Introduction. A precise and early diagnosis of the underlying cause of Cushing's syndrome is necessary for successful treatment. The treatment of choice in ACTH-dependent Cushing's syndrome of pituitary origin is transsphenoidal pituitary adenoma resection. In patients, without visible pituitary adenoma on magnetic resonance imaging (MRI), surgical treatment should only be considered if the results of dynamic tests are unequivocal. Objectives. To assess usefulness of the desmopressin test in comparison with high-dose dexamethasone suppression test and CRH test in establishing the diagnosis of ACTH-dependent Cushing's syndrome of pituitary origin. Patients and methods. 15 patients with ACTH-dependent Cushing's syndrome were studied. Pituitary microadenoma was surgically and histologically confirmed in all patients (only in 10 of them did pituitary MRI show a microadenoma). A control group consisted of 15 subjects, in whom Cushing's syndrome and other endocrine abnormalities were excluded. The following procedures were performed in all studied patients: daily rhythm of cortisol secretion, high-dose dexamethasone suppression test, CRH test and desmopressin test. Results. False negative responses were observed: in 1 patient to dexamethasone, in 1 patient to CRH and in 2 patients to desmopressin. In the other patients results of all 3 tests were positive. In 4 out of 5 patients without microadenoma seen on pituitary MRI, the desmopressin test yielded positive results. In the control group the results of dexamethasone and CRH test were positive in all patients, whereas the desmopressin test gave negative results (neither ACTH nor cortisol secretion increased after desmopressin administration in any patient). Conclusions. 1) The desmopressin test performed together with high-dose dexamethasone suppression test and CRH test may, in some cases, enhance the precision of final diagnosis of ACTH-dependent Cushing's syndrome of pituitary origin. 2) The desmopressin test allows a very precise identification of healthy subjects.
ObjectiveManagement of Graves’ orbitopathy remains a challenge. Our previous case report has shown promising results for rabbit antithymocyte globulin (rATG) in the treatment of Graves’ orbitopathy.DesignWe present the response of 7 individuals with active moderate-to-severe steroid-resistant Graves’ orbitopathy to rATG, representing preliminary results from a prospective single-center study.MethodsrATG was administered intravenously at a dose of 0.8–1.0 mg/kg daily (cumulative dose of 150–200 mg). The primary outcome measures at weeks 24 and 48 were ≥2-point reduction in Clinical Activity Score from baseline, a proptosis response, a diplopia response, and improvement of distant best-corrected visual acuity and mean retinal sensitivity. Key secondary outcomes included stabilization of ganglion cell complex thickness, a decrease of retinal nerve fiber layer in OCT, and a reduction in CD4/CD8 ratio and TRAb at 48 weeks.ResultsAn improvement in clinical activity score was observed in all patients, with disease inactivation in 3 cases. Proptosis reduction equal to or greater than 2 mm was noted for 8 of 10 eyes. Diplopia improved in three of 6 patients. There was an improvement in best-corrected visual acuity (from 0.69 to 0.78) and mean retinal sensitivity (from 20.8 to 23.5 dB). In addition, there was a long-lasting improvement in CD4/CD8 ratio in 6 patients. Two patients experienced adverse events (influenza and serum sickness).ConclusionrATG therapy offers a long-lasting improvement in moderate-to-severe steroid-resistant Graves’ orbitopathy with improvement in functional vision (reduction of diplopia, improvement of visual acuity, retinal sensitivity, and VEP pattern). The therapy is well-tolerated.Clinical Trial RegistrationClinicalTrials.gov, identifier NCT05199103.
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