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It is a relief and a pleasure when a complex case turns out to be easy.  An orthomolecular physician in Upstate New York sent me a fax regarding a 32 year old woman he is treating for shoulder pain following a motor vehicle accident.  Injections of cortisone (triamcinolone) had been dramatically beneficial: her pain disappeared, good sleep returned, energy level and mood improved, and her skin "acne" cleared.  All symptoms relapsed when the effects of the shot wore off.  In addition she reported additional symptoms: abdominal bloat, thinning hair and green finger nails.  Cortisone taken by mouth did not work, so she had already had 3 injections.   The doctor wondered if she might have a genetic problem.  He was specifically intrigued by the possibility of phenylketonuria because she claimed that diet Coke relieved her symptoms!  He had heard one of my lectures on ADD-Autism and thought I might be able to answer this for him.

However the question of genetic disorder is not very relevant, especially since the observation that she feels better after drinking diet 'Coke'.  That says she is not reacting badly to phenylalanine.  Instead it suggests that caffeine from 'Coke' is acting like a shot of cortisone.  Caffeine stimulates the the release of adrenalin and this stimulates the pituitary gland, which signals the adrenal glands to release cortisone.  Phenylalanine might also work for her by supporting the production of adrenalin.  Does the reference to diet Coke mean that she is a junk food junkie? 

At that point a flurry of possibilities came to mind, and of course I was intrigued by the green fingernails because I have seen green hair, which can occur when blonde haired swimmers use pools that are treated with copper sulfate.  Such water takes on a blue color and it is chemically reactive with the sulfur protein, keratin, in hair.  Blue and yellow combine to make green and that is the color of blonde hair when exposed to blue copper.  If you know someone who is worried about their green hair, tell them about the hair mineral hair test, for it will show copper at 200 to 300 parts per million in the green hair of these swimmers.

But this patient did not have green hair; only green fingernails.  How to explain that one?  Green is not a natural color of any human tissue except breakdown products of blood pigments, as happens when heme (purple) is oxidized to biliverdin (green) in bruised tissues.  But this patient's fingers were not injured only her shoulder, and those bruises had already cleared up.  My guess is that her nail beds have had a bluish tinge due to sluggish circulation and that she had yellowing of her tissues due to increased carotene since the accident.  Blue blood filtered through yellow tissues makes for a greenish tinge to the nail beds.  Green fingernails. 

Why would carotene be increased after an accident?  Because she has been taking vitamins, including carotene, and juices, and eating more vegetables.  It is also important to consider the possibility of a low thyroid condition, which is more common after acute and chronic stress, such as prolonged pain states.  Low thyroid might also explain her intestinal gas and hair loss.  Low thyroid status causes sluggish intestinal activity and inefficient digestion.  Because thyroid is required for full activity of the vitamin folic acid, there is a decline in production of nucleic acids and polyamines, substances required for cell repair and healing.  This can cause hair loss, as happens in cancer therapy, which uses chemicals to block folic acid. 

The connection between green fingernails and high carotene increases the likelihood of vitamin A deficiency as well, for if carotene is high, it is not likely being converted adequately into vitamin A.  Few people these days get enough vitamin A by eating liver, eggs and/or cream.  Carotene is vegetable vitamin A but it is not active until oxidized by an enzyme in the intestine, one that is often impaired, especially in those who are hypo-thyroid or diabetic.

Hair loss is a classic symptom of vitamin A deficiency and also of low thyroid activity.  In cases of vitamin A deficiency the hair loss is due to changes in the cells (keratinocytes), which produce keratin, a form of collagen found in hair and skin.  Both mucous and keratin contain sulfur containing proteins, called glycos-amino-glycans, i.e. GAG proteins.  One of the critical factors in producing these GAG proteins is an enzyme called PAPS, Phospho-Adenosine Phospho Sulfate. This enzyme is required for transfer of sulfate for collagen protein in hair, skin and connective tissues.  PAPS requires vitamin A and that is a big part of why vitamin A is important in hair growth.  Of course, sulfate is derived primarily from sulfur amino acids, such as methionine; hence low protein intake or intestinal malabsorption, can also cause hair loss, reduction of keratin in hair, and lack of binding sites for hair dyes--which shows up in the beauty salon as a customer complaint.

