It seems that there has to be more and more justification to do a lab test these days. To help you understand The Underutilization of Diagnostic Blood Tests in a Primary Care Setting, Dr. Brian P. Jakes, Jr., ND, Ph.D., has prepared a review of tests reasons.
By Dr. Brian P. Jakes, Jr., ND, Ph.D.
While there has been great efforts to reduce diagnostic laboratory blood tests in primary care settings I would like to advance the supposition that these blood tests are not over used, but actually underutilized. While initial cost saving can be easily verified by the reduction of number of tests ordered the long term costs of treating delayed or undiagnosed disease will far exceed any minor cost savings of withholding these blood tests. Just one common example of failure to diagnose can be found in the estimated multimillion numbers of undiagnosed diabetics.
If there is any question to the preceding statement just consider the yearly cost of just mono drug therapy for only one year of just one disease or condition. Now multiply that figure annually then add the inevitable hospital visits and stays for emergency intervention and treatment. Finally, there are the enormous costs associated with the typical heroic measures used to try to save the patients life after many years or a lifetime of living with this condition or disease.
I believe a much more intelligent approach is to practice from a more preventive or prophylactic posture. Not only could it be ultimately more cost effective, but considerably better for the patient. Also, the practice of this type of defensive medicine could keep you the practitioner from legal action and the very unpleasant process of a medical review board. Standards of Care guidelines for testing should be the absolute minimum used and not withheld for just a few select patients.
There are any number of diseases or conditions that can be discovered early and addressed by selectively choosing diagnostic blood tests. The selection can be based on patient history, family history, current symptoms and diagnosis, and applicable risk factors. I think we can all agree that prevention is the best cure in many cases. Even if complete prevention is not possible the delay of a disease onset could still save countless thousands of dollars as well as dramatically improve your patient’s quality of life.
I have been consulted by numerous Family and Internal Medicine practices to evaluate and treat patients especially for metabolic conditions. I can not tell you just how many diabetic and pre-diabetic diagnoses I have made even in the best of practices. I think the problem lies with the type of screening that is commonly use. Fasting Blood Glucose (FBG) is typically used to make initial determination on diabetes. However, this test is completely inadequate because many patients with undiagnosed diabetes will have normal FBG, especially during the early stages of the disease. The test that should always be given when diabetes is suspected or risk factors warrant is hemoglobin A1c (HbA1c). Hemoglobin A1c will average approximately the last 90 days of all blood glucose values of the patient. Depending on the manufacture of this particular test the normal values usually range between 4.8-5.9 %. This number can be converted to give an average blood glucose value in the more common numerical range.
Now I know the Glucose Tolerance Test (GTT) has been used for the purpose of diabetes diagnoses, but I believe its has some drawbacks. There is the extended time and inconvenience to the patient needed to complete the test, not to mention multiple venous punctures. This may decrease or delay compliance of the test. Also, due to these issues the practitioner may be hesitant to order it thus making it less effective as a diagnostic tool. The HbA1c can easily be ordered with a routine blood draw even without fasting, which will insure compliance. There are also instant HbA1c testing devices that can be used in clinic and require no more blood than a conventional glucometer.
To give you the significance of using the HbA1c as compared to using just the FBG I will tell you that in most of my diabetes diagnoses the FBG is normal while the HbA1c is well within the diabetic range. Furthermore, I routinely see HbA1c values not only in the 6 or 7 % range, but sometimes even over 8 %. That would equate to an average blood glucose of 200 mg/dl. To achieve those averages and still have a normal FBG the patient might be experiencing post prandial blood glucose values nearing 300 mg/dl. Recent studies suggest that elevated post prandial glucose values might play a more significant role in the development of diabetic complications not just the overall blood glucose average.
The interpretation of the HbA1c or any diagnostic test for that matter can be equally as important as ordering the test itself. For example, your patient’s HbA1c returns with a value of 5.8 or 5.9, which is within normal range. Since it is within normal range your patient doesn’t have anything to worry about right? Nothing could be farther from the truth. Typically if no type of intervention is undertaken this patient will more than likely be within the diabetic range within the next year. I realize that HbA1c is not currently recognized as a diagnostic tool, however, it still exposes your patient’s inability to properly metabolize glucose and this condition is not going to improve without intervention.
I have to comment about the interpretation or should I say misinterpretation of many diagnostic blood tests. More times than I would like to remember I have seen patients treated by primary care providers, specialists as well as in the emergency room with lab values within a fraction of a point of abnormal and this condition is summarily ruled out or completely ignored. I realize that with most common tests this fractional difference is not critical, however it does give an indication or a trend, which deserves to be investigated further. Now for tests like blood glucose, thyroid and various other hormones, which are typically more dynamic, I believe a movement towards intervention and treatment would be more prudent.
