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Table of Contents    
Year : 2012  |  Volume : 60  |  Issue : 3  |  Page : 304-306

Coexistence of ectopic pituitary adenoma and empty sella in a patient with acromegaly : A case report and review of literature

1 Department of Neurosurgery, Fuzhou General Hospital, Fuzhou, China
2 Department of Neurosurgery, Changzheng Hospital of Second Military Medical University, Shanghai, China

Date of Submission22-Dec-2012
Date of Decision16-Jan-2012
Date of Acceptance16-Mar-2012
Date of Web Publication14-Jul-2012

Correspondence Address:
Jing-Fang Hong
Department of Neurosurgery, Fuzhou General Hospital, No. 156 Xihuanbei Road, Fuzhou 350025
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0028-3886.98517

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 » Abstract 

Ectopic pituitary adenoma with an empty sella is extremely rare. We report an unusual patient with an ectopic growth hormone-secreting pituitary adenoma in the sphenoid sinus with an empty sella. The association is related to a development disorder of the anterior pituitary tissues. Tumor in the sphenoid sinus was completely removed by endoscopic endonasal transsphenoidal approach. During the follow-up, the patient met the criteria for endocrinological cure.

Keywords: Acromegaly, ectopic pituitary adenoma, empty sella, sphenoid sinus

How to cite this article:
Hong JF, Ding XH, Wang SS. Coexistence of ectopic pituitary adenoma and empty sella in a patient with acromegaly : A case report and review of literature. Neurol India 2012;60:304-6

How to cite this URL:
Hong JF, Ding XH, Wang SS. Coexistence of ectopic pituitary adenoma and empty sella in a patient with acromegaly : A case report and review of literature. Neurol India [serial online] 2012 [cited 2023 Dec 6];60:304-6. Available from:

 » Introduction Top

Acromegaly resulting from ectopic growth hormone-releasing hormone (GHRH) secreting pituitary adenoma is rare, with a prevalence about 0.5% all cases of acromegaly. [1] Also, the coexistence of acromegaly and a normal-sized empty sella with a pituitary adenoma limited to the sphenoid sinus is extremely rare. We report here such an unusual case and discuss the possible pathogenesis of the coexistence of both conditions and also review all such reported cases in the literature.

 » Case Report Top

A 48-year-old man noticed gradual enlarging of his hands, feet, lips, and nose since 10 years and developed holocranial headache since 3 years. He did not have any visual symptoms. Physical examination revealed typical acromegalic features and no visual field defects. Laboratory data showed elevated serum growth hormone (GH; 18 ng/ml, measured by chemiluminescence assay) and insulin-like growth factor-1 (IGF-1; 1120 ng/ml, measured by immunoradiometric assay). An oral glucose tolerance test (OGTT) showed no suppression of GH values. Serum levels of prolactin (PRL), adrenocorticotropic hormone (ACTH), cortisol (CS), thyroid-stimulating hormone (TSH), follicle-stimulating hormone (FSH), and luteinizing hormone (LH) were normal. T1-weighted magnetic resonance imaging (MRI) revealed an empty sella and a mass with increased signal intensity within the sphenoid sinus in the midline [Figure 1]. Sphenoid sinus tumor was removed completely by endoscopic endonasal transsphenoidal approach. Intraoperatively, some of the bone floor of the sella was found to be absent, but the dura mater of the sellar floor was intact and the tumor was separated from the intrasellar contents. Normal pituitary tissues were not found in the sphenoid sinus. Hematoxylin and eosin staining and immunohistochemical study of the resected tumor confirmed the diagnosis of GH pituitary adenoma. Postoperative course was uneventful. At 5 months postoperative follow-up, serum GH and IGF-1 levels were decreased to 2 ng/ml and 290 ng/ml (normal, 100-306 ng/ml for 41-50-year-old men), respectively, and nadir GH value after OGTT was 0.3 ng/ml. Repeat follow-up MRI did not show any recurrence of tumor in the sphenoid sinus [Figure 2]. Another endoscopic procedure showed that some remaining tissues in the sphenoid sinus were scar tissue and inflammatory tissue.
Figure 1: T1-weighted MRI revealed a sphenoid pituitary tumor associated with an empty sella. A pituitary stalk in the center of the sella was surrounded by CSF, indicating an empty sella. The tumor in the sphenoid sinus was delineated radiologically from the pituitary fossa and slightly enhanced by contrast media, gadolinium-DTPA, in sagittal MR image

