James K. Rone, MD, FACP

THIS PATIENT EMAILED ME ABOUT FEELING FATIGUED, MOODY, AND UNINTERESTED IN SEX 2 YEARS AFTER HER DAUGHTER WAS BORN. SHE MENTIONED HER MARRIAGE WAS ON “THIN ICE” AS WELL.

Let me start with a few general caveats and a few comments upon some of your statements, then I’ll try to provide you some helpful guidance. And please try not to take offense at anything I say—I wouldn’t be doing my best for you if I weren’t honest.

1. If there is a role for testosterone replacement in women—and there probably is, we just haven’t worked out the safety questions, the proper reasons to use it, how to dose it, and there is no practical FDA-approved product that can be adapted easily to the lower doses that would be appropriate in women compared to men—that role would not be in premenopausal menstruating women, but rather in postmenopausal women, especially those who have had a total hysterectomy (taking the ovaries, which still produce testosterone after menopause), and who are disturbed by a lack of libido, which is the main testosterone effect in women, though there may also be some role with respect to fatigue and maintenance of lean body mass (as opposed to fat mass).
2. My reason for excluding premenopausal menstruating women from this potential role for female testosterone replacement, is because the existence of mostly regular monthly menses proves the proper functioning of the brain, pituitary, and ovaries with respect to sex-steroid production—it doesn’t take much to interrupt regular menses, so if you are regular, chances are everything is running as it was physiologically intended to, and if you are not, it is extremely doubtful taking testosterone would be the solution (the opposite might even be the case).
3. By the way, the presence of underarm and pubic hair proves the presence of testosterone and/or DHEAS, the largely similar adrenal hormone, and speaks against the need for replacement of either.
4. Now, giving supplemental testosterone to a premenopausal menstruating woman, is profitable to the clinic doing it, and may well improve energy and libido, but none of that means it’s safe, especially over the long run. Cocaine makes people feel good, but most of us would agree using it is a bad idea, right? Potential side effects of testosterone replacement in young women would include acne, facial and body hair growth, clitoris enlargement, and potentially cancer promotion and potentially birth defects in a female fetus should pregnancy occur. In short, no matter how beneficial it might seem, it’s a bad idea, at least given the current state of our knowledge.
5. With regard to your situation, obviously the best outcome would be for some relatively simple to treat medical condition to turn out to be responsible for your symptoms. I’m forced to point out though that it is not at all unusual—for all kinds of reasons—for young mothers to be fatigued, irritable, distracted, and to have a low sex drive. I don’t need to tell you that having an infant or toddler in the house adds stresses, changes established lifestyles, can be exhausting (especially if you’re working outside the home as well—you don’t say), and not unusually alters the marital relationship, not always for the better. My point being: your friends who say it is “just motherhood” aren’t necessarily wrong—and you finding the answer “unacceptable” doesn’t change that, nor does the fact that your “marriage is on thin ice.” Don’t misunderstand—I’m not unsympathetic to your plight, but the acceptability of the answer is irrelevant. I’m sure many patients with cancer find that unacceptable too.
6. Along the same lines, I will freely admit that depression is diagnosed and treated in situations such as this, excessively, and often wrongly. That fact alone, however, does not automatically make the diagnosis wrong. Food for thought.
7. You mention “hormone balancing.” I don’t know what that means. It’s not a concept any real endocrinologist embraces. It is hype, a catch phrase that alternative-medicine providers—who don’t really know what they are talking about—use. To the extent that hormones need to be “balanced,” our bodies are generally much better at it than you or I or the compounding pharmacist are. (I’m not attacking you, I’m attacking practitioners who throw cool-sounding terms like that around like they mean something.)
8. Don’t be taken in by saliva hormone testing that is used and promoted by many purveyors of bio-identical hormones. Most such testing is unvalidated with respect to accurately diagnosing endocrine disorders. For the most part, real endocrine disorders are only confirmed by carefully done and timed serum testing.

