From: The Endocrine Society
3.0. DIAGNOSIS OF CUSHING’S SYNDROME
Who should be tested
3.1. We recommend obtaining a thorough drug history to
exclude excessive exogenous glucocorticoid exposure leading
to iatrogenic Cushing’s syndrome before conducting
biochemical testing (1 ).
3.2. We recommend testing for Cushing’s syndrome in the
following groups:
• Patients with unusual features for age (e.g. osteoporosis,
hypertension) (Table 1) (1 )
• Patients with multiple and progressive features,
particularly those who are more predictive of Cushing’s
syndrome (Table 1) (1 )
• Children with decreasing height percentile and increasing
weight (1 )
• Patients with adrenal incidentaloma compatible with
adenoma (1 ).
3.3. We recommend against widespread testing for Cushing’s
syndrome in any other patient group (1 ).
Initial testing
3.4. For the initial testing for Cushing’s syndrome, we
recommend one of the following tests based on its suitability
for a given patient (Fig. 1) (1 ):
3.4.1. Urine free cortisol (UFC; at least two measurements)
3.4.2. Late-night salivary cortisol (two measurements)
3.4.3. 1-mg overnight dexamethasone suppression test
(DST)
3.4.4. Longer low-dose DST (2 mg/d for 48 h)
3.5. We recommend against the use of the following to test for
Cushing’s syndrome (1 ):
• Random serum cortisol or plasma ACTH levels
• Urinary 17-ketosteroids
• Insulin tolerance test
• Loperamide test
• Tests designed to determine the cause of Cushing’s
syndrome (e.g. pituitary and adrenal imaging, 8 mg DST).
3.6. In individuals with normal test results in whom the
pretest probability is high (patients with clinical features
suggestive of Cushing’s syndrome and adrenal incidentaloma
or suspected cyclic hypercortisolism), we recommend further
evaluation by an endocrinologist to confirm or exclude the
diagnosis (1 ).
3.7. In other individuals with normal test results (in whom
Cushing’s syndrome is very unlikely), we suggest reevaluation
in 6 months if signs or symptoms progress (2 ).
3.8. In individuals with at least one abnormal test result (for
whom the results could be falsely positive or indicate
Cushing’s syndrome), we recommend further evaluation by an
endocrinologist to confirm or exclude the diagnosis
(1 ).
Subsequent evaluation
3.9. For the subsequent evaluation of abnormal initial test
results, we recommend performing another recommended test
(Fig. 1, 1 ).
3.9.1. We suggest the additional use of the dexamethasone-
CRH test or the midnight serum cortisol test in specific
situations (Fig. 1, 1 ).
3.9.2. We suggest against the use of the desmopressin
test, except in research studies, until additional data validate
its utility (2 ).
3.9.3. We recommend against any further testing for
Cushing’s syndrome in individuals with concordantly negative
results on two different tests (except in patients suspected of
having the very rare case of cyclical disease) (1 ).
3.9.4. We recommend tests to establish the cause of
Cushing’s syndrome in patients with concordantly positive
results from two different tests, provided there is no concern
regarding possible non-Cushing’s hypercortisolism (Table 2)
(1 ).
3.9.5. We suggest further evaluation and follow-up for
the few patients with concordantly negative results who are
suspected of having cyclical disease and also for patients with
discordant results, especially if the pretest probability of
Cushing’s syndrome is high (2 ).
4.0. SPECIAL POPULATIONS/CONSIDERATIONS
4.1. Pregnancy: We recommend the use of UFC and against
the use of dexamethasone testing in the initial evaluation of
pregnant women (1 ).
4.2. Epilepsy: We recommend against the use of
dexamethasone testing in patients receiving antiepileptic
drugs known to enhance dexamethasone clearance and
recommend instead measurements of nonsuppressed cortisol
in blood, saliva, or urine (1 ).
4.3. Renal failure: We suggest using the 1-mg overnight DST
rather than UFC for initial testing for Cushing’s syndrome in
patients with severe renal failure (2 ).
4.4. Cyclic Cushing’s syndrome: We suggest use of UFC or
midnight salivary cortisol tests rather than DSTs in patients
suspected of having cyclic Cushing’s syndrome (2 ).
4.5. Adrenal incidentaloma: We suggest use of the 1-mg DST
or late-night cortisol test, rather than UFC, in patients
suspected of having mild Cushing’s syndrome (2 ).
Thursday, April 16, 2009
Non- Classic CAH (Congential Adrenal Hyperplasia)
Question 1 Patient is tested for non-classic CAH in all these cases except:
1-Women with early hirsuitism including those with early premature adrenarche.
2- Women who have family history of CAH.
3- Women with hirsuitism and hyperkalemia.
4- Women with hirsuitism of from some ethnic groups with high CAH.
5- women with sudden new onset of hirsuitism after the age of 30.