The doctor was quite impressed with these ideas and came back with an additional piece of information.  It turns out that the mother and maternal grandmother of this woman had suffered from excessive fatigue and depression during pregnancy.  This raises the question of a familial problem, such as gestational diabetes, which is often related to vitamin B6 deficiency.  Vitamin B6 needs increase by at least a third during pregnancy.  Deficiency is associated with accumulation of high levels of XA (xanthurenic acid), a by-product of the amino acid, tryptophan.  The connection to B6 is so reliable that XA is used as a laboratory test for vitamin B6 deficiency.  Xanthurenic acid is known to cause or aggravate pancreatic damage, just a bit weaker than its look-alike, alloxan, which is so toxic to the pancreas that it is used to cause diabetes for research purposes in the laboratory.   

My colleague was grateful for our time together but had to get back to his busy day.  I left him with my advice to perform laboratory confirmation of her vitamin B6 status and to test her saliva for cortisone.  He had been puzzled by her complete remission from all symptoms after receiving injections of the synthetic cortisone, triamcinolone (10 mg) and her failure to respond to natural cortisone (20 mg).  Triamcinolone (Aristocort) is 5 times more active than natural cortisone and has a duration of action 2 to 3 times as long; hence it would require two doses of 20 to 30 mg of hydrocortisone to compare with 10 mg of triamcinolone.  This was in conflict with his expectation to wean her completely from cortisone; hence his puzzlement. 

Hormonal diagnosis has been facilitated recently by the introduction of saliva testing, which has the advantage that hormones are in the free form, rather than bound to transport proteins as is the case in blood testing.   Free hormones are the active form of the hormones, hence they more nearly reflect the activity of the hormone.  Testing saliva is also more convenient and less expensive than blood testing--and most people would rather not have a needle stick.  The biggest change that I forsee is panel testing of multiple hormones.  The lower costs makes it possible for general practice physicians to diagnose, understand and treat hormone related disorders that previously would have been unrecognized. 

The improvement in laboratory testing does not necessarily simplify the process of diagnosis however.  I recall a similar case in my own practice:  a 50 year old woman with shoulder and neck pain that came on after her car was broad-sided by a truck.  Complete recovery from pain and numbness in her hands was delayed for six months before re-testing made the diagnosis clear. The initial salivary hormone panel showed her estrogens, progesterone, DHEA, and cortisone were all low normal except testosterone, which was truly low.  I prescribed natural progesterone cream based on reports of success in osteoporosis and because it is also very safe.  However my patient continued to complain about persistent skeletal symptoms in her neck, arms, hips--it seemed like everywhere for the next few months.  In other ways she looked better and had more energy; but her target symptoms persisted.  I was perplexed so when it was time for follow-up testing, I ordered a test to measure the amount of bone peptide lost in the urine and a repeat saliva hormones panel. 

The results made the diagnosis easy: steroids and cortisone had improved, in keeping with her general energy and well-being; but progesterone and testosterone remained low.  At the same time she showed a 50 percent excess of bone peptides in her urine.  This explains the persistence of her symptoms: her bones are weakening and if the process goes unchecked she is destined to suffer deposition of calcium in soft tissues, including blood vessels and skin, and accelerated aging, stooped posture, hip fractures--and premature death.  That is the syndrome of osteoporosis.

Now it was my turn to be puzzled--why was the progesterone creme not working?   The answer is in the saliva test.  It showed that she was not using enough of the creme.  In fact, questioning her now revealed that she had only used one tube in 6 months!  Once that was corrected the rest is a happy ending: she is feeling better, and by keeping doses within physiological limits, and monitoring with the advantage of laboratory support, a disaster has been prevented.  It is now quite rational to try a low dose testosterone supplement because this hormone is an anabolic steroid and promotes tissue repair.  If bone loss can be prevented she will be spared the accelerated aging that afflicts so many people in their later years. 

Green fingernails are a dramatic clue to clinical diagnosis the old-fashioned way, but hormone testing offers more drama and excitement-- a true glimpse of the orthomolecular microcosm of life. 

 

©2014 Richard A. Kunin, M.D.

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