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Keywords:

  • Melanin;
  • Phenylalanine;
  • Thyroxine;
  • Tyrosine

Abstract

  1. Top of page
  2. Abstract
  3. Materials and Methods
  4. Results
  5. Discussion
  6. Acknowledgment
  7. References

Background

Hyperthyroidism is common among older cats, but its pathogenesis remains poorly understood. Siamese and Himalayan cats have a reduced risk of hyperthyroidism compared with domestic short-hair cat breeds. A mechanism of risk reduction in pointed-coat breeds is unknown.

Objectives

To determine if tyrosine, phenylalanine, iodine, or selenium blood concentrations are altered in hyperthyroid cats and to describe the plasma amino acid profiles of client-owned cats with naturally occurring hyperthyroidism.

Animals

Twenty-seven client-owned cats with (n = 12) and without (n = 15) hyperthyroidism were studied.

Methods

Cross-sectional study. Hyperthyroid cats were prospectively recruited among cats presenting for radioiodine therapy. Control cats were recruited among pets of hospital personnel. Blood was collected for total thyroxine, plasma amino acid, selenium, and iodine determination. Coat color (8 white or pointed; 19 dark), breed, and diet history were recorded.

Results

Tyrosine, phenylalanine, iodine, and selenium levels were not significantly different among light or dark cats or cats with or without hyperthyroidism (P > .05). Plasma amino acid profiles of hyperthyroid cats and control cats were similar, and neither group was deficient in any of the amino acids. l-glutamine was significantly lower in cats with hyperthyroidism (mean ± SD: 648 ± 193) compared with control cats (816 ± 134; P < .05).

Conclusions and Clinical Importance

Altered tyrosine, iodine, and selenium metabolism were not associated with coat color or hyperthyroidism in pointed or light coat–colored cats.

Abbreviations
AAFCO

Association of American Feed Control Officials

T3

triiodothyronine

TT4

total thyroxine

UTCVM

University of Tennessee College of Veterinary Medicine

Siamese and Himalayan cats have a significantly lower risk of developing hyperthyroidism than domestic short-haired or long-haired cats.[1, 2] It has been hypothesized that there might be a genetic basis for this protective effect. Another explanation is that light coat color may be protective because of a lower tyrosine requirement for melanin production compared with cats with dark coats. Although tyrosine is considered a nonessential amino acid in the diet of cats, it can replace up to 50% of the phenylalanine requirement in the diet and has essential biologic functions.[3] Tyrosine is a limiting amino acid in some feline foods resulting in poor coat melanin production and lightening of coat color in dark-coated cats.[4] In cats with lower tyrosine availability (ie, dark cats), limitation of tyrosine for the production of thyroid hormone could result in ongoing stimulation of the thyroid gland because of increased TSH levels.[5] As such, limited tyrosine availability could increase the risk of hyperthyroidism by a mechanism similar to toxic nodular goiter. Conversely, light cats with reduced tyrosine needs for melanin production could be protected. Increased tyrosine utilization for melanin production in cats with dark coats would be expected to lower whole-body tyrosine concentrations, which should be detectible by a reduction in plasma tyrosine concentration.

There might be a role for altered iodine, or selenium intake or both in the occurrence of feline hyperthyroidism.[6, 7] However, plasma selenium concentration in cats from countries with a high prevalence of hyperthyroidism are not different from regions with a low prevalence of hyperthyroidism.[8] Iodine and selenium are important cofactors in the production of active thyroid hormone, and the association of these cofactors with tyrosine levels in hyperthyroid cats has not been reported.

A study by Yu et al[4] demonstrated that previously established phenylalanine and tyrosine dietary recommendations were inadequate for optimal coat color in dark cats. Limited dietary tyrosine and phenylalanine deficiency in commercial foods may have been addressed by some pet food manufacturers; however, no studies have been published evaluating tyrosine intake and thyroid function in domestic cats, nor have there been obvious broad additions of tyrosine across all feline foods.