The right answer is 5, all 1-4 are right indications to test for CAH. Although hirsuitism get worse with time in CAH, women with new onset sudden hisrutism at this age should be evaluated particularly for adrenal or ovarian tumors. Not all women with hirsuitims are tested for CAH since it is a rare cause of hirsuitism, the more common are polycystic ovaries and idiopathic. Every now and then you will find a woman who will not be satisfied with the diagnosis of idiopathic hirsuitism and you may need to test her for this diagnosis.
Question 2: in testing for non-classic CAH which is not true:
1- 17-OHP (17-hydroxyprogesterone) is greater than 82 ng/dl in children with this diagnosis.
2- 17-OHP is greater than 200 ng/dl in early follicular phase of women with this diagnosis.
3- 17 OHP greater than 1000 ng/dl 1 hour after 250 micrograms ACTH stimulation test confirms the diagnosis.
4- Genetic testing is important before starting treatment with dexamethazone.
The correct answer is 4. Though genotype and phenotype usually correlate most patients are diagnosed with 17-OHP response after ACTH as above. The increase in 17-OHP in this syndrome is due to the congenital deficiency of the enzyme 21- hydroxylase that convert 17 OHP to 11-deoxycortisol. Thus 17-OHP will be elevated and cause rise in androgens. 11 deoxycortisol is normally converted in the adrenal to cortisol and patients with CAH are severely deficient in cortisol in the classic or neonatal form and non or mildly so in the classic CAH. In neonatal form 17 OHP is in the thousands of ng/dl (normal newborns <100>
1-Women with early hirsuitism including those with early premature adrenarche.
2- Women who have family history of CAH.
3- Women with hirsuitism and hyperkalemia.
4- Women with hirsuitism of from some ethnic groups with high CAH.
5- women with sudden new onset of hirsuitism after the age of 30.
The right answer is 5, all 1-4 are right indications to test for CAH. Although hirsuitism get worse with time in CAH, women with new onset sudden hisrutism at this age should be evaluated particularly for adrenal or ovarian tumors. Not all women with hirsuitims are tested for CAH since it is a rare cause of hirsuitism, the more common are polycystic ovaries and idiopathic. Every now and then you will find a woman who will not be satisfied with the diagnosis of idiopathic hirsuitism and you may need to test her for this diagnosis.
Question 2: in testing for non-classic CAH which is not true:
1- 17-OHP (17-hydroxyprogesterone) is greater than 82 ng/dl in children with this diagnosis.
2- 17-OHP is greater than 200 ng/dl in early follicular phase of women with this diagnosis.
3- 17 OHP greater than 1000 ng/dl 1 hour after 250 micrograms ACTH stimulation test confirms the diagnosis.
4- Genetic testing is important before starting treatment with dexamethazone.
The correct answer is 4. Though genotype and phenotype usually correlate most patients are diagnosed with 17-OHP response after ACTH as above. The increase in 17-OHP in this syndrome is due to the congenital deficiency of the enzyme 21- hydroxylase that convert 17 OHP to 11-deoxycortisol. Thus 17-OHP will be elevated and cause rise in androgens. 11 deoxycortisol is normally converted in the adrenal to cortisol and patients with CAH are severely deficient in cortisol in the classic or neonatal form and non or mildly so in the classic CAH. In neonatal form 17 OHP is in the thousands of ng/dl (normal newborns <100>
Question 3 In treating non-classic CAH with glucocorticoids which is not true:
1- Dexamethazone is given in doses of 0.25 mg to 0.75 mg at bed time.
2- Most women and men with the disease will require glucocorticoids.
3- Glucocorticoids are given mainly to suppress ACTH secretion.
4- Cushing features and osteoporosis can result.
5- 17 OHP is used to monitor therapy.
The rigth answer is 2. Glucocorticoids are given mainly to suppress ACTH that would stimulate further synthesis of 17 OHP which would convert into androstendione that forms testosterone. It is given at night since the surge of ACTH occurs more overnight. Unlike the classic form where all patients need glucocorticoids as permanent replacement, in the non-classic form it is indicated only in females with anovulatory cycles that desire fertility, males with testicular mass or oligospermia desiring fertility. Women with non classic CAH with hirsuitism and acne are treated with oral contraceptives or anti-androgens. Patient with irregular periods are treated with contraceptive pills. The long term significant side effects of glucocorticoids even at mild doses preclude its use except mainly for the indications stated.
Treatment of Low HDL
By: Maged Taman
The National Cholesterol Education Program (Adult Treatment Program [ATP] III) guidelines, published in 2001, identified the following HDL cholesterol levels as high risk:
1- HDL less than 40 mg/dL (1.0 mmol/L)
2- For patients with the metabolic syndrome (insulin resistance syndrome or syndrome X), gender adjusted HDL-cholesterol levels of less than 40 mg/dL in men and 50 mg/dL in women.
ATP III recommends the following approach to the management of patients with low HDL :
The primary target of therapy is LDL cholesterol; this goal should be reached before treating low HDL cholesterol.
1- For all patients: intensify weight management, increase physical activity, and encourage smoking cessation.
