During a routine physical examination, a 65-year-old man wants to find out if he has “Low T.” He complains of fatigue, decreased libido, and erectile dysfunction (ED) for the past five years. He has a history of type 2 diabetes, hypertension, hyperlipidemia, obstructive sleep apnea, and chronic low back pain. His current medications include metformin, glipizide, lisinopril, atorvastatin, and hydrocodone for back pain. Given these clinical features, the next step will be to find out if he has hypogonadism (androgen ­deficiency).

The Endocrine Society defines hypogonadism as a clinical syndrome in which the testes produce insufficient testosterone as a consequence of an interruption of the hypothalamic-­pituitary-testicular axis. Although prevalence is high in older men, the Endocrine Society does not recommend screening the general population for hypogonadism.¹ Rather, screening should be limited to patients with clinical conditions associated with high prevalence of hypogonadism. Of note, approximately 30% of adults with type 2 diabetes have a subnormal testosterone concentration.²

Q: What is pertinent in the history?

The first step in evaluation of hypogonadism is a detailed history. Signs and symptoms such as decreased libido, hot flashes, decreased shaving frequency, breast enlargement/tenderness, and decreased testicular size are highly suggestive of hypogonadism. Other, less specific signs and symptoms include dysthymia, poor concentration, sleep disturbances, fatigue, reduction in muscle strength, and diminished work performance.

If these signs and symptoms are present, the likelihood of hypogonadism is high and further evaluation is needed.^1,3 Note any history of alcoholism, liver problems, and testicular trauma or surgery.

A detailed medication history is also important. Some medications, such as opiates, can affect the release of gonadotropins. Among men taking long-term opiates for chronic noncancer pain, the prevalence of hypogonadism is 75%.⁴ Other drugs, such as spironolactone, can block the androgen effect and lead to hypogonadism.¹

Recent reports have suggested an association between testosterone replacement therapy and increased cardiovascular events, making a detailed cardiovascular history essential.^5,6 One study found that men ages 75 and older with limited mobility and other comorbidities who used testosterone gel had an increased risk for cardiovascular events.⁷ Therefore, clinicians need to be cognizant of this risk when considering testosterone therapy for their patients.

On the next page: Physical exam, lab tests, and treatments >>

Q: What does the physical exam reveal?

In hypogonadotropic hy­ po­gonadism, physical examination does not usually provide much information, as compared to congenital hypogonadal syndromes (eg, Klinefelter and ­Kallmann syndromes). However, small testicular volume and/or gynecomastia would indicate hypogonadism.

Q: What lab tests should be ordered?

Serum total and free testosterone should be measured, preferably by liquid gas chromatography. The sample should be drawn before 10 am to limit the effects of diurnal variation. If the total testosterone is less than
300 ng/dL, a second morning sample should be drawn and tested. Serum prolactin, follicle-stimulating hormone (FSH) and luteinizing hormone (LH), complete blood count, prostate-specific antigen (PSA), comprehensive metabolic panel, and ferritin should also be measured.

There is generally little benefit to testosterone therapy when total testosterone is greater than 350 ng/dL.⁸ The level of testosterone at which hypogonadal symptoms manifest and testosterone replacement provides improvement is yet to be determined. Buvat et al suggest that men with total testosterone levels less than 230 ng/dL usually benefit from therapy.⁸ If the total testosterone level is less than 150 ng/dL in the setting of secondary hypogonadism (low to low-normal LH/FSH) or if prolactin is elevated, MRI of the sella is recommended to rule out pituitary adenoma.¹

Q: Once the diagnosis is confirmed, what treatment should you recommend?

The goal of therapy for confirmed hypogonadism is to normalize the testosterone level. Testosterone replacement therapy may help to improve libido, fatigue, muscle strength, and bone density. However, in the elderly (particularly those older than 70), these therapeutic benefits have not been proven. Therefore, before initiating therapy, the clinician should discuss in detail the risks versus the benefits of testosterone replacement for a particular patient.

Simple lifestyle modifications, such as weight loss and exercise, have been shown to increase total and free testosterone levels.^3,8 For patients with obstructive sleep apnea (OSA), a known risk factor for hypogonadism, compliance with CPAP therapy has been associated with modest improvement in testosterone level. If it is appropriate for the patient to discontinue use of certain medications, such as opiates, he or she may experience an improvement in testosterone level as a result.

If the patient’s testosterone levels remain low after these changes have been implemented, consider testosterone therapy. Testosterone products currently available in the United States include transdermal preparations (gel, patch), intramuscular injection, and subcutaneous pellets.

On the next page: Contraindications, adverse effects, and follow-up >>

Q: What are the contraindications to testosterone therapy?

Testosterone therapy is contraindicated in patients with metastatic prostate cancer and breast cancer. An unevaluated prostate nodule, indurated prostate, PSA greater than 4 ng/mL, elevated hematocrit (>50%), severe lower urinary tract symptoms, poorly controlled congestive heart failure, and untreated severe OSA are associated with moderate to high risk for adverse outcomes; the Endocrine Society has recommended against using testosterone in affected patients.¹

Q: What are the adverse effects of testosterone replacement therapy?

Testosterone replacement may worsen symptoms of benign prostatic hyperplasia (ie, urinary urgency, hesitancy, and frequency). Also, testosterone replacement can lead to marked elevation of hemoglobin and hematocrit levels.

Increased cardiovascular events have been associated with androgen replacement, especially in men with prior coronary artery disease. A positive cardiovascular history necessitates discussion with the patient regarding the risks versus the benefits of testosterone replacement therapy.⁵ In a recent study of obese, hypogonadal men with severe OSA, testosterone therapy was associated with transient worsening of sleep apnea.⁹

Q: What does monitoring/ follow-up entail?

In patients with long-standing hypogonadism, a lower starting dose of testosterone is recommended, which can be gradually increased. After starting testosterone therapy, patients should be monitored in the first three to six months for total ­testosterone, PSA, and hematocrit and for improvement of symptoms (ie, fatigue, ED, decreased libido) or worsening of benign prostatic hyperplasia signs/symptoms.

For men ages 40 and older, if the baseline PSA is greater than 0.6 ng/mL, a digital rectal exam (DRE) is recommended prior to initiation of therapy and should be followed in accordance with prostate cancer screening guidelines.¹

Patients placed on testosterone cypionate/enanthate IM in­jections should have their testosterone checked at a midpoint between their injections, with the target testosterone level between 400 and 700 ng/dL.¹ For those using gel or transdermal preparations, a morning total testosterone level should be measured.

Urology consultation is recommended if the PSA concentration rises by 1.4 ng/dL within 12 months, if the American Urological Association/International Prostate Symptom Score is greater than 19, or if there is an abnormal DRE.^1,8 Treatment with testosterone should be postponed or withheld if the patient’s hematocrit is greater than 54% but may be resumed when it has decreased to normal levels.¹ 

On the next page: References >>

REFERENCES

1. Bhasin S, Cunningham GR, Hayes FJ, et al. Testosterone therapy in men with androgen deficiency syndromes: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2010;95(6):2536-2559.

2. Dandona P, Dhindsa S. Update: hypogonadotropic hypogonadism in type 2 diabetes and obesity. J Clin Endocrinol Metab. 2011;96(9): 2643-2651.

3. Tajar A, Forti G, O’Neill TW, et al. Characteristics of secondary, primary, and compensated hypogonadism in aging men: evidence from the European Male Ageing Study. J Clin Endocrinol Metab. 2010;95(4):1810-1818.

4. Fraser LA, Morrison D, Morley-Forster P, et al. Oral opioids for chronic non-cancer pain: higher prevalence of hypogonadism in men than in women. Exp Clin Endocrinol Diabetes. 2009;117(1):38-43.

5. Vigen R, O’Donnell CI, Baron AE, et al. Association of testosterone therapy with mortality, myocardial infarction, and stroke in men with low testosterone levels. JAMA. 2013;310(17): 1829-1836.

6. Finkle WD, Greenland S, Ridgeway GK, et al. Increased risk of non-fatal myocardial infarction following testosterone therapy prescription in men. PloS One. 2014;9(1): e85805.

7. Basaria S, Coviello AD, Travison TG, et al. Adverse events associated with testosterone admin­istration. N Engl J Med. 2010;363(2):109-122.

8. Buvat J, Maggi M, Guay A, Torres LO. Testosterone deficiency in men: systematic review and standard operating procedures for diagnosis and treatment. J Sex Med. 2013;10(1): 245-284.

9. Hoyos CM, Killick R, Yee BJ, et al. Effects of testosterone therapy on sleep and breathing in obese men with severe obstructive sleep apnoea: a randomized placebo-controlled trial. Clin Endocrinol (Oxf). 2012;77(4):
599-607.

