Overview

• Thyroxine (total thyroxine/tT4/T4) is the main secretory product of thyroid gland, as both free and protein bound forms.
• Over 99.9% of thyroxine is reversibly bound to carrier proteins.
• The minimal free unbound fraction (free T4/fT4/fT4eq/fT4d) is metabolically active and also converted to tri-iodothyronine (T3) for cellular effects.
• Diagnostic assays for thyroxine measure both protein-bound (inactive) and free forms.
• Free T4 assays Thyroid: free T4 assay are designed to measure only the free unbound component but have varied accuracy.

Sampling

Tests

Methodologies

• Requires canine specific or validated assays.
• Varied Fluorescent and Enzymatic ImmunoAssays (EIAs) Enzyme linked immunosorbent assay (ELISA) or RadioImmunological Assays (IRMA / RIAs).
• Laboratory testing should ideally use external quality assurance schemes to validate performance, eg VEEEQAS / ESVE.

Availability

• In house and most commercial laboratories (EIAs), few reference laboratories (RIAs).

Validity

• Varies with study, test methodology and reference method used, historically often relative to dynamic TSH stimulation testing, or rarely thyroid gland histopathology.

Sensitivity

• 75-100%.

Specificity

• 75-82%.
• 10-20% sick-euthyroid dogs have decreased T4.

Predictive value

• Positive predictive value 55-75% (depending on test and which group of dogs are being tested).
• Negative predictive value 90-100% (depending on test and which group of dogs are being tested).

Technique (intrinsic) limitations

• Dependent upon the test method, especially spectrophotometric EIAs, the dynamic range of the test is designed to accommodate both cats and dogs. Its performance is then worse (greater imprecision and variance) at the low (hypothyroid) end of this range (eg <15 nmol/L).
• Spectrophotometric in-house analyzers are often more prone to hemolytic and lipemic interference-artifact.

Technician (extrinsic) limitations

• Minimal risk of technician errors.
• Therapeutic monitoring: consistent sample timing relative to dosing is crucial for accurate interpretation, alongside similar feeding regime when administering the dose (so that bioavailability does not change when comparing values and times).

Result Data

Further Reading

Publications

Refereed papers

• Recent references from VetMedResource and PubMed.
• Dixon R M & Mooney C T (1999) Evaluation of serum free thyroxine and thyrotropin concentrations in the diagnosis of canine hypothyroidism. JSAP 40(2), 72-78.
• Panciera D L (1999) Is it possible to diagnose hypothyroidism? JSAP 40(4), 152-157.
• Behrend E N, Kemppainen R J & Young D W (1998) Effect of storage conditions on cortisol, total thyroxine, and free thyroxine concentrations in serum and plasma of dogs. JAVMA 212, 1564-1568.
• Peterson M E, Melian C & Nichol R (1997) Measurement of serum total thyroxine, triodothyronine, free thyroxine and thyrotropin concentrations for diagnosis of hypothyroidism in dogs. JAVMA 211, 1396-1402.
• Miller A B, Nelson R W, Scott-Moncrieff J C, Neal L & Bottoms G D (1992) Serial thyroid hormone concentrations in healthy dogs, dogs with hypothyroidism, and euthyroid dogs with atopic dermatitis. Br Vet J 148, 451-458.
• Nelson R W, Ihle S L, Feldma E C & Bottoms G D (1991) Serum free thyroxine concentration in healthy dogs, dogs with hypothyroidism, and euthyroid dogs with concurrent illness. JAVMA 198, 1401-1407.
• Beale K M (1990) Current diagnostic techniques for evaluating thyroid gland function in the dog. Vet Clin North Am Sm Anim Pract 20, 1429-1441.
• Reimers T J, Lawler D F, Sutaria P M, Correa M T & Erb H N (1990) Effects of age, sex and body size on serum concentrations of thyroid and adrenocortical hormones in dogs. Am J Vet Res 51, 454-457.

Other sources of information

• Feldman and Nelson's (2015) Canine and Feline Endocrinology and Reproduction. 4th edn, Elsevier Science, USA.

Organisation(s)

• Most commercial laboratories.