Serum metabolome analysis in hyperthyroid cats before and after radioactive iodine therapy.

Hyperthyroidism is the most common feline endocrinopathy. In hyperthyroid humans, untargeted metabolomic analysis identified persistent metabolic derangements despite achieving a euthyroid state. Therefore, we sought to define the metabolome of hyperthyroid cats and identify ongoing metabolic changes after treatment. We prospectively compared privately-owned hyperthyroid cats (n = 7) admitted for radioactive iodine (I-131) treatment and euthyroid privately-owned control (CON) cats (n = 12). Serum samples were collected before (T0), 1-month (T1), and three months after (T3) I-131 therapy for untargeted metabolomic analysis by MS/MS. Hyperthyroid cats (T0) had a distinct metabolic signature with 277 significantly different metabolites than controls (70 increased, 207 decreased). After treatment, 66 (T1 vs. CON) and 64 (T3 vs. CON) metabolite differences persisted. Clustering and data reduction analysis revealed separate clustering of hyperthyroid (T0) and CON cats with intermediate phenotypes after treatment (T1 & T3). Mevalonate/mevalonolactone and creatine phosphate were candidate biomarkers with excellent discrimination between hyperthyroid and healthy cats. We found several metabolic derangements (e.g., decreased carnitine and α-tocopherol) do not entirely resolve after achieving a euthyroid state after treating hyperthyroid cats with I-131. Further investigation is warranted to determine diagnostic and therapeutic implications for candidate biomarkers and persistent metabolic abnormalities.

Blood pressure in hyperthyroid cats before and after radioiodine treatment.

BACKGROUND: Hyperthyroid cats commonly have systemic hypertension, with a reported prevalence of 7% to 48%. Although hypertension might be expected to resolve once treatment restores euthyroidism, it can persist or only first develop after treatment. OBJECTIVES: To determine the proportion of hyperthyroid cats with hypertension (systolic blood pressure [SBP] ≥160 mm Hg), persistence or first development of hypertension after successful radioiodine treatment, and correlation of post-treatment hypertension with azotemia or hypothyroidism. ANIMALS: Four hundred one hyperthyroid nonazotemic cats were included in the study. METHODS: Prospective, cross-sectional and before-and-after studies. All hyperthyroid cats had SBP measured by Doppler; 255 had SBP rechecked 6 months after successful radioiodine (131I) treatment. RESULTS: Of untreated hyperthyroid cats, 108/401 (27%) were hypertensive. A higher proportion of hypertensive cats were nervous/excited compared with normotensive cats (47% vs 12%; P < .001). Of the initially hypertensive cats, 87/108 cats were reexamined after 131I treatment; 43/87 (49%) cats normalized SBP, whereas 44/87 (51%) remained hypertensive. Of the initially normotensive cats, 16/168 (9.5%) first developed hypertension after successful 131I treatment. 7/60 (12%) of the 131I-treated hypertensive cats were azotemic and 9/60 (15%) were hypothyroid. A higher proportion of cats remaining hypertensive had nervous/excited demeanor than did normotensive cats (50% vs 17%; P < .001). CONCLUSIONS/CLINICAL IMPORTANCE: Hypertension, when present, resolves in many hyperthyroid cats after successful treatment. Hyperthyroid cats uncommonly develop new hypertension after treatment. Persistent or newly detected hypertension was unrelated to azotemia or iatrogenic hypothyroidism. More frequently perceived nervousness/anxiety in radioiodine-treated hypertensive cats suggests that many of these cats might have "situational" hypertension, as hyperthyroid-induced hypertension should resolve after treatment.

Evaluation of a novel, sensitive thyroid-stimulating hormone assay as a diagnostic test for thyroid disease in cats.

