Long-term outcome in patients after treatment for Cushing’s disease in childhood

Abstract

IntroductionCushing’s disease (CD) is a rare cause of hypercortisolemia presenting a major diagnostic and therapeutic challenge. Data on pituitary function in long-term follow-up after CD treatment in childhood is limited.AimLong-term assessment of patients of the Children’s Memorial Health Institute (CMHI) after CD treatment in childhood.Materials and methodsRetrospective analysis of 29 CD patients, mean age at the time of diagnosis 13.46 yrs. The long-term follow-up (FU) was done by: 1) obtaining the data from a patient’s questionnaire (75% of adult patients); 2) using the data from the last clinic visit for patients who did not respond to the questionnaire and for current CMHI patients. The average long-term FU from transsphenoidal pituitary surgery (TSS) was 10.23 yrs.ResultsAt the latest FU: 18 patients (62%) had long-term disease remission after TSS1, 2 patients (6.9%) after TSS2, 1 patient (3.4%) after the post-TSS radiotherapy (XRT) cycle and 3 patients (10.3%) after bilateral adrenalectomy (BA). One patient (3.4%) died after TSS2 due to postoperative complications, 1 patient (3.4%) had persistent disease at latest FU, in 1 patient (3.4%) the long-term FU was not possible to perform. CD recurrence occurred in 4 out of 28 patients (14%) at an average time 3.6 yrs. from definitive treatment. One patient (3.4%) after BA was operated because of Nelson's syndrome. Two patients (6.9%) were suspected of relapse at latest assessment. At the time of the last evaluation, 17 patients (63%) were on levothyroxine therapy since definitive treatment, 16 patients (59%) were on hydrocortisone treatment, 10 patients (37%) were taking sex hormones replacement, 4 patients (15%)—antidiuretic hormone.ConclusionsRelatively large number of patients after CD treatment in childhood have hormonal pituitary deficits as well as mood and cognitive disorders. CD recurrence can occur even after a long time post effective treatment.

Predictive factors for recurrence of Cushing’s disease after surgical treatment in childhood.

“…Three of these four recurred patients (75%) had hypocortisolism after TSS, and one (25%) patient had hypocortisolism after radiotherapy, which was used because biochemical remission after the second TSS was not achieved. Detailed characteristics of patients with recurrence were presented in the previous article [14]. Key characteristics of the variables used in the logistic regression for patients with and without CD recurrence are presented in Table 1.…”

“…Twenty-nine consecutive paediatric CD patients who had undergone endocrine evaluation and/or pituitary surgery at the Children's Memorial Health Institute (CMHI) between 1993 and 2018 were initially included. The data of all patients had been previously reported [14]. The Institutional Bioethical Commission (48/KBE/2018) approved this study.…”

“…The investigation and diagnosis of CD was performed as previously described [14]. Patients with negative preoperative magnetic resonance imaging or an incomplete endocrine evaluation underwent bilateral inferior petrosal sinus sampling to determine the source of ACