberman pinschers, Great Danes).13  Group 1 dogs have one or more signs of hypothyroidism, most commonly including indications of decreased basal metabolic rate (weight gain without historical increase in appetite, cold intolerance or heat seeking, exercise intolerance, lethargy) and dermatological changes (alopecia, seborrhea, dry coat and skin, hyperpigmentation, myxedema, or recurrent pyoderma or otitis externa).  Other systems that may be affected are cardiovascular (bradycardia) and neurologic, with signs related to the peripheral nervous system (i.e., facial nerve paralysis), vestibular and central nervous systems (ataxia, seizures, obtundation), and polyneuropathy (weakness).7 4 JAAHA | 59:3 May/Jun 2023  It is critical to consider the dog’s signalment, such as age and breed, before proceeding with additional testing for hypothyroidism. Clinically normal dogs of certain breeds such as greyhounds, Alaskan sled dogs (particularly when racing), shar peis, salukis, and deerhounds are routinely reported to have TT4 concentrations that are lower than established laboratory reference ranges. The guidelines task force recommends using breed-specific reference ranges when interpreting hormone levels in these breeds, especially if no clinical signs are present.25  Review current and previous medications. Drugs such as phenobarbital, clomipramine, toceranib phosphate, glucocorticoids, and sulfonamides are reported to lower TT4 and/or fT4 concentrations; TSH may be increased or within the reference range, depending on the mechanism of the effect on thyroid function. These changes are reversible in most cases once the medications are discontinued.18,26,27  Investigate for nonthyroidal illness if the dog is sick. Euthyroid sick syndrome can decrease circulating thyroid hormone concentrations, with preferential impact on TT4. In severe illness, fT4 is also impacted. TSH may be subnormal or within the reference range.19 Ideally, further thyroid testing should be delayed until clinical illness has resolved and the dog is clinically well.  Review symptoms of hypothyroidism with owner and consider measurement of fT4 and TSH levels if symptoms develop.  Monitor for development of clinical signs. 2023 AAHA Selected Endocrinopathies of Dogs and Cats Guidelines—Final GROUP 3: DOGS WITH CLINICAL SIGNS OF TABLE 2 HYPOTHYROIDISM AND A NORMAL TT4 Clinical Presentation Group 3 dogs have a similar clinical presentation to Group 1 dogs, Clinicopathologic Findings That Can Occur with Cushing’s Syndrome but the TT4 does not confirm hypothyroidism. Increased alkaline phosphatase Next Steps Hypercholesterolemia  Investigate for other causes of clinical presentation by reviewing history with client and pursuing additional diagnostics.  Perform an fT4ed with TSH and consider additional testing to rule out thyroiditis, specifically assessing for the presence of antithyroid autoantibodies. Dogs with thyroiditis can have antibodies that falsely elevate TT4 levels because of cross-reactivity of the T4 autoantibodies. Signs of hypothyroidism can develop slowly over time in some of these dogs.3  A TSH response test could be considered if the TT4 or fT4 concentrations are in the low-normal reference range and the patient lacks circulating antithyroid antibodies.  Dogs should be treated with supplementation if the diagnosis is confirmed, and therapy is monitored as described for Group 1. However, if the TT4 concentration was within reference range at diagnosis owing to the presence of T4 autoantibodies, an fT4ed is the preferred test to accurately monitor therapy. Mild hyperglycemia Canine Hypercortisolism (Cushing’s Syndrome) Overview Cushing’s syndrome (CS) refers to clinical signs associated with excessive glucocorticoid exposure, including polyuria, polydipsia, polyphagia, and panting. It can be caused by endogenous oversecretion of cortisol or by exogenous administration of glucocorticoids (iatrogenic etiology). Naturally occurring CS can be adrenocorticotropic hormone (ACTH) dependent (85%) or ACTH independent (15%). The vast majority of cases of ACTH-dependent CS are caused by a pituitary tumor (pituitary-dependent hypercortisolism, PDH), Dilute urine (specific gravity <1.020) Proteinuria Stress leukogram (mature neutrophilia, lymphopenia, eosinopenia, monocytosis) Thrombocytosis Erythrocytosis Systemic hypertension known comorbidities (such as diabetes mellitus) before pursuing CS testing when possible.29 The low-dose dexamethasone suppression test (LDDST) is the preferred diagnostic test of the guidelines panel members. False positives can occur with stress or nonadrenal illness such as uncontrolled diabetes.30,31 Results of the LDDST may also differentiate between PDH and ADH. Low-Dose Dexamethasone Suppression Test Technique 1. Draw a serum sample for baseline cortisol measurement. 2. Administer 0.01 mg/kg of dexamethasone IV (if dexa- and most cases of ACTH-independent CS are caused by adrenal methasone sodium phosphate is used, calculate dose tumors (adrenal-dependent hypercortisolism, or ADH). Other using a concentration of 3 mg/mL, instead of 4 mg/mL causes, including ectopic ACTH secretion and food-dependent as listed on the bottle).32 hypercortisolism, will not be discussed here. 3. Collect serum samples for cortisol measurement at 4 and 8 hr. Diagnostic Testing and Monitoring All diagnostic tests for Cushing’s syndrome have limitations and can yield false-positive results when performed in patients with concurrent nonadrenal illness or stress.28 Therefore, proper patient selection is essential before testing and likely impacts diagnostic accuracy more than which specific test is selected. Practitioners should only test patients when clinical suspicion of CS is high (i.e., the presence of two or more clinical or biochemical abnormalities suggesting CS). Additionally, attempts should be made to stabilize or resolve any Test results are interpreted as follows:  Refer to laboratory’s diagnostic cutoffs for interpretation. The values below are used as examples only.  Assess the 8 hr result. Cortisol .1.4 mcg/dL is consistent with a diagnosis of CS; continue with differentiation.  If the 8 hr cortisol concentration is between 1.0 and 1.39 mcg/dL but clinical suspicion for CS is high, consider performing an ACTH stimulation test (ACTHST) or repeating the LDDST in 2–3 mo. JAAHA.ORG 5 an LDDST should be performed if iatrogenic hypercortisolism is excluded. TABLE 3 Clinical Signs Associated with Naturally Occurring Cushing’s Syndrome Polyuria (± worsened incontinence, urinary accidents, and/or nocturia) Polydipsia Pot-bellied appearance Polyphagia Relevant considerations for the ACTHST are as follows: 1. False-positive results can occur in dogs that are chronically or moderately stressed or have nonadrenal illness but are less common than with LDDST.30 2. This test lacks sensitivity in dogs with adrenal tumors, leading to false-negative results in up to 41% of dogs with ADH.36 If the stimulated cortisol concentration is below the diagnostic cutoff and clinical suspicion of CS remains high, an LDDST should be performed. 3. See “Relevant Considerations” for LDDST, above. The urine cortisol-to-creatinine ratio (UCCR) test is highly senExcessive panting sitive but poorly specific, leading to a large number of false positives, particularly in dogs with polyuric conditions. It is most appropriately Dermatopathy used to exclude hypercortisolism in patients with a low clinical suspiMuscle weakness or wasting cion of CS, such as an asymptomatic dog with an alkaline phosphatase (ALP) elevation. To minimize the risk of false-positive results, urine samples are best collected in a nonstressed, home environ-  If the 8 hr result was consistent with a diagnosis of CS, then assess for evidence of partial suppression; if any criteria are present, the result is consistent with PDH.  4 hr cortisol concentration is ,1.4 mcg/dL.  4 or 8 hr cortisol concentration is ,50% of the baseline concentration.  Up to 35% of dogs with PDH do not fulfill at least one of these criteria; therefore, failure to observe suppression does NOT confirm ADH. If differentiation is still desired, abdominal ultrasound and/or an endogenous ACTH concentration can be pursued.  Relevant considerations:  Samples should be collected in a manner consistent with laboratory recommendations. Fasting is generally not required, but excessive lipemia may affect results. If lipemia is present, seek laboratory guidance for interpretation.  Glucocorticoid withdrawal before testing should be 2 wk for short-acting glucocorticoids, whereas up to 4 wk may be required following use of longer-acting glucocorticoids (such as triamcinolone).33–35 ment.37 A low value (based on the laboratory’s diagnostic cutoff) almost always rules out the disease. Therapy Adrenalectomy is the preferred therapy for ADH. However, clients may decline this option because of cost, potential complications, and comorbidities. Mitotane is an adrenocorticolytic drug that was previously the primary treatment option for PDH and is still preferred by some clinicians. Please see Behrend for more information.38 Trilostane is FDA approved for treatment of PDH and ADH. Although labeled to be administered once daily, there are several peer-reviewed references that have found that twice-daily use may be preferable.39–41 The FDA-approved dose is 2.2–6.7 mg/kg/day, but it has been commonly used at lower doses such as 2–3 mg/kg/day. Several members of the guidelines task force use a starting dosage of 1 mg/kg twice per day, dependent on the FDA-approved commer- The ACTHST appears to be less impacted than the LDDST by stress 29,30 cially available capsule sizes. The ACTHST should Monitoring requires close attention to clinical signs and cortisol also be considered if the LDDST does not support a diagnosis of hyper- testing. There are many published monitoring and testing protocols; cortisolism but clinical suspicion remains high, to confirm iatrogenic CS, there is no universal consensus on one protocol.42 The ACTHST has and to monitor CS therapy. The testing procedure is detailed in the historically been used for monitoring mitotane and trilostane ther- ACTH Stimulation Technique box, with results interpreted as follows: apy, but more recent research shows that ACTH-stimulated cortisol and nonadrenal illness, particularly diabetes. 1. Refer to laboratory’s diagnostic cutoffs for interpretation. Values indicated here are used as examples only. 2. If the 1 hr post-ACTH cortisol exceeds 22 mcg/dL, this is consistent with CS. 3. If the ACTHST returns with both the pre- and stimulated cortisol in ranges that mimic hypoadrenocorticism, this is consistent with iatrogenic CS, and additional investigation into glucocorticoid exposure is warranted. This pattern may also be seen in dogs with ADH; 6 JAAHA | 59:3 May/Jun 2023 has poor correlation with clinical signs in dogs treated with trilostane.43,44 As the ACTHST is the only definitive diagnostic test for diagnosis of hypoadrenocorticism, the primary role for its use in monitoring treatment of naturally occurring CS is to rule out oversuppression of cortisol production. Because CS is a highly variable disease, clinician judgment and discretion are important in deciding on a specific monitoring protocol. There is consensus among the guidelines 2023 AAHA Selected Endocrinopathies of Dogs and Cats Guidelines—Final TABLE 4 Summary of Categorical Approach to Diagnosing Suspected Canine Hypercortisolism (Cushing’s Syndrome) panel that the protocols and testing guidance described below have The primary purpose of the first recheck at 2 wk following initia- been effective. Initial response is assessed at 2 wk, then 1 mo later, tion of trilostane treatment is to ensure cortisol is not becoming too and then every 3–6 mo. Clinical signs are the primary indicator of low. Therefore, at the first 2 wk recheck following trilostane initiation, whether the patient is controlled or needs a dose adjustment. the guidelines authors do not usually recommend increasing the dose Measurement of cortisol concentrations (before pill or following but may decrease the dose. After the first month of treatment, neces- ACTHST) is recommended to help determine whether it is safe to con- sary dose increases are typically by 25–50% based on commercially tinue with the current dose or to adjust the dose. Pre-pill cortisol testing available capsule sizes. Owners should not give trilostane if the dog is involves obtaining a sample for cortisol measurement before the morn- not feeling well. The guidelines task force does not routinely recom- ing pill. The ACTHST should be done 3–5 hr after trilostane adminis- mend, but recognizes, that patients are sometimes on unequal doses tration, with a lower dose of synthetic ACTH (1 mcg/kg IV) being twice daily. Cortisol monitoring should always be performed follow- acceptable for monitoring.45 Timing of when the ACTHST is started ing the higher dose. For example, if a patient is receiving 40 mg and following trilostane administration should be consistent between visits. 30 mg, an ACTHST should be performed after the 40 mg dose. JAAHA.ORG 7 Clinical Tips • A follow-up client questionnaire (available at aaha.org/ endocrine-disease under the Resource tab) is a useful instrument for the client to complete at presentation of the patient. Answers to this questionnaire and follow-up questions about clinical signs are the primary determinants of whether the patient needs a dose adjustment. • Cortisol measurements help determine whether the cur- rent dose is appropriate or if dose adjustment is needed  Computed tomography of the head may be performed in dogs with PDH if the dog has signs compatible with a macroadenoma or if the owner would pursue radiation therapy or hypophysectomy.  In patients with ADH, abdominal computed tomography is usually pursued before adrenalectomy.  If the LDDST is not confirmatory, perform an ACTHST. If the ACTHST is confirmatory, consider differentiation and therapy. If the ACTHST is not confirmatory, consider referral to a specialist.  Note that endocrine diagnostics should not be performed within 2 wk of administration of short-acting glucocorticoids (oral, otic, or ophthalmic) or within 4 wk of receiving long-acting glucocorticoids.33–35 for a patient. GROUP 2: DOGS WITH NO CLINICAL SIGNS, BUT WITH CLINICOPATHOLOGIC ABNORMALITIES SUGGESTIVE OF CUSHING’S SYNDROME Categorical Approach to Diagnosis Based on Clinical Presentation Clinical presentation In the past, patients have been diagnosed with CS based on classic clin- Group 2 dogs are those for whom the owners report no clinical signs ical signs (polyuria, polydipsia, polyphagia, panting, and dermatologic consistent with CS but have one or more compatible clinicopatho- abnormalities), clinicopathologic abnormalities (increased ALP and logic abnormalities (Table 2). cholesterol, stress leukogram, thrombocytosis, urine specific gravity ,1.020, and proteinuria), and definitive diagnostics (LDDST or ACTHST). However, as awareness of CS has increased, clinical suspicion has also increased in patients with more ambiguous presentations that may lack some of the classic clinical signs or clinicopathologic abnormalities. The purpose of the information in this section of the guidelines is to help the practitioner navigate the diagnostic pathway in patients with various presentations. GROUP 1: CLINICAL SIGNS AND CLINICOPATHOLOGIC FINDINGS CONSISTENT WITH CUSHING’S SYNDROME Clinical presentation These are the dogs with classic signs and clinicopathologic abnormalities expected with CS (Tables 2 and 3). Next Steps  The first step in managing these patients is to thoroughly probe the patient’s history, with specific questions about water intake, urination habits, worsened incontinence, or nocturia. Potential administration of glucocorticoids, including ophthalmic or otic preparations, should also be ruled out.  Repeat testing to confirm persistence of previous abnormalities.  If no clinical signs of CS are identified, consider alternative differentials for clinicopathologic abnormalities, and pursue appropriate diagnostics. For example, for an increased ALP concentration, abdominal imaging may be performed.  Specific endocrine testing is not necessary unless or until clinical signs of CS are present.  A UCCR test may be considered if the veterinarian or client is highly motivated to rule out the diagnosis of CS. Note that the UCCR test is a very sensitive but nonspecific test. Although a negative result makes CS very unlikely, a positive result does not confirm the presence of CS. Next Steps  Minimum database should include complete blood count, serum biochemistry, and urinalysis. Consider assessing blood pressure, urine culture, and urine protein:creatinine ratio.  Specific endocrine testing should be performed. The guidelines panel recommends an LDDST as a routine first step. If the LDDST confirms CS, consider differentiation between PDH and ADH (if not differentiated by the LDDST) and appropriate therapy.  