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Article

Prospective Evaluation of the Prevalence and Laboratory Findings in Adult Cats with Low Thyroxine and Increased Thyrotropin Concentration

1
Clinic for Small Animals (Internal Medicine, Clinical Pathology and Clinical Pathophysiology), Justus-Liebig-University, 35392 Giessen, Germany
2
Antech Lab Germany GmbH, 86156 Augsburg, Germany
*
Author to whom correspondence should be addressed.
Pets 2024, 1(3), 500-517; https://doi.org/10.3390/pets1030034
Submission received: 26 September 2024 / Revised: 12 December 2024 / Accepted: 16 December 2024 / Published: 21 December 2024

Abstract

:
Adult-onset spontaneous feline hypothyroidism (SH) is considered rare, but its prevalence is unknown. This study aimed to screen laboratory submissions for cats with laboratory suspected SH (LSSH) and to identify laboratory abnormalities associated with LSSH. Submissions to a commercial laboratory in Germany between January 2022 and April 2023 were prospectively screened for cats aged 3–12 years with low total thyroxine (TT4); in these cats, thyrotropin (TSH) was measured. Iatrogenic hypothyroidism was excluded by contacting submitting veterinarians. Creatinine, triglyceride and cholesterol concentration and red blood cell count (RBC) of cats with LSSH (low TT4, TSH > 0.53 ng/mL; i.e., [one sided TSH reference change value (76%) of TSH upper reference interval (RI)] + [TSH upper RI] = 0.53) were compared to euthyroid cats (TT4 within RI) and cats with suspected non-thyroidal illness (SNTIS) (low TT4, normal TSH (<0.3 ng/mL; upper RI)) by non-parametric tests. p < 0.05 was significant. In total, 31,572 submissions of cats were included, 25,169 (79.7%) were euthyroid, 3818 (12.1%) had SNTIS and 61 (0.2%) had LSSH. Cats with LSSH had higher creatinine (p = 0.002) and lower RBC count (p < 0.0001) than euthyroid cats as well as higher creatinine (p = 0.00035) than cats with SNTIS. Azotaemia (creatinine > 140 µmol/L) and anaemia (RBC < 7.2 × 1012/L) were present in 28/49 (57%) and 19/44 (43%) cats with LSSH, respectively. There was no difference between LSSH and SNTIS for the remaining parameters. In cats with low TT4, azotaemia and anaemia might indicate the presence of SH and reinforce the need for TSH testing. Hypercholesterolaemia and hypertriglyceridaemia are not indicators of SH.

1. Introduction

While primary hypothyroidism is a common endocrinopathy in dogs, naturally occurring/spontaneous feline hypothyroidism is considered a rare disease [1]. The most common form of feline hypothyroidism is iatrogenic, secondary to treatment of hyperthyroidism [2]. Naturally occurring hypothyroidism has mainly been described in kittens or young cats that are affected by a congenital form of the disease but is rare in adult cats, with only a few cases described in the literature [1,3,4,5,6].
While congenital hypothyroidism is associated with early clinical signs like disproportionate dwarfism [2], clinical features in those few reported cases of adult-onset spontaneous hypothyroidism (abbreviated to SH throughout this article) in cats seemed non-specific (changes in hair coat like hair thinning and hair loss, weight gain and obesity, lethargy) [1,3,4,5,6]. Although this is largely similar to the clinical presentation of hypothyroid dogs, some hypothyroid cats also showed polyuria and polydipsia (PU/PD), which is not a feature of canine hypothyroidism. PU/PD is most likely related to azotaemia, which was described in 5/11 cases of naturally occurring adult-onset hypothyroidism reported in the literature [1,6]. In congenital hypothyroidism, azotaemia is also one of the most common laboratory features, but PU/PD has not been reported. Other laboratory abnormalities in cats with hypothyroidism (both adult-onset and congenital) included mild anaemia (mostly normocytic, normochromic), hypertriglycidaemia and hypercholesterolaemia [1,5,7,8], similar to findings in hypothyroid dogs [9,10].
Because SH in cats is thought to be rare and the clinical and laboratory findings are non-specific, the condition is rarely considered as a potential differential during work-up of feline cases. Although total thyroxine (TT4) is routinely measured as a part of laboratory profiles in cats, TT4 concentrations below the reference interval (RI) are often considered to occur secondary to the effect of non-thyroidal illness (NTIS) [11,12] and in most cases no further testing of thyroid function is requested. This is different to the situation in dogs, where TT4 values are usually interpreted in combination with thyroid-stimulating hormone (TSH) concentration, especially when TT4 is low [13]. In cats, TSH is usually only measured when there is suspicion of iatrogenic hypothyroidism secondary to treatment of hyperthyroidism. In one study in cats treated with radioiodine treatment (RAIT), TSH was the best parameter to identify iatrogenic hypothyroidism when compared to thyroid scintigraphy [14]. There is little information on TSH concentration in cats with SH, but in those cases, where it was measured, it was increased [1,4,5,6]. Interestingly, in the largest case series of feline SH, TSH was increased in all seven affected cats, while TT4 and free T4 (fT4) were below RI in 6/7 cases [1]. Therefore, TSH might be a good marker of SH and its measurement could be considered at least in cases with low TT4, which is a good practice in dogs. Currently, TSH in cats is measured using a chemiluminescent (CLIA) assay [1,15,16], but recently a new assay that is able to detect very low concentrations of feline TSH has been developed and validated [17] and is now commercially available.
Measurement of fT4 might also be useful in aiding diagnosis of SH in cats [18], but its use as a screening parameter is hampered by the availability of the equilibrium dialysis (ED) radioimmunoassay (ED-RIA, the recommended fT4 assay type), which is only performed in some laboratories and is costly [19,20]. In dogs, some authors suggested that a veterinary-specific CLIA fT4 analogue assay is highly accurate in diagnosing hypothyroidism [21], however, a recent study of 146 dogs with NTIS found that a third had a low fT4 [22]. Therefore, ED-RIA still remains the preferred assay for measurement of fT4 in this species [23,24]. In cats, fT4 measurement has been mainly evaluated for diagnosing hyperthyroidism [15], but a recent study using the veterinary-specific CLIA fT4 analogue method found it useful in diagnosing iatrogenic hypothyroidism following RAIT when compared to TSH stimulation testing [25]. However, another publication that also followed up cats after RAIT found that the CLIA method consistently underestimated fT4 concentration when compared to ED-RIA [20]. Importantly, fT4 was low in 40% and 9% of euthyroid cats (assessed by thyroid scintigraphy) in that study when measured by CLIA and ED-RIA, respectively. The main advantage of the measurement of fT4 over TT4 in dogs is that fT4 measured by ED-RIA is less prone to the effect of NTIS [13], and it has been suggested by some experts that fT4 is the most useful test to confirm diagnosis of hypothyroidism in suspected cases. In a study that included 54 dogs with hypothyroidism, 54 dogs with NTIS and 150 clinically normal dogs, fT4 measurement was the single most accurate test for diagnosing hypothyroidism, with a 98% sensitivity, 93% specificity and 95% diagnostic accuracy [26]. Unfortunately, the sensitivity and specificity of fT4 measurement for diagnosing SH in cats are, to the authors’ knowledge, not known.
Because of the limited availability of the fT4 ED-RIA, assessment of TT4 in combination with TSH might be more accessible in clinical practice in cats (and also dogs). However, how frequent a finding of increased TSH alongside low TT4 (laboratory findings suspicious of hypothyroidism) really is in cats and what proportion of cats with these findings truly is hypothyroid has not yet been assessed in a large-scale fashion. As mentioned above, clinical signs of SH in cats in those few reported cases were mild [1,3,4,5,6], and could therefore be easily overlooked, hampering diagnosis of SH in clinical practice. In a cat with low TT4, however, the presence of laboratory abnormalities associated with increased TSH could flag the possibility of SH to the veterinarian and prompt them to request TSH measurement (which is not routinely performed at the moment) and perform further thyroid function tests when indicated. Laboratory abnormalities reported in cases of feline hypothyroidism such as anaemia, hyperlipidaemia or azotaemia [1,6] could be such potential indicators of increased TSH in cats, but this has not yet been assessed in large-scale studies.
Therefore, our study had three aims. The first aim was to screen laboratory submissions of adult cats for cases of suspected SH based on low TT4 and increased TSH and to determine its prevalence. Bearing in mind that diagnosis of hypothyroidism cannot be made without the knowledge of history (including previous drug therapy, which might affect thyroid hormone measurements) [13,24] and clinical signs, these cases will be termed “laboratory suspected cases of SH” and abbreviated LSSH throughout this article. Our second aim was to compare the concentration of selected laboratory parameters (red blood cell count, creatinine, cholesterol and triglyceride concentration) between cats with LSSH and euthyroid cats (TT4 within RI) as well as cats with low TT4/normal TSH (suspicious of NTIS; abbreviated SNTIS throughout this article), and the third aim was to compare the prevalence of selected laboratory abnormalities (anaemia, azotaemia, hyperlipidaemia) between cats with LSSH, euthyroid cats and cats with SNTIS.

