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What’s the best treatment for gestational diabetes?
There is no single approach to glycemic control that is better than another for reducing neonatal mortality and morbidity. Glycemic control—regardless of whether it involves diet, glyburide, or insulin—leads to fewer cases of shoulder dystocia, hyperbilirubinemia requiring phototherapy, nerve palsy, bone fracture, being large for gestational age, and fetal macrosomia (strength of recommendation: A).
Customize the intervention
Jon O. Neher, MD
Valley Family Medicine, Renton, Wash
Achieving solid glucose control for patients with gestational diabetes should be easy—most patients are healthy and motivated to do what is best for their babies. But a new diagnosis and blood sugar monitoring requirements can be daunting. Lifestyle changes and medications can quickly add to the sense of being overwhelmed. Fortunately, whatever brings down the blood sugar will do as therapy, so the patient can negotiate with her doctor to develop an intervention—be it diet, exercise, oral medications, insulin, or a combination—that works for her.
Evidence summary
Findings from 2 studies support the notion that the treatment of gestational diabetes decreases neonatal morbidity and mortality (TABLE).1,2 Both studies found a decrease in neonatal morbidity and mortality for those patients treated either with diet or insulin. One study found a higher rate of NICU admission in the treatment group, but the authors attributed this to physician awareness of the patient having gestational diabetes.1
TABLE
Treatment of gestational diabetes reduces neonatal morbidity and mortality
| TYPE OF STUDY | CONTROL(S) | INTERVENTION | MEONATAL MORBIDITY AND MORTALITY | ADMISSIONS TO NICU | NNT |
|---|---|---|---|---|---|
| RCT1 | GDM routine care (N=510) | GDM treated with diet or insulin (N=490) | Control: 4% Intervention: 1% | 71% diet and insulin vs 61% routine care NNH: 100 | 34 |
| Cohort2 | 1) No GDM (N=1110) | GDM treated diet or insulin (N=1110) | Control 1: 11% Control 2: 59% | Not reported | 2* |
| 2) GDM not treated (due to late entry to care) (N=555) | Intervention: 15% | ||||
| *Compared with patients presenting late. | |||||
| GDM, gestational diabetes mellitus; NNH, number needed to harm; NNT, number needed to treat. | |||||
Glyburide vs insulin
A high-quality randomized controlled trial comparing glyburide with insulin among 404 women found no difference in maternal hypoglycemia, neonatal mortality, or neonatal features and outcomes (including birthweight, NICU admissions, hyperbilirubinemia, and hypoglycemia; P ≥.25).3 Although this was a fairly large trial, it may have been underpowered since it found small differences in such rare outcomes.
Similarly, a retrospective study comparing glyburide with insulin in 584 women found little difference between the 2 approaches. Women in the glyburide group had better glycemic control, but the women in the insulin group started with higher initial blood sugars.4 The glyburide group had fewer NICU admissions than the insulin group (number needed to treat [NNT]=11), but higher rates of jaundice (number needed to harm [NNH]=25), pre-eclampsia (NNH=17), and maternal hypoglycemia (NNH=8). All other neonatal outcomes were similar between groups.
Diet alone vs diet + insulin
A meta-analysis combined 6 RCTs comparing diet alone with diet plus insulin in a total of 1281 women.5 Insulin was moderately superior to diet in preventing fetal macrosomia (NNT=11; 95% confidence interval, 6–36), but not in rates of hypoglycemia, hypocalcemia, hyperbilirubinemia, or congenital malformations.
Recommendations from others
The American Diabetes Association (ADA) recommends that women diagnosed with gestational diabetes by a 3-hour glucose tolerance test receive nutritional counseling from a registered dietician. The ADA also recommends insulin therapy if diet is unsuccessful in achieving fasting glucose <105 mg/dL, 1-hour postprandial <155 mg/dL, or 2-hour postprandial <130 mg/dL.6
The American College of Obstetricians and Gynecologists (ACOG) recommends the use of diet or insulin to achieve 1-hour postprandial blood sugar of 130 mg/dL.7 Both ADA and ACOG indicate that further studies are needed to establish the safety of glyburide before general use can be recommended.
1. Crowther CA, Hiller JE, Moss JR, et al. Effect of treatment of gestational diabetes mellitus on pregnancy outcomes. N Engl J Med 2005;352:2477-2486.
2. Langer O, Yogev Y, Most O, Xenakis EM. Gestational diabetes: The consequences of not treating. Am J Obstet Gynecol 2005;192:989-997.
3. Langer O, Conway DL, Berkus MD, Xenakis EM, Gonzales O. A comparison of glyburide and insulin in women with gestational diabetes mellitus. N Engl J Med 2000;343:1134-1138.
