Welcome to the all-new Vetlearn

  • Vetlearn is becoming part of NAVC VetFolio.
    Starting in January 2015, Compendium and
    Veterinary Technician articles will be available on
    NAVC VetFolio. VetFolio subscribers will have
    access to not only the journals, but also:
  • Over 500 hours of CE
  • Community forums to discuss tough cases
    and networking with your peers
  • Three years of select NAVC Conference
    Proceedings
  • Free webinars for the entire healthcare team

To access Vetlearn, you must first sign in or register.

registernow

  Sign up now for:
Become a Member

Veterinarian Technician March 2012 (Vol 33, No 3)

Testing the Endocrine System for Thyroid and Parathyroid Disorders: It Is All About Signaling Hormones!

by David Liss, BA, RVT, VTS (ECC)

    CETEST This course is approved for 1.0 CE credits

    Start Test

    Click here to read the companion article: "Testing the Endocrine System for Adrenal Disorders and Diabetes Mellitus: It Is All About Signaling Hormones!"

    The endocrine system is complex and sometimes poorly understood. Although veterinary technicians are often involved with preparing and submitting endocrine tests and caring for patients with endocrinopathies, it may be difficult to understand what is happening in affected patients. This article unravels some of the mysteries of the endocrine system and highlights the need for testing to evaluate endocrine functions. A complete discussion of the endocrinopathies mentioned here is beyond the scope of this article. However, understanding endocrine testing can greatly enhance a technician’s role in helping to manage endocrinopathies. The endocrine system comprises many glands and organs; this article focuses on testing the thyroid and parathyroid glands.

    Thyroid Disorders: Hypothyroidism and Hyperthyroidism

    The thyroid gland, pituitary, and hypothalamus form part of a feedback loop that helps the body regulate thyroid hormone levels. The hypothalamus secretes thyrotropin-releasing hormone, which stimulates the pituitary to release thyroid-stimulating hormone (TSH). TSH signals the thyroid gland to release thyroid hormones, with the major ones being triiodothyronine (T3) and thyroxine (T4).

    Hypothyroidism

    Hypothyroidism—low levels of circulating thyroid hormones—can cause clinical signs. Hypothyroidism is reportedly the most common canine endocrinopathy,1 but it rarely affects cats. Hypothyroidism is typically caused by thyroid gland failure, in which the gland atrophies (or is attacked by the immune system), causing a decrease in T3 and T4 production. Rarely is hypothyroidism caused by a pituitary or hypothalamic condition. Clinical signs include lethargy, mental dullness, and alopecia (bilateral and nonpruritic) and may include recurrent skin infections, hypothermia, bradycardia, and myopathies or neuropathies.1

    In patients suspected of having hypothyroidism, concentrations of the following hormones can be tested: total T3, total T4, free T3, free T4, TSH, and antithyroid autoantibody hormone. Because total and free T3 concentrations are not typically used for diagnosing hypothyroidism, they have been excluded from this discussion.

    The total T4 concentration is typically used as a screening test, meaning that if the level is low, further testing is probably needed. Because the total T4 concentration refers to both bound (to proteins) and unbound (biologically available) portions of the total amount of T4, other factors can affect its measurement. Patients that are critically ill or undergoing certain drug therapies can have a low total T4 concentration but a normal biologically active free T4 concentration; this is called euthyroid sick syndrome. Thus, if a patient has a low total T4 concentration on routine blood work, follow-up tests should be performed. A patient with a low total T4 concentration, apparent or nonapparent concurrent disease, and a normal free T4 concentration may have euthyroid sick syndrome.

    A low free T4 level correlates highly with clinical illness,1 but the free T4 level should be measured only by equilibrium dialysis, which is more accurate for detecting hypothyroidism than the total T4 test.1

    The TSH level can also be measured. If the thyroid gland is not functioning properly and circulating thyroid hormone levels are low, the TSH level should be high. However, the accuracy of the TSH assay for diagnosing hypothyroidism is quite low. Although the TSH level would be expected to be high if hypothyroidism is present, it can often be high, low, or normal. Therefore, hypothyroidism should not be diagnosed based on a TSH level alone, and errors may occur when the free T4 and TSH levels are interpreted together as a unit; however, a low free T4 level combined with a high TSH level is highly predictive of hypothyroidism. For example, a patient with a low free T4 level and a normal TSH level may not be considered to have hypothyroidism if the TSH level is taken at face value.