2- When a low HDL is associated with high triglycerides (200 to 499 mg/dL [2.3 to 5.6 mmol/dL]), first achieve non-HDL goals. Thus the goal of LDL according to patient risk of cardiovascular disease.
3- If triglycerides are <200 name="32">Exercise
1- weight loss (in overweight subjects)
2- smoking cessation
3- substitution of monounsaturated for saturated fatty acids
4- Avoiding if possible medications that lower HDL-cholesterol (beta blockers and androgens)
5- Lipid lowering drugs: most effective nicotinc acid, fibrate and statin in this order. However the choice depend in the LDL levels and trigylcerides. Thus a statin is used if LDL is elevated and fibrate is used if triglyerides are elevated while in isolated low HDL nicotinc acid is the drug of choice.
Lipid lowering in Common clinical scenarios:
1- Patient with elevated LDL, normal triglycerides and low HDL: use statin to acheive LDL goal, HDL may go up some highest with crestor 10%. Nicotinc acid may be added if HDL is still low. Statin and Nicotinc acid combination cause slight increase in myopathy over statin alone.
2- If elevated LDL is accompanied with high triglycerides (200-499 mg/dl) and low HDL: statin is first started according to targeted cholesterol level, then if targets for triglycerides not achieved add fibrates. The lesser myopathy would be expected with combination of paravastatin and Fenofibrate (Tricor).
3- LDL is not elevated while triglyceride is elevated (200-499 mg/dl) with or without low HDL: Fibrate is the lipid lowering agent of choice in patients with CAD, strong family history of CAD or multiple risk factors for CAD.
4- LDL is minimally elevated while triglycerides is elevated (200-499 mg/dl) and low HDL: Fibrate is used for its main effect in triglycerides in this case and HDL. It may as well bring LDL to target. If still some elevation of LDL a statin can be added. Attentively, Ezetimibe or Bile acid sequestrant are used for statin intolerant patients.
5- Very high triglycerides (> 500 mg/dl): should be treaterd first and quickly by treating the cause as high blood sugar, stopping alcohol or drug like estrogen or tamoxifen. Meantime low fat diet and a fibrate shoud be started. Nicotnic acid may need to be added with good attention to potential rise of blood glucose. After triglyerides are lowered to less than 500 mg/dl and the risk of pancreatitis is prevented a LDL level should be addressed.
6- Isolated low HDL in high risk patients: Nicotinc acid is the drug of first choice. It raises HDL by about 30% , if goal not achieved adding fibrate like gemfibrozil may increase HDL by 45%. For patients who can not tolerate nictoinc acid gemfibrozil can be use alone. Statin like rosuvastatin (crestor) raises HDL by 10% can be considered as an add on to fenofibrate rather than gemfibrozil to minimize risk of myopathy.
The National Cholesterol Education Program (Adult Treatment Program [ATP] III) guidelines, published in 2001, identified the following HDL cholesterol levels as high risk:
1- HDL less than 40 mg/dL (1.0 mmol/L)
2- For patients with the metabolic syndrome (insulin resistance syndrome or syndrome X), gender adjusted HDL-cholesterol levels of less than 40 mg/dL in men and 50 mg/dL in women.
ATP III recommends the following approach to the management of patients with low HDL :
The primary target of therapy is LDL cholesterol; this goal should be reached before treating low HDL cholesterol.
1- For all patients: intensify weight management, increase physical activity, and encourage smoking cessation.
2- When a low HDL is associated with high triglycerides (200 to 499 mg/dL [2.3 to 5.6 mmol/dL]), first achieve non-HDL goals. Thus the goal of LDL according to patient risk of cardiovascular disease.
3- If triglycerides are <200 name="32">Exercise
1- weight loss (in overweight subjects)
2- smoking cessation
3- substitution of monounsaturated for saturated fatty acids
4- Avoiding if possible medications that lower HDL-cholesterol (beta blockers and androgens)
5- Lipid lowering drugs: most effective nicotinc acid, fibrate and statin in this order. However the choice depend in the LDL levels and trigylcerides. Thus a statin is used if LDL is elevated and fibrate is used if triglyerides are elevated while in isolated low HDL nicotinc acid is the drug of choice.
Lipid lowering in Common clinical scenarios:
1- Patient with elevated LDL, normal triglycerides and low HDL: use statin to acheive LDL goal, HDL may go up some highest with crestor 10%. Nicotinc acid may be added if HDL is still low. Statin and Nicotinc acid combination cause slight increase in myopathy over statin alone.
2- If elevated LDL is accompanied with high triglycerides (200-499 mg/dl) and low HDL: statin is first started according to targeted cholesterol level, then if targets for triglycerides not achieved add fibrates. The lesser myopathy would be expected with combination of paravastatin and Fenofibrate (Tricor).
3- LDL is not elevated while triglyceride is elevated (200-499 mg/dl) with or without low HDL: Fibrate is the lipid lowering agent of choice in patients with CAD, strong family history of CAD or multiple risk factors for CAD.