4. Jacobson GF, Ramos GA, Ching JY, Kirby RS, Ferrara A, Field DR. Comparison of glyburide and insulin for the management of gestational diabetes in a large managed care organization. Am J Obstet Gynecol 2005;193:118-124.
5. Giuffrida FM, Castro AA, Atallah AN, Dib SA. Diet plus insulin compared to diet alone in the treatment of gestational diabetes mellitus: A systematic review. Braz J Med Biol Res 2003;36:1297-1300.
6. American Diabetes Association. Gestational diabetes mellitus. Diabetes Care 2004;27 Suppl 1:S88-S90.
7. American College of Obstetricians and Gynecologists Committee on Practice Bulletins—Obstetrics. ACOG Practice Bulletin. Clinical Management Guidelines for Obstetrician-Gynecologists. Gestational diabetes. Obstet Gynecol 2001;98:525-538.
There is no single approach to glycemic control that is better than another for reducing neonatal mortality and morbidity. Glycemic control—regardless of whether it involves diet, glyburide, or insulin—leads to fewer cases of shoulder dystocia, hyperbilirubinemia requiring phototherapy, nerve palsy, bone fracture, being large for gestational age, and fetal macrosomia (strength of recommendation: A).
Customize the intervention
Jon O. Neher, MD
Valley Family Medicine, Renton, Wash
Achieving solid glucose control for patients with gestational diabetes should be easy—most patients are healthy and motivated to do what is best for their babies. But a new diagnosis and blood sugar monitoring requirements can be daunting. Lifestyle changes and medications can quickly add to the sense of being overwhelmed. Fortunately, whatever brings down the blood sugar will do as therapy, so the patient can negotiate with her doctor to develop an intervention—be it diet, exercise, oral medications, insulin, or a combination—that works for her.
Evidence summary
Findings from 2 studies support the notion that the treatment of gestational diabetes decreases neonatal morbidity and mortality (TABLE).1,2 Both studies found a decrease in neonatal morbidity and mortality for those patients treated either with diet or insulin. One study found a higher rate of NICU admission in the treatment group, but the authors attributed this to physician awareness of the patient having gestational diabetes.1
TABLE
Treatment of gestational diabetes reduces neonatal morbidity and mortality
| TYPE OF STUDY | CONTROL(S) | INTERVENTION | MEONATAL MORBIDITY AND MORTALITY | ADMISSIONS TO NICU | NNT |
|---|---|---|---|---|---|
| RCT1 | GDM routine care (N=510) | GDM treated with diet or insulin (N=490) | Control: 4% Intervention: 1% | 71% diet and insulin vs 61% routine care NNH: 100 | 34 |
| Cohort2 | 1) No GDM (N=1110) | GDM treated diet or insulin (N=1110) | Control 1: 11% Control 2: 59% | Not reported | 2* |
| 2) GDM not treated (due to late entry to care) (N=555) | Intervention: 15% | ||||
| *Compared with patients presenting late. | |||||
| GDM, gestational diabetes mellitus; NNH, number needed to harm; NNT, number needed to treat. | |||||
Glyburide vs insulin
A high-quality randomized controlled trial comparing glyburide with insulin among 404 women found no difference in maternal hypoglycemia, neonatal mortality, or neonatal features and outcomes (including birthweight, NICU admissions, hyperbilirubinemia, and hypoglycemia; P ≥.25).3 Although this was a fairly large trial, it may have been underpowered since it found small differences in such rare outcomes.
Similarly, a retrospective study comparing glyburide with insulin in 584 women found little difference between the 2 approaches. Women in the glyburide group had better glycemic control, but the women in the insulin group started with higher initial blood sugars.4 The glyburide group had fewer NICU admissions than the insulin group (number needed to treat [NNT]=11), but higher rates of jaundice (number needed to harm [NNH]=25), pre-eclampsia (NNH=17), and maternal hypoglycemia (NNH=8). All other neonatal outcomes were similar between groups.
Diet alone vs diet + insulin
A meta-analysis combined 6 RCTs comparing diet alone with diet plus insulin in a total of 1281 women.5 Insulin was moderately superior to diet in preventing fetal macrosomia (NNT=11; 95% confidence interval, 6–36), but not in rates of hypoglycemia, hypocalcemia, hyperbilirubinemia, or congenital malformations.
Recommendations from others
The American Diabetes Association (ADA) recommends that women diagnosed with gestational diabetes by a 3-hour glucose tolerance test receive nutritional counseling from a registered dietician. The ADA also recommends insulin therapy if diet is unsuccessful in achieving fasting glucose <105 mg/dL, 1-hour postprandial <155 mg/dL, or 2-hour postprandial <130 mg/dL.6
The American College of Obstetricians and Gynecologists (ACOG) recommends the use of diet or insulin to achieve 1-hour postprandial blood sugar of 130 mg/dL.7 Both ADA and ACOG indicate that further studies are needed to establish the safety of glyburide before general use can be recommended.
There is no single approach to glycemic control that is better than another for reducing neonatal mortality and morbidity. Glycemic control—regardless of whether it involves diet, glyburide, or insulin—leads to fewer cases of shoulder dystocia, hyperbilirubinemia requiring phototherapy, nerve palsy, bone fracture, being large for gestational age, and fetal macrosomia (strength of recommendation: A).
Customize the intervention
Jon O. Neher, MD
Valley Family Medicine, Renton, Wash
Achieving solid glucose control for patients with gestational diabetes should be easy—most patients are healthy and motivated to do what is best for their babies. But a new diagnosis and blood sugar monitoring requirements can be daunting. Lifestyle changes and medications can quickly add to the sense of being overwhelmed. Fortunately, whatever brings down the blood sugar will do as therapy, so the patient can negotiate with her doctor to develop an intervention—be it diet, exercise, oral medications, insulin, or a combination—that works for her.
Evidence summary
Findings from 2 studies support the notion that the treatment of gestational diabetes decreases neonatal morbidity and mortality (TABLE).1,2 Both studies found a decrease in neonatal morbidity and mortality for those patients treated either with diet or insulin. One study found a higher rate of NICU admission in the treatment group, but the authors attributed this to physician awareness of the patient having gestational diabetes.1
TABLE
Treatment of gestational diabetes reduces neonatal morbidity and mortality
| TYPE OF STUDY | CONTROL(S) | INTERVENTION | MEONATAL MORBIDITY AND MORTALITY | ADMISSIONS TO NICU | NNT |
|---|---|---|---|---|---|
| RCT1 | GDM routine care (N=510) | GDM treated with diet or insulin (N=490) | Control: 4% Intervention: 1% | 71% diet and insulin vs 61% routine care NNH: 100 | 34 |
| Cohort2 | 1) No GDM (N=1110) | GDM treated diet or insulin (N=1110) | Control 1: 11% Control 2: 59% | Not reported | 2* |
| 2) GDM not treated (due to late entry to care) (N=555) | Intervention: 15% | ||||
| *Compared with patients presenting late. | |||||
| GDM, gestational diabetes mellitus; NNH, number needed to harm; NNT, number needed to treat. | |||||
Glyburide vs insulin
A high-quality randomized controlled trial comparing glyburide with insulin among 404 women found no difference in maternal hypoglycemia, neonatal mortality, or neonatal features and outcomes (including birthweight, NICU admissions, hyperbilirubinemia, and hypoglycemia; P ≥.25).3 Although this was a fairly large trial, it may have been underpowered since it found small differences in such rare outcomes.
Similarly, a retrospective study comparing glyburide with insulin in 584 women found little difference between the 2 approaches. Women in the glyburide group had better glycemic control, but the women in the insulin group started with higher initial blood sugars.4 The glyburide group had fewer NICU admissions than the insulin group (number needed to treat [NNT]=11), but higher rates of jaundice (number needed to harm [NNH]=25), pre-eclampsia (NNH=17), and maternal hypoglycemia (NNH=8). All other neonatal outcomes were similar between groups.
Diet alone vs diet + insulin
A meta-analysis combined 6 RCTs comparing diet alone with diet plus insulin in a total of 1281 women.5 Insulin was moderately superior to diet in preventing fetal macrosomia (NNT=11; 95% confidence interval, 6–36), but not in rates of hypoglycemia, hypocalcemia, hyperbilirubinemia, or congenital malformations.
Recommendations from others
The American Diabetes Association (ADA) recommends that women diagnosed with gestational diabetes by a 3-hour glucose tolerance test receive nutritional counseling from a registered dietician. The ADA also recommends insulin therapy if diet is unsuccessful in achieving fasting glucose <105 mg/dL, 1-hour postprandial <155 mg/dL, or 2-hour postprandial <130 mg/dL.6
The American College of Obstetricians and Gynecologists (ACOG) recommends the use of diet or insulin to achieve 1-hour postprandial blood sugar of 130 mg/dL.7 Both ADA and ACOG indicate that further studies are needed to establish the safety of glyburide before general use can be recommended.