    Patients with an autoimmune component to hypothyroidism (autoimmune thyroiditis) can have elevated levels of thyroid hormone antibodies, which can be measured as a high thyroglobulin autoantibody titer. An elevated T3 or T4 autoantibody titer results in a high thyroglobulin autoantibody titer.1 Because antibodies can cross-react, the total T4 level may be normal to slightly low if antibodies are present, but the free T4 level determined by equilibrium dialysis will be significantly low.1 However, antibody levels are not routinely measured because the presence of thyroglobulin autoantibodies does not change the approach to treatment.

    Hyperthyroidism

    Hyperthyroidism is common in cats but rare in dogs. Affected patients often have cachexia, hyperactivity, polyuria, polydipsia, polyphagia, hypertension, tachycardia, and thyroid “slip”—a palpable thyroid nodule that is typically a benign adenoma; however, adenocarcinoma is possible.  These neoplasms increase production of thyroid hormones. Most hyperthyroid cats have an elevated total T4 level; however, this level may be in the middle to high range of normal in some cats (an average of ~33.5% of subjects in one study2 of more than 900 cats). Therefore, testing the total T4 level is somewhat useful for screening, but additional testing is often required to confirm clinical suspicion.2 As in dogs, testing the free T4 level can confirm a normal (within reference range) total T4 level in cats. In one study,2 more than 98% of hyperthyroid cats had an elevated free T4 level. Therefore, in cats, hyperthyroidism is generally diagnosed based on either an elevated serum total T4 level or a “normal” total T4 level and an elevated free T4 level.2  TABLE 1 summarizes the test results for hyperthyroidism, hypothyroidism, and sick euthyroid syndrome.

    Parathyroid Disorders: Hypoparathyroidism and Hyperparathyroidism

    The parathyroid hormone regulatory system can also be deranged in disease. The four parathyroid glands are located above the thyroid gland in the neck; two parathyroid glands reside on each cranial pole of the thyroid gland. These glands are responsible for secreting parathyroid hormone (PTH), which is the primary regulator of the calcium level in the body.

    PTH regulates calcium in the following ways3:

    • PTH increases resorption of calcium and phosphorus in the renal tubules

    • PTH stimulates conversion of inactive vitamin D (cholecalciferol) to active 1,25-dihydrocholecalciferol, increasing calcium absorption by the intestines

    • PTH increases osteoclast activity in bone, enhancing resorption of calcium and phosphorus

    Vitamin D is absorbed in the small intestine and has multiple functions. It stimulates bone and kidney resorption of calcium and phosphorus, although these effects are minor compared with its gastrointestinal (GI) effects. Renal 1α-hydroxylase is required for the final step in converting the absorbed inactive metabolite form of vitamin D (cholecalciferol) to its active form (1,25-dihydrocholecalciferol). Calcitonin is produced in the thyroid gland, secreted as the calcium level rises, and blocks bone and renal resorption of calcium.3

    Hypoparathyroidism

    The pathophysiology of hypoparathyroidism is poorly understood. Iatrogenic causes are the best described, based on observation of the results of unintended parathyroidectomy during a thyroidectomy; however, immune-mediated and congenital causes have been proposed.3 The most common cause is idiopathic in dogs and iatrogenic in cats.3

    Patients with primary hypoparathyroidism exhibit hypocalcemia due to urinary loss of calcium and decreased absorption of calcium in the GI tract,3 hyperphosphatemia (PTH tries to elevate the calcium level, stimulating phosphorus retention), normal renal function, and an inappropriately low PTH level. Clinical signs include weakness, lethargy, twitching, ataxia, and disorientation; polyuria, polydipsia, vomiting, and diarrhea are less common.3 A hypocalcemic patient should have an elevated PTH level; therefore, an inappropriately low PTH level in conjunction with hypocalcemia is considered diagnostic of hypoparathyroidism. Calcium and PTH levels should be measured together to document an inappropriately low PTH level along with hypocalcemia.