I would also like to expound on the benefits of routinely complimenting the HbA1c with serum insulin and c-peptide levels. I believe these tests are a necessity when diagnosing and treating a diabetic as well as evaluating a patient in a pre-diabetic phase. These additional tests are essential when trying to determine endogenous insulin production. This will also assess the need for or the success of treatment with sulfonylurea and meglitinide class oral hypoglycemics. When elevated glucose levels will not trigger significant insulin release first stage beta cell failure is usually the likely cause. Sulfonylurea and meglitinide class drugs will at least temporarily correct this condition. However, insulin levels should be monitored periodically to detect complete beta cell failure, which will cause virtual sensation of insulin production.
In your patients that are using injected exogenous insulin residual endogenous insulin production can be monitored by checking c-peptide levels. C-peptides are released in a one to one molecular ratio to insulin. There is also a specific serum insulin test that will differentiate between injected insulin and endogenous insulin as well. The levels of c-peptides and serum insulin should usually correspond with each other except in a few rare conditions.
Now what would you do with an overweight or obese patient with a family history of diabetes and their FBG and HbA1c are both well within normal limits? You might say since their FBG and HbA1c are safely in the normal range there shouldn’t be any additional testing needed. This could be a hasty mistake. While their FGB and HbA1c might be normal it could be kept under control at the expense of secreting enormous amounts of insulin. Hyperinsulinemia is an extremely common condition in pre-diabetic and newly diagnosed Type II diabetics. Glucose control will be maintained until insulin production decreases or insulin resistance increases. Hyperinsulinemia may appear many years before any elevation can be seen in FBG and HbA1c. Routinely using serum insulin testing in high risk patients will expose this condition and allow early intervention.
We all know the importance of monitoring cholesterol levels for cardiovascular risks, but has too much attention been made to them resulting in the exclusion of other risk factors? I believe that studies show the nearly equal importance of examining other cardiovascular risk factors concurrently. Homocysteine, C-reactive protein, Lipoprotein A and B are just a few common tests that need to be considered if symptoms warrant. Homocysteine is a radical amino acid, which had an affinity for the intima lining of blood vessels. Like all radicals they tend to destabilize susceptible substances and in this particular situation it is the inner most lining of blood vessels. The corruption of the intima lining can more easily allow cholesterol accumulation and occlusions. Fortunately homocysteine is controlled by a combination of three B vitamins.
C-reactive protein (CRP) monitors inflammatory processes both systemically and also specifically in the vascular system. The measurement of highly sensitive or cardio specific CRP (hs-CRP) can alone be an independent predictor of coronary heart disease.
There are a number of agents both pharmacological and non-pharmacological that can effectively reduce CRP levels. Most statins, ACE inhibitors, ARB’s and anti platelet drugs can lower CRP, while aspirin and vitamin E can work equally as well. Lipoprotein and apolipoprotein could also be predictors of coronary heart disease and as well as other cardiovascular diseases. These tests can easily be included at the next cholesterol draw and truly should be offered given the risks as well as the benefits with intervention.
Discussing the intricacies of thyroid testing could easily consume this whole article and it still would require further discussion. One of the first areas I would like to explore is diagnosis of hypothyroidism. I can’t tell you just how many times patients complain of typical hypothyroid symptoms, but they have been told that they are not hypothyroid by their physician. One of the first considerations is determining what thyroid stimulating hormone (TSH) test scale is being used.
The American Association of Clinical Endocrinologists as well as other professional groups have accepted a lower upper limit for normal TSH. The suggested normal range would now be between 0.5 – 3.0 mIU/L and this would expand the subclinical range of hypothyroidism from 3.01-10.0 mIU/L. While there is some disagreement on this issue I and many other physicians I know have seen nothing but clinical benefit in the patients treated for subclinical hypothyroidism. Fatigue, weight gain, alopecia, hyperlipidemia, dry skin, hypotension and constipation have been either significantly improved or even resolved with treatment without any adverse side effects.
Another issue concerning the diagnosis of hypothyroidism or hyperthyroidism deals with what tests are being used to make the diagnosis. The use of TSH alone or in conjunction with T4 are truly not enough to make an accurate determination of thyroid function. First, there is no way of knowing what the status and levels of T3 or if there is the presence of thyroid antibodies. When symptoms and family history warrant I typically will run the following tests: TSH, T4 free, T4 total, T3 free, T3 total, T3 resin uptake, thyroxin binding globulin (TBG), thyroid peroxidase (TPO). If there is also known patient history of thyroid dysfunction I will additional include more specific testing.