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Figure 2: A 5-month postoperative T1-weighted magnetic resonance image with enhanced gadolinium-DPTA revealed the tumor in the sphenoid sinus was not detected

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 » Discussion Top

Acromegaly disorder results from uncontrolled hypersecretion of GH and secondary increase in IGF-1 levels. Most cases of acromegaly are due to a benign pituitary adenoma which develops from somatotrope cells that normally produce GH in the pituitary. Less than 0.5% of acromegaly cases are due to an ectopic source, including ectopic hypothalamic GHRH-secreting tumor or ectopic peripheral GHRH hypersecretion (pancreatic or bronchial carcinoid tumor). Acromegaly can also occur from an ectopic pituitary adenoma (sphenoidal sinus, nasopharyngeal cavity, clivus) in exceptional cases. [1],[2],[3]

An ectopic pituitary adenoma is the adenoma that originates from the extrasellar region without any connection to a normal pituitary gland and stalk. [2] Most of these tumors are located outside the blood-brain barrier, with a preference for the sphenoid sinus or suprasellar region. About 27% of cases are located sporadically along the clivus, cavernous sinus, petrous bone, sphenoid bone, mid-nasal ductus, or third ventricle. [4] Empty sella refers to a neuroradiological entity characterized by a cerebrospinal fluid-filled sella, with a normal pituitary gland compressed to the rim of the fossa. [5] The coexistence of a normal-sized empty sella with an ectopic pituitary adenoma confined to the sphenoid sinus is extremely rare. Developmental disorders of the glandular pituitary are relatively common. [6],[7] During ingrowth of Rathke's pouch, remnants of the pituitary tissue can be retained in the sphenoid sinus, sphenoid bone, or within the sella turcica separate from the normal pituitary gland. [8] These cell rests can become the sites for ectopic pituitary adenomas. Therefore, an ectopic pituitary adenoma in the sphenoid sinus is thought to originate from embryological remnants of pituitary tissue. Review of the literature revealed of the 37 published cases of ectopic growth hormone-secreting pituitary adenomas, five cases were of ectopic pituitary adenomas with an empty sella [Table 1]. [2],[9],[10],[11],[12]
Table 1: Reported cases of ectopic pituitary adenoma in the sphenoid sinus with an empty sella

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Because of their rarity, the origin and pathogenesis of the coexistence of an ectopic pituitary adenoma and empty sella remains unclear. Several explanations have been proposed and the issue remains debatable. One explanation is that there exists primarily an empty sella and a pituitary adenoma subsequently developed. With the increasing downward intrasellar pressure, the adenoma extends into the sphenoid sinus through a small defect in the sellar floor. The second explanation is that an empty sella is secondary. A pituitary adenoma in the sella turcica first extends into the sphenoid sinus. In the course of tumor growth, the intrasellar adenoma undergoes necrosis, resulting in secondary empty sella. Finally, adenoma remains only in the sphenoid sinus. The third explanation is that during the course of formation of the anterior pituitary gland, most of the precursors of nasopharyngeal origin remain in the sphenoid sinus, from which the ectopic adenoma arises, and the anterior pituitary gland is constituted from only a small number of cells, which leads to the empty sella. [2],[6],[10] For the first two explanations, we would consider that the tumor is an "invasive adenoma," which results from constant growth of pituitary adenoma from the sella turcica into the sphenoid sinus, but not an "ectopic adenoma," which arises from embryological remnants of pituitary tissue in the sphenoid sinus. In this patient, there was no obvious history of pituitary apoplexy and intact dura was found during the operation. Therefore, it would be reasonable to assume that the last explanation is the best for our patient. Radiological examination is very important for the diagnosis of this entity. In most cases, MRI helps to differentiate "invasive" from "ectopic" pituitary adenomas based on delineating the tumor from the pituitary gland and the apparently intact dura mater of the sellar floor. [8],[10] However, the surgical finding of intact dura is the gold standard for diagnosis. In our patient, surgery confirmed that a GH-secreting adenoma in the sphenoid sinus was completely separated from the normal pituitary stalk and gland with intact dura, as observed by pre- and postoperative MRI. These findings confirmed the ectopic origin of the adenoma arising in the sphenoid sinus and excluded the possibility of direct extension from an intrasellar pituitary adenoma into the sphenoid sinus.

