Mean Serum T4 Concentrations Research Articles

OR01-05 Long-Term Efficacy of T3 Analogue Triac in MCT8 Deficiency

Background: MCT8 deficiency is a severe disorder caused by mutations in the thyroid hormone transporter MCT8. MCT8 deficiency is characterized by severe intellectual and motor disability and high serum T3 concentrations that result in thyrotoxic symptoms in peripheral tissues. This predisposes to substantial morbidity and mortality. Preclinical studies showed that the T3 analogue Triac can bypass defective MCT8 at the cellular level. Recently, we reported the results of an international multicenter trial, in which biochemical and clinical outcomes improved in patients with MCT8 deficiency who were treated with Triac for 12 months (1). However, long-term follow-up data of patients with MCT8 deficiency treated with Triac are lacking, particularly in young children. Therefore, we aimed to investigate the long-term efficacy of Triac therapy in a worldwide cohort of patients with MCT8 deficiency. Methods: We investigated the efficacy of oral Triac treatment in pediatric (n=78) and adult (n=5) patients with MCT8 deficiency in 20 countries. Triac dose was titrated according a predefined dose-escalation scheme aiming to normalize serum T3 concentrations (target 1.4-2.5 nmol/L). Thyroid function tests and biochemical markers of thyroid hormone action in peripheral tissues (SHBG, creatine kinase, creatinine) were measured at baseline and during control visits. Findings: In total, 83 patients with a median baseline age of 5 years (range 6 months – 66 years) were treated, including 24 patients aged 0-2.5 years and 17 patients aged 2.5-5 years. They were treated with Triac during 144 patient years, of whom the follow-up time was >5 years in 9 patients and 2-5 years in 22 patients. Mean dose was 45 µg/kg/day (range 11-107 µg/kg/day). Once a stable dose was achieved, no further dose adjustments were needed.Mean serum T3 concentrations decreased from 5.02 to 1.94 nmol/L (normal 1.4 – 2.5 nmol/L). SHBG concentrations improved from 238 to 204 nmol/L (normal 40-140 nmol/L). Mean creatine kinase and creatinine concentrations improved from 113 to 140 U/L (normal <230 U/L) and from 32 to 38 µmol/L (normal 31-68 μmol/L), respectively. No drug-related severe adverse events were reported. Interpretation: Triac is a safe treatment that results in sustainable improvements of the severe thyrotoxic state in pediatric and adult patients with MCT8 deficiency.

Relationships between thyroid hormones and serum energy metabolites with different patterns of postpartum luteal activity in high-producing dairy cows

This study investigated the relationships of thyroid hormones, serum energy metabolites, reproductive parameters, milk yield and body condition score with the different patterns of postpartum luteal activity in the postpartum period. A total of 75 multiparous healthy (free of detectable reproductive disorders) Holstein dairy cows (mean peak milk yield = 56.5 ± 7.0 kg/day) were used in this study. Transrectal ultrasound scanning and blood sample collection were performed twice weekly. Serum concentrations of progesterone (P4) were measured twice weekly and beta-hydroxybutyrate (BHBA), non-esterified fatty acids, thyroxine (T4), 3,30,5-tri-iodothyronine (T3), free thyroxine (fT4) and free 3,30,5-tri-iodothyronine (fT3) were measured every 2 weeks from the 1st to the 8th week postpartum. On the basis of the serum P4 profile of the cows, 25 (33.4%) had normal luteal activity (NLA), whereas 30 (40%), 10 (13.3%), 6 (8%) and 4 (5.3%) had prolonged luteal phase (PLP), delayed first ovulation (DOV), anovulation (AOV) and short luteal phase, respectively. Serum T4 concentrations in PLP cows were higher than that in NLA cows at the 3rd week postpartum and did not change during the period of study, whereas in the NLA cows the concentrations increased (P < 0.05). Further, the least square (LS) mean of serum fT4 concentrations in the DOV and AOV cows were significantly lower than in the NLA cows during the study period (P < 0.05). In addition, the AOV cows had higher LS mean serum BHBA and T4 concentrations than the NLA cows in early weeks postpartum (P < 0.05). In conclusion, the serum thyroid hormones’ profile differs in high-producing dairy cows showing PLP, AOV and DOV in comparison with the postpartum NLA cows.