Now, on to the, hopefully, helpful part of this:
1. I’ve treated a great number of patients for hypothyroidism in recent years, whose other doctors said their thyroid levels were “normal,” and it was life changing for some, not all of course. Suffice it to say—I never accept a report of “normal” thyroid functions without looking at the numbers myself. So please send me whatever thyroid test results you can get ahold of and I’ll let you know what I think—send the result and the normal range as they differ from lab to lab. Bare minimum I need a Free T4 and TSH to make a reasonable assessment—but send me whatever you have.
2. Did you experience any peripartum hemorrhage/serious delivery complications? Sometimes that damages the thyroid and other endocrine control mechanisms in ways that are not always easily discernable.
3. Did you breast feed successfully?—if so, that rules out what I was getting at in #2.
4. You mention exercising regularly and that it is mostly “cardio.” I strongly suggest adding resistance training to the mix. Endurance training as you are doing is important and valuable, but resistance training (i.e., weightlifting, and, yes, yoga and stretching to engage muscles we don’t even think about) builds muscle, improves ability to manage activities of daily living, helps weight management more so than endurance training does—and, most relevant for this discussion, the more muscle you have the less fat you have and the enzyme aromatase in fat converts testosterone to estrogen, depleting your body of testosterone.
5. And by the way, dovetailing with my earlier points, it is in fact physiologically normal for the female body to try to rid itself of testosterone, enhancing “estrogen effect” and, frankly maximizing fat deposition (within reason) to assure available caloric resources to maintain a pregnancy and nourish the infant. In other words, to repeat, this notion of supplementing testosterone in young women is just plain wrongheaded. Focusing on profit and “feeling good” over normality.
6. Also, you say you eat healthy, and perhaps you do, but I believe much of what is popularly labeled “healthy” is in fact not, or at least not the best diet for all. Consider increasing protein and fat intake, and limiting carbs, especially breads, and I have virtually eliminated high-fructose corn syrup from my diet. Hydrate well with water, and frankly black coffee is a pretty healthful drink and the caffeine may help your energy.
7. To summarize—send me your thyroid levels and I’ll advise you accordingly. No to testosterone. Yes to resistance training, perhaps yoga. Try changing up your diet since you feel lousy doing whatever it is you are doing. Don’t just assume what everybody says is healthy really is for you. And, frankly, if your marriage is on “thin ice,” regardless of the cause, I’d advise couples counseling. Can’t hurt. Read More 

THIS PATIENT CONTACTED ME WITH QUESTIONS ABOUT THE MANAGEMENT OF HER POSTSURGICAL HYPOPARATHYROIDISM (WHICH CAUSES LOW SERUM CALCIUM LEVELS—SHE WORRIED ABOUT THE FACT THAT HER URINE CALCIUM WAS HIGH ON HER NEEDED CALCIUM AND VITAMIN D SUPPLEMENTATION:

My usual tx for hypoparaT is around 2000 mg calcium (Ca++) per day in 2 or 3 divided doses with meals (Ca++ carbonate or Ca++ citrate are fine). That should be enough Ca++ for most people. Any further adjusting of the Ca++ level is done with calcitriol, which is an activated form of vitamin D. We have to use that instead of Vitamin D2 or D3 (the typical Vit D supplement products) because parathyroid hormone (PTH) is needed for the activation step in the body. If you’re hypoparathyroid, we have to give a form of Vit D that skips that step.

I'll just go through your email and address your questions as they come:

--in hypoparaT Ca++ blood levels should be low normal or even a bit low, as long as symptoms are controlled (little or no tingling or cramping or spasms)--this helps avoid exposing the kidneys to too much Ca++, which can cause kidney failure over years.

--you mention albumin in the urine--that's likely unrelated to the Ca++ issues but if present above certain levels indicates kidney disease, such as the type caused by diabetes. The only way the Ca++ issue would relate to albumin in the urine would be that if you had low renal function due to some other problem, or likely future deterioration in function due to some other problem, you'd want to be as careful as you can that the Ca++ doesn't add to the kidney trouble.

--That said, it is critically important to keep adequate Ca++ levels in the blood, and it sounds like you're where you need to be, so I wouldn't worry about the urine Ca++ level. This is never going to be an ideal situation--hypoparaT puts the patient between a rock and a hard place--renal damage from the Ca++ tx is a real risk if things aren't done very carefully. It's not an easy disease for the doctor to manage.

--I especially wouldn't worry about the urine Ca++ if you don't have recurring kidneys stones or known renal insufficiency

--you are correct--active Vit D mainly helps gut absorption of dietary Ca++ and Ca++ tablets. It also tells the kidneys to reabsorb Ca++ into the blood and reduce loses via the urine. PTH does the same thing to Ca++ in the kidney but if you're missing that then the Vit D is more important. Eventually though, once the blood levels of Ca++ get high enough the Vit D effect is overwhelmed and Ca++ "spills" in the urine--and you want that--if it didn't happen you could get a dangerous high Ca++ in the blood. That's why I say, for the most part, let the kidneys do their thing and ignore the urine Ca++. The kidneys, if they're working right, are smarter than we are--we shouldn't be trying to outguess them.

--I think I've answered your question about Ca++ intake already--whatever combination of around 1800-2000mg Ca++/day plus calcitriol that results in the goal Ca++ level (right around the low end of normal) and good symptom control. If those criteria are met then I wouldn't adjust anything to "fix" the urine Ca++. If there are stones or other significant renal disease going on besides the hypoparaT then that is a complicated situation your doctor (preferably an endocrinologist or nephrologist in that case) has to figure out.

--I don't have a clue what good potassium bicarbonate would do--manipulating urine pH is something nephrologists do and if you need that you should be seeing one--I doubt you need it though, and my knee-jerk answer is don't take it, especially on your own, without the advise of the doctor managing this problem.

