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Are overweight children more likely to be overweight adults?
Yes. Overweight at any age in childhood increases the risk for overweight in adulthood. The relative risk (RR) ranges from 1.9 to 10.1 and increases as children get older. Not all overweight children become overweight adults, however (strength of recommendation: A, systematic review of consistent prospective and retrospective cohort studies).
Take a direct approach to excess weight
Mark B. Stephens, MD, MS
Uniformed Services Hospital, Bethesda, Md
For reasons of sensitivity and “correctness,” clinicians often avoid using the term obesity when talking about children. Does our zeal to be polite actually make things worse?
Studies show that parents often fail to recognize that their children are overweight.1 And physicians caring for overweight children often fail to record overweight as a diagnosis in their young patients’ medical records.2
Failure to document excess weight in children virtually guarantees that little if any constructive weight-oriented counseling occurs. By refusing to face the issue head-on, we enable denial of this essential point: Overweight children are far more likely to become obese adults. As we have done with tobacco, it’s now time to ask about weight problems in children, advise families about strategies for safe weight management, and assist where needed.
Evidence summary
The Centers for Disease Control and Prevention (CDC) doesn’t use the term obesity to describe weight in children. Instead, the CDC defines overweight as body mass index (BMI) or weight-for-length for age and sex greater than the 95th percentile. Children above the 85th percentile are called “at risk for overweight.” A national expert panel recently recommended changing “at risk for overweight” to “overweight” and “overweight” to “obese”—the terminology used in this Clinical Inquiry.3
Studies find a clear connection
A 2008 systematic review found 25 prospective or retrospective longitudinal studies that examined the risk of overweight in adulthood based on overweight in childhood or adolescence. Studies had to include at least 1 anthropomorphic measurement before age 18 and at least 1 after age 18. The informativeness and validity of the studies were assessed using a standard evaluation tool. Because the review sought to provide results that could be generalized to large populations, it didn’t include studies of specific populations, such as former premature infants.
All of the 13 studies judged to be high quality found an elevated RR or odds ratio (OR) for adult obesity among participants who had been overweight as children. The authors didn’t calculate a composite measure of effect, but RRs in the individual studies ranged from 1.9 to 10.1.4
Older overweight children are at heightened risk
The systematic review considered children (≤12 years) and adolescents (>12 years) separately. Four high-quality studies assessed how many overweight children became overweight adults; 2 high-quality studies examined how many overweight children became obese adults. Overweight children had RRs between 1.9 and 3.6 for being overweight in adulthood compared with average-weight children; 1 study reported an OR of 7.0.
One study showed older overweight children to be at greater risk than younger children for overweight in adulthood: children who were overweight at 2 years of age had an RR of 2.7, whereas children who were overweight at 11 years had an RR of 3.6.
Obese children had similar results. A study of 4 age cohorts showed that children who were obese at 1 or 2 years of age had an OR of 1.3 for obesity in adulthood compared with average-weight peers. Obese children in the 3- to 5-year-old cohort had an OR of 4.7; obese children in the 6- to 9-year-old cohort had an OR of 8.8; and obese 10- to 14-year-olds had an OR of 22.3.
Risk increases with age
As with children, overweight adolescents had a higher risk of being overweight in adulthood. And the association between older age and higher ORs persisted into adolescence. One study found an OR of 17.5 for adult overweight among youngsters who were overweight at 10 to 14 years of age and an OR of 22.3 for adolescents who were overweight at 15 to 17 years.
Boys are at greater risk than girls
The systematic review also revealed sex differences. Two studies showed that overweight or obese boys were not only more likely to be overweight in adulthood than their average-weight peers (OR=15.0 in 1 study; RR=9.8 in the other), but also more likely to be overweight later in life than overweight or obese girls. The girls had an OR of 12.0 for adult overweight in 1 study and an RR of 6.8 in the other.
Recommendations
The American Academy of Family Physicians emphasizes that weight management in childhood is an important goal, but notes a lack of evidence regarding the effectiveness of screening and treating overweight in children.5 The American Academy of Pediatrics recommends calculating and plotting BMI yearly to identify excessive weight gain.6
The United States Preventive Services Task Force, citing lack of evidence for treatment benefit, finds insufficient evidence for or against screening for overweight in children.7
1. Carnell S, Edwards C, Croker H, et al. Parental perceptions of overweight in 3-5 y olds. Int J Obesity. 2005;29:353-355.
2. Bardia A, Holtan SG, Slezak JM, et al. Diagnosis of obesity by primary-care physicians and impact on obesity management. Mayo Clin Proc. 2007;82:927-932.
3. Barlow SE. Expert Committee. Expert committee recommendations regarding the prevention, assessment, and treatment of child and adolescent overweight and obesity: summary report. Pediatrics. 2007;120(suppl 4):S164-S192.
4. Singh AS, Mulder C, Twisk JW, et al. Tracking of childhood overweight into adulthood: a systematic review of the literature. Obes Rev. 2008;9:474-488.
5. American Academy of Family Physicians. Recommendations for clinical preventive services. Available at: www.aafp.org/online/en/home/clinical/exam/k-o.html. Accessed September 17, 2007.
6. Krebs NF, Jacobson MS. American Academy of Pediatrics Committee on Nutrition. Prevention of pediatric overweight and obesity. Pediatrics. 2003;112:424-430.
7. US Preventive Services Task Force. Screening and interventions for overweight in children and adolescents. In: Guide to Clinical Preventive Services, 2006. Recommendation Statement. Rockville, MD: AHRQ; July 2005. AHRQ publication 05-0574-A.
Yes. Overweight at any age in childhood increases the risk for overweight in adulthood. The relative risk (RR) ranges from 1.9 to 10.1 and increases as children get older. Not all overweight children become overweight adults, however (strength of recommendation: A, systematic review of consistent prospective and retrospective cohort studies).
Take a direct approach to excess weight
Mark B. Stephens, MD, MS
Uniformed Services Hospital, Bethesda, Md
For reasons of sensitivity and “correctness,” clinicians often avoid using the term obesity when talking about children. Does our zeal to be polite actually make things worse?
Studies show that parents often fail to recognize that their children are overweight.1 And physicians caring for overweight children often fail to record overweight as a diagnosis in their young patients’ medical records.2
Failure to document excess weight in children virtually guarantees that little if any constructive weight-oriented counseling occurs. By refusing to face the issue head-on, we enable denial of this essential point: Overweight children are far more likely to become obese adults. As we have done with tobacco, it’s now time to ask about weight problems in children, advise families about strategies for safe weight management, and assist where needed.
Evidence summary
The Centers for Disease Control and Prevention (CDC) doesn’t use the term obesity to describe weight in children. Instead, the CDC defines overweight as body mass index (BMI) or weight-for-length for age and sex greater than the 95th percentile. Children above the 85th percentile are called “at risk for overweight.” A national expert panel recently recommended changing “at risk for overweight” to “overweight” and “overweight” to “obese”—the terminology used in this Clinical Inquiry.3
Studies find a clear connection
A 2008 systematic review found 25 prospective or retrospective longitudinal studies that examined the risk of overweight in adulthood based on overweight in childhood or adolescence. Studies had to include at least 1 anthropomorphic measurement before age 18 and at least 1 after age 18. The informativeness and validity of the studies were assessed using a standard evaluation tool. Because the review sought to provide results that could be generalized to large populations, it didn’t include studies of specific populations, such as former premature infants.
All of the 13 studies judged to be high quality found an elevated RR or odds ratio (OR) for adult obesity among participants who had been overweight as children. The authors didn’t calculate a composite measure of effect, but RRs in the individual studies ranged from 1.9 to 10.1.4
Older overweight children are at heightened risk
The systematic review considered children (≤12 years) and adolescents (>12 years) separately. Four high-quality studies assessed how many overweight children became overweight adults; 2 high-quality studies examined how many overweight children became obese adults. Overweight children had RRs between 1.9 and 3.6 for being overweight in adulthood compared with average-weight children; 1 study reported an OR of 7.0.
One study showed older overweight children to be at greater risk than younger children for overweight in adulthood: children who were overweight at 2 years of age had an RR of 2.7, whereas children who were overweight at 11 years had an RR of 3.6.