OBJECTIVE: Clinicians commonly use thyroid-stimulating hormone (TSH) concentrations to diagnose thyroid disorders in humans and dogs. In cats, canine TSH chemiluminescent immunoassays (CLIA) assays are commonly used to measure TSH, but these TSH-CLIAs cannot measure low TSH concentrations (< 0.03 ng/mL) and therefore cannot distinguish between low-normal concentrations and truly low TSH concentrations (characteristic of hyperthyroidism). Our aim was to evaluate a novel TSH assay based on bulk acoustic wave (BAW) technology that has lower functional sensitivity (0.008 ng/mL) than TSH-CLIAs. ANIMALS: 169 untreated hyperthyroid cats, 53 cats treated with radioiodine (131I), 12 cats with chronic kidney disease (CKD), and 78 clinically healthy cats. METHODS: Serum concentrations of T4, TSH-CLIA, and TSH-BAW were measured in all cats. Untreated hyperthyroid cats were divided into 4 severity groups (subclinical, mild, moderate, and severe), whereas 131I-treated cats were divided into euthyroid and hypothyroid groups. RESULTS: Test sensitivity, specificity, and positive predictive value for identifying hyperthyroidism were higher for TSH-BAW (90.5%, 98.9%, and 86.9%) than TSH-CLIA (79.9%, 76.7%, and 21.7%; P < .001). Test sensitivity for identifying 131I-induced hypothyroidism was only 45.5% for T4 versus 100.0% for both TSH-CLIA and TSH-BAW (P = .03), whereas TSH-BAW had a higher positive predictive value (100%) than did either TSH-CLIA (81.2%) or T4 (71.9%). CLINICAL RELEVANCE: Serum TSH-BAW alone or together with T4 is a highly sensitive and specific diagnostic test for evaluating feline hyperthyroidism and iatrogenic hypothyroidism. Finding low serum TSH-BAW concentrations is most useful for diagnosing subclinical and mild hyperthyroidism, in which serum T4 remains within or only slightly above the reference interval.

Urine concentrating ability in cats with hyperthyroidism: Influence of radioiodine treatment, masked azotemia, and iatrogenic hypothyroidism.

BACKGROUND: Hyperthyroid cats often have urine specific gravity (USG) values <1.035. It remains unclear how USG changes after treatment, if USG can be used to predict azotemia after treatment, or how iatrogenic hypothyroidism influences USG values. OBJECTIVES: To determine the proportion of hyperthyroid cats with USG <1.035 vs ≥1.035; if USG changes after treatment; and whether USG <1.035 correlated with unmasking of azotemia or hypothyroidism. ANIMALS: Six hundred fifty-five hyperthyroid cats treated with radioiodine; 190 clinically normal cats. METHODS: Prospective, before-and-after study. Hyperthyroid cats had serum thyroxine, thyroid-stimulating hormone, and creatinine concentrations, and USG measured before and 6 months after successful treatment with radioiodine. RESULTS: Of untreated hyperthyroid cats, USG was ≥1.035 in 346 (52.8%) and <1.035 in 309 (47.2%). After treatment, 279/346 (80.6%) maintained USG ≥1.035, whereas 67/346 (19.4%) became <1.035; 272/309 (88%) maintained USG <1.035, whereas 37/309 (12%) became ≥1.035. Only 22/346 (6.4%) with USG ≥1.035 developed azotemia after treatment, compared with 136/309 (44%) with <1.035 (P < .001). Of cats remaining nonazotemic, 38% had USG <1.035, compared with 20% of normal cats (P < .001). The 137 cats with iatrogenic hypothyroidism had lower USG after treatment than did 508 euthyroid cats (1.024 vs 1.035), but USGs did not change after levothyroxine supplementation. USG <1.035 had high sensitivity (86.1%) but moderate specificity (65.2%) in predicting azotemia after treatment. CONCLUSIONS AND CLINICAL IMPORTANCE: Hyperthyroidism appears not to affect USG in cats. However, cats with evidence of sub-optimal concentrating ability before radioiodine treatment (USG < 1.035) are more likely to develop azotemia and unmask previously occult chronic kidney disease. Iatrogenic hypothyroidism itself did not appear to affect USG values.

Biological variation of serum thyrotropin and thyroid hormones concentrations determined at 8-week intervals for 1 year in clinically healthy cats.

BACKGROUND: Cats commonly develop thyroid disease but little is known about the long-term biological variability of serum thyroid hormone and thyrotropin (thyroid-stimulating hormone; TSH) concentrations. OBJECTIVES: We aimed to determine the long-term biological variation of thyroid hormones and TSH in clinically healthy cats. METHODS: A prospective, observational study was carried out. Serum samples for analysis of total thyroxine (T4, by radioimmunoassay [RIA] and homogenous enzyme immunoassay [EIA]), triiodothyronine (T3 ), free T4 (by dialysis), and TSH were obtained every 8 weeks for 1 year from 15 healthy cats, then frozen until single-batch analysis. Coefficients of variation (CV) within individual cats ( CV I ) and among individual cats ( CV G ), as well as the variation between duplicates (ie, analytical variation [ CV A ]) were determined with restricted maximum likelihood estimation. The indices of individuality (IoI) and reference change values (RCVs) for each hormone were calculated. RESULTS: Some thyroid hormones showed similar (total T4 by EIA) or greater (TSH) interindividual relative to intraindividual variation resulting in intermediate to high IoI, consistent with previous studies evaluating the biological variation of these hormones weekly for 5-6 weeks. By contrast, total T4 (by RIA) and free T4 had a low IoI. Total T3 had a high ratio of CV A to CV I ; therefore, interindividual variation could not be distinguished from analytical variation. No seasonal variability in the hormones could be demonstrated. CONCLUSIONS: Clinicians might improve the diagnosis of feline thyroid disease by establishing baseline concentrations for analytes with intermediate-high IoI (total T4, TSH) for individual cats and applying RCVs to subsequent measurements.

