Thyroid Medications

Chapter 52


Thyroid Medications







Therapeutic Overview


Anatomy and Physiology


Regulation of a basal metabolism is achieved through complex coordination of the hypothalamic-pituitary-thyroid feedback control system (Figure 52-1). T4 and T3 are released from the thyroid gland in response to circulating serum levels of thyroid stimulating hormone (TSH) secreted by the pituitary gland. In turn, TSH secretion is influenced by thyroid-releasing hormone (TRH) that is secreted by the hypothalamus. The feedback mechanism creates an inverse relationship between serum levels of T3-T4 and TSH-TRH. When T3 and T4 serum levels rise, TSH and TRH secretions are suppressed.


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FIGURE 52-1 Regulation of thyroid-stimulating hormone secretion.
Thyroxine (T4) and triiodothyronine (T3) from the thyroid gland exert negative feedback on the pituitary by blocking the action of TRH. Negative feedback of T4 and T3 at the level of the hypothalamus is less well established. Somatostatin and dopamine each tonically inhibits TSH secretion. (From Berne RM, Levy MN: Physiology, ed 4, St Louis, 1998, Mosby; The Endocrine Society: Management of thyroid dysfunction during pregnancy and postpartum, 2007. Accessed at www.endo-society.org.)

TRH and TSH levels can be measured directly. An elevated TSH, along with low circulating levels of free (unbound) T3 and T4, is diagnostic of primary hypothyroidism. Conversely, a low or undetectable TSH with high circulating levels of free T3 and T4 is diagnostic of thyrotoxicosis. A low TSH accompanied by low T4 and T3 or a high TSH with high levels of T4 and T3 is characteristic of a central cause (secondary or tertiary) of hypothyroidism or thyrotoxicosis, respectively. Although rarely indicated, a stimulation test for TRH may be obtained if secondary hypothyroidism is suspected.


The thyroid gland releases T4 (90%), T3 (10%), and reverse T3 (rT3) (<1%). Elevated rT3 may be an indication of euthyroid sick syndrome. This test usually is reserved for use when standard thyroid function tests (TFTs) yield inconclusive results.


T3 and T4 have a high affinity for protein. T3 is 99.7% protein bound, whereas T4 is 99.97% protein bound. Only the unbound portion is metabolically active. In the peripheral tissue, T4 is converted to T3 through the removal of iodine. Therefore, in most cases, it is necessary to administer only T4 because the body will produce T3 from T4. The physiologic effects of thyroid hormones are attributed to the peripheral T3.


Thyroid hormones exert their effect on nearly every system of the body through a variety of mechanisms. Basal metabolic rate is regulated by thyroid hormones. Thyroid hormones also influence oxygen consumption, respiratory rate, body temperature, heart rate, stroke volume, enzyme system activity, the rate of fat, protein, and carbohydrate metabolism, and growth and maturation. They are especially important in central nervous development.



Pathophysiology


In children, thyroid hormones are essential for overall normal growth and development. Without thyroid hormone, development of the central nervous system is impaired. Undetected deficiency of thyroid hormone may begin to affect children shortly after birth (as evidenced by cretinism).


Adults also may develop numerous problems related to a decreased metabolic rate. Cardiovascular, gastrointestinal, musculoskeletal, and neurologic function may be impaired by inadequate thyroid hormones.


Primary hypothyroidism, the most common form of hypothyroidism, is caused by a failure within the thyroid gland. Secondary hypothyroidism is caused by lack of TSH secretion from the pituitary. Tertiary hypothyroidism is caused by lack of TRH secretion from the hypothalamus.


Primary hypothyroidism has a variety of causes. One common cause is iatrogenic—that is, the result of therapy for thyrotoxicosis or other drugs such as lithium. Other causes include idiopathic thyroid atrophy and autoimmune destruction of the thyroid, such as Hashimoto’s thyroiditis or postpartum thyroid disease.



Disease Process


Hypothyroidism is the metabolic state that results from deficient thyroid hormones. In adults, it is most common in women and is characterized by signs and symptoms consistent with altered energy metabolism, such as fatigue, lethargy, sensitivity to cold, dry skin, and menstrual disturbances. If untreated, it can progress to life-threatening myxedema, with characteristic appearance and physical symptoms, especially of the skin, and cardiovascular instability.


Table 52-1 lists altered laboratory findings in thyroid dysfunction. TSH is the most sensitive and useful test in the diagnosis of hypothyroidism. Free T4 and T3 are also useful. The amount of circulating and unbound hormones is reduced in patients with this disorder.





Treatment Principles


Standardized Guidelines






Cardinal Points of Treatment




• Treat hypothyroidism with levothyroxine.


• Dosage of all thyroid medication must be individualized. Dosage is based on laboratory findings and the patient’s clinical response. Treatment of choice for hypothyroidism is T4. It has a relatively slow onset of action, and its effects are cumulative over several weeks. T3 has a more rapid onset of action and dissipation of action. T3 may be the preferred treatment for use in rapidly correcting a hypothyroid state, in radioisotope scanning procedures, and in thyroid cancer. No evidence shows that the addition of T3 to T4 supplement has any benefit except in the very rare instances when patients cannot convert or metabolize T4 to T3.