Obese children had similar results. A study of 4 age cohorts showed that children who were obese at 1 or 2 years of age had an OR of 1.3 for obesity in adulthood compared with average-weight peers. Obese children in the 3- to 5-year-old cohort had an OR of 4.7; obese children in the 6- to 9-year-old cohort had an OR of 8.8; and obese 10- to 14-year-olds had an OR of 22.3.
Risk increases with age
As with children, overweight adolescents had a higher risk of being overweight in adulthood. And the association between older age and higher ORs persisted into adolescence. One study found an OR of 17.5 for adult overweight among youngsters who were overweight at 10 to 14 years of age and an OR of 22.3 for adolescents who were overweight at 15 to 17 years.
Boys are at greater risk than girls
The systematic review also revealed sex differences. Two studies showed that overweight or obese boys were not only more likely to be overweight in adulthood than their average-weight peers (OR=15.0 in 1 study; RR=9.8 in the other), but also more likely to be overweight later in life than overweight or obese girls. The girls had an OR of 12.0 for adult overweight in 1 study and an RR of 6.8 in the other.
Recommendations
The American Academy of Family Physicians emphasizes that weight management in childhood is an important goal, but notes a lack of evidence regarding the effectiveness of screening and treating overweight in children.5 The American Academy of Pediatrics recommends calculating and plotting BMI yearly to identify excessive weight gain.6
The United States Preventive Services Task Force, citing lack of evidence for treatment benefit, finds insufficient evidence for or against screening for overweight in children.7
Yes. Overweight at any age in childhood increases the risk for overweight in adulthood. The relative risk (RR) ranges from 1.9 to 10.1 and increases as children get older. Not all overweight children become overweight adults, however (strength of recommendation: A, systematic review of consistent prospective and retrospective cohort studies).
Take a direct approach to excess weight
Mark B. Stephens, MD, MS
Uniformed Services Hospital, Bethesda, Md
For reasons of sensitivity and “correctness,” clinicians often avoid using the term obesity when talking about children. Does our zeal to be polite actually make things worse?
Studies show that parents often fail to recognize that their children are overweight.1 And physicians caring for overweight children often fail to record overweight as a diagnosis in their young patients’ medical records.2
Failure to document excess weight in children virtually guarantees that little if any constructive weight-oriented counseling occurs. By refusing to face the issue head-on, we enable denial of this essential point: Overweight children are far more likely to become obese adults. As we have done with tobacco, it’s now time to ask about weight problems in children, advise families about strategies for safe weight management, and assist where needed.
Evidence summary
The Centers for Disease Control and Prevention (CDC) doesn’t use the term obesity to describe weight in children. Instead, the CDC defines overweight as body mass index (BMI) or weight-for-length for age and sex greater than the 95th percentile. Children above the 85th percentile are called “at risk for overweight.” A national expert panel recently recommended changing “at risk for overweight” to “overweight” and “overweight” to “obese”—the terminology used in this Clinical Inquiry.3
Studies find a clear connection
A 2008 systematic review found 25 prospective or retrospective longitudinal studies that examined the risk of overweight in adulthood based on overweight in childhood or adolescence. Studies had to include at least 1 anthropomorphic measurement before age 18 and at least 1 after age 18. The informativeness and validity of the studies were assessed using a standard evaluation tool. Because the review sought to provide results that could be generalized to large populations, it didn’t include studies of specific populations, such as former premature infants.
All of the 13 studies judged to be high quality found an elevated RR or odds ratio (OR) for adult obesity among participants who had been overweight as children. The authors didn’t calculate a composite measure of effect, but RRs in the individual studies ranged from 1.9 to 10.1.4
Older overweight children are at heightened risk
The systematic review considered children (≤12 years) and adolescents (>12 years) separately. Four high-quality studies assessed how many overweight children became overweight adults; 2 high-quality studies examined how many overweight children became obese adults. Overweight children had RRs between 1.9 and 3.6 for being overweight in adulthood compared with average-weight children; 1 study reported an OR of 7.0.
One study showed older overweight children to be at greater risk than younger children for overweight in adulthood: children who were overweight at 2 years of age had an RR of 2.7, whereas children who were overweight at 11 years had an RR of 3.6.
Obese children had similar results. A study of 4 age cohorts showed that children who were obese at 1 or 2 years of age had an OR of 1.3 for obesity in adulthood compared with average-weight peers. Obese children in the 3- to 5-year-old cohort had an OR of 4.7; obese children in the 6- to 9-year-old cohort had an OR of 8.8; and obese 10- to 14-year-olds had an OR of 22.3.
Risk increases with age
As with children, overweight adolescents had a higher risk of being overweight in adulthood. And the association between older age and higher ORs persisted into adolescence. One study found an OR of 17.5 for adult overweight among youngsters who were overweight at 10 to 14 years of age and an OR of 22.3 for adolescents who were overweight at 15 to 17 years.
Boys are at greater risk than girls
The systematic review also revealed sex differences. Two studies showed that overweight or obese boys were not only more likely to be overweight in adulthood than their average-weight peers (OR=15.0 in 1 study; RR=9.8 in the other), but also more likely to be overweight later in life than overweight or obese girls. The girls had an OR of 12.0 for adult overweight in 1 study and an RR of 6.8 in the other.
Recommendations
The American Academy of Family Physicians emphasizes that weight management in childhood is an important goal, but notes a lack of evidence regarding the effectiveness of screening and treating overweight in children.5 The American Academy of Pediatrics recommends calculating and plotting BMI yearly to identify excessive weight gain.6
The United States Preventive Services Task Force, citing lack of evidence for treatment benefit, finds insufficient evidence for or against screening for overweight in children.7
1. Carnell S, Edwards C, Croker H, et al. Parental perceptions of overweight in 3-5 y olds. Int J Obesity. 2005;29:353-355.
2. Bardia A, Holtan SG, Slezak JM, et al. Diagnosis of obesity by primary-care physicians and impact on obesity management. Mayo Clin Proc. 2007;82:927-932.
3. Barlow SE. Expert Committee. Expert committee recommendations regarding the prevention, assessment, and treatment of child and adolescent overweight and obesity: summary report. Pediatrics. 2007;120(suppl 4):S164-S192.
4. Singh AS, Mulder C, Twisk JW, et al. Tracking of childhood overweight into adulthood: a systematic review of the literature. Obes Rev. 2008;9:474-488.
5. American Academy of Family Physicians. Recommendations for clinical preventive services. Available at: www.aafp.org/online/en/home/clinical/exam/k-o.html. Accessed September 17, 2007.
6. Krebs NF, Jacobson MS. American Academy of Pediatrics Committee on Nutrition. Prevention of pediatric overweight and obesity. Pediatrics. 2003;112:424-430.
7. US Preventive Services Task Force. Screening and interventions for overweight in children and adolescents. In: Guide to Clinical Preventive Services, 2006. Recommendation Statement. Rockville, MD: AHRQ; July 2005. AHRQ publication 05-0574-A.
1. Carnell S, Edwards C, Croker H, et al. Parental perceptions of overweight in 3-5 y olds. Int J Obesity. 2005;29:353-355.
2. Bardia A, Holtan SG, Slezak JM, et al. Diagnosis of obesity by primary-care physicians and impact on obesity management. Mayo Clin Proc. 2007;82:927-932.
3. Barlow SE. Expert Committee. Expert committee recommendations regarding the prevention, assessment, and treatment of child and adolescent overweight and obesity: summary report. Pediatrics. 2007;120(suppl 4):S164-S192.
4. Singh AS, Mulder C, Twisk JW, et al. Tracking of childhood overweight into adulthood: a systematic review of the literature. Obes Rev. 2008;9:474-488.
5. American Academy of Family Physicians. Recommendations for clinical preventive services. Available at: www.aafp.org/online/en/home/clinical/exam/k-o.html. Accessed September 17, 2007.
6. Krebs NF, Jacobson MS. American Academy of Pediatrics Committee on Nutrition. Prevention of pediatric overweight and obesity. Pediatrics. 2003;112:424-430.