Efficacy of iopanoic acid for treatment of spontaneous hyperthyroidism in cats

Iopanoic acid is an iodine containing oral cholecystographic agent that has been used to treat hyperthyroidism in humans and has recently been evaluated in an experimental model of feline hyperthyroidism. The aim of this study was to evaluate the efficacy of iopanoic acid in cats with spontaneous hyperthyroidism. Eleven cats were included in the study. Eight were treated initially with 50mg orally q 12h and three were treated with 100mg orally q 12h. Prior to treatment (baseline) and at 2, 4, and 12 weeks of treatment, owner questionnaires, physical exams, complete blood count, biochemistry analyses, and T(3) and T(4) concentrations were evaluated. The mean serum T(3) concentration decreased with treatment at all time periods compared to baseline. Mean T(4) concentrations were increased at weeks 4 and 12 compared to baseline. Five cats had a partial response during the initial 4 weeks of therapy, but the effects were transient and no significant improvements in clinical signs or physical exam findings were noted at any time period. Results suggest that iopanoic acid may be beneficial for acute management of thyrotoxicosis in some cats, but is not suitable for long-term management.

Low T3 syndrome in psychiatric depression

In euthyroid sick syndrome [non-thyroidal illness (NTI)], a number of investigators have described TSH and serum thyroid hormone abnormalities, low T3, low T3 and T4, increased T4, low TSH, etc. Those cases of NTI where there is only T3 decrease [and normal serum T4, free T4 (FT4), and TSH levels] are specifically referred to as low T3 syndrome. However, the information in regard to low T3 syndrome in psychiatric subjects who are clinically euthyroid and do not have any other systemic illness is scanty. In our facility, since thyroid function is routinely assessed in psychiatric patients at admission, this provided the opportunity to study low T3 syndrome in a large group of psychiatric patients. Out of 250 subjects with major psychiatric depression, 6.4% exhibited low T3 syndrome (mean serum T3 concentration 0.94 nmol/l vs normal mean serum concentration of 1.77 nmol/l). The low T3 levels could not be ascribed to malnutrition or any other illness and the metabolic parameters were all normal. Possible mechanisms contributing to low T3 are discussed. The depression might constitute an illness having the same relation to low T3 as found in the low T3 syndrome previously described in euthyroid sick subjects. The present findings, besides describing low T3 syndrome in psychiatric patients without systemic illnesses, suggest the possibility of subgrouping in clinical psychiatric depression which may have a broader clinical significance.

Effects of deracoxib and aspirin on serum concentrations of thyroxine, 3,5,3′-triiodothyronine, free thyroxine, and thyroid-stimulating hormone in healthy dogs

To evaluate the effects of deracoxib and aspirin on serum concentrations of thyroxine (T4), 3,5,3'-triiodothyronine (T3), free thyroxine (fT4), and thyroid-stimulating hormone (TSH) in healthy dogs. 24 dogs. Dogs were allocated to 1 of 3 groups of 8 dogs each. Dogs received the vehicle used for deracoxib tablets (PO, q 8 h; placebo), aspirin (23 to 25 mg/kg, PO, q 8 h), or deracoxib (1.25 to 1.8 mg/kg, PO, q 24 h) and placebo (PO, q 8 h) for 28 days. Measurement of serum concentrations of T4, T3, fT4, and TSH were performed 7 days before treatment (day -7), on days 14 and 28 of treatment, and 14 days after treatment was discontinued. Plasma total protein, albumin, and globulin concentrations were measured on days -7 and 28. Mean serum T4, fT4, and T3 concentrations decreased significantly from baseline on days 14 and 28 of treatment in dogs receiving aspirin, compared with those receiving placebo. Mean plasma total protein, albumin, and globulin concentrations on day 28 decreased significantly in dogs receiving aspirin, compared with those receiving placebo. Fourteen days after administration of aspirin was stopped, differences in hormone concentrations were no longer significant. Differences in serum TSH or the free fraction of T4 were not detected at any time. No significant difference in any of the analytes was detected at any time in dogs treated with deracoxib. Aspirin had substantial suppressive effects on thyroid hormone concentrations in dogs. Treatment with high dosages of aspirin, but not deracoxib, should be discontinued prior to evaluation of thyroid function.

Circulating iodide concentrations during and after pregnancy.

Early, indirect studies suggested that an important aspect of thyroid economy during pregnancy was a decline in plasma or serum inorganic iodide (PII) concentrations, but there is little information concerning circulating iodide concentrations as assessed by direct measurement. The present study was undertaken to determine the relationship between gestation and serum iodide concentrations as assessed by direct measurement of PII. PII concentrations, urinary iodide levels, and other parameters of thyroid economy were measured during the first, second, and third trimesters and after delivery in 16 women. Mean serum T4 concentrations were significantly higher in all 3 trimesters than those after delivery. Serum free T4 index concentrations were significantly higher in the first trimester than during later periods of gestation or after delivery, but serum TSH concentrations were not depressed in the first trimester. Serum thyroglobulin concentrations were similar during pregnancy and after delivery. There was wide variability in PII and urinary iodide concentrations during and after pregnancy, but there was no trend for PII concentrations to be depressed during pregnancy. Pregnancy, at least in iodine-sufficient regions, does not have an important influence on circulating concentrations of iodide.