4- LDL is minimally elevated while triglycerides is elevated (200-499 mg/dl) and low HDL: Fibrate is used for its main effect in triglycerides in this case and HDL. It may as well bring LDL to target. If still some elevation of LDL a statin can be added. Attentively, Ezetimibe or Bile acid sequestrant are used for statin intolerant patients.
5- Very high triglycerides (> 500 mg/dl): should be treaterd first and quickly by treating the cause as high blood sugar, stopping alcohol or drug like estrogen or tamoxifen. Meantime low fat diet and a fibrate shoud be started. Nicotnic acid may need to be added with good attention to potential rise of blood glucose. After triglyerides are lowered to less than 500 mg/dl and the risk of pancreatitis is prevented a LDL level should be addressed.
6- Isolated low HDL in high risk patients: Nicotinc acid is the drug of first choice. It raises HDL by about 30% , if goal not achieved adding fibrate like gemfibrozil may increase HDL by 45%. For patients who can not tolerate nictoinc acid gemfibrozil can be use alone. Statin like rosuvastatin (crestor) raises HDL by 10% can be considered as an add on to fenofibrate rather than gemfibrozil to minimize risk of myopathy.
PCO
By: Maged Taman
Question 1- Diagnosis of PCO by INH criteria requires all except:
1- the presence of oligomenorrhea,
2- evidence of hyperandrogenism (clinical: acne/hisrsuitism/male type baldness or chemical: elevated testosterone level)
3- exclusion of other causes of hyperandrogenism and menstrual irregularity.
4- Poylcystic ovaries on US.
the right answer is 4. It in the Rotterdam criteria that PCO in ultrasound that is required. Two out of three of the following are required to make the diagnosis: oligomenorrhea, hyperandrogenism, and polycystic ovaries on ultrasound.
Question 2: in initial biochemical evaluation of the oligomenorrhea and/or hyperandrogenism all is required except:
1- Serum UCG
2- FSH
3- Prolactin
4- TSH
5- Total testosterone
6- 24 h urine cortisol.
The right answer is 6. 1 is first step to role out pregnancy. 2 will role out primary ovarian failure as a cause. 3 will role out prolacinoma as a cause, 4 will role out hypothyroidism as a cause. Total testosterone is measured to role out the rare cases of ovarian and adrenal tumors where the levels are likely to be high compared by PCO which will be mostly <150>
Question 1- Diagnosis of PCO by INH criteria requires all except:
1- the presence of oligomenorrhea,
2- evidence of hyperandrogenism (clinical: acne/hisrsuitism/male type baldness or chemical: elevated testosterone level)
3- exclusion of other causes of hyperandrogenism and menstrual irregularity.
4- Poylcystic ovaries on US.
the right answer is 4. It in the Rotterdam criteria that PCO in ultrasound that is required. Two out of three of the following are required to make the diagnosis: oligomenorrhea, hyperandrogenism, and polycystic ovaries on ultrasound.
Question 2: in initial biochemical evaluation of the oligomenorrhea and/or hyperandrogenism all is required except:
1- Serum UCG
2- FSH
3- Prolactin
4- TSH
5- Total testosterone
6- 24 h urine cortisol.
The right answer is 6. 1 is first step to role out pregnancy. 2 will role out primary ovarian failure as a cause. 3 will role out prolacinoma as a cause, 4 will role out hypothyroidism as a cause. Total testosterone is measured to role out the rare cases of ovarian and adrenal tumors where the levels are likely to be high compared by PCO which will be mostly <150>
Question 3: The use of metformin in PCO was found to do all of the below except:
1- Non or mild effect on improving hirsuitism.
2- Non or non-proven mild effect on endometrial protection.
3- moderate effect on restoring ovulation (4 times the placebo).
4- Non or mild effect in restoring fertility.
5- moderate effect in improving insulin resistance.
6- moderate Birth defects in women on the drug during pregnancy.
7- Fetal loss is less in women with PCO who are in metformin than placebo.
Right answer is 6. For 1 and 2 BCP are more effective. Though metformin reduces elevated testosterone level it is not effective in treating hirsusitism in these patients. For 3 and 4 weight loss and exercise are the primary approach if it fails clomiphine is the most effective. Metformin induces ovulation in PCO and was found to be effective in some studies in treating infertility in these women, but in other studies found ineffective, the consensus is it is not effective. Clomphine induces ovulation in about 80% of PCO patients and 50% conceive with it. the effect of metformin however in obese women with obese women with PCO and insulin resistance is favorable. It is considered safe in pregnancy from metanalysis of studies conducted so far. Fetal loss is less in women who get pregnant on metformin than placebo and women with PCO on metformin may need a contraception method if pregnancy is not desired.
Types of Lipid Disorders
By: Maged Taman
Type I hyperlipoproteinemia:
increase in chylomicrons.
Total cholesterol is normal with high triglycerides 2000-25000
A referigerated overnight sample shows one layer of creamy chylomicrons.
Is due to to absence of LPL activity or apo- C-II. Both are autosomal recessive.