7. US Preventive Services Task Force. Screening and interventions for overweight in children and adolescents. In: Guide to Clinical Preventive Services, 2006. Recommendation Statement. Rockville, MD: AHRQ; July 2005. AHRQ publication 05-0574-A.
Evidence-based answers from the Family Physicians Inquiries Network
For fibromyalgia, which treatments are the most effective?
There is no single most effective modality for the treatment of fibromyalgia syndrome, and no objective comparison of the results from the different studies is available. Low-dose tricyclic antidepressants (TCAs) improve sleep quality and global well-being and have a moderate beneficial effect on tenderness and stiffness (strength of recommendation [SOR]: A, based on a systematic review of randomized controlled trials [RCTs]).
Selective serotonin reuptake inhibitors (SSRIs) may moderately improve fibromyalgia-related symptoms (SOR: B, based on a few RCTs). The serotonin and norepinephrine reuptake inhibitors (SNRIs) duloxetine (Cymbalta) and milnacipran (Ixel, not currently available in the US) improve pain and other symptoms (SOR: B, based on single RCTs). Tramadol (Ultram) improves pain and other outcomes (SOR: A, based on a few RCTs). Cyclobenzaprine (Flexeril) improves both pain and sleep quality (SOR: A, based on a systematic review of RCTs).
Aerobic exercise improves overall functional capacity and sense of well-being for patients with fibromyalgia (SOR: A, based on a systematic review of RCT). Cognitive behavioral therapy improves patients’ self-reported symptoms (SOR: A, based on RCTs).
Reassure patients that their condition is real and treatable
The care of patients with fibromyalgia can be very challenging. An important component of successful management of these patients’ condition is helping them realize that we, as physicians, believe that their pain is real. It is important to reassure them that even though fibromyalgia is not curable, it is treatable and is not a life-threatening condition. Based on expert opinion, combining 2 or more of treatments with the best supporting evidence for effectiveness seems to be the most successful approach to the management of fibromyalgia syndrome.
Evidence summary
Evidence supporting the effectiveness of TCAs is strong, especially amitriptyline, in fibromyalgia-related symptoms. A metaanalysis that included 10 trials of low-dose TCAs (eg, 25–50 mg of amitriptyline) showed moderate improvement in sleep, pain, fatigue, and overall well-being (number needed to treat [NNT] for improvement=4).1 A meta-analysis of 5 RCTs on cyclobenzaprine, a muscle relaxant chemically related to TCAs, demonstrated its effect in improving pain and sleep disturbance (NNT=5).2
There is less evidence that other medications are effective. Two of 3 RCTs of fluoxetine (Prozac) have shown that it was more effective than placebo, and 2 RCTs have shown that fluoxetine and sertraline (Zoloft) are comparable to amitriptyline.3 Single RCTs conducted on duloxetine and milnacipran, new SNRIs, demonstrated them to be more effective than placebo in improving pain and scores on the Fibromyalgia Impact Questionnaire (FIQ).3 Three RCTs have shown that tramadol (with or without acetaminophen) is more effective than placebo in improving pain, number of tender points and FIQ score.3
A single RCT has demonstrated that pregabalin (Lyrica), a new anticonvulsant, reduces pain more than placebo.3
Among nonpharmacological interventions, aerobic exercise and cognitive behavioral therapy have the strongest evidence of effectiveness. A systematic review assessing various exercise programs on symptoms of fibromyalgia showed that aerobic exercise produces short-term improvements in cardiovascular fitness, tender-point pressure pain threshold, and patient- and physicianrated global well-being. Three of these trials included long-term follow-up of the exercise group participants. Patients who continued exercising maintained their improved physical functioning.4
Cognitive behavioral therapy has been shown to reduce symptoms in 5 RCTs.3 Combining cognitive behavioral therapy with education and exercise has also been effective in 5 additional RCTs.3 Some evidence suggests that acupuncture, massage, warm baths, and biofeedback are effective, but this is limited because of methodological issues in the studies that have been conducted to date.3
Recommendations from others
A recently published evidence-based guideline sponsored by the American Pain Society recommends low-dose TCAs, cyclobenzaprine, cardiovascular exercise, and cognitive behavioral therapy alone or with exercise as first-line therapy along with patient education and treatment of comorbid conditions. For patients that do not improve, it recommends a trial of an SSRI, an SNRI, tramadol, an anticonvulsant, combination medications, or referral.3
1. O’Malley PG, Balden E, Tomkins G, Santoro J, Kroenke K, Jackson JL. Treatment of fibromyalgia with antidepressants. J Gen Intern Med. 2000;15:659-666.
2. Tofferi JK, Jackson JL, O’Malley PG. Treatment of fibromyalgia with cyclobenzaprine: a meta-analysis. Arthritis Rheum. 2004;51:9-13.
3. Goldenberg DL, Burckhardt C, Crofford L. Management of fibromyalgia syndrome. JAMA. 2004;292:2388-2395.
4. Busch A, Schachter CL, Peloso PM, Bombardier C. Exercise for treating fibromyalgia syndrome. Cochrane Database Syst Rev. 2002;2:CD003786.
There is no single most effective modality for the treatment of fibromyalgia syndrome, and no objective comparison of the results from the different studies is available. Low-dose tricyclic antidepressants (TCAs) improve sleep quality and global well-being and have a moderate beneficial effect on tenderness and stiffness (strength of recommendation [SOR]: A, based on a systematic review of randomized controlled trials [RCTs]).
Selective serotonin reuptake inhibitors (SSRIs) may moderately improve fibromyalgia-related symptoms (SOR: B, based on a few RCTs). The serotonin and norepinephrine reuptake inhibitors (SNRIs) duloxetine (Cymbalta) and milnacipran (Ixel, not currently available in the US) improve pain and other symptoms (SOR: B, based on single RCTs). Tramadol (Ultram) improves pain and other outcomes (SOR: A, based on a few RCTs). Cyclobenzaprine (Flexeril) improves both pain and sleep quality (SOR: A, based on a systematic review of RCTs).
Aerobic exercise improves overall functional capacity and sense of well-being for patients with fibromyalgia (SOR: A, based on a systematic review of RCT). Cognitive behavioral therapy improves patients’ self-reported symptoms (SOR: A, based on RCTs).
Reassure patients that their condition is real and treatable
The care of patients with fibromyalgia can be very challenging. An important component of successful management of these patients’ condition is helping them realize that we, as physicians, believe that their pain is real. It is important to reassure them that even though fibromyalgia is not curable, it is treatable and is not a life-threatening condition. Based on expert opinion, combining 2 or more of treatments with the best supporting evidence for effectiveness seems to be the most successful approach to the management of fibromyalgia syndrome.
Evidence summary
Evidence supporting the effectiveness of TCAs is strong, especially amitriptyline, in fibromyalgia-related symptoms. A metaanalysis that included 10 trials of low-dose TCAs (eg, 25–50 mg of amitriptyline) showed moderate improvement in sleep, pain, fatigue, and overall well-being (number needed to treat [NNT] for improvement=4).1 A meta-analysis of 5 RCTs on cyclobenzaprine, a muscle relaxant chemically related to TCAs, demonstrated its effect in improving pain and sleep disturbance (NNT=5).2
There is less evidence that other medications are effective. Two of 3 RCTs of fluoxetine (Prozac) have shown that it was more effective than placebo, and 2 RCTs have shown that fluoxetine and sertraline (Zoloft) are comparable to amitriptyline.3 Single RCTs conducted on duloxetine and milnacipran, new SNRIs, demonstrated them to be more effective than placebo in improving pain and scores on the Fibromyalgia Impact Questionnaire (FIQ).3 Three RCTs have shown that tramadol (with or without acetaminophen) is more effective than placebo in improving pain, number of tender points and FIQ score.3
A single RCT has demonstrated that pregabalin (Lyrica), a new anticonvulsant, reduces pain more than placebo.3
Among nonpharmacological interventions, aerobic exercise and cognitive behavioral therapy have the strongest evidence of effectiveness. A systematic review assessing various exercise programs on symptoms of fibromyalgia showed that aerobic exercise produces short-term improvements in cardiovascular fitness, tender-point pressure pain threshold, and patient- and physicianrated global well-being. Three of these trials included long-term follow-up of the exercise group participants. Patients who continued exercising maintained their improved physical functioning.4
Cognitive behavioral therapy has been shown to reduce symptoms in 5 RCTs.3 Combining cognitive behavioral therapy with education and exercise has also been effective in 5 additional RCTs.3 Some evidence suggests that acupuncture, massage, warm baths, and biofeedback are effective, but this is limited because of methodological issues in the studies that have been conducted to date.3
Recommendations from others
A recently published evidence-based guideline sponsored by the American Pain Society recommends low-dose TCAs, cyclobenzaprine, cardiovascular exercise, and cognitive behavioral therapy alone or with exercise as first-line therapy along with patient education and treatment of comorbid conditions. For patients that do not improve, it recommends a trial of an SSRI, an SNRI, tramadol, an anticonvulsant, combination medications, or referral.3
There is no single most effective modality for the treatment of fibromyalgia syndrome, and no objective comparison of the results from the different studies is available. Low-dose tricyclic antidepressants (TCAs) improve sleep quality and global well-being and have a moderate beneficial effect on tenderness and stiffness (strength of recommendation [SOR]: A, based on a systematic review of randomized controlled trials [RCTs]).