Ipodate treatment of hyperthyroidism in cats

Objective— To evaluate the efficacy and safety of ipodate in the treatment of hyperthyroidism in cats. Design— Prospective case series. Animals— 12 cats with hyperthyroidism treated at The Animal Medical Center between November 1994 and March 1996. Procedure— Each cat initially received 100 mg of ipodate/d, PO, The drug's effects on clinical signs, body weight, heart rate, and serum triiodothyronine (T3) and thyroxine concentrations were evaluated 2, 4, 6, 10, and 14 weeks after initiation of treatment. A CBC and serum biochemical analyses were performed at each evaluation to monitor potential adverse effects of the drug. Dosage of ipodate was increased to 150 mg/d and then to 200 mg/d at 2-week intervals if a good clinical response was not observed. Results— 8 cats responded to treatment and 4 did not. Among cats that responded, mean body weight increased and mean heart rate and serum T3 concentration decreased during the study period. Among cats that did not respond, mean body weight decreased and mean heart rate and serum T3 concentration were not significantly changed. Serum thyroxine concentration remained high in all cats. Adverse clinical signs or hematologic abnormalities attributable to ipodate treatment were not reported in any of the cats. Clinical Implications— Ipodate may be a feasible alternative to methimazole for medical treatment of hyperthyroidism in cats, particularly those that cannot tolerate methimazole and are not candidates for surgery or radiotherapy. Cats with severe hyperthyroidism are less likely to respond to ipodate than are cats with mild or moderate disease, and cats in which serum T3 concentration does not return to the reference range are unlikely to have an adequate improvement in clinical signs. (J Am Vet Med Assoc 1997; 211:63–67)

A new family with hyperthyroxinemia caused by transthyretin Val109 misdiagnosed as thyrotoxicosis and resistance to thyroid hormone--a clinical research center study.

Serum transthyretin (TTR) is a protein of liver origin that under normal conditions transports approximately 20% T4. Missense mutations of the TTR gene produce familial amyloidotic polyneuropathy and rarely, euthyroid hyperthyroxinemia (EHT). Of the 3 TTR variants so far identified with increased affinity for T4, Ser6, Thr109, and Met119, only TTR-Thr109 has high enough affinity for T4 to produce consistent hyperthyroxinemia in the heterozygous individuals. Because the mutation GCC-->ACC in codon 109 results in the loss of one Bso FI site in exon 4 of the TTR gene, the use of this enzyme was suggested to screen for TR-Thr109 in subjects with EHT. We investigated a family with dominantly inherited EHT, in which two of eight affected members received ablative thyroid treatment for presumed thyrotoxicosis, and one was misdiagnosed as having resistance to thyroid hormone. All affected individuals had serum reverse T3 concentrations above normal and average T4 50% above the mean of unaffected relatives. Total T3 and TSH levels were within the normal range. Although loss of the Bso FI site in one allele of the two TTR suggested the presence of Thr109, gene sequencing revealed a different mutation in the same codon (GCC-->GTC) producing TTR-Val109. T4-binding to TTR-Val109 was compared to that of the normal TTR-Ala109 and the formerly identified variant TTR-Thr109. Association constants were 1.3, 9.5, and 13.6 X 10(7) M-1 for TTR-Ala109, Val109, and Thr109, respectively. Thus, for equally expressed mutant and normal allele and 20% of serum T4 bound to TTR, the calculated mean serum T4 concentration of heterozygotes for TTR-Val109 should be 50% above the normal mean; the observed value being 55%. These results are in agreement with the observations based on the crystallographic structure of TTR-Thr109 indicating that the extra atoms in Val as in Thr, which are absent in the Ala of the wild type TTR, widen the ligand binding site.

Changes in renal function associated with treatment of hyperthyroidism in cats

Summary We measured glomerular filtration rate (gfr) estimated by plasma disappearance of 99mTc-labeled diethylenetriaminepentaacetic acid, serum concentrations of thyroxine (T4), creatinine, and urea nitrogen, and urine specific gravity in 13 cats with naturally acquired hyperthyroidism before and 30 days after treatment by bilateral thyroidectomy, and in a group of 11 control cats. Mean (±sd) serum T4 concentration decreased from a pretreatment value of 120.46 (± 39.21) nmol/L to a posttreatment value of 12.15 (± 6.26) nmol/L (P &lt; 0.0001; reference range, 10 to 48 nmol/L). Treatment of hyperthyroidism resulted in a decrease in mean (± sd) glomerular filtration rate, from 2.51 (± 0.69) ml/kg of body weight/min to a posttreatment value of 1.40 (± 0.41) ml/kg/min (P &lt; 0.0001). Mean serum creatinine concentration increased from 1.26 (± 0.34) mg/dl to 2.05 (± 0.60) mg/dl (P &lt; 0.01). Mean serum urea nitrogen concentration increased from 26.62 (± 6.83) mg/dl to a mean postthyroidectomy concentration of 34.92 (± 8.95) mg/dl (P &lt; 0.01). All changes were significant. Two cats developed overt renal azotemia after treatment of hyperthyroidism. Our results provide further evidence that treatment of hyperthyroidism can result in impaired renal function. In addition, our results suggest that, in some instances, thyrotoxicosis might mask underlying chronic renal insufficiency.

Use of the thyrotropin releasing hormone stimulation test to diagnose mild hyperthyroidism in cats.

We evaluated serum T4 and T3 concentrations before and after administration of thyrotropin releasing hormone (TRH) in 35 cats with mild to moderate hyperthyroidism, 15 cats with nonthyroidal disease, and 31 clinically normal cats. The TRH stimulation test was performed by collecting blood for serum T4 and T3 determinations before and 4 hours after IV administration of 0.1 mg/kg TRH. Mean basal serum thyroid hormone concentrations in hyperthyroid cats were significantly (P < .05) higher than concentrations in normal cats and in those with nonthyroidal disease, but there was considerable overlap among the 3 groups. After administration of TRH, mean serum T4 concentrations increased significantly in all groups of cats, whereas mean T3 concentrations increased significantly in normal cats and in those with nonthyroidal disease, but not in cats with hyperthyroidism. The absolute difference between mean basal and TRH-stimulated serum concentrations of T4 in cats with hyperthyroidism (10.7 nmol/L) was significantly lower than the difference in the cats with nonthyroidal disease (20.0 nmol/L) and in clinically normal cats (28.3 nmol/L), but there was considerable overlap in values among groups. The mean value for relative change in serum T4 concentration after TRH was significantly lower in cats with hyperthyroidism (18.9%) than in those with nonthyroidal disease (110.0%) and in clinically normal cats (130.2%). Serum T4 concentrations increased by > 50% in all normal cats and cats with nonthyroidal disease, whereas only 4 (11.4%) of the 35 hyperthyroid cats had an increase of > 50% after TRH administration.(ABSTRACT TRUNCATED AT 250 WORDS)

The thyroid status of the Yanomamö Indians of southern Venezuela: 1992 update.

Previous reports described an apparent paradox in the clinical expression of endemic iodine deficiency in Amazonian Indians, who were severely iodine deficient but had no goiter and were clinically euthyroid. To confirm and explain this unique observation, we estimated the iodine intake and evaluated the functional and structural thyroid status of an isolated population of Yanomamö Indians (n = 104) in southern Venezuela. Twenty-six children, 32 adolescents, and 46 adults were studied with serum thyroid function tests, spot urinary iodide concentration determinations, and sonographic measurement of thyroid gland volume. A subset of adolescents and adults (n = 35) had 24-h fractional thyroidal 131I uptake determinations. No individual with goiter, clinical hypothyroidism, or cretinism was observed. Children had higher mean serum T4 (114.5 vs. 102.9 nmol/L; P < 0.02) and serum T3 (2.96 vs. 2.46 nmol/L; P < 0.02) concentrations than adults, with 2% and 50%, respectively, of children having levels more than 2 SD above the mean for a North American reference population. Serum TSH concentrations were also higher in children than adults (3.3 vs. 2.3 mU/L; P < 0.02), with 25% of the subjects above the reference range. Mean urinary iodide was 61 +/- 29 micrograms/L (range, 10-178 micrograms/L), reflecting borderline iodine sufficiency. Thyroidal 131I uptake values were 28 +/- 7%, with 33% above the upper limit of normal (30%). Compared to an iodine-replete Swedish population, the thyroid gland volume was above normal (> mean + 2 SD) in 71% of the study children. We conclude that the Yanomamö have borderline iodine deficiency, associated in children with predictably higher serum T3 and TSH concentrations and a high prevalence of small goiters. The basis for the apparent change in their dietary iodide intake over the past 30 yr is unclear, as is the explanation for their previously postulated resistance to goitrogenesis with more profound iodine deficiency.

Recognition of triiodothyronine-containing epitopes in canine thyreoglobulin by circulating thyroglobulin autoantibodies

SUMMARY Serum triiodothyronine autoantibody (T3 AA), triiodothyronine (T3), and thyroxine (T4) concentrations were determined in 45 canine sera containing substantial amounts of thyroglobulin autoantibodies (Tg AA); sera also were assayed to investigate the ability of free T3 to inhibit Tg AA binding to canine Tg, Serum T3 AA concentrations defined 2 groups of sera; 28 sera had low T3 AA concentration (≤ 20 ng/ ml) and 17 sera had high T3 aa concentration (≥ 250 ng/ml). Direct linear correlation between T3 AA concentration and apparent serum T3 concentration was observed (r = 0.75). Serum with low T3 AA concentration had apparent T3 concentration that was significantly (P &lt; 0.01) lower than that in serum with high T3 AA concentration. Mean serum T4 concentration was not significantly different between serum with low or high T3 AA concentration. Mean Tg AA activity was significantly (P &lt; 0.05) lower in serum with low T3 AA concentration than in serum with high T3 AA concentration. Addition of free T3 to serum significantly (P &lt; 0.05) decreased detectable activity of Tg AA in both groups of sera. However, significant difference in magnitude of the reduction was not observed between sera with low or high T3 AA concentration. Results indicate that a fraction of Tg AA recognizes T3-containing epitopes in Tg. Increased prevalence of T3 AA for serum with high Tg AA activity indicates that T3 AA may be another valid indicator of lymphocytic thyroiditis. These antibodies may be generated against the hormonogenic epitopes of Tg.

Thyroxine-binding globulin deficiencydetected by newborn screening

We examined the results of the Northwest Regional Screening Program from May 1975 to June 1991 to determine the prevalence of inherited thyroxine-binding globulin (TBG) deficiency and its effect on thyroid hormone concentrations in infants. Serum thyroxine (T4), triiodothyronine resin uptake (T3RU), and thyrotropin values were requested of physicians caring for all infants with a single filter paper T4 level < 38.6 nmol/L (3 micrograms/dl) or a T4 level < 3rd percentile on two filter paper tests (at birth and 2 to 6 weeks of age). From 1,367,724 infants screened in five states, TBG deficiency, an X-linked disorder, was identified in 317 infants (285 boys). For the entire screening program the calculated frequency of TBG deficiency was 1:4315 infants (1:2400 for boys). In Oregon, where 95% of infants have two screening tests performed, the calculated frequency was somewhat higher (1:3080 infants; 1712 boys) and is probably more accurate. The mean serum T4 concentration for TBG-deficient boys was 41.9 nmol/L (3.26 micrograms/dl); 31% had values < 25.7 nmol/L (2.0 micrograms/dl). The mean serum T4 concentration for TBG-deficient girls was 60.2 nmol/L (4.68 micrograms/dl), with none < 2.0 micrograms/dl. The mean T3RU value was 0.472 in TBG-deficient boys, and 0.412 in TBG-deficient girls; the T3RU value was > 0.55 in 24% of TBG-deficient boys but was > 0.55 in only one girl. Free serum T4 levels were normal in all 56 TBG-deficient infants studied, and TBG levels were low in all 20 infants studied. Inherited TBG deficiency is common in boys in the Northwest, with a frequency of 1:1700 and a male/female ratio of 8.9:1. Boys with TBG deficiency have mild, moderate, or severe alterations in total T4 and T3RU values, but severe deficiency is rare in girls.

Thyroxine sulfate is a major thyroid hormone metabolite and a potential intermediate in the monodeiodination pathways in fetal sheep.

T3 and rT3 production rates in the fetus account for roughly only a third of the total T4 production rate; thus, the fate of the majority of T4 produced in the fetus is unknown (the "T4 disposal gap"). We developed sensitive and specific T4 sulfate (T4S) and T3 sulfate (T3S) RIAs to investigate the roles of these compounds in fetal T4 metabolism. T3, T4, T3S, and T4S were determined in a variety of tissue fluid and/or serum samples obtained from fetal, newborn (n = 6), and adult (n = 6) sheep. Four groups of fetal animals, with gestational ages of 94 days (n = 5), 110-111 days (n = 6), 130-131 days (n = 6), and 145 days (n = 6; term = 150 days), were studied. In addition, type I 5'-monodeiodinase (5'-MDI) activity was quantified in liver and kidney tissues. 5'-MDI activities were lower in 94- to 131-day-old fetuses than in fetuses near term or in newborn animals. Mean serum T3 concentrations increased progressively from 94 days (19 ng/dl) to term (371 ng/dl), while mean T3S and T4S serum concentrations were highest at 130 days gestation (237 and 989 ng/dl), decreasing to term. Serum T3S and T4S concentrations decreased further in newborns and adult sheep. T4S and T3S levels in allantoic fluid were significantly higher than those in urine and amniotic fluid in all fetal age groups studied. T4S levels in bile were high from 94-130 days gestation (873-1006 ng/dl), decreasing by 50% at term (529 ng/dl). T4S concentrations in meconium were 46- to 83-fold higher than those in bile from 94 days gestation to term. In contrast, bile T3S levels increased progressively from 94-145 days gestation (191-605 ng/dl), while meconium T3S levels decreased during the same period (33-14 micrograms/100 g). These data demonstrate that 1) sulfated iodothyronines, particularly T4S, are major thyroid hormone metabolites in the fetus; 2) both T4S and T3S are excreted into bile and urine and concentrated in meconium and allantoic fluid; and 3) the high levels of T4S and T3S in serum and other fluids may reflect lower tissue type I 5'-MDI activities. We speculate that T4S and T3S may be further metabolized to other sulfated metabolites and may account in part for the T4 disposal gap in fetal sheep.

