Cushing's Disease in a Child Caused by a Corticotropin-releasing Hormone-secreting Intrasellar Gangliocytoma Associated with an Adrenocorticotropic Hormone-secreting Pituitary Adenoma

Abstract

Cushing's disease resulting from intrasellar corticotropin-releasing hormone (CRH)-secreting gangliocytomas is very rare, and only two such cases have been reported in the literature to date. The authors present a third case in which an adrenocorticotropic hormone-secreting pituitary adenoma was found in addition to a gangliocytoma in a 10-year-old girl with clinical and endocrinological symptoms of Cushing's disease. Computed tomographic and magnetic resonance imaging scans showed a suprasellar and parasellar tumor. A green-colored, heterogeneous tumor and a small adenoma were removed transsphenoidally. Histological examination revealed a large gangliocytoma immunoreactive for CRH and a small, mucoid cell pituitary adenoma immunoreactive for ACTH. This is the first case of such a tumor causing Cushing's disease in a child. It might exemplify induction of an ACTH-secreting pituitary adenoma by means of chronic overstimulation of CRH.

Ganglion cell tumours in the sella turcica in close morphological connection with pituitary adenomas

“…They are composed of mature ganglion cells with or without a glial component. Gangliocytomas of the pituitary gland are exceptionally rare and usually coexist with a pituitary adenoma, most commonly a GH-secreting adenoma, with the clinical manifestation of acromegaly [4][5][6]12,17,23,27,32,35,39,44,46]; less often, they are associated with ACTH-producing adenomas, and present with Cushing's disease [25,36,40].…”

“…The majority of ganglion cell tumours appear in association with growth hormone-secreting pituitary adenoma presenting with acromegaly [2,[4][5][6]12,[17][18][19]23,25,32,38,40,42]. They appear less often with adrenocorticotropic hormone-producing adenomas with clinical presentation of Cushing's disease [25,36,40].…”

Ectopic Cushing’s Syndrome due to an Adrenal Ganglioneuroma

“…Interestingly, intrasellar gangliocytomas have been described to be associated with secreting pituitary tumors. They are able to synthesize hypothalamic and pituitary hormones [27,28,29]. Whether these very rare cases of ganglion cell proliferations and gland hyperplasia or adenoma can be compared remains to be established.…”

Suprasellar Germinoma Associated with Cushing’s Disease and Diabetes insipidus in a Child

“…Other unusual presentations of Cushing's syndrome have included the single report of a 12-year-old girl with intractable retroperitoneal paraganglioma who was the first patient with a malignant paraganglioma with the capacity of producing cortisol, androgens and ACTH [17]. Additionally, Puchner et al [18,19] previously described a child who presented with Cushing's disease and had a CRH secreting intrasellar gangliocytoma associated with an ACTH-secreting pituitary adenoma. Conversely, a review of the clinical behavior of suprasellar germinomas notes pituitary dwarfism, hypodipsic hypernatremia syndrome, galactorrhea, precocious puberty, and obesity as being the more common atypical presentations [3,20].…”