From: http://www.springerlink.com/content/54181u74353284m3/
A prospective analysis of testicular androgenic function in recipients of a renal allograft
Rajiv Yadav1, S. N. Mehta2, A. Kumar3, S. Guleria2, V. Seenu2 and S. C. Tiwari4
(1)
Department of Urology, All India Institute of Medical Sciences, Ansari Nagar, New Delhi, India
(2)
Department of Surgical Disciplines, All India Institute of Medical Sciences, New Delhi, 110029, India
(3)
Department of Reproductive Biology, All India Institute of Medical Sciences, Ansari Nagar, New Delhi, India
(4)
Department of Nephrology, All India Institute of Medical Sciences, New Delhi, 110029, India
Received: 3 February 2007 Accepted: 16 August 2007 Published online: 8 April 2008
Abstract Eighteen adult males with end stage renal disease (ESRD) were studied to determine the serum levels of gonadotropins (LH and FSH), prolactin (PRL) and testosterone. All of the patients were studied longitudinally while undergoing maintenance hemodialysis (HD) and six months after renal transplantation. Prior to transplantation, significantly high levels of gonadotropins and PRL were observed. During HD the serum testosterone levels tended to be subnormal in most of the uremic patients and low normal in some of the subjects. Renal transplantation led to a significant improvement (P < 0.05) in serum testosterone. Elevated gonadotropin and PRL levels observed in patients on HD returned to the normal range in most of the patients after successful renal transplantation.
Keywords End stage renal disease - Hemodialysis - Renal transplantation - Prolactin - Testosterone
Thursday, March 11, 2010
Friday, May 8, 2009
American Association of Clinical Endocrinology Recommendations for Inpatient Glycemic Control
I. Critically Ill Patients
• Insulin therapy should be initiated for treatment of
persistent hyperglycemia, starting at a threshold of no
greater than 180 mg/dL (10.0 mmol/L).
• Once insulin therapy has been started, a glucose range
of 140 to 180 mg/dL (7.8 to 10.0 mmol/L) is recommended
for the majority of critically ill patients.
• Intravenous insulin infusions are the preferred method
for achieving and maintaining glycemic control in
critically ill patients.
• Validated insulin infusion protocols with demonstrated
safety and efficacy, and with low rates of occurrence
of hypoglycemia, are recommended.
• With IV insulin therapy, frequent glucose monitoring
is essential to minimize the occurrence of hypoglycemia
and to achieve optimal glucose control.
II. Noncritically Ill Patients
• For the majority of noncritically ill patients treated
with insulin, the premeal BG target should generally
be <140 mg/dL (<7.8 mmol/L) in conjunction with
random BG values <180 mg/dL (<10.0 mmol/L), provided
these targets can be safely achieved.
• More stringent targets may be appropriate in stable
patients with previous tight glycemic control.
• Less stringent targets may be appropriate in terminally
ill patients or in patients with severe comorbidities.
• Scheduled subcutaneous administration of insulin,
with basal, nutritional, and correction components, is
the preferred method for achieving and maintaining
glucose control.
• Prolonged therapy with SSI as the sole regimen is
discouraged.
• Noninsulin antihyperglycemic agents are not appropriate
in most hospitalized patients who require therapy
for hyperglycemia.
• Clinical judgment and ongoing assessment of clinical
status must be incorporated into day-to-day decisions
regarding treatment of hyperglycemia.
III. Safety Issues
• Overtreatment and undertreatment of hyperglycemia
represent major safety concerns.
• Education of hospital personnel is essential in engaging
the support of those involved in the care of inpatients
with hyperglycemia.
• Caution is required in interpreting results of POC glucose
meters in patients with anemia, polycythemia,
hypoperfusion, or use of some medications.
• Buy-in and financial support from hospital administration
are required for promoting a rational systems
approach to inpatient glycemic management.
IV. Cost
• Appropriate inpatient management of hyperglycemia
is cost-effective.
V. Discharge Planning
• Preparation for transition to the outpatient setting
should begin at the time of hospital admission.
• Discharge planning, patient education, and clear communication
with outpatient providers are critical for
ensuring a safe and successful transition to outpatient
glycemic management.
VI. Needed Research
• A selected number of research questions and topics for
guiding the management of inpatient hyperglycemia
in various hospital settings are proposed.
• Insulin therapy should be initiated for treatment of
persistent hyperglycemia, starting at a threshold of no
greater than 180 mg/dL (10.0 mmol/L).
• Once insulin therapy has been started, a glucose range
of 140 to 180 mg/dL (7.8 to 10.0 mmol/L) is recommended
for the majority of critically ill patients.
• Intravenous insulin infusions are the preferred method
for achieving and maintaining glycemic control in
critically ill patients.
• Validated insulin infusion protocols with demonstrated
safety and efficacy, and with low rates of occurrence
of hypoglycemia, are recommended.
• With IV insulin therapy, frequent glucose monitoring
is essential to minimize the occurrence of hypoglycemia
and to achieve optimal glucose control.
II. Noncritically Ill Patients
• For the majority of noncritically ill patients treated
with insulin, the premeal BG target should generally
be <140 mg/dL (<7.8 mmol/L) in conjunction with
random BG values <180 mg/dL (<10.0 mmol/L), provided
these targets can be safely achieved.
• More stringent targets may be appropriate in stable
patients with previous tight glycemic control.
• Less stringent targets may be appropriate in terminally
ill patients or in patients with severe comorbidities.
• Scheduled subcutaneous administration of insulin,
with basal, nutritional, and correction components, is
the preferred method for achieving and maintaining
glucose control.
• Prolonged therapy with SSI as the sole regimen is
discouraged.
• Noninsulin antihyperglycemic agents are not appropriate
in most hospitalized patients who require therapy
for hyperglycemia.
• Clinical judgment and ongoing assessment of clinical
status must be incorporated into day-to-day decisions
regarding treatment of hyperglycemia.
III. Safety Issues
• Overtreatment and undertreatment of hyperglycemia
represent major safety concerns.
• Education of hospital personnel is essential in engaging
the support of those involved in the care of inpatients
with hyperglycemia.
• Caution is required in interpreting results of POC glucose
meters in patients with anemia, polycythemia,
hypoperfusion, or use of some medications.
• Buy-in and financial support from hospital administration
are required for promoting a rational systems
approach to inpatient glycemic management.
IV. Cost
• Appropriate inpatient management of hyperglycemia
is cost-effective.
V. Discharge Planning
• Preparation for transition to the outpatient setting
should begin at the time of hospital admission.
• Discharge planning, patient education, and clear communication
with outpatient providers are critical for
ensuring a safe and successful transition to outpatient
glycemic management.
VI. Needed Research
• A selected number of research questions and topics for
guiding the management of inpatient hyperglycemia
in various hospital settings are proposed.
Thursday, April 16, 2009
Diagnosis of Cushing Syndrome: SUMMARY OF RECOMMENDATIONS
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 ).
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 ).
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
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