Plasma amino acids are influenced by many factors, including diet composition, food intake, endogenous protein turnover, and disease status.

Siamese and Himalayan cats have a reduced risk of hyperthyroidism,[1, 2] and these cats have unique tyrosine metabolism responsible for a pointed coat color. This study examines the relationship between tyrosine status and coat color in hyperthyroid cats. In addition, key cofactors in thyroid hormone metabolism (iodine and selenium) were evaluated as codependent variables. The primary objective of this study was to determine if tyrosine, phenylalanine, iodine, or selenium levels are altered in hyperthyroid cats and if light or pointed coat color is protective. A secondary objective was to describe the fasted plasma amino concentrations of client-owned cats with naturally occurring hyperthyroidism.

Materials and Methods

  1. Top of page
  2. Abstract
  3. Materials and Methods
  4. Results
  5. Discussion
  6. Acknowledgment
  7. References

Hyperthyroid Cats

Twelve client-owned hyperthyroid cats of various breeds and coat colors presenting to the University of Tennessee were enrolled in the study between September 2010 and September 2011. The diagnosis of hyperthyroidism was established with traditional methods[9, 10] by either an elevated total thyroxine (TT4) >4.0 μg/dLa or increased uptake of technetium-99 (99Tc)b on thyroid scintigraphy. Criteria for inclusion in the study were a diagnosis of hyperthyroid disease, client consent, and completion of a client survey. Methimazole was discontinued for at least 2 weeks before blood sampling. Hyperthyroid cats were excluded from the study if they had a previous history of radioactive iodine treatment or thyroidectomy. Overtly fractious cats, cats on glucocorticoid medications, or cats with significant coexisting medical disorders unrelated to their hyperthyroid state were also excluded from the study. Hyperthyroid cats with mild-to-moderate azotemia, mildly to moderately elevated liver enzyme values, or a heart murmur were included in the study.

Healthy Control Cats

Control cats were recruited among pets of hospital personnel by sending out e-mails offering free bloodwork to healthy cats that were volunteered for the study. Five healthy white colored or pointed cats and 10 healthy age-matched control cats of various darker colors were included in the study between September 2010 and September 2011. For inclusion in the study, a client consent form and a client survey had to be completed, and cats had to have a TT4 value in the middle to lower half of the reference range, normal CBC and chemistry, and the absence of overt clinical signs of hyperthyroidism. Control cats were not on any medications apart from routine parasite preventatives. The 5 healthy white or pointed control cats were combined with the 10 healthy age-matched control cats of various darker colors to make up a combined control group.

Data Collection

A history and routine physical examination was performed on cats upon entry into the study. A detailed dietary history form was also completed for each cat.

Client Survey and Dietary History

To participate in the study, each client was required to complete a detailed dietary and medical history form describing whether their cat ate primarily dry or canned feline food (noting specific brands and flavors of each), indoor/outdoor status, color coat and breed description, and full notation of any clinical signs or current medications. Clients were also asked to describe when and where they obtained their cat and in what areas of the country the cat had lived throughout its lifetime. The diet questionnaire captured information on food brand, food type, daily intake, feeding methods, and access to other sources of food such as neighbors, hunting, or treats. Duration of the current feeding plan and previous diet exposures were also determined based on owner recall.

Blood Collection and Sample Handling

The study protocol was approved by the Institutional Animal Care and Use Committee of the University of Tennessee. Before blood collection, all of the hyperthyroid and control cats were fasted for 8–12 hours, the dietary and medical history was recorded, and a complete physical examination was performed. Using venipuncture of the jugular vein with a 20-gauge needle and 12-mL syringe, approximately 5–8 mL of blood was collected from each cat, and portions of each sample were transferred to plastic EDTA tubes, heparinized tubes, and serum red top containers. For each cat, a CBC, chemistry, and serum total thyroxine analysisa were performed at the University of Tennessee on the day of blood collection. The remainder of serum red top tubes and heparinized tubes were immediately centrifuged at 3000 × g for 10 minutes and serum and heparinized plasma were then transferred to individual plastic tubes for storage at −80°C. Blood samples were collected from hyperthyroid cats at the time of their initial presentation, and blood sampling for the control population was performed at the end of the study period. No follow-up blood sampling was done on any of the cats. At the end of the study period, all frozen heparinized plasma samples were shipped together on dry ice, for plasma amino acid determination, to the University of California at Davis.c Frozen serum samples for serum iodine and selenium determination were shipped together on dry ice to the University of Missouri-Columbia Research Reactor Center.

Plasma Amino Acid Determination

The heparinized plasma samples were analyzed at the University of California-Davis School of Veterinary Medicine, as previously described.[11]

Serum Iodine and Serum Selenium Determination

The serum samples were analyzed, as received, for both selenium and iodine content at the University of Missouri-Columbia Research Reactor Center as previously described.[12] Briefly, selenium concentrations were determined via standard neutron activation analysis (sample irradiated 5 seconds, decayed 15 seconds, and counted for 30 seconds). Iodine concentrations were determined via epiboron neutron activation analysis by a cycled irradiation procedure (samples irradiated 5 times for 15 seconds each, decayed for 7.5 minutes, and counted for 15 minutes). The resulting concentrations were reported in micrograms per gram of sample (ppm).

Statistical Analysis

Continuous data are reported as median and range, mean ± 1 SD, or both depending on the distribution of the data. A t-test or nonparametric equivalent, depending on the distribution of data, was used to compare age, weight, and body condition scores among hyperthyroid and control cats. Distribution of data was evaluated by the test statistic of Shapiro-Wilk. A chi-square or Fisher's exact test was used to compare categorical data among study groups (hyperthyroid and nonhyperthyroid and pointed versus nonpointed groups) depending on whether an expected cell size was <5. An ANOVA model (PROC GLIMMIX)d was used to compare amino acid, selenium, and iodine values among groups (hyperthyroid versus control and pointed versus nonpointed groups). Cat and group were included in the model as class variables. Group was included as the independent variable and amino acid, selenium, or iodine measurement as the dependent variables. The fit of the model to the data was evaluated by comparing the residuals to a normal distribution by the test statistic of Shapiro-Wilk. Data were transformed when necessary to meet the assumption of normality of residuals. A P value of <.05 was used to determine statistical significance in all tests.

Population Analysis

A medical records search was conducted to determine whether point-colored cats were overrepresented in the hyperthyroid population when compared with the proportion of all point-colored cats accessed during the study period. All medical records from September 1, 2010 to September 1, 2011 with a breed or color description of Siamese, Himalayan, or pointed were included in the analysis. A separate medical records search was conducted for all records with an entry of hyperthyroidism and feline. All records were reviewed to determine breed, color, and treatment for each cat.

Results

  1. Top of page
  2. Abstract
  3. Materials and Methods
  4. Results
  5. Discussion
  6. Acknowledgment
  7. References

Animals

Twelve hyperthyroid cats were referred to UTCVM for radioiodine treatment and initially included in the study. All of these cats were previously diagnosed with hyperthyroidism by their referring veterinarian within 1 year of presentation (median 3.5 months; range 0–10 months), and four of these cats had never received methimazole. Two of the hyperthyroid cats that presented for radioiodine treatment were subsequently removed from the study (1 Siamese cat in which blood was inadvertently collected into an EDTA top tube, and 1 black domestic short-hair cat that was incidentally found to have chyloabdomen without any overt evidence of heart failure).

Two additional hyperthyroid cats were newly diagnosed at UTCVM and included in the study. One of these cats was intended for the Siamese control population; this cat was found to have an incidentally moderately elevated TT4 and was subsequently removed from the control group and included in the hyperthyroid group. The combined control population consisted of 15 healthy cats (10 control cats that were age-matched to the hyperthyroid group and 5 pointed or white cats of various ages). Thus, blood samples from a total of 12 hyperthyroid cats and 15 control cats were submitted for analysis.

History and Clinical Signs

All of the hyperthyroid cats were client-owned pets fed various commercial feline food diets and were not receiving any medications at the time of blood sampling. All cats in the study resided in east Tennessee within the year before blood sampling. In the hyperthyroid group, clients reported a history of vomiting in 6/12 cats, diarrhea in 2/12 cats, polyphagia in 4/12 cats, mild-to-moderate weight loss (0.23–1.8 kg) in 10/12 cats, and polydipsia/polyuria in 5/12 cats. Apart from occasional vomiting (less than once a week) that was reported in 2 cats, all control cats were free of clinical signs or medications. All control cats were receiving commercial feline food diets.

Signalment and Physical Examination

Age, weight, body condition score, and indoor/outdoor status were not significantly different among hyperthyroid and control study groups (P > .05). The median age of the groups was as follows: hyperthyroid cats 12 years (range 5–16); age-matched control cats 11 years (range 5–13); white- or point-colored control cats 8 years (range 6–14). All of the cats in the study were neutered, and sex was fairly similar among the groups (hyperthyroid: male 8/12, female 4/12; control: male 7/15, female 8/15). The hyperthyroid group had an average weight of 4.4 kg (range 3.7–6.1 kg) and the following body condition scores: 2 cats with a BCS of 2/5; 5 cats with a BCS of 3/5; and 5 cats with a BCS of 4/5. The combined control group had an average weight of 4.2 kg (range 2.8–6.1 kg) and the following body condition scores: 1 cat with a BCS of 2/5; 7 cats with a BCS of 3/5; 4 cats with a BCS of 4/5; and 3 cats with a BCS of 5/5. Two hyperthyroid cats were indoor/outdoor and 2 control cats were indoor/outdoor. The remainder of the cats in the study were strictly indoor.

Diet Analysis

Upon completion of the study, the protein, fat, and carbohydrate composition of each diet being fed at the time of sampling was determined by label or manufacturer report, and the results were compared among study groups. There was no significant difference in the diet composition of hyperthyroid cats and control cats (P > .05). The hyperthyroid group had an average dietary protein intake of 42.8% dry matter (range 30.6–56.2%), an average fat intake of 17.3% dry matter (range 8.5–29.2%), and an average carbohydrate intake of 28.4% dry matter (range 7.1–45.9%). The control group had an average dietary protein intake of 41.7% dry matter (range 34.5–57.9%), an average fat intake of 14.1% dry matter (range 8.5–22.3%), and an average carbohydrate intake of 29.7% dry matter (range 15.0–41.7%).

CBC/Chem/TT4 Results

Chemistry and CBC values were similar among groups except for TT4 levels. Mildly to moderately elevated ALT (mean 166 U/L; range 40–551 U/L) was present in 6/12 hyperthyroid cats, and none of the hyperthyroid cats was azotemic. Total T4 values were mildly to moderately elevated in 10/12 hyperthyroid cats (mean 7.6 μg/dL; range 3.6–12.1 μg/dL). The remaining 2 hyperthyroid cats had high to normal TT4, and their diagnosis of hyperthyroidism was confirmed with thyroid scintigraphy. One control cat had a BUN that was mildly elevated (40 mg/dL; ref 19–39), but the creatinine and urine concentration was within normal limits, so it remained in the control group. Otherwise, all control cats had CBC and chemistry values within the normal reference range. The TT4 values in the control population were all in the middle to lower half of the reference range (mean 2.0 μg/dL; range 1.2–2.5 μg/dL).

Plasma Amino Acid Results

Tyrosine and phenylalanine levels were not significantly different (P > .05) among light or dark cats or cats with or without hyperthyroidism (see Figs 1, 2). When the hyperthyroid group was compared with the combined control group, statistically significant differences in amino acids were noted. Hyperthyroid cats had significantly (P < .05) higher plasma levels of l-arginine, b-alanine, l-a-amino butyric acid, and l-cystine compared with control cats. Compared with controls, hyperthyroid cats had significantly (P < .05) lower levels of l-glutamine, l-citrulline, cystathionine1, d-hydroxylysine, and tryptophan (see Table 1). Neither group was deficient in any of the amino acids (see Table 1, column 3). The branched chain amino acid (BCAA; isoleucine, leucine, and valine) to aromatic amino acid (AAA; phenylalanine and tyrosine) ratio was calculated for each of the study groups, and the results were not statistically different. The BCAA : AAA in hyperthyroid cats was 3.3 ± 0.5 (mean ± SD, range 2.5–4.3), and BCAA : AAA in the combined control group was 3.0 ± 0.5 (range 2.4–3.9).

Table 1. Amino acid profiles of hyperthyroid cats and control cats
Amino AcidRef Range as Defined[11] Mean ± SD (μmol/L)Ref Range at Deficiency[18] Mean ± SD (μmol/L)Ref Value at Requirement[18] Mean (μmol/L)Hyperthyroid (n = 12) Mean ± SD (μmol/L)Control (n = 15) Mean ± SD (μmol/L)Hyperthyroid versus Control (P-Value)a
  1. Reference range ‘as defined’ is the normal reference range that is listed by the laboratory in which the samples were submitted; it is used as the normal reference range for cats of all ages. Reference range ‘at deficiency’ is the plasma amino acid concentrations of cats that had been fed diets in which each respective essential amino acid was left out of the diet. Reference value ‘at requirement’ is the concentration of amino acid in plasma from kittens fed each respective amino acid at the minimum requirement.

  2. a

    Unadjusted P values significant at P value <.05.

  3. b

    Statistically significant after Bonferroni adjustment of the P value to <.0015.

l-Alanine347 ± 52  575 ± 117570 ± 149.926
b-Alanine   13 ± 511 ± 2 .019
l-Arginine138 ± 2428 ± 375134 ± 20111 ± 31 .040
l-Asparagine26 ± 818 ± 3.7 99 ± 1896 ± 23.813
l-Aspartic Acid35 ± 7  5 ± 58 ± 5.062
l-a-Am-n-Butyric Acid   21 ± 513 ± 4 <.0001 b
l-Carnosine   47 ± 1345 ± 12.558
l-Citrulline 6.7 ± 1.2714 ± 319 ± 5 .012
l-cystine42 ± 5  12 ± 67 ± 4 .033
Cystathionine9 ± 3  10 ± 318 ± 11 .016
l-Glutamic Acid32 ± 8  45 ± 543 ± 8.420
l-Glutamine933 ± 204  648 ± 193816 ± 134 .016
Glycine613 ± 166  277 ± 47299 ± 64.337
l-Histidine150 ± 309.4 ± 455136 ± 19141 ± 19.492
1-Methyl-l-Histidine   17 ± 517 ± 7.826
3-Methyl-l-Histidine   12 ± 415 ± 7.209
l-Isoleucine64 ± 148.1 ± 3.13090 ± 1784 ± 21.426
l-Leucine136 ± 2525 ± 1270157 ± 32157 ± 35.986
l-Lysine100 ± 1645 ± 6.660153 ± 51124 ± 51.162
d-hydroxylysine   11 ± 824 ± 17 .025
l-methionine51 ± 1111 ± 4.73048 ± 654 ± 43.475
l-Ornithine39 ± 158.7 ± 21116 ± 516 ± 4.882
l-Phenylalanine80 ± 1411 ± 2.72581 ± 789 ± 18.145
O-phosphoethanolamine   6 ± 17 ± 4.390
l-Proline296 ± 6281 ± 9.9 121 ± 18149 ± 59.147
Hproxy-l-proline   12 ± 1425 ± 36.669
l-Serine291 ± 41  162 ± 48138 ± 41.147
O-Phosphol-l-Serine   13 ± 411 ± 3.190
l-Anserine   8 ± 38 ± 3.841
Taurine127 ± 30  122 ± 31136 ± 42.270
l-Threonine206 ± 3560 ± 3.380141 ± 22156 ± 36.231
Tryptophan65 ± 138.9 ± 2.32552 ± 768 ± 13 .0008 b
l-Tyrosine55 ± 534 ± 2.93566 ± 965 ± 15.949
l-Valine233 ± 3433 ± 1365229 ± 38210 ± 45.258
image