During a routine physical examination, a 65-year-old man wants to find out if he has “Low T.” He complains of fatigue, decreased libido, and erectile dysfunction (ED) for the past five years. He has a history of type 2 diabetes, hypertension, hyperlipidemia, obstructive sleep apnea, and chronic low back pain. His current medications include metformin, glipizide, lisinopril, atorvastatin, and hydrocodone for back pain. Given these clinical features, the next step will be to find out if he has hypogonadism (androgen ­deficiency).

The Endocrine Society defines hypogonadism as a clinical syndrome in which the testes produce insufficient testosterone as a consequence of an interruption of the hypothalamic-­pituitary-testicular axis. Although prevalence is high in older men, the Endocrine Society does not recommend screening the general population for hypogonadism.¹ Rather, screening should be limited to patients with clinical conditions associated with high prevalence of hypogonadism. Of note, approximately 30% of adults with type 2 diabetes have a subnormal testosterone concentration.²

Q: What is pertinent in the history?

The first step in evaluation of hypogonadism is a detailed history. Signs and symptoms such as decreased libido, hot flashes, decreased shaving frequency, breast enlargement/tenderness, and decreased testicular size are highly suggestive of hypogonadism. Other, less specific signs and symptoms include dysthymia, poor concentration, sleep disturbances, fatigue, reduction in muscle strength, and diminished work performance.

If these signs and symptoms are present, the likelihood of hypogonadism is high and further evaluation is needed.^1,3 Note any history of alcoholism, liver problems, and testicular trauma or surgery.

A detailed medication history is also important. Some medications, such as opiates, can affect the release of gonadotropins. Among men taking long-term opiates for chronic noncancer pain, the prevalence of hypogonadism is 75%.⁴ Other drugs, such as spironolactone, can block the androgen effect and lead to hypogonadism.¹

Recent reports have suggested an association between testosterone replacement therapy and increased cardiovascular events, making a detailed cardiovascular history essential.^5,6 One study found that men ages 75 and older with limited mobility and other comorbidities who used testosterone gel had an increased risk for cardiovascular events.⁷ Therefore, clinicians need to be cognizant of this risk when considering testosterone therapy for their patients.

On the next page: Physical exam, lab tests, and treatments >>

Q: What does the physical exam reveal?

In hypogonadotropic hy­ po­gonadism, physical examination does not usually provide much information, as compared to congenital hypogonadal syndromes (eg, Klinefelter and ­Kallmann syndromes). However, small testicular volume and/or gynecomastia would indicate hypogonadism.

Q: What lab tests should be ordered?

Serum total and free testosterone should be measured, preferably by liquid gas chromatography. The sample should be drawn before 10 am to limit the effects of diurnal variation. If the total testosterone is less than
300 ng/dL, a second morning sample should be drawn and tested. Serum prolactin, follicle-stimulating hormone (FSH) and luteinizing hormone (LH), complete blood count, prostate-specific antigen (PSA), comprehensive metabolic panel, and ferritin should also be measured.

There is generally little benefit to testosterone therapy when total testosterone is greater than 350 ng/dL.⁸ The level of testosterone at which hypogonadal symptoms manifest and testosterone replacement provides improvement is yet to be determined. Buvat et al suggest that men with total testosterone levels less than 230 ng/dL usually benefit from therapy.⁸ If the total testosterone level is less than 150 ng/dL in the setting of secondary hypogonadism (low to low-normal LH/FSH) or if prolactin is elevated, MRI of the sella is recommended to rule out pituitary adenoma.¹

Q: Once the diagnosis is confirmed, what treatment should you recommend?

The goal of therapy for confirmed hypogonadism is to normalize the testosterone level. Testosterone replacement therapy may help to improve libido, fatigue, muscle strength, and bone density. However, in the elderly (particularly those older than 70), these therapeutic benefits have not been proven. Therefore, before initiating therapy, the clinician should discuss in detail the risks versus the benefits of testosterone replacement for a particular patient.

Simple lifestyle modifications, such as weight loss and exercise, have been shown to increase total and free testosterone levels.^3,8 For patients with obstructive sleep apnea (OSA), a known risk factor for hypogonadism, compliance with CPAP therapy has been associated with modest improvement in testosterone level. If it is appropriate for the patient to discontinue use of certain medications, such as opiates, he or she may experience an improvement in testosterone level as a result.

If the patient’s testosterone levels remain low after these changes have been implemented, consider testosterone therapy. Testosterone products currently available in the United States include transdermal preparations (gel, patch), intramuscular injection, and subcutaneous pellets.

On the next page: Contraindications, adverse effects, and follow-up >>

Q: What are the contraindications to testosterone therapy?

Testosterone therapy is contraindicated in patients with metastatic prostate cancer and breast cancer. An unevaluated prostate nodule, indurated prostate, PSA greater than 4 ng/mL, elevated hematocrit (>50%), severe lower urinary tract symptoms, poorly controlled congestive heart failure, and untreated severe OSA are associated with moderate to high risk for adverse outcomes; the Endocrine Society has recommended against using testosterone in affected patients.¹

Q: What are the adverse effects of testosterone replacement therapy?

Testosterone replacement may worsen symptoms of benign prostatic hyperplasia (ie, urinary urgency, hesitancy, and frequency). Also, testosterone replacement can lead to marked elevation of hemoglobin and hematocrit levels.

Increased cardiovascular events have been associated with androgen replacement, especially in men with prior coronary artery disease. A positive cardiovascular history necessitates discussion with the patient regarding the risks versus the benefits of testosterone replacement therapy.⁵ In a recent study of obese, hypogonadal men with severe OSA, testosterone therapy was associated with transient worsening of sleep apnea.⁹

Q: What does monitoring/ follow-up entail?

In patients with long-standing hypogonadism, a lower starting dose of testosterone is recommended, which can be gradually increased. After starting testosterone therapy, patients should be monitored in the first three to six months for total ­testosterone, PSA, and hematocrit and for improvement of symptoms (ie, fatigue, ED, decreased libido) or worsening of benign prostatic hyperplasia signs/symptoms.

For men ages 40 and older, if the baseline PSA is greater than 0.6 ng/mL, a digital rectal exam (DRE) is recommended prior to initiation of therapy and should be followed in accordance with prostate cancer screening guidelines.¹

Patients placed on testosterone cypionate/enanthate IM in­jections should have their testosterone checked at a midpoint between their injections, with the target testosterone level between 400 and 700 ng/dL.¹ For those using gel or transdermal preparations, a morning total testosterone level should be measured.

Urology consultation is recommended if the PSA concentration rises by 1.4 ng/dL within 12 months, if the American Urological Association/International Prostate Symptom Score is greater than 19, or if there is an abnormal DRE.^1,8 Treatment with testosterone should be postponed or withheld if the patient’s hematocrit is greater than 54% but may be resumed when it has decreased to normal levels.¹ 

On the next page: References >>

REFERENCES

1. Bhasin S, Cunningham GR, Hayes FJ, et al. Testosterone therapy in men with androgen deficiency syndromes: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2010;95(6):2536-2559.

2. Dandona P, Dhindsa S. Update: hypogonadotropic hypogonadism in type 2 diabetes and obesity. J Clin Endocrinol Metab. 2011;96(9): 2643-2651.

3. Tajar A, Forti G, O’Neill TW, et al. Characteristics of secondary, primary, and compensated hypogonadism in aging men: evidence from the European Male Ageing Study. J Clin Endocrinol Metab. 2010;95(4):1810-1818.

4. Fraser LA, Morrison D, Morley-Forster P, et al. Oral opioids for chronic non-cancer pain: higher prevalence of hypogonadism in men than in women. Exp Clin Endocrinol Diabetes. 2009;117(1):38-43.

5. Vigen R, O’Donnell CI, Baron AE, et al. Association of testosterone therapy with mortality, myocardial infarction, and stroke in men with low testosterone levels. JAMA. 2013;310(17): 1829-1836.

6. Finkle WD, Greenland S, Ridgeway GK, et al. Increased risk of non-fatal myocardial infarction following testosterone therapy prescription in men. PloS One. 2014;9(1): e85805.

7. Basaria S, Coviello AD, Travison TG, et al. Adverse events associated with testosterone admin­istration. N Engl J Med. 2010;363(2):109-122.

8. Buvat J, Maggi M, Guay A, Torres LO. Testosterone deficiency in men: systematic review and standard operating procedures for diagnosis and treatment. J Sex Med. 2013;10(1): 245-284.

9. Hoyos CM, Killick R, Yee BJ, et al. Effects of testosterone therapy on sleep and breathing in obese men with severe obstructive sleep apnoea: a randomized placebo-controlled trial. Clin Endocrinol (Oxf). 2012;77(4):
599-607.

During a routine physical examination, a 65-year-old man wants to find out if he has “Low T.” He complains of fatigue, decreased libido, and erectile dysfunction (ED) for the past five years. He has a history of type 2 diabetes, hypertension, hyperlipidemia, obstructive sleep apnea, and chronic low back pain. His current medications include metformin, glipizide, lisinopril, atorvastatin, and hydrocodone for back pain. Given these clinical features, the next step will be to find out if he has hypogonadism (androgen ­deficiency).