Differentiation between PDH and ADH is helpful because it helps direct therapeutic options and provides the owner with prognostic information. However, if the owner has no intention of pursuing adrenalectomy if an adrenal tumor is identified, patients can be treated with trilostane without knowing whether the dog has PDH or ADH.  Diagnostics that help differentiate PDH from ADH include LDDST, abdominal ultrasound, and endogenous ACTH concentration. 8 JAAHA | 59:3 May/Jun 2023 GROUP 3: DOGS WITH CLINICAL SIGNS SUGGESTIVE OF CUSHING’S SYNDROME WITHOUT CLINICOPATHOLOGIC ABNORMALITIES Clinical presentation Clinical signs in Group 3 dogs may include polyuria, polydipsia, polyphagia, excessive panting, and dermatopathy (Table 3). Next Steps  Carefully question the owner to rule out administration of glucocorticoids that could cause CS.  If clinical suspicion of CS is low, monitor the patient’s progression or change in clinical signs. A UCCR test can be considered to rule out CS. 2023 AAHA Selected Endocrinopathies of Dogs and Cats Guidelines—Final  If clinical suspicion is high, specific endocrine testing is recommended. In patients without significant comorbidities (such as diabetes mellitus), an LDDST is recommended.  If CS is confirmed, consider differentiation (see GROUP 1). If CS is not confirmed, consider other differential diagnoses for the specific clinical signs.  If CS is still strongly suspected, ACTHST and/or consultation with a specialist may be pursued. TABLE 5 Diseases with a Hypoadrenocorticism Similar Clinical Presentation Conditions with similar clinical presentation to classic HA • Acute kidney injury • Severe gastrointestinal disease GROUP 4: SICK PATIENTS PRESENTING WITH SIGNS Diseases with a similar clinical presentation to atypical HA AND/OR CLINICOPATHOLOGIC FINDINGS CONSISTENT • Severe gastrointestinal disease • Hepatic dysfunction WITH CUSHING’S SYNDROME Clinical presentation Group 4 dogs are patients that may have CS but whose presenting to HA, hypoadrenocorticism. signs must be addressed before pursuing diagnostics for CS. Note that hypercortisolism does not cause anorexia, vomiting, or diarrhea. Patients in this category may include:  Dogs in whom the presenting signs are due to a disease process that is unrelated to CS (e.g., acute gastroenteritis)  Dogs with presenting signs caused by a comorbidity associated with CS (e.g., pulmonary thromboembolism, gall bladder mucocele, or diabetic ketoacidosis)  Dogs with signs of an enlarging macroadenoma (decreased appetite, behavior change, or other neurologic signs). In these cases, the macroadenoma is causing the presenting signs; hypercortisolism is not. (steroids), pituitary surgery, or cancer sporadically result in ACTH deficiency. The variable clinical signs correspond to a loss of the vital functions of cortisol in maintaining metabolism, immunity, and gastrointestinal health and of aldosterone in maintaining sodium and volume status. Recent studies suggest up to 25–30% of patients with HA have normal electrolytes (i.e., “atypical” HA).46–48 The clinical signs of HA can occur in dogs of any age or breed. Most dogs are diagnosed in middle age, with a female predisposition inconsistently reported. Commonly affected breeds include the stan- Next Steps  Address the presenting clinical signs and underlying cause of the acute illness.  Do not perform specific endocrine testing for CS until the acute illness is managed or controlled. Acute illness causes stress that can lead to false-positive results, particularly with the LDDST. Additionally, because CS is not causing the presenting clinical signs, diagnosis and treatment of CS will not immediately ameliorate the presenting clinical signs.  If relevant, treatment of diabetes mellitus should not be delayed in dogs with suspected CS.  The guidelines task force recommends, if possible, waiting at least 2–4 wk after improvement of the acute illness to test for CS.  If the acute or chronic illness is unlikely to resolve or improve without addressing the possible underlying CS, consider consultation with a specialist to discuss the need for and timing of specific endocrine testing. Canine Hypoadrenocorticism (Addison’s disease) dard poodle, Portuguese water dog, and Great Dane. Often, sudden signs of volume depletion (shock) predominate in “typical” HA (cortisol deficiency with aldosterone deficiency), although the atypical form (clinical signs reflecting cortisol deficiency without electrolyte TABLE 6 Conditions That Biochemically Resemble Hypoadrenocorticism (Pseudo-Addisonian Conditions) Whipworms Third spacing of fluids Chronic gastrointestinal disease Renal failure Hepatic failure Overview Hypoadrenocorticism (HA), or Addison’s disease, describes a spectrum of conditions resulting in deficiencies of important adrenal hormones (i.e., cortisol and aldosterone). HA usually results from direct adrenocortical injury (primarily autoimmune disease) Reperfusion injury Acidosis Artifact (thrombocytosis, hemolysis) although the rapid withdrawal of adrenal suppressive medications JAAHA.ORG 9 TABLE 7 Laboratory Changes That Can Occur with Hypoadrenocorticism derangements) is more often chronic. Atypical HA is characterized Therapy by vomiting, lethargy, anorexia, and diarrhea; hypoalbuminemia For cortisol deficiency, a small daily dose of glucocorticoids is recom- and/or hypocholesterolemia are common laboratory findings.49 mended. Many dogs require doses ,0.1 mg/kg/day of prednisone or The presence of a lymphopenia makes cortisol deficiency extremely prednisolone, and 0.25 mg/kg/day should be enough to manage all clin- unlikely.50 ically stable dogs with HA long term. Other glucocorticoids are acceptable, and the dose should be calculated on a prednisone-equivalent Diagnostic Testing and Monitoring basis. The daily dose should be doubled or tripled before known stress- The diagnosis relies on confirming cortisol deficiency by means of ful events. an ACTHST. A sodium-to-potassium ratio ,27 is suggestive, al- Dose should be further adjusted based on clinical signs and though sodium and/or potassium concentrations are within the ref- side effects. Dose should be increased when a dog shows clinical erence range in nearly one in four cases of HA, and many other signs of Addison’s disease, such as anorexia, lethargy, vomiting, Aldosterone diarrhea, hematochezia, and melena. Dose should be decreased measurement is available through multiple laboratories and can be when the dog has side effects of glucocorticoid administration 49,51 disorders can impact the sodium-to-potassium ratio. 52 used to further determine adrenal function if appropriate. The finding of a baseline or “resting” serum cortisol .2 mcg/dL including polyuria/polydipsia, polyphagia, panting, muscle wasting, elevated ALP, or hair loss. rules out HA with nearly 100% confidence, assuming that the patient Patients with hyperkalemia and/or hyponatremia require min- has not received exogenous glucocorticoids known to cross-react eralocorticoid supplementation. The labeled dose of desoxycorticos- with the cortisol assay (such as prednisone).53 However, most dogs terone pivalate (DOCP) is 2.2 mg/kg given intramuscularly or sub- with a baseline cortisol ,2 mcg/dL do not in fact have hypoadreno- cutaneously, but research has demonstrated efficacy with lower corticism, so this finding is not sufficient to establish the diagnosis. doses.59,60 Starting doses of 1.1–1.5 mg/kg may be appropriate in The diagnosis is confirmed by a post-ACTH stimulation cortisol value most cases.61,62 ,2 mcg/dL or below the laboratory-specific diagnostic cutoffs (see The dose and the dosing interval are determined by electrolyte box, ACTH Stimulation Technique). Reference ranges derived from monitoring. Check electrolyte levels 10–14 days after injection and healthy pets are not the same as diagnostic cutoffs, which are devel- again 25 days after injection. If hyperkalemia or hyponatremia are oped by sampling dogs with HA. Measurement of endogenous persistent, the dose is typically increased. If electrolytes are normal, ACTH, specifically the cortisol-to-endogenous ACTH ratio, or a the dose may be gradually decreased with monitoring. If the dose is UCCR are promising sensitive and specific tests for dogs with pri- already low, extending the dosing interval to 28–30 days is reason- mary adrenocortical injury, although this test is not yet routinely able.60 If DOCP cannot be used, consideration can be given to using performed.54–58 fludrocortisone. 