Figure 1. The boxes represent the interquartile ranges, the horizontal bars within the boxes indicate the medians, and the whiskers show the ranges. Each X represents an outlier. Hyperthyroid NP is defined as hyperthyroid nonpointed cats of various colors. Hyperthyroid P is defined as hyperthyroid pointed cats (two Siamese cats). Nonhyperthyroid NP is defined as nonhyperthyroid nonpointed cats of various colors. Nonhyperthyroid P is defined as nonhyperthyroid pointed cats (2 Siamese cats, 2 white cats, and a Himalayan cat).

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image

Figure 2. See Figure 1 for legend.

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Serum Iodine and Selenium Results

Serum iodine and selenium concentrations were not statistically different between hyperthyroid cats and control cats (P > .05), and neither group was considered to be deficient in either of these minerals (see Table 2).[12-14]

Table 2. Serum iodine and selenium results in hyperthyroid (n = 12) and control (n = 15) cats (ppm)
 Mean ± SDP-ValueaReference[12-14]
  1. a

    Unadjusted P values.

Iodine
Hyperthyroid0.218 ± 0.089.180.110
Control0.177 ± 0.059
Selenium
Hyperthyroid0.465 ± 0.063.750.22–4.61
Control0.473 ± 0.066

Population Analysis

Within the total population of cats presenting to UTCVM during the study period, the prevalence of pointed hair coat or Siamese-type breed was 46 of 771 (6%). Out of a population of 46 point-colored cats that presented to UTCVM during the same period, 12 were reported as Himalayan, 12 as Persian, 17 as Siamese, and 5 as mixed or miscellaneous breeds. The total number of hyperthyroid cats that presented to UTCVM during the study period was 45. Of the total hyperthyroid population, 8 of 45 (18%) were described as Siamese, Himalayan, or mixed point-colored cats. Point-colored cats were more likely to be hyperthyroid, OR 3.9 (95% CI 1.7–9.0; P = .004), when compared with all point-colored cats that presented to UTCVM during the study period.

Many (38%; 17/45) of the hyperthyroid cats that presented to the hospital during the study period were being medically managed for hyperthyroidism with methimazole while being seen at UTCVM for other problems and were not eligible for inclusion in the study. Out of the remaining 28/45 hyperthyroid cats that were eligible for study inclusion, 14/28 (50%) of cats were initially included in the study. Cause for exclusion included lack of client consent (9/14), the presence of concurrent disease (2/14), previous radioiodine treatment (1/14), or fractious temperament (2/14). Both of the fractious hyperthyroid cats that were excluded from the study were point-colored breeds (1 Balinese and 1 Siamese).

Discussion

  1. Top of page
  2. Abstract
  3. Materials and Methods
  4. Results
  5. Discussion
  6. Acknowledgment
  7. References

There were no significant differences in tyrosine, phenylalanine, iodine, or selenium levels among light- or dark-coated cats with or without hyperthyroidism. However, the small sample size decreased the opportunity to identify important differences should they exist. These findings suggest that decreased tyrosine utilization associated with decreased melanin production in light or pointed coat color may not explain the reduced risk of hyperthyroidism that was previously reported in Siamese and Himalayan cats.[1, 2]

Dietary intake of the key metabolites associated with thyroid hormone production (ie, iodine, selenium, tyrosine, phenylalanine) was not directly measured in this study; however, serum and plasma concentrations were utilized to assess whole-body status. As differences in earlier feeding practices of cats in this study might not be reflected in these results, the role of tyrosine, iodine, and selenium in the pathogenesis of hyperthyroidism cannot be discounted; however, it does not appear to be associated with hyperthyroidism at the time of diagnosis.