The Endocrine Society defines hypogonadism as a clinical syndrome in which the testes produce insufficient testosterone as a consequence of an interruption of the hypothalamic-­pituitary-testicular axis. Although prevalence is high in older men, the Endocrine Society does not recommend screening the general population for hypogonadism.¹ Rather, screening should be limited to patients with clinical conditions associated with high prevalence of hypogonadism. Of note, approximately 30% of adults with type 2 diabetes have a subnormal testosterone concentration.²

Q: What is pertinent in the history?

The first step in evaluation of hypogonadism is a detailed history. Signs and symptoms such as decreased libido, hot flashes, decreased shaving frequency, breast enlargement/tenderness, and decreased testicular size are highly suggestive of hypogonadism. Other, less specific signs and symptoms include dysthymia, poor concentration, sleep disturbances, fatigue, reduction in muscle strength, and diminished work performance.

If these signs and symptoms are present, the likelihood of hypogonadism is high and further evaluation is needed.^1,3 Note any history of alcoholism, liver problems, and testicular trauma or surgery.

A detailed medication history is also important. Some medications, such as opiates, can affect the release of gonadotropins. Among men taking long-term opiates for chronic noncancer pain, the prevalence of hypogonadism is 75%.⁴ Other drugs, such as spironolactone, can block the androgen effect and lead to hypogonadism.¹

Recent reports have suggested an association between testosterone replacement therapy and increased cardiovascular events, making a detailed cardiovascular history essential.^5,6 One study found that men ages 75 and older with limited mobility and other comorbidities who used testosterone gel had an increased risk for cardiovascular events.⁷ Therefore, clinicians need to be cognizant of this risk when considering testosterone therapy for their patients.

On the next page: Physical exam, lab tests, and treatments >>

Q: What does the physical exam reveal?

In hypogonadotropic hy­ po­gonadism, physical examination does not usually provide much information, as compared to congenital hypogonadal syndromes (eg, Klinefelter and ­Kallmann syndromes). However, small testicular volume and/or gynecomastia would indicate hypogonadism.

Q: What lab tests should be ordered?

Serum total and free testosterone should be measured, preferably by liquid gas chromatography. The sample should be drawn before 10 am to limit the effects of diurnal variation. If the total testosterone is less than
300 ng/dL, a second morning sample should be drawn and tested. Serum prolactin, follicle-stimulating hormone (FSH) and luteinizing hormone (LH), complete blood count, prostate-specific antigen (PSA), comprehensive metabolic panel, and ferritin should also be measured.

There is generally little benefit to testosterone therapy when total testosterone is greater than 350 ng/dL.⁸ The level of testosterone at which hypogonadal symptoms manifest and testosterone replacement provides improvement is yet to be determined. Buvat et al suggest that men with total testosterone levels less than 230 ng/dL usually benefit from therapy.⁸ If the total testosterone level is less than 150 ng/dL in the setting of secondary hypogonadism (low to low-normal LH/FSH) or if prolactin is elevated, MRI of the sella is recommended to rule out pituitary adenoma.¹

Q: Once the diagnosis is confirmed, what treatment should you recommend?

The goal of therapy for confirmed hypogonadism is to normalize the testosterone level. Testosterone replacement therapy may help to improve libido, fatigue, muscle strength, and bone density. However, in the elderly (particularly those older than 70), these therapeutic benefits have not been proven. Therefore, before initiating therapy, the clinician should discuss in detail the risks versus the benefits of testosterone replacement for a particular patient.

Simple lifestyle modifications, such as weight loss and exercise, have been shown to increase total and free testosterone levels.^3,8 For patients with obstructive sleep apnea (OSA), a known risk factor for hypogonadism, compliance with CPAP therapy has been associated with modest improvement in testosterone level. If it is appropriate for the patient to discontinue use of certain medications, such as opiates, he or she may experience an improvement in testosterone level as a result.

If the patient’s testosterone levels remain low after these changes have been implemented, consider testosterone therapy. Testosterone products currently available in the United States include transdermal preparations (gel, patch), intramuscular injection, and subcutaneous pellets.

On the next page: Contraindications, adverse effects, and follow-up >>

Q: What are the contraindications to testosterone therapy?

Testosterone therapy is contraindicated in patients with metastatic prostate cancer and breast cancer. An unevaluated prostate nodule, indurated prostate, PSA greater than 4 ng/mL, elevated hematocrit (>50%), severe lower urinary tract symptoms, poorly controlled congestive heart failure, and untreated severe OSA are associated with moderate to high risk for adverse outcomes; the Endocrine Society has recommended against using testosterone in affected patients.¹

Q: What are the adverse effects of testosterone replacement therapy?

Testosterone replacement may worsen symptoms of benign prostatic hyperplasia (ie, urinary urgency, hesitancy, and frequency). Also, testosterone replacement can lead to marked elevation of hemoglobin and hematocrit levels.

Increased cardiovascular events have been associated with androgen replacement, especially in men with prior coronary artery disease. A positive cardiovascular history necessitates discussion with the patient regarding the risks versus the benefits of testosterone replacement therapy.⁵ In a recent study of obese, hypogonadal men with severe OSA, testosterone therapy was associated with transient worsening of sleep apnea.⁹

Q: What does monitoring/ follow-up entail?

In patients with long-standing hypogonadism, a lower starting dose of testosterone is recommended, which can be gradually increased. After starting testosterone therapy, patients should be monitored in the first three to six months for total ­testosterone, PSA, and hematocrit and for improvement of symptoms (ie, fatigue, ED, decreased libido) or worsening of benign prostatic hyperplasia signs/symptoms.

For men ages 40 and older, if the baseline PSA is greater than 0.6 ng/mL, a digital rectal exam (DRE) is recommended prior to initiation of therapy and should be followed in accordance with prostate cancer screening guidelines.¹

Patients placed on testosterone cypionate/enanthate IM in­jections should have their testosterone checked at a midpoint between their injections, with the target testosterone level between 400 and 700 ng/dL.¹ For those using gel or transdermal preparations, a morning total testosterone level should be measured.

Urology consultation is recommended if the PSA concentration rises by 1.4 ng/dL within 12 months, if the American Urological Association/International Prostate Symptom Score is greater than 19, or if there is an abnormal DRE.^1,8 Treatment with testosterone should be postponed or withheld if the patient’s hematocrit is greater than 54% but may be resumed when it has decreased to normal levels.¹ 

On the next page: References >>

REFERENCES

1. Bhasin S, Cunningham GR, Hayes FJ, et al. Testosterone therapy in men with androgen deficiency syndromes: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2010;95(6):2536-2559.

2. Dandona P, Dhindsa S. Update: hypogonadotropic hypogonadism in type 2 diabetes and obesity. J Clin Endocrinol Metab. 2011;96(9): 2643-2651.

3. Tajar A, Forti G, O’Neill TW, et al. Characteristics of secondary, primary, and compensated hypogonadism in aging men: evidence from the European Male Ageing Study. J Clin Endocrinol Metab. 2010;95(4):1810-1818.

4. Fraser LA, Morrison D, Morley-Forster P, et al. Oral opioids for chronic non-cancer pain: higher prevalence of hypogonadism in men than in women. Exp Clin Endocrinol Diabetes. 2009;117(1):38-43.

5. Vigen R, O’Donnell CI, Baron AE, et al. Association of testosterone therapy with mortality, myocardial infarction, and stroke in men with low testosterone levels. JAMA. 2013;310(17): 1829-1836.

6. Finkle WD, Greenland S, Ridgeway GK, et al. Increased risk of non-fatal myocardial infarction following testosterone therapy prescription in men. PloS One. 2014;9(1): e85805.

7. Basaria S, Coviello AD, Travison TG, et al. Adverse events associated with testosterone admin­istration. N Engl J Med. 2010;363(2):109-122.

8. Buvat J, Maggi M, Guay A, Torres LO. Testosterone deficiency in men: systematic review and standard operating procedures for diagnosis and treatment. J Sex Med. 2013;10(1): 245-284.

9. Hoyos CM, Killick R, Yee BJ, et al. Effects of testosterone therapy on sleep and breathing in obese men with severe obstructive sleep apnoea: a randomized placebo-controlled trial. Clin Endocrinol (Oxf). 2012;77(4):
599-607.

ANSWER

There are three significant findings on this ECG. First, the rhythm shows complete heart block. The ventricular rate is 56 beats/min, and the QRS complex is narrow, resulting in a junctional rhythm. The atrial rate is 98 beats/min (consistent with a sinus rhythm), and there is no relationship of the P waves to the QRS complexes.