--You said "Vit K2"--Vitamin K affects blood clotting and has nothing to do with this--I assume you mean Vit D2, and I've already addressed that--D2 and D3 build up the storage form of Vit D but they can't be converted to the active form in HypoparaT (or for that matter, if there is significant kidney damage from any cause, because the activation step is done by the kidney). So, no, Vit D2 or D3--the stuff you can get over the counter--would be of no use in the situation as you described it to me. Calcitriol is your only Vit D (there are other similar prescription products but I just use calcitriol).

jkr Read More 

A LARGELY STAND-ALONE DISCUSSION FROM THE APPENDIX OF MY UPCOMING BOOK ON OBESITY:

I have concerns about how the academic elite of medicine develop clinical practice guidelines intended to direct the care given by other physicians, as well as to inform insurers what ought and ought not be covered. There is a special need for scrutiny in this era where legitimate cost-containment, coupled with the increasing influence of third party payers, like federal and state governments, and the massive private insurance industry—which prioritize costs often over the wants and needs of patients and doctors—are driving “evidence-based medicine” and risk denying patients care and treatments not anointed by the “evidence.”

By this I mean a certain treatment or test, unless called for by a few top docs, at major medical schools, in their published guidelines, or supported by excellently conducted research reported in a scientific journal, might not be available to real-world patients. Perhaps worse, I think physicians today come out of training cowed by these top experts, devaluing their own thoughts and practice styles, subjugating them to evidence-based (“cookbook”) medicine. Keep in mind that every licensed medical doctor has an undergraduate degree, a four-year medical degree, and usually three-to-five-or-more years of post-graduate training. Such professionals are well trained enough to formulate their own preferred ways of managing patients, if encouraged and allowed (that is, paid) to do so, which they are often not.

Now, don’t misunderstand. Well-conducted research and peer-reviewed papers and clinical practice guidelines are necessary to good medicine. But once that information is out there, it should be the independent physician figuring out how to apply that data to each unique patient. No matter how good the research and conclusions, they can never anticipate all the variables confounding a real-world situation. And even if evidence-based medicine’s answers could be accepted as 100 percent valid, there will never be adequate evidence to answer every question faced by every physician in the course of one routine week.

Our original question from the text was:
Why did it take until less than ten years ago for low-glycemic-index dieting to get taken scientifically seriously? Smart people were talking about it. Why didn’t opposing theories get a fair shot at the height of the gung-ho all-fat-is-bad days? Isn’t the job of science to consider all possibilities, test for them, throw out ideas proved wrong, and refine ideas proved right, until gradually, inexorably we approach some great universal truth?

I used to think so.

Yet my experience has not always shown science to work that way.

There are several questions—low-fat versus low-carb being one, but there are others—in just my subspecialized area of medicine, where it seems to me experts wear bizarre blinders about even contemplating dogma-threatening new ideas. And I stumbled upon an explanation—or at least, objective confirmation of what I’ve observed—a mere few weeks prior to this writing.

Harvard-trained physicist, turned historian and philosopher of science, Thomas S. Kuhn (1922–1996) published a landmark book in 1962 titled, The Structure of Scientific Revolutions. In it, he threw out the notion that I had, and most of us have: That romantic view of science as, in the words of North Carolina State University philosopher, Jeffery L. Kasser, “straightforwardly cumulative, progressive, or truth-tracking.”

This traditional, romanticized image of science includes an “openness to criticism,” an almost obsession with disproving itself, that Kuhn felt did not exist in real-world science.

Normal science, according to Kuhn is governed instead by paradigms. A paradigm is an object of consensus, not open to criticism. The paradigm is assumed to be correct. It is dogma. It determines the puzzles to be solved, which involve fitting nature into the paradigm, and defines the expected results and the standards for evaluating those results. Science doesn’t seek truth, it seeks to prove the paradigm. “Dietary fat is unhealthy and the main promoter of obesity” was the paradigm in our discussion, and few mainstream researchers were allowed to, funded to, do research other than to prove that proposition. Read More 

RECENTLY THE MEDICAL DIRECTOR OF MY CLINIC’S WEIGHT LOSS PROGRAM LEFT AND I TEMPORARILY TOOK OVER THAT ROLE. AFTER RETURNING FROM THE ANNUAL AACE MEETING IN PHOENIX, I OFFERED THE FOLLOWING DISCUSSION TO MY PARTNERS:

As Interim Medical Director of NexSlim at MMC, I wanted to take this opportunity to update you on the just-published AACE (Amer. Assn. of Clinical Endocrinologists) Comprehensive Diabetes Algorithm, which includes sections on prediabetes management, glycemic control in T2DM, and dyslipidemia—each of which begins, no surprise, with lifestyle modification. But, in each case that recommendation expressly includes “medically assisted weight loss.” Further, a separate algorithm for overweight and obesity calls for “medical therapy” if BMI is greater than 27 with cardiometabolic or biomechanical complications of either low, medium, or high severity, if lifestyle modification fails to achieve goals. They specify this medical therapy can include phentermine, orlistat, lorcaserin, or phentermine/topiramate ER—the latter two being Belviq and Qsymia, both approved by the FDA in 2012.

