Canine Hypothyroidism – part 2
Victor Castillo, PhD
Diagnosis of hypothyroidism
For the diagnosis of hypothyroidism in any of its phases, the author has adopted three evaluations.
• Clinical examination by palpation... with the animal’s head raised the clinician stands behind the dog and uses both hands to gently palpate the area of the larynx/trachea with an up/down movement until both glands are detected.
• Imaging diagnosis... thyroid ultrasound (Figure 7) is the technique of choice for evaluating thyroid gland morphology. It allows diagnosis of goitre, gland atrophy, and suspected thyroid carcinoma. In puppies with suspected congenital hypothyroidism, ultrasound can determine the size of the gland and the anatomical location. The total thyroid volume (TTV) can also be determined (13).
Thyroid scintigraphy evaluates thyroid gland function. Together with ultrasound, scintigraphy is indicated for congenital hypothyroidism evaluation, as it can detect ectopic or atrophic thyroid tissue, or diminished radiotracer uptake by the gland. This is important, since a lack of thyroid migration, deficient development of the gland, or the absence of tracers can indicate genetic alterations that may be inherited from the parents.
Evaluation of the lipid profile: 30-40% of all dogs with hypothyroidism present with total cholesterol elevation (1,14). It is important to measure LDL-cholesterol, since an increase in relation to HDL-cholesterol can indicate thyroid deficiency (14).
Evaluation of TSH and THs (FT4 and T4): TSH is the best estimator of the thyroid gland axis, and is the most sensitive marker for evaluating thyroid function. TSH elevation per se is diagnostic of hypothyroidism, independently of the T4 values found (3,5,7).
With regard to THs, FT4 is the fraction that best reflects the peripheral thyroid condition and is the first to become affected (3,5,15,16). A decrease in FT4 is indicative of hypothyroidism, and in the author’s experience, of all dogs diagnosed with clinical hypothyroidism, 30% presented with protein-bound T4 levels close to the lower limit, with diminished FT4 and increased TSH levels, together with morphological alterations of the gland and clinical signs. However the best method for evaluating FT4 is debatable, for although equilibrium dialysis is widely accepted as the gold standard, its high cost and scant availability make it practically inaccessible. The more modern radioimmunoanalysis techniques and chemiluminescence have been shown to be effective in measuring FT4 without error and in a reliable manner (16,17). Puppies do not show variations in FT4. In contrast, the protein-bound T4 levels are comparatively higher between 1-6 months of age (18) and therefore TSH and FT4 measurement, together with the lipid profile and ultrasound findings, is the best diagnostic method for thyroid pathology. If TSH and FT4 (or total T4 if the latter is measured) are in the normal range but close to the cut-off values (upper and lower, respectively), and there is firm suspicion of the disease (altered thyroid gland image, presence of at least one clinical sign consistent with hypothyroidism), diagnostic confirmation of the disorder is obtained by the TRH stimulation test (6,7,16). It makes no sense to perform this test if TSH is already elevated. The test involves obtaining a basal sample of TSH, i/v injection of TRH, and a second TSH sample obtained 15-20 minutes later. HoS is assumed when TSH exceeds 0.50 ng/mL or its change in value (DTSH: TSH 15 minutes - basal TSH) is > 0.2 (7).
When congenital hypothyroidism is suspected, and if 1-2 mL of blood can be collected between 7 and 20 days of age, direct evaluation of TSH and FT4 is indicated. If the sample obtained is insufficient for evaluating both hormones, attention should centre on FT4 (2,5).
Anti-thyroglobulin (AbTg) and anti-TPO antibody titers (AbTPO): approximately 40-50% of all studied dogs show elevations of these antibodies (19). However, the absence of such elevation does not discard the possibility of autoimmune thyroiditis (AIT). Elevation in turn is diagnostic only of AIT, and the TSH and FT4 levels may prove normal even with the stimulus or challenge test. It therefore only serves to complement the diagnosis.
Treatment of hypothyroidism
The aim of treatment is to normalize the thyroid axis and circulating T4 levels. Levothyroxine replacement doses are advised, with the purpose of restoring the euthyrotic state without suppressing the axis. The idea is to normalize TSH and T4 – it being important for the latter to be close to its upper cutoff value which avoids periods of low T4 between doses.
The author recommends the following:
• Subclinical hypothyroidism versus clinical hypothyroidism: administration of lower doses in subclinical hypothyroidism.
• The age of the dog: administration of lower doses in elderly animals.
• Presence of heart failure or kidney disease: administration of lower doses in order not to overburden the affected organs.
• Gestation or proximity to mating: administration of higher doses (between 25-50%) in order to secure good ovulation or spermatogenesis and avoid embryonic and foetal deaths/reabsorptions.
• Dogs with oncological diseases or chronic infections, where metabolic rest is indicated: administration of lower doses.
The recommended dose in clinical hypothyroidism is 11-22 μg/kg, starting with the lower dose and gradually increasing the dosage until the desired concentration has been reached. For subclinical hypothyroidism a lower dose of between 3-10 μg/kg is recommended. Some authorities advise initially administering levothyroxine every 12h, progressing to once daily dosing (16,20), but given that the intracellular half-life of T4 is 24h, and the tissues deionize the amount of T4 they need, treatment can commence at once-daily dosing (20).