The second finding is a rightward axis deviation. Note that the QRS complexes are negative in lead I and positive in lead aVF. To meet criteria for a right-axis deviation, the QRS complex must also be positive in lead aVR. In this case, the QRS complex appears to be isoelectric in aVR, so we call the axis rightward.

The presence of rightward axis deviation is a result of the third finding, an anterior MI. This is due to the LAD artery occlusion discovered at catheterization. It is evident on the ECG by the absence of significant R waves in leads V₁ through V₄.

Given the need for a β-blocker with titration of dose, the patient underwent implantation of a permanent pacemaker system.

ANSWER

There are three significant findings on this ECG. First, the rhythm shows complete heart block. The ventricular rate is 56 beats/min, and the QRS complex is narrow, resulting in a junctional rhythm. The atrial rate is 98 beats/min (consistent with a sinus rhythm), and there is no relationship of the P waves to the QRS complexes.

The second finding is a rightward axis deviation. Note that the QRS complexes are negative in lead I and positive in lead aVF. To meet criteria for a right-axis deviation, the QRS complex must also be positive in lead aVR. In this case, the QRS complex appears to be isoelectric in aVR, so we call the axis rightward.

The presence of rightward axis deviation is a result of the third finding, an anterior MI. This is due to the LAD artery occlusion discovered at catheterization. It is evident on the ECG by the absence of significant R waves in leads V₁ through V₄.

Given the need for a β-blocker with titration of dose, the patient underwent implantation of a permanent pacemaker system.

ANSWER

There are three significant findings on this ECG. First, the rhythm shows complete heart block. The ventricular rate is 56 beats/min, and the QRS complex is narrow, resulting in a junctional rhythm. The atrial rate is 98 beats/min (consistent with a sinus rhythm), and there is no relationship of the P waves to the QRS complexes.

The second finding is a rightward axis deviation. Note that the QRS complexes are negative in lead I and positive in lead aVF. To meet criteria for a right-axis deviation, the QRS complex must also be positive in lead aVR. In this case, the QRS complex appears to be isoelectric in aVR, so we call the axis rightward.

The presence of rightward axis deviation is a result of the third finding, an anterior MI. This is due to the LAD artery occlusion discovered at catheterization. It is evident on the ECG by the absence of significant R waves in leads V₁ through V₄.

Given the need for a β-blocker with titration of dose, the patient underwent implantation of a permanent pacemaker system.

ANSWER

The correct answer is eruptive xanthomata (choice “b”) caused by an accumulation of lipid-filled macrophages as a result of pathologic levels of serum triglyceride—a situation discussed more fully below.

Neurofibromatosis type I (choice “a”), also known as von Recklinghausen disease, can present with multiple intradermal nodules. However, it usually appears in the second or third decade of life, with lesions that are fixed and soft. Biopsy would have confirmed this diagnosis.

Diabetic dermopathy (choice “c”) manifests with atrophic patches on anterior tibial skin. The patches occasionally become superficially eroded but do not resemble this patient’s lesions at all.

Juvenile xanthogranuloma (choice “d”) usually presents on children as a solitary yellowish brown papule. It can resemble eruptive xanthomata histologically but not clinically.

DISCUSSION

Eruptive xanthomata (EX) are relatively common, manifesting rapidly as papules and nodules, most frequently in the setting of hypertriglyceridemia. The latter can be familial and may be worsened by poorly controlled diabetes. Persons with Fredrickson types I, IV, and V hyperlipidemia are especially prone to EX.

As might be expected, patients with EX are at risk for several associated morbidities, including acute pancreatitis (especially in childhood cases) and atherosclerotic vessel disease. EX have also been associated with hypothyroid states and nephrotic syndromes.

Elevations in cholesterol, with normal triglyceride levels, can be associated with several types of xanthoma, including plane xanthomas and xanthelasma. The latter, often benign, can manifest in a normolipemic patient as well (necessitating a problem-directed history, physical, and lipid check).

Biopsy is often required to confirm the diagnosis of EX. As in this case, it typically shows monotonous collections of lipid-laden macrophages. Frozen sections of EX can be successfully stained for lipids, but routine processing of specimens effectively removes any lipids, replacing them with paraffin.

TREATMENT

Treatment entails controlling lipids with medication (fenofibrate), diet, and exercise and getting diabetes under control, as indicated. It is also essential to assess for atherosclerotic vessel disease and rule out pancreatitis.

Within a month of institution of treatment, this patient’s lesions had all but disappeared. His serum amylase and lipase were within normal limits, and testing for atherosclerotic vessel disease was pending.

Click here for more DermaDiagnosis cases, including 
• The Value of Certainty in Diagnosis
• A Purplish Rash on the Instep
• Hair Loss at a Very Young Age.

ANSWER

The correct answer is eruptive xanthomata (choice “b”) caused by an accumulation of lipid-filled macrophages as a result of pathologic levels of serum triglyceride—a situation discussed more fully below.

Neurofibromatosis type I (choice “a”), also known as von Recklinghausen disease, can present with multiple intradermal nodules. However, it usually appears in the second or third decade of life, with lesions that are fixed and soft. Biopsy would have confirmed this diagnosis.

Diabetic dermopathy (choice “c”) manifests with atrophic patches on anterior tibial skin. The patches occasionally become superficially eroded but do not resemble this patient’s lesions at all.

Juvenile xanthogranuloma (choice “d”) usually presents on children as a solitary yellowish brown papule. It can resemble eruptive xanthomata histologically but not clinically.

DISCUSSION

Eruptive xanthomata (EX) are relatively common, manifesting rapidly as papules and nodules, most frequently in the setting of hypertriglyceridemia. The latter can be familial and may be worsened by poorly controlled diabetes. Persons with Fredrickson types I, IV, and V hyperlipidemia are especially prone to EX.

As might be expected, patients with EX are at risk for several associated morbidities, including acute pancreatitis (especially in childhood cases) and atherosclerotic vessel disease. EX have also been associated with hypothyroid states and nephrotic syndromes.

Elevations in cholesterol, with normal triglyceride levels, can be associated with several types of xanthoma, including plane xanthomas and xanthelasma. The latter, often benign, can manifest in a normolipemic patient as well (necessitating a problem-directed history, physical, and lipid check).

Biopsy is often required to confirm the diagnosis of EX. As in this case, it typically shows monotonous collections of lipid-laden macrophages. Frozen sections of EX can be successfully stained for lipids, but routine processing of specimens effectively removes any lipids, replacing them with paraffin.

TREATMENT

Treatment entails controlling lipids with medication (fenofibrate), diet, and exercise and getting diabetes under control, as indicated. It is also essential to assess for atherosclerotic vessel disease and rule out pancreatitis.

Within a month of institution of treatment, this patient’s lesions had all but disappeared. His serum amylase and lipase were within normal limits, and testing for atherosclerotic vessel disease was pending.

Click here for more DermaDiagnosis cases, including 
• The Value of Certainty in Diagnosis
• A Purplish Rash on the Instep
• Hair Loss at a Very Young Age.

ANSWER

The correct answer is eruptive xanthomata (choice “b”) caused by an accumulation of lipid-filled macrophages as a result of pathologic levels of serum triglyceride—a situation discussed more fully below.

Neurofibromatosis type I (choice “a”), also known as von Recklinghausen disease, can present with multiple intradermal nodules. However, it usually appears in the second or third decade of life, with lesions that are fixed and soft. Biopsy would have confirmed this diagnosis.

Diabetic dermopathy (choice “c”) manifests with atrophic patches on anterior tibial skin. The patches occasionally become superficially eroded but do not resemble this patient’s lesions at all.

Juvenile xanthogranuloma (choice “d”) usually presents on children as a solitary yellowish brown papule. It can resemble eruptive xanthomata histologically but not clinically.

DISCUSSION

Eruptive xanthomata (EX) are relatively common, manifesting rapidly as papules and nodules, most frequently in the setting of hypertriglyceridemia. The latter can be familial and may be worsened by poorly controlled diabetes. Persons with Fredrickson types I, IV, and V hyperlipidemia are especially prone to EX.

As might be expected, patients with EX are at risk for several associated morbidities, including acute pancreatitis (especially in childhood cases) and atherosclerotic vessel disease. EX have also been associated with hypothyroid states and nephrotic syndromes.

Elevations in cholesterol, with normal triglyceride levels, can be associated with several types of xanthoma, including plane xanthomas and xanthelasma. The latter, often benign, can manifest in a normolipemic patient as well (necessitating a problem-directed history, physical, and lipid check).

Biopsy is often required to confirm the diagnosis of EX. As in this case, it typically shows monotonous collections of lipid-laden macrophages. Frozen sections of EX can be successfully stained for lipids, but routine processing of specimens effectively removes any lipids, replacing them with paraffin.

TREATMENT

Treatment entails controlling lipids with medication (fenofibrate), diet, and exercise and getting diabetes under control, as indicated. It is also essential to assess for atherosclerotic vessel disease and rule out pancreatitis.

