Spontaneous Adrenocorticotropic Hormone (acth) Normalisation Due To Tumour Regression Induced By Metyrapone In A Patient With Ectopic Acth Syndrome: Case Report And Literature Review
Iwayama, H., Hirase, S., Nomura, Y., Ito, T., Morita, H., Otake, K., Okumura, A., & Takagi, J. (2018). Spontaneous adrenocorticotropic hormone (ACTH) normalisation due to tumour regression induced by metyrapone in a patient with ectopic ACTH syndrome: case report and literature review. BMC endocrine disorders, 18(1), 19. https://doi.org/10.1186/s12902-018-0246-2
View Original Source →Abstract
BACKGROUND: Ectopic adrenocorticotropic hormone (ACTH) syndrome (EAS) is caused by tumours releasing ACTH. Ectopic ACTH-producing tumour regression is rarely induced using steroidogenesis inhibitors. We presented a case of EAS in which ACTH production by a lung tumour was reduced by metyrapone (MTP) and also reviewed previous cases of ectopic ACTH production suppressed via steroidogenesis inhibition. CASE PRESENTATION: A 71-year-old female with general fatigue, central obesity and impaired glucose tolerance was diagnosed with Cushing's syndrome due to elevated ACTH (192.9 pg/mL; normal range, 7.2-63.3 pg/mL), cortisol (73.1 μg/dL; 6.4-21.0 μg/dL) and 24-h urinary free cortisol (UFC) (6160 μg/day; 11.2-80.3 μg/day) levels. Chest computed tomography identified a solid 26.6 × 22.9 × 30.0 mm tumour with a cavity in the upper lobe of the left lung. There was no adrenal gland enlargement. Tumour markers were not significantly elevated; ACTH levels were not suppressed by 8-mg dexamethasone. A corticotropin-releasing hormone stimulation test revealed blunted ACTH response (basal ACTH, 204.6 pg/mL; highest ACTH level during the 120-min stimulation test, 214.0 pg/mL). She was diagnosed with EAS due to a lung lesion. MTP treatment was started to reduce cortisol production. ACTH levels and cortisol and UFC levels were normalised and the ACTH-producing lung tumour was ablated after MTP treatment. In several reported cases, plasma ACTH levels reduced during steroidogenesis inhibitor treatment for EAS. Among the 10 patients, three cases of pheochromocytoma, one of thymic carcinoid and one of islet cell carcinoma were reported. In four cases, the tumour was not detected. In our case, the pathology of the lung tumour was unknown because of lack of tumour cells in biopsy. The patients were treated with ketoconazole (KTZ) and/or MTP and exhibited ACTH and cortisol/UFC suppression, but tumour regression was observed only in our case. CONCLUSION: MTP and/or KTZ may reduce ACTH and cortisol production. The tumour spontaneously regressed after MTP treatment, indicating that MTP may reduce the tumour size without surgery. The mechanisms of therapeutic effects of steroidogenesis inhibitors and prognosis of spontaneous remission should be elucidated further via molecular biology studies.
Case Details
Disease Location
Lung
Personal Characteristics
71-year-old female. History of graves’ disease, colon polyp, sarcoidosis and uveitis following glucocorticoid treatment.
Clinical Characteristics
Presented with general fatigue, leg oedema, and impaired glucose tolerance. Brain magnetic resonance imaging revealed an empty sella with no pituitary adenoma. Chest computed tomography (CT) identified a solid tumour of 26.6 mm × 22.9 mm × 30.0 mm in size with a cavity in the upper lobe of the left lung. An overnight 8-mg dexamethasone suppression test was performed. Lack of suppression of acth and cortisol by 8-mg of dexamethasone was consistent with ectopic adrenocorticotropic hormone syndrome (eas). The patient was diagnosed with eas due to a lung lesion. Metyrapone (mtp) treatment was started to reduce cortisol production on the first day of hospitalization. On day 3, because cortisol levels fell below the normal range, hydrocortisone treatment was started for supplementation. On the same day, the patient developed pneumonia and pleural effusion. Imipenem/cilastatin (1 g/day, days 3–12) and caspofungin acetate (50 mg/day, days 5–20) were administered. On day 14, CT detected enlargement of the lung tumour to a 5-cm-diameter mass. Along with enlargement of the lung tumour, acth levels increased the nodular lesion was considered an acth-producing tumour
Remission Characteristics
On day 19, her serum acth level decreased. Concurrently with the decline of the serum cortisol content. Brush cytology using bronchoscopy showed only a few neutrophils, dust cells, ciliated columnar cells, and squamous cells, and no malignant findings were found. Second, CT-guided biopsy was performed. Histological examination showed organizing pneumonia-like reaction, thickening alveolar wall due to fibrosis, and accumulating histiocytes in the alveoli. Malignant findings were not found
Treatment & Mechanisms
Proposed Remission Mechanisms
The lung tumour gradually shrunk without a mixed pattern suspected to have haemorrhage or infarction
Clinical Treatment
Biopsy, dexamethasone, metyrapone, imipenem/cilastatin, caspofungin acetate