Biological variation of biochemical analytes determined at 8-week intervals for 1 year in clinically healthy cats.

BACKGROUND: Biological variation helps determine whether population-based or subject-based reference intervals are more appropriate to assess changes in serial analytical values. Previous studies have investigated the biological variation of biochemical analytes weekly or with variable frequency over 5-14 weeks in cats, but none have considered biological variation at less frequent intervals over 1 year. OBJECTIVES: We aimed to evaluate the long-term biological variation of 19 biochemical analytes in clinically healthy cats. METHODS: A prospective, observational study in which 15 clinically healthy, client-owned cats were sampled for serum biochemical analyses every 8 weeks for 1 year. Frozen serum samples were single-batch analyzed. Restricted maximum likelihood estimation was used to determine the coefficients of variation (CV), describing variation within each cat, between cats, and the analytical variation. These CVs were used to determine the indices of individuality and reference change values (RCVs). RESULTS: Albumin, alkaline phosphatase, creatine kinase, and globulin had high indices of individuality, indicating that they are best evaluated by RCVs. Phosphorus, potassium, chloride, sodium, symmetric dimethylarginine, and total CO2 had low indices of individuality, indicating that population-based reference intervals are appropriate. Alanine aminotransferase, aspartate aminotransferase, blood urea nitrogen, calcium, cholesterol, creatinine, glucose, total bilirubin, and total protein had intermediate indices of individuality, indicating that RCVs may provide additional insight into the interpretation of analyte measurements beyond the population-based reference intervals. CONCLUSIONS: For many analytes, the biological variation detected was similar to that reported in prior studies. Clinicians should consider the biological variation of analytes to best interpret clinically relevant changes in serial analyte measurements.

Effect of radioiodine treatment on muscle mass in hyperthyroid cats.

BACKGROUND: Approximately 75% of hyperthyroid cats lose muscle mass as accessed with a muscle condition scoring (MCS) system. After treatment, MCS improves as the cats regain muscle mass. OBJECTIVES: To quantify the degree of muscle loss in hyperthyroid cats using ultrasonography and evaluate changes in muscle mass after treatment. ANIMALS: Forty-eight clinically normal cats and 120 cats with untreated hyperthyroidism, 75 of which were reevaluated after radioiodine-131 therapy. METHODS: Prospective cross-sectional and before-after studies. All cats underwent ultrasonography and measurement of epaxial muscle height (EMH), with subsequent calculation of vertebral and forelimb epaxial muscle scores (VEMS and FLEMS). A subset of hyperthyroid cats underwent repeat muscle imaging 6 months after treatment. RESULTS: Untreated hyperthyroid cats had a lower EMH than did clinically normal cats (median [25th-75th percentile], 0.98 [0.88-1.16] cm vs 1.34 [1.23-1.58] cm, P < .001). Seventy-seven (64.2%) untreated cats had subnormal EMH. Similarly, compared to normal cats, hyperthyroid cats had lower VEMS (0.93 [0.84-1.07] vs 1.27 [1.18-1.39], P < .001) and FLEMS (1.24 [1.10-1.35] vs 1.49 [1.39-1.63], P < .001). After treatment, EMH increased (1.03 [0.89-1.03] cm to 1.33 [1.17-1.41] cm, P < .001), with abnormally low EMH normalizing in 36/41 (88%). Both VEMS (0.94 [0.87-1.10] to 1.21 [1.10-1.31], P < .001) and FLEMS (1.31 [1.17-1.40] to 1.47 [1.38-1.66], P < .001) also increased after treatment. CONCLUSIONS AND CLINICAL IMPORTANCE: Almost two-thirds of hyperthyroid cats have abnormally low muscle mass when measured quantitatively by ultrasound. Successful treatment restores muscle mass in >85% of cats. EMH provided the best means of quantitating muscle mass in these cats.

Association of recessive c.430G>A (p.(Gly144Arg)) thyroid peroxidase variant with primary congenital hypothyroidism in cats.