Within a month of institution of treatment, this patient’s lesions had all but disappeared. His serum amylase and lipase were within normal limits, and testing for atherosclerotic vessel disease was pending.

Click here for more DermaDiagnosis cases, including 
• The Value of Certainty in Diagnosis
• A Purplish Rash on the Instep
• Hair Loss at a Very Young Age.

Researchers in the lab

Credit: Rhoda Baer

Researchers say they have identified a source of drug resistance in chronic lymphocytic leukemia (CLL).

In a letter to The New England Journal of Medicine, the team described how a mutation in Bruton’s tyrosine kinase (BTK) triggers resistance to ibrutinib, a drug that treats CLL by inhibiting BTK.

The researchers discovered this point mutation in a CLL patient enrolled in a clinical trial. The patient initially responded well to ibrutinib but stopped responding after almost 20 months.

“In a way, we are repeating, at a faster pace, the story of Gleevec [imatinib],” said study author Y. Lynn Wang, MD, PhD, of the University of Chicago in Illinois.

“That story began with development of an effective drug with few side effects, but, in many patients, the leukemia eventually found a way around it after long-term use. So researchers developed second-line drugs to overcome resistance.”

The ibrutinib study began in 2010 at Weill Cornell Medical College in New York, one of several sites for a phase 1 trial of ibrutinib. The researchers recruited 16 patients with CLL whose disease had progressed or relapsed despite multiple treatments.

Dr Wang arranged to track the progress of each patient’s leukemic cells before and during treatment and to correlate any cellular or molecular changes with each patient’s disease activity.

One of the 16 patients in the trial seemed to be unusual. This 61-year-old woman was diagnosed in 2000 at age 49. She had unsuccessfully received several different treatments before entering the study.

Within 18 months of starting ibrutinib, she showed significant improvement. At about 20 months, however, she started to decline, developing a respiratory infection that did not improve with treatment. By 21 months, it was clear she was having a relapse. The clinical team increased her dose, with no discernable effect.

Dr Wang’s team quickly began analyzing her blood samples, looking for changes that occurred between the period when she was responding well to ibrutinib and after she began to relapse.

Because complete gene sequencing would be time consuming, Dr Wang asked a graduate student working on the project, Menu Setty from Memorial Sloan-Kettering in New York, to first focus on 3 proteins that were likely candidates. One of the candidates was BTK.

And sure enough, Setty discovered a tiny but consistent change in BTK in about 90% of post-relapse cells. It was a thymidine-to-adenine mutation at nucleotide 1634 of the BTK complementary DNA, leading to a substitution of serine for cysteine at residue 481 (C481S).

When the researchers later analyzed the entire set of the patient’s genes, they found no other genetic changes that correlated with the patient’s clinical course. BTK made perfect sense as the cause for drug resistance, the researchers noted, as it’s the primary target of ibrutinib binding, and it plays a central role in rapid cell proliferation.

Dr Wang and her colleagues used structural and biochemical measures to confirm that the C481S mutation made CLL cells resistant to ibrutinib. The studies indicated that ibrutinib was 500 times less likely to bind to mutant BTK.

In an attempt to save the patient, the researchers tested alternative kinase inhibitors against the patient’s leukemic cells in the lab.

They found some kinase inhibitors remained effective against ibrutinib-resistant cells. (These studies are described in a separate manuscript that has been submitted for publication.) Unfortunately, despite this effort, the patient passed away a few weeks later, due to sepsis.

The researchers noted that the C481S mutation is one of several mechanisms that underlie resistance to ibrutinib, but this research highlights the mutation’s role in disease development and drug resistance.

Understanding the molecular and cellular mechanisms of resistance is the first step toward monitoring, early detection, and development of novel strategies to overcome drug resistance.

Researchers in the lab

Credit: Rhoda Baer

Researchers say they have identified a source of drug resistance in chronic lymphocytic leukemia (CLL).

In a letter to The New England Journal of Medicine, the team described how a mutation in Bruton’s tyrosine kinase (BTK) triggers resistance to ibrutinib, a drug that treats CLL by inhibiting BTK.

The researchers discovered this point mutation in a CLL patient enrolled in a clinical trial. The patient initially responded well to ibrutinib but stopped responding after almost 20 months.

“In a way, we are repeating, at a faster pace, the story of Gleevec [imatinib],” said study author Y. Lynn Wang, MD, PhD, of the University of Chicago in Illinois.

“That story began with development of an effective drug with few side effects, but, in many patients, the leukemia eventually found a way around it after long-term use. So researchers developed second-line drugs to overcome resistance.”

The ibrutinib study began in 2010 at Weill Cornell Medical College in New York, one of several sites for a phase 1 trial of ibrutinib. The researchers recruited 16 patients with CLL whose disease had progressed or relapsed despite multiple treatments.

Dr Wang arranged to track the progress of each patient’s leukemic cells before and during treatment and to correlate any cellular or molecular changes with each patient’s disease activity.

One of the 16 patients in the trial seemed to be unusual. This 61-year-old woman was diagnosed in 2000 at age 49. She had unsuccessfully received several different treatments before entering the study.

Within 18 months of starting ibrutinib, she showed significant improvement. At about 20 months, however, she started to decline, developing a respiratory infection that did not improve with treatment. By 21 months, it was clear she was having a relapse. The clinical team increased her dose, with no discernable effect.

Dr Wang’s team quickly began analyzing her blood samples, looking for changes that occurred between the period when she was responding well to ibrutinib and after she began to relapse.

Because complete gene sequencing would be time consuming, Dr Wang asked a graduate student working on the project, Menu Setty from Memorial Sloan-Kettering in New York, to first focus on 3 proteins that were likely candidates. One of the candidates was BTK.

And sure enough, Setty discovered a tiny but consistent change in BTK in about 90% of post-relapse cells. It was a thymidine-to-adenine mutation at nucleotide 1634 of the BTK complementary DNA, leading to a substitution of serine for cysteine at residue 481 (C481S).

When the researchers later analyzed the entire set of the patient’s genes, they found no other genetic changes that correlated with the patient’s clinical course. BTK made perfect sense as the cause for drug resistance, the researchers noted, as it’s the primary target of ibrutinib binding, and it plays a central role in rapid cell proliferation.

Dr Wang and her colleagues used structural and biochemical measures to confirm that the C481S mutation made CLL cells resistant to ibrutinib. The studies indicated that ibrutinib was 500 times less likely to bind to mutant BTK.

In an attempt to save the patient, the researchers tested alternative kinase inhibitors against the patient’s leukemic cells in the lab.

They found some kinase inhibitors remained effective against ibrutinib-resistant cells. (These studies are described in a separate manuscript that has been submitted for publication.) Unfortunately, despite this effort, the patient passed away a few weeks later, due to sepsis.

The researchers noted that the C481S mutation is one of several mechanisms that underlie resistance to ibrutinib, but this research highlights the mutation’s role in disease development and drug resistance.

Understanding the molecular and cellular mechanisms of resistance is the first step toward monitoring, early detection, and development of novel strategies to overcome drug resistance.

Researchers in the lab

Credit: Rhoda Baer

Researchers say they have identified a source of drug resistance in chronic lymphocytic leukemia (CLL).

In a letter to The New England Journal of Medicine, the team described how a mutation in Bruton’s tyrosine kinase (BTK) triggers resistance to ibrutinib, a drug that treats CLL by inhibiting BTK.

The researchers discovered this point mutation in a CLL patient enrolled in a clinical trial. The patient initially responded well to ibrutinib but stopped responding after almost 20 months.

“In a way, we are repeating, at a faster pace, the story of Gleevec [imatinib],” said study author Y. Lynn Wang, MD, PhD, of the University of Chicago in Illinois.

“That story began with development of an effective drug with few side effects, but, in many patients, the leukemia eventually found a way around it after long-term use. So researchers developed second-line drugs to overcome resistance.”

The ibrutinib study began in 2010 at Weill Cornell Medical College in New York, one of several sites for a phase 1 trial of ibrutinib. The researchers recruited 16 patients with CLL whose disease had progressed or relapsed despite multiple treatments.

Dr Wang arranged to track the progress of each patient’s leukemic cells before and during treatment and to correlate any cellular or molecular changes with each patient’s disease activity.

One of the 16 patients in the trial seemed to be unusual. This 61-year-old woman was diagnosed in 2000 at age 49. She had unsuccessfully received several different treatments before entering the study.

Within 18 months of starting ibrutinib, she showed significant improvement. At about 20 months, however, she started to decline, developing a respiratory infection that did not improve with treatment. By 21 months, it was clear she was having a relapse. The clinical team increased her dose, with no discernable effect.

Dr Wang’s team quickly began analyzing her blood samples, looking for changes that occurred between the period when she was responding well to ibrutinib and after she began to relapse.