I find these recommendations groundbreaking, and no doubt will be controversial. Use of anorectic drugs has a historically poor reputation, and has been fraught with toxicity issues—in fact, every drug introduced prior to 2012 for long-term use for weight loss has had to be withdrawn from the market for that purpose, starting with thyroid extracts 120 years ago. My own experience with anorectics is admittedly limited, nor have I been impressed with their efficacy to the extent that I have used them. To be sure, there are genuine concerns about a lack of long-term maintenance of any weight loss that is achieved, but lifestyle interventions have the same failing.

All that said, we need to sit up and take notice that a major mainstream medical organization is strongly calling for the use of these drugs as part of a comprehensive, multifaceted effort. This is a recognition, and a call to action, that mainstream clinicians need to be managing overweight/obesity seriously, and specifically, and with every tool in the box, not just with vague advice, if we are to curb the epidemic of obesity and obesity-related diseases.

In light of the new AACE guidelines, I ask you to give consideration to the use of medically supervised weight loss, to include anorectic drugs when appropriate. Perhaps if we all used these drugs more, and smartly, as part of a comprehensive effort, we might see better results from them. Too often patients use them in a vacuum and street-corner weight-loss clinics dispense them that way, such that their failure is inevitable—perhaps we can do better.

Additionally, the prediabetes portion of the AACE algorithm called for metformin or acarbose use in mild prediabetes not resolving with lifestyle change, and consideration of adding pioglitazone and/or a GLP-1 receptor agonist, like exenatide, if needed, in more severe cases (high fasting and post-meal glucoses, for example).

jkr  Read More 

THIS WAS MY REPLY TO MY WIFE'S OLDEST, DEAREST FRIEND, SEEKING INFORMATION WHEN HER DAUGHTER-IN-LAW WAS DIAGNOSED LATE IN PREGNANCY WITH DIABETES.

As your research suggests, gestational diabetes (GDM) usually occurs in mothers who are already predisposed to diabetes (obesity, family history, poor lifestyle habits, irregular periods and infertility). Your daughter-in-law’s lack of these features is unusual and I don’t know enough about the situation to explain it. Pregnancy is an insulin-resistant state which can tip someone on the verge of diabetes over the edge, and the fact that it’s taken 7 months to show up suggests that she had to be “tipped” further than average.

Your genetic background is of no importance—this is a maternal issue—not one the baby’s genes causes. Poor control of the GDM though can affect the baby—at this late stage probably no birth defects, but GDM babies tend to be bigger and harder to deliver.

Not sure what the acne has to do with anything—if she had it pre-pregnancy that would be a sign of insulin resistance though.

I can speculate about 2 possibilities—she either does have some occult genetic predisposition that hasn’t obviously manifested up till now, or this is the onset of type 1 diabetes (“juvenile onset diabetes”) which young healthy thin people without family history certainly can get.

Usual treatment is insulin, but the pills glyburide and metformin have been used more lately. My personal preference, if this is not type 1 diabetes which has to have insulin, is metformin, but that must be the obstetrician’s decision.

Good luck.

jkr
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THIS IS A LADY, WHO I AM PLEASED TO REPORT, READ THE BLOG AND CONTACTED ME THROUGH THE WEBSITE. SHE LIVES WITHIN DRIVING DISTANCE OF MY OFFICE AND WAS WONDERING IF IT WOULD BE WORTH MAKING AN APPT. HER STORY IS THE SAME OL' ONE--LOTS OF SYMPTOMS SUGGESTIVE OF HYPOTHYROIDISM, BUT HER THYROID FUNCTION TESTS (TFT'S) ARE "NORMAL" AND SHE KEEPS BEING TOLD IT'S NOT HER THYROID:

Good to know somebody out there is reading the blog.

If you have your lab reports available, what is your lab’s normal range for FT4? The values you documented certainly sound low-normal, I was just wondering how close to the lower normal limit they are.

The TSHs are obviously “normal” by any standard, but the question is might you have hypothyroidism due to or in addition to a defect in TSH production from the pituitary.

Any history of head injury, even something minor like knocked unconscious in an auto accident or fall?

Also, let me know all the meds you are on now.

You have enough symptoms that could be due to hypothyroidism, coupled with the lowish FT4’s and family history, that I do think a trial of thyroid replacement would be reasonable. It baffles me why “antidepressants, bcp, adhd medications” and the like are so often considered preferable to thyroid hormone, which is at least a substance that God/Mother Nature intended for us to have in our systems.

Please answer the ?’s I’ve underlined and I’ll get back to you.