BACKGROUND: Primary congenital hypothyroidism (CH) is a rare endocrine disorder in cats with a largely unknown genetic cause. OBJECTIVES: Describe the clinical presentation of CH in 11 affected cats and identify the causal genetic variant. ANIMALS: Eleven CH-cats from 10 unrelated families, 11 CH-free family members, 21 unrelated CH-free cats, and 155 unrelated nondiagnosed cats from different breeds. METHODS: Case control study of CH-cats and their siblings (2019-2021). Diagnosis was based on low to low-normal serum thyroxine (T4) concentrations, high thyroid-stimulating hormone (TSH) concentrations and clinical signs compatible with CH. We identified the causal variant using Sanger sequencing, genotyping via PCR-RFLP and variant interpretation using ACMG/AMP guidelines. RESULTS: All CH-cats (5 weeks-8 years) had disproportionate dwarfism. A goiter was not palpable in all. Thyroid scintigraphy with radiopertechnetate showed abnormally high uptake by thyroid glands, whereas scintigraphy with radioiodine showed abnormally low uptake, compatible with a defect in iodine organification by thyroid peroxidase (TPO). All cases were homozygous for TPO variant XM_006930524.4:c.430G>A(p.(Gly144Arg)), while none of the CH-free cats were. All sampled parents were heterozygous for this recessive variant. This variant was found in 15 cat breeds with an estimated allele frequency of 9%. CONCLUSIONS AND CLINICAL IMPORTANCE: Disproportionate dwarfism, abnormally high TSH and abnormally low to low-normal T4 concentrations are diagnostic for CH in cats. All cases had dyshormonogenesis demonstrated by thyroid scintigraphy. This novel TPO missense variant (not described in humans) causes CH in cats and awareness of it can assist in diagnosis and breeding.

Radioiodine treatment of hyperthyroidism in cats: results of 165 cats treated by an individualised dosing algorithm in Spain.

OBJECTIVES: Although radioiodine (131I) is the treatment of choice for feline hyperthyroidism, 131I-dosing protocols commonly induce iatrogenic hypothyroidism and expose azotaemia. A recently reported patient-specific 131I dosing algorithm minimised the risk of 131I-induced hypothyroidism and azotaemia, while maintaining high cure rates. The aim of the study was to report results of 131I treatment in a European population of hyperthyroid cats using this patient-specific dosing algorithm. METHODS: This prospective case series (before-and-after study) evaluated 165 hyperthyroid cats referred for 131I treatment. All cats had serum concentrations of thyroxine (T4), triiodothyronine (T3) and thyroid-stimulating hormone (TSH) measured (off methimazole ⩾1 week). Thyroid volume and percentage uptake of 99mTc-pertechnetate (TcTU) were determined using thyroid scintigraphy. An initial 131I dose was calculated by averaging dose scores for T4/T3 concentrations, thyroid volume and TcTU; 70% of that composite dose was then administered. Twenty-four hours later, percentage 131I uptake was measured, and additional 131I administered as needed to deliver an adequate radiation dose to the thyroid tumour(s). Serum concentrations of T4, TSH and creatinine were determined 6-12 months later. RESULTS: Median calculated 131I dose was 2.15 mCi (range 1.2-7.5), with only 51 (30.9%) receiving ⩾2.5 mCi. Of 165 cats, 124 (75.2%) became euthyroid, seven (4.2%) became overtly hypothyroid, 27 (16.4%) became subclinically hypothyroid and seven (4.2%) remained hyperthyroid. A higher proportion of overtly (85.7%) and subclinically (26.9%) hypothyroid cats developed azotaemia than euthyroid cats (13.6%; P = 0.0002). Hypothyroid cats were older (P = 0.016) and more likely to have detectable TSH concentrations (P = 0.025) and symmetrical bilateral distribution of 99mTc-pertechnetate uptake (P = 0.0002), whereas persistently hyperthyroid cats had higher severity scores (P = 0.012). CONCLUSIONS AND RELEVANCE: Our results confirm that 131I dosing with this new algorithm results in high cure rates, with a lowered prevalence of 131I-induced overt hypothyroidism and azotaemia. Age, serum TSH concentrations, bilateral, symmetrical uptake and severity score help predict outcome.

Predicting outcomes in hyperthyroid cats treated with radioiodine.