Because complete gene sequencing would be time consuming, Dr Wang asked a graduate student working on the project, Menu Setty from Memorial Sloan-Kettering in New York, to first focus on 3 proteins that were likely candidates. One of the candidates was BTK.

And sure enough, Setty discovered a tiny but consistent change in BTK in about 90% of post-relapse cells. It was a thymidine-to-adenine mutation at nucleotide 1634 of the BTK complementary DNA, leading to a substitution of serine for cysteine at residue 481 (C481S).

When the researchers later analyzed the entire set of the patient’s genes, they found no other genetic changes that correlated with the patient’s clinical course. BTK made perfect sense as the cause for drug resistance, the researchers noted, as it’s the primary target of ibrutinib binding, and it plays a central role in rapid cell proliferation.

Dr Wang and her colleagues used structural and biochemical measures to confirm that the C481S mutation made CLL cells resistant to ibrutinib. The studies indicated that ibrutinib was 500 times less likely to bind to mutant BTK.

In an attempt to save the patient, the researchers tested alternative kinase inhibitors against the patient’s leukemic cells in the lab.

They found some kinase inhibitors remained effective against ibrutinib-resistant cells. (These studies are described in a separate manuscript that has been submitted for publication.) Unfortunately, despite this effort, the patient passed away a few weeks later, due to sepsis.

The researchers noted that the C481S mutation is one of several mechanisms that underlie resistance to ibrutinib, but this research highlights the mutation’s role in disease development and drug resistance.

Understanding the molecular and cellular mechanisms of resistance is the first step toward monitoring, early detection, and development of novel strategies to overcome drug resistance.

Thrombus

Credit: Andre E.X. Brown

The US Food and Drug Administration has cleared for marketing a device that facilitates the treatment of pulmonary embolism (PE).

The EkoSonic Endovascular System is intended for controlled and selective infusion of physician-specified fluids, including thrombolytics, into the peripheral vasculature.

The device is designed to gently accelerate the penetration of thrombolytic agents into thrombi, thereby providing high levels of lysis.

The EkoSonic Endovascular System is the only minimally invasive endovascular therapy that is FDA-cleared for the treatment of PE. The device is manufactured by EKOS Corporation.

“The EKOS clinical data established that patients stricken with a life-threatening pulmonary embolism can be successfully and safely treated with the EkoSonic system,” said Samuel Z. Goldhaber, MD, of Brigham and Woman’s Hospital in Boston, Massachusetts.

The system produced favorable results in the ULTIMA and SEATTLE II trials.

Results of the ULTIMA trial were published in Circulation. The trial showed that, for PE patients at intermediate risk of adverse events, EKOS treatment was clinically superior to anticoagulation with heparin alone in reversing right ventricular dilation at 24 hours, without an increase in bleeding complications.

The results of SEATTLE II, the prospective, single-arm, multicenter trial of 150 patients, were released at the American College of Cardiology’s 63rd Annual Scientific Session & Expo.

SEATTLE II showed that ultrasound-facilitated catheter-directed low-dose fibrinolysis for acute PE minimizes the risk of intracranial hemorrhage, improves right ventricle function, and decreases pulmonary hypertension.

Thrombus

Credit: Andre E.X. Brown

The US Food and Drug Administration has cleared for marketing a device that facilitates the treatment of pulmonary embolism (PE).

The EkoSonic Endovascular System is intended for controlled and selective infusion of physician-specified fluids, including thrombolytics, into the peripheral vasculature.

The device is designed to gently accelerate the penetration of thrombolytic agents into thrombi, thereby providing high levels of lysis.

The EkoSonic Endovascular System is the only minimally invasive endovascular therapy that is FDA-cleared for the treatment of PE. The device is manufactured by EKOS Corporation.

“The EKOS clinical data established that patients stricken with a life-threatening pulmonary embolism can be successfully and safely treated with the EkoSonic system,” said Samuel Z. Goldhaber, MD, of Brigham and Woman’s Hospital in Boston, Massachusetts.

The system produced favorable results in the ULTIMA and SEATTLE II trials.

Results of the ULTIMA trial were published in Circulation. The trial showed that, for PE patients at intermediate risk of adverse events, EKOS treatment was clinically superior to anticoagulation with heparin alone in reversing right ventricular dilation at 24 hours, without an increase in bleeding complications.

The results of SEATTLE II, the prospective, single-arm, multicenter trial of 150 patients, were released at the American College of Cardiology’s 63rd Annual Scientific Session & Expo.

SEATTLE II showed that ultrasound-facilitated catheter-directed low-dose fibrinolysis for acute PE minimizes the risk of intracranial hemorrhage, improves right ventricle function, and decreases pulmonary hypertension.

Thrombus

Credit: Andre E.X. Brown

The US Food and Drug Administration has cleared for marketing a device that facilitates the treatment of pulmonary embolism (PE).

The EkoSonic Endovascular System is intended for controlled and selective infusion of physician-specified fluids, including thrombolytics, into the peripheral vasculature.

The device is designed to gently accelerate the penetration of thrombolytic agents into thrombi, thereby providing high levels of lysis.

The EkoSonic Endovascular System is the only minimally invasive endovascular therapy that is FDA-cleared for the treatment of PE. The device is manufactured by EKOS Corporation.

“The EKOS clinical data established that patients stricken with a life-threatening pulmonary embolism can be successfully and safely treated with the EkoSonic system,” said Samuel Z. Goldhaber, MD, of Brigham and Woman’s Hospital in Boston, Massachusetts.

The system produced favorable results in the ULTIMA and SEATTLE II trials.

Results of the ULTIMA trial were published in Circulation. The trial showed that, for PE patients at intermediate risk of adverse events, EKOS treatment was clinically superior to anticoagulation with heparin alone in reversing right ventricular dilation at 24 hours, without an increase in bleeding complications.

The results of SEATTLE II, the prospective, single-arm, multicenter trial of 150 patients, were released at the American College of Cardiology’s 63rd Annual Scientific Session & Expo.

SEATTLE II showed that ultrasound-facilitated catheter-directed low-dose fibrinolysis for acute PE minimizes the risk of intracranial hemorrhage, improves right ventricle function, and decreases pulmonary hypertension.

LAS VEGAS– A newly introduced statement proposes to change how obesity is diagnosed and treated.

The American Association of Clinical Endocrinologists and the American College of Endocrinology are suggesting algorithms to determine stages for the disease, each of which comes with a set of therapy recommendations. 

"Right now it’s obesity, or overweight/obesity, or Class 1, 2, 3 obesity – it’s all [body mass index]. BMI doesn’t convey actionability. It doesn’t convey a medical meaning," said Dr. W. Timothy Garvey, chair of the AACE Obesity Scientific Committee at the annual meeting of the American Association of Clinical Endocrinologists.

Naseem Miller/Frontline Medical News

AACE/ACE leaders hope that their new diagnostic algorithm will fill that gap.

"We’re using weight loss therapy to treat the complications of obesity in a medical model," Dr. Garvey said.

According to the framework, which is not finalized yet, the diagnostic categories of obesity will be:

• Overweight: BMI of 25-29.9 kg/m², with no obesity-related complications.

• Obesity Stage 0: BMI of at least 30, with no obesity-related complications.

• Obesity Stage 1: BMI of at least 25 and one or more complications that are mild to moderate in severity.

• Obesity stage 2: BMI of greater than or equal to 25 and one or more severe complications.

Also, a four-step diagnosis and treatment approach is recommended for all patients:

1. BMI screening and adjusting for ethnic differences.

2. Clinical evaluation for the presence of obesity-related complications, by using a checklist.

3. Staging for the severity of complications using complication-specific criteria.

4. Selection of prevention and/or intervention strategies targeting specific complications guided by the AACE/ACE obesity management algorithm.

AACE/ACE leaders pointed out that today there are better tools to treat obesity than ever before, including improvements in lifestyle intervention, new medications, and improvements in bariatric surgery, yet there’s limited access and penetrance of these tools in the clinic. They said they hoped the new algorithm would help incorporate available therapies into treating obese patients.

The algorithm emerged from the AACE/ACE 2014 Consensus Conference on Obesity, which included medical professionals, industry representatives, advocacy groups, and regulators. One of the findings that everyone agreed on was that the diagnostic definition of obesity needed to improve.

The current definition of obesity "didn’t give all the stakeholders a reason to buy into a concerted plan." Employers would say, "I bring somebody down from a BMI of 38 to 34. But what does that mean? "How is it benefiting me? How is it benefiting my company? Why would I want to invest in that? But if they’re treating Stage 2, that’s telling them that that person is overweight, has excessive body fat, and it’s impacting their health and they have complications that can be remedied by weight loss and use of more aggressive therapies. All of that is embedded in that simple term," Dr. Garvey said. 

The AACE/ACE is not the first to issue a diagnosis or treatment guideline for obesity, which was declared a disease by the American Medical Association in 2013. 