10 JAAHA | 59:3 May/Jun 2023 2023 AAHA Selected Endocrinopathies of Dogs and Cats Guidelines—Final ACTH Stimulation Technique Categorical Approach to Diagnosis Based on Clinical Presentation 1. Collect a baseline serum cortisol sample. The patient Although some dogs with hypoadrenocorticism present with typical may need to be fasted to avoid lipemia. 2. Inject cosyntropin (5 mcg/kg intramuscularly or IV up to 250 mcg per dog) and collect a second serum sample 1 hr later. a. A 1 mcg/kg dose of cosyntropin has been shown equivalent to a 5 mcg/kg dose of cosyntropin for most dogs suspected of HA.63 b. A 1 mcg/kg dose of cosyntropin has been shown appro- physical examination and laboratory abnormalities, making diagnosis relatively straightforward, other cases may have a vague or atypical presentation. The clinical signs or laboratory findings associated with hypoadrenocorticism can mimic several other diseases, making diagnosis challenging. The guidelines panel has organized clinical presentations into four groups to aid in diagnosis. GROUP 1: CLASSIC CLINICAL DISEASE priate for monitoring of dogs with Cushing’s syndrome Clinical Presentation being treated with trilostane or mitotane but is not reliable Group 1 dogs present with chronic or episodic clinical signs and lab- for the diagnosis of Cushing’s syndrome.45 oratory abnormalities consistent with hypoadrenocorticism. c. The absorption of compounded ACTH-depot (“gel”) may be delayed from the intramuscular space. Thus, Next Steps samples for cortisol should be collected at both 1 If suspicion for disease is high, an ACTHST should be performed to and 2 hr after injection. confirm diagnosis. If suspicion for disease is low, a resting cortisol 3. The cost of the cosyntropin can be decreased by using could be performed. If the resting cortisol is ,2 mcg/dL, an lower doses when appropriate and by freezing the ACTHST should be performed to diagnose hypoadrenocorticism. If reconstituted product in small aliquots.64 the resting cortisol is .2 mcg/dL, other differentials for these clinical a. Using an aseptic technique, reconstitute the ACTH and laboratory abnormalities should be pursued. solution for injection as instructed on the package (1 mL NaCl for a 250 mcg/mL solution). b. With a tuberculin syringe, draw up 0.1–0.2 mL aliquots. Draw up an additional 0.1 mL of air to pro- Once the diagnosis of hypoadrenocorticism is confirmed, appropriate treatment(s) and monitoring should be instituted. For patients with classic clinical disease, treatment generally consists of both mineralocorticoid and glucocorticoid supplementation. vide space for expansion during freezing. Store at 20 C for up to 6 mo. c. At the time of use, thaw one or more syringes in the palm of a gloved hand. The solution will quickly liquefy. Expel the small air bubble from the hub before use and double-check drug volume. d. Once thawed, use or discard the solution. Do not refreeze. GROUP 2: NO CLINICAL SIGNS, BUT WITH CLASSIC LABORATORY ABNORMALITIES Clinical Presentation Group 2 dogs present without clinical signs of disease and have laboratory derangements on routine laboratory work, which include hyperkalemia and/or hyponatremia. Additional laboratory abnormalities may be present (Table 7). Next Steps In these cases, the owner should be requestioned as to the presence of Clinical Tips associated clinical signs including questions related to gastrointestinal • Clients as well as veterinary health care professionals health (appetite and stool), energy, and water intake. If upon deeper can learn to administer subcutaneous injections. Once a analysis there are still no clinical signs of hypoadrenocorticism, other stable dose and dosing interval are achieved, monthly causes of laboratory changes such as spurious causes should be ruled DOCP injections may be administered by someone out (Table 6). If the blood sample was run on serum, consider reeva- other than the veterinarian. luation of plasma because serum potassium levels can be artificially • Other health care team members may serve as the pri- high due to potassium release from platelets during clot formation.65 If mary client educators regarding symptoms of illness no clinical signs are present and spurious causes have been excluded, and side effects. monitor clinical signs and repeat the laboratory testing as indicated. • Routine biannual health care visits are still encouraged. If laboratory abnormalities are persistent or progressive, or upon deeper analysis clinical signs are present, either a resting JAAHA.ORG 11 TABLE 8 Summary of Categorical Approach to Diagnosing Suspected Canine Hypoadrenocorticism cortisol should be considered to exclude this disease or an ACTH Next Steps stimulation test (ACTHST) could be performed.52 If a resting cortisol Immediate stabilization should be implemented, with IV fluids being test is chosen and results are ,2 mcg/dL, an ACTHST should be the cornerstone of therapy. Treatment should target correcting hypo- performed to confirm the diagnosis. volemia and hypotension. Specific therapy to correct hyperkalemia, hypoglycemia, and acidosis may be required. Gastrointestinal support GROUP 3: ADDISONIAN CRISIS Clinical Presentation including early enteral nutrition should be implemented as needed. Once stable, these patients may need to be transferred to a facil- Group 3 dogs present in hypovolemic shock with or without historic ity that provides 24 hr care to provide continued support. Frequent episodic signs consistent with hypoadrenocorticism. This is the most monitoring of electrolytes is required. The guidelines task force serious and life-threatening manifestation of hypoadrenocorticism recommends daily packed cell volume monitoring as these patients and typically presents as hypovolemic shock accompanied by severe can become severely anemic following rehydration.66 hyperkalemia and hyponatremia. Other laboratory abnormalities may be seen (Table 7). 12 JAAHA | 59:3 May/Jun 2023 Once stable, perform a baseline cortisol test to rule out this diagnosis, or, if suspicion for disease is high, perform an ACTHST to 2023 AAHA Selected Endocrinopathies of Dogs and Cats Guidelines—Final confirm diagnosis. In some cases, administering a single dose of a T4 values according to the reference laboratory may actually be steroid before testing is required for stabilization. Dexamethasone hyperthyroid. Following trends on annual screenings should reveal (0.1 mg/kg IV) is the steroid of choice because it does not interfere T4 levels either static or dropping. Elevation over time with develop- with the cortisol assay.66 Consider aldosterone measurement. Miner- ment of clinical signs warrants further confirmation testing, even if alocorticoids can be started once the patient is stable, there is a con- the T4 level is technically within the laboratory’s normal range. firmed diagnosis, and sodium is .130 mEq/dL. Diagnosis and Monitoring GROUP 4: CLINICAL SIGNS WITH NONSPECIFIC LABORATORY ABNORMALITIES (ATYPICAL PRESENTATION) The classic presentation of FHT (also known as Group 1 in the 2016 AAFP guidelines and in Table 8) is a cat that is losing weight, eating Clinical Presentation Group 4 dogs present with chronic or episodic clinical signs without the characteristic findings associated with classic hypoadrenocorticism. Because signs of canine hypoadrenocorticism can mimic many other diseases, patients may present with episodic clinical signs that could be consistent with this disease without the hallmark laboratory findings of hyperkalemia or hyponatremia (Table 6). voraciously, and hyperactive. Many cats, however, do not have these classic signs and can be assigned to one of the other five diagnostic groups. Cats with elevated T4 levels on basic blood screens may be minimally symptomatic or asymptomatic. Regardless of the cat’s clinical presentation, a repeatedly elevated T4 level requires treatment to prevent progression of the disease and subsequent secondary organ damage. Concurrent disease may cause the serum T4 level to be lower Next Steps When signalment and clinical signs are consistent with hypoadreno- than expected in a cat suspected to be hyperthyroid. In these cases, a corticism (e.g., episodic gastrointestinal signs after periods of stress, fT4 will be helpful to confirm the diagnosis. For cats that fall into polyuria/polydipsia) or if there are other suggestive laboratory find- Groups 4 or 6 that may be considered