Serial thyroid hormone concentrations in healthy euthyroid dogs, dogs with hypothyroidism, and euthyroid dogs with atopic dermatitis

Serum thyroxine (T4) and 3,5,3′-triiodothyronine (T3) concentrations were determined every 3 h for 12 h beginning at 8 a.m. in 20 healthy euthyroid dogs, 19 dogs with hypothyroidism, and 18 euthyroid dogs with atopic dermatitis. Status of thyroid function was based on history, physical findings, results of thyrotropin response testing, and requirement for thyroid hormone replacement therapy. Mean serum T4 and T3 concentrations did not vary significantly between blood samplings within each of the three groups of dogs. Between groups of dogs, mean serum T4 concentration was significantly ( P < 0.05) higher at each blood sampling time in healthy euthyroid dogs and euthyroid dogs with atopic dermatitis when compared to dogs with hypothyroidism. There was no significant difference in mean serum T4 concentration at any blood sampling time between healthy euthyroid dogs and euthyroid dogs with atopic dermatitis or in mean serum T3 concentrations at any blood sampling time between any of the three groups of dogs. Random fluctuation in serum T4 and T3 concentrations was found in dogs in all three groups. Random fluctuations were more common with serum T3 versus T4 concentrations. Consequently, sensitivity (0.88 versus 0.52), specificity (0.73 versus 0.45), predictive value for a positive test (0.75 versus 0.32), predictive value for a negative test (0.87 versus 0.65), and accuracy (0.80 versus 0.47) were better for serum T4 concentration than serum T3 concentration, respectively, when all blood samples were analysed. Measurement of serum T4 concentration was more accurate than serum T3 concentration in assessing the status of thyroid gland function.

Serum free and total iodothyronine concentrations in dogs with hyperadrenocorticism

SUMMARY Serum concentrations of total and free thyroxine (T4 and FT4, respectively), 3,5,3'-triiodothyronine (T3), 3,3',5'-triiodothyronine (reverse T3) were measured in 42 dogs with hyperadrenocorticism, and were compared with values determined in clinically normal dogs. Mean total T4 concentration in dogs with hyperadrenocorticism (14.3 nmol/L) was significantly (P &lt; 0.001) lower than the normal value (25.7 nmol/L), with 38% of the dogs having low serum T4 concentration. Although 16 (38%) of the 42 dogs with hyperadrenocorticism had a high FT4 fraction, indicative of diminished serum T4 binding, normal FT4 concentration was found in only 6 of the 16 dogs (38%) with low total T4 values. Mean serum T3 concentration in dogs with hyperadrenocorticism (0.79 nmol/L) was also significantly (P &lt; 0.001) lower than the normal value (1.16 nmol/L), with 39% of the dogs having T3 values below the normal range. Individual T3-to-T4 and T3-to-FT4 ratios, indices of T3 production and/or clearance, were above the normal range in 29 and 24% of dogs with hyperadrenocorticism, respectively. Mean reverse T3 concentration in dogs with hyperadrenocorticism (0.17 nmol/L) was also significantly (P &lt; 0.001) lower than the normal mean value (0.39 nmol/L), with 48% of the dogs having reverse T3 values below the normal range. Of the 21 dogs in which all iodothyronines were measured, 6 (29%) had undetectable values for all hormones. Therefore, of dogs with hyperadrenocorticism, a subgroup had reduced serum T4 binding and another group had low values for all iodothyronines consistent with secondary hypothyroidism, but few dogs had low T3-to-FT4 ratio (indicative of inhibition of T4 to T3 conversion) commonly seen in human patients with Cushing's syndrome. The pattern of changes in dogs was reminiscent of the changes observed in rats with chronic glucocorticoid excess, in which pituitary thyrotropin secretion is suppressed and T3 production and degradation are depressed. Despite the severity of the changes in FT4 concentration in some dogs, it is possible that overt hypothyroidism is averted by maintenance of serum T3 concentration.

