James K. Rone, MD, FACP, FACE

Unilateral vs. Bilateral Surgery for Primary Hyperparathyroidism

August 26, 2012

Tags: Hyperparathyroidism


(1) Unilateral surgery misses 75% of incidental thyroid cancers
--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
--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
(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?

Going Forward...

August 9, 2012

Tags: Miscellany

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

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Doctors keeping secrets

August 9, 2012

Tags: Academic medicine

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!”


Then why doesn’t anybody ever say it?

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

Food for thought…



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Strengths and Weakness of TSH and Other Testing in Athyrotic Patients

August 5, 2012

Tags: Thyroid


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.



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More Hypothyroidism with Normal Thyroid Function Tests

August 4, 2012

Tags: Thyroid


Sorry you didn’t have a good experience with Dr. XXX. He really is a top-flight endocrinologist—it’s just that you and I aren’t on the same page with many otherwise top-flight endocrinologists when it comes to hypothyroidism-diagnosis-and-treatment philosophy.

There are a few important points for you to consider--for you wife’s good, and from a practical standpoint, before you bother to travel to see me:

(1) I agree with you that a TSH of .14 does not necessarily equal a “massive overdose,” but unfortunately that’s a tough nut to crack with a lot of doctors. That is because hyperthyroidism is dangerous. I just don’t think we should be assuming that everybody with a low TSH in hyperthyroid.

(2) I’ll be blunt here: those “holistic GP’s” are wrong about a lot of things; they’re right about some things too, and as I’ve said, the mainstream is, I think, wrong about some things. One group is too aggressive with thyroid hormone and the other too cautious. My book talks a lot about this--I really think you should read it if you haven’t. Basically they’re saying that patients feel better on their treatments, but they ignore the potential for harm years down the road. Just remember feeling good, is good, but it isn’t a good physician’s only goal. It has to be at least reasonably safe. Cocaine makes people feel good, but I assume you agree people shouldn’t be using it.

(3) The reason her T4 went down on Armour is because Armour doesn’t contain enough T4 and it contains too much T3, which is a potent, more potentially dangerous form of thyroid hormone. You don’t say if a T3 was checked, but I bet it’s too high or getting close to being too high.

(4) And remember, the natural situation--that is, normal human physiology--is for there to be a lot of T4 and a little bit of T3, only enough. Proponents of T3 and Armour (hyped as “natural thyroid hormone—perhaps it is, but it does not mimic natural human thyroid status) ignore this.

(5) Again, I’ll be blunt, and this is a very important point if you decide to come see me: I think starting with Armour, and insisting on it’s continued use is a mistake. I use it occasionally, but as a last resort when other options fail. Again, the book describes this in great detail and you should read it when deciding whether you want to come to me. If you come, I very likely will insist that Armour be stopped and that we try Synthroid alone (but perhaps in higher doses than most would use). I did exactly that with a new patient on Armour yesterday.

Please consider these comments.


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Fiction: Mystery
PI Sherry Russell vs. the reigning "Miss Nazi" in 1968 Huntsville, during the run-up to the Apollo moon landings
Dr. Rone's 1st Southern Noir novel
Hate crimes in 1967 Alabama; unflinching follow up to 'No Nice Girls'
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