early or subclinically hyperthy- ings (Table 7), a resting cortisol should be performed. If the resting roid, there may be some benefit to measuring TSH levels before cortisol is ,2 mcg/dL, an ACTHST should be performed. If the rest- deciding on treatment options. Cats with detectable serum TSH con- ing cortisol is .2 mcg/dL, other differentials should be considered. centrations ($0.03 ng/mL) are at much higher risk for development of If hypoadrenocorticism is diagnosed, consider testing for aldosterone 131 I-induced hypothyroidism.68 A commercially available feline TSH deficiency as many of these patients have hypoaldosteronism, even test was recently released; however, the canine TSH test is a reasonable with normal electrolytes.51 Appropriate treatment and monitoring alternative.69,70 A measurable TSH level may make a cat more suscepti- should be instituted based on diagnosis. ble to hypothyroidism following radioactive iodine treatment. Waiting until TSH declines to an unmeasurable level may be beneficial.68,70 TSH levels are not sensitive for initial diagnosis of hyperthyroidism Feline Hyperthyroidism and must be used in conjunction with elevated T4 or fT4 levels.70 Overview The management of FHT has been covered extensively in other publications, notably the 2016 AAFP Guidelines for the Management of 2 Therapy Feline Hyperthyroidism. Much of the information in the 2016 AAFP Left untreated, FHT will eventually be fatal. Hyperthyroidism affects guidelines remains applicable today. This discussion of FHT will multiple organ systems. Until FHT is corrected, management and serve to highlight certain key points and present recent findings assessment of comorbidities cannot be accurately assessed. Options related to the disease. for treatment include radioactive iodine, oral antithyroid medication, FHT is an extremely common endocrinopathy in cats, resulting surgical removal of the adenomatous thyroid gland, and an iodine- from excessive circulating levels of T4 and T3. These excess hormone deficient therapeutic diet. The treatment of choice is radioactive levels are most often caused by benign adenomatous hyperplasia of iodine (131I), which will provide a cure in more than 95% of cases. one or both thyroid glands and create a state of increased metabo- Radioactive iodine avoids anesthesia, requires no ongoing medica- lism. Thyroid carcinoma is a rare FHT etiology, present in fewer tion administration, and does not require the cat to have a restrictive 67 than 3% of cats at the time of initial diagnosis. Although FHT is diet. Radioactive iodine may be used as an initial treatment for stable typically diagnosed in cats older than 10 yr, elevated T4 levels in hyperthyroid cats, even in the presence of some concurrent diseases. younger cats may be found more often as annual blood screening Cats with elevated N-terminal pro-B-type natriuretic peptide levels becomes more commonplace. It is important to note that T4 levels and mild heart disease will likely benefit from having the hyperthy- naturally decrease with age. A senior or geriatric cat with high normal roid state corrected. Cats with mild renal changes (IRIS stage 1) can JAAHA.ORG 13 TABLE 9 Summary of Categorical Approach to Diagnosing Suspected Feline Hyperthyroidism also be treated with 131I without a therapeutic medication trial first.2 Note that cats with normal renal and symmetric dimethylarginine values may develop abnormalities after the hyperthyroidism is corrected, and a normal symmetric dimethylarginine cannot be used to predict renal function after hyperthyroid resolution.71 Iatrogenic hypothyroidism is a risk of 131I, so ensuring the TSH concentration is nondetectable before referral may be ideal.70 Unfortunately, radioactive iodine treatment may not be available to all practitioners. Thyroidectomy may be curative, but it includes the risk of anesthetizing a cat with potential cardiac compromise. The parathyroid glands are at risk of being damaged during thyroidectomy even by skilled surgeons. Infrequently, there may be ectopic thyroid tissue that is not easily surgically removed that will continue to be overactive. Before surgical intervention, the cat should be medically stabilized. Important Note • The AAHA guidelines task force recommends for AAFP groups 4 and 6, the practitioner should consider checking TSH prior to 131I treatment and postponing if measurable (.0.03 ng/mL) to help avoid creating iatrogenic hypothyroidism.70 An iodine-deficient diet is commercially available by prescription and is effective for many cats in controlling hyperthyroidism. Depending on the degree of initial elevation of the T4 level, some cats may take several months to become regulated.72 For the therapeutic diet to be effective, cats must not be allowed access to any other food, including other pets’ foods and human food, as well as items that they may hunt and eat outdoors. In some cats, the T4 level 14 JAAHA | 59:3 May/Jun 2023 2023 AAHA Selected Endocrinopathies of Dogs and Cats Guidelines—Final feeding the restrictive diet. It has been shown that feeding the Categorical Approach to Diagnosis Based on Clinical Presentation will fail to normalize even after prolonged periods of exclusively iodine-deficient diet to nonhyperthyroid cats in the household is not GROUP 1: CLASSIC CLINICAL DISEASE harmful if it is not possible for owners to feed separate diets in multi- Clinical Presentation cat homes.72 Cats with uncomplicated clinical hyperthyroidism and elevated T4. Medical management with methimazole is a common and These are cats with one or more clinical signs consistent with FHT effective way of controlling hyperthyroidism. To minimize potential that have an elevated T4 and no identifiable concurrent disease. T4 is adverse effects, methimazole should be started at a low dose and above the laboratory reference interval in FHT cases. titrated up to the dose needed to maintain T4 levels between 1.0 and 2.5 mcg/dL. Dosing of 1.25–2.5 mg every 24 hr for the first week Next Steps of treatment, increasing to 2.5–5 mg every 12–24 hr, will help mini- The AAFP Guidelines Panel recommends that reference laboratory mize side effects, although adverse effects including vomiting, bone testing be utilized for diagnosis and monitoring of FHT so that pre- marrow dyscrasias, and skin excoriations can occur up to several cise serum hormone levels can be followed throughout treatment months after initiating therapy. Gastrointestinal side effects may and to avoid quality control discrepancies. Ideally, for purposes of be mitigated by using a transdermal preparation of methimazole; however, all other adverse drug effects require discontinuation and selection of a different treatment method. Methimazole doses will need to be adjusted over time because the drug does not affect the growth of the adenomatous hyperplasia. Avoidance of hypothyroidism is imperative and requires periodic veterinary monitoring. consistency, monitoring should be performed at the same reference laboratory. If in-clinic testing is performed for geriatric screening and significant changes are noted in thyroid hormone levels, obtain confirmatory testing at a reference laboratory. Complete blood count (CBC) findings are generally unremarkable, although macrocytosis may be present. Cats with marked anemia may suffer from a comorbidity and further work-up should be performed. Serum chemistry findings often include elevated serum Clinical Tips alanine transferase (ALT) or alkaline phosphatase. Serum ALT levels • For many practitioners, it has become commonplace for can be markedly elevated. pet owners to do their own research when a diagnosis is made and subsequently propose alternative therapies. For cats with FHT, there is no effective homeopathic remedy despite the availability of products claiming to be effective.73 Clients should be advised to pursue traditional treatments for this disease. • If initial regulation is with methimazole, T4 monitoring should occur every 2–4 wk until the goal levels are reached. Complete blood count, chemistry profiles, and urinalysis will provide information on potential bone marrow dyscrasias, development or progression of azotemia, resolution of any liver enzyme changes, and any other issues that may have been concealed by the hyperthyroid state. • Blood samples for T4 measurement may be taken at any time during the day after methimazole administration. There is no need to schedule sampling for a specific time after medication