In a post I wrote almost 8 years ago (“A non-genetic risk factor for pheo?” in February 2015), I described an article that suggests cyanotic congenital heart diseases may predispose people to develop pheo. Since then, a few seminal papers have provided insights into that phenomenon. In my own practice, I have taken care of several patients with cyanotic congenital heart disease who develop pheo at young ages.
In 2018, a paper showed for the first time that 4 out 5 patients
with pheo and cyanotic congenital heart disease had somatic mutations in the
gene EPAS1 (which encodes hypoxia-inducible factor 2-alpha) in their pheo
tumors. These mutations are not inherited but develop spontaneously. Similar
mutations are also responsible for the polycythemia-paraganglioma-somatostatinoma
syndrome (see post “The story of Para and Poly: Are they related?” in September
2012). The difference is that the EPAS1 mutations in the pheo of people with cyanotic
congenital heart disease appear to only happen in the cells that give rise to
pheo (paraganglia cells, including cells of the adrenal medulla). In this year
(2022), a larger study confirmed the findings. It is thus pretty clear that hypoxia
favors the proliferation of paraganglia cells that harbor EPAS1 mutations,
resulting in pheo formation.
In my experience, people with cyanotic congenital heart disease
often have frequent imaging evaluations so that a pheo or para can be easily seen
so long as the doctors have a high alertness about those tumors. It is not
unusual for a small tumor to be omitted first but re-discovered years later.
The typical locations and imaging features of the tumors make the diagnosis
quite straightforward. It is not easy, however, to determine if the tumors are
functional in that whether they secrete catecholamines, because people with cyanotic
congenital heart disease often have slightly high pheo marker levels in the
absence of such tumors. Timing of surgical removal of the tumors is also quite
complicated. A tumor with clear evidence of catecholamine secretion should be
removed as soon as possible.
Dr. Pheo
This was interesting to read. I have a medium pfo with shunt, an ASA, prominent chiari network, and a Hyperdynamic left ventricle. I am occasionally hypoxic, but only when standing. I have POTS and erythromelalgia too. I have an adrenal adenoma and elevated metanephrines, but they are never 4 fold and usually a bit under double the upper limit. I have had metanephrines come back normal on a couple of the 24 hour urine tests, but they are always elevated in blood. I had one parathyroid removed about 10 years ago at age 30, but had high calcium and intermittently high pth starting at 22 (was told I was too young for hyperthyroidism for a number of years). I have not had any genetic testing done regarding the parathyroid/adrenal issues. I don’t know how relevant this is, but I have a CT contrast allergy and about 18 months ago was scheduled to have one (my first CT since allergy was discovered) and was doing pre-medication with prednisone and Benadryl. After about 75mg of prednisone I had to stop. My heart rate was about 150 resting, my CO2 was low, my potassium was low, my anion gap was high, I was shaking and nauseous. Immediately I wondered if this was related to the adrenal adenoma but everyone brushed off the question. Instead, prednisone was just marked as an allergy in my chart. Is it possible these things - the heart issues and the strange reaction to prednisone - are related to the adrenal adenoma (or I guess that the heart issues are related to the adrenal adenoma which then caused the strange prednisone response)? The endocrinologist “doesn’t know what to do with me” and doesn’t feel comfortable not monitoring it, so I get all the blood/urine done once a year and an mri once a year as well. I feel like this will drag on indefinitely and I feel terrible most of the time, so just looking for any connections that might yield more answers.
ReplyDeleteDear Anonymous,
DeleteWhat is the size of your adrenal tumor?
What is the "Hounsfield units" of your adrenal tumor on CT without contrast?
The details of your adrenal tumor imaging characteristics are important to determine if it could be a pheo.
Dr. Pheo
Sorry for the long delay in response. I don’t see anything about hounsfield units in the ct report. Is that something the endocrinologist would be able to see or just the radiologist? The MRI says Left adrenal nodule which is stable in size measuring approximately 1.1 cm and shows likely signal dropout on out of phase images as would be seen with adrenal adenoma (5/28). This lesion was present on prior examination and was more clearly characterized as an adenoma.
ReplyDeleteDear Anonymous,
DeleteThe MRI features are consistent with a benign adenoma. Overall it is unlikely a pheo.
Dr. Pheo