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Q1: What is the probable diagnosis?
The diagnosis of Cushing’s syndrome is confirmed by the low dose dexamethasone test and the considerably increased 24 hour urinary free cortisol concentrations. The imaging studies show tumours in the pituitary and the adrenal, while a large anterior mediastinal mass is seen on the thoracic image. The presence of hyperpigmentation, further supported by a raised ACTH level makes ACTH dependent Cushing’s syndrome probable. In this case, the non-suppressibility of cortisol to a high dose of dexamethasone and the short duration of symptoms point to ectopic Cushing’s syndrome. The common causes for ectopic Cushing’s syndrome are small cell carcinoma of the lung, bronchial carcinoid, islet cell tumours of the pancreas, and thymic carcinoids. Therefore the probable cause of ectopic Cushing’s syndrome in this case is the mediastinal mass, the first possibility being a carcinoid tumour arising from the thymus and a malignant thymoma being a rarer possibility.
Q2: Which is the best test to confirm the diagnosis?
As all the clinical and biochemical tests lack a 100% specificity,1 a bilateral inferior petrosal sinus sampling would have been the best test to confirm the diagnosis. Most corticotrophin secreting thymic carcinoids are larger than 2 cm and mostly detectable by chest computed tomography or magnetic resonance imaging on first presentation.2 As a second line option, computed tomographic guided biopsy of the anterior mediastinal mass was also considered in this case. These options were discussed with the patient and he opted for the second. The biopsy of the mediastinal mass showed a thymic carcinoid with a positive immunohistochemistry for ACTH confirming the diagnosis. Thymic carcinoids account for about 10% of ectopic ACTH producing tumours.3 The pituitary lesion was probably an incidental tumour, considering that the prevalence of incidentalomas on routine magnetic resonance imaging in a normal population is about 10%.4
Q3: How would you manage this patient?
In the presence of a demonstrable tumour, the longest survival rates are seen in those patients in whom a complete surgical resection is possible.5,6 Other modalities include chemotherapy, radiotherapy, and adrenalectomy.
This patient underwent surgery. He had a large anterior mediastinal tumour that at the time of surgery was found to have infiltrated the phrenic nerves and the pericardium. Therefore complete resection was not possible. Histopathological examination of the tumour was reported as an atypical carcinoid with immunopositivity for ACTH. Subsequently he had chemotherapy with cisplatin and etoposide followed by radiotherapy. At three month follow up, his 24 hour urinary free cortisol was 1319 nmol/day. Six months postoperatively his serum cortisol after 1 mg dexamethasone suppression was 50.5 nmol/l.