May cause eruptive xanthomata, hepatosplenomegaly, lipemia retinalis, acute pancreatitis.
Type IIa: Familial hypercholesterolemia:
increase total cholesterol and LDL with normal triglycerides and HDL.
Total cholesterol is 275-500 in the heterozygous and >500 in the hemozygus.
second to defective LDL receptor. Autosomal dominant.
Present as premature CAD, tendinous xanthomas, xanthelsma, corneal arcus.
Faimial defective Apo B100 is a similar condition with lipid profile similar to the hemozygus above.
Type IIb: Combined Hyperlipidemia:
Increase LDL and VLDL
Total cholesterol is about 250-500 with trglycerides 250-750. with high LDL and low HDL.
gentic defect causing increase apo B 100. Autosmoal dominant.
Premature CAD.
Type III: Familial dysbetalipoproteinemia:
increase VLDL and IDL, VLDL-cholestrol to triglycerides is greater than 0.3 (normal rati is 0.2)
Both total cholestroal and trigylerides are about 250-500 range. with high LDL and normal HDL. it is autosomal recessive.
Beta-VLDL detected in agarose gel electrophoresis.
Autosomal recessive second to defective or absent apo E apo-E2 instead of apo E3 that lead to less clearance of chylomicrons remanants.
Patient present with tuberoeruptive xanthoma, plamar xanthoma.
Type IV: Familial hypertriglycerdemia:
Increase triglycerides (200-500 mg/dl) and commonly low HDL . Total cholesterol and LDL are normal.
Autosmal dominant Second to heterozygous mutation of LPL gene.
Causes increase risk of premature CAD.
Type V Mixed Hypertriglycerdemia:
increase in both Chylomicrons and VLDL
A refreigerated sample overnight will show two layers creamy supernatant from chylomicorns and lower turbid from VLDL.
Mostly secondary to partial type I due to partial LPL deficiency in patient with risk for increase triglyceride as obesity, ETOH, DM, hypothyroidism, nephrotic syndrome, estorgens or tamoxifen. Primary form is possibly due to defect on apo E.
May cause hepatosplenomgaly and eruptive xanthoma as type I
Type I hyperlipoproteinemia:
increase in chylomicrons.
Total cholesterol is normal with high triglycerides 2000-25000
A referigerated overnight sample shows one layer of creamy chylomicrons.
Is due to to absence of LPL activity or apo- C-II. Both are autosomal recessive.
May cause eruptive xanthomata, hepatosplenomegaly, lipemia retinalis, acute pancreatitis.
Type IIa: Familial hypercholesterolemia:
increase total cholesterol and LDL with normal triglycerides and HDL.
Total cholesterol is 275-500 in the heterozygous and >500 in the hemozygus.
second to defective LDL receptor. Autosomal dominant.
Present as premature CAD, tendinous xanthomas, xanthelsma, corneal arcus.
Faimial defective Apo B100 is a similar condition with lipid profile similar to the hemozygus above.
Type IIb: Combined Hyperlipidemia:
Increase LDL and VLDL
Total cholesterol is about 250-500 with trglycerides 250-750. with high LDL and low HDL.
gentic defect causing increase apo B 100. Autosmoal dominant.
Premature CAD.
Type III: Familial dysbetalipoproteinemia:
increase VLDL and IDL, VLDL-cholestrol to triglycerides is greater than 0.3 (normal rati is 0.2)
Both total cholestroal and trigylerides are about 250-500 range. with high LDL and normal HDL. it is autosomal recessive.
Beta-VLDL detected in agarose gel electrophoresis.
Autosomal recessive second to defective or absent apo E apo-E2 instead of apo E3 that lead to less clearance of chylomicrons remanants.
Patient present with tuberoeruptive xanthoma, plamar xanthoma.
Type IV: Familial hypertriglycerdemia:
Increase triglycerides (200-500 mg/dl) and commonly low HDL . Total cholesterol and LDL are normal.
Autosmal dominant Second to heterozygous mutation of LPL gene.
Causes increase risk of premature CAD.
Type V Mixed Hypertriglycerdemia:
increase in both Chylomicrons and VLDL
A refreigerated sample overnight will show two layers creamy supernatant from chylomicorns and lower turbid from VLDL.
Mostly secondary to partial type I due to partial LPL deficiency in patient with risk for increase triglyceride as obesity, ETOH, DM, hypothyroidism, nephrotic syndrome, estorgens or tamoxifen. Primary form is possibly due to defect on apo E.
May cause hepatosplenomgaly and eruptive xanthoma as type I
Hirsuitism
Question 1: In the process of evaluation of a patient with hirsuitism, which statment is false:
1-Total testesterone is less than 150 ng/dl in most patients with PCO
2-LH:FSH ratio is more than 3 is diagostic in patients with PCO.
3- Adrenal CT or MRI is indicated to role out adrenal androgen-secreting tumor if serum DHEA-s is > 700 mcg/dL .
4- A transvaginal ultrasound if serum total testesterone is > 150 ng/dL, and DHA is not significantly elevated.