administration.68 • Once the patient has been regulated, a physical exami- nation and minimum database should be performed at least every 6 mo and more frequently if there are significant comorbidities. If liver enzymes do not normalize after successful treatment for FHT, further diagnostic work-up is warranted. Azotemia may suggest dehydration or underlying renal failure. Urinalysis results are variable, although the urine specific gravity may be less than 1.030 due to primary polydipsia or inability to concentrate the urine due to hyperthyroidism. Management of Group 1 cats consists of treatment for their hyperthyroid disease. GROUP 2: POSSIBLE FHT WITH PROBABLE NON-THYROIDAL DISEASE Clinical Presentation Cats with clinical hyperthyroidism and normal T4. Cats in this category have clinical signs suggestive of FHT along with T4 within the laboratory reference interval. Next Steps The AAFP Guidelines Panel recommends the following approaches for Group 2 cats:  Further testing for FHT should consist of T4 and fT4 assays measured 2–4 weeks after the initial blood screening. A T4 value in the upper half of the reference interval combined with an elevated fT4 supports a diagnosis of hyperthyroidism. JAAHA.ORG 15  If the T4 and fT4 are both within the reference interval, the cat should be evaluated for non-thyroidal disease.  If no concurrent illness is found and FHT is still suspected, further testing is warranted, including triiodothyronine (T3) suppression testing, serum TSH concentration in conjunction with T4 and fT4ed, or thyroid scintigraphy. Common comorbidities associated with FHT: Thyrotoxic heart disease Hypertension Retinopathy CKD Gastrointestinal disease, malabsorption, cobalamin deficiency Insulin resistance NOTE: Common conditions with signs similar to FHT: Certain classic       signs of hyperthyroidism (polydipsia, polyuria, weight loss in the face GROUP 6: CLINICALLY NORMAL of a good appetite) have similarities with the following morbidities Clinical Presentation that are plausible differential diagnoses: Cats with no clinical signs of hyperthyroidism and no palpable thy-  Diabetes mellitus  Gastrointestinal malabsorption, maldigestion  Gastrointestinal neoplasia, especially lymphosarcoma roid nodule but with an elevated T4 on screening lab test. Next Steps Because falsely elevated T4 values may occur, repeat the T4 test prefera- GROUP 3: ENLARGED THYROID GLAND WITHOUT bly using radioimmunoassay or chemiluminescent enzyme assay.74,75 If CLINICAL FHT the T4 is now normal, monitor the cat and retest T4 every 6 months, Clinical Presentation Cats without clinical hyperthyroidism, T4 within the reference inter- or sooner if clinical signs develop. If the T4 is elevated, treat for FHT. *Carney HC, Ward CR, Bailey SJ, et al. 2016 AAFP Guide- val, but with enlarged thyroid gland(s). lines for the Management of Feline Hyperthyroidism. J Feline Med Surg. 2016;18(5):400-416, copyright © 2016 by SAGE Publi- Next Steps cations. Reprinted by Permission of SAGE Publications. Access Monitor clinical signs in these cats and repeat a serum T4 assay in the AAFP Guidelines for Management of Feline Hyperthyroidism 6 months. and additional resources at catvets.com/hyperthyroidism. GROUP 4: SUBCLINICAL FHT Clinical Presentation Less Common Feline Endocrinopathies Cats without overt clinical hyperthyroidism but with an elevated T4 Three feline endocrinopathies are encountered in clinical practice and with some physical exam findings suggestive of hyperthyroidism. with a lesser frequency than the other feline diseases discussed in these guidelines: feline hyperaldosteronism, feline hypothyroidism, Next Steps and feline hyperadrenocorticism. This section provides general over- Repeat the T4 test in 1–2 weeks. If serum T4 is still elevated, treat views of these less prevalent but still important endocrinologic dis- the cat for FHT. While no data exist for the best way to manage eases of cats. Group 4 cats, the consensus of the Panel is to treat these cats for hyperthyroidism. If a repeat T4 is normal, then re-evaluate the patient in 6 months with a complete physical exam and a T4 assay. GROUP 5: CLINICAL FHT WITH CONFIRMED NON-THYROIDAL DISEASE Clinical Presentation Cats with clinical hyperthyroidism confirmed by elevated T4, and one or more concurrent diseases. Feline Hyperaldosteronism The adrenal gland is the primary producer of the hormone aldosterone, which is responsible in part for sodium and potassium homeostasis. Feline primary hyperaldosteronism (PHA) is most commonly caused by a unilateral adrenocortical adenoma, with malignant adenocarcinomas reported less commonly.76 Cats with PHA are typically middle-aged to older cats. Presenting signs are typical of increased potassium loss/hypokalemia and Next Steps retained sodium. Hypokalemia, usually less than 3 mEq/L, will lead Hyperthyroid cats are commonly middle-aged or older and often to progressive muscle weakness. The owner may notice reluctance to have concurrent diseases. But because FHT is a serious disease that jump, abnormal gait (plantigrade stance), lethargy, or cervical ven- can result in rapid deterioration of the patient, the Panel recom- troflexion. Because the cats are considered mature to senior, owners mends the treatment of all diagnosed cats, including those animals often perceive clinical signs to be normal aging changes. Sudden with comorbidities. Appropriate monitoring and careful manage- blindness due to retinal detachment is a consequence of persistent ment of concurrent diseases will optimize the patient’s health. systemic hypertension (SHT) and may or may not be noticed by the 16 JAAHA | 59:3 May/Jun 2023 2023 AAHA Selected Endocrinopathies of Dogs and Cats Guidelines—Final TABLE 10 Key Factors in Managing Feline Primary Hyperaldosteronism Presentation • Hypokalemia, frequently under 3 mEq/L, which may not respond well to supplementation. • • Serum sodium concentrations are usually normal. • Plasma aldosterone levels are elevated. • Abdominal ultrasound or other imaging may show adrenal mass. Therapeutic Recommendations • Control hypertension. • Supplement potassium. • Use aldosterone receptor blocker. • Consider surgical removal of the adrenal tumor. Diagnostic Red Flags for Hyperaldosteronism • Hypokalemia with no obvious cause, which may not respond well to supplementation. • Hypophosphatemia +/- metabolic alkalosis despite azotemia. • • Hypertension without concurrent cardiac or thyroid disease. Take-Home Messages for Practice Team Members • Signs of PHA can be subtle in the early stages. • Blood pressure measurement should be a standard of care for adult cats at least annually, and any time a middle-age to older cat presents with nonspecific clinical signs. PHA, primary hyperaldosteronism. owner. Hypertension before this catastrophic stage may cause non- stabilized medically before surgical intervention. Medical treatment specific changes in behavior such as lethargy, hiding, and irritability. is focused on resolution of the hypokalemia and SHT. Potassium Physical examination findings in cats with PHA may be related supplementation, usually with potassium gluconate, is necessary, to hypokalemia, systemic hypertension, or both. Muscle weakness and higher-than-standard doses may be required to restore normal and atrophy may be present. Chronic kidney disease (CKD) is a fre- serum potassium concentrations. The aldosterone receptor blocker quent comorbidity and can exacerbate the clinical impact of PHA. spironolactone at 1–2 mg/kg given twice daily should be used to Minimum database and Doppler blood pressure measurement help control hypokalemia. SHT must be corrected. Amlodipine should be performed on cats with suspected PHA. Diagnostic imag- administered at 0.625–1.25 mg per cat per day is an effective and ing with abdominal ultrasound (or cross-sectional imaging) may affordable calcium channel blocker that is frequently used for SHT. reveal an adrenal mass. Ultrasound evaluation may reveal a unilateral adrenal mass, up to 5 cm in diameter, but in some cases the adrenal Feline Hypothyroidism glands may appear normal.77 Plasma aldosterone testing is currently Although naturally occurring hypothyroidism in cats occurs rarely the most readily available and reliable laboratory diagnostic tool, and compared with its incidence in dogs,79 it is occasionally reported in a single very high value may be confirmatory. More complex testing this species. A single low T4 level should be interpreted in light of