Delayed Diagnosis of Cushing's Disease in a Pediatric Patient due to Apparent Remission from Spontaneous Apoplexy

Abstract

We report here a pediatric patient whose Cushing's Disease was diagnosed late because of her cyclical presentation, presumably due to subclinical pituitary apoplexy. Starting at age 8, she presented with observable signs of Cushing's but was not clinically assessed for Cushing's Syndrome until the age of 15. Initial tests at age 15 were consistent with Cushing's Disease, however, the patient presented with spontaneous remission of hypercortisolemia just a few short months later. Her cushingoid features never subsided, and at age 17, her MRI showed a partially empty sella; this finding of an empty sella contributed evidence to our suspicion of asymptomatic apoplexy, especially since the patient never reported an episode of acute headache. Pituitary apoplexy in corticotroph adenomas is very uncommon, but even more rare in microadenomas, making this case very unusual. Lost to follow-up, she was not reevaluated for Cushing's Disease until age 25, and her laboratory tests were consistent with an adrenocorticotrophic-dependent pituitary tumor; Pituitary magnetic resonance imaging revealed a 9 mm X 6 mm X 8 mm mass projecting on the superior aspect of pituitary and abutting the wall of the right cavernous sinus. The patient had a transsphenoidal surgery to remove the microadenoma and is planned to undergo radiation therapy. To the best of our knowledge, this is the first report of subclinical apoplexy of a microadenoma in a pediatric patient with Cushing's Disease. It brings to light the importance of long term follow up for pediatric patients presenting with clinical symptoms of Cushing's Syndrome.

Keywords: Cushing’s Syndrome; Hypercortisolemia; adolescent; cyclical Cushing’s; pituitary tumor.

Figure 1

2008 MRI T1-weighted sequences, coronal (A) and sagittal (B) views showing relatively small pituitary with the superior half of the sella filled by spinal fluid. These findings are consistent with a partially empty sella. 2015 MRI T1-weighted sequences, coronal (C) and sagittal (D) views in patient with 9 mm X 6 mm X 8 mm lesion arising from the superior aspect of the pituitary gland on the right side, with extension into the right cavernous sinus.

Figure 2

(A) Macroscopic evaluation of tumor resected June 2015 reveals a soft red-brown tissue fragment measuring 0.8 cm×0.5 cm x0.4 cm. (B) Strong and diffuse ACTH staining is visualized (20X). (C) Hematoxylin and eosin (H&E) staining (20X) shows sheets of large cells with abundant cytoplasm. (D) Reticulin stain (20X) shows lack of normal reticulin framework.

Figure 3

Urine free cortisol (UFC) levels expressed as ratio of patient’s value to the upper limit of normal of the assay at various ages of the patient. The patient initially showed hypercortisolemia, later showed cortisol insufficiency, followed by a resurgence of cortisol levels. The letters correspond to the lab values reported in Table 1: (A) February 2005. (B) June 2005. (C) June 2008. (D) April 2015.