Selective serotonin reuptake inhibitors (SSRIs) may moderately improve fibromyalgia-related symptoms (SOR: B, based on a few RCTs). The serotonin and norepinephrine reuptake inhibitors (SNRIs) duloxetine (Cymbalta) and milnacipran (Ixel, not currently available in the US) improve pain and other symptoms (SOR: B, based on single RCTs). Tramadol (Ultram) improves pain and other outcomes (SOR: A, based on a few RCTs). Cyclobenzaprine (Flexeril) improves both pain and sleep quality (SOR: A, based on a systematic review of RCTs).
Aerobic exercise improves overall functional capacity and sense of well-being for patients with fibromyalgia (SOR: A, based on a systematic review of RCT). Cognitive behavioral therapy improves patients’ self-reported symptoms (SOR: A, based on RCTs).
Reassure patients that their condition is real and treatable
The care of patients with fibromyalgia can be very challenging. An important component of successful management of these patients’ condition is helping them realize that we, as physicians, believe that their pain is real. It is important to reassure them that even though fibromyalgia is not curable, it is treatable and is not a life-threatening condition. Based on expert opinion, combining 2 or more of treatments with the best supporting evidence for effectiveness seems to be the most successful approach to the management of fibromyalgia syndrome.
Evidence summary
Evidence supporting the effectiveness of TCAs is strong, especially amitriptyline, in fibromyalgia-related symptoms. A metaanalysis that included 10 trials of low-dose TCAs (eg, 25–50 mg of amitriptyline) showed moderate improvement in sleep, pain, fatigue, and overall well-being (number needed to treat [NNT] for improvement=4).1 A meta-analysis of 5 RCTs on cyclobenzaprine, a muscle relaxant chemically related to TCAs, demonstrated its effect in improving pain and sleep disturbance (NNT=5).2
There is less evidence that other medications are effective. Two of 3 RCTs of fluoxetine (Prozac) have shown that it was more effective than placebo, and 2 RCTs have shown that fluoxetine and sertraline (Zoloft) are comparable to amitriptyline.3 Single RCTs conducted on duloxetine and milnacipran, new SNRIs, demonstrated them to be more effective than placebo in improving pain and scores on the Fibromyalgia Impact Questionnaire (FIQ).3 Three RCTs have shown that tramadol (with or without acetaminophen) is more effective than placebo in improving pain, number of tender points and FIQ score.3
A single RCT has demonstrated that pregabalin (Lyrica), a new anticonvulsant, reduces pain more than placebo.3
Among nonpharmacological interventions, aerobic exercise and cognitive behavioral therapy have the strongest evidence of effectiveness. A systematic review assessing various exercise programs on symptoms of fibromyalgia showed that aerobic exercise produces short-term improvements in cardiovascular fitness, tender-point pressure pain threshold, and patient- and physicianrated global well-being. Three of these trials included long-term follow-up of the exercise group participants. Patients who continued exercising maintained their improved physical functioning.4
Cognitive behavioral therapy has been shown to reduce symptoms in 5 RCTs.3 Combining cognitive behavioral therapy with education and exercise has also been effective in 5 additional RCTs.3 Some evidence suggests that acupuncture, massage, warm baths, and biofeedback are effective, but this is limited because of methodological issues in the studies that have been conducted to date.3
Recommendations from others
A recently published evidence-based guideline sponsored by the American Pain Society recommends low-dose TCAs, cyclobenzaprine, cardiovascular exercise, and cognitive behavioral therapy alone or with exercise as first-line therapy along with patient education and treatment of comorbid conditions. For patients that do not improve, it recommends a trial of an SSRI, an SNRI, tramadol, an anticonvulsant, combination medications, or referral.3
1. O’Malley PG, Balden E, Tomkins G, Santoro J, Kroenke K, Jackson JL. Treatment of fibromyalgia with antidepressants. J Gen Intern Med. 2000;15:659-666.
2. Tofferi JK, Jackson JL, O’Malley PG. Treatment of fibromyalgia with cyclobenzaprine: a meta-analysis. Arthritis Rheum. 2004;51:9-13.
3. Goldenberg DL, Burckhardt C, Crofford L. Management of fibromyalgia syndrome. JAMA. 2004;292:2388-2395.
4. Busch A, Schachter CL, Peloso PM, Bombardier C. Exercise for treating fibromyalgia syndrome. Cochrane Database Syst Rev. 2002;2:CD003786.
1. O’Malley PG, Balden E, Tomkins G, Santoro J, Kroenke K, Jackson JL. Treatment of fibromyalgia with antidepressants. J Gen Intern Med. 2000;15:659-666.
2. Tofferi JK, Jackson JL, O’Malley PG. Treatment of fibromyalgia with cyclobenzaprine: a meta-analysis. Arthritis Rheum. 2004;51:9-13.
3. Goldenberg DL, Burckhardt C, Crofford L. Management of fibromyalgia syndrome. JAMA. 2004;292:2388-2395.
4. Busch A, Schachter CL, Peloso PM, Bombardier C. Exercise for treating fibromyalgia syndrome. Cochrane Database Syst Rev. 2002;2:CD003786.
Evidence-based answers from the Family Physicians Inquiries Network
Should we screen women for hypothyroidism?
Though evidence is insufficient to recommend screening all women for hypothyroidism, women aged >50 years are at increased risk. Screening is most likely to detect subclinical hypothyroidism. Studies evaluating treatment of subclinical hypothyroidism in women aged >50 years offer a mix of potential benefits and harms but without long-term outcome information. No studies address asymptomatic women aged <50.
Testing for thyroid-stimulating hormone (TSH) finds more cases of unrecognized hypothyroidism than history and physical examination (strength of recommendation [SOR]: A, based on cohort studies). Women with an initial screening TSH >10 mU/L are more likely to develop complications of hypothyroidism and to benefit from treatment (SOR: A, based on prospective cohort studies).
Treating women who have asymptomatic hypothyroidism and a screening TSH >10 mU/L prevents progression to symptomatic overt disease (SOR: A, based on prospective cohort studies) and reduces serum lipid levels (SOR: A, based on randomized controlled trials).
Treating women who have subclinical hypothyroidism found by screening does not reduce symptoms (SOR: A, small randomized controlled trials), and its effect on cardiac disease remains controversial. Treatment may increase bone loss in premenopausal women (SOR: A, based on randomized controlled trials and controlled cross-sectional studies), and it may cause symptoms in certain individuals (SOR: C, based on observational studies).
Evidence Summary
Screening for hypothyroidism is more likely to detect the elevated TSH and normal free thyroxine level (FT4) of subclinical hypothyroidism than it is to detect overt hypothyroidism with a high TSH and a low FT4. We reviewed the accuracy of detection, natural history, and benefits and harms of treating subclinical hypothyroidism.
