Hypothyroidism: Challenges when Treating Older Adults

Etiology

While iodine deficiency is the leading cause of hypothyroidism worldwide, the most common etiology in North America is an autoimmune disorder known as Hashimoto’s thyroiditis (Almandoz & Gharib, 2012; Jameson & Weetman, 2012). This autoimmune process involves a slow progressive decline in thyroid function (Jameson & Weetman, 2012). Some of the less frequent causes of hypothyroidism include radioactive iodine therapy and specific thyroid surgical procedures (Biondi & Cooper, 2008).

Also, certain medications diminish hormone synthesis, inhibit release of thyroid hormones, or interfere with components of the hypothalamic-pituitary-thyroid feedback mechanism. All of these effects can result in hypothyroidism. Drugs that may decrease TSH levels include glucocorticoids, opiates, and dopamine (Almandoz & Gharib, 2012). Other medications, such as amiodarone (Cordarone^®, Pacerone^®), chemotherapy agents, lithium, and cytokine blockers, diminish secretion of thyroid hormones (Almandoz & Gharib, 2012; Biondi & Cooper, 2008). Due to underlying chronic conditions, older adults tend to take many of the medications that can contribute to the development of hypothyroidism.

Diagnosis

Primary hypothyroidism results from a problem with hormone synthesis in the thyroid gland itself. This primary disorder is evidenced by a higher than normal TSH level (>4.0 mIU/L) and a decreased level of free T4 hormone. Thyroid disease may also be subclinical, which occurs when normal levels of T3 and T4 hormones are maintained in response to an elevated TSH level during the compensatory phase of an autoimmune process (Biondi & Cooper, 2008; Jameson & Weetman, 2012). Table 1 presents a concise classification of laboratory values associated with both primary and subclinical hypothyroidism (Almandoz & Gharib, 2012; Wilson, 2008).

Table 1: Laboratory Values Used To Diagnose Hypothyroidism

Pharmacodynamics

Current management of hypothyroidism involves replacing T4 hormones with synthetic thyroxine. Investigations into the effectiveness of liothyronine (synthetic T3) replacement or of using a combination of T3 and T4 hormones have not shown a significant benefit over replenishing thyroxine alone (Almandoz & Gharib, 2012). Synthetic thyroxine (levothyroxine [Levoxyl^®, Synthroid^®, and others]) demonstrates less biological activity to suppress TSH levels than the naturally occurring T4 isomer; thus, careful monitoring and dose adjustments are required (Dong & Greenspan, 2012). The plasma half-life of levothyroxine is 7 days, and a steady state is reached at six half-lives. Therefore, TSH and T4 levels should be evaluated approximately 6 weeks after initiation of levothyroxine. Dosage requirements of levothyroxine in older adults may be affected by a declining metabolic rate, decreased body mass, and interaction with other concurrent medications (Papaleontiou & Haymart, 2012). It is important to note that gender influences the needed dose of levothyroxine, with women often requiring a higher dose than men (Almandoz & Gharib, 2012).

Solid clinical guidelines regarding how to treat hypothyroidism in older adults do not exist at this time (Papaleontiou & Haymart, 2012). Consensus among most researchers and practitioners is that synthetic levothyroxine should be started at a low dose (12.5 mcg or 25 mcg) in older adults and increased at small increments based on individual response (Almandoz & Gharib, 2012; Chakera et al., 2012). In adults older than 65, the recommended starting dose of levothyroxine is 25 mcg daily unless there is underlying cardiovascular disease (Almandoz & Gharib, 2012; Chakera et al., 2012; Papaleontiou & Haymart, 2012). In patients with known cardiac disease, the initial dose of levothyroxine should be 12.5 mcg daily (Chakera et al., 2012). Due to the potential effects of levothyroxine, such as angina, titration must occur slowly. Once tolerance of a low initial dose is established, the dosage can be increased by 12.5 mcg increments every 6 to 8 weeks until a state of euthyroid is attained (Papaleontiou & Haymart, 2012).

Careful monitoring of TSH levels in older adult patients taking synthetic thyroxine for hypothyroidism is necessary to adjust the treatment regimen if indicated. Overreplacement of thyroxine can result in increased fracture risk and/or atrial fibrillation (Chakera et al., 2012). Underreplacement of thyroxine will fail to correct the symptoms and associated risks of hypothyroidism. Consistent utilization of brand-name levothyroxine should be encouraged rather than the less-regulated generic versions of synthetic thyroxine. Due to variations in the amount of active thyroxine within synthetic preparations, monitoring of TSH levels is recommended 6 weeks after any change to the thyroxine formulation a patient is taking (Almandoz & Gharib, 2012). The goal of treatment is to reach a steady state level of thyroxine, with laboratory results indicating a euthyroid state along with improvement of symptoms.

Pharmacokinetics

Absorption of levothyroxine occurs mostly in the duodenum and is affected by food, gastric acidity, medications, and supplements (Dong & Greenspan, 2012). For example, caffeine, fiber, and soy interfere with absorption of levothyroxine (Chakera et al., 2012). To promote optimal absorption, levothyroxine should be taken when the least interactions may occur, such as 30 minutes prior to breakfast when the person is essentially in a fasting state. If an alternative dosing time is needed in older adult patients because of adherence or convenience issues, levothyroxine can be taken at least 1 to 2 hours after an evening meal or at bedtime (Chakera et al., 2012). Ideal dosing of levothyroxine for absorption can be especially difficult to arrange in a patient who is receiving enteral feedings (Almandoz & Gharib, 2012).

Levothyroxine may interact with a variety of medications and commonly used supplements, resulting in a change in the metabolism of this synthetic hormone. Table 3 provides a general list of substances that interact with levothyroxine. To avoid potential drug-drug interactions that can result in decreased absorption of levothyroxine, medicines that change acidity should not be taken within 4 hours of levothyroxine (Dong & Greenspan, 2012). Other medications, such as phenytoin (Dilantin^®) and nicardipine (Cardene^®), interact with levothyroxine in a way that causes rapid hormone clearance via increased hepatic metabolism or enhanced degradation (Dong & Greenspan, 2012). Selective estrogen receptor modulators, such as tamoxifen (Nolvadex^®) or raloxifene (Evista^®), enhance binding of thyroxine to protein, which leaves less T4 biologically available (Chakera et al., 2012; Dong & Greenspan, 2012). All of these interactions can affect the bioavailability of synthetic thyroxine. When treating older adults, it is imperative to remember that medications being used to treat their chronic conditions may affect the breakdown or absorption of synthetic thyroxine.

Table 3: Medications and Supplements That Affect Levothyroxine

On the other hand, older adult patients may have an underlying condition that is well controlled on a medication that will require a dose adjustment because of an interaction with levothyroxine. For example, the dosage of amitriptyline (Elavil^®) and warfarin (Coumadin^®) may need to be lowered due to the fact that the levothyroxine enhances the effect of both drugs (Chakera et al., 2012). Conversely, the dose of propranolol (Inderal^®) may need to be increased due to a drug-drug interaction with levothyroxine that results in diminished effectiveness of this beta blocker. Awareness of potential interactions and the need for modification with medications for chronic conditions is imperative when prescribing levothyroxine.