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2018 ; 5
(ä): 54
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The Many Faces of Primary Aldosteronism and Cushing Syndrome: A Reflection of
Adrenocortical Tumor Heterogeneity
#MMPMID29594118
Mete O
; Duan K
Front Med (Lausanne)
2018[]; 5
(ä): 54
PMID29594118
show ga
Adrenal cortical tumors constitute a heterogeneous group of neoplasms with
distinct clinical, morphological, and molecular features. Recent discoveries of
specific genotype-phenotype correlations in adrenal cortical adenomas have
transformed our understanding of their respective endocrine syndromes. Indeed, a
proportion of patients with primary aldosteronism are now known to harbor adrenal
cortical adenomas with heterogeneous molecular alterations (KCNJ5, ATP1A1,
ATP2B3, and CACNA1D) involving the calcium/calmodulin kinase signaling pathway.
Several lines of evidence suggest that KCNJ5-mutant aldosterone-producing
adenomas have distinct clinicopathological phenotype compared to those harboring
ATP1A1, ATP2B3, and CACNA1D mutations. Benign adrenal cortical tumors presenting
with Cushing syndrome often have diverse mutations (PRKACA, PRKAR1A, GNAS,
PDE11A, and PDE8B) involving the cyclic AMP signaling pathway. In addition to
cortisol-producing adenomas, bilateral micronodular adrenocortical disease and
primary bilateral macronodular adrenal hyperplasia (PBMAH) have also expanded the
spectrum of benign neoplasms causing adrenal Cushing disease. The recent
discovery of inactivating ARMC5 germline mutations in PBMAH has challenged the
old belief that this disorder is mainly a sporadic disease. Emerging evidence
suggests that PBMAH harbors multiple distinct clonal proliferations, reflecting
the heterogeneous genomic landscape of this disease. Although most solitary
adrenal cortical tumors are sporadic, there is an increasing recognition that
inherited susceptibility syndromes may also play a role in their pathogenesis.
This review highlights the molecular and morphological heterogeneity of benign
adrenal cortical neoplasms, reflected in the diverse presentations of primary
aldosteronism and adrenal Cushing syndrome.