Adrenocortical-pituitary hybrid tumor causing Cushing's syndrome.
We describe the first case of an adrenocortical-pituitary hybrid tumor causing Cushing's syndrome in a 17-yr-old boy. Adrenal vein sampling confirmed elevated secretion of both cortisol and ACTH precursors from a right adrenal mass, whereas pituitary ACTH levels, as determined by bilateral inferior petrosal sinus samples (IPSS), were unresponsive to CRH and equal to peripheral levels. There was no biochemical or histological evidence for a pheochromocytoma, but, rather, the tumor demonstrated lipid-rich clear cells characteristic of an adrenocortical adenoma. Immunohistochemical analysis revealed ACTH immunoreactivity and synaptophysin proteins in the tumor. Isolation of tumor cells by the novel technique of laser capture microdissection and subsequent RT-PCR showed expression of POMC messenger ribonucleic acid and cytochrome p450 enzyme messenger ribonucleic acid within the same cells. Finally, ultrastructural analysis provided ultimate proof for adrenocortical-pituitary hybrid cells exhibiting the characteristic vesicular mitochondria and abundant smooth endoplasmic reticulum of steroid cells and the typical secretory granules of corticotrophs within the cytoplasm of the same cells. The adrenocortical tumor expressed the pituitary transcription factor pituitary homeobox factor 1 and the steroidogenic factor 1. The intermingling of the centrally located ectodermally derived pituitary tissue with the mesodermally derived adrenocortical tissue in this adenoma suggests a hitherto unrecognized genetic and phenotypic plasticity within the hypothalamic-pituitary-adrenal axis.
Hiroi
N
N
Pediatric and Reproductive Endocrinology Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892, USA.
Chrousos
G P
GP
Kohn
B
B
Lafferty
A
A
Abu-Asab
M
M
Bonat
S
S
White
A
A
Bornstein
S R
SR
D000236:Adenoma / Q000150:complications* / Q000378:metabolism / Q000473:pathology; D000293:Adolescent; D000306:Adrenal Cortex Neoplasms / Q000150:complications* / Q000378:metabolism / Q000473:pathology; D000324:Adrenocorticotropic Hormone / Q000378:metabolism; D003480:Cushing Syndrome / Q000209:etiology*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008854:Microscopy, Electron; D010902:Pituitary Gland / Q000378:metabolism; D010911:Pituitary Neoplasms / Q000150:complications* / Q000378:metabolism / Q000473:pathology; D011333:Pro-Opiomelanocortin / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D018043:Receptors, Corticotropin / Q000235:genetics; D013254:Steroid 17-alpha-Hydroxylase / Q000235:genetics; D054339:Steroidogenic Factor 1; D014157:Transcription Factors
C515057:NR5A1 protein, human; D012333:RNA, Messenger; D018043:Receptors, Corticotropin; D054339:Steroidogenic Factor 1; D014157:Transcription Factors; D011333:Pro-Opiomelanocortin; D000324:Adrenocorticotropic Hormone; D013254:Steroid 17-alpha-Hydroxylase