may be needed in equivocal cases. Blood and urine changes consis- the entire clinical picture because nonthyroidal illness can lead to tent with CKD may also be present and must be addressed. reductions of serum T4 levels. The magnitude of serum T4 suppres- Confirmation of unilateral or bilateral disease is important, as 74 it will influence treatment decisions. sion is proportionate to the severity of the underlying disease. Final Surgical removal of the interpretation of thyroid function should be made when any non- affected adrenal gland is the treatment of choice for unilateral dis- thyroidal illness is stabilized, as well as in relation to the cat’s clinical 78 ease but may not always be an option. Affected cats need to be presentation. JAAHA.ORG 17 TABLE 11 Does this cat have concurrent disease? Clinical Signs of Feline Hypothyroidism yes no Congenital Disease • Slow growth rate • Short limbs • Broad head • Lethargy • Constipation • Mental dullness • Retained deciduous teeth • Gingival overgrowth • Retained kitten hair coat Iatrogenic or Adult-Onset Disease • Lethargy • Weight gain, obesity • Seborrhea, poor haircoat • Poor regrowth of hair • Inappetence • Bradycardia Clinical signs of feline hypothyroidism are shown in Table 11. Congenital hypothyroidism is usually identified in cats younger than Treat concurrent disease, then recheck T4 and TSH Has this cat been treated for FHT with 131I or surgical removal of the thyroid? If <3–4 months and not symptomatic, monitor to see if values rebound. If >4 months, if T4 is low and TSH is elevated, supplement with levothyroxine Decrease dose by 25% and recheck in 2–4 weeks. Continue to reduce as needed until T4 is between 1.0 and 2.5 mcg/dL Treat with levothyroxine yes no Is this cat currently on methimazole for FHT? yes no Is this a cat younger than 2 years with clinical signs? yes no 1 yr of age and most frequently in kittens younger than 8 mo. Affected kittens are usually stocky, with shorter limbs and a broader- Is this cat asymptomatic with no concurrent disease? than-usual head and neck. Lethargy, constipation, retained deciduous teeth, abnormal hair coat, and thickened gingiva are common findings.76 Diagnosis of hypothyroidism requires demonstration of a low serum T4 (,0.8 mcg/dL) and elevated TSH concentrations. Demonstration of low serum fT4 levels may also suggest hypothyroidism. A commercially available feline-specific TSH test was recently released; Monitor laboratory values every 6 months and watch for clinical signs, azotemia, etc. yes maybe Goiter present, equivocal dermatologic signs: consider TSH testing no however, the historically used canine TSH test will also be elevated in cats with hypothyroidism.68 In contrast to hypothyroidism in dogs, Is this cat older than 2 years and symptomatic? cats with naturally occurring hypothyroidism are more likely to be azotemic.80 Figure 1 shows a diagnostic and treatment algorithm for deciding if a low T4 indicates a patient has feline hypothyroidism. Treatment of hypothyroidism in cats is straightforward and similar to treatment in dogs. Levothyroxine sodium is recommended, yes Recheck T4 in 2–4 weeks, if still low, check TSH and treat for hypothyroidism if elevated no If T4 is normal, not hypothyroid with an initial dose range of 0.05–0.1 mg daily. The dosage is adjusted to target T4 levels between 1.0 and 3.0 mcg/dL; however, clinical signs may persist for 2–3 mo before responding to treatment. Adult-onset hypothyroidism, although rare, may in fact be underdiagnosed in cats.81 Even if that proves to be true, it is still an 18 JAAHA | 59:3 May/Jun 2023 FHT, feline hyperthyroidism; T4, thyroxine; TSH, thyroid-stimulating hormone level. FIGURE 1 Decision Tree for Feline Hypothyroidism Diagnosis and Treatment. 2023 AAHA Selected Endocrinopathies of Dogs and Cats Guidelines—Final extremely uncommon problem. Treatment should only be consid- only half of feline cases. Definitive diagnosis in cats may be challeng- ered for cats with repeatable laboratory abnormalities and clinical ing, with the most reliable diagnosis coming from the LDDST. It is signs consistent with hypothyroidism, such as lethargy, poor hair important to note that dexamethasone dosing for cats is greater than coat, and obesity. Confirmation of decreased serum T4 on more the effective canine dose. Cats must be dosed at 0.1 mg/kg dexameth- than one occasion, along with elevated TSH levels, is required to asone IV.82 The interpretative criteria are similar to those used in establish the diagnosis. dogs, with a lack of suppression at 4 or 8 hr after administration con- Iatrogenic hypothyroidism is caused by overdosing with antithy- firming the diagnosis of HAC. UCCR testing may also be used for roid drugs such as methimazole, surgical removal of the thyroid initial screening. At least two morning samples should be collected at I treatment. Once patients have been stabilized on home by the owner and submitted for evaluation.85 A positive result methimazole, monitoring at least every 6 mo will ensure proper thy- from UCCR testing should be followed up with an LDDST, but a roid control and avoidance of hypothyroidism. When treating with negative result likely rules out the diagnosis of HAC. An ACTH 131 stimulation test is not recommended as a diagnostic tool in cats glands, or 131 I, consideration should be given to the T4 and TSH levels and the 131 82 I should be dosed appropriately. Failing to recognize and address iatrogenic hypothyroidism can contribute to decreased renal func- because of its poor sensitivity to detect feline HAC compared with the other available testing.85 tion.83 Maintaining T4 levels between 1.0 and 2.5 mcg/dL is ideal, and Differentiation testing to determine if the HAC is caused by a treatment should be initiated for patients with T4 values ,1.0 mcg/dL pituitary tumor or adrenal tumor can be considered, as adrenalect- and an elevated TSH level. Additionally, cats with T4 levels within the omy may be curative in cats with unilateral adrenal tumors. Radia- reference range but an elevated TSH who develop a new or progres- tion therapy may be beneficial in cats with PDH. sive azotemia may benefit from methimazole dose reduction or levothyroxine supplementation if surgically or 131 I treated. Medical treatment with trilostane is the mainstay of HAC treatment in cats, with a recommended dosing of 1 mg/kg given two to three times daily with food.83 The licensed product may be reformulated Feline Hyperadrenocorticism/Hypercortisolism Hyperadrenocorticism (HAC), also referred to as hypercortisolism or Cushing’s syndrome, is an infrequent diagnosis of cats. Similar to dogs, cats usually have pituitary-dependent HAC, and the hormonal mechanism of action is the same as in dogs. Clinical signs are due to the excess circulating glucocorticoid levels. Cats seem to be rarely negatively affected by chronic use of exogenous glucocorticoids, so the incidence of iatrogenic Cushing’s syndrome in cats is much less frequent compared with dogs.84 HAC usually affects middle-aged to older cats, with the majority having concurrent diabetes mellitus that may be considered difficult to regulate. It is important to note that most difficult diabetic cases if doses significantly less than 5 mg per dose are needed. The goal of treatment for feline HAC is control of clinical signs, and strict monitoring of cortisol levels may not be critical for treatment success. Improvement of weight, polyuria/polydipsia, polyphagia, and overall quality of life are the primary treatment goals. Laboratory monitoring with CBC, biochemical profiles, and urinalysis 7–14 days after starting trilostane and every 3–4 mo thereafter is recommended. If cortisol monitoring is pursued, the UCCR testing and ACTH stimulation test have been most commonly used to ensure trilostane is not leading to hypocortisolism. Final decisions on dosing, however, should be based on clinical assessment of the cat by both the veterinarian and the owner, the status of any concurrent disease, and the prevention of hypocortisolism. do not have HAC, and other causes of poor diabetic regulation should be pursued first. Clinical signs of HAC in cats are often nonspecific and include weakness, abdominal distension, and dermato- Clinical Tips logical issues such as fragile skin and failure to regrow hair. Cats • Poorly regulated diabetes in cats usually has an etiology with concurrent diabetes mellitus are usually polyuric, polydipsic, other than HAC. and polyphagic, but