There are a lot of commonalities to the guidelines," said Dr. Garvey, professor and chair at the department of Nutrition Sciences at the University of Alabama at Birmingham. They’re all addressing obesity and therapy and attempt to improve patients’ health. "I think we’re more focused on using weight loss as a therapy to treat obesity-related complications," Dr. Garvey said. 

AACE/ACE is holding another consensus conference later this year as a step toward finalizing the framework.

Dr. Garvey is a consultant for Daiichi Sankyo, Liposcience, Takeda, Vivus, Boehringer Ingelheim, Janssen, Eisai, and Novo Nordisk. He has received research funding from Merck, Astra Zeneca, Weight Watchers, Eisai, and Sanofi.

[email protected]

On Twitter @naseemmiller

LAS VEGAS– A newly introduced statement proposes to change how obesity is diagnosed and treated.

The American Association of Clinical Endocrinologists and the American College of Endocrinology are suggesting algorithms to determine stages for the disease, each of which comes with a set of therapy recommendations. 

"Right now it’s obesity, or overweight/obesity, or Class 1, 2, 3 obesity – it’s all [body mass index]. BMI doesn’t convey actionability. It doesn’t convey a medical meaning," said Dr. W. Timothy Garvey, chair of the AACE Obesity Scientific Committee at the annual meeting of the American Association of Clinical Endocrinologists.

Naseem Miller/Frontline Medical News

AACE/ACE leaders hope that their new diagnostic algorithm will fill that gap.

"We’re using weight loss therapy to treat the complications of obesity in a medical model," Dr. Garvey said.

According to the framework, which is not finalized yet, the diagnostic categories of obesity will be:

• Overweight: BMI of 25-29.9 kg/m², with no obesity-related complications.

• Obesity Stage 0: BMI of at least 30, with no obesity-related complications.

• Obesity Stage 1: BMI of at least 25 and one or more complications that are mild to moderate in severity.

• Obesity stage 2: BMI of greater than or equal to 25 and one or more severe complications.

Also, a four-step diagnosis and treatment approach is recommended for all patients:

1. BMI screening and adjusting for ethnic differences.

2. Clinical evaluation for the presence of obesity-related complications, by using a checklist.

3. Staging for the severity of complications using complication-specific criteria.

4. Selection of prevention and/or intervention strategies targeting specific complications guided by the AACE/ACE obesity management algorithm.

AACE/ACE leaders pointed out that today there are better tools to treat obesity than ever before, including improvements in lifestyle intervention, new medications, and improvements in bariatric surgery, yet there’s limited access and penetrance of these tools in the clinic. They said they hoped the new algorithm would help incorporate available therapies into treating obese patients.

The algorithm emerged from the AACE/ACE 2014 Consensus Conference on Obesity, which included medical professionals, industry representatives, advocacy groups, and regulators. One of the findings that everyone agreed on was that the diagnostic definition of obesity needed to improve.

The current definition of obesity "didn’t give all the stakeholders a reason to buy into a concerted plan." Employers would say, "I bring somebody down from a BMI of 38 to 34. But what does that mean? "How is it benefiting me? How is it benefiting my company? Why would I want to invest in that? But if they’re treating Stage 2, that’s telling them that that person is overweight, has excessive body fat, and it’s impacting their health and they have complications that can be remedied by weight loss and use of more aggressive therapies. All of that is embedded in that simple term," Dr. Garvey said. 

The AACE/ACE is not the first to issue a diagnosis or treatment guideline for obesity, which was declared a disease by the American Medical Association in 2013. 

There are a lot of commonalities to the guidelines," said Dr. Garvey, professor and chair at the department of Nutrition Sciences at the University of Alabama at Birmingham. They’re all addressing obesity and therapy and attempt to improve patients’ health. "I think we’re more focused on using weight loss as a therapy to treat obesity-related complications," Dr. Garvey said. 

AACE/ACE is holding another consensus conference later this year as a step toward finalizing the framework.

Dr. Garvey is a consultant for Daiichi Sankyo, Liposcience, Takeda, Vivus, Boehringer Ingelheim, Janssen, Eisai, and Novo Nordisk. He has received research funding from Merck, Astra Zeneca, Weight Watchers, Eisai, and Sanofi.

[email protected]

On Twitter @naseemmiller

LAS VEGAS– A newly introduced statement proposes to change how obesity is diagnosed and treated.

The American Association of Clinical Endocrinologists and the American College of Endocrinology are suggesting algorithms to determine stages for the disease, each of which comes with a set of therapy recommendations. 

"Right now it’s obesity, or overweight/obesity, or Class 1, 2, 3 obesity – it’s all [body mass index]. BMI doesn’t convey actionability. It doesn’t convey a medical meaning," said Dr. W. Timothy Garvey, chair of the AACE Obesity Scientific Committee at the annual meeting of the American Association of Clinical Endocrinologists.

Naseem Miller/Frontline Medical News

AACE/ACE leaders hope that their new diagnostic algorithm will fill that gap.

"We’re using weight loss therapy to treat the complications of obesity in a medical model," Dr. Garvey said.

According to the framework, which is not finalized yet, the diagnostic categories of obesity will be:

• Overweight: BMI of 25-29.9 kg/m², with no obesity-related complications.

• Obesity Stage 0: BMI of at least 30, with no obesity-related complications.

• Obesity Stage 1: BMI of at least 25 and one or more complications that are mild to moderate in severity.

• Obesity stage 2: BMI of greater than or equal to 25 and one or more severe complications.

Also, a four-step diagnosis and treatment approach is recommended for all patients:

1. BMI screening and adjusting for ethnic differences.

2. Clinical evaluation for the presence of obesity-related complications, by using a checklist.

3. Staging for the severity of complications using complication-specific criteria.

4. Selection of prevention and/or intervention strategies targeting specific complications guided by the AACE/ACE obesity management algorithm.

AACE/ACE leaders pointed out that today there are better tools to treat obesity than ever before, including improvements in lifestyle intervention, new medications, and improvements in bariatric surgery, yet there’s limited access and penetrance of these tools in the clinic. They said they hoped the new algorithm would help incorporate available therapies into treating obese patients.

The algorithm emerged from the AACE/ACE 2014 Consensus Conference on Obesity, which included medical professionals, industry representatives, advocacy groups, and regulators. One of the findings that everyone agreed on was that the diagnostic definition of obesity needed to improve.

The current definition of obesity "didn’t give all the stakeholders a reason to buy into a concerted plan." Employers would say, "I bring somebody down from a BMI of 38 to 34. But what does that mean? "How is it benefiting me? How is it benefiting my company? Why would I want to invest in that? But if they’re treating Stage 2, that’s telling them that that person is overweight, has excessive body fat, and it’s impacting their health and they have complications that can be remedied by weight loss and use of more aggressive therapies. All of that is embedded in that simple term," Dr. Garvey said. 

The AACE/ACE is not the first to issue a diagnosis or treatment guideline for obesity, which was declared a disease by the American Medical Association in 2013. 

There are a lot of commonalities to the guidelines," said Dr. Garvey, professor and chair at the department of Nutrition Sciences at the University of Alabama at Birmingham. They’re all addressing obesity and therapy and attempt to improve patients’ health. "I think we’re more focused on using weight loss as a therapy to treat obesity-related complications," Dr. Garvey said. 

AACE/ACE is holding another consensus conference later this year as a step toward finalizing the framework.

Dr. Garvey is a consultant for Daiichi Sankyo, Liposcience, Takeda, Vivus, Boehringer Ingelheim, Janssen, Eisai, and Novo Nordisk. He has received research funding from Merck, Astra Zeneca, Weight Watchers, Eisai, and Sanofi.

[email protected]

On Twitter @naseemmiller

Frontotemporal dementia (FTD) is a neu­rologic disease that affects the frontal and the temporal lobes of the cerebral cortex.¹ This disorder is observed most often in people between age 45 to 65, but also can manifest in younger or older persons.¹ The cause varies among a range of pathologies affecting the anterior portions of the brain.²

Presentations
FTD presents with changes in personality, social skills, ability to concentrate, motiva­tion, reasoning, and language abnormal­ity.³ Memory loss is less prominent in this condition compared with other dementias; therefore, identification may be a diagnos­tic challenge. FTD can be misdiagnosed as a psychiatric illness or not recognized because social symptoms dominate over cognitive dysfunction. As the disease progresses, patients may become increasingly unable to plan or organize activities of daily living, behave appropriately, and react normally in social interactions.¹

FTD has 3 diagnostic variants^1-4:

Behavioral variant. Known as Pick dis­ease or the “frontal variant,”^1,2 this type of FTD manifests as changes in personality, improper behavior in social settings, per­sonal neglect, or impulsivity, such as shop­lifting or hypersexuality.

