ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Endocrine Abstracts (2017) 50 EP071 | DOI: 10.1530/endoabs.50.EP071

Cushing's disease caused by pituitary macroadenoma exhibiting Crooke's hyaline changes and immunoreactivity for adrenocorticotrophic hormone and growth hormone

Peter Novodvorsky1,2, Paul G Ince3, Saurabh Sinha4 & Miguel Debono1


1Department of Endocrinology, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, UK; 2Department of Human Oncology and Metabolism, University of Sheffield, Sheffield, UK; 3Department of Neuroscience, Sheffield Institute for Translational Neuroscience, University of Sheffield, Sheffield, UK; 4Department of Neurosurgery, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, UK.


Introduction: Cushing’s disease is usually caused by functional corticotroph microadenomas of the pituitary. Crooke’s cell adenomas are rare, representing approximately 2% of corticotroph adenomas and mostly present as aggressive macroadenomas. Pituitary adenomas showing immunoreactivity for both ACTH and GH are also very uncommon. We present two cases of Cushing’s disease caused by macroadenomas with Crooke’s cell changes and immunoreactivity for ACTH and GH.

Case #1: A 51-year old woman presented with a self-limiting episode of right eye visual loss. MRI revealed a 21×19 mm pituitary macroadenoma. Arterial hypertension, long-standing irregular periods and 1-year history of tiredness were noted. Investigations confirmed ACTH-dependent hypercortisolism. CRH-stimulation test showed a flat ACTH response (max. rise from baseline below 20%) and cortisol rise from baseline of approximately 50%. The patient underwent endoscopic trans-sphenoidal surgery (ETSS) in June 2016 with a post-surgery cortisol 60 nmol/L. Immunohistochemistry showed moderate diffuse immunoreactivity for ACTH and GH. Extensive areas of Crooke’s hyaline changes were detected in the adenoma tissue. The Ki67 labelling fraction was <3% with no evidence of P53 mutation.

Case #2: A 50-year old man presented with tiredness and erectile dysfunction and was found to have secondary hypogonadism and hypothyroidism. Arterial hypertension, obesity and obstructive sleep apnoea were noted. MRI detected a 27×19×23 mm macroadenoma. Investigations confirmed ACTH-dependent hypercortisolism. He underwent ETSS in April 2017 with good outcome (post-surgery cortisol 31 nmol/L). Histology revealed extensive Crooke’s cell changes with strong immunoreactivity for ACTH and widespread GH staining. The Ki67 labelling fraction was low with no evidence of P53 mutation.

Neither patient had clinical or biochemical features of acromegaly.

Conclusion: To our knowledge cases of Cushing’s disease caused by Crooke’s cell adenomas with immunoreactivity for ACTH and GH have never been reported. These tumours should be considered as high-risk for recurrence warranting strict surveillance.

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