5- Labroscopy is indicated if testesterone level is > 200 ng/dL with negative imaging of ovaries and adrenals to look for a small ovarian tumor (likely a hilus-cell tumor) that is too small to be detected by ultrasonography.
The right answer is 2, LH:FSH ratio used to one of the criteria to diagnose PCO however due to the pulsatility of LH as well findings of same ratio in some normal women the test is not helpful.
Most patients with PCO have mildly elevated or even normal testosterone level high level of 150 or more suggests ovarian or adrenal tumors. An elevated DHEA-s will suggest to adrenal tumor while a normal a DHEA will suggest ovarian tumor in this condition.
Question -2 In treatment of women with hirsuitism which is the wrong answer:
1-BCP is added if cosmetic measures and direct hair removal methods are commonly ineffective alone.
2-BCP may take more than 6 months to show effect in hirsuitism.
3- Anti-androgens typically spironolactone is added if BCP is not effective.
4- Avandia is effective in treating hirsuitism due to PCO.
5- Metformin have been shown to be effective in hirsuitism due to PCO.
6- Vaniqa cream for short course of 6 months will cure hirsuitism.
7- Flutamide to be avoided for hepatotoxicity.
The right answer is 6. BCP (Birth Control Pills) is the drug of choice if cosmetic measures are not effective alone. If it fails anti-androgens is added on or if used alone patient has to be in highly effective way of contraception since have effect on sex organs of male fetus. Typically spironolactone is used, flutamide has high risk of hepatoxicity. Cyproterone and finasteride are two other antiadnrogens. Though avandia (rosiglitzone) is effective in decreasing hirsuitism it cause weight gain and has a cardiovascular risk. Metformin in metanalysis of 8 studies found to be ineffective in diminishing hirsuitsim. Vaniqa cream will suppress hair growth temporarily and recurrence is common unless it is continued or BCP and anti-androgens are used as well.
LDL Pearls
By: Maged Taman
1- Adults 20 years old or more should have fasting lipid profile. If normal they can retested at least once every 5 years.
2- Lipid profile is fasting Total cholesterol, triglycerides, LDL (bad cholesterol and HDL (good cholesterol).
3- Lipid profile assessment:
Total cholesterol: <200>150 normal (preferable <100>140/90 or in blood pressure medicine.
Low HDL
Family history of premature CAD: father, brother or son <55>45 years old and women >55 years old.
HDL > 60 cancells one of the above risk factors.
5- CAD equivalents: these are other astherosclerotic manifestations that lead to same risks of CAD death and nonfatal MI like that of established CAD. They are:
peripheral vascular disease
Abdominal Aortic aneurysm.
Carotid artery disease.
Diabetes Mellitus.
10-year risk> 20%
6- LDL and non HDL goals:
CAD or CAD equivalents:
LDL goal is <100>100 or even >70
Non-HDL goal (total cholesterol - HDL) <130>130
drug for LDL > 130 and 10 year risk of 10-20%
Drug for LDL >160 and 10 year risk is <10> 160
Drug for LDL > 190
Non-HDL goal <190
7- Statins are the drug of choice for above patients decreases LDL 20-60%, resins 15-30 %, nicotinc acid 10-25 %, fibrates 5-20%, cholesterol absorption blocker Zetia 17%.
8- Patients with premature CAD and normal lipid profile: check LP (a), apo B and homocysteine.
1- Adults 20 years old or more should have fasting lipid profile. If normal they can retested at least once every 5 years.
2- Lipid profile is fasting Total cholesterol, triglycerides, LDL (bad cholesterol and HDL (good cholesterol).
3- Lipid profile assessment:
Total cholesterol: <200>150 normal (preferable <100>140/90 or in blood pressure medicine.
Low HDL
Family history of premature CAD: father, brother or son <55>45 years old and women >55 years old.
HDL > 60 cancells one of the above risk factors.
5- CAD equivalents: these are other astherosclerotic manifestations that lead to same risks of CAD death and nonfatal MI like that of established CAD. They are:
peripheral vascular disease
Abdominal Aortic aneurysm.
Carotid artery disease.
Diabetes Mellitus.
10-year risk> 20%
6- LDL and non HDL goals:
CAD or CAD equivalents:
LDL goal is <100>100 or even >70
Non-HDL goal (total cholesterol - HDL) <130>130
drug for LDL > 130 and 10 year risk of 10-20%
Drug for LDL >160 and 10 year risk is <10> 160
Drug for LDL > 190
Non-HDL goal <190
7- Statins are the drug of choice for above patients decreases LDL 20-60%, resins 15-30 %, nicotinc acid 10-25 %, fibrates 5-20%, cholesterol absorption blocker Zetia 17%.
8- Patients with premature CAD and normal lipid profile: check LP (a), apo B and homocysteine.
Saturday, April 11, 2009
Bronchial Carcinoid Tumors
All are true about bronchial carcinoids except:
1- arises from Kulchitsky cells one type of the neuroendocrine cells APUD.