Detection. Subclinical hypothyroidism is found in 7% to 26% of women (with increasing prevalence as women reach age 60 and 70 years); overt hypothyroidism occurs in approximately 5%.1-4 Two studies assessed the ability of the history and physical to detect hypothyroidism.
The first study evaluated 1154 women (aged 50–72) in a primary care setting using both history and physical and TSH testing. TSH testing found 3 women with overt hypothyroidism not identified by history and physical. History and physical identified 286 women with indications for TSH testing, 2 of whom had mild hypothyroidism and 1 with mild hyperthyroidism.5
In the second study, 2000 adults from a primary care population underwent history and physical and TSH testing. The TSH screen identified 19 cases of hypothyroidism not found by history and physical, while the history and physical prompted evaluation of 35 patients without abnormal TSH.6
Natural history of subclinical hypothyroidism. Among 1210 primary care patients (700 women) aged >60 years, 73 women with subclinical hypothyroidism were identified and followed for 12 months. Of these, 13 (18%) progressed to overt disease.7 Another prospective study of 30 patients (6 women) with subclinical hypothyroidism found 16 (3 women) who progressed to overt disease within 24 months. The remaining patients maintained normal FT4 levels for at least 15 years despite persistently elevated TSH.8 A third study followed 2779 adults (1494 women) with all types of thyroid disease for 20 years and found that 55% of women with TSH >6 and a positive antibody test developed overt hypothyroidism. Ninety percent of patients with an initial TSH >10 eventually progressed to overt disease.2
Serum lipid reduction. A retrospective study of 709 women referred to an endocrine clinic for evaluation of abnormal lipoprotein levels identified 34 (4.8%) with undiagnosed hypothyroidism. Thyroid hormone treatment significantly reduced total cholesterol and low-density lipoprotein (LDL) cholesterol in patients with initial TSH >10, but not in those with a TSH <10.9
A randomized trial involving 42 women with subclinical hypothyroidism measured lipid levels before and after 6 months of levothyroxine treatment. Levothyroxine reduced total cholesterol and LDL significantly compared with placebo. Additionally, the subclinical hypothyroidism patients had higher baseline lipid levels when compared with 27 euthyroid controls.10
A meta-analysis combined 13 studies, involving 247 patients with subclinical hypothyroidism, all of whom were given thyroid replacement. All studies reported a decrease in total cholesterol (mean –7.9 mg/dL), and 9 reported a decrease in LDL (mean –10 mg/dL).11 A second meta-analysis with 278 hypothyroid patients given thyroid replacement also found a reduction of total cholesterol (mean –15 mg/dL). LDL effects were not reported.12 The clinical significance of lipid changes in these circumstances is unknown.
Symptom relief. Four small randomized controlled trials used symptom-rating scales to measure symptom relief with treatment of subclinical hypothyroidism. One study involved patients found by screening; the other 3 did not indicate means of diagnosis. Three studies found no significant improvement.13-15 The most recent, involving 33 unblinded patients, found that those taking thyroid replacement had lower symptom scores (number needed to treat [NNT]=3.5).16
Cardiac manifestations. Subclinical hypothyroidism may be associated with ventricular dysfunction, myocardial infarction, and atherosclerosis.18-20 A randomized controlled trial of 20 people with subclinical hypothyroidism found significantly improved left ventricular function assessed by echocardiography after 6 months of treatment with levothyroxine vs placebo.18 Whether treatment prevents myocardial infarction and atherosclerosis is unknown.19,20 A cohort study, involving 2779 adults studied aged >20 years, did not find an association between subclinical hypothyroidism and ischemic heart disease.2
Risks of replacement. A meta-analysis of 41 controlled, cross-sectional studies involving 1250 women treated with thyroid replacement for all causes (ie, not specifically subclinical hypothyroidism) found that replacement therapy (mean duration of treatment, 7 to 9 years) was associated with bone loss in premenopausal women, but not in postmenopausal women.17
A randomized trial of 37 patients over 55 with subclinical hypothyroidism (28 of whom were women), found that thyroid hormone reduced bone mineral density, as assessed by dual-energy x-ray absorptiometry (DEXA) scans over a 10-month period.14 In several trials, patients withdrew due to adverse effects. Two of 37 patients receiving L-thyroxine in 1 study withdrew because of new atrial fibrillation and worsened angina, and 2 of 20 patients in another study withdrew because of nervousness and palpitations.13,14
Recommendations from others
The US Preventive Services Task Force concluded the evidence is insufficient to recommend for or against routine screening for thyroid disease in adults. The yield of screening is greater in high-risk groups such as postpartum women, people with Down syndrome, and the elderly; however, there is poor evidence that screening these groups leads to clinically important benefits.21
The American Thyroid Association recommends screening men and women beginning at age 35 and every 5 years thereafter.22 The American Academy of Family Physicians recommends screening for men and women over age 60.23 The American College of Physicians states screening may be indicated in women over age 50.24
Consider screening all female patients, particularly those over age 50
Julian T. Hsu, MD
A.F. Williams Family Medicine Center, University of Colorado Health Sciences Center, Denver
In my practice, there recently seems to be increased pressure from patients to screen for hypothyroidism, perhaps based on media or Internet information. I have used an individual “risk factor” approach when patients ask me for testing, based on their age, family history, and current symptoms. Based on the data, using the history and physical examination to tailor screening is an ineffective method of detecting hypothyroidism.
Until we have more evidence, I believe a reasonable approach is to offer screening to all of our female patients, particularly those over age 50, along with a careful acknowledgment of the lack of data for or against screening.
1. Tunbridge WM, Evered DC, Hall R, et al. The spectrum of thyroid disease in a community: the Whickham Survey. Clin Endocrinol (Oxf) 1977;7:481-493.
2. Vanderpump MP, Turnbridge WM, French JM, et al. The incidence of thyroid disorders in the community: a twenty-year follow up of the Whickham Survey. Clin Endocrinol (Oxf) 1995;43:55-68.
3. Canaris GJ, Manowitz NR, Mayor G, Ridgway EC. The Colorado thyroid disease prevalence study. Arch Intern Med 2000;160:526-534.
4. Sawin CT, Chopra D, Azizi F, Mannix JE, Bacharach P. The aging thyroid.Increasing prevalence of elevated serum thyrotropin levels in the elderly. JAMA 1979;242:247-250.
5. Petersen K, Lindstedt G, Lundberg PA, Bengtsson C, Lapidus L, Nystrom E. Thyroid disease in middle-aged and elderly Swedish women: thyroid-related hormones, thyroid dysfunction and goitre in relation to age and smoking. J Intern Med 1991;229:407-413.
6. Eggertsen R, Petersen K, Lundberg PA, Nystorm E, Lindstedt G. Screening for thyroid disease in a primary care unit with a thyroid stimulating hormone assay with a low detection limit. BMJ 1988;297:1586-1592.
7. Parle JV, Franklyn JA, Cross KW, Jones SC, Sheppard MC. Prevalence and follow up of abnormal thyrotropin (TSH) concentrations in the elderly in the United Kingdom. Clin Endocrinol (Oxf) 1991;34:77-83.
8. Kabadi UM. ‘Subclinical hypothyroidism’. Natural course of the syndrome during a prolonged follow-up study. Arch Intern Med 1993;153:957-961.
9. Diekman T, Lansberg PJ, Kastelein JJ, Wiersinga WM. Prevalence and correction of hypothyroidism in a large cohort of patients referred for dyslipidemia. Arch Intern Med 1995;155:1490-1495.
10. Caraccio N, Ferrannini E, Monzani F. Lipoprotein profile in subclinical hypothyroidism: response to levothyroxine replacement, a randomized placebo-controlled study. J Clin Endocrinol Metab 2002;87:1533-1538.
11. Danese MD, Ladenson PW, Meinert CL, Powe NR. Clinical review 115: effect of thyroxine therapy on serum lipoproteins in patients with mild thyroid failure: a quantitative review of the literature. J Clin Endocrinol Metab 2000;85:2993-3001.
12. Tanis BC, Westerndorp GJ, Smelt HM. Effect of thyroid substitution on hypercholesterolaemia in patients with subclinical hypothyroidism: a reanalysis of intervention studies. Clin Endocrinol (Oxf) 1996;44:643-649.
