Endocrine Abstracts

Background: Subclinical Cushing disease is defined by mild hypercortisolism that results from a corticotroph pituitary adenoma, without any typical sign of the disease. The patients often have coexisting metabolic diseases such as diabetes mellitus, and hypertension. Conversely, silent corticotroph adenomas demonstrate normal cortisol secretion, but positive immunochemistry for ACTH, most usually without ACTH hypersecretion, although they and can progress to clinical Cushing disease. A subcategory of the corticotroph adenomas are the Crooke’s cell adenomas characterised by cytoplasmic accumulation of cytokeratin filaments in >60% of the cells. These adenomas are usually invasive and recur frequently. We present a case of pituitary Crook adenoma with subclinical Cushing disease.

Case presentation: A 73-year-old male patient was diagnosed with a pituitary adenoma in the MRI performed for recent-onset headaches. He was on treatment for hypertension, atrial fibrillation and had a right-eye strabismus since birth. He did not report any symptom related to pituitary hormones deficiency or hypersecretion and the physical examination was also normal. Optical field test revealed a right-eye strabismus without eyelid ptosis and normal pupil reflex. MRI revealed ‘a large pituitary adenoma with small optic chiasm pressure, small encapsulation of the right cavernous sinus, and extension to the borders of the left cavernous sinus.’ 1st–2nd blood test results (normal range): morning serum cortisol: 23.9–23.1 μg/dl (5–25), ACTH: 128.7–105.7 pg/ml (7.3–63.3), night serum cortisol: 9.5 μg/dl (<7.5), urine 24-h cortisol: 195–163 nM, cortisol after overnight 1 mg-dexamethasone test: 4.4–4.6 μg/dl, FT3: 3.9–3.4 pmol/l (3.1–6.8), FT4: 11.7–11.4 pmol/l (12.0–22.0), TSH: 2.3–1.6 μU/ml (0.7–4.2), FSH: 0.9IU/L (1.0–9.7), LH: 0.5IU/L (1.0–8.0), Testosterone: 0.8 ng/ml (1.4–4.0), PRL: 27.1 ng/ml (3.3–11.9), IGF-1: 15ng/ml (40–400), urine osmolality: 942 mOsm/KgH2O (>300). The patient was diagnosed with subclinical Cushing disease because of the lack of signs of clinical Cushing syndrome and the non-suppressed cortisol level after the overnight 1mg-dexamethasone test, and with coexisting deficiency of the other pituitary hormones. The slight elevation of the PRL was probably due to stalk pressure. The patient received L-thyroxin and underwent a transsphenoidal resection of the pituitary adenoma. The pathology report described a corticotroph ACTH-secreting pituitary adenoma, compatible with a Crooke adenoma (Ki-67 2-3%).

Conclusion: Patients with a pituitary adenoma and elevated ACTH, without the clinical signs of Cushing syndrome, should be evaluated for the pituitary-adrenal axis function. A Crooke’s adenoma can be the underlying aetiology of subclinical Cushing disease.