Cushing's Disease Associated with both Pituitary Microadenoma and Corticotroph Hyperplasia

 

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Abstract

Herein, we present the case of a 63-year old female patient with initial symptoms of myopathy, hypokaliemia, glucosuria and psychotic symptoms. Laboratory analysis demonstrated elevated plasma levels of ACTH and cortisol. Additionally, urine cortisol excretion was increased approximately 60-fold. MRI imaging revealed a possible pituitary microadenoma. To confirm the diagnosis a bilateral inferior petrosal sinus sampling was performed presenting higher ACTH levels on the right side. However, after surgery cortisol levels did not return to normal range. Histological examination of the tumor revealed a microadenoma. Six days postoperatively, the patient developed several pneumonic infiltrations and fever therefore antibiotic and antifungal therapy was started immediately. In addition aspergillus antigen was elevated. During this septic condition, cortisol levels further increased. The patient died despite optimal intensive care under septical conditions 8 days after surgery. Microbiological analysis identified Aspergillus fumigatus in broncho-alveolar lavage and several organ systems including the heart and brain. Neuropathological autopsy revealed nodular proliferations of corticotropic cells in the pituitary gland that are assumed to be morphological entities between diffuse hyperplasias and adenomas, termed as tumorlets. In single reports, multiple pituitary lesions in patients with Cushing's disease have been demonstrated, but to our knowledge none of these cases presented the combination of an ACTH-producing microadenoma and corticotroph cell hyperplasia in the same patient. Therefore, even after resection of a pituitary microadenoma one should be aware of the possibility of continuously elevated ACTH level being due to multifocal nodular corticotroph hyperplasia which is invisible by neuroradiological examination.

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Correspondence

Dr. M. Mittelbronn

Institute of Neuropathology

University Hospital of Zürich

Schmelzbergstraße 12

8091 Zürich

Switzerland

Tel: +41/44/255 28 49

Fax: +41/44/255 44 02

Email: michel.mittelbronn@usz.ch