2. Materials and Methods

2.1. Study Design and Inclusion Criteria

This was a prospective, large-scale cross-sectional study conducted in collaboration with the commercial veterinary laboratory Antech Lab Germany GmbH (formerly SYNLAB.Vet GmbH) with five locations in Germany between January 2022 and April 2023. The study screened laboratory submissions for cases with low TT4/increased TSH and compared their laboratory test results to euthyroid cats (TT4 within RI) and cats with SNTIS (low TT4/TSH within RI) (details below). The study was approved by the regional authority (Regierungspräsidium Giessen, 19 c 20 15 h 02 Gi 18/17 kTV 7/2).
At Antech Lab Germany GmbH, TT4 is measured routinely alongside haematology and serum biochemistry in the “geriatric profile”, which is the most frequently requested profile at this laboratory from adult cats. In the present study, laboratory submissions of all cats aged 3–12 years with available TT4 measurement were included, because all reported cases of spontaneous adult-onset hypothyroidism were of this age category [1,3,4,5,6]. This age category was also selected to minimise inclusion of cats with congenital hypothyroidism as these are usually diagnosed within the first year of life (most frequently younger than 8 months) [18]. The only exclusion criterion was missing TT4 value. In all cats with TT4 < RI, TSH measurement was offered to the submitting veterinarians and performed free of charge unless the veterinarian declined the measurement. For the purpose of this study, where multiple submissions from the same cat were received, the following rules were applied to retain only one submission per cat:
-
if none of the TT4 values was <12.2 nmol/L (lower limit of the RI), then the first submission of this cat was retained in the study
-
if one or more submissions had TT4 < 12.2 nmol/L, then the submission with the lowest TT4 value was kept in the study.

2.2. Laboratory Tests and Definition of Laboratory Abnormalities and Thyroid Status

2.2.1. Haematology and Serum Biochemistry

Full haematology was performed using ADVIA 2120i (Siemens Diagnostics GmbH, Erfurt, Germany) and serum biochemistry was conducted using AU 5822 (Beckman Coulter GmbH, Krefeld, Germany). In this study, selected laboratory parameters were evaluated: RBC and concentration of creatinine (CREA), cholesterol (CHOL) and triglyceride (TRI). Red blood cell counts rather than haematocrit value or packed cell volume were evaluated because these parameters are affected by storage-induced erythrocyte swelling, which can lead to significantly increased values within 12 h of blood collection [27]. Anaemia was defined as RBC < 7.2 × 1012/L (lower limit of the RI of the laboratory). Azotaemia was defined as CREA > 140 µmol/L according to International Renal Interest Society (IRIS) Guidelines [28]. Hypercholesterolaemia was defined as CHOL > 9 mmol/L (upper limit of the RI of the laboratory) and hypertriglycaridaemia as TRI > 1.9 mmol/L (upper limit of the RI of the laboratory).

2.2.2. Thyroid Parameters and Thyroid Status

Total thyroxine was measured using chemiluminescence immunoassay for TT4 (Immulite 2000, Siemens Healthineers, Erlangen, Germany) and TSH was measured using chemiluminescence assay for measurement of canine TSH (Immulite 2000, Siemens Healthineers, Erlangen, Germany) [15]. The reference interval for TT4 was 12.2–46.4 nmol/L, with a lower limit of quantification of 6.43 nmol/L, and RI for TSH was 0.03–0.3 ng/mL, with a lower limit of quantification of 0.03 ng/mL. The RI of TT4 was determined by Antech Lab Germany GmbH itself; the TSH RI is based on a previous study [15].
Cats with TT4 within RI (12.2–46.4 nmol/L) were considered euthyroid and cats with TT4 > 46.4 nmol were suspected to have uncontrolled hyperthyroidism. Among cats with low TT4 (<12.2 nmol/L), only those with available TSH value could be classified. In cats with low TT4 and TSH within RI, euthyroid sick syndrome/non-thyroidal illness was suspected (SNTIS). Spontaneous hypothyroidism was suspected in cats with low TT4 and TSH above a cut-off value calculated from the one-sided TSH reference change value (RCV) of 76% of the upper limit of the TSH RI added to the upper limit of the TSH RI (i.e., [0.3 ng/mL × 0.76] + 0.3 ng/mL = 0.53 ng/mL) [29]. One-sided RCV added to the upper limit of the TSH RI rather than the upper limit of the TSH RI itself was used to screen for cats with LSSH to account for an inherent biological variation of TSH and variation between individuals.
Where hypothyroidism was suspected based on TT4/TSH measurement, the veterinarian was informed about the possibility of SH by an automated message provided alongside the test results by Antech Lab. This message also included brief information about our study and contact details of the investigators. Furthermore, for every case with low TT4 and TSH > 0.53 ng/mL, the main author contacted the submitting veterinarian to ask about any clinical signs of hypothyroidism as well as any antithyroid medication or other treatment for hyperthyroidism (e.g., RAIT, thyroidectomy) to identify cats with iatrogenic hypothyroidism. Cats with iatrogenic hypothyroidism were excluded from the statistical analysis. The submitting veterinarian was then advised that in cats with no evidence of iatrogenic hypothyroidism, SH might be present and further tests are needed to confirm/refute this suspicion. The veterinarians were asked to forward the information about options of further testing onto owners of cats with LSSH. Where cat owners were willing to undergo further testing for hypothyroidism with their cats, they were invited for several tests including thyroid ultrasound, TSH stimulation test and thyroid scintigraphy at the internal medicine department of the Small Animal Clinic—Justus Liebig University (Giessen, Germany) (reported elsewhere [30]).

2.3. Statistical Analysis

The data were assessed for normality by visual inspection of histograms and by Shapiro–Wilk tests. Because the majority of the data were not normally distributed, the data are reported as median (range, interquartile range (IQR)). The prevalence of SNTIS and LSSH is reported as percentage and 95% confidence interval (CI). Non-parametric tests were used for the analysis. Red blood cell count, CREA, CHOL and TRI were compared between the groups (euthyroid, SNTIS, LSSH) using a Kruskal–Wallis test followed by Dunn’s post hoc test. Bonferroni correction was applied to the p-values to account for multiple comparisons. Categorical variables (proportion of cats with anaemia, azotaemia, hypercholesterolaemia, hypertriglyceridaemia) were compared between cats with LSSH and euthyroid cats, cats with LSSH and SNTIS as well as cats with SNTIS and euthyroid cats using a χ2 test. Bonferroni correction was applied to the p-values to account for multiple comparisons. p < 0.05 was considered significant.
All statistical analyses were performed with commercially available software packages (IBM SPSS Statistics v. 28, GraphPad Prism v. 9, Microsoft Excel v. 16.0 for Windows).

3. Results

3.1. Cleaning up the Received Laboratory Submissions

During the study period, 149,566 laboratory submissions from cats were received at Antech Lab. The reasons for excluding submissions from the study and the final number of cats included in the study can be found in Figure 1 and are described below.
In 33,170/149,566 (22.2%) submissions, there was no TT4 measurement available, and these were excluded from the study. Of the 116,396 submissions with TT4 measurement, 22,392 (19.2%) had to be excluded to keep only one submission per cat. Of the remaining 94,004 submissions, 62,432 (66.4%) cats were younger than 3 years or older than 12 years or the age was unknown. These cats were also excluded from the study, leaving 31,572 cats in the study. These included cats were 9.3 years (3–12, 7.1–10.8) old; 1154/31,572 (3.7%) were male entire, 15,090/31,572 (47.8%) were male-neutered, 1484/31,572 (4.7%) were female entire, 12,670/31,572 (40.1%) were female neutered and in 1174/31,572 (3.7%) the sex was not stated on the laboratory submission form.

3.2. Thyroid Status and Prevalence of Suspected Hypothyroidism in Adult Cats

Thyroid status of the included cats is visualised in Figure 2 and is described below.
Of the 31,572 included cats, 25,169 (79.7%) had TT4 within RI (12.2–46.4 nmol/L) (euthyroid cats), 1512 (4.8%) had TT4 > RI (>46.4 nmol/L) (suspected uncontrolled hyperthyroidism) and 4891 (15.5%) had a low TT4 (<12.2 nmol/L). Of the 4891 cats with low TT4, TSH was within RI (0.03–0.3 ng/mL) in 3818 cats, representing 12.1% of the study patients (i.e., cats with SNTIS). Only 227 cats (0.7% of the study patients) had low TT4 and TSH above 0.3 ng/mL, and 126 cats (0.4% of the study patients) had low TT4 and TSH above 0.53 ng/mL (suspected hypothyroidism). TSH was not measured in 846/4891 (17.3%) cats with low TT4, which were not considered in the statistical analysis below (Section 3.3). Based on the information obtained by contacting the submitting veterinarians, 65/126 (51.6%) cats with TT4/TSH indicating suspected hypothyroidism (TSH > 0.53 ng/mL) were receiving treatment for hyperthyroidism and were therefore considered to suffer from iatrogenic hypothyroidism (0.2% of the study patients). Therefore, spontaneous hypothyroidism (SH) was suspected in 61 cats (0.2% of the study patients; the LSSH cohort). The LSSH cats had a median TT4 of 6.4 nmol/L (range: 6.4–11.9, IQR: 6.4–7.6) and TSH of 1.17 ng/mL (range: 0.54–12.01, IQR: 0.7–2.18). An overview of the prevalences and the respective confidence intervals of the main thyroid status categories (euthyroid, suspected uncontrolled hyperthyroidism, SNTIS, LSSH, iatrogenic hypothyroidism) described in this study is in Table 1. The age and sex distribution of cats that could be classified based on thyroid status is in the Supplementary Materials.

3.3. Comparison of Selected Laboratory Parameters Between Cats with Suspected Spontaneous Hypothyroidism (LSSH), Cats with Suspected Non-Thyroidal Illness (SNTIS) and Euthyroid Cats

The results of comparison of RBC, CREA, CHOL and TRI between cats with LSSH, cats with SNTIS and euthyroid cats are in Table 2 and Figure 3.
There was a significant difference in RBC, CREA and TRI across the three groups (cats with LSSH, cats with SNTIS and euthyroid cats), but there was no difference in CHOL (Table 2, Figure 2). The post hoc analysis revealed that cats with LSSH had significantly higher median CREA than euthyroid cats (p = 0.002) and cats with SNTIS (p = 0.00035). Furthermore, euthyroid cats had higher median CREA than cats with SNTIS (p = 0.001) (also see Table 2, Figure 2). Both cats with LSSH (p < 0.0001) and cats with SNTIS (p < 0.0001) had lower median RBCs when compared to euthyroid cats, but there was no difference in RBCs between these two groups (p = 0.76) (also see Table 2, Figure 2). Median TRI was significantly higher in cats with SNTIS when compared to euthyroid cats (p < 0.0001) but there was no difference between the other groups (SNTIS vs. LSSH: p = 1.0; LSSH vs. euthyroid: p = 0.93) (also see Table 2, Figure 2).

3.4. Comparison of the Prevalence of Laboratory Abnormalities Between Cats with Suspected Spontaneous Hypothyroidism (LSSH), Cats with Suspected Non-Thyroidal Illness (SNTIS) and Euthyroid Cats

Results of the comparison of frequencies of anaemia, azotaemia, hypercholesterolaemia and hypertriglyceridaemia between cats with LSSH and euthyroid cats, cats with LSSH and cats with SNTIS as well as cats with SNTIS and euthyroid cats can be found in Table 3.
Cats with LSSH had higher frequency of both anaemia (p < 0.0001) and azotaemia (p = 0.009) in comparison to euthyroid cats (Table 3). When compared to cats with SNTIS, cats with LSSH also had a higher frequency of azotaemia (p = 0.018), but frequencies of anaemia, hypercholesterolaemia or hypertriglyceridaemia did not differ between these two groups (Table 3). When compared to euthyroid cats, cats with SNTIS had a higher frequency of all selected laboratory abnormalities (anaemia, hypercholesterolaemia, hypertriglyceridaemia all p < 0.0001) but azotaemia (p = 0.27).
Because azotaemia and anaemia were the most frequent laboratory abnormalities in all three groups (Table 3), the frequencies of concurrent azotaemia and anaemia were compared between the three groups (Table 3). Both cats with LSSH and cats with SNTIS had higher frequency of concurrent azotaemia and anaemia when compared to euthyroid cats (both p < 0.0001) but there was no difference in their concurrent occurrence between these two groups (p = 0.36).

3.5. Confirmed Cases of Spontaneous Hypothyroidism

Primary care veterinarians of the 61 cats with LSSH were informed about the suspicion of this disease and were asked to inform cat owners about the possibility of further testing of thyroid function (thyroid ultrasound, TSH stimulation test and thyroid scintigraphy) as a part of our study. Three owners were willing to present their cats to the Small Animal Clinic, JLU Giessen and in all three cats hypothyroidism was confirmed based on scintigraphy and TSH stimulation test results. Information about these three cats and a fourth cat identified after completion of this study can be found elsewhere [30].

4. Discussion

This is the first large-scale screening study to date to examine the prevalence of the combination of low TT4/increased TSH, findings indicating possible spontaneous hypothyroidism (SH) in adult cats, using laboratory submissions of 31,572 cats with TT4 measurement. As a secondary aim, our study also for the first time examined the frequency of the combination of low TT4/TSH within RI, a finding commonly attributed to the presence of non-thyroidal illness (NTIS). Furthermore, our aim was also to identify laboratory abnormalities associated with LSSH. The prevalence of LSSH in our study was low (0.2%), but SNTIS was fairly common (12.1%). Cats with LSSH had higher CREA and lower RBC in comparison to euthyroid cats and also higher CREA in comparison to cats with SNTIS. Azotaemia was the most frequent laboratory abnormality in cats with LSSH (57.1%), followed by anaemia (43.2%). Both azotaemia and anaemia were present concurrently in 22.7% of cats with LSSH. Hypercholesterolaemia and hypertriglyceridaemia were not features of LSSH.
Less than 5% of cats in our study had a combination of low TT4/increased TSH (above RI). To account for an inherent biological variation of TSH and variation between individuals, a TSH cut-off above the one-sided reference change value of the upper limit of the TSH RI added to the upper limit of the RI of the laboratory (>0.53 ng/mL) was used in our study to identify cats with LSSH. Therefore, also following exclusion of cats with iatrogenic hyperthyroidism, the prevalence of LSSH was relatively low with 0.2%. This finding was not surprising, given the paucity of published cases in the literature [1,3,4,5,6]. On the other hand, if all those 61 cats identified in our study over a period of just over a year were truly hypothyroid, SH would be considered an uncommon, but not a rare, condition. Certainly, correct diagnosis and appropriate treatment in any identified cases would be essential to reverse the multisystemic effects of hypothyroidism on the body, especially given the high prevalence of azotaemia in the cases of LSSH identified in this study (discussed below). Unfortunately, only three cat owners were willing to travel to our hospital to have further confirmatory tests performed. In those three cases, hypothyroidism could be confirmed (as well as in a fourth cat, that presented to our hospital shortly after completion of our screening study) [30], but whether the remaining 58 cats also were hypothyroid is unknown. Because of the rarity of the disease, further testing of thyroid function (e.g., TSH stimulation test, thyroid scintigraphy) before treatment start would in our eyes be prudent in suspected cases, because the specificity of the combination of low TT4/increased TSH (>RI or >one-sided reference change value of the upper limit of the TSH RI added to the upper limit of the RI of the laboratory as used in this study) for diagnosis of SH in cats is currently unknown. In dogs, although the specificity of the low TT4/increased TSH for diagnosis of hypothyroidism is high, false positives have been reported as increased TSH might occasionally be identified in association with recovery from NTIS [31,32]. This might also be the case in cats, but it has, to our knowledge, not yet been reported in this species. Furthermore, at least in dogs, some drugs might affect TT4 as well as TSH concentration, e.g., low TT4/increased TSH have been reported in dogs treated with phenobarbital, sulfonamides (either low or high dose), toceranib and trilostane [23,24,32]. It cannot be ruled out that the same applies to cats, but the influence of drugs on thyroid function has not been extensively investigated in this species. However, it appears that glucocorticoids have a lowering effect on TT4 concentration [32].
In our study, low TT4 in conjunction with TSH within RI was used as an indicator of possible NTIS. The lowering effect of systemic illness on TT4 concentration has been described in a number of studies in dogs but also in cats. The severity of NTIS might also be a prognostic indicator [11,31,32,33,34,35]. Because our study merely screened laboratory data, we cannot confirm that the cats truly suffered from a non-thyroidal disease. In fact, we cannot rule out that some of these cats might even have suffered from true hypothyroidism. In dogs, up to 40% of hypothyroid dogs have low TT4 in conjunction with TSH within RI [18,32,36].
Because our study merely screened laboratory data, it was essential in cases with low TT4/TSH > 0.53 ng/mL to rule out iatrogenic hypothyroidism. Iatrogenic hypothyroidism is the most common form of hypothyroidism in cats, that has been described with all therapy forms but low-iodine diet [37]. The prevalence of iatrogenic hypothyroidism has been mainly evaluated in cats treated with RAIT and seems to differ between studies using different protocols for iodine dose estimation [16,38], but it can occur when cats are treated with antithyroid drugs (ATDs) as well [39,40]. Based on the information provided by the primary care veterinarians of the 65 cats with iatrogenic hypothyroidism identified in our study, overtreatment with ATDs was the cause of iatrogenic hypothyroidism in all of them. Although 65 is not a high number given the number of cats included in our study (n = 31,572), iatrogenic hypothyroidism might in fact be more common because, at least in RAI-treated cats, increased TSH is a better indicator of hypothyroidism than TT4, and TT4 might be within the lower RI in some hypothyroid cats [14]. Whether iatrogenic hypothyroidism might occur in ATD-treated cats with TT4 within lower RI is, to the authors’ knowledge, unreported, but these cats would have been missed in our study, because TSH measurement was only performed in cats with low TT4. Also, even among cats with low TT4 and increased TSH, cases of iatrogenic hypothyroidism might have been missed, because 227 cats in our study had low TT4 and TSH > 0.3 ng/mL, but only 126 had TSH > 0.53 ng/mL and their veterinarians were contacted to enquire about possible hyperthyroidism treatment (i.e., possibility of iatrogenic hypothyroidism) or clinical signs of hypothyroidism. Therefore, at least some of the 101 cats whose veterinarians were not contacted as their TSH was below our cut-off suspicious for SH might also have suffered from iatrogenic hypothyroidism. Furthermore, the low incidence of iatrogenic hypothyroidism in our study is also due to inclusion criteria, as only cats aged 3–12 years were included and hyperthyroidism (and therefore also iatrogenic hypothyroidism) is a common condition of older cats (mainly above 10 years of age) [41,42,43,44,45]. According to current textbooks, hyperthyroidism is rarely diagnosed in cats younger than 8 [46] or 9 [19] years old.
As expected, creatinine values were higher in cats with LSSH than in euthyroid cats and cats with SNTIS. Cats with LSSH also had a higher prevalence of azotaemia than euthyroid cats and cats with SNTIS. In fact, azotaemia was the most common laboratory abnormality in cats with LSSH (57.1%) and could therefore represent a useful indicator for clinicians that requesting TSH measurement might be warranted in a cat with low TT4 because this cat could potentially suffer from SH. The most likely reason for this high prevalence of azotaemia is the reduced GFR, that occurs in association with hypothyroidism. Impaired renal function has been documented in hypothyroid humans [47,48,49] and decreased GFR and increased serum creatinine concentration have been reported in hypothyroid dogs as well [50,51]. Azotaemia related to the reduction of GFR [52] also occurs in cats with iatrogenic hypothyroidism following treatment of hyperthyroidism with ATDs, thyroidectomy or RAIT [14,40], and approximately half of the cats with spontaneous adult hypothyroidism reported in the literature were azotaemic too [1,3,4,5,6]. However, it should be noted that azotaemia does not necessarily reflect the presence of CKD in affected cats, as repeated creatinine measurements, urinalysis and ideally ultrasound to assess renal pathology are needed to establish the diagnosis of CKD [28].
Azotaemia is a well-known prognostic indicator for several conditions in cats such as diabetes mellitus [53] or pancreatitis [54], and more specifically, the degree of azotaemia based on IRIS staging is associated with survival in cats with chronic kidney disease (CKD) [55]. In cats with iatrogenic hypothyroidism due to ATDs or thyroidectomy, the presence of azotaemia was also associated with shorter survival in comparison to hypothyroid cats without azotaemia [52]. Azotaemia, however, has been reported to improve or even resolve after restoration of euthyroidism following ATD dose reduction [39] or, in cats with RAIT-induced hypothyroidism, after starting LT4 replacement [14]. Importantly, those cats with RAIT-induced iatrogenic hypothyroidism that were treated with levothyroxine had longer survival in comparison to cats that did not receive LT4 supplementation [14]. Whether levothyroxine treatment in cats with SH improves survival time is currently unknown, but improvement or resolution of azotaemia has been demonstrated in all seven cats with SH described in a recent case series [1]. Early diagnosis and appropriate treatment of SH in cats therefore might offer a survival advantage.
Interestingly, cats with SNTIS not only had CREA lower than cats with suspected SH but also the CREA was lower than in euthyroid cats. Although the pathogenesis of NTIS is complex and not yet completely understood, it seems that tissue concentrations of thyroid hormones in animals or humans with NTIS do not necessarily reflect the low blood concentrations [56,57] and a clear benefit of thyroid hormone supplementation in people with NTIS has not been shown [56]. Therefore, unless the non-thyroidal illness is a condition causing reduction of GFR (e.g., kidney disease), a negative effect on GFR, which has been demonstrated in truly hypothyroid humans, dogs and cats [47,48,49,50,51,52], would not be expected in individuals with low TT4 due to NTIS. This explains why cats with SNTIS had lower CREA when compared to cats with LSSH. A possible reason for lower CREA in cats with SNTIS when compared euthyroid cats could be due to reduced muscle condition/muscle wasting, which is a common finding in cats with chronic disease (suffering from NTIS). Whether this hypothesis is correct, however, could not be assessed in our study lacking data of physical examination.
Our study also showed that RBC was lower and frequency of anaemia was higher in cats with LSSH than in euthyroid cats, but there was no difference in comparison to cats with SNTIS. Mild anaemia also was a common finding in the few feline cases of SH [1,6] and could therefore, together with azotaemia, be a helpful indicator of SH in cats and facilitate early disease recognition. Likewise, mild, non-regenerative, normocytic and normochromic anaemia is a frequent finding in hypothyroid dogs [9,10], arising from a lack of thyroid hormone stimulation of erythropoietic precursors, resulting in a diminished red blood cell synthesis. Diminished plasma erythropoietin, a reduced erythroid progenitor response to erythropoietin and a direct effect of thyroid hormone on early hematopoietic pluripotent stem cells are thought to take part in the mechanisms leading to anaemia in hypothyroid humans [58]. Some studies suggest that the same mechanisms might also apply to hypothyroid dogs [10] and cats [7].
Furthermore, our study found that cats with SNTIS also had lower RBC and higher prevalence of anaemia compared to euthyroid cats. This is not unexpected, because anaemia (usually mild), termed “anaemia of chronic disease” or “anaemia of inflammation”, commonly accompanies infectious, neoplastic, metabolic (e.g., liver disease) and hormonal disorders. Several different pathomechanisms are involved in the pathogenesis of anaemia of inflammation, including inflammatory cytokines leading to a diminished iron availability, reduced red blood cell survival and an impaired regeneration ability in the bone marrow [59,60]. However, lacking the clinical information and reticulocyte count or erythrocyte indices, the exact pathomechanism or underlying disease leading to anaemia in cats included in this study could not be ascertained.
Interestingly, there was no difference in cholesterol concentrations between the examined groups. Furthermore, post hoc analysis revealed that triglyceride concentration was higher in cats with SNTIS when compared to euthyroid cats, but no significant difference was detected between the other groups. Therefore, neither hypercholesterolaemia nor hypertriglyceridaemia was associated with LSSH in our study. This is unexpected, because in hypothyroid dogs, both fasting hypercholesterolaemia and hypertriglyceridaemia are common, arising due to decreased hepatic metabolism, leading to reduced degradation of lipids and thus decreased faecal excretion of cholesterol and higher lipid concentrations in plasma [8,10]. Hypercholesterolaemia has also been noted in one case of adult-onset SH in cats, but information about cholesterol concentration was not consistently provided across case series and case reports, and there was no mention of hypertriglyceridaemia [1,3,4,5,6]. Therefore, how frequent lipid derangements in cats with SH are is currently unclear. In our study, the median cholesterol and triglyceride concentrations of all three groups were within the laboratory RI and the proportion of cats with hypercholesterolaemia or hypertriglyceridemia in all three groups was rather low (<15%, mostly < 10%). Because information about fasting prior to blood sampling was not available, some of the cats with hypertriglyceridaemia and/or hypercholesterolaemia might not have been fasted. Generally, lipid derangements are not common in cats but might be detected in cats with some specific conditions such as diabetes mellitus [61], cholangiohepatitis [62], pancreatitis [63], Cushing’s disease (very rare) [64] or with hepatic lipidosis, that can occur secondary to any disease in cats associated with hypo- or anorexia [65,66]. Therefore, the frequency of hypercholesterolaemia and/or hypertriglyceridaemia in our study most likely reflects the presence of these above-mentioned conditions (alongside non-fasting), although lacking the clinical data (clinical signs, liver function testing, abdominal ultrasound), we cannot be sure about the aetiology in the cats included in this study. The presence of these underlying conditions might also explain why the frequency of lipid metabolism derangements was higher in cats with SNTIS when compared to euthyroid cats. Low TT4 (and normal TSH) values indicating NTIS have been documented in cats with diabetes mellitus or Cushing’s disease [11,12,35] and are likely to occur with a multitude of diseases that can lead to hepatic lipidosis.
The main limitation of our study is that our data and results relate to the prevalence of only suspected and not confirmed cases of SH in adult cats, because out of sixty-one suspected cases, only in three cats could further testing of thyroid function (TSH stimulation test, thyroid scintigraphy) be performed. In all three cats, however, hypothyroidism could be confirmed (data presented elsewhere [30]). Furthermore, the aetiology of the suspected SH could not be assessed in this cross-sectional study, because further testing (e.g., scintigraphy) is needed [67]. It also cannot be ruled out that some of these cats might have suffered from congenital hypothyroidism, because a mild form of congenital hypothyroidism caused by dyshormonogenesis has been discussed as a potential cause of adult-onset spontaneous hypothyroidism with goitre in a recent cases series [1]. Because of the financial constraints (costs of TSH measurement), we could only focus on screening of cats with low TT4, but it is possible that some cats with SH have low normal TT4 concentrations and were therefore not identified in our study. Indeed, in a recent case series, 1/7 cats with SH had TT4 within RI (and increased TSH) [1]. Generally, the sensitivity and specificity of the combination of low TT4/high TSH for diagnosis of SH in cats are unknown. There are only a few studies looking at the usefulness of TT4, free T4 and TSH to diagnose iatrogenic hypothyroidism following RAIT [14,25]. As discussed previously, a proportion of hypothyroid dogs has TSH within RI and low TT4 is the only indicator of hypothyroidism on routine screening [18,32]. If cases of feline SH with TSH within RI also exist, these would have been missed in our study, because veterinarians were contacted and owners invited for further testing only if low TT4 occurred in combination with TSH > 0.53 ng/mL. Another limitation is that although our study was conducted prospectively, in 17.3% of cats with low TT4, TSH was not measured. The most likely reason was that a sufficient residual blood sample was not available. Also, fT4 was not measured in our study due to the lack of availability of the ED-RIA at the laboratory we cooperated with and financial constraints. This parameter has been useful in making diagnosis of hypothyroidism in dogs [26] as well as in some studies investigating iatrogenic hypothyroidism following RAIT[25]. Furthermore, our study focused on laboratory parameters, changes in which would be expected to occur in hypothyroid cats (because of information provided for feline cases in the literature or changes known to be frequent in dogs), rather than assessing all haematological or biochemistry parameters. Because no other laboratory abnormalities have been consistently described to occur in hypothyroid cats or dogs and we wanted to avoid comparisons of multiple variables leading to some significant results by chance, we have decided to focus on RBC, CREA, CHOL and TRI. When more cases of adult-onset SH are identified and published, analysis of additional laboratory parameters for their potential association with SH might be warranted. Another important limitation of our study is that clinical data were not available and therefore the presence of comorbidities or medications administered to the included cats, which might have affected laboratory results, could not be assessed. Additionally, it was not known if cats were fasted before blood collection, which might have affected measurement of CHOL and TRI. Of note, azotaemia identified in this study is not necessarily indicating the presence of CKD or renal pathology, because repeated measurements of creatinine or further tests (urinalysis, ultrasound) were not performed or were not available for review given the cross-sectional design and lack of clinical data. Information on urine specific gravity would have been helpful to differentiate between renal and prerenal causes of azotaemia, although, in cats, the interpretation might not be straightforward as they can retain concentrating ability at early stages of CKD [68,69]. However, urine samples are frequently analysed at the cats’ primary care practices and are not submitted alongside samples for haematology and biochemistry and the results therefore were not available for review. Furthermore, at Antech, urinalysis is not a part of the “geriatric profile”, which the selected haematology and biochemistry parameters were derived from, but if at all submitted, urine samples receive a different submission ID and cannot be directly matched to the blood test results, preventing their evaluation in this study (personal communication, Antech Laboratory). Similarly, in cats with anaemia no further information regarding the aetiology of anaemia was available. Finally, the information about the breed was not consistently provided in the laboratory submissions by the veterinarians and breed predisposition could therefore not be assessed in this study. Breed predisposition could be interesting if any of the cases of LSSH were found to have goitre, which could raise suspicion of dyshormonogenesis as a possible cause of LSSH, which might represent a congenital form of the disease with a possible genetic cause [1].

5. Conclusions

The prevalence of LSSH in our study was low (0.2%), but SNTIS was fairly common (12.1%). Cats with LSSH had higher CREA and lower RBC in comparison to euthyroid cats and also higher CREA in comparison to cats with SNTIS. There was no difference in CHOL between the three groups, but TRI was higher in cats with SNTIS when compared to euthyroid cats. Azotaemia and anaemia were more prevalent than lipid abnormalities in all three groups, with LSSH cats having the highest prevalence of azotaemia (57.1%) and anaemia (43.2%) among the three groups, although the latter was not significantly different when compared to SNTIS cats. Both azotaemia and anaemia were present concurrently in 22.7% of cats with LSSH, but only in 14.4% of cats with SNTIS and 3.8% of euthyroid cats. Azotaemia and anaemia could be used as indicators for possible SH and their presence should prompt clinicians to request TSH measurement in cats with low TT4. Hypercholesterolaemia and hypertriglyceridaemia were not features of LSSH in cats.

6. Author Note

Preliminary data from the study were presented as an oral research communication at the 34th ECVIM-CA Congress, 2024 in Lyon, France.

Supplementary Materials

The following supporting information can be downloaded at: https://www.mdpi.com/article/10.3390/pets1030034/s1, Table S1. The age and gender distribution of cats based on thyroid status (euthyroid, suspected uncontrolled hyperthyroidism, suspected non-thyroidal illness (SNTIS), suspected spontaneous hypothyroidism (SSH), iatrogenic hypothyroidism).

Author Contributions

Conceptualisation, K.H., N.B., C.S. and J.L.; methodology, K.H., N.B., C.S. and J.L.; software, not applicable; validation, not applicable; formal analysis, J.L. and K.H.; investigation, J.L.; resources, not applicable; data curation, J.L. and K.H.; writing—original draft preparation, J.L. and K.H.; writing—review and editing, K.H., N.B., C.S. and J.L.; visualisation, K.H.; supervision, K.H. and N.B.; project administration, J.L. and K.H.; funding acquisition, J.L. and K.H. All authors have read and agreed to the published version of the manuscript.

Funding

The study received funding from the ECVIM-CA Clinical Studies Fund (European Society of Veterinary Endocrinology Pilot Research Award 2021), which was used to cover the costs of TSH measurements. The remaining costs of TSH measurement were covered by Antech Lab Germany, who provided TSH measurement for a reduced price.

Institutional Review Board Statement

The study was approved by the regional authority (Regierungspräsidium Giessen, 19 c 20 15 h 02 Gi 18/17 kTV 7/2).

Informed Consent Statement

Not applicable.

Data Availability Statement

The data presented in this study is contained within the article or Supplementary Materials.

Acknowledgments

We thank Krzysztof Fritsch-Glowa for his help with formatting and filtering Excel spreadsheets containing the laboratory data. We are also grateful for the collaboration with Antech Lab Germany GmbH and, finally, we thank all owners as well as the veterinarians who contributed to this study.