BACKGROUND: Radioiodine (131 I) is the treatment of choice for cats with hyperthyroidism. After 131 I, however, euthyroidism is not always achieved, with 5% to 10% of cats remaining persistently hyperthyroid and 20% to 50% developing iatrogenic hypothyroidism. OBJECTIVES: To identify pretreatment factors that may help predict persistent hyperthyroidism and iatrogenic hypothyroidism after treatment of cats using a novel 131 I dosing algorithm. ANIMALS: One thousand and four hundred hyperthyroid cats treated with 131 I. METHODS: Prospective, before-and-after study. Pretreatment predictors (clinical, laboratory, scintigraphic, 131 I dose, 131 I uptake measurements) of treatment failure or iatrogenic hypothyroidism were identified by multivariable logistic regression analysis. RESULTS: Cats that developed iatrogenic hypothyroidism were more likely to be older (odds ratio [OR] = 1.10; 95% confidence interval [CI], 1.04-1.17; P = .001), female (OR = 2.04; 95% CI, 1.54-2.70; P < .001), have detectable serum thyroid-stimulating hormone (TSH) concentrations (OR = 4.19; 95% CI, 2.0-8.81; P < .001), have bilateral thyroid nodules (OR = 1.57; 95% CI, 1.19-2.08; P < .001), have homogeneous, bilateral distribution of 99m Tc-pertechnetate uptake (OR = 2.93; 95% CI, 2.05-4.19; P < .001), have milder severity score (OR = 0.62; 95% CI, 0.49-0.79; P < .001), and have higher 131 I uptake (OR = 2.40; 95% CI, 1.75-3.28; P < .001). In contrast, cats remaining persistently hyperthyroid were more likely to be younger (OR = 0.81; 95% CI, 0.72-0.92; P < .001), have higher severity score (OR = 1.87; 95% CI, 1.51-2.31; P < .001), and have lower 131 I uptake (OR = 3.50; 95% CI, 1.8-6.80; P < .001). CONCLUSIONS AND CLINICAL IMPORTANCE: Age, sex, serum TSH concentration, bilateral and homogeneous 99m Tc-pertechnetate uptake on scintigraphy, severity score, and percent 131 I uptake are all factors that might help predict outcome of 131 I treatment in hyperthyroid cats. Cats with persistent hyperthyroidism had many predictive factors that directly contrasted those of cats that developed 131 I-induced hypothyroidism.

A dosing algorithm for individualized radioiodine treatment of cats with hyperthyroidism.

BACKGROUND: Radioiodine (131 I) is the treatment of choice for hyperthyroidism in cats, but current 131 I-dosing protocols can induce iatrogenic hypothyroidism and expose azotemia. OBJECTIVES: To develop a cat-specific algorithm to calculate the lowest 131 I dose to resolve hyperthyroidism, while minimizing risk of iatrogenic hypothyroidism and subsequent azotemia. ANIMALS: One thousand and four hundred hyperthyroid cats treated with 131 I. METHODS: Prospective case series (before-and-after study). All cats had serum concentrations of thyroxine (T4 ), triiodothyronine (T3 ), and thyroid-stimulating hormone (TSH) measured (off methimazole ≥1 week). Using thyroid scintigraphy, each cat's thyroid volume and percent uptake of 99m Tc-pertechnatate (TcTU) were determined. An initial 131 I dose was calculated by averaging dose scores for T4 /T3 concentrations, thyroid volume, and TcTU; 80% of that composite dose was administered. Twenty-four hours later, percent 131 I uptake was measured, and additional 131 I administered, as needed, to deliver an adequate radiation dose to the thyroid tumor(s). Serum concentrations of T4 , TSH, and creatinine were determined 6 to 12 months later. RESULTS: The median calculated 131 I dose was 1.9 mCi (range, 1.0-10.6 mCi); 1380 cats required additional 131 I administration on day 2. Of the cats, 1047 (74.8%) became euthyroid, 57 (4.1%) became overtly hypothyroid, 240 (17.1%) became subclinically hypothyroid, and 56 (4%) remained hyperthyroid. More overtly (71.9%) and subclinically (39.6%) hypothyroid cats developed azotemia than euthyroid cats (14.2%; P < .0001). CONCLUSIONS AND CLINICAL IMPORTANCE: Our algorithm for calculating individual 131 I doses resulted in cure rates similar to historical treatment rates, despite much lower 131 I doses. This algorithm appears to lower prevalence of both 131 I-induced overt hypothyroidism and azotemia.

Serum thyroxine and thyrotropin concentrations decrease with severity of nonthyroidal illness in cats and predict 30-day survival outcome.