Again, I have diagnosed a number of patients with either hypo or hyperthyroidism with normal TSH. While it is not as common as compared to those with altered TSH it is always something to consider. Also, when treating hypothyroid patients presenting with fatigue or chronic fatigue issues the tight control of TSH between 1.0- 2.0 mIU/L appears to effectively alleviate symptoms without the risk of hyperthyroidism. Furthermore, I prefer the use of Armour Thyroid as compared to Levoxyl or Synthroid because it supplies a natural version of both T3 and T4. Studies suggest its superiority to synthetic treatment for symptom improvement even when TSH, T3 and T4 levels are comparatively matched.
I feel I need to make mention of two very common gastroenterology (GI) conditions that often get overlooked. The first would be helicobacter pylori or H. pylori. It is a bacterial infection found usually in the gut. It can responsible for a number of GERD diagnoses as well as typical ulcer symptoms. I find about one third of the patients I test for H. pylori, that are currently under proton pump inhibitor (PPI) therapy, are infected. Many of these patients I test are under treatment by a gastroenterologist, so it is always good to rule it out despite specialist treatment. The addition of two weeks of two specific antibiotics to the PPI therapy has resolved most or sometimes all of the GERD symptoms and GI pain.
Candida yeast infection can cause GI pain, bloating, weight gain and constipation, but in severe cases fatigue, myalgia and joint pain can be common. It appears that its diagnosis is more common in diabetics and obese patients. Candida is associated with cravings of carbohydrates and elevated blood glucose levels, which can create an ideal environment for its growth. Testing would include both serum candida antibodies as well as a stool culture. Please note that stool cultures are usually more revealing for most diagnosis and treatment purposes.
One of the most overlooked areas for patients with depression, anxiety, weight gain and fatigue are both male and female hormones. I find virtually every woman I test no matter what age having below normal progesterone levels. Once treated with natural progesterone the previously mentioned symptoms improve significantly to dramatically. Estrogen therapy needs to be approached much more carefully due to potential risks. However, the use of bio-identical hormone therapy greatly reduces these risks. Testosterone levels should always be a consideration for men experiencing erectile dysfunction, decreased libido, fatigue, depression and weight gain. Also, the precursors for these hormones may play a direct role in their decreased levels. Dehydroepiandrosterone (DHEA) and dehydroepiandrosterone sulfate levels peak typically in the 20’s then decline dramatically throughout someone’s lifetime. Because DHEA is involved in the production of virtually every hormone in the body, treatment with DHEA can moderately increase both male and female hormones. Also, the supplementation with DHEA is essential for patients suffering from fatigue, adrenal insufficiency or chronic fatigue syndrome.
Hepatic and Renal function
Several important notes regarding renal and hepatic function. As with many organs a decrease in function may not be reflected in typical lab testing. The liver can absorb a considerable amount of impairment without alterations in alanine aminotransferase (ALT), aspartate aminotransferase (AST), or alkaline phosphatase levels. Gamma glutamyl transferase (GGT) is additional liver function test that might reveal impairment that would have otherwise gone unnoticed. Additionally, I have seen treatment with N- acetyl-cysteine symptomatically benefit patients with normal hepatic levels who have had a history of hepatitis and cirrhosis. So while these lab numbers are important they should not be the absolute when treating your patient. Also be aware that not only thiazolidinediones class hypoglycemics such as Avandia and Actos can elevate liver function tests, but metformin can as well due to the tissues it targets. Routine monitoring of all liver function tests should coincide with the current frequency of HbA1c testing.
Diabetic and hypertensive patients should have routine monitoring of creatinine, blood urea nitrogen (BUN), glomerular filtration rate (GFR) and microalbumin. Please keep in mind that kidneys can accrue nearly 50% percent of injury without revealing any elevations in creatinine and BUN. Furthermore, just because creatinine and BUN are within normal limits does not mean GFR or microalbumin are normal as well, so both comprehensive testing and careful interpretation should be used. Early intervention with ACE inhibitors, ARB’s and specific supplements can stabilize and even improve renal function.
In conclusion this very limited review is an attempt to make practitioners more aware of the uses of common diagnostic tests that can aid in both the treatment and prognosis of their patients. Due to submission limitation I have purposefully withheld references and citations, but will supply them upon request.