Conflicts of Interest

Christina Schwens is an employee of Antech Lab Germany GmbH. Antech Lab Germany GmbH performed TSH measurements as a part of this study for a reduced price.

Abbreviations

ATDantithyroid drug
CHOLCholesterol
CIconfidence interval
CKDchronic kidney disease
CREACreatinine
EUEuthyroid
fT4free thyroxine
GFRglomerular filtration rate
IQRinterquartile range
IRISInternational Renal Interest Society
LT4Levothyroxine
NTISnon-thyroidal illness
PU/PDpolyuria/polydipsia
RAIRadioiodine
RAITradioiodine treatment
RBCred blood cell count
RCVreference change value
RIreference interval
SHspontaneous hypothyroidism
SNTISsuspected non-thyroidal illness
LSSHlaboratory suspected spontaneous hypothyroidism/laboratory suspected cases of SH
TSHthyroid-stimulating hormone/thyrotropin
T4Thyroxine
TRITriglyceride
TT4total thyroxine

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Figure 1. The reasons for excluding laboratory submissions from the study and the final number of cats included in the study screening laboratory submissions for possible cases of suspected spontaneous hypothyroidism between January 2022 and April 2023. Abbreviations: TT4 = total thyroxine.
Figure 1. The reasons for excluding laboratory submissions from the study and the final number of cats included in the study screening laboratory submissions for possible cases of suspected spontaneous hypothyroidism between January 2022 and April 2023. Abbreviations: TT4 = total thyroxine.
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Figure 2. Information on thyroid status of the 31,572 cats included in the study screening laboratory submissions for possible cases of suspected spontaneous hypothyroidism. Absolute numbers and proportions (percentages out of the study population of 31,572 cats) are provided for each category. Cats with TT4 within RI (12.2–46.4 nmol/L) were considered euthyroid and cats with TT4 > RI (>46.4 nmol/L) were suspected to have uncontrolled hyperthyroidism. Euthyroid sick syndrome/non-thyroidal illness (NTIS) was suspected in cats with low TT4 and TSH within the RI (0.03–0.3ng/mL). Spontaneous hypothyroidism (SH) was suspected in cats with low TT4 (<12.2 nmol/L) and TSH above a cut-off value of 0.53 ng/mL derived from the one-sided TSH reference change value of the upper RI limit of the TSH RI added to the upper limit of the RI of the laboratory [17]. Upper limit of the RI for TSH is marked with asterisk (*) and TSH above the cut-off value of 0.53 ng/mL is marked with cross (†). Abbreviations: TT4 = total thyroxine, TSH = thyroid-stimulating hormone, RI = reference interval.
Figure 2. Information on thyroid status of the 31,572 cats included in the study screening laboratory submissions for possible cases of suspected spontaneous hypothyroidism. Absolute numbers and proportions (percentages out of the study population of 31,572 cats) are provided for each category. Cats with TT4 within RI (12.2–46.4 nmol/L) were considered euthyroid and cats with TT4 > RI (>46.4 nmol/L) were suspected to have uncontrolled hyperthyroidism. Euthyroid sick syndrome/non-thyroidal illness (NTIS) was suspected in cats with low TT4 and TSH within the RI (0.03–0.3ng/mL). Spontaneous hypothyroidism (SH) was suspected in cats with low TT4 (<12.2 nmol/L) and TSH above a cut-off value of 0.53 ng/mL derived from the one-sided TSH reference change value of the upper RI limit of the TSH RI added to the upper limit of the RI of the laboratory [17]. Upper limit of the RI for TSH is marked with asterisk (*) and TSH above the cut-off value of 0.53 ng/mL is marked with cross (†). Abbreviations: TT4 = total thyroxine, TSH = thyroid-stimulating hormone, RI = reference interval.
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Figure 3. Boxwhisker plots representing comparison of red blood cell count (RBC) (a), creatinine (CREA) (b), cholesterol (CHOL) (c) and triglyceride (TRI) (d) concentration between cats with suspected spontaneous hypothyroidism (LSSH), cats with suspected non-thyroidal illness (SNTIS) and euthyroid (EU) cats. Significant differences between groups are indicated by horizontal brackets and p-values are represented by asterisks (** p ≤ 0.01, *** p ≤ 0.001, **** p ≤ 0.0001). Each box represents interquartile range, with the horizontal central line representing the median. The whiskers represent range.
Figure 3. Boxwhisker plots representing comparison of red blood cell count (RBC) (a), creatinine (CREA) (b), cholesterol (CHOL) (c) and triglyceride (TRI) (d) concentration between cats with suspected spontaneous hypothyroidism (LSSH), cats with suspected non-thyroidal illness (SNTIS) and euthyroid (EU) cats. Significant differences between groups are indicated by horizontal brackets and p-values are represented by asterisks (** p ≤ 0.01, *** p ≤ 0.001, **** p ≤ 0.0001). Each box represents interquartile range, with the horizontal central line representing the median. The whiskers represent range.
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Table 1. An overview of the prevalences and the respective confidence intervals of the main thyroid status categories (euthyroid, suspected uncontrolled hyperthyroidism, suspected non-thyroidal illness (SNTIS), laboratory suspected spontaneous hypothyroidism (LSSH), iatrogenic hypothyroidism) described in this study including laboratory submissions of 31,572 cats. Cats with TT4 within RI (12.2–46.4 nmol/L) were considered euthyroid and cats with TT4 > RI (>46.4 nmol/L) were suspected to have uncontrolled hyperthyroidism. Non-thyroidal illness was suspected in cats with low TT4 and TSH within the RI (0.03–0.3 ng/mL). Spontaneous hypothyroidism was suspected in cats with low TT4 (<12.2 nmol/L) and TSH > 0.53 ng/mL derived from the one-sided TSH reference change value of the upper RI limit of the TSH RI added to the upper limit of the RI of the laboratory [17].
Table 1. An overview of the prevalences and the respective confidence intervals of the main thyroid status categories (euthyroid, suspected uncontrolled hyperthyroidism, suspected non-thyroidal illness (SNTIS), laboratory suspected spontaneous hypothyroidism (LSSH), iatrogenic hypothyroidism) described in this study including laboratory submissions of 31,572 cats. Cats with TT4 within RI (12.2–46.4 nmol/L) were considered euthyroid and cats with TT4 > RI (>46.4 nmol/L) were suspected to have uncontrolled hyperthyroidism. Non-thyroidal illness was suspected in cats with low TT4 and TSH within the RI (0.03–0.3 ng/mL). Spontaneous hypothyroidism was suspected in cats with low TT4 (<12.2 nmol/L) and TSH > 0.53 ng/mL derived from the one-sided TSH reference change value of the upper RI limit of the TSH RI added to the upper limit of the RI of the laboratory [17].