1. Crowther CA, Hiller JE, Moss JR, et al. Effect of treatment of gestational diabetes mellitus on pregnancy outcomes. N Engl J Med 2005;352:2477-2486.
2. Langer O, Yogev Y, Most O, Xenakis EM. Gestational diabetes: The consequences of not treating. Am J Obstet Gynecol 2005;192:989-997.
3. Langer O, Conway DL, Berkus MD, Xenakis EM, Gonzales O. A comparison of glyburide and insulin in women with gestational diabetes mellitus. N Engl J Med 2000;343:1134-1138.
4. Jacobson GF, Ramos GA, Ching JY, Kirby RS, Ferrara A, Field DR. Comparison of glyburide and insulin for the management of gestational diabetes in a large managed care organization. Am J Obstet Gynecol 2005;193:118-124.
5. Giuffrida FM, Castro AA, Atallah AN, Dib SA. Diet plus insulin compared to diet alone in the treatment of gestational diabetes mellitus: A systematic review. Braz J Med Biol Res 2003;36:1297-1300.
6. American Diabetes Association. Gestational diabetes mellitus. Diabetes Care 2004;27 Suppl 1:S88-S90.
7. American College of Obstetricians and Gynecologists Committee on Practice Bulletins—Obstetrics. ACOG Practice Bulletin. Clinical Management Guidelines for Obstetrician-Gynecologists. Gestational diabetes. Obstet Gynecol 2001;98:525-538.
1. Crowther CA, Hiller JE, Moss JR, et al. Effect of treatment of gestational diabetes mellitus on pregnancy outcomes. N Engl J Med 2005;352:2477-2486.
2. Langer O, Yogev Y, Most O, Xenakis EM. Gestational diabetes: The consequences of not treating. Am J Obstet Gynecol 2005;192:989-997.
3. Langer O, Conway DL, Berkus MD, Xenakis EM, Gonzales O. A comparison of glyburide and insulin in women with gestational diabetes mellitus. N Engl J Med 2000;343:1134-1138.
4. Jacobson GF, Ramos GA, Ching JY, Kirby RS, Ferrara A, Field DR. Comparison of glyburide and insulin for the management of gestational diabetes in a large managed care organization. Am J Obstet Gynecol 2005;193:118-124.
5. Giuffrida FM, Castro AA, Atallah AN, Dib SA. Diet plus insulin compared to diet alone in the treatment of gestational diabetes mellitus: A systematic review. Braz J Med Biol Res 2003;36:1297-1300.
6. American Diabetes Association. Gestational diabetes mellitus. Diabetes Care 2004;27 Suppl 1:S88-S90.
7. American College of Obstetricians and Gynecologists Committee on Practice Bulletins—Obstetrics. ACOG Practice Bulletin. Clinical Management Guidelines for Obstetrician-Gynecologists. Gestational diabetes. Obstet Gynecol 2001;98:525-538.
Evidence-based answers from the Family Physicians Inquiries Network
What evaluation is best for an isolated, enlarged cervical lymph node?
The evaluation and follow-up of an isolated, enlarged cervical lymph node is determined by the presence of inflammation, duration, size, and associated symptoms. For patients with inflammatory symptoms (ie, fever, pain, erythema, and recent infection), a single course of broad-spectrum antibiotic and reassessment in 1 to 2 weeks is reasonable (strength of recommendation [SOR]: C, expert opinion). If lymph node enlargement persists despite antibiotics, yet an infectious or inflammatory cause is still suspected, further evaluation may include a PPD skin test and chest radiograph1 (SOR: C, expert opinion). For patients without initial inflammatory symptoms, biopsy is recommended if the lymph node enlargement persists beyond 4 to 6 weeks, continues to enlarge, or is >3 cm1 (SOR: C, expert opinion). Biopsy is also indicated if there is a supraclavicular lymph node or concomitant constitutional symptoms (weight loss or night sweats)2 (SOR: B, case series). Ultrasound or computerized tomography (CT) can also be helpful in determining which method of biopsy to choose3 (SOR: B, case series). Fine-needle aspiration is a minimally invasive method for obtaining a tissue sample, but excisional biopsy can provide a definitive diagnosis2-6 (SOR: B, case series).
For those with no risk factors and an uncomplicated exam, counsel “tincture of time”
Paul Crawford, MD
US Air Force–Eglin Family Practice Residency, Eglin, Air Force Base, Fla
The foundation of managing solitary enlarged cervical nodes is a good history and physical. For patients with a benign story, no risk factors, and an uncomplicated exam, I always counsel “tincture of time” as the first-line diagnostic test.