these signs reflect persistent hyperglycemia • Compared with the canine dose for LDDST, a higher rather than CS per se. Weight loss, lethargy, and gastrointestinal dexamethasone dose is needed in cats: 0.1 mg/kg of signs are possible but uncommon. dexamethasone is consistently effective in suppressing A minimum database will most commonly show hyperglycemia and glucosuria. Changes that are common in canine HAC are not as healthy cats but not cats with HAC.86 • Three-times-a-day dosing of trilostane may be needed predictable in feline patients. Alkaline phosphatase levels are usually to reach therapeutic doses with standard capsule sizes. normal in cats who lack the steroid-induced isoenzyme, and hyper- • Reformulation of the licensed product may be required cholesterolemia may be present. A stress leukogram is present in for smaller doses. JAAHA.ORG 19 • Clinical evaluation of the cat and any concurrent dis- eases may be more important than targeted monitoring of adrenal function. The Team Approach From initial patient presentation to long-term management, the pet owner interacts with every veterinary health care team member. Embracing a team-based approach can help establish clients’ trust, promote communication and compliance, and improve overall patient care and quality of life.  Let the client gather their thoughts. Try not to rush them to fill the silence.  Practice positive nonverbal communication. Use open body postures, direct eye contact, and head nodding.  Engage in reflective listening.  After the client finishes talking, reflect on what was heard and ask if the situation has been understood correctly. For example, “Annabelle vomited five times since yesterday; is that correct?”  Express empathy.  When talking to pet owners, the veterinary health care team should be able to understand the owner’s situation and be able to communicate that to them. For example, “I know you care for Simon, and I understand this can be overwhelming.” In addition to acquiring a patient history from the owner Receptionists and client-service coordinators are often the first regarding the presenting complaint, one must also inquire about the interaction the pet owner will have with the veterinary practice. general status of the pet (including diet) and past pertinent medical Developing communication resources and telephone triage skills will history and obtain an accurate medication history. When asking help the nonclinical staff determine appropriate scheduling for ill about medications, one must be clear to specifically ask about pre- patients and those requiring ongoing monitoring with timed testing ventives, over-the-counter medications, supplements or nutraceuti- or even potentially life-threatening situations. cals, and any topical medications. Owners often only think of oral The patient history that is obtained by the credentialed veteri- prescription medications and may not think to divulge important nary technician or veterinary assistant plays an essential role in veter- information, such as the use of topical exogenous corticosteroid inary case management for endocrinopathies. The patient history products. focuses on the pet’s health from the point of view of the pet owner, Clear communication with the pet owner and the veterinary which is invaluable as this information cannot be wholly determined team facilitates ongoing care and monitoring. Without proper com- by physical examination and diagnostic test results alone. An accu- munication and established protocols, scheduling something as sim- rate history is helpful in determining the duration and severity of ple as an ACTHST can be problematic if the owner, client-service clinical signs, developing a problem list or prioritizing differentials, coordinator, credentialed veterinary technician, or veterinary assis- and monitoring a patient’s response to therapeutic interventions. For tant does not know when an ACTHST should begin after trilostane example, knowing the likelihood of toxin exposure may help the vet- administration. Additionally, one must remember that dose adjust- erinarian assess a patient in a hypoadrenocortical crisis, when the ments are not made in a diagnostic vacuum. Clinical signs and phys- possibility of an acute kidney injury may confound the diagnosis. ical examination are equally important factors in successful ongoing Communication tips on how to take a quality patient  Encourage the use of a pet owner questionnaire.  Standardized history taking may promote continuity of care and monitoring of trends.  Templates can be tailored for different situations—wellness, sick visits, ongoing monitoring for chronic diseases, etc.  Address clients in a clear and courteous manner.  Speak respectfully and avoid using medical jargon or slang.  Start with open-ended questions.  Establish the presenting complaint and pet owner’s concerns with questions such as, “Can you describe to me what happened?” or “What brings you in today?”  Endeavor not to interrupt the pet owner, as valuable information may be missed.  After identifying the presenting complaint, progress to more focused closed-ended questions to clarify the situation, such as, “How long has this been happening?” or “How often does this occur?”  Allow for pauses. 20 JAAHA patient management. As these patients visit the veterinary practice more frequently history: | 59:3 May/Jun 2023 for monitoring, prioritizing patient comfort and reducing stress will go a long way in building the veterinary health care team’s relationship with the pet and their owner. Not only will low-stress visits reinforce pet owner compliance for timely follow-up, but they will also encourage more reliable diagnostic results as stress can influence many endocrine-related diagnostics. For example, using devices such as butterfly catheters for ACTHST and LDDST to facilitate both obtaining a baseline sample and administering the appropriate medication with a single venipuncture has the benefit of reducing stress and minimizing discomfort and vessel trauma when compared with repeated venipuncture events. Another example of prioritizing patient comfort to support consistent diagnostic values to monitor trends is blood pressure measurement. The 2018 ACVIM Consensus Statement: Guidelines for the 2023 AAHA Selected Endocrinopathies of Dogs and Cats Guidelines—Final Identification, Evaluation, and Management of Systemic Hypertension in Dogs and Cats includes a helpful protocol for accurate blood pressure measurement in small animal patients.87 Regardless of the endocrinopathy, the veterinary health care team is instrumental in educating the pet owner. For successful management, the client should have a basic understanding of the disease, the clinical signs, adverse events, long-term goals, and recommendations regarding treatment and ongoing care. Conclusion Canine and feline practitioners will inevitably encounter the endocrinopathies discussed in these guidelines. The clinical signs of these diseases are typically nonspecific and often highly variable and in some cases can be iatrogenic in origin. Early-stage disease can be subclinical. Adding to the complexity of endocrine disease is the possibility of comorbidities, some of which can be secondary to advancing age, as in the case of canine hypothyroidism and hypercortisolism and feline hyperthyroidism. Collectively, these factors place a premium on diagnostic testing and an accurate patient history to arrive at a diagnosis and effective treatment plan. Careful treatment monitoring is indicated in endocrinopathy management, including noting the presence or resolution of clinical signs, trends in endogenous hormone levels, and therapeutic dose adjustments. The guidelines are intended to help practitioners logically deconstruct the ambiguous presentations that often characterize endocrine diseases. The algorithm tables included in the guidelines are designed to enable practitioners to quickly work through a diagnostic and treatment progression to address these often-challenging cases. The authors declare no conflicts of interest. The authors gratefully acknowledge the contribution of Mark Dana of Kanara Consulting Group, LLC, in the preparation of the manuscript and Robyn Jolly for her assistance during the task force meeting. REFERENCES 1. Behrend E, Holford A, Lathan P, et al. 2018 AAHA Diabetes Management Guidelines for Dogs and Cats. J Am Anim Hosp Assoc 2018;54(1): 1–21. 2. 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