***

--the 0.5 lower normal limit for FT4 is a little lower than I’m accustomed to thinking in terms of—meaning that your levels aren’t as low as I was thinking, but they are nevertheless still in the lower half of the relevant reference range. In other words I haven’t changed my mind about the possibility thyroid hormone replacement would help.
--the head injuries increase the possibility that there is a pituitary defect explaining the inappropriately normal TSHs in the face of the hypothyroidism we are postulating.
--I can’t prove this, but my feeling based on seeing a lot of patients with stories similar to yours, is that chronic pain (your headaches), narcotic use for the chronic pain, and various CNS-acting drugs, many different ones of which you are or have been on, contribute to a “soup” that hobbles TSH release—creating a central hypothyroidism-type pathophysiology.
--So, no guarantees as to our success, but I think it would be you coming to see me.

jkr
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THIS ONE IS MORE FOR PHYSICIANS--IT IS MY COMMENTARY, AS REQUESTED BY A SURGEON COLLEAGUE, ON A SERIES OF LETTERS TO THE EDITOR IN THE JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS ON THE BEST SURGERY FOR HYPERPARATHYROIDISM, THE MOST COMMON CAUSE OF HIGH CALCIUM LEVELS:

(1) Unilateral surgery misses 75% of incidental thyroid cancers
--IRRELEVANT
--PT surgery is not done to find thyroid cancer
--Not clear that finding occult PTC improves survival
--Many clinically significant thyroid cancers will be evident on exam or u/s and such findings should dictate a more extensive exploration
--Routine preop thyroid u/s with FNA as needed should identify most patients needing a bilateral operation for thyroid-related indications
(2) Unilateral surgery necessitates life-long f/u for recurrence
--INSIGNIFICANT
--Life-long f/u need consist of no more than an annual exam with an internist that includes a serum Ca++ level
(3) ioPTH is unreliable
--INTRIGUING (but not crippling, unless one is seeking 100% perfection, which is rarely achievable in medicine)
--PT adenomas are not autonomous, they retain negative feedback but simply have a higher set point for Ca++; that is, it takes a higher than normal Ca++ to suppress PTH release
--I can therefore easily imagine a “dominant” adenoma suppressing a smaller adenoma, leading to a “normal” post-resection ioPTH, which then rises in the future, manifesting as a recurrence or persistence of the pHPT
--Recurrent or persistent pHPT has always been to my thinking a possible outcome of a 1st surgery—not ideal, but if sufficiently infrequent, acceptable
--Thus I wouldn’t reject unilateral surgery solely on the basis of a low-level failure rate
--I don’t know the quantitative criteria you use to make intraoperative decisions based on ioPTH, but on the basis of the Tampa group’s findings, I might suggest that some very substantial drop be required (say, <75%) to head off extension of a planned unilateral surgery into a 4-gland exploration
--And if such a protocol led to an intraoperative shift from unilateral to bilateral procedures in an excessive # of cases, then I would interpret that as a reason to just do 4-gland explorations routinely
--The Tampa group cites some 2nd adenomas being missed even when postop PTHs dropped <90% compared to preop baseline
--20 patients, they state, out of their 18,000; that sounds like a low-level acceptable failure rate that would be picked up on follow up
(4) 1/3 of Tampa’s new patients had been denied operations because the tumor couldn’t be localized preoperatively
(5) Surgeons observe and rescan every 6-12 months, even in symptomatic pts
(6) Surgeons usually perform at least 2 localizing studies, and may decline to operate without 2 studies in concordance
--I consider the last 3 bullet points SHOCKING, DISTURBING, and representative of MISMANAGEMNT of pHPT
--pHPT is a biochemical diagnosis and the decision to operate is based on clinical and biochemical criteria
--imaging does not enter into that decision
--Positive imaging helps the surgeon but a negative scan DOES NOT alter the decision to do surgery
--The only time I would do more than one study would be prior to a reoperation after an initial failure
--Multiple preop studies would seem to me to be a disturbing waste of healthcare dollars
(7) The third letter states that unilateral surgery should not be abandoned, but that the striving for a unilateral operation may have gotten out of hand, especially considering time and cost factors
--AGREE
(8) Final thoughts:
--The decision to operate is a medical one
--After that, the selection of procedure—unilateral vs. bilateral—is a surgical one, which should not inordinately delay getting the pt to the OR
--Certainly putting off appropriate surgery simply in order to be able to do a unilateral procedure is wrong
--Also, unilateral surgery and associated imaging must not be used as a crutch to promote the performance of parathyroidectomies by less experienced surgeons
--I don’t know your protocol in this regard, but I would propose that one sestamibi scan be done preop and if positive, go unilateral, and if negative go bilateral
--Failure to drop the ioPTH to at or below (??) the lower limit of normal should lead to consideration of extending the surgery to bilateral
--To do multiple preop imagining studies is not cost effective
--Medical f/u to detect occasional recurrent or persistent disease is not onerous
--Having said that, I admit, I generally tell people they don’t need to see me again once they have their surgery—perhaps I need to rethink that in the case of unilateral procedures
--Lastly, as with anything there are pros and cons to be weighed in deciding between unilateral and bilateral operations—seems to me the unilateral procedure might fall short with respect to outcomes, cost, and OR efficiency. Are there enough pro’s to offset those con’s? Read More 