Study cats did not demonstrate a decreased risk of hyperthyroidism among point-coat–colored cats. Surprisingly, pointed coat color was overrepresented in the population of hyperthyroid cats that presented to UTCVM during the study period. The control population was obtained from cats that were owned by hospital personnel, whereas the hyperthyroid cats were primarily obtained from a population of cats that were referred for I-131 treatment. There might have been a bias to the inclusion of more purebred cats in the population of cats treated with radioactive iodine when compared with the general population of healthy cats owned by hospital personnel. The pointed cats in this study were of various breeds, and genetic analysis was not performed to evaluate whether or not they were purebred. Therefore, the population of Siamese- and Himalayan-appearing cats enrolled in this study might not be representative of cats from previous studies where a breed-related risk reduction for hyperthyroidism was described.[1, 2] Reasons for this difference in relative risk might be caused by a difference in populations, the low number of cats in this study, or other environmental differences between the study populations. It is possible that there remains an underlying genetic factor that explains the previously reported reduced risk of hyperthyroidism in Siamese and Himalayan cats. Although our study questions the strength of the associated risk reduction in breed with hyperthyroidism, this along with genetic traits of hyperthyroid cats requires further investigation.

These results suggest that the amino acid profiles of hyperthyroid cats are similar to the amino acid profiles of control cats with minor exceptions with unknown clinical relevance (Table 1). Differences (P < .05) in plasma amino acid concentrations from hyperthyroid cats compared with control cats in this study included lower concentrations of l-glutamine, l-citrulline, cystathionine1, tryptophan, and d-hydroxylysine, and higher concentrations of l-cystine, b-alanine, l-arginine, and l-a-amino-n-butyric acid. The pattern of these changes does not point to a broad alteration in energy metabolism among multiple pathways, but might be attributable to a higher demand for energy production and protein turnover. This might account for the increased concentrations noted in l-a-amino-n-butyric acid in cats with hyperthyroidism. Increased arginine concentrations might be explained by its role in the urea cycle and the higher rate of nitrogen turnover associated with the hypermetabolic state. Cats with moderate-to-severe hyperthyroidism are commonly recognized as having lean mass loss or muscle wasting.

Shifts in flux through various metabolic pathways may account for opposite changes in concentrations among related amino acids such as between lysine and hydroxylysine, and between cystine and cystathione. Alternative explanations for decreases in cystine and cystathionine concentration in hyperthyroid cats are increased utilization as antioxidants or higher cystine or sulfur amino acid requirement needed for increased hair growth, or both. Fur production and increased urinary production of the unique amino acid, felinine, have been identified as metabolic factors related to the high sulfur amino acid requirements of cats.[15] As such, the impact of hypermetabolism on utilization of these amino acids might account for the noted differences between hyperthyroid and control cats in this study.

Because tryptophan is a common limiting amino acid in commercial feline diets,[5] the decline in plasma tryptophan concentrations in hyperthyroid cats might simply reflect increased protein turnover.

The amino acid profiles of the hyperthyroid cats in our study were not consistent with total nitrogen or protein deficiency. During starvation in people and other animals, concentrations of branched chain amino acids and certain glucogenic amino acids are increased while alanine and others are decreased.[16]

The pattern of change from the above study does not fit the alteration in amino acid profiles that were noted in the authors’ study. Although initial elevations of lysine and valine occur with protein deficiency,[17] arginine was significantly decreased. If the hyperthyroid cats in our study were experiencing whole-body protein or nitrogen deficiency at the time of the study, they would have been expected to have significant decreases in arginine and several other amino acids.[18]

The vast majority of amino acid concentrations were well above values noted in kittens on sufficient dietary intake (Table 1, column 4). Hyperthyroid cats in this study were fed diets relatively high in protein compared to AAFCO minimums, although not significantly different from control cats. A clear explanation of increased amino acid levels is not obvious, but likely related to nutrient composition within the diets, increased dietary intake caused by polyphagia, or increased release of amino acids related to muscle catabolism in response to the hyperthyroid state and energy deficiency.