However, this changes when patients present with risk factors for malignancy (such as being older, male, white. or with a supraclavicular node) and a worrisome story or exam finding. In these cases, watchful waiting may delay diagnosis. Sometimes, in spite of my best efforts to reassure low-risk patients, their fear and anxiety derail my attempts to practice good medicine. For these patients, the only harm an ultra-sound does is to the wallet.
Evidence summary
Limited research exists in this area. Practice today is guided by clinical judgment, anecdotal evidence, and historical teaching. Assessment for inflammation and malignancy risk factors contributes to the diagnosis.
Lymph nodes with concomitant malignancy risk factors warrant immediate evaluation. For lymph nodes without signs or symptoms of inflammation or malignancy, observation for 4 to 6 weeks has been recommended. Further evaluation with imaging or biopsy is indicated if the node persists beyond 4 to 6 weeks, continues to enlarge, is located within the supraclavicular fossa, or is >3 cm.1
A study of 550 patients identified 5 significant predictors of malignancy: male gender (risk ratio [RR]=2.72; 95% confidence interval [CI], 1.63–4.56), increasing age (RR=1.05; 95% CI, 1.04–1.07), white ethnicity (RR=3.01; 95% CI, 1.19–7.6), supraclavicular lymph nodes (RR=3.72; 95% CI, 1.52–9.12), and 2 or more regions of lymph nodes (RR=6.41; 95% CI, 2.82–14.58).5
For lymph nodes with inflammatory symptoms, further evaluation (including imaging) is indicated if there is no response to antibiotics. CT with contrast is considered the gold standard. However, a study of 50 patients with lymphadenopathy on CT demonstrated the sensitivity of ultrasound was 92% in identifying the same nodes.3 Another study demonstrated an ultrasound sensitivity of 100% and specificity of 97% for 154 patients with lymphadenopathy.5
Histologic evaluation after excisional biopsy is the gold standard for diagnosis. Fine-needle aspiration is an alternate, minimally invasive option for further work-up. Fine-needle aspiration had a sensitivity of 49% and specificity of 97% in a study of 550 patients.5 In a study of 309 patients with supraclavicular lymphadenopathy, fine-needle aspiration had a sensitivity of 97%, a specificity of 98%, and a positive predictive value of 98%. A study of 94 patients found that clinical exam alone was 78% sensitive in diagnosing the cause of lymphadenopathy; this improved to 93% sensitivity with fine-needle aspiration.6
Fine-needle aspiration has a higher rate of false negatives. A study of 1103 patients found a 97% sensitivity (3.4% false-negative rate) and a 99% specificity (0.9% false-positive rate) for fine-needle aspiration.4 In cases where pathology is equivocal, or where concern for malignancy is exceptionally high, excisional biopsy provides a more definitive diagnosis.
Recommendations from others
Cecil’s Textbook of Medicine recommends observing the nodes when they are soft and smaller than 2 to 3 cm and the patient has no obvious systemic illness. They note that performing a complete blood count and peripheral smear exam can aid in diagnosing systemic illness and that antibiotics are often given. They suggest performing a biopsy if the lymph node does not regress within a few weeks or if it grows. They also say the art of medicine is at play here and that if patients are particularly anxious, biopsy may be done more quickly.7
Harrison’s Manual of Medicine specifies that nodes >4 cm located in the subclavicular or scalene area or hard nodes fixed to surrounding tissues should be biopsied immediately, and that tender nodes are most often benign.8
1. Schwetschenau E, Kelley DJ. The adult neck mass. Am Fam Physician 2002;66:831-838.
2. Ellison E, LaPuerta P, Martin SE. Supraclavicular masses: Results of a series of 309 cases biopsied by fine needle aspiration. Head Neck 1999;21:239-246.
3. Beissert M, Jenett M, Wetzler T, Hinterseher I, Kessler C, Hahn D. Enlarged lymph nodes of the neck: evaluation with parallel extended field-of-view sonographic sequences. J Ultrasound Med 2000;19:195-200.
4. Steel BL, Schwartz MR, Ramzy I. Fine needle aspiration biopsy in the diagnosis of lymphadenopathy in 1,103 patients. Role, limitations and analysis of diagnostic pitfalls. Acta Cytol 1995;39:76-81.
5. Chau I, Kelleher MT, Cunningham D, et al. Rapid access multidisciplinary lymph node diagnostic clinic: Analysis of 550 patients. Br J Cancer 2003;88:354-361.
6. Al-Mulhim AS, Al-Ghamdi AM, Al-Marzooq YM, et al. The role of fine needle aspiration cytology and imprint cytology in cervical lymphadenopathy. Saudi Med J 2004;25:862-865.
