Musings of a Dinosaur

A Family Doctor in solo private practice; I may be going the way of the dinosaur, but I'm not dead yet.

Thursday, March 12, 2009

Horse-Zebra Hybrid

When you hear hoofbeats, think horses, not zebras.
This old medical expression is the way we doctors express the truism that common things are common. It is also true that, on occasion, we see rare diseases or conditions and this is why we call them "zebra" diagnoses. Another version of this is a "zebra" presentation: a common condition presenting in an atypical or unusual way. Then there's the in-between version, like a case I had a few weeks back: a relatively common condition presenting in a common way, but with a statistically uncommon cause.

I saw an 85-year-old man with weakness and fatigue. Before you go generating hundred-page-long lists of differential diagnoses (not hard to do, I know) let me add that this was relatively recent in onset. Up until about three weeks ago, he was just fine. Mentally intact; living alone and caring for himself unassisted, although he no longer drives. About the same time this began, he'd been started on a new drug by another doctor, but because of the fatigue he'd stopped it after only three days and hadn't gotten better. Now, three weeks later, he was getting worse.

[I'm not presenting this as a full-blown clinical puzzle, in which case I'd rattle off his med list (three blood pressure meds, one cholesterol pill, and an aspirin and a diuretic) and the findings on physical exam (BP 110/50; 30 pound intentional weight loss over the last two years; otherwise nothing) now, but none of that applies to the point I'm trying to make.]

His workup revealed a calcium level of 12.4 (normal range 8.6 - 10.2)

This is a condition called hypercalcemia, and causes muscle weakness, fatigue and depression, among other things (usually kidney stones and inflammation of the pancreas.) If the level gets very high, it can cause coma and cardiac arrest. It was clearly the source of his symptoms.

What causes hypercalcemia?

The two major causes are malignancies (classically multiple myeloma and prostate cancer; basically any cancer that metastasizes to bone, which is where the calcium comes from) and an over-production of parathyroid hormone. This hormone, which increases calcium levels, is produced in the parathyroid glands. These are four little niblets of tissue nestled in the back of the thyriod gland in the neck. Sometimes one of them can grow a tumor that produces PTH regardless of serum calcium levels, which are normally held within a narrow range by multiple regulatory mechanisms.

Multiple myeloma and other cancers are more common the older you get. Prostate cancer in particular is incredibly common in men over eighty.

Parathyroid tumors are most common in women over sixty.

If you took one hundred 85-year-old men with hypercalcemia, ninety-five of them would have prostate cancer as the etiology of the condition; four of them would have multiple myeloma or another cancer.


This patient had just seen the urologists for a relatively slight increase in PSA (actually, it was his PSA velocity that prompted the consult) that turned out not to be cancer. Tests for multiple myeloma and other cancers were also negative. But his PTH level was elevated almost four-fold.

A true zebra-like presentation of a condition that isn't all that rare. If you went with the odds, though, you'd never come up with it. The correct diagnosis in this case came from my being thorough and ordering a test, the PTH, that I really thought was going to be normal.

I consulted with a surgeon and put the guy through a mega-workup of imaging, trying to locate a single parathyroid adenoma which could be removed. As it happened, we didn't find one and the surgeon didn't want to operate. So I sent him for an infusion of Zometa, which knocked his calcium down beautifully. I'm following him once a month, and whenever it climbs back above 10.5 -- or he gets symptoms again, now that he knows what they're from -- I'll send him for more Zometa. Three, four times a year; whatever it takes. He's 85, after all. He and his family are fine with this as a management plan, as they weren't crazy about the idea of surgery either.

So there you have it: a true hybrid between a horse and a zebra.


At Thu Mar 12, 08:12:00 AM, Blogger Alpine, R.N. said...

Wow! I just heard of hypercalcemia of malignancy on monday when I had a patient with it. Lovely article in one of the journals on it, and all the problems that go with it. My guy spiked 14 on admission, and has been on calcitonin ever since.

Odd that now that I know about it I see it EVERYWHERE.

At Fri Mar 13, 10:17:00 AM, Blogger Jill said...

In reply to the above comment, and as one of my teachers in med school used to say, "You only see what you know to look for." Also, "An uncommon presentation of a common disease is still more common than a zebra."

At Mon Mar 16, 09:54:00 AM, Anonymous Anonymous said...

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At Tue Mar 17, 10:50:00 PM, Anonymous Anonymous said...

First, let me say I'm a fan of the blog, and of the Laws.

But, I disagree that prostate cancer is a common cause of hypercalcemia. Classically, prostate mets to bone are "blastic" - that is, over-calcified, rather than "lytic". Other than myeloma, common malignancies that cause hypercalcemia are squamous cells of lung (or head and neck), breast, renal cell, and some lymphomas.

Hyperparathyroidism is actually not rare at all in older folks - the atypical feature of your case is that it occurred in a man (women develop it more commonly).

Best regards, and keep up the good work.

At Tue Mar 24, 08:41:00 AM, Blogger Bookhorde said...

So, would you call his case a zorse or a hebra?

It must be great at 85 to go to a doctor and not find out it's just old age -- that there's something he can actually do to feel better. Hope he does feel better soon!


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