In the case of congenital hypothyroidism, treatment should start as soon as possible in order to avoid irreparable damage to the central nervous system. Indeed, immediate treatment for clinically suspected congenital hypothyroidism, where diagnostic tests are not possible or delayed for any reason, is recommended. The dosage in puppies with congenital hypothyroidism or juvenile hypothyroidism is 5-20 μg/kg.
Treatment efficacy should be assessed every two months, with sampling 3-4h after dosing. Depending on the results, the hormone dose is gradually adjusted (by 25-50% increments), until the desired T4 level is reached. Reassessment can then be performed every 6-12 months (20). The clinician may also consider repeat thyroid ultrasound in order to determine if gland volume normalizes (if previously seen to be increased).
Although hypothyroidism is the most common canine endocrinopathy, the nature of the disease, the subclinical form of the disorder and the variability in biochemical and hormone measurements can mean that its diagnosis may present a challenge. Oversimplification of the problem can be misleading and the veterinarian should be mindful that this is not simply a disease of older dogs that presents in a uniform manner.
This article was kindly provided by Royal Canin, makers of a range of veterinary diets for dogs and cats. For the full range please visit www.RoyalCanin.co.uk or speak to your Veterinary Business Manager:
1. Feldman EC, Nelson RW. The thyroid gland. Canine and feline endocrinology and reproduction. 2nd ed. Philadelphia: WB Saunders, 1996; 67-185.
2. Morreale de Escobar G, de Vijlder J, Butz S, et al. The thyroid and brain, European Thyroid Symposium. NY: Schattauer, 2002; 33-233.
3. Wang R, Nelson JC, Weiss RM, et al. Accuracy of free thyroxine measurements across natural ranges of thyroxine binding to serum proteins. Thyroid 2000; 10: 31-9.
4. Duncan Basset JH, Harvey CB, Williams GR. Mechanism of thyroid hormone receptor-specific nuclear and extra nuclear actions. Mol Cell Endocrinol 2003; 213: 1-11.
5. Snyder PJ. The pituitary in hypothyroidism. In: Braverman LE, Utiger RD, eds. The Thyroid. A Fundamental and Clinical Text. 8th ed. Philadelphia: Lippincott, Willians & Wilkins A, Wolter Kluwer Company, 2000; 811-814.
6. Kooistra HS, Dias-Espineira M, Mol JA, et al. Secretion pattern of thyroidstimulating hormone in dogs during euthyroidism and hypothyroidism. Domest Anim Endocrinol 2000; 18:19-29.
7. Castillo V, Rodriguez MS, Lalia J. Estimulación con TRH y evaluación de la respuesta de la TSH en perros. Su importancia en el diagnóstico de la enfermedad tiroidea subclínica (hipotiroidismo subclínico y tiroiditis autoinmune eutiroidea). Revista Científica 2001; 11: 35-40.
8. Gebhard R, Stone B, Andreini J, et al. Thyroid hormone differentially augments biliary sterol secretion in the rat. I. The isolated perfused liver model. J Lipid Res 1992; 33:1459-1466.
9. Nunez J, Celi S, Ng L, et al. Multigenic control of thyroid hormone functions in the nervous system. Mol Cell Endocrinol 2008; 287:1-12.
10. Rudas P, Rónai ZS, Bartha T. Thyroid hormone metabolism in the brain of domestic animals. Domest Anim Endocrinol 2005; 29: 88-96.
11. Beaver BV, Haug LI. Canine behaviors associated with hypothyroidism. J Am Anim Hosp Assoc 2003; 39: 431-437.
12. Glinoer D. Potential consequences of maternal hypothyroidism on the offspring: evidence and implications. Horm Res 2001; 55: 109-114.
13. Rezzonico J, Guntsche Z, Bossa N. Determinación ecográfica de volume tiroideo normal en niños y adolescentes en Mendoza-Argentina. Revista Argentina Endocrinología Metabolismo 1994; 31: 72-78.
14. Xenoulis PG, Steiner JM. Lipid metabolism and hyperlipidemia in dogs. Vet J 2010; 183: 12-21.
15. Sparkes AH, Gruffydd-Jones TJ, Wotton PR et al. Assesment of dose and time responses to TRH and thyrotropin in healthy dogs. J Small Anim Pract 1995; 36: 245-251.
16. Dixon RM, Mooney CT. Evaluation of serum free thyroxine and thyrotropin concentrations in the diagnosis of canine hypothyroidism. J Small Anim Pract 1999; 40: 72-78.
17. Ramírez Benavides GF, Osorio JH. Niveles séricos de tetrayodotironina libre (T4L), mediante el método de electroquimioluminiscencia en caninos. Revista Científica 2009; 19: 238-241.
18. Castillo V, Rodriguez MS, Lalia J, et al. Parámetros bioquímicos-endócrinos de utilidad en la etapa de crecimiento del ovejero alemán, doberman y gran danés. Archivos Medicina Veterinaria 1997; 29: 105-111.
19. Skopek E, Martina Patzl M, Nachreiner R. Detection of autoantibodies against thyroid peroxidase in serum samples of hypothyroid dogs. Am J Vet Res 2006; 7: 809-814.
20. Dixon RM, Reid SW, Mooney CT. Treatment and therapeutic monitoring of canine hypothyroidism. J Small Anim Pract 2002; 43: 334-344.
This article was first published in 2011.