7. Armitage JO. Approach to the patient with lymphadenopathy and splenomegaly. In Goldman L, Ausiello A (eds), Cecil Textbook of Medicine, 22nd ed. Chapter 164. Philadelphia, Pa: WB Saunders Co; 2004.
8. Braunwald E, Fauci AS, Kasper DL, et al. Harrison’s Manual of Medicine. Chapter 28. New york: McGraw-Hill Professional; 2002.
The evaluation and follow-up of an isolated, enlarged cervical lymph node is determined by the presence of inflammation, duration, size, and associated symptoms. For patients with inflammatory symptoms (ie, fever, pain, erythema, and recent infection), a single course of broad-spectrum antibiotic and reassessment in 1 to 2 weeks is reasonable (strength of recommendation [SOR]: C, expert opinion). If lymph node enlargement persists despite antibiotics, yet an infectious or inflammatory cause is still suspected, further evaluation may include a PPD skin test and chest radiograph1 (SOR: C, expert opinion). For patients without initial inflammatory symptoms, biopsy is recommended if the lymph node enlargement persists beyond 4 to 6 weeks, continues to enlarge, or is >3 cm1 (SOR: C, expert opinion). Biopsy is also indicated if there is a supraclavicular lymph node or concomitant constitutional symptoms (weight loss or night sweats)2 (SOR: B, case series). Ultrasound or computerized tomography (CT) can also be helpful in determining which method of biopsy to choose3 (SOR: B, case series). Fine-needle aspiration is a minimally invasive method for obtaining a tissue sample, but excisional biopsy can provide a definitive diagnosis2-6 (SOR: B, case series).
For those with no risk factors and an uncomplicated exam, counsel “tincture of time”
Paul Crawford, MD
US Air Force–Eglin Family Practice Residency, Eglin, Air Force Base, Fla
The foundation of managing solitary enlarged cervical nodes is a good history and physical. For patients with a benign story, no risk factors, and an uncomplicated exam, I always counsel “tincture of time” as the first-line diagnostic test.
However, this changes when patients present with risk factors for malignancy (such as being older, male, white. or with a supraclavicular node) and a worrisome story or exam finding. In these cases, watchful waiting may delay diagnosis. Sometimes, in spite of my best efforts to reassure low-risk patients, their fear and anxiety derail my attempts to practice good medicine. For these patients, the only harm an ultra-sound does is to the wallet.
Evidence summary
Limited research exists in this area. Practice today is guided by clinical judgment, anecdotal evidence, and historical teaching. Assessment for inflammation and malignancy risk factors contributes to the diagnosis.
Lymph nodes with concomitant malignancy risk factors warrant immediate evaluation. For lymph nodes without signs or symptoms of inflammation or malignancy, observation for 4 to 6 weeks has been recommended. Further evaluation with imaging or biopsy is indicated if the node persists beyond 4 to 6 weeks, continues to enlarge, is located within the supraclavicular fossa, or is >3 cm.1
A study of 550 patients identified 5 significant predictors of malignancy: male gender (risk ratio [RR]=2.72; 95% confidence interval [CI], 1.63–4.56), increasing age (RR=1.05; 95% CI, 1.04–1.07), white ethnicity (RR=3.01; 95% CI, 1.19–7.6), supraclavicular lymph nodes (RR=3.72; 95% CI, 1.52–9.12), and 2 or more regions of lymph nodes (RR=6.41; 95% CI, 2.82–14.58).5
For lymph nodes with inflammatory symptoms, further evaluation (including imaging) is indicated if there is no response to antibiotics. CT with contrast is considered the gold standard. However, a study of 50 patients with lymphadenopathy on CT demonstrated the sensitivity of ultrasound was 92% in identifying the same nodes.3 Another study demonstrated an ultrasound sensitivity of 100% and specificity of 97% for 154 patients with lymphadenopathy.5
Histologic evaluation after excisional biopsy is the gold standard for diagnosis. Fine-needle aspiration is an alternate, minimally invasive option for further work-up. Fine-needle aspiration had a sensitivity of 49% and specificity of 97% in a study of 550 patients.5 In a study of 309 patients with supraclavicular lymphadenopathy, fine-needle aspiration had a sensitivity of 97%, a specificity of 98%, and a positive predictive value of 98%. A study of 94 patients found that clinical exam alone was 78% sensitive in diagnosing the cause of lymphadenopathy; this improved to 93% sensitivity with fine-needle aspiration.6
Fine-needle aspiration has a higher rate of false negatives. A study of 1103 patients found a 97% sensitivity (3.4% false-negative rate) and a 99% specificity (0.9% false-positive rate) for fine-needle aspiration.4 In cases where pathology is equivocal, or where concern for malignancy is exceptionally high, excisional biopsy provides a more definitive diagnosis.