I have now posted my entire backlog of interesting topics. From this point forward I will post more discussions as queries come to me, and from time to time I may pontificate on some topic unprompted--mostly these will be medical issues, but on occasion I hope you'll permit me to veer into non-medical comments on politics, society, my other writing projects, etc.--jkr  Read More 

THIS IS A EMAIL I SENT TO A COLLEAGUE, A SURGEON, IN FACT, AS A FOLLOW UP TO A DISCUSSION ABOUT A CHALLENGING SITUATION HE ENCOUNTERED IN THE OPERATING ROOM. HE BASED HIS INTRAOPERATIVE MANAGEMENT ON STANDARD, WELL-ESTABLISHED, WIDELY TAUGHT PRACTICES AND ASSUMPTIONS REGARDING THE DISEASE PROCESS INVOLVED. YET, THE FINAL SURGICAL PATHOLOGY YIELDED AN UNEXPECTED RESULT. WHEN I QUIZZED A WORLD-RENOWNED EXPERT ABOUT THIS CASE, HE ALLOWED, QUITE MATTER-OF-FACTLY, THAT THE RELEVANT ASSUMPTIONS ARE NOT PERHAPS VALID. YET THESE ARE ASSUMPTIONS WIDELY TAUGHT TO MED STUDENTS, RESIDENTS, ETC., BY HIM,AND ALL OTHER PROFESSORS IN THE FIELD (I’M BEING DELIBERATELY VAGUE HERE SO AS TO PROTECT THE PRIVACY OF ALL THE PARTIES. ANYWAY, I GOT TO THINKING…

It occurs to me that you have run headlong into what I see as a flaw in how contemporary allopathic, evidence-based Western medicine is practiced and taught—which I believe (at the risk of sounding melodramatic) puts our profession at risk. It is this issue which, in part, led me to write The Thyroid Paradox.

Namely, I believe that the inestimable diversity that is the nature of the biological sciences in general, and medicine in particular, demands that physicians recognize and be equipped to deal with that diversity—i.e., that almost every rule we come up with (in say the form of a clinical practice guideline[CPG]) will at some point be broken. It may only be broken one in a million times, but I believe a conscientious physician needs to be alert for that one case.

Thus, everything that we are taught and that is published in CPGs is by necessity an estimate of how things usually go, but they can’t reflect and be valid in all situations the physician will encounter in a lifetime of practice. My fear is that our current emphasis on evidence-based medicine codifies for younger, less-experienced, less-wise physicians “the typical” and deemphasizes and perhaps even devalues diversity.

In the book, I talk about the “academic elite,” who I believe, because they are super-intelligent and well-read and well-experienced, are aware of and embrace the diversity that I’m talking about, the fact that the “rules are made to be broken.” They are aware of and embrace these things in their own practices, and ruminations amongst themselves, and perhaps if we are lucky the occasional obscure case report. But when they teach medical students, residents, general internists, general surgeons, and when they write CPGs, they become very guarded, very dogmatic; the exceptions to the rules don’t get talked about much. And perhaps that is understandable, to a point—there is obviously a practical limit how much, say, endocrinology gets taught in a board-review course geared for family practitioners, for example.

It is also my belief, however, that there is a component of: They can’t handle the truth! That the “unwashed masses slogging the trenches of real-world medicine” need to be spoon-fed sound bites, rather than be trusted with the full width and breadth of the pathophysiology that’s out there. Subspecialists get let in on a few of the secrets, but often in an off-the-grid way.

I’ll give you two examples I cited in The Thyroid Paradox:

(1) Dr. Y is an eminent thyroidologist. I was fortunate enough that he flipped through a manuscript of The Thyroid Paradox when I happened to be sitting with him at an American Thyroid Assn. meeting. He zeroed in on a statement I made about considering thyroid hormone replacement for people with high-normal TSHs (say, >2.0). He said he disagreed, and his rationale was that the average clinical laboratory across the U.S. could not be trusted to run TSHs accurately enough, to support a standard of practice like that. Now, he has a point—we all must be cognizant of the statistical possibility of error in the diagnostic technologies we employ—but think about what he’s implying… He’s saying real doctors in the real world shouldn’t even consider trying to “heal” a whole population of possibly mildly hypothyroid patients, solely because they can’t be trusted to properly interpret and manage the data.