BACKGROUND: In cats, nonthyroidal illness affects serum thyroid hormone concentrations. Serum thyroxine (T4 ) and triiodothyronine (T3 ) concentrations commonly decrease, whereas free T4 (fT4 ) concentrations vary unpredictably. Limited information exists regarding effects on serum thyrotropin (thyroid-stimulating hormone [TSH]) concentrations in cats with nonthyroidal illness syndrome (NTIS). OBJECTIVES: To characterize alterations in thyroid function that develop in cats with NTIS and to correlate these alterations with severity and outcome of the nonthyroidal illness. ANIMALS: Two hundred and twenty-two cats with NTIS and 380 clinically normal cats of similar age and sex. METHODS: Prospective, cross-sectional study. All cats had serum T4 , T3 , free T4 , and TSH concentrations measured. Cats were grouped based on illness severity and 30-day survival. RESULTS: Cats with NTIS had lower serum T4 and T3 concentrations than did normal cats (P < .001). Serum fT4 and TSH concentrations did not differ between groups. Serum T4 , T3 , and fT4 concentrations progressively decreased with increasing disease severity (P < .001). The 56 cats that died had lower T4 , T3 , and TSH concentrations than did the 166 survivors, with no difference in fT4 concentration. Multivariable logistic regression modeling indicated that serum T4 and TSH concentrations both predicted survival (P < .02). CONCLUSIONS AND CLINICAL IMPORTANCE: Cats with NTIS commonly develop low serum T4 , T3 , and TSH concentrations, the prevalence and extent of which increases with disease severity. Clinicians should consider evaluating thyroid function in cats with severe NTIS, because doing so could help determine probability of successful treatment responses before investing considerable time, effort, and finances in addressing the underlying disease.

Hyperthyroidism in Cats: Considering the Impact of Treatment Modality on Quality of Life for Cats and Their Owners.

In cats, hyperthyroidism can be treated in 4 ways: medical management with methimazole or carbimazole, nutritional management (low-iodine diet), surgical thyroidectomy, and radioactive iodine (131I). Each form of treatment has advantages and disadvantages that should be considered when formulating a treatment plan for the individual hyperthyroid cat. Medical and nutritional managements are considered "reversible" or palliative treatments, whereas surgical thyroidectomy and 131I are "permanent" or curative treatments. The author discusses how each treatment modality could be the optimal choice for a specific cat-owner combination and reviews the advantages and disadvantages of each treatment option.

Biologic variation of symmetric dimethylarginine and creatinine in clinically healthy cats.

BACKGROUND: Biologic variation of biochemical analytes, both within individuals and between individuals, determines whether population-based reference intervals (RIs) are appropriate when interpreting if a particular change is clinically relevant for a specific individual. OBJECTIVES: We aimed to evaluate the biologic variation of symmetric dimethylarginine (SDMA) in clinically healthy cats. METHODS: A prospective, observational study was performed in which 10 clinically healthy, client-owned cats were sampled for serum biochemical analyses once weekly for 6 weeks. Serum samples were frozen, and then single batches were analyzed for SDMA, using both liquid chromatography-mass spectroscopy (LC-MS), and an enzyme multiplied immunoassay technique (EMIT), and creatinine by modified Jaffe method. Restricted maximum likelihood estimations were used to determine the coefficients of variation (CVs) describing variation within each cat, between cats, and the analytical variation. These CVs were used to determine the indices of individuality and reference change values (RCVs). RESULTS: SDMA had an intermediate index of individuality that could be evaluated by both RCV and population-based RIs. In contrast, creatinine had a high index of individuality best evaluated with RCVs. Serum SDMA concentrations evaluated with either the reference standard, LC-MS, or the clinically used EMIT yielded similar results. CONCLUSIONS: Clinicians should consider biologic variation when selecting the best method for interpreting changes in biochemical analytes. Specifically, establishing each cat's baseline serum creatinine and SDMA concentrations during health, and applying RCVs to subsequent measurements could improve the recognition of meaningful biologic changes.

Hyperthyroidism is not a risk factor for subclinical bacteriuria in cats: A prospective cohort study.

BACKGROUND: Subclinical bacteriuria is defined as a positive bacterial urine culture in the absence of clinical evidence of urinary tract infection (UTI). Studies have reported that hyperthyroid cats have UTIs (mostly subclinical) with prevalence rates of 12%-22%. Consequently, clinicians consider hyperthyroidism a risk factor for development of subclinical bacteriuria, and many recommend urine culture when evaluating hyperthyroid cats. OBJECTIVES: To compare the prevalence of subclinical bacteriuria (based on positive urine culture) in untreated hyperthyroid cats to that in euthyroid cats of similar age and sex. ANIMALS: Three hundred and ninety-three hyperthyroid cats presented for radioiodine treatment and 131 euthyroid cats (≥7 years of age) presented for routine examination. Cats with signs of lower urinary tract disease were excluded. METHODS: Prospective cohort study. Both hyperthyroid and euthyroid cats had urine collected by cystocentesis for complete urinalysis and culture. Data pertaining to age, sex, body condition, and serum thyroxine and creatinine concentrations also were acquired. Logistic regression was performed to evaluate for potential risk factors for subclinical bacteriuria. RESULTS: Hyperthyroid cats showed a low prevalence of subclinical bacteriuria (4.3%), which did not differ from that found in euthyroid cats (4.6%). Of the signalment factors evaluated, only female sex was a significant risk factor (odds ratio [OR], 6.9; P = .002). Furthermore, positive urine cultures were more likely in specimens with dilute urine concentration (<1.035), pyuria, or microscopic bacteriuria. CONCLUSIONS AND CLINICAL IMPORTANCE: Hyperthyroid cats are not at risk for subclinical bacteriuria. In the absence of lower urinary tract signs, no clinical benefit exists in routinely performing urine cultures when evaluating hyperthyroid cats.