Recommendations from others
Cecil’s Textbook of Medicine recommends observing the nodes when they are soft and smaller than 2 to 3 cm and the patient has no obvious systemic illness. They note that performing a complete blood count and peripheral smear exam can aid in diagnosing systemic illness and that antibiotics are often given. They suggest performing a biopsy if the lymph node does not regress within a few weeks or if it grows. They also say the art of medicine is at play here and that if patients are particularly anxious, biopsy may be done more quickly.7
Harrison’s Manual of Medicine specifies that nodes >4 cm located in the subclavicular or scalene area or hard nodes fixed to surrounding tissues should be biopsied immediately, and that tender nodes are most often benign.8
The evaluation and follow-up of an isolated, enlarged cervical lymph node is determined by the presence of inflammation, duration, size, and associated symptoms. For patients with inflammatory symptoms (ie, fever, pain, erythema, and recent infection), a single course of broad-spectrum antibiotic and reassessment in 1 to 2 weeks is reasonable (strength of recommendation [SOR]: C, expert opinion). If lymph node enlargement persists despite antibiotics, yet an infectious or inflammatory cause is still suspected, further evaluation may include a PPD skin test and chest radiograph1 (SOR: C, expert opinion). For patients without initial inflammatory symptoms, biopsy is recommended if the lymph node enlargement persists beyond 4 to 6 weeks, continues to enlarge, or is >3 cm1 (SOR: C, expert opinion). Biopsy is also indicated if there is a supraclavicular lymph node or concomitant constitutional symptoms (weight loss or night sweats)2 (SOR: B, case series). Ultrasound or computerized tomography (CT) can also be helpful in determining which method of biopsy to choose3 (SOR: B, case series). Fine-needle aspiration is a minimally invasive method for obtaining a tissue sample, but excisional biopsy can provide a definitive diagnosis2-6 (SOR: B, case series).
For those with no risk factors and an uncomplicated exam, counsel “tincture of time”
Paul Crawford, MD
US Air Force–Eglin Family Practice Residency, Eglin, Air Force Base, Fla
The foundation of managing solitary enlarged cervical nodes is a good history and physical. For patients with a benign story, no risk factors, and an uncomplicated exam, I always counsel “tincture of time” as the first-line diagnostic test.
However, this changes when patients present with risk factors for malignancy (such as being older, male, white. or with a supraclavicular node) and a worrisome story or exam finding. In these cases, watchful waiting may delay diagnosis. Sometimes, in spite of my best efforts to reassure low-risk patients, their fear and anxiety derail my attempts to practice good medicine. For these patients, the only harm an ultra-sound does is to the wallet.
Evidence summary
Limited research exists in this area. Practice today is guided by clinical judgment, anecdotal evidence, and historical teaching. Assessment for inflammation and malignancy risk factors contributes to the diagnosis.
Lymph nodes with concomitant malignancy risk factors warrant immediate evaluation. For lymph nodes without signs or symptoms of inflammation or malignancy, observation for 4 to 6 weeks has been recommended. Further evaluation with imaging or biopsy is indicated if the node persists beyond 4 to 6 weeks, continues to enlarge, is located within the supraclavicular fossa, or is >3 cm.1
A study of 550 patients identified 5 significant predictors of malignancy: male gender (risk ratio [RR]=2.72; 95% confidence interval [CI], 1.63–4.56), increasing age (RR=1.05; 95% CI, 1.04–1.07), white ethnicity (RR=3.01; 95% CI, 1.19–7.6), supraclavicular lymph nodes (RR=3.72; 95% CI, 1.52–9.12), and 2 or more regions of lymph nodes (RR=6.41; 95% CI, 2.82–14.58).5
For lymph nodes with inflammatory symptoms, further evaluation (including imaging) is indicated if there is no response to antibiotics. CT with contrast is considered the gold standard. However, a study of 50 patients with lymphadenopathy on CT demonstrated the sensitivity of ultrasound was 92% in identifying the same nodes.3 Another study demonstrated an ultrasound sensitivity of 100% and specificity of 97% for 154 patients with lymphadenopathy.5
Histologic evaluation after excisional biopsy is the gold standard for diagnosis. Fine-needle aspiration is an alternate, minimally invasive option for further work-up. Fine-needle aspiration had a sensitivity of 49% and specificity of 97% in a study of 550 patients.5 In a study of 309 patients with supraclavicular lymphadenopathy, fine-needle aspiration had a sensitivity of 97%, a specificity of 98%, and a positive predictive value of 98%. A study of 94 patients found that clinical exam alone was 78% sensitive in diagnosing the cause of lymphadenopathy; this improved to 93% sensitivity with fine-needle aspiration.6
Fine-needle aspiration has a higher rate of false negatives. A study of 1103 patients found a 97% sensitivity (3.4% false-negative rate) and a 99% specificity (0.9% false-positive rate) for fine-needle aspiration.4 In cases where pathology is equivocal, or where concern for malignancy is exceptionally high, excisional biopsy provides a more definitive diagnosis.
