Primary Aldosteronism: An Approach

Someone asked in the chatbox for me to elaborate on why the CT scan isn't definitive in the diagnostic evaluation of primary aldosteronism. This is probably too long of an explanation to fit in there, so I thought I'd write a post about it.

Primary aldosteronism implies that the adrenal(s) is autonomously making inappropriate amounts of aldosterone, independent of the usual kidney-mediated renin-angiotensin system. The evaluation is undertaken usually in one of two situations- the discovery of an adrenal incidentaloma, or in the investigation of resistant hypertension.

In these cases, the first step is to document autonomous aldosterone secretion; we do this by means of a morning serum aldosterone and renin activity assuming that interfering drugs are not in the picture. A positive screening test includes an elevated aldosterone level, typically greater than 15 ng/dL, and an elevated aldosterone to renin ratio. Many of us use 15 or even 20:1. If this is positive, we move on to the confirmatory biochemical test of showing nonsuppressed aldosterone levels despite a good amount of salt in the system. This can be done by oral salt loading and measurement of 24-hour urine Sodium (should be greater than 200) with concomitant high urinary aldosterone (more than 12).

Alternatively, one can do the IV Saline suppression test showing a high (greater than 10) serum aldosterone despite 2 liters of Normal Saline.

(diagram pilfered fromNature Clinical Practice Endocrinology & Metabolism 2005)

At this point, you've documented that the patient is making inappropriate amounts of aldosterone and that the problem lies within the adrenal (ie not a case of renal artery stenosis leading to secondary hyperaldosteronism). However, as it turns out there are several subtypes of primary aldosteronism:

The exam-favorite Conn's syndrome or aldosterone-producing adenoma is often quoted.

However there can often also be adrenal hyperplasia which can bilateral.

(will not really mention the rare glucocorticoid remediable aldosteronism).

And so the problem is although you know the patient has the biochemical pathology, you don't know which adrenal is causing it. And without going into too much detail, as it turns out nonfunctioning adrenal adenomas are not uncommon, while adrenal hyperplasia may often not be visible on CT or MRI. And so, even if you see a juicy 2 cm right adrenal adenoma, you won't know if this is the source of the high aldosterone, or if this was just an innocent bystander while it's really microscopic pathology in the LEFT gland that's churning out the hormone and causing the blood pressure problems. And the last thing you want to do is to have your surgeon colleague remove the wrong gland, only to find out post-op that your patient remains hypertensive and hypokalemic.

And so, if you look at many of the guidelines out there, IF a patient is deemed to be a good surgical candidate, then often adrenal vein sampling for aldosterone (often normalized to cortisol, to correct for the dilutional effect of the converging veins) is required to lateralize the lesion. And AVS is a technically challenging procedure that only the most experienced of interventional radiologists can do skillfully.

The good news is, medical treatment with Spironolactone is usually very successful. So for most of my patients I try to direct them in this route, rather than the surgical. Because the truth is, if it's hypertension that they're hoping to cure, with many patients (first degree relative with hypertension, or prolonged history of hypertension etc) even if the surgeon took out the correct adrenal, they will STILL be hypertensive (though improved). There, a longish explanation for a fascinating clinical problem. I'd direct you to the Endocrine Society Clinical Practice Guideline if you wanted more bedtime reading.

Happy Birthday Alli!

Now that I'm a parent, I think I understand the phrase "A face only a mother (father) can love". The truth is, every parent thinks their baby is beautiful. Even the newborns. Except they are blinded to another truth: All newborns are ugly. Yup, all of 'em. They're swollen, wrinkly and bruised. Their eyes don't open, or if they do they're cock-eyed and looking in different directions. But yet, the estrogen surges inside you (yes, men make estrogen too, by the way) and you swoon at the sight of your baby, thinking that she is just the most beautiful thing in the world. You hand her around like she's a prize to beheld. You spend big bucks taking professional studio pictures and give them to family and friends.

Blissfully ignorant of the truth.

I know we were. Looking back at the large photo hanging in our hall, the one that was professionally photographed, we catch ourselves thinking, what were we thinking?? We should have waited a few months!But I digress. The months do fly by quickly. And in those 12 magical months, our little potato-looking baby has grown so much, into (what we think; again back to the theory of parents being blinded. For all I know you all might think like she looks like a monkey) beautiful little girl.