(2) It occurred to me after a number of years of treating hyperthyroidism and rendering people hypothyroid as a result—that some of them seemed to run lower TSHs than I expected as I adjusted their levothyroxine dose--in fact, some seemed to have undetectable TSHs on doses that otherwise seemed appropriate, or even too low. I reasoned that past hyperthyroidism, sometimes, resulted in hypothalamic-pituitary-thyroid-axis suppression that never recovered. Now, since this is a particular interest of mine, I have read everything I can get hold of, and listened to every lecture I can on this subject, over >15 years, and I can honestly say that I have never seen or heard it acknowledged that hyperthyroidism could cause permanent HPT axis dysfunction—transient, yes, not permanent. However, when I caught Dr. Z, a top endocrinologist, in the hallway at another ATA meeting, and proposed my thesis: He grinned and tossed back, and exclaimed, “Oh, yes, of course!”

OH YES OF COURSE!

Then why doesn’t anybody ever say it?

Because, methinks, we can’t handle the truth.

Food for thought…

Best,

jkr
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THE FOLLOWING ARE MY RESPONSES TO A SERIES OF QUESTIONS ASKED ME BY A POST-THYROIDECTOMY PATIENT BY EMAIL:

Pardon me for starting with shameless self-promotion, but I assume since you’re contacting me you’re familiar with my book The Thyroid Paradox (2007, Basic Health Publications); if not, it addresses a lot of the issues you raise and is available from Amazon.com as a trade paperback or Kindle download; also any bookstore should be able to special order it.

I consider this book to be a good middle-of-the-road analysis of the state of modern thyroidology--criticizing what most physicians do wrong, without throwing away what they do right, which much of the hyped-up rhetoric about thyroid disease in popular books and on the internet does. In other words, I try not to throw out the baby with the bath water,

That said, I’ll address your most specific questions individually:

(1) It seems such a paradox to me to be testing the pituitary thyroid stimulating hormone in a thyroidless person

You are of course correct that TSH is a pituitary hormone—however, it is produced in response to any perceived lack of thyroid gland function by the brain, and it stimulates the thyroid gland to make thyroid hormone. Thus, TSH levels are integrally related to the proper functioning of the whole thyroid system which include the brain, pituitary and thyroid.

My disagreement with most physicians is not that they test TSH levels, but that they often only test TSH levels and ignore everything else, including FT4, FT3, and symptoms.

In other words, my position is that TSH is very useful—I just don’t assume that it tells me everything.

I know your questions relates to the athyrotic (“thyroid-less”) patient, following total thyroidectomy. Obviously in that situation the role of TSH stimulating the thyroid gland is moot--but, the pituitary still releases TSH when there is a perceived lack of thyroid hormone (in the case of the athyrotic patient, a perceived lack of Synthroid or whatever other thyroid replacement drug is being used).

So, put very simply—a patient with a high TSH is almost certainly not getting enough Synthroid—which is a very useful thing to know. Also the person not getting enough Synthroid will more often have a high TSH, and have it sooner, than an obviously low FT4 or FT3. TSH is a more sensitive test for hypothyroidism than FT4 and FT3 are. To not use it in these people would be crazy.

Now, what about monitoring for over-replacement--too much Synthroid. Almost everybody on too much thyroid medicine will have a low TSH, and they will have it before the high FT4 and FT3. In other words, TSH is also a very sensitive test for hyperthyroidism.

The problem is: TSH is NOT a very SPECIFIC test for hyperthyroidism. Other things can cause a low TSH besides too much Synthroid. That’s the mistake that gets made--almost every doctor out there--including endocrinologists--automatically assume or at least respond as if a low TSH means the person is on too much thyroid medicine and they lower the dose. That might be the right interpretation, but it might not, and the only way to know is to look at FT4, FT3, and consider the patient’s signs and symptoms.

Bottom line--TSH is a very useful test, but there are weakness which are often ignored. That is a reason to change how we think about TSH, not a reason not to use it.


(2) Shouldn't the emphasis be on the actual thyroid metabolic state reflected by serum FT4 and FT3 concentration?

It would be incorrect to assume that any given FT4 or FT3 level accurately reflects the “actual thyroid metabolic state.” And since we are talking about athyrotic patients, these levels don’t even reflect the metabolic activity of the thyroid gland to produce thyroid hormone--these levels are instead totally under the control of the Synthroid et al. prescriber’s pen or keystroke. To be clear, by “actual thyroid metabolic state” you mean the amount of thyroid hormone that is getting to the thyroid hormone receptors deep inside the nucleus of each of our cells, and the resulting intracellular actions that are triggered by those activated receptors.

Looked at that way, I think you can see that a blood level of FT4 or FT3 (which are the only measurements technically practical) does not necessarily reflect what is going on OUTSIDE the blood, deep inside cells. It’s helpful; it’s an estimate of what’s going on, but that’s all it is. That’s especially true for FT3, since much T3 is produced inside these cells and never makes it to the blood.

The fact is, just because a FT4 or FT3 blood level is “normal” doesn’t mean that cellular thyroid hormone action is normal, because there are several physical barriers and physiologic processes separating those points. Who’s to say that a low-normal FT4 of .89 is enough--maybe a high-normal level of 1.7 would be better. For that matter, who’s to say a low blood level isn’t getting the job done, or that a high level is.