Primary progressive aphasia. Two types of language dysfunction are observed in FTD:
   • Semantic dementia (SD)³: Left-sided SD presents with “meaningless speech” or “word substitutions” (eg, “chair” instead of “table”). Right-sided SD, however, is char­acterized by forgetting the faces of familiar people or objects.
   • Primary nonfluent aphasia³: Language fluency is compromised. Persons with such language dysfunction cannot produce words easily, and their speech is stumbling and nonfluent.

FTD with motor neuron disease.⁴ The most common type of motor neuron dis­ease associated with FTD is amyotrophic lateral sclerosis. Afflicted patients exhibit muscle weakness, spasms, and rigidity. This leads to difficulty in swallowing or breathing because the diaphragm and pharynx are paralyzed. Other diseases associated with FTD include corticobasal degeneration and progressive supranu­clear palsy.

Diagnosis
In DSM-5, FTD has been renamed “fronto­temporal lobar degeneration” under the cat­egory of “Major and Mild Neurocognitive Disorders.”⁵ The workup begins with a his­tory, physical examination, and mental sta­tus assessment. Physical signs can include frontal-release, primitive reflexes. Early in the disease course, a palmomental reflex often is observed; later, as disease progress, the rooting reflex or palmar grasp may become apparent.^1,5

Diagnosing FTD requires recognizing its symptoms and ruling out conditions such as Alzheimer’s disease, depression, and schizophrenia.⁶ Laboratory studies may help identify other conditions. Brain imaging, such as MRI, can depict fronto­temporal pathology and rule in or exclude other diseases.^3,5

Psychometric testing can evaluate mem­ory or cognitive ability, which might be unremarkable during the initial phases of FTD.⁴ Further psychological assessments may provide objective verification of frontal lobe deficiencies in social skills or activities of daily living.³ Positron emission tomogra­phy and single-photon emission computed tomography may demonstrate areas of decreased activity or hypoperfusion in fron­tal and temporal lobes.⁷

Interventions
Treatment of FTD is limited to symp­tomatic therapy⁸; there are no specific, approved countermeasures available. Comorbid conditions, such as diabetes mellitus or hypertension, should be treated medically. Social interventions such as day care, increased supervision, and emotional support from the family can be effective adjuvants.²

Disclosures
The authors report no financial relationship whose products are mentioned in this article or with manufacturers of competing products.

Frontotemporal dementia (FTD) is a neu­rologic disease that affects the frontal and the temporal lobes of the cerebral cortex.¹ This disorder is observed most often in people between age 45 to 65, but also can manifest in younger or older persons.¹ The cause varies among a range of pathologies affecting the anterior portions of the brain.²

Presentations
FTD presents with changes in personality, social skills, ability to concentrate, motiva­tion, reasoning, and language abnormal­ity.³ Memory loss is less prominent in this condition compared with other dementias; therefore, identification may be a diagnos­tic challenge. FTD can be misdiagnosed as a psychiatric illness or not recognized because social symptoms dominate over cognitive dysfunction. As the disease progresses, patients may become increasingly unable to plan or organize activities of daily living, behave appropriately, and react normally in social interactions.¹

FTD has 3 diagnostic variants^1-4:

Behavioral variant. Known as Pick dis­ease or the “frontal variant,”^1,2 this type of FTD manifests as changes in personality, improper behavior in social settings, per­sonal neglect, or impulsivity, such as shop­lifting or hypersexuality.

Primary progressive aphasia. Two types of language dysfunction are observed in FTD:
   • Semantic dementia (SD)³: Left-sided SD presents with “meaningless speech” or “word substitutions” (eg, “chair” instead of “table”). Right-sided SD, however, is char­acterized by forgetting the faces of familiar people or objects.
   • Primary nonfluent aphasia³: Language fluency is compromised. Persons with such language dysfunction cannot produce words easily, and their speech is stumbling and nonfluent.

FTD with motor neuron disease.⁴ The most common type of motor neuron dis­ease associated with FTD is amyotrophic lateral sclerosis. Afflicted patients exhibit muscle weakness, spasms, and rigidity. This leads to difficulty in swallowing or breathing because the diaphragm and pharynx are paralyzed. Other diseases associated with FTD include corticobasal degeneration and progressive supranu­clear palsy.

Diagnosis
In DSM-5, FTD has been renamed “fronto­temporal lobar degeneration” under the cat­egory of “Major and Mild Neurocognitive Disorders.”⁵ The workup begins with a his­tory, physical examination, and mental sta­tus assessment. Physical signs can include frontal-release, primitive reflexes. Early in the disease course, a palmomental reflex often is observed; later, as disease progress, the rooting reflex or palmar grasp may become apparent.^1,5

Diagnosing FTD requires recognizing its symptoms and ruling out conditions such as Alzheimer’s disease, depression, and schizophrenia.⁶ Laboratory studies may help identify other conditions. Brain imaging, such as MRI, can depict fronto­temporal pathology and rule in or exclude other diseases.^3,5

Psychometric testing can evaluate mem­ory or cognitive ability, which might be unremarkable during the initial phases of FTD.⁴ Further psychological assessments may provide objective verification of frontal lobe deficiencies in social skills or activities of daily living.³ Positron emission tomogra­phy and single-photon emission computed tomography may demonstrate areas of decreased activity or hypoperfusion in fron­tal and temporal lobes.⁷

Interventions
Treatment of FTD is limited to symp­tomatic therapy⁸; there are no specific, approved countermeasures available. Comorbid conditions, such as diabetes mellitus or hypertension, should be treated medically. Social interventions such as day care, increased supervision, and emotional support from the family can be effective adjuvants.²

Disclosures
The authors report no financial relationship whose products are mentioned in this article or with manufacturers of competing products.

Frontotemporal dementia (FTD) is a neu­rologic disease that affects the frontal and the temporal lobes of the cerebral cortex.¹ This disorder is observed most often in people between age 45 to 65, but also can manifest in younger or older persons.¹ The cause varies among a range of pathologies affecting the anterior portions of the brain.²

Presentations
FTD presents with changes in personality, social skills, ability to concentrate, motiva­tion, reasoning, and language abnormal­ity.³ Memory loss is less prominent in this condition compared with other dementias; therefore, identification may be a diagnos­tic challenge. FTD can be misdiagnosed as a psychiatric illness or not recognized because social symptoms dominate over cognitive dysfunction. As the disease progresses, patients may become increasingly unable to plan or organize activities of daily living, behave appropriately, and react normally in social interactions.¹

FTD has 3 diagnostic variants^1-4:

Behavioral variant. Known as Pick dis­ease or the “frontal variant,”^1,2 this type of FTD manifests as changes in personality, improper behavior in social settings, per­sonal neglect, or impulsivity, such as shop­lifting or hypersexuality.

Primary progressive aphasia. Two types of language dysfunction are observed in FTD:
   • Semantic dementia (SD)³: Left-sided SD presents with “meaningless speech” or “word substitutions” (eg, “chair” instead of “table”). Right-sided SD, however, is char­acterized by forgetting the faces of familiar people or objects.
   • Primary nonfluent aphasia³: Language fluency is compromised. Persons with such language dysfunction cannot produce words easily, and their speech is stumbling and nonfluent.

FTD with motor neuron disease.⁴ The most common type of motor neuron dis­ease associated with FTD is amyotrophic lateral sclerosis. Afflicted patients exhibit muscle weakness, spasms, and rigidity. This leads to difficulty in swallowing or breathing because the diaphragm and pharynx are paralyzed. Other diseases associated with FTD include corticobasal degeneration and progressive supranu­clear palsy.

Diagnosis
In DSM-5, FTD has been renamed “fronto­temporal lobar degeneration” under the cat­egory of “Major and Mild Neurocognitive Disorders.”⁵ The workup begins with a his­tory, physical examination, and mental sta­tus assessment. Physical signs can include frontal-release, primitive reflexes. Early in the disease course, a palmomental reflex often is observed; later, as disease progress, the rooting reflex or palmar grasp may become apparent.^1,5

Diagnosing FTD requires recognizing its symptoms and ruling out conditions such as Alzheimer’s disease, depression, and schizophrenia.⁶ Laboratory studies may help identify other conditions. Brain imaging, such as MRI, can depict fronto­temporal pathology and rule in or exclude other diseases.^3,5

Psychometric testing can evaluate mem­ory or cognitive ability, which might be unremarkable during the initial phases of FTD.⁴ Further psychological assessments may provide objective verification of frontal lobe deficiencies in social skills or activities of daily living.³ Positron emission tomogra­phy and single-photon emission computed tomography may demonstrate areas of decreased activity or hypoperfusion in fron­tal and temporal lobes.⁷

Interventions
Treatment of FTD is limited to symp­tomatic therapy⁸; there are no specific, approved countermeasures available. Comorbid conditions, such as diabetes mellitus or hypertension, should be treated medically. Social interventions such as day care, increased supervision, and emotional support from the family can be effective adjuvants.²

Disclosures
The authors report no financial relationship whose products are mentioned in this article or with manufacturers of competing products.