Yes, our Alli turns one today! As a parent, it's amazing to see how much your baby develops and learns in that short amount of time. There's just so much fun watching them grow, and learn new things (like how to open drawers and scatter the contents all over the floor).

My dad once told me. A man will have 3 greatest joys: Marriage, being a Father, and then becoming a Grandfather. So true. I'm sure many of you understand this firsthand, while many others will eventually experience this magical journey. Seeing and playing with your daughter at the end of a hard long day, and seeing her light up at the sight of you walking through the door, is an experience that is beyond explanation. And despite the fatigue and stress and of course the evergrowing cost of being a parent, I'm loving every moment of it!

Happy 1st Birthday, Allison! We love you!

Graduation Ceremony

So tonight the wife and I attended the family medicine residency graduation dinner. It was a pleasure to see the residents I worked with graduate and to be given their wings to go out into the real world.

It didn't seem that long ago when I graduated from residency, until I actually sit down and think about it. 2005. SIX. F*CKING. YEARS.

And so, when Mike asked me for advise on what's in store, I simply said: "Be prepared for a steep learning curve your first year."

Because it's true- what residency and fellowship does is give you the paper knowledge, and hopefully adequate clinical experience. But it never teaches you much about the real-life practical stuff.

• Like how to bill/code for a certain level of care you provided.



• Or how to run a clinic, or manage employees. Because for the first time, you're not on the bottom rung of the ladder anymore.



• How to manage money. Clinic overhead. Lab or transcription expenses.



• How to think independently. Really independently for the first time. With no 'supervising consultant' watching over you in case you screw up; no one to catch your mistakes and guide you. It was pretty unnerving to me, having the final say in treatment (well, the patient really has the final say, but you know what I mean).



• How to balance work and family.



• Life insurance. Disability insurance. Umbrella coverage.

Yup. The first year you'll learn a lot more than you thought you would. But it is also in that year, that you begin to blossom as a physician.

To all the residents graduating this weekend, congratulations. Be proud of what you have achieved, and take pride in your first few steps as a full-fledged physician.

And to all the fresh incoming interns, Good Luck! (that'll be a different story)(tip to patients: avoid teaching hospitals for the next couple of weeks unless you absolutely need medical help!

88 Minutes

Ok, this has nothing to do with work. But I was watching the 2007 movie '88 Minutes' the other day. Starring Al Pacino as Dr. Jack Gramm, a forensic psychiatrist who incidentally drives around a Porsche 911 Carrera Turbo. The show was pretty entertaining though like most guys (girls too, if you're into these sort of thing) I cringed when his 911 was blown up by the bad guys.
Until I realized something looked very fishy (one of the beauties of a Digital Video Recorder- you can pause and rewind).

Can you see it?

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The outer tailpipes of the 911 Turbo is connected to nothing, while the inner tailpipes are connected directly to the fake rear axle!

Yes, I don't expect them to blow up real cars, but I thought this was a pretty glaring mistake they made...

