Category: Pituitary Disorders/Neuroendocrinology
We present a case of clinically silent corticotroph macroadenoma presenting with abrupt and acute hypercortisolism during radiotherapy.
A 25-year-old man was diagnosed with a pituitary macroadenoma when he underwent workup for recurrent headaches, vision loss,lack of libido and 10lb weight gain.The adenoma measured 4 x 5 cm with compression of optic chiasm and complete encasement of the left carotid artery.Other than weight gain, he had no signs of Cushing’s disease.Workup showed low testosterone with low LH, normal free T4, normal prolactin, and IGF-1 levels. AM cortisol level was 11.4 mcg/dL, ACTH level was not available at the time of initial consultation. Patient underwent a subtotal trans-sphenoidal resection. Cosyntropin stimulation test prior to surgery showed baseline cortisol 20.2 mcg/dL, 34.3 mcg/dL at 30 mins and 37.0 mcg/dL at 60 mins. Pathology showed tumor cells to be weakly immunoreactive for ACTH. Post-operatively cortisol ranged from 1.6 to 7.5 mcg/dL, despite ACTH remaining between 57 – 92 pg/ml. Patient was on hydrocortisone during some of these lab draws. Patient subsequently underwent a left craniotomy for residual tumor.Fractionated radiotherapy(RT) was administered at a dose of 50.4 Gy in 42 fractions since the tumor was invasive and showed rapid interval growth. Prior to RT, ACTH level was 99 pg/ml with cortisol level 9.5 mcg/dL.Urine free cortisol was normal at 41.2 mcg/24hrs. After receiving 30 doses (~36 Gy), he developed facial plethora, proximal muscle weakness, hypertension and hypokalemia with potassium 2.8 meq/L. ACTH level was 468 pg/ml and cortisol 110.2 mcg/dL, and improved by the end of RT, to ACTH 108 pg/ml and cortisol 16.5 mcg/dL.Two weeks later, cortisol dropped to 0.8 mcg/dL with ACTH 31 pg/mL, requiring hydrocortisone replacement. There was substantial tumor shrinkage observed on MRI 3 months after RT, which has been sustained, and patient remains adrenally insufficient 3 years later.
We suspect that this patient had no clinical features of Cushing’s disease despite elevated ACTH due to the presence of a biologically less active ACTH molecule, which although less active was able to induce hypercortisolism at very high levels of secretion.
The hypercortisolism induced during radiotherapy is a rare, but important clinical lesson. Only 2 other similar cases have been reported. Postulated mechanisms are acute tumor cell death or ACTH leakage in response to RT induced cell damage.
Significant hypercortisolism can be a rare complication of radiotherapy in large corticotroph adenomas suggesting the need for close monitoring, and portends a favorable prognosis for longterm tumor control.
University of Florida
I am currently in my second year of fellowship in the department of Endocrinology, Diabetes and Metabolism at University of Florida. I completed internal medicine training at University of Illinois at Peoria.