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On-line version ISSN 1678-4227
Arq. Neuro-Psiquiatr. vol.67 no.1 São Paulo Mar. 2009
Spoiled gradient recalled acquisition in the steady state for magnetic resonance imaging diagnosis of Cushing disease
Ressonância magnética tridimensional no diagnóstico da doença de Cushing
Carolina G.S. Leães; Júlia F.S. Pereira-Lima; Rene Lenhardt; Vera M.F. Silveira; Nelson P. Ferreira; Miriam C. Oliveira
Neuroendocrinology Center, Complexo Hospitalar Santa Casa, Universidade Federal de Ciências da Saúde de Porto Alegre (UFCSPA), Porto Alegre RS, Brazil
Cushing disease (CD) is a rare and debilitating endocrinopathy caused by an adrenocorticotropin (ACTH)-secreting pituitary adenoma. The diagnosis of CD consists in signs, symptoms and laboratorial detection of endogenous hypercortisolism along with identification of the pituitary tumor1. Detection of ACTH-secreting pituitary adenomas by imaging techniques has always been a challenge. Gadolinium-enhanced magnetic resonance imaging (MRI) has diagnostic accuracy for CD ranging from 40 to 50%1,2, and new techniques, such as the spoiled gradient recalled acquisition in the steady state (SPGR) MRI have been developed to improve the rate of pituitary tumor detection3-5.
We report on a case in which SPGR MRI proved essential for achieving an accurate diagnosis of CD.
A 48-year-old female presented with 12 months of weight gain, rounded and red face, hair loss, intense and activity-limiting fatigue, arthralgias, increase in blood pressure levels, and severe osteoporosis with schium fractures. She denied previous use of glucocorticoids or chronic diseases, headache or visual alteration. History of continued use of enalapril 20 mg qid, alendronate sodium 70 mg/week, calcium, 500 mg bid, vitamin D 200IU bid. On physical examination, she presented moon facies, facial plethora, blood pressure levels of 140/90 mmHg, bufallo hump, centripetal obesity, proximal upper and lower limb muscle weakness, and hair fragility. No violaceous striae, hirsutism or acne. Laboratory evaluation revealed basal cortisol levels at 8 h: 28.2 mg/dL; cortisol at 24 h: 26 mg/dL; 24-h cortisoluria: 303.4 (25213.7 mg/24 h); basal ACTH: 58.6 (046 pg/mL); 0.5-mg dexamethasone suppression testing every 6 h for 8 doses: cortisol: 25.5 and 24-h cortisoluria: 740.0; 2-mg dexamethasone suppression testing every 6 h for 8 doses: cortisol: 20.1 and 24-h cortisoluria: 986.4.
Pituitary MRI showed normal pituitary gland (Fig 1) and computed tomography (CT) scan of the chest and abdomen disclosed normal tomographic and morphological aspect of the adrenal glands, and a nodular image of 0.8 cm in the central region of the inferior lobe of the left lung, with density of soft parts, slightly wavy contour, and of uncertain evolutive nature and potential. Magnetic resonance images were reconstructed by means of three-dimensional SPGR, exhibiting a 0.4 ' 0.3-cm posterolateral right-sided pituitary microadenoma; pituitary stalk with slightly asymmetric implantation corresponding to the anatomic variable (Fig 2). Inferior petrosal sinus sampling (IPSS) was performed after desmopressin stimulation (10 mg IV), which indicated ACTH hypersecretion from the right inferior petrosal sinus (Table). The patient underwent transsphenoidal surgery, with histological confirmation of the pituitary adenoma immunohistochemically positive for ACTH.
In the case presented here, the patient showed clinical features compatible with Cushing syndrome: centripetal obesity, bufallo hump, moon facies, facial plethora, proximal muscle weakness, muscular hypotrophy, hair fragility, hypertension, and osteoporosis1. Screening examinations were positive with increased 24-h cortisoluria and midnight cortisol. ACTH value >15 pg/mL suggested ACTH-dependent hypercortisolism. No suppression with high-dose dexamethasone associated with normal pituitary MRI and presence of small pulmonary nodule suggested an ectopic ACTH-secreting tumor. However, although the precise nature of the pulmonary nodule could not be confirmed, reconstruction MRI using the SPGR technique to identify right-sided pituitary microadenoma combined with the IPSS clearly positive result proved essential for achieving an accurate etiological diagnosis of CD. Classically, the diagnosis of CD is considered as an IPS/peripheral-ACTH ratio >2.0 in the basal state and >3.0 after stimulation. Moreover, a bilateral (left/right or right/left) IPS gradient >1.4 suggests lateralization of the lesion1. Although IPS catheterization has accuracy of only 57% for lateralization of the lesion due to asymmetries in venous drainage and tumor location close to the mean line, in the present case lateralization of the lesion could be clearly indicated (IPS gradient/peripheral-ACTH and baseline right/left=10.0 and=33.0 after stimulation).
However, some factors hinder the correct identification of the corticotropinomas, mainly their tipically small size (90% of them are microadenomas)1,3 and tendency to present signs and enhancement similar to those of the normal pituitary tissue3,4.
Recent studies have demonstrated that postgadolinium SPGR MRI doubled the detection rate of pituitary adenomas in adults3 and children5 when compared to conventional MRI with T1-weighted spin echo (SE) sequences. Patronas et al.3 have demonstrated SPGR MRI sensitivity of 80% in the detection of corticotropinomas, superior to the 49% obtained by means of conventional MRI SE. Factors contributing to a better performance of SPGR MRI include superior soft tissue contrast and images obtained from thinner sections of 1 to 1.5 mm with consequently higher image resolution3,4. Furthermore, the SPGR method is characterized by faster acquisition of images, minimizing artifacts from motion and vascular pulsation3. Another recent application of this method is the intraoperative SPGR MRI as a surgical modality in transsphenoidal surgery, which allows a differentiation between normal pituitary tissue, residual tumor tissue, fibrosis, reactive inflammatory alterations, and hematoma formation, decreasing morbidity associated with the surgery and increasing overall success rate after surgery6.
It is important to recognize that in the case reported here, both studies were carried out simultaneously, discarding the possibility of different results between the techniques due to possible tumor growth.
The cure rate for CD patients with detected tumor is 8090%, but drops to 5070% when the lesion cannot be localized preoperatively7,8. Besides increasing the cure rate, the identification of the ACTH-secreting tumor decreases morbidity associated with CD in transsphenoidal surgery, reducing the incidence of hypopituitarism and cerebrospinal fluid leak caused by multiple surgical pituitary exploration1,4. Thus, we highlight the importance of the development of techniques and use of associated high-accuracy imaging methods in these patients.
In conclusion, SPGR MRI proved superior to conventional MRI SE in the detection of pituitary tumors, especially of suspected corticotropinomas. For this reason, the authors suggest the inclusion of this method in the evaluation protocol for these lesions.
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8. Barrou Z, Abecassis JP, Guilhaume B, et al. Magnetic resonance imaging in Cushing disease: prediction of surgical results. Presse Med 1997; 26:7-11. [ Links ]
Received 7 July 2008, received in final form 30 September 2008. Accepted 10 November 2008.
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