13. Nystrom E, Caidahl K, Fager G, Wikkelso C, Lundberg PA, Lindstedt G. A double–blind cross-over 12-month study of L-thyroxine treatment of women with ‘subclinical’ hypothyroidism. Clin Endocrinol (Oxf) 1988;29:63-76.
14. Jaeschke R, Guyatt G, Gerstein H, et al. Does treatment with L-thyroxine influence health status in middle-aged and older adults with subclinical hypothyroidism? J Gen Intern Med 1996;11:744-749.
15. Kong WM, Sheikh MH, Lumb PJ, et al. A 6-month randomized trial of thyroxine treatment in women with mild subclinical hypothyroidism. Am J Med 2002;112:348-354.
16. Cooper DS, Halpern R, Wood LC, Levin AA, Ridgeway EC. L-thyroxine therapy in subclinical hypothyroidism. A double-blind, placebo-controlled trial. Ann Intern Med 1984;101:18-24.
17. Uzzan B, Campos J, Cucherat M, Nony P, Boissel JP, Perret GY. Effects on bone mass of long term treatment with thyroid hormones: a meta-analysis. J Clin Endocrinol Metab 1996;81:4278-4289.
18. Monzani F, Di Bello V, Caraccio N, et al. Effects of levothyroxine on cardiac function and structure in subclinical hypothyroidism: a double-blind, placebo-controlled study. J Clin Endocrinol Metab 2001;86:1110-1115.
19. Biondi B, Palmieri EA, Lombardi G, Fazio S. Effects of subclinical thyroid dysfunction on the heart. Ann Intern Med 2002;137:904-914.
20. Hak AE, Pols HAP, Visser TJ, et al. Subclinical hypothyroidism is an independent risk factor for atherosclerosis and myocardial infarction in elderly women: the Rotterdam Study. Ann Intern Med 2000;132:270-278.
21. U. S. Preventive Services Task Force. Guide to Clinical Preventive Services: report of the US Preventive Services Task Force. Screening for thyroid disease, January 2004.
22. Ladenson PW, Singer PA, Ain KB, et al. American Thyroid Association guidelines for detection of thyroid dysfunction. Arch Intern Med 2000;160:1573-1575.
23. Recommendations for Periodic Health Examinations. Revision 5.4. Leawood, Kansas: American Academy of Family Physicians, 2003. Available at: www.aafp.org/x24973.xml. Accessed on July 8, 2004.
24. Helfand M, Redfern CC. Clinical guidelines, part 2. Screening for thyroid disease: an update. American College of Physicians. Ann Intern Med 1998;129:144-158.
Though evidence is insufficient to recommend screening all women for hypothyroidism, women aged >50 years are at increased risk. Screening is most likely to detect subclinical hypothyroidism. Studies evaluating treatment of subclinical hypothyroidism in women aged >50 years offer a mix of potential benefits and harms but without long-term outcome information. No studies address asymptomatic women aged <50.
Testing for thyroid-stimulating hormone (TSH) finds more cases of unrecognized hypothyroidism than history and physical examination (strength of recommendation [SOR]: A, based on cohort studies). Women with an initial screening TSH >10 mU/L are more likely to develop complications of hypothyroidism and to benefit from treatment (SOR: A, based on prospective cohort studies).
Treating women who have asymptomatic hypothyroidism and a screening TSH >10 mU/L prevents progression to symptomatic overt disease (SOR: A, based on prospective cohort studies) and reduces serum lipid levels (SOR: A, based on randomized controlled trials).
Treating women who have subclinical hypothyroidism found by screening does not reduce symptoms (SOR: A, small randomized controlled trials), and its effect on cardiac disease remains controversial. Treatment may increase bone loss in premenopausal women (SOR: A, based on randomized controlled trials and controlled cross-sectional studies), and it may cause symptoms in certain individuals (SOR: C, based on observational studies).
Evidence Summary
Screening for hypothyroidism is more likely to detect the elevated TSH and normal free thyroxine level (FT4) of subclinical hypothyroidism than it is to detect overt hypothyroidism with a high TSH and a low FT4. We reviewed the accuracy of detection, natural history, and benefits and harms of treating subclinical hypothyroidism.
Detection. Subclinical hypothyroidism is found in 7% to 26% of women (with increasing prevalence as women reach age 60 and 70 years); overt hypothyroidism occurs in approximately 5%.1-4 Two studies assessed the ability of the history and physical to detect hypothyroidism.
The first study evaluated 1154 women (aged 50–72) in a primary care setting using both history and physical and TSH testing. TSH testing found 3 women with overt hypothyroidism not identified by history and physical. History and physical identified 286 women with indications for TSH testing, 2 of whom had mild hypothyroidism and 1 with mild hyperthyroidism.5
In the second study, 2000 adults from a primary care population underwent history and physical and TSH testing. The TSH screen identified 19 cases of hypothyroidism not found by history and physical, while the history and physical prompted evaluation of 35 patients without abnormal TSH.6
Natural history of subclinical hypothyroidism. Among 1210 primary care patients (700 women) aged >60 years, 73 women with subclinical hypothyroidism were identified and followed for 12 months. Of these, 13 (18%) progressed to overt disease.7 Another prospective study of 30 patients (6 women) with subclinical hypothyroidism found 16 (3 women) who progressed to overt disease within 24 months. The remaining patients maintained normal FT4 levels for at least 15 years despite persistently elevated TSH.8 A third study followed 2779 adults (1494 women) with all types of thyroid disease for 20 years and found that 55% of women with TSH >6 and a positive antibody test developed overt hypothyroidism. Ninety percent of patients with an initial TSH >10 eventually progressed to overt disease.2
Serum lipid reduction. A retrospective study of 709 women referred to an endocrine clinic for evaluation of abnormal lipoprotein levels identified 34 (4.8%) with undiagnosed hypothyroidism. Thyroid hormone treatment significantly reduced total cholesterol and low-density lipoprotein (LDL) cholesterol in patients with initial TSH >10, but not in those with a TSH <10.9
A randomized trial involving 42 women with subclinical hypothyroidism measured lipid levels before and after 6 months of levothyroxine treatment. Levothyroxine reduced total cholesterol and LDL significantly compared with placebo. Additionally, the subclinical hypothyroidism patients had higher baseline lipid levels when compared with 27 euthyroid controls.10
A meta-analysis combined 13 studies, involving 247 patients with subclinical hypothyroidism, all of whom were given thyroid replacement. All studies reported a decrease in total cholesterol (mean –7.9 mg/dL), and 9 reported a decrease in LDL (mean –10 mg/dL).11 A second meta-analysis with 278 hypothyroid patients given thyroid replacement also found a reduction of total cholesterol (mean –15 mg/dL). LDL effects were not reported.12 The clinical significance of lipid changes in these circumstances is unknown.
