Ectopic sphenoidal ACTH-secreting adenoma revealed by 11C Methionine PET scan: case report

Abstract

Background: Ectopic ACTH pituitary adenomas (EAPA), located outside the sella turcica and deriving from cellular remnants of Rathke's pouch are a very rare cause of Cushing's syndrome (CS). The diagnosis is often difficult and delayed, even after comprehensive work-up. To our knowledge, we report for the first time an ectopic corticotroph tumor of the posterior wall of the sphenoid sinus, leading to false positive results of bilateral inferior petrosal sinus sampling (BIPPS) and which was finally localized by a co-registered¹¹ C Methionine PET/MR imaging.

Case presentation: A 48-year-old woman was referred for a high clinical suspicion of ACTH-dependent CS. Biological testing comprising low dose dexamethasone suppression and CRH stimulation tests were indicative of pituitary Cushing's disease, but comprehensive pituitary MRI did not reveal any pituitary adenoma. BIPSS confirmed however a central origin of ACTH secretion (central-to-peripheral ACTH ratio > 100) and revealed a significant right-to-left gradient (6.2), leading to a first right-sided exploratory hypophysectomy, that did not cure the patient. BIPSS images were reviewed and revealed preferential drainage of the left pituitary to the right petrosal sinus, leading us to a left sided exploratory hypophysectomy, which was again unsuccessful. A¹¹ C Methionine PET/MRI was performed and revealed a hypermetabolic lesion adjacent to the posterior wall of the sphenoidal sinus. After surgical resection, this polypoid mass was identified as an ectopic ATCH-secreting pituitary adenoma expressing ACTH and T-Pit and complete remission of hypercortisolism was observed.

Conclusions: In conclusion, we report a case of ACTH-dependent Cushing's syndrome, caused by an ectopic corticotroph adenoma located in the sphenoidal sinus, which perfectly mimicked the biological features of a classical pituitary ACTH adenoma on a comprehensive hormonal evaluation including BIPPS, and the features of a benign naso-sinusal polyp at MRI. We report for the first time a key role of¹¹ C Methionine PET co-registered to high resolution MRI for localizing ectopic adenomas, efficiently guiding surgical removal and leading to complete remission of hypercortisolism.

Keywords: 11C Methionine PET/MRI; ACTH-secreting adenoma; Cushing’s syndrome; Ectopic pituitary adenoma.

Fig. 1

Pituitary magnetic resonance imaging (MRI) at diagnosis. A Thin coronal T2-weighted slice showing a normal pituitary gland (arrow); B Contrast-enhanced (CE) thin coronal T1-weighted slice in similar location as Fig. 1A, failing to reveal any abnormality in the pituitary gland; C Pre-contrast thin mid-sagittal T1-weighted slice showing normal anterior and posterior pituitary lobes (thin arrow) and a polypoid-like mass on the posterior wall of the sphenoid sinus, clearly distant from the sellar region and first considered as a benign naso-sinusal polyp (thick arrow)

Fig. 2

Co-registered magnetic resonance imaging (MRI) and ¹¹C-methionine positron emission tomography (PET) performed after two unsuccessful pituitary surgeries. A Coronal view showing normal and homogeneous tracer uptake within residual pituitary parenchyma (between arrows); B Coronal view on a slightly more posterior view than Fig. 2A showing intense tracer uptake within the posterior sphenoid mass (large arrow), SUV_max at 3.3; C Axial transverse view showing similar features as Fig. 2B. D ⁶⁸Ga-Dotatate-PET/CT showing normal uptake at the pituitary level (thin arrow) and no uptake of the tracer in the posterior sphenoid mass (large arrow)

Fig. 3

Histological and immunohistochemical analysis of the sphenoidal mass after surgical excision. A Hematoxylin and eosin staining of a tumor section, showing cells with sparsely granulated slightly basophilic cytoplasm. B Immunohistochemistry performed for ACTH, showing diffuse intra-cytoplasmic ACTH staining in the majority of tumoral cells. C Immunohistochemistry performed for T-Pit, revealing nuclear staining of the tumor cells. (Bar = 10 μm)