Serum free thyroxine concentration in healthy dogs, dogs with hypothyroidism, and euthyroid dogs with concurrent illness

Summary Serum free thyroxine (fT4), thyroxine (T4), and 3,5,3'-triiodothyronine (T3) concentrations were determined in 62 healthy dogs, 51 dogs with hypothyroidism, and 59 euthyroid dogs with concurrent dermatopathy or concurrent illness for which hypothyroidism was a diagnostic consideration. Status of thyroid function was based on history, physical findings, results of thyrotropin response testing, requirement for thyroid hormone replacement therapy, and in 31 dogs, on results of histologic examination of a thyroid gland biopsy specimen. Serum fT4 concentration was determined, using a single-stage radioimmunoassay. Mean (±sd)serumfT4 concentration was significantly (P &lt; 0.05) greater in healthy dogs vs dogs with hypothyroidism (0.51 ± 0.27 ng/dl vs 0.10 ± 0.07 ng/dl). Significant difference in mean serum fT4 concentration was not evident between dogs with hypothyroidism and euthyroid dogs with hyperadrenocorticism (0.16 ± 0.13 ng/dl) or peripheral neuropathy (0.19 ± 0.10 ng/dl). Mean serum fT4 concentration in all other groups of euthyroid dogs with concurrent illness was similar to values in healthy dogs and was significantly (P &lt; 0.05) greater, compared with values in dogs with hypothyroidism. Similar results were found for mean serum T4 concentration. Comparison of serum fT4 vs T4 concentration revealed: sensitivity, 0.97 vs 0.98; specificity, 0.78 vs 0.73; predictive value for a positive test result, 0.79 vs 0.80; predictive value for a negative test result, 0.97 vs 0.97; and accuracy, 0.78 vs 0.86, respectively. Ten (17%) and 12 (20%) of 59 serum fT4 and T4 concentrations, respectively, were inappropriately low in euthyroid dogs with concurrent illness. Of euthyroid dogs with concurrent illness, those with hyperadrenocorticism, peripheral neuropathy, or idiopathic generalized megaesophagus had the lowest serum fT4 and T4 concentrations. Significant difference in mean serum T3 concentration was not detected among healthy dogs, dogs with hypothyroidism, or euthyroid dogs with concurrent illness. Measurement of serum fT4 concentration using the single-stage radioimmunoassay, did not provide additional information about thyroid gland function other than that gained by measurement of serum T4 concentration.

Effect of nonthyroidal illness on serum thyroxine concentrations in cats: 494 cases (1988)

Summary We reviewed the medical records of 494 cats with a variety of nonthyroidal diseases in which serum thyroxine (T4) concentration was determined as part of diagnostic evaluation. The cats were grouped by category of disease (ie, renal disease, congestive heart failure, diabetes mellitus, focal neoplasia, systemic neoplasia, hepatopathy, inflammatory bowel disease, inflammatory pulmonary disease, miscellaneous diseases, or undiagnosed disease), degree of illness (ie, mild, moderate, or severe), survival (ie, lived, died, or euthanatized), and presence or absence of a palpable thyroid gland. The mean (± sd) serum T4 concentrations in all 10 groups of cats, which ranged from 10.5 ± 11.1 nmol/L in cats with diabetes mellitus to 18.7 ± 7.8 nmol/L in cats with focal neoplasia, were significantly (P &lt; 0.001) lower than those of normal cats (27.0 ± 10.4 nmol/L). The number of ill cats with low serum T4 concentrations (&lt;10 nmol/L) was highest in the cats with diabetes mellitus (59%), hepatopathy (54%), renal failure (48%), and systemic neoplasia (41%). When the serum T4 concentrations in cats with mild, moderate, and severe illness were compared, mean concentrations were progressively lower (21.3 ± 6.8, 14.8 ± 8.1, and 6.5 ± 5.8 nmol/L, respectively) as degree of illness increased. Severity of illness had a more significant (P &lt; 0.001) effect in lowering serum T4 concentrations than did disease category. Mean serum T4 concentrations in the cats that died (7.8 ± 9.8 nmol/L) or were euthanatized (10.0 ± 7.0 nmol/L) were also significantly (P &lt; 0.001) lower than those of cats that survived (15.2 ± 8.8 nmol/L). Of the 182 cats with low serum T4 concentrations, 74 (41%) died or were euthanatized. The 63 cats with palpable thyroid nodules had significantly (P &lt; 0.001) higher mean serum T4 concentrations (21.7 ± 10.4 nmol/L) than the cats in which a thyroid nodule was not palpated (12.7 ± 8.1 nmol/L). Adenomatous hyperplasia of the thyroid gland was confirmed at necropsy in 2 cats with a palpable thyroid gland, and 4 cats that survived have subsequently developed overt hyperthyroidism. This suggests that, in some cats with early or mild hyperthyroidism, concomitant nonthyroidal disease may suppress serum T4 concentrations into the normal range.