Number 18

This past call, I dealt with the 2nd sickest pheo patients in my career (yet). This would have been my 18th pheochromocytoma patient.
Mr. K presented to the ER with pleuritic chest pains. During the workup which included a CT chest to rule out a pulmonary embolism; that caught a glimpse of his adrenals which contained a 6.6 cm heterogenous mass. Aside from the chest pains, he was pretty asymptomatic, with reportedly a history of benign essentially hypertension well controlled with an ACE-inhibitor.
When I saw him in the hospital, I reviewed the function of the gland, but also assured him that most masses are nonfunctioning though the sheer size of the tumor probably will necessitate adrenalectomy eventually. He looked great, and was normotensive. We also started biochemical testing then, though I'm often hesitant to initiate testing in inpatients as the probability of a false positive increases.
I was called that night by the nurses because they had trouble with his blood pressure. 'Trouble' was probably the understatement of the year. So fluctuant was his BP, that they transferred him to telemetry. One minute his BP was 90/50, while the next it was clear up into 240/120s. Even on the arterial line. My pretest probability for a pheochromocytoma went from 'low' to 'almost definite'.
In the outpatient setting, treatment of pheochromocytoma begins with adequate hydration as although patients may be hypertensive (caveat: most patients are NOT hypertensive) they tend to be intravascularly dry. I also tell them to tank up on salt (one of the 2, well maybe 3 conditions in which an endo might tell you to take MORE salt. Can you guess the other 2?). Alpha blockade is started first (classic medschool exam question) and while there are numerous you can pick from, I start with the shorter acting Phenoxybenzamine. The shorter duration of action allows for better titration of doses. My personal goal is to see a systolic drop of 15 to 20 mm Hg on standing with no reflex tachycardia though you may also pick an absolute BP goal. Once the patient is adequately blocked, a beta blocker is then started. For select patients, we add a 3rd line agent a few days before surgery: Metyrosine, to deplete adrenal catecholamine levels, that is if you can get your hands on it.
For Mr. K, by the time I got to the hospital, his primary team had decided to intubate him for respiratory distress; his blood pressure remained mostly high though these were peppered with marked drops. In these situations, regular alpha blockade would not be fast-acting enough. Throughout the night, we resorted to Nitroglycerin and then Nipride, Nicardipine and finally Phentolamine. For the next 24 hours he remained fluctuant, at times with his BP so high that many of us feared he would stroke out, while at other times his BP was so low that they had trouble feeling a pulse. It was touch and go for the 5 days he was in the ICU though things eventually stabilized enough that he was extubated and we transitioned him to the usual Phenoxybenzamine and then a beta blocker.
And so, when I saw him in clinic 2 days ago for follow up, I could not help myself but to give him a big handshake and a hug- he was out of it for most of the time in the ICU, but his family was there and they knew how worried we were. It was with a great sense of relief to see Mr. K walking and talking normally, cognitively intact.
He's not out of the woods yet obviously. But I'm pleased by his progress and the level of his alpha and beta blockade. He's probably pretty well-prepped for surgery which will happen in a week. And God willing, things should turn out well.
Post-op, it's necessary to reassess things biochemically as there is a chance of metastatic pheochromocytoma- patients should undergo repeat 24-hour urine catecholamine and metanephrine testing. If biochemistry remain abnormal, then imaging for metastatic disease is necessary, whether you use MIBG or Octreotide or some other scan.

Some experts suggest that the biochemistry be done annually for life. At the recent meeting I attended, some actually advocate genetic testing in ALL pheo patients (not just paraganglioma) as the incidence of familial pheo appears to be much higher than what the 10% rule suggests.

Will keep my fingers crossed that Mr. K sails through surgery, which he should. We had him see a very skilled surgeon and he's young enough that I don't anticipate any problems.

And so, that was my 2nd scariest pheo patient. One of these days, I'll tell you about my SICKEST patient.

Shopping

The meeting is going well. My brain has expanded a bit since Day 1, from all those lectures (or maybe from all that food?). Anyhow, I ran into some Malaysian endocrinologists at the meeting. Yes, how I ran into them with 10000 attendees, I don't know. But I do have a bad habit of chatting people up when I hear a familiar Malaysian accent.
It was their first visit to the US. And they heard I was somewhat familiar with Boston, their question was "Eh, where is good shopping, ar?"
Which got me thinking. When Malaysians come to the US, they shop like there was no tomorrow because 'things are cheaper here'. I know that's what my family does. But when overseas Malaysians like myself head back to Malaysia for a visit, WE go on a shopping spree because we think things are cheaper there.
So which one is it???

-- Sent from my Palm Pre

Boston

See you in Boston!

Headed for the 2011 meeting of the Endocrine Society. And it's a bonus that Allison and Kristin get to join me (we have family there). We'll also get to meet up with some old classmates from my alma mater.

Plus, it's a bonus that our hotel is only 2 blocks from the Malaysian restaurant there!

While I'm still unsure of where I stand on this matter, I am however amazed and awed by their gallantry.

Japanese seniors volunteer for Fukushima 'suicide corps'
The group, consisting only of retirees age 60 and up, says it is uniquely poised to work at the radiation-contaminated plant, as the cells of an older person's body divide more slowly than a younger individual.

In times of crises, the Japanese can certainly rise up to the challenge. If this was, indeed, a suicide mission, is it not logical then for the elderly to volunteer?

(I suppose medically this makes sense as well, cancer risk increases inversely proportional to the age of the patient at radiation exposure, no? Ethically, well, I don't know what would be the right thing to do)

Let's hope the matter can be resolved soon.