Hypothyroidism is a common disorder among older adults and can affect physical well-being, cognitive ability, and quality of life. The reported incidence of hypothyroidism among older adults varies in the research literature due to the use of diverse patient inclusion criteria and differences in groups targeted for study (Maselli, Inelmen, Giantin, & Manzato, 2012; Papaleontiou & Haymart, 2012). The National Health and Nutrition Examination Survey III Survey, which represents the general U.S. population older than 12, found a 4.6% overall incidence of hypothyroidism (Hollowell et al., 2002). Other epidemiological studies that focused only on adults reported that hypothyroidism affects 47% of adults older than 55 and 67% of those older than 73 (Papaleontiou & Haymart, 2012). The prevalence of hypothyroidism increases with age; consequently, the mean age at diagnosis is 60 (Jameson & Weetman, 2012). Also, more women than men develop hypothyroidism, which indicates some type of gender influence in this disorder, which is not completely understood (Canaris, Manowitz, Mayor, & Ridgway, 2000; Hollowell et al., 2002). Both the physical and mental effects of hypothyroidism may be severe, which underscores the need to identify and treat this condition early and appropriately in older adults. This article provides a brief review of the pathophysiology of hypothyroidism and will focus on recommended pharmacological management in older adults.
Normal thyroid function involves a complex system with multiple interconnected physiological processes and an essential feedback mechanism. First, the hypothalamus secretes thyrotropin-releasing hormone (TRH), which triggers the anterior pituitary gland to synthesize and release thyroid-stimulating hormone (TSH). In turn, the thyroid gland produces and releases thyroxine (T4) and triiodothyronine (T3). Thyroid hormones help regulate metabolism and play an integral part in growth, brain development, and many functions of the cardiovascular, nervous, and reproductive systems (Jameson & Weetman, 2012). Most T3 and T4 hormones are bound to plasma proteins, leading to the term free to refer to the bioavailable amounts that are not bound. Through a negative feedback mechanism, the circulating thyroid hormones suppress the amount of TRH and TSH secreted, causing inhibition of T3 and T4 production. Hypothyroidism occurs from either a breakdown at any point in the hypothalamus-pituitary-thyroid feedback system or from a defect in hormone synthesis and release from the thyroid gland (Almandoz & Gharib, 2012).
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.
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
Challenges of Diagnosis In Older Adults
Many clinical manifestations of hypothyroidism are non-specific and often attributed to aging. The outcomes of hypothyroidism may be evident in every physiological system normally influenced by thyroid hormones (Biondi & Cooper, 2008). For example, changes in physical and mental health often reflect consequences of inadequate levels of T4 hormone. Signs and symptoms of fatigue, weakness, cold intolerance, constipation, dry skin, thinning hair, depression, and cognitive changes should elicit suspicion for hypothyroidism (Papaleontiou & Haymart, 2012). Underlying cardiac conditions in older adults may compound the difficulty of recognizing symptoms resulting from hypothyroidism and may cause a more significant impact from hypothyroidism on the cardiovascular system (Danzi & Klein, 2012; Papaleontiou & Haymart, 2012).
The lack of obvious signs and symptoms in subclinical hypothyroidism creates another dilemma to disease recognition in older adults (Biondi & Cooper, 2008; Jameson & Weetman, 2012). For example, decreased cardiac output and endothelial dysfunction may result from both overt and subclinical hypothyroidism, but differentiating the causes of these problems is not possible (Biondi & Cooper, 2008; Danzi & Klein, 2012; Jameson & Weetman, 2012; Papaleontiou & Haymart, 2012). Thus, being aware of the diversity of hypothyroidism disease presentations and the challenges of identification in older adults is essential. Aggressive case finding of hypothyroidism in patients older than 60 is recommended (Papaleontiou & Haymart, 2012).
Treatment of Hypothyroidism
Decisions regarding treatment of hypothyroidism and subclinical hypothyroidism should be based on laboratory findings along with the older adult’s symptoms, as delineated in Table 2 (Chakera, Pearce, & Vaidya, 2012; Gharib et al., 2005; Papaleontiou & Haymart, 2012). Older adults who have been diagnosed with primary hypothyroidism should be prescribed medication to bring their TSH level to a range of 1.0 to 4.0 mIU/L (Chakera et al., 2012; Papaleontiou & Haymart, 2012). Although the goal when treating younger patients is aimed at the lower end of normal, disease management recommendations for older adults target higher TSH levels to prevent risks associated with overtreatment such as atrial fibrillation and fractures (Chakera et al., 2012; Papaleontiou & Haymart, 2012). In older adults with subclinical hypothyroidism, treatment should begin when the TSH level is over 10 mIU/L or between 5 and 10 mIU/L if the person is symptomatic (Chakera et al., 2012; Gharib et al., 2005). The treatment goal in subclinical hypothyroidism is a TSH level of 3.0 to 4.0 mIU/L for individuals ages 60 to 75 and a TSH of 4.0 to 6.0 mIU/L in those older than 75 (Biondi & Cooper, 2008).
Table 2: Treatment Thresholds and Goals, by TSH Levels
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.
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.
Hypothyroidism is often difficult to recognize in older adults but can impact all aspects of their health. Definitive treatment guidelines for older adults do not exist. However, consensus recommendations for treatment goals in older adults have been issued based on laboratory data and symptom presentation. As noted in the discussion above, levothyroxine should be taken when an older adult is in a fasting state or 4 hours postprandial due to probable interactions with medications and supplements and to avoid absorption issues that can occur with certain foods, such as fiber and caffeine. The starting dosage to treat hypothyroidism in older adult patients should be 12.5 mcg to 25 mcg and titrated slowly every 6 weeks according to tolerance and symptom response. Following a routine schedule and adhering to the same brand of medication are important aspects of the treatment regimen for older adults to reach a euthyroid state.
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Laboratory Values Used To Diagnose Hypothyroidism
|Thyroid State||TSH||Free T4|
|Normal||0.4 to 4.0 mIU/L||0.8 to 2.7 ng/dL|
|Primary hypothyroidism||>4.0 mIU/L||Decreased|
|Subclinical hypothyroidism||>5.0 to 10.0 mIU/L||Normal|
Treatment Thresholds and Goals, by TSH Levels
|Thyroid State||Treatment Threshold||Treatment Goal|
|Primary hypothyroidism||>4.0 mIU/L||1.0 to 4.0 mIU/L|
|Subclinical hypothyroidism||>10 mIU/L||3.0 to 4.0 mIU/L (ages 60 to 74)4.0 to 6.0 mIU/L (75 and older)|
|Symptomatic subclinical hypothyroidism||5.0 to 10.0 mIU/L||3.0 to 4.0 mIU/L (ages 60 to 74)4.0 to 6.0 mIU/L (75 and older)|
Medications and Supplements That Affect Levothyroxine
|Decreases Absorption||Increases Clearance|
|Calcium||Phenobarbital (Luminal®, Solfoton®)|
|Magnesium||Rifampin (Rifadin®, Rimactane®)|
|Zinc||Carbamazepine (Tegretol® and others)|
|Antacid agents||Nicardipine (Cardene®)|
|Proton pump inhibitors|
|Sodium polystyrene sulfonate (Kayexalate®)|
|Bile acid sequestrants|