2- Serum chromogranin A mild elevated.
3- Causes carinoid syndrome in less than 5%.
4- Causes acromegaly due to releasing GHRH.
5- Can cause Cushing second to the release of ectopic ACTH.
6- Silver stain is the gold standard to identify the tumors histologically.
7- CT lung will identify most of the tumors. MR with gado will show enhancement of T2 if CT can not distinguish them from vessels. Octreotide scan will show metastasis however these are rare and the scan picks up other tumors and granuloma.
8- In bronchoscopy the tumor have characteristic appearance.
9- Central carcionids are diagnosed by biopsy through bronchoscopy.
10- peripheral carcinoids are diagnosed by CT-guided transthoracic needle aspiration.
11- Treatment of choice is surgical excision with mediastinal lymph node resection.
12- Liver is the most common site of metastasis that are better image by MRI, resection would prolong survival.
13- In patient with more advanced disease the treatment of choice is somatostatin analogue.
All are correct except silver stain it used to be the common stain used in the past now the confirmatory immunohistochemical stain in diagnosing Carcinoids are NSE, synaptophysin and chromogranin. The tumors are commonly locally malignant and slowly growing with 10 years survival is over 80% atypical carinoids however tends to have worse prognosis. MRI of the liver will identify metastasis to the liver. Though carcinoids rarely metastasis less than 5%. The liver is the main site of their metastasis.
1- arises from Kulchitsky cells one type of the neuroendocrine cells APUD.
2- Serum chromogranin A mild elevated.
3- Causes carinoid syndrome in less than 5%.
4- Causes acromegaly due to releasing GHRH.
5- Can cause Cushing second to the release of ectopic ACTH.
6- Silver stain is the gold standard to identify the tumors histologically.
7- CT lung will identify most of the tumors. MR with gado will show enhancement of T2 if CT can not distinguish them from vessels. Octreotide scan will show metastasis however these are rare and the scan picks up other tumors and granuloma.
8- In bronchoscopy the tumor have characteristic appearance.
9- Central carcionids are diagnosed by biopsy through bronchoscopy.
10- peripheral carcinoids are diagnosed by CT-guided transthoracic needle aspiration.
11- Treatment of choice is surgical excision with mediastinal lymph node resection.
12- Liver is the most common site of metastasis that are better image by MRI, resection would prolong survival.
13- In patient with more advanced disease the treatment of choice is somatostatin analogue.
All are correct except silver stain it used to be the common stain used in the past now the confirmatory immunohistochemical stain in diagnosing Carcinoids are NSE, synaptophysin and chromogranin. The tumors are commonly locally malignant and slowly growing with 10 years survival is over 80% atypical carinoids however tends to have worse prognosis. MRI of the liver will identify metastasis to the liver. Though carcinoids rarely metastasis less than 5%. The liver is the main site of their metastasis.
Friday, April 10, 2009
Glucagonoma
All of the following are true about glucagnoma except:
1- The tumore arises from the alpha cells of the pancreas.
2- The tumor most often arise from the tail of the pancrease.
3- Necrolytic migratory erythema rash is specific to glucagonoma.
4- Glucagon level > 1000pg/ml is diagnostic.
5- CT abdomen with contrast is intial study for localization.
6- Endoscopic US of pancreas will help both the localization and obtaining biopsy of the tumor.
7- It is among endocrine tumors that is uniquely associated with venous thromboembolism.
All are true except 3, this rash can occur in other conditions, however it is commonly the clue to this rare diagnosis. Weight loss and diabetes mellitus are common as well. Neuropsychiatric symptoms are common. The diagnosis is usally established late after the tumor have metastasized. The diagnosis is usually made after the skin rash occured and glucagon level is commonly quite elevated > 500 the normal is 100 level can be at high normal in few patients. CT is usually the test ordered to localize the tumor and potential metastasis which are commonly to the liver. Octreotoide scan will also show the tumor and metastasis however rarely needed since the CT will visualize the tumor in most cases. The second study is usually through endoscopic US that can identify tumors and as well allow needle biopsy of the tumors in the pancreas. In the early cases with no metastasis surgical removal of the tumor is done. In hepatic predominant disease from metastasis resection of hepatic metastasis or hepatic artery embolization may be effective in slowing the disease. Octretoide is quite effective in controlling the symptoms however regress of tumor is not clearly shown. Alpha interferon and chemotherapy are other options. Disease is monitored regularly with serum glucagon and CT. It is not uncoomon to have 5 year survival of 50% in metastatic slowly progressing disease.
1- The tumore arises from the alpha cells of the pancreas.
2- The tumor most often arise from the tail of the pancrease.
3- Necrolytic migratory erythema rash is specific to glucagonoma.
4- Glucagon level > 1000pg/ml is diagnostic.
5- CT abdomen with contrast is intial study for localization.
6- Endoscopic US of pancreas will help both the localization and obtaining biopsy of the tumor.
7- It is among endocrine tumors that is uniquely associated with venous thromboembolism.