Triiodothyronine (T3) Suppression Test

The purpose of this study was to develop a T3 suppression test to help in the diagnosis of mild hyperthyroidism in cats. We evaluated the response in circulating T4 concentrations to exogenous T3 (liothyronine) administration in 44 clinically normal cats, 77 cats with hyperthyroidism, and 22 cats with nonthyroidal disease. The test was performed by first collecting blood samples for basal serum T4 and T3 determinations, administering liothyronine at an oral dosage of 25 micrograms three times daily for seven doses, and, on the morning of the third day, again collecting serum samples for T4 and T3 determinations 2 to 4 hours after the seventh dose of liothyronine. The mean basal serum concentrations of T4 (53.1 nmol/L) and T3 (1.8 nmol/L) were significantly higher in the cats with hyperthyroidism than in the normal cats (T4 = 25.3 nmol/L, T3 = 1.3 nmol/L) and the cats with nonthyroidal disease (T4 = 29.5 nmol/L, T3 = 1.4 nmol/L); however, there was a great deal of overlap of basal values between the three groups of cats. Of the 77 cats with mild hyperthyroidism, 41 (53%) had serum T4 values and 55 (71%) had T3 values that were within the established normal ranges. After administration of liothyronine, mean serum T4 concentrations fell much more markedly in the normal cats and the cats with nonthyroidal disease than in the hyperthyroid cats.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of age, sex, and body size on serum concentrations of thyroid and adrenocortical hormones in dogs

SUMMARY Thyroxine (T4), 3,5,3′-triiodothyronine (T3), and cortisol frequently are quantified in canine serum or plasma samples to aid in the diagnosis of hypothyroidism, hypoadrenocorticism, and hyperadrenocorticism. Many laboratories have established reliable references values for concentrations of these hormones in blood of clinically normal animals. However, nonpathologic factors that affect thyroidal and adrenocortical secretion may lead to misinterpretation of test results when values for individual animals are compared with reference values. The objective of the study reported here was to identify effects of age, sex, and body size (ie, breed) on serum concentrations of T3, T4, and cortisol in dogs. Blood samples were collected from 1,074 healthy dogs, and serum concentrations of the iodothyronines and cortisol were evaluated for effects of breed/size, sex, and age. Mean (± sem) serum concentration of T4 was greater in small (2.45 ± 0.06 μg/dl)- than in medium (1.94 ± 0.04 μg/dl)- or large (2.03 ± 0.03 μg/dl)-breed dogs, the same in females (2.11 ± 0.04 μg/dl) and males (2.08 ± 0.04 μ/dl), and greater in nursing pups (3.04 ± 0.05 μg/dl) than in weanling pups (1.94 ± 0.05 μg/dl), rapidly growing dogs (1.95 ± 0.04 μg/dl), and young adult (1.90 ± 0.06 μg/dl), middle-aged adult (1.72 ± 0.05 μg/dl), or old adult (1.50 ± 0.05 μg/dl) dogs. Dogs &gt; 6 years old had lower mean serum T4 concentration than did dogs of all other ages, except middle-aged adults. Mean serum T3 concentration in medium-sized dogs (1.00 ± 0.01 ng/ml) was greater than that in small (0.90 ± 0.01 ng/ml)- and large (0.88 ± 0.01 ng/ml)-breed dogs. Serum T3 concentration was lowest in nursing (0.85 ± 0.01 ng/ml) and weanling (0.77 ± 0.02 ng/ml) pups, increased in rapidly growing dogs (0.99 ± 0.01 ng/ml) and young adult dogs (1.10 ± 0.04 ng/ml), and decreased slightly in middleaged (0.98 ± 0.02 ng/ml) and old (1.01 ± 0.03 ng/ml) adult dogs. Serum T3 concentration was unaffected by sex. Mean serum cortisol concentration was greater in small (1.06 ± 0.07 μg/dl)- than in large (0.79 ± 0.03 μg/ dl)-breed dogs. Serum from nursing pups (0.57 ± 0.04 μg/ dl) contained less cortisol than did serum from older dogs (mean values ≥ 0.92 μg/dl). Serum cortisol concentration was not different between males and females. These effects of breed/size and age on serum T3, T4, and cortisol concentrations should be considered when evaluating thyroid and adrenocortical functions in dogs.