Abstract
Pituitary adenomas (PA) and pheochromocytomas/paragangliomas (PHEO/PGL) are rare tumors.
Although they may co-exist by coincidence, there is mounting evidence that genes predisposing
in PHEO/PGL development, may play a role in pituitary tumorigenesis. In 2012, we described
a GH-secreting PA caused by an SDHD mutation in a patient with familial PGLs and found loss of heterozygosity at the
SDHD locus in the pituitary tumor, along with increased hypoxia-inducible factor 1α (HIF-1α)
levels. Additional patients with PAs and SDHx defects have since been reported. Overall,
prevalence of SDHx mutations in PA is very rare (0.3–1.8% in unselected cases) but
we and others have identified several cases of PAs with PHEOs/PGLs, like our original
report, a condition which we termed the 3 P association (3PAs). Interestingly, when
3PAs is found in the sporadic setting, no SDHx defects were identified, whereas in familial PGLs, SDHx mutations were identified in 62.5–75% of the reported cases. Hence, pituitary surveillance
is recommended among patients with SDHx defects. It is possible that the SDHx germline mutation-negative 3PAs cases may be due to another gene, epigenetic changes,
mutations in modifier genes, mosaicism, somatic mutations, pituitary hyperplasia due
to ectopic hypothalamic hormone secretion or a coincidence. PA in 3PAs are mainly
macroadenomas, more aggressive, more resistant to somatostatin analogues, and often
require surgery. Using the Sdhb
+/−
mouse model, we showed that hyperplasia may be the first abnormality in tumorigenesis
as initial response to pseudohypoxia. We also propose surveillance and follow-up
approach of patients presenting with this association.
Key words
pituitary adenoma - pheochromocytoma - paraganglioma - succinate dehydrogenase