Recommendations from others
Cecil’s Textbook of Medicine recommends observing the nodes when they are soft and smaller than 2 to 3 cm and the patient has no obvious systemic illness. They note that performing a complete blood count and peripheral smear exam can aid in diagnosing systemic illness and that antibiotics are often given. They suggest performing a biopsy if the lymph node does not regress within a few weeks or if it grows. They also say the art of medicine is at play here and that if patients are particularly anxious, biopsy may be done more quickly.7
Harrison’s Manual of Medicine specifies that nodes >4 cm located in the subclavicular or scalene area or hard nodes fixed to surrounding tissues should be biopsied immediately, and that tender nodes are most often benign.8
1. Schwetschenau E, Kelley DJ. The adult neck mass. Am Fam Physician 2002;66:831-838.
2. Ellison E, LaPuerta P, Martin SE. Supraclavicular masses: Results of a series of 309 cases biopsied by fine needle aspiration. Head Neck 1999;21:239-246.
3. Beissert M, Jenett M, Wetzler T, Hinterseher I, Kessler C, Hahn D. Enlarged lymph nodes of the neck: evaluation with parallel extended field-of-view sonographic sequences. J Ultrasound Med 2000;19:195-200.
4. Steel BL, Schwartz MR, Ramzy I. Fine needle aspiration biopsy in the diagnosis of lymphadenopathy in 1,103 patients. Role, limitations and analysis of diagnostic pitfalls. Acta Cytol 1995;39:76-81.
5. Chau I, Kelleher MT, Cunningham D, et al. Rapid access multidisciplinary lymph node diagnostic clinic: Analysis of 550 patients. Br J Cancer 2003;88:354-361.
6. Al-Mulhim AS, Al-Ghamdi AM, Al-Marzooq YM, et al. The role of fine needle aspiration cytology and imprint cytology in cervical lymphadenopathy. Saudi Med J 2004;25:862-865.
7. Armitage JO. Approach to the patient with lymphadenopathy and splenomegaly. In Goldman L, Ausiello A (eds), Cecil Textbook of Medicine, 22nd ed. Chapter 164. Philadelphia, Pa: WB Saunders Co; 2004.
8. Braunwald E, Fauci AS, Kasper DL, et al. Harrison’s Manual of Medicine. Chapter 28. New york: McGraw-Hill Professional; 2002.
1. Schwetschenau E, Kelley DJ. The adult neck mass. Am Fam Physician 2002;66:831-838.
2. Ellison E, LaPuerta P, Martin SE. Supraclavicular masses: Results of a series of 309 cases biopsied by fine needle aspiration. Head Neck 1999;21:239-246.
3. Beissert M, Jenett M, Wetzler T, Hinterseher I, Kessler C, Hahn D. Enlarged lymph nodes of the neck: evaluation with parallel extended field-of-view sonographic sequences. J Ultrasound Med 2000;19:195-200.
4. Steel BL, Schwartz MR, Ramzy I. Fine needle aspiration biopsy in the diagnosis of lymphadenopathy in 1,103 patients. Role, limitations and analysis of diagnostic pitfalls. Acta Cytol 1995;39:76-81.
5. Chau I, Kelleher MT, Cunningham D, et al. Rapid access multidisciplinary lymph node diagnostic clinic: Analysis of 550 patients. Br J Cancer 2003;88:354-361.
6. Al-Mulhim AS, Al-Ghamdi AM, Al-Marzooq YM, et al. The role of fine needle aspiration cytology and imprint cytology in cervical lymphadenopathy. Saudi Med J 2004;25:862-865.
7. Armitage JO. Approach to the patient with lymphadenopathy and splenomegaly. In Goldman L, Ausiello A (eds), Cecil Textbook of Medicine, 22nd ed. Chapter 164. Philadelphia, Pa: WB Saunders Co; 2004.
8. Braunwald E, Fauci AS, Kasper DL, et al. Harrison’s Manual of Medicine. Chapter 28. New york: McGraw-Hill Professional; 2002.
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