Mixed gangliocytoma-pituitary adenoma containing GH and GHRH co-secreting adenoma cells

Abstract

Summary A 67-year-old woman with a past history of type 2 diabetes mellitus presented with worsening glycemic control. She had some acromegaly symptoms and magnetic resonance imaging demonstrated a pituitary tumor. Endocrinological examination found the resting growth hormone (GH) level within the normal range, but elevated insulin-like growth factor 1 level. A 75 g oral glucose tolerance test showed inadequate suppression of nadir GH levels. Acromegaly due to GH-secreting pituitary tumor was diagnosed. The patient underwent endoscopic transsphenoidal surgery resulting in gross total removal of the tumor and recovered well postoperatively. Histological examination of the tumor showed coexistence of relatively large gangliocytoma cells and pituitary adenoma cells, suggesting mixed gangliocytoma-pituitary adenoma. In addition, colocalization of GH and GH-releasing hormone (GHRH) in pituitary adenoma cells was revealed, so the adenomatous components were more likely to produce GHRH in our mixed gangliocytoma-pituitary adenoma case. Mixed gangliocytoma-pituitary adenoma is very rare, and the present unique case demonstrated only the adenomatous components associated with GHRH production. Learning points: Sellar gangliocytoma coexisting with pituitary adenoma is recognized as a mixed gangliocytoma-pituitary adenoma and is very rare. A proposed developmental mechanism of growth hormone (GH)-secreting mixed gangliocytoma-pituitary adenoma involves GH-releasing hormone (GHRH) produced by the gangliocytic components promoting the growth of tumor including GH-secreting adenomatous components. Since our present case indicated that the adenomatous components of mixed gangliocytoma-pituitary adenoma could secrete both GH and GHRH simultaneously, progression of GH-secreting mixed gangliocytoma and pituitary adenoma may involve exposure to spontaneously produced GHRH due to the adenomatous components.

Pituitary Gangliocytoma Producing TSH and TRH: A Review of “Gangliocytomas of the Sellar Region”

“…The phenomena in pituitary tumors exhibiting co-secretion of hypothalamic upstream hormones and pituitary downstream hormones in the same tumor cell have been reported on rare occasions. In acromegaly, co-secreting GH-GHRH-producing adenoma has been reported in cases of both pure pituitary adenoma and adenomatous components in MGA ( 76 , 77 ). Moreover, some investigations have demonstrated that GHRH can synthesize not only in the normal pituitary gland, but also concurrently in somatotroph adenoma cells ( 78 , 79 ).…”

Neuronal Differentiation in a Pituitary Macroadenoma with Focal Small Blue Round Cell Morphology: Report of a Rare Pattern

“…The second theory is that heterotopic hypothalamic neurons within the adenohypophysis can produce stimulatory peptides (for example growth hormone releasing hormone) leading to hyperplasia and subsequent neoplastic transformation of adenohypophysial cells. A recent publication by Teramoto et al [13] revealed colocalization of GH and GH-releasing hormone (GHRH) in pituitary adenoma cells. The third hypothesis suggests the pituitary adenoma as the initial lesion.…”

Acromegaly Caused by Ectopic Growth Hormone Releasing Hormone Secretion: A Review

“…Since the initial report of the possible association between the neuroendocrine functional tumor and acromegaly, suggested by Altmann et al. in 1959, around 170 cases of suspected ectopic acromegaly have been described in literature to date, mostly as case reports ( 4 , 6 , 9 – 21 ). To our best knowledge, only 19 cases were described as caused by an ectopic source of GH ( 22 – 27 ).…”

“…The term ‘ectopic’ is used in a broader sense in this review, applying not only to its most common meaning of an abnormal localization, but also basically to the secretion of a hormone by a tissue that does not produce it under physiological circumstances ( 5 ). Therefore, GHRH-secreting pituitary gangliocytoma will also be included in the review, as they fall under given definition ( 6 ). Ectopic acromegaly clinical features are indistinguishable from those of acromegaly caused by a pituitary somatotropinoma ( 7 ).…”