All are true except 3, this rash can occur in other conditions, however it is commonly the clue to this rare diagnosis. Weight loss and diabetes mellitus are common as well. Neuropsychiatric symptoms are common. The diagnosis is usally established late after the tumor have metastasized. The diagnosis is usually made after the skin rash occured and glucagon level is commonly quite elevated > 500 the normal is 100 level can be at high normal in few patients. CT is usually the test ordered to localize the tumor and potential metastasis which are commonly to the liver. Octreotoide scan will also show the tumor and metastasis however rarely needed since the CT will visualize the tumor in most cases. The second study is usually through endoscopic US that can identify tumors and as well allow needle biopsy of the tumors in the pancreas. In the early cases with no metastasis surgical removal of the tumor is done. In hepatic predominant disease from metastasis resection of hepatic metastasis or hepatic artery embolization may be effective in slowing the disease. Octretoide is quite effective in controlling the symptoms however regress of tumor is not clearly shown. Alpha interferon and chemotherapy are other options. Disease is monitored regularly with serum glucagon and CT. It is not uncoomon to have 5 year survival of 50% in metastatic slowly progressing disease.
Glucocorticoid-Remediable Aldosteronism
In Glucocorticoid-Remediable Aldosteronism (GRA) all are true except:
1- It is an autosomal dominant condition.
2- Patients commonly present before age of 21 years old with hypertension.
3- Family history may be obtained of GRA, brain aneurysms or intracranial hemorrhage.
4- It is due to increase production of ACTH-sensitive aldosterone in the zona fasciulata.
5- Aldosterone:renin ratio and hypokalemia are not as significant as in primary hyperaldosteronism.
6- It is primarily diagnosed with dexamthazone suppression test and the presence of elevated 18 hydroxycortisol and 18 oxocortisol.
7- It is well treatable with glucocorticoid or aldosterone receptor antagonist.
All are true except 6 the primary diagnosis now is with demonstration of the chimeric gene. It should be considered in patients with early hypertension, family history or early strokes <40>
1- It is an autosomal dominant condition.
2- Patients commonly present before age of 21 years old with hypertension.
3- Family history may be obtained of GRA, brain aneurysms or intracranial hemorrhage.
4- It is due to increase production of ACTH-sensitive aldosterone in the zona fasciulata.
5- Aldosterone:renin ratio and hypokalemia are not as significant as in primary hyperaldosteronism.
6- It is primarily diagnosed with dexamthazone suppression test and the presence of elevated 18 hydroxycortisol and 18 oxocortisol.
7- It is well treatable with glucocorticoid or aldosterone receptor antagonist.
All are true except 6 the primary diagnosis now is with demonstration of the chimeric gene. It should be considered in patients with early hypertension, family history or early strokes <40>
Craniopharyngioma
All are true about Craniopharyngioma except:
1- Arises from remnants of Rhathke pouch.
2- A cystic calcified lesion in CT is very suggestive of the tumor.
3- Is malignant with metastasis in 20%.
4- Primary treatment is surgery.
5- Edema along optic tract is common finding in MRI.
6- Both anterior and posterior pituitary can be affected.
All are true except 3 it is a benign tumor but has high recurrence rate that it is dealt with as locally malignant tumor. Histologically it can be cystic epithelia, epithelial islands with degenerative cysts or epithelial humps like the enamel of developing teeth. It rarely metastasizes. Surgery is commonly incomplete and is followed by radiation. Attempt of total or subtotal excision using microsurgery decreases recurrence but has high operative mortality and morbidity rates. Cyst aspiration or intracystic radiation or chemotherapy may be used for recreant cysts. Patients commonly present in childhood with delay growth and in adult age with sexual dysfunction of amenorrhea in females and erectile dysfunction in males. hypothyroidism, adrenal insufficiency increase prolactin and central DI can also occur. Headaches and change in vision due to pressure in the optic chiasma can also occur.
1- Arises from remnants of Rhathke pouch.
2- A cystic calcified lesion in CT is very suggestive of the tumor.
3- Is malignant with metastasis in 20%.
4- Primary treatment is surgery.
5- Edema along optic tract is common finding in MRI.
6- Both anterior and posterior pituitary can be affected.
All are true except 3 it is a benign tumor but has high recurrence rate that it is dealt with as locally malignant tumor. Histologically it can be cystic epithelia, epithelial islands with degenerative cysts or epithelial humps like the enamel of developing teeth. It rarely metastasizes. Surgery is commonly incomplete and is followed by radiation. Attempt of total or subtotal excision using microsurgery decreases recurrence but has high operative mortality and morbidity rates. Cyst aspiration or intracystic radiation or chemotherapy may be used for recreant cysts. Patients commonly present in childhood with delay growth and in adult age with sexual dysfunction of amenorrhea in females and erectile dysfunction in males. hypothyroidism, adrenal insufficiency increase prolactin and central DI can also occur. Headaches and change in vision due to pressure in the optic chiasma can also occur.
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