Silicone Pet Tags Associate Tris(1,3-dichloro-2-isopropyl) Phosphate Exposures with Feline Hyperthyroidism.

Feline hyperthyroidism is the most commonly diagnosed endocrine-related disease among senior and geriatric housecats, but the causes remain unknown. Exposure to endocrine-disrupting compounds with thyroid targets, such as flame retardants (FRs), may contribute to disease development. Silicone passive sampling devices, or pet tags, quantitatively assessed the bioavailable FR exposures of 78 cats (≥7 y) in New York and Oregon using gas chromatography-mass spectrometry. Pet tags were analyzed for 36 polybrominated diphenyl ethers, six organophosphate esters (OPEs), and two alternative brominated FRs. In nonhyperthyroid cats, serum free thyroxine (fT4), total T4 (TT4), total triiodothyronine, and thyroid-stimulating hormone concentrations were compared with FR concentrations. Tris(1,3-dichloro-2-isopropyl) phosphate (TDCIPP) concentrations were higher in hyperthyroid pet tags in comparison to nonhyperthyroid pet tags (adjusted odds ratio, p < 0.07; Mantel-Cox, p < 0.02). Higher TDCIPP concentrations were associated with air freshener use in comparison to no use (p < 0.01), residences built since 2005 compared to those pre-1989 (p < 0.002), and cats preferring to spend time on upholstered furniture in comparison to no preference (p < 0.05). Higher TDCIPP concentrations were associated with higher fT4 and TT4 concentrations (p < 0.05). This study provides proof-of-concept data for the use of silicone pet tags with companion animals and further indicates that bioavailable TDCIPP exposures are associated with feline hyperthyroidism.

Spontaneous primary hypothyroidism in 7 adult cats.

BACKGROUND: Naturally occurring hypothyroidism in adult cats is rare, with only 4 cases reported. OBJECTIVES: To describe the historical, clinical, laboratory, and scintigraphic features of adult cats with spontaneous hypothyroidism. ANIMALS: Seven adult cats referred for suspected hypothyroidism. METHODS: Prospective case series. We collected data on cats' signalment, clinical signs, results of physical examination, routine laboratory and thyroid hormone testing, and thyroid imaging (thyroid scintigraphy or ultrasound). We subsequently treated cats with levothyroxine and evaluated their response to treatment. RESULTS: Cats ranged from 3.5 to 11 years, with no apparent breed predilection; 6/7 cats were male. Only 2/7 cats were initially tested because of signs of hypothyroidism (hair-coat changes, lethargy, obesity); others were tested for routine thyroid monitoring or palpable thyroid nodules. Four were azotemic (serum creatinine, 2.2-3.4 mg/dL). Six of the cats had low serum thyroxine (T4 ) and free T4 (fT4 ) concentrations, whereas all 7 cats had high thyroid-stimulating hormone (TSH) concentrations. In 6/7 cats, thyroid scintigraphy revealed bilateral goiter with intense radionuclide uptake; imaging showed no visible thyroid tissue in the other. After levothyroxine treatment, serum concentrations of T4 and fT4 increased and TSH fell; high serum creatinine normalized in azotemic cats; and repeat imaging showed reduction in goiter size. CONCLUSIONS AND CLINICAL IMPORTANCE: Primary hypothyroidism develops in adult cats, with a higher prevalence than previously thought. Most cats appear to develop a goitrous form of hypothyroidism associated with thyroid hyperplasia, whereas thyroid atrophy appears to be less common. With levothyroxine replacement, clinical and laboratory abnormalities improve or resolve.

Contrast-enhanced ultrasound complements two-dimensional ultrasonography in diagnosing gallbladder diseases in dogs.