Glutamine is the most abundant free amino acid in the blood and muscle of mammals. While altered flux through various metabolic pathways may explain the significant decrease in glutamine in hyperthyroid cats compared with control cats, more likely, lower plasma levels of l-glutamine in the hyperthyroid cats are explained by the increase in whole-body catabolic state and the preferential use of glutamine as an energy substrate. Although cats in this study were not considered starving or cachectic, weight loss was frequently a reported presenting clinical sign. Similarly, vomiting is frequently reported in cats with hyperthyroidism. Although further evaluation is needed, the clinical benefit of increased dietary intake or supplementation with glutamine to hyperthyroid cats for support of energy metabolism or control of gastrointestinal signs of vomiting and diarrhea warrants further investigation.

This study had a number of limitations. First, there was a small sample of cats in each group, which may have led to a type II error. We performed a power calculation using a hypothetical ‘biologically meaningful’ increase, or decrease, of 15% for the hyperthyroid cats when compared with the values observed in the control cats for tyrosine and phenylalanine. If we wish to detect a 15% or greater difference in tyrosine concentration between the hyperthyroid and control cats with an 80% probability of finding that difference to be statistically significant at the level of <0.05, we would need to enroll 24 cats per group. Similarly, to detect a 15% difference in phenylalanine among the groups, we would need to enroll 14 cats per group. Second, the majority of the hyperthyroid cats in this study lacked significant abnormalities in clinical signs, body condition, or routine bloodwork. None of the hyperthyroid cats in this study was azotemic, and only about half of the hyperthyroid cats had elevated liver enzyme activities. The hyperthyroid cats in this study represent a subset of hyperthyroid cats that are only mildly to moderately affected clinically, and these results may not be applicable to more severely affected hyperthyroid cats with severe cachexia or severe renal and/or liver dysfunction. In addition, some of the hyperthyroid cats in this study had only been off methimazole for 2 weeks before blood collection, so plasma amino acid profiles in these cats may not have been reflective of a more chronic hyperthyroid state. Further studies to determine the amino acid profiles in cats with severe thyrotoxicosis may be warranted in the future. Routine geriatric wellness bloodwork has led to increased surveillance for hyperthyroidism. Compliance with such screening recommendations may be particularly common among conscientious clients that are likely to want to pursue radioiodine treatment.

Another limitation in this study was that diet was not standardized, and the cats in this study were fed various commercial diets. Nevertheless, diet composition did not demonstrate any significant differences among the study groups, and both groups were consuming moderate-to-high protein diets.

Although variations in plasma tyrosine levels do occur in cats fed different commercial diets (especially at levels exceeding the minimum requirement), these differences are inconsequential when looking for absolute deficiencies or marginal blood levels that would be expected to occur in cats fed commercial diets yet having an increased metabolic need (such as hyperthyroid cats). Tyrosine plasma levels in cats are well defined at both marginal and deficient levels of dietary intake.[18] Moreover, blood samples were collected from fasting cats, and fasting plasma samples are reflective of whole-body amino acid status.[5]

Acknowledgment

  1. Top of page
  2. Abstract
  3. Materials and Methods
  4. Results
  5. Discussion
  6. Acknowledgment
  7. References

Conflict of Interest Declaration: Authors disclose no conflict of interest.

Footnotes
  1. 1

    Serum total thyroxine values at the University of Tennessee are measured using a standard radioimmunoassay technique and are reported in ng/mL. Please note that 40 ng/mL = 4.0 μg/dL. Also note that for total thyroxine, 1 μg/dL = 12.87 nmol/L

  2. 2

    TECHNELITE; Lantheus Medical Imaging, N. Billerica, MA

  3. 3

    Model 7300; Beckman Instruments, Palo Alto, CA/Amino Acid Lab, Department of Molecular Biosciences, School of Veterinary Medicine, University of California at Davis, Davis, CA

  4. 4

    SAS version 9.2; SAS Institute, Inc, Cary, NC

References

  1. Top of page
  2. Abstract
  3. Materials and Methods
  4. Results
  5. Discussion
  6. Acknowledgment
  7. References
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