Number of CatsPrevalence (%) Within Study Patients (Confidence Interval)
Euthyroid25,16979.7% (79.3–80.2%)
Suspected uncontrolled hyperthyroidism15124.8% (4.6–5%)
SNTIS381812.1% (11.7–12.5%)
LSSH610.2% (0.1–0.2%)
Iatrogenic hypothyroidism650.2% (0.1–0.2%)
Abbreviations: SNTIS = suspected non-thyroidal illness, LSSH = laboratory suspected spontaneous hypothyroidism, TT4 = total thyroxine, TSH = thyroid-stimulating hormone, RI = reference interval.
Table 2. Comparison of red blood cell count (RBC), creatinine (CREA), cholesterol (CHOL) and triglyceride (TRI) concentration between cats with suspected spontaneous hypothyroidism (LSSH), cats with suspected non-thyroidal illness (SNTIS) and euthyroid cats. Number of cats in the respective thyroid status category (N) as well as number (Na) and percentage (%) of cats within that respective category with available test results for the particular laboratory parameter is indicated. Significant p-values (after applying Bonferroni correction, level of significance p < 0.05) are in bold.
Table 2. Comparison of red blood cell count (RBC), creatinine (CREA), cholesterol (CHOL) and triglyceride (TRI) concentration between cats with suspected spontaneous hypothyroidism (LSSH), cats with suspected non-thyroidal illness (SNTIS) and euthyroid cats. Number of cats in the respective thyroid status category (N) as well as number (Na) and percentage (%) of cats within that respective category with available test results for the particular laboratory parameter is indicated. Significant p-values (after applying Bonferroni correction, level of significance p < 0.05) are in bold.
Reference IntervalEuthyroid
N = 25,169
SNTIS
N = 3818
LSSH
N = 61
p-Value
RBC [×1012/L]
median (range, IQR)
Na (%)
7.2–11.09.07 (0.64–20.14, 8.16–9.92)
Na = 23016 (91.4%)
8.13 (0.58–14.69, 6.76–9.32)
Na = 3424 (89.7%)
7.85 (2.78–12.2, 5.58–8.86)
Na = 44 (72.1%)
<0.0001
CREA µmol/L
median (range, IQR)
Na (%)
60–166129 (4–2298, 110–152)
Na = 24,448 (97.1%)
122 (26–2733, 96–181)
Na = 3629 (95.1%)
152 (73–895, 120–200)
Na = 49 (90.3%)
<0.0001
CHOL [mmol/L]
median (range, IQR)
Na (%)
2.70–9.004.6 (0.4–31.8, 3.7–7.2)
Na = 23,017 (91.4%)
4.6 (0.4–42.7, 3.6–6.2)
Na = 3425 (89.7%)
4.5 (1.7–12.3, 3.2–6.3)
Na = 47 (77.1%)
0.3
TRI [mmol/L]
median (range, IQR)
Na (%)
0.30–1.900.6 (0.4–179.7, 0.4–0.9)
Na = 23,206 (92.2%)
0.7 (0.1–107.2, 0.4–1.2)
Na = 3441 (90.1%)
0.6 (0.2–10.6, 0.4–1.2)
Na = 45 (73.8%)
<0.0001
Abbreviations: IQR = interquartile range.
Table 3. Comparison of prevalences of anaemia (red blood cell count (RBC) < 7.2 × 1012/L), azotaemia (creatinine (CREA) > 140 µmol/L), hypercholesterolaemia (cholesterol (CHOL) > 9 mmol/L) and hypertriglyceridaemia (triglycerides (TRI) > 1.9 mmol/L) between cats with suspected spontaneous hypothyroidism (LSSH) and euthyroid cats, cats with LSSH and cats with suspected non-thyroidal illness (SNTIS) as well as cats with SNTIS and euthyroid cats. Number (Na) of cats for which the result of RBC, CREA, CHOL and TRI measurement was available and number (N) and percentage (%) of cats with anaemia, azotaemia, hypercholesterolaemia and hypetriglyceridaemia in each group are indicated. Significant p-values (after applying Bonferroni correction) are in bold. Level of significance was p < 0.05.
Table 3. Comparison of prevalences of anaemia (red blood cell count (RBC) < 7.2 × 1012/L), azotaemia (creatinine (CREA) > 140 µmol/L), hypercholesterolaemia (cholesterol (CHOL) > 9 mmol/L) and hypertriglyceridaemia (triglycerides (TRI) > 1.9 mmol/L) between cats with suspected spontaneous hypothyroidism (LSSH) and euthyroid cats, cats with LSSH and cats with suspected non-thyroidal illness (SNTIS) as well as cats with SNTIS and euthyroid cats. Number (Na) of cats for which the result of RBC, CREA, CHOL and TRI measurement was available and number (N) and percentage (%) of cats with anaemia, azotaemia, hypercholesterolaemia and hypetriglyceridaemia in each group are indicated. Significant p-values (after applying Bonferroni correction) are in bold. Level of significance was p < 0.05.
EuthyroidSNTISLSSHLSSH vs. EuthyroidLSSH vs. SNTISSNTIS vs. Euthyroid
RBC measurement Na = 23016Na = 3424Na = 44
RBC < 7.2 × 1012/LN (%)2353 (10.2%)1093 (31.9%)19 (43.2%)p < 0.0001p = 0.34p < 0.0001
CREA measurementNa = 24,448Na = 3629Na = 49
CREA > 140 µmol/LN (%)8907 (36.4%)1375 (37.9%)28 (57.1%)p = 0.009p = 0.018p = 0.27
CHOL measurementNa = 23,017Na = 3425Na = 47
CHOL > 9 mmol/LN (%)646 (2.8%)210 (6.1%)4 (8.5%)p = 0.054p = 1.00p < 0.0001
TRI measurementNa = 23,206Na = 3441Na = 45
TRI > 1.9 mmol/LN (%)1625 (7.0%)465 (13.5%)6 (13.3%)p = 0.29p = 1.00p < 0.0001
Concurrent RBC and CREA measurementsNa = 2299Na = 3408Na = 44
RBC < 7.2 × 1012/Land CREA > 140 µmol/LN (%)863 (3.8%)490 (14.4%)10 (22.7%)p < 0.0001p = 0.36p < 0.0001
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Lin, J.; Schwens, C.; Bauer, N.; Hazuchova, K. Prospective Evaluation of the Prevalence and Laboratory Findings in Adult Cats with Low Thyroxine and Increased Thyrotropin Concentration. Pets 2024, 1, 500-517. https://doi.org/10.3390/pets1030034

AMA Style

Lin J, Schwens C, Bauer N, Hazuchova K. Prospective Evaluation of the Prevalence and Laboratory Findings in Adult Cats with Low Thyroxine and Increased Thyrotropin Concentration. Pets. 2024; 1(3):500-517. https://doi.org/10.3390/pets1030034

Chicago/Turabian Style

Lin, Joanna, Christina Schwens, Natali Bauer, and Katarina Hazuchova. 2024. "Prospective Evaluation of the Prevalence and Laboratory Findings in Adult Cats with Low Thyroxine and Increased Thyrotropin Concentration" Pets 1, no. 3: 500-517. https://doi.org/10.3390/pets1030034

APA Style

Lin, J., Schwens, C., Bauer, N., & Hazuchova, K. (2024). Prospective Evaluation of the Prevalence and Laboratory Findings in Adult Cats with Low Thyroxine and Increased Thyrotropin Concentration. Pets, 1(3), 500-517. https://doi.org/10.3390/pets1030034

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