Acromegaly due to a growth hormone-releasing hormone-secreting intracranial gangliocytoma

Abstract

In more than 95% of cases acromegaly is due to GH hypersecretion by a pituitary adenoma. GHRH hypersecretion accounts for about 0.5% of cases of acromegaly. Intracranial GHRH-secreting tumors are extremely rare and only a few well-documented cases have been reported. The clinical features of acromegaly due to intracranial GHRH-secreting tumor are indistinguishable from those of other patients with "classical acromegaly". In cases of intrasellar gangliocytomas, not even radiological findings help to make the correct diagnosis, which can only be made with the hystological study. We present the case of a woman with acromegaly; the magnetic resonance demonstrated a 2x1.8x1.2 cm mass in the jugum sphenoidalis region, associated with a partial empty sella. There was a partial response to high-dose lanreotide therapy, so surgical treatment was decided, although only part of the tumor could be removed. Histopathological diagnosis was consistent with gangliocytoma, and immunostaining in the ganglionic cells was positive for GHRH. After surgery, hormone hypersecretion persisted, so medical treatment was reintroduced. In summary, we report a well-documented case of an intracranial GHRH-secreting gangliocytoma, an exceedingly rare cause of acromegaly. Clinical and biochemical data did not allow to make the correct diagnosis, which was only made on the pathological study. This case underscores that acromegaly can be due to causes other than a GH-secreting adenoma, and underlines that finding an image not typical of a pituitary adenoma should raise the suspicion that an unusual cause subsides the acromegaly.

Acromegaly: a challenging condition to diagnose

“…Alternatively, increased levels of growth hormone-releasing hormone (GHRH) produced in the hypothalamus account for 0.5% of acromegaly cases. 10 Hence, serum IGF-1 concentration is considered as a sensitive measure of integrated GH levels in patients with acromegaly. 9 Furthermore, some correlation between acromegaly and familial syndromes, such as McCune–Albright syndrome, multiple neoplasia type I, Carney complex, and isolated familial acromegaly, has been detected.…”

Clinical Manifestations and Diagnosis of Acromegaly

“…As previously discussed, acromegaly is rarely caused by ectopic tumors that produce GHRH (only 0.5% of acromegalic cases) or GH [8]. The suspicion for ectopic sources should arise when there is a biochemical diagnosis of acromegaly, with radiographic absence of a pituitary tumor or presence of diffuse pituitary enlargement or when the postsurgical pathology report indicates somatotroph hyperplasia rather than adenoma.…”

“…Familial syndromes of acromegaly are rare. Excessive production of GHRH from central hypothalamic sources (usually gangliocytomas) or peripheral sources can lead to somatotroph hyperplasia and acromegaly [8]. …”

Lesions within and around the Pituitary

“…Germinomas usually show prominent contrast enhancement and present well-defined margins. Individual case reports describe sellar lesions that radiologically cannot be differentiated from pituitary adenomas, such as chondrosarcomas, granular cell tumors [ 68,69], gangliocytomas [70,71], fibrosarcomas [72,73], hemangiopericytomas [74], esthesioneuroblastomas [75], melanomas [76], ependymomas [77], or lymphomas [78].…”