• The mean replacement dosage of levothyroxine is 1.6 mcg/kg of body weight per day, although the appropriate dosage varies among patients. The pace of treatment depends on the duration and severity of hypothyroidism and on whether other associated medical problems are present. The patient should undergo reassessment, and therapy should be titrated after an interval of 4 to 6 weeks following any change in levothyroxine brand or dose. Dosage should be titrated until a normal TSH is obtained. Adults younger than age 65 without coronary artery disease may begin with 50 to 100 mcg per day. Elderly patients and those with coronary artery disease generally should be started on a daily dose of 25 mcg. The usual maintenance dose is 75 to 150 mcg po daily.


• Thyroid hormone should be administered as a single daily dose, preferably before breakfast. Levothyroxine doses are commonly measured in micrograms rather than milligrams to avoid confusion regarding the dosage. A correct dose is 75 mcg, which is the equivalent of 0.075 mg.


• The AACE emphasizes that many brands of levothyroxine are available, and these are not compared against a levothyroxine standard. Bioequivalence of levothyroxine preparations is based on total T4 measurement and not on TSH levels; therefore, bioequivalence is not the same as therapeutic equivalence. It is recommended that patients should receive the same brand of levothyroxine throughout treatment. In general, desiccated thyroid hormone, combinations of thyroid hormones, or triiodothyronine should not be used as replacement therapy.



How to Monitor


See Tables 52-2 and 52-3.



TABLE 52-2


Laboratory Evaluation of Thyroid Disorders
























































Test Hormone Evaluated Interpretation of Test Results
TRH (thyrotropin) Thyrotropin-releasing hormone Assesses the function of the hypothalamic-pituitary-thyroid axis. Most useful when other tests are inconclusive
TSH Thyroid-stimulating hormone Assesses the function of the hypothalamic-pituitary-thyroid axis
TBG (thyroglobulin) Thyroxine-binding globulin As the primary protein for hormone binding, it is most useful for evaluating discrepancies in clinical findings and other serum hormone levels
T4 (T4 RIA, thyroxine) Tetraiodothyronine, thyroxine Concentration of bound and unbound thyroid hormone (T4) in the serum
FT4 Free thyroxine, free T4 Concentration of unbound thyroid hormone (T4) in the serum. It is most helpful for diagnosis when TBG level is abnormal.
T3 (T3 RIA) Triiodothyronine Concentration of bound and unbound thyroid hormone (T3) in the serum
FT3 Free triiodothyronine, free T3 Concentration of unbound, active T3 in the serum
T3-U (T3 RU) Resin T3 uptake Indirectly measures the concentration of thyroglobulin (TBG) by measuring the empty TBG binding sites in serum. Direct measurement of TBG may be more useful.
rT3 Reverse T3 A T3 antagonist, rT3 can be increased in euthyroid sick syndrome.
FTI (F T4-I, T7, T12) Free T4 index Derived by multiplying T4 and T3-U, it reflects the free (unbound) T4 in serum. This test essentially has been replaced by direct FT3 and FT4 measurements.
LATS Long-acting thyroid stimulator A positive test supports the diagnosis of Graves’ disease.
Antithyroid antibodies Antithyroglobulin antibodies and/or antithyroid peroxidase antibodies
Anti-TSH receptor antibodies		 High titers in individuals with Hashimoto’s thyroiditis and Graves’ disease
High titers in individuals with Graves’ disease


The test for T4 measures total thyroxine, both bound and unbound in the serum. Free thyroxine (FT4) measures only unbound T4. Normally, only T4 must be measured; thyroid-binding globulin (TBG) is the protein to which thyroid hormones are bound. It can be measured directly by the TBG test. Resin T3 uptake (T3 RU) is an indirect measure that is no longer used. If the patient has an abnormal TBG, free T4 may have to be evaluated.


Usually, measuring the TSH within 4 to 6 weeks is sufficient. Full therapeutic effectiveness may not be achieved for 3 to 6 weeks. TSH and symptom review usually are monitored monthly until normal and stable. Annual evaluation is recommended once maintenance therapy has been achieved. Levels also should be evaluated whenever patients experience signs and/or symptoms that could be related to underdosage/overdosage.


Children younger than 3 years of age should be maintained on the upper end of the T4 therapeutic range with a normal serum TSH. It is recommended that children undergo laboratory assessment of medication effectiveness every 1 to 2 months for the first year, every 2 to 3 months from 1 to 3 years old, and every 3 to 12 months thereafter.


Patients with a history of thyroid cancer who have had partial or total removal of their thyroid gland must take thyroid hormone supplements to suppress endogenous levels of TSH and to regulate their metabolism. However, a high level of TSH in a patient’s bloodstream is necessary for radioiodine imaging to detect remnant thyroid tissue or metastatic disease, and for optimal sensitivity of serum thyroglobulin testing to be achieved. In the past, patients had to stop taking their hormone supplements for 2 to 6 weeks prior to testing, causing them to experience symptoms of thyroid deficiency. Thyrogen, which is a recombinant form of TSH, allows the patients to avoid hormone withdrawal and its debilitating effects while they are undergoing diagnostic testing. Specifically, thyrogen is a new diagnostic agent for adjunctive use in serum thyroglobulin testing with or without radioiodine imaging in the follow-up of patients with well-differentiated thyroid cancer.



Patient Variables


Geriatrics


Hypothyroidism is common in the elderly. Atypical presentation includes CHF. Administration of thyroid hormone may exacerbate cardiovascular disease, particularly angina, in elderly patients. It is advisable to start low (25 mcg) and gradually increase the dosage. Absorption of the drug may increase with aging, so dosage adjustments may be required.


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Jul 22, 2016 | Posted by in PHARMACY | Comments Off on Thyroid Medications

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