    To diagnose hypoparathyroidism, the ionized calcium, phosphorus, and PTH levels should be tested. Diagnostic differentials for a patient with hypocalcemia include eclampsia (puerperal tetany), acute pancreatitis, renal failure, hypoalbuminemia, ethylene glycol toxicosis, laboratory error (use of EDTA), and hypomagnesemia.3

    Hyperparathyroidism

    Hyperparathyroidism is often due to a neoplastic process, such as a parathyroid adenoma or carcinoma. However, hyperparathyroidism can be due to hypertrophy of parathyroid chief cells, which can be overstimulated due to low calcium and/or phosphorus levels. Renal secondary hyperparathyroidism can potentiate this. However, in primary hyperparathyroidism, the most common clinicopathologic finding is hypercalcemia.4

    Renal secondary hyperparathyroidism occurs in some cases of chronic renal disease. The loss of nephron function results in several mechanisms that lower the ionized calcium level. This chronically stimulates PTH secretion, causing hypertrophy of the parathyroid chief cells.

    Hypercalcemia is a consistent finding in hyperparathyroidism, regardless of the cause, and is often found through routine blood work. The mnemonic GOSH DARN IT can be used to remember the diagnostic differentials associated with hypercalcemia: Granulomatous (e.g., fungal infection), Orthopedic (e.g., osteosarcoma, osteomyelitis), Spurious (e.g., laboratory error), Hyperparathyroidism; vitamin D toxicosis (e.g., due to cholecalciferol rodenticides), Addison disease, Renal disease, Neoplasia (e.g., PTH-related protein release); Idiopathic, Temperature (e.g., hypothermia may cause hypercalcemia).3 Patients with hypercalcemia unrelated to hyperactive parathyroid glands should have a low PTH level in the presence of an elevated calcium level. A total calcium test—which tests protein-bound, ionized, and complexed calcium levels—is often performed in biochemical panels. The total calcium level may be the first parameter that is elevated, signaling hypercalcemia. Additional testing may include the levels of ionized calcium (the biologically active form of calcium in the blood), PTH, PTH-related protein, and vitamin D. Diagnosis of hyperparathyroidism is based on high ionized calcium, low or low-normal phosphorus, and elevated PTH levels.4 Results of the tests discussed above are summarized in  TABLE 2 to help differentiate between the various causes of hypercalcemia.

    Conclusion

    The endocrine system is highly complex, so critical thinking is necessary to understand test results. Concentrations of hormones and other components in serum are the result of multiple influences and feedback mechanisms. For veterinary technicians, a basic understanding of how to interpret endocrine test results is essential for caring for small animals.

    Downloadable PDF

    Mr. Liss discloses that he serves on the Merck Speaker's Bureau, the International Veterinary Academy of Pain Management Speaker's Bureau, and the VPI Pet Insurance Advisory Board.

    1. Ferguson DC. Testing for hypothyroidism in dogs. Vet Clin Small Anim Pract 2007;37:647-669.

    2. Shiel RE, Mooney CT. Testing for hyperthyroidism in cats. Vet Clin Small Anim Pract 2007;37:671-691.

    3. Henderson A, Mahony O. Hypoparathyroidism: pathophysiology and diagnosis. Compend Contin Educ Pract Vet 2005;27(4):270-279.

    4. Schaefer C, Goldstein RE. Canine primary hyperparathyroidism. Compend Contin Educ Pract Vet 2009;31(8):382-390.

    5. Brown C, Schulman RL, Graves TK. Hypercalcemia. Stand Care 2003;5(5):1-5.

    References »

    NEXT: Equine Essentials: Biosecurity in Equine Practice

    CETEST This course is approved for 1.0 CE credits

    Start Test

    didyouknow

    Did you know... Neurologic signs occur in 7.5% of hypothyroid dogs.Read More

    These Care Guides are written to help your clients understand common conditions. They are formatted to print and give to your clients for their information.

    Stay on top of all our latest content — sign up for the Vetlearn newsletters.
    • More
    Subscribe