Gall-bladder diseases are common in dogs and two-dimensional ultrasonography is a current standard method for diagnosis and treatment planning. However, findings from this modality can be nonspecific. The aim of this retrospective, case series study was to describe conventional and contrast-enhanced ultrasound (using SonoVue® ) findings in a group of dogs with histologically confirmed gall bladder disease. A total of 65 dogs were included. Branchlike, heterogeneous, and homogeneous contrast enhancement of echogenic intraluminal mass-forming lesions was a contrast-enhanced ultrasound characteristic of polypoid lesions due to cystic mucosal hyperplasia of the gallbladder and/or tumor, which had different wash-in and washout characteristics. In dogs with mobile or immobile biliary sludge or mucocele, the echogenic intraluminal masses remained unenhanced. A double rim mark or enhancement defect in the gallbladder wall was a characteristic of edema or necrosis/rupture of the wall, respectively. Conventional ultrasonography correctly identified biliary sludge or mucocele in 36/37 dogs, cholecystitis/edema in 44/47 dogs, necrosis/rupture in 19/25 dogs, and gallbladder neoplasia in three of three dogs with these pathologies. It falsely identified biliary sludge or mucocele in eight of 28 dogs, cholecystitis/edema in three of 15 dogs, necrosis/rupture in 13/37 dogs, and gall-bladder neoplasia in 20/59 dogs that did not have these pathologies. Contrast-enhanced ultrasound correctly identified cholecystitis/edema in 42/47 dogs, but falsely identified cholecystitis/edema in three of 18 dogs. It correctly identified necrosis/rupture, benign polypoid lesions, and gallbladder neoplasia in all dogs with no false-positive results. Findings supported contrast-enhanced ultrasound as a complement to conventional ultrasonography for dogs with suspected gallbladder pathologies such as edema, necrosis, and rupture.

Comparison of in-clinic point-of-care and reference laboratory total thyroxine immunoassays for diagnosis and post-treatment monitoring of hyperthyroid cats.

Objectives The Catalyst One Chemistry Analyzer (IDEXX Laboratories) is a point-of-care instrument that can measure total thyroxine (TT4) by immunoassay. The aims of this study were to evaluate the analytic performance of the Catalyst TT4 assay in feline sera and to examine agreement of the Catalyst TT4 results with those measured by immunoassay at a veterinary reference laboratory. Methods Assay precision, reproducibility and linearity were evaluated for the Catalyst TT4 assay. For method comparison, TT4 concentrations in serum samples from 157 cats (127 hyperthyroid, 30 radioiodine-treated cats) were analyzed by both in-clinic and reference laboratory methods. Results The Catalyst TT4 demonstrated good precision and reproducibility (coefficients of variation ⩽8.5%) and excellent linearity in the diagnostic range of 6-150 nmol/l. Differences between the two TT4 methods showed no proportional or fixed bias (Bland-Altman plots) but did demonstrate greater spread of values at higher TT4 concentrations. Statistical analysis of percent differences between methods indicated 95% limits of agreement of ± 30%. When serum TT4 concentrations were classified as low, high or within the reference interval (12-50 nmol/l) for each assay, there was strong agreement (96.8%) in classification between methods. Conclusions and relevance The Catalyst TT4 assay provided precise serum TT4 concentrations in the 157 samples analyzed, which agreed well with results provided by a reference laboratory. Cats with Catalyst TT4 concentrations near decision thresholds (eg, normal vs high) should either have TT4 concentration repeated a few weeks later and/or undergo further testing (eg, free T4, serum thyroid-stimulating hormone, thyroid scintigraphy) to determine thyroid status.

EVALUATION OF CONTRAST-ENHANCED ULTRASONOGRAPHY AS A METHOD FOR DETECTING GALLBLADDER NECROSIS OR RUPTURE IN DOGS.

Gall bladder necrosis and rupture are life-threatening conditions in dogs requiring surgical intervention and early diagnosis is essential. Human patients with suspected gall bladder necrosis/rupture are commonly evaluated with contrast-enhanced ultrasonography (CEUS), however this procedure has not been described in dogs with suspected gall bladder necrosis/rupture. In a prospective diagnostic cohort study, CEUS (using SonoVue contrast medium) was performed in 93 dogs with gallbladder lesions identified by abdominal conventional ultrasonography. Necrosis/rupture was identified by CEUS as a focal lack of enhancement of the gallbladder wall. Dogs with positive CEUS finding for necrosis/rupture (complete lack of regional wall enhancement) underwent immediate surgery as did dogs with other biliary disorders requiring surgery. Dogs with negative CEUS findings or those not requiring surgery were managed medically. In cases undergoing surgery, necrosis/rupture was confirmed intraoperatively (and via histopathology). Absence of necrosis/rupture was confirmed either intraoperatively (via histopathology) or was assumed to be absent by complete recovery with medical management. Forty-nine dogs underwent surgery and cholecystectomy: 24 had necrosis/rupture. CEUS was more accurate (100% sensitive and specific) in diagnosing gallbladder wall necrosis/rupture than conventional ultrasonography (75% sensitive and 81% specific) (P < 0.03). In conclusion, CEUS provides accurate characterization of gallbladder wall integrity that can impact decisions regarding clinical management, either surgical or medical.