Cushing’ disease in three patients with chronic kidney disease

Castillo Iratxe Martínez; Mariana Aziz; Di Palma María Isabel; Marta Ciaccio; Laura López; Alicia Chaparro; Ramos Javier González; Silvia Gil

Introduction: Cushing's disease (CD) in the context of chronic kidney disease (CKD) is very rare. CKD causes physiological hypercortisolism making the diagnosis of CD extremely difficult.

Aim: To report 3 female patients with CKD and CD and to outline the principles that may guide the diagnosis of CD in this context.

Case report: P1. A 12.3-year-old patient with CKD secondary to steroid-resistant nephrotic syndrome on hemodialysis (HD) and a medical history of aseptic meningitis, secondary hydrocephalus, and epilepsy. She was referred due to the incidental finding of pituitary macroadenoma diagnosed as prolactinoma (prolactin 162 ng/ml) at another center and treated with cabergoline. P2. A patient with CKD secondary to bilateral renal hypodysplasia in conservative treatment. At age 16.4 years she had significant weight gain, purple-red stretch marks, galactorrhea, and menstrual irregularities. P3. A 15.3-year-old patient with CKD secondary to steroid-resistant nephrotic syndrome in conservative treatment was referred for weight gain, secondary amenorrhea and hypertension. In all patients, diagnosis of CD was confirmed by clinical and biochemical findings. P1 and P3 underwent transsphenoidal surgery and in P2 transcranial surgery resection was performed. Pathological examination revealed a corticotroph adenoma in P1 and P2, in P3 inmunohistochemistry demonstrated ACTH and prolactin positivity, with ACTH predominance. Postoperatively, P1 evolved with transient hypernatremia treated with free water corrections; P2 presented with transient diabetes insipidus. All patients achieved remission. P1 and P2 developed pituitary deficiencies.

Clinical data and complementary exams are listed in the table.
Patient	P1	P2	P3
Weight (SDS)	-2	1.2	2.1
Height (SDS)	-1.2	-2.7	-1.9
Tanner stage	III	IV	IV
Cushing phenotype	absent	mild	mild
Blood pressure	hypertension	normal	hypertension
ACTH (pg/ml)	27.2	22.4	30.7
Serum cortisol (μg/dl)	10.7	17	14.4
Post Nugent test	15.9	3.5	13
Post LDDST		2.8	10.4
Midnight salivary cortisol (μg/dl)	0.44	0.18	0.35
Prolactin (ng/ml)	4.9 *	58.1	84
Creatinine (mg/dl)	HD	3.34	1.96
Pituitary MRI	macroadenoma compressing optic chiasm	hemorrhagic macroadenoma compressing optic chiasm	microadenoma
Ophthalmological assessment	compromise of optic fibers of right eye	scotomas in peripapillary region, superior bitemporal quadranthopsia
*Under cabergoline

Conclusion: The loss of cortisol circadian rhythm is the most accurate indicator of CD in CKD. Midnight salivary cortisol is the diagnostic test of choice. UFC is not useful in CKD. Biochemical findings can be discrepant after tumor hemorrhage. Renal dysfunction produces hyperprolactinemia posing the differential diagnosis with prolactinoma. Good clinical judgement is fundamental to guide the diagnosis.

IMPE Abstracts

EP65