“Statistically normal” which is that range printed on a lab report is not the same thing as “physiologically normal” Something else very few physicians, sadly, ever think about in my experience.

Getting back to TSH--if the pituitary is working properly (I don’t think it always is in athyrotic patients) but IF IT IS then TSH gets produced by the pituitary as a result of the brain’s perception of the adequacy of intracellular thyroid-hormone action. So really, in fact, it could be argued that the blood TSH level does, in many cases, more accurately reflect “actual thyroid metabolic state” than blood FT4 and FT3 levels. You might say that TSH reflects the “ACTUAL thyroid metabolic state,” while FT4 and FT3 reflect “POTENTIAL thyroid metabolic state.”

Bottom line--none of these tests are perfect--all have strengths and weaknesses which need to be better understood by all of us. The right answer is to evaluate them all to come up with what is never going to be any better than an estimate of what is really going on.


(3) Could you please cite any studies/information showing that a low but not suppressed TSH is acceptable as long as the free T4 and free T3 are within range and there are no hyperthyroid symptoms

As you probably know, there is a virtual obsession amongst most physicians about avoiding low, and especially undetectable TSHs. The concern is that the low TSH equals hyperthyroidism, which is of course wrong—it is a marker for it, but the problem is hyperthyroidism (too much T4 and/or T3 for the person), not low TSH. Hyperthyroidism does need to be avoided; it does do harm. There are other reasons, though, why the TSH might be low, and those other reasons are almost never considered. This obsession with avoiding low TSHs often in my experience leads to an underdosing of patients, and a lot of frustration and poor quality of life for patients—especially athyrotic ones.

I’m frankly dumbfounded why endocrinologists smarter than I am don’t see and teach the “disconnect” between “low TSH” and actual hyperthyroidism. It has a lot to do, though, with the Hippocratic principle of “first do no harm.” If we never get the TSH low then we will never do harm with hyperthyroidism. If we let TSHs get low then some of the time we might err and do harm with hyperthyroidism, and that is a possibility that mainstream medicine isn’t comfortable with.

Hopefully, most physicians out there at least see that a mildly low TSH of say 0.31 is probably okay relative to one below, say, 0.1--but alas, many do not split these hairs in actual practice.

Your specific question was about “low but not suppressed TSH” being “acceptable as long as…”

I would modify that by saying that in some but not all cases even a suppressed (undetectable, that is) TSH might be acceptable.

Unfortunately there really isn’t much literature to support this position. Common sense supports it, but the modern obsession with evidence-based medicine doesn’t give as much credence to common sense as one would like--hopefully we are seeing a slow backswing.

I will list and comment upon a few articles I referenced in my book that might be of help:

--Shimon, I., et al. “Thyrotropin Suppression by Thyroid Hormone Replacement is Correlated with Thyroxine Level Normalization in Central Hypothyroidism.” Thyroid 12 (2002): 823–827.

(This is the strongest argument for our position. Central hypothyroidism is hypothyroidism caused by a defect in TSH secretion by the pituitary--it is thought to be rare--I think it’s common but under-recognized. When I say that it’s okay for a patient to have a low or undetectable TSH, what I’m really saying is that the patient is either all or partly centrally hypothyroid, rather than pure primary hypothyroidism.)

--Zulewski, et al. “Estimation of Tissue Hypothyroidism by a New Clinical Score: Evaluation of Patients with Various Grades of Hypothyroidism and Controls.” Journal of Clinical Endocrinology and Metabolism 82 (1997): 771–777.

(Good analysis of symptoms vs. labs in the diagnosis of hypothyroidism.)

--Andersen, S., et al. “Narrow Individual Variations in Serum T4 and T3 in Normal Subjects: A Clue to the Understanding of Subclinical Thyroid Disease.” Journal of Clinical Endocrinology and Metabolism 87 (2002): 1068–1072.

--Dickey, R., L. Wartofsky, and S. Feld. “Optimal Thyrotropin Level: Normal Ranges and Reference Intervals are Not Equivalent.” Thyroid 15 (2005): 1035–1039.

(Two papers that telling us that what is “statistically” normal for the population isn’t the same as “physiologically” normal for the individual.)

--Demers, L., and C. Spencer. “Laboratory Medicine Practice Guidelines: Laboratory Support for the Diagnosis and Monitoring of Thyroid Disease.” Thyroid 13 (2003): 3–126.

(Any paper by Carol Spencer from UCLA, I believe, will be very open-minded about the weaknesses of and precautions to take when using modern thyroid function tests.)


(4) Shouldn't dosage be based more on free T4 and free T3 levels and clinical symptoms rather than so much emphasis on TSH?

Yes, it should be based on all 4 parameters: FT4, FT3, TSH, and clinical evaluation. Yes, there is too much emphasis on TSH—just don’t make the mistake of thinking that TSH is worthless.

Good questions—I hope this helps.

Best,

jkr
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