Treatment of these cases is by surgical excision using the transsphenoidal route. [2],[11] Significant clinical and endocrinological improvement was observed after surgical therapy; postoperative diabetes insipidus was not found because the pituitary stalk is neither involved by the tumor nor affected by surgery. In this case, serum nadir GH after OGTT and IGF-1 decreased to normal levels after surgery. Based on the recent criteria to define active acromegaly and disease control, [12] the patient was believed to have met the criteria for endocrinological cure. [13] No further treatment was given, and follow-up with endocrinological examination or MRI will determine whether further treatment is needed.

 » References Top

1.Thorner MO, Frohman LA, Leong DA, Thominet J, Downs T, Hellmann P, et al. Extrahypothalamic growth-hormone-releasing factor (GRF) secretion is a rare cause of acromegaly : p0 lasma GRF levels in 177 acromegalic patients. J Clin Endocrinol Metab 1984;59:846-9.  Back to cited text no. 1
2.Matsuno A, Katayama H, Okazaki R, Toriumi M, Tanaka H, Akashi M, et al. Ectopic pituitary adenoma in the sphenoid sinus causing acromegaly associated with empty sella. ANZ J Surg 2001;71:495-8.  Back to cited text no. 2
3.Chanson P, Salenave S. Acromegaly. Orphanet J Rare Dis 2008;3:3-17.  Back to cited text no. 3
4.Ali R, Noma U, Jansen M, Smyth D. Ectopic pituitary adenoma presenting as midline nasopharyngeal mass. Ir J Med Sci 2010;179:593-5.  Back to cited text no. 4
5.Del Monte P, Foppiani L, Cafferata C, Marugo A, Bernasconi D. Primary "empty sella" in adults : e0 ndocrine findings. Endocr J 2006;53:803-9.  Back to cited text no. 5
6.Warczy,ska A, Zieli,ski G, Koziarski A, Podgórski JK. Ectopic pituitary adenoma. Case report and review of literature. Neurol Neurochir Pol 2002;36:1185-96.  Back to cited text no. 6
7.Kurowska M, Tarach JS, Zgliczy,ski W, Malicka J, Zieli,ski G, Janczarek M. Acromegaly in a patient with normal pituitary gland and somatotropic adenoma located in the sphenoid sinus. Endokrynol Pol 2008;59:348-51.  Back to cited text no. 7
8.Ciocca DR, Puy LA, Stati AO. Immunocytochemical evidence for the ability of the human pharyngeal hypophysis to respond to change in endocrine feedback. Virchows Arch A Pathol Anat Histopathol 1985;405:497-502.  Back to cited text no. 8
9.Gondim JA, Schops M, Ferreira E, Bulcao T, Mota JI, Silveira C. Acromegaly due to an ectopic pituitary adenoma in the sphenoid sinus. Acta Radiol 2004;45:689-91.  Back to cited text no. 9
10.Hori E, Akai T, Kurimoto M, Hirashima Y, Endo S. Growth hormone-secreting pituitary adenoma confined to the sphenoid sinus associated with a normal-sized empty sella. J Clin Neurosci 2002;9:196-9.  Back to cited text no. 10
11.Das CJ, Seith A, Gamanagatti S, Goswami R. On the AJR viewbox. Ectopic pituitary adenoma with an empty sella. AJR Am J Roentgenol 2006;186:1468-9.  Back to cited text no. 11
12.Madonna D, Kendler A, Soliman AM. Ectopic growth hormone-secreting pituitary adenoma in the sphenoid sinus. Ann Otol Rhinol Laryngol 2001;110:99-101.  Back to cited text no. 12
13.Giustina A, Chanson P, Bronstein MD, Klibanski A, Lamberts S, Casanueva FF, et al. Acromegaly Consensus Group. A consensus on criteria for cure of acromegaly. J Clin Endocrinol Metab 2010;95:3141-8.  Back to cited text no. 13


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  [Table 1]

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