Symptom relief. Four small randomized controlled trials used symptom-rating scales to measure symptom relief with treatment of subclinical hypothyroidism. One study involved patients found by screening; the other 3 did not indicate means of diagnosis. Three studies found no significant improvement.13-15 The most recent, involving 33 unblinded patients, found that those taking thyroid replacement had lower symptom scores (number needed to treat [NNT]=3.5).16
Cardiac manifestations. Subclinical hypothyroidism may be associated with ventricular dysfunction, myocardial infarction, and atherosclerosis.18-20 A randomized controlled trial of 20 people with subclinical hypothyroidism found significantly improved left ventricular function assessed by echocardiography after 6 months of treatment with levothyroxine vs placebo.18 Whether treatment prevents myocardial infarction and atherosclerosis is unknown.19,20 A cohort study, involving 2779 adults studied aged >20 years, did not find an association between subclinical hypothyroidism and ischemic heart disease.2
Risks of replacement. A meta-analysis of 41 controlled, cross-sectional studies involving 1250 women treated with thyroid replacement for all causes (ie, not specifically subclinical hypothyroidism) found that replacement therapy (mean duration of treatment, 7 to 9 years) was associated with bone loss in premenopausal women, but not in postmenopausal women.17
A randomized trial of 37 patients over 55 with subclinical hypothyroidism (28 of whom were women), found that thyroid hormone reduced bone mineral density, as assessed by dual-energy x-ray absorptiometry (DEXA) scans over a 10-month period.14 In several trials, patients withdrew due to adverse effects. Two of 37 patients receiving L-thyroxine in 1 study withdrew because of new atrial fibrillation and worsened angina, and 2 of 20 patients in another study withdrew because of nervousness and palpitations.13,14
Recommendations from others
The US Preventive Services Task Force concluded the evidence is insufficient to recommend for or against routine screening for thyroid disease in adults. The yield of screening is greater in high-risk groups such as postpartum women, people with Down syndrome, and the elderly; however, there is poor evidence that screening these groups leads to clinically important benefits.21
The American Thyroid Association recommends screening men and women beginning at age 35 and every 5 years thereafter.22 The American Academy of Family Physicians recommends screening for men and women over age 60.23 The American College of Physicians states screening may be indicated in women over age 50.24
Consider screening all female patients, particularly those over age 50
Julian T. Hsu, MD
A.F. Williams Family Medicine Center, University of Colorado Health Sciences Center, Denver
In my practice, there recently seems to be increased pressure from patients to screen for hypothyroidism, perhaps based on media or Internet information. I have used an individual “risk factor” approach when patients ask me for testing, based on their age, family history, and current symptoms. Based on the data, using the history and physical examination to tailor screening is an ineffective method of detecting hypothyroidism.
Until we have more evidence, I believe a reasonable approach is to offer screening to all of our female patients, particularly those over age 50, along with a careful acknowledgment of the lack of data for or against screening.
Though evidence is insufficient to recommend screening all women for hypothyroidism, women aged >50 years are at increased risk. Screening is most likely to detect subclinical hypothyroidism. Studies evaluating treatment of subclinical hypothyroidism in women aged >50 years offer a mix of potential benefits and harms but without long-term outcome information. No studies address asymptomatic women aged <50.
Testing for thyroid-stimulating hormone (TSH) finds more cases of unrecognized hypothyroidism than history and physical examination (strength of recommendation [SOR]: A, based on cohort studies). Women with an initial screening TSH >10 mU/L are more likely to develop complications of hypothyroidism and to benefit from treatment (SOR: A, based on prospective cohort studies).
Treating women who have asymptomatic hypothyroidism and a screening TSH >10 mU/L prevents progression to symptomatic overt disease (SOR: A, based on prospective cohort studies) and reduces serum lipid levels (SOR: A, based on randomized controlled trials).
Treating women who have subclinical hypothyroidism found by screening does not reduce symptoms (SOR: A, small randomized controlled trials), and its effect on cardiac disease remains controversial. Treatment may increase bone loss in premenopausal women (SOR: A, based on randomized controlled trials and controlled cross-sectional studies), and it may cause symptoms in certain individuals (SOR: C, based on observational studies).
Evidence Summary
Screening for hypothyroidism is more likely to detect the elevated TSH and normal free thyroxine level (FT4) of subclinical hypothyroidism than it is to detect overt hypothyroidism with a high TSH and a low FT4. We reviewed the accuracy of detection, natural history, and benefits and harms of treating subclinical hypothyroidism.
Detection. Subclinical hypothyroidism is found in 7% to 26% of women (with increasing prevalence as women reach age 60 and 70 years); overt hypothyroidism occurs in approximately 5%.1-4 Two studies assessed the ability of the history and physical to detect hypothyroidism.
The first study evaluated 1154 women (aged 50–72) in a primary care setting using both history and physical and TSH testing. TSH testing found 3 women with overt hypothyroidism not identified by history and physical. History and physical identified 286 women with indications for TSH testing, 2 of whom had mild hypothyroidism and 1 with mild hyperthyroidism.5
In the second study, 2000 adults from a primary care population underwent history and physical and TSH testing. The TSH screen identified 19 cases of hypothyroidism not found by history and physical, while the history and physical prompted evaluation of 35 patients without abnormal TSH.6
Natural history of subclinical hypothyroidism. Among 1210 primary care patients (700 women) aged >60 years, 73 women with subclinical hypothyroidism were identified and followed for 12 months. Of these, 13 (18%) progressed to overt disease.7 Another prospective study of 30 patients (6 women) with subclinical hypothyroidism found 16 (3 women) who progressed to overt disease within 24 months. The remaining patients maintained normal FT4 levels for at least 15 years despite persistently elevated TSH.8 A third study followed 2779 adults (1494 women) with all types of thyroid disease for 20 years and found that 55% of women with TSH >6 and a positive antibody test developed overt hypothyroidism. Ninety percent of patients with an initial TSH >10 eventually progressed to overt disease.2
Serum lipid reduction. A retrospective study of 709 women referred to an endocrine clinic for evaluation of abnormal lipoprotein levels identified 34 (4.8%) with undiagnosed hypothyroidism. Thyroid hormone treatment significantly reduced total cholesterol and low-density lipoprotein (LDL) cholesterol in patients with initial TSH >10, but not in those with a TSH <10.9
A randomized trial involving 42 women with subclinical hypothyroidism measured lipid levels before and after 6 months of levothyroxine treatment. Levothyroxine reduced total cholesterol and LDL significantly compared with placebo. Additionally, the subclinical hypothyroidism patients had higher baseline lipid levels when compared with 27 euthyroid controls.10
A meta-analysis combined 13 studies, involving 247 patients with subclinical hypothyroidism, all of whom were given thyroid replacement. All studies reported a decrease in total cholesterol (mean –7.9 mg/dL), and 9 reported a decrease in LDL (mean –10 mg/dL).11 A second meta-analysis with 278 hypothyroid patients given thyroid replacement also found a reduction of total cholesterol (mean –15 mg/dL). LDL effects were not reported.12 The clinical significance of lipid changes in these circumstances is unknown.
Symptom relief. Four small randomized controlled trials used symptom-rating scales to measure symptom relief with treatment of subclinical hypothyroidism. One study involved patients found by screening; the other 3 did not indicate means of diagnosis. Three studies found no significant improvement.13-15 The most recent, involving 33 unblinded patients, found that those taking thyroid replacement had lower symptom scores (number needed to treat [NNT]=3.5).16
Cardiac manifestations. Subclinical hypothyroidism may be associated with ventricular dysfunction, myocardial infarction, and atherosclerosis.18-20 A randomized controlled trial of 20 people with subclinical hypothyroidism found significantly improved left ventricular function assessed by echocardiography after 6 months of treatment with levothyroxine vs placebo.18 Whether treatment prevents myocardial infarction and atherosclerosis is unknown.19,20 A cohort study, involving 2779 adults studied aged >20 years, did not find an association between subclinical hypothyroidism and ischemic heart disease.2
Risks of replacement. A meta-analysis of 41 controlled, cross-sectional studies involving 1250 women treated with thyroid replacement for all causes (ie, not specifically subclinical hypothyroidism) found that replacement therapy (mean duration of treatment, 7 to 9 years) was associated with bone loss in premenopausal women, but not in postmenopausal women.17
A randomized trial of 37 patients over 55 with subclinical hypothyroidism (28 of whom were women), found that thyroid hormone reduced bone mineral density, as assessed by dual-energy x-ray absorptiometry (DEXA) scans over a 10-month period.14 In several trials, patients withdrew due to adverse effects. Two of 37 patients receiving L-thyroxine in 1 study withdrew because of new atrial fibrillation and worsened angina, and 2 of 20 patients in another study withdrew because of nervousness and palpitations.13,14
Recommendations from others
The US Preventive Services Task Force concluded the evidence is insufficient to recommend for or against routine screening for thyroid disease in adults. The yield of screening is greater in high-risk groups such as postpartum women, people with Down syndrome, and the elderly; however, there is poor evidence that screening these groups leads to clinically important benefits.21
The American Thyroid Association recommends screening men and women beginning at age 35 and every 5 years thereafter.22 The American Academy of Family Physicians recommends screening for men and women over age 60.23 The American College of Physicians states screening may be indicated in women over age 50.24
Consider screening all female patients, particularly those over age 50
Julian T. Hsu, MD
A.F. Williams Family Medicine Center, University of Colorado Health Sciences Center, Denver
In my practice, there recently seems to be increased pressure from patients to screen for hypothyroidism, perhaps based on media or Internet information. I have used an individual “risk factor” approach when patients ask me for testing, based on their age, family history, and current symptoms. Based on the data, using the history and physical examination to tailor screening is an ineffective method of detecting hypothyroidism.
Until we have more evidence, I believe a reasonable approach is to offer screening to all of our female patients, particularly those over age 50, along with a careful acknowledgment of the lack of data for or against screening.
1. Tunbridge WM, Evered DC, Hall R, et al. The spectrum of thyroid disease in a community: the Whickham Survey. Clin Endocrinol (Oxf) 1977;7:481-493.
2. Vanderpump MP, Turnbridge WM, French JM, et al. The incidence of thyroid disorders in the community: a twenty-year follow up of the Whickham Survey. Clin Endocrinol (Oxf) 1995;43:55-68.
3. Canaris GJ, Manowitz NR, Mayor G, Ridgway EC. The Colorado thyroid disease prevalence study. Arch Intern Med 2000;160:526-534.
4. Sawin CT, Chopra D, Azizi F, Mannix JE, Bacharach P. The aging thyroid.Increasing prevalence of elevated serum thyrotropin levels in the elderly. JAMA 1979;242:247-250.
5. Petersen K, Lindstedt G, Lundberg PA, Bengtsson C, Lapidus L, Nystrom E. Thyroid disease in middle-aged and elderly Swedish women: thyroid-related hormones, thyroid dysfunction and goitre in relation to age and smoking. J Intern Med 1991;229:407-413.
6. Eggertsen R, Petersen K, Lundberg PA, Nystorm E, Lindstedt G. Screening for thyroid disease in a primary care unit with a thyroid stimulating hormone assay with a low detection limit. BMJ 1988;297:1586-1592.
7. Parle JV, Franklyn JA, Cross KW, Jones SC, Sheppard MC. Prevalence and follow up of abnormal thyrotropin (TSH) concentrations in the elderly in the United Kingdom. Clin Endocrinol (Oxf) 1991;34:77-83.
8. Kabadi UM. ‘Subclinical hypothyroidism’. Natural course of the syndrome during a prolonged follow-up study. Arch Intern Med 1993;153:957-961.
9. Diekman T, Lansberg PJ, Kastelein JJ, Wiersinga WM. Prevalence and correction of hypothyroidism in a large cohort of patients referred for dyslipidemia. Arch Intern Med 1995;155:1490-1495.
10. Caraccio N, Ferrannini E, Monzani F. Lipoprotein profile in subclinical hypothyroidism: response to levothyroxine replacement, a randomized placebo-controlled study. J Clin Endocrinol Metab 2002;87:1533-1538.
11. Danese MD, Ladenson PW, Meinert CL, Powe NR. Clinical review 115: effect of thyroxine therapy on serum lipoproteins in patients with mild thyroid failure: a quantitative review of the literature. J Clin Endocrinol Metab 2000;85:2993-3001.
12. Tanis BC, Westerndorp GJ, Smelt HM. Effect of thyroid substitution on hypercholesterolaemia in patients with subclinical hypothyroidism: a reanalysis of intervention studies. Clin Endocrinol (Oxf) 1996;44:643-649.
13. Nystrom E, Caidahl K, Fager G, Wikkelso C, Lundberg PA, Lindstedt G. A double–blind cross-over 12-month study of L-thyroxine treatment of women with ‘subclinical’ hypothyroidism. Clin Endocrinol (Oxf) 1988;29:63-76.
14. Jaeschke R, Guyatt G, Gerstein H, et al. Does treatment with L-thyroxine influence health status in middle-aged and older adults with subclinical hypothyroidism? J Gen Intern Med 1996;11:744-749.
15. Kong WM, Sheikh MH, Lumb PJ, et al. A 6-month randomized trial of thyroxine treatment in women with mild subclinical hypothyroidism. Am J Med 2002;112:348-354.
16. Cooper DS, Halpern R, Wood LC, Levin AA, Ridgeway EC. L-thyroxine therapy in subclinical hypothyroidism. A double-blind, placebo-controlled trial. Ann Intern Med 1984;101:18-24.
17. Uzzan B, Campos J, Cucherat M, Nony P, Boissel JP, Perret GY. Effects on bone mass of long term treatment with thyroid hormones: a meta-analysis. J Clin Endocrinol Metab 1996;81:4278-4289.
18. Monzani F, Di Bello V, Caraccio N, et al. Effects of levothyroxine on cardiac function and structure in subclinical hypothyroidism: a double-blind, placebo-controlled study. J Clin Endocrinol Metab 2001;86:1110-1115.
19. Biondi B, Palmieri EA, Lombardi G, Fazio S. Effects of subclinical thyroid dysfunction on the heart. Ann Intern Med 2002;137:904-914.
20. Hak AE, Pols HAP, Visser TJ, et al. Subclinical hypothyroidism is an independent risk factor for atherosclerosis and myocardial infarction in elderly women: the Rotterdam Study. Ann Intern Med 2000;132:270-278.
21. U. S. Preventive Services Task Force. Guide to Clinical Preventive Services: report of the US Preventive Services Task Force. Screening for thyroid disease, January 2004.
22. Ladenson PW, Singer PA, Ain KB, et al. American Thyroid Association guidelines for detection of thyroid dysfunction. Arch Intern Med 2000;160:1573-1575.
23. Recommendations for Periodic Health Examinations. Revision 5.4. Leawood, Kansas: American Academy of Family Physicians, 2003. Available at: www.aafp.org/x24973.xml. Accessed on July 8, 2004.
24. Helfand M, Redfern CC. Clinical guidelines, part 2. Screening for thyroid disease: an update. American College of Physicians. Ann Intern Med 1998;129:144-158.
1. Tunbridge WM, Evered DC, Hall R, et al. The spectrum of thyroid disease in a community: the Whickham Survey. Clin Endocrinol (Oxf) 1977;7:481-493.
2. Vanderpump MP, Turnbridge WM, French JM, et al. The incidence of thyroid disorders in the community: a twenty-year follow up of the Whickham Survey. Clin Endocrinol (Oxf) 1995;43:55-68.
3. Canaris GJ, Manowitz NR, Mayor G, Ridgway EC. The Colorado thyroid disease prevalence study. Arch Intern Med 2000;160:526-534.
4. Sawin CT, Chopra D, Azizi F, Mannix JE, Bacharach P. The aging thyroid.Increasing prevalence of elevated serum thyrotropin levels in the elderly. JAMA 1979;242:247-250.
5. Petersen K, Lindstedt G, Lundberg PA, Bengtsson C, Lapidus L, Nystrom E. Thyroid disease in middle-aged and elderly Swedish women: thyroid-related hormones, thyroid dysfunction and goitre in relation to age and smoking. J Intern Med 1991;229:407-413.
6. Eggertsen R, Petersen K, Lundberg PA, Nystorm E, Lindstedt G. Screening for thyroid disease in a primary care unit with a thyroid stimulating hormone assay with a low detection limit. BMJ 1988;297:1586-1592.
7. Parle JV, Franklyn JA, Cross KW, Jones SC, Sheppard MC. Prevalence and follow up of abnormal thyrotropin (TSH) concentrations in the elderly in the United Kingdom. Clin Endocrinol (Oxf) 1991;34:77-83.
8. Kabadi UM. ‘Subclinical hypothyroidism’. Natural course of the syndrome during a prolonged follow-up study. Arch Intern Med 1993;153:957-961.
9. Diekman T, Lansberg PJ, Kastelein JJ, Wiersinga WM. Prevalence and correction of hypothyroidism in a large cohort of patients referred for dyslipidemia. Arch Intern Med 1995;155:1490-1495.
10. Caraccio N, Ferrannini E, Monzani F. Lipoprotein profile in subclinical hypothyroidism: response to levothyroxine replacement, a randomized placebo-controlled study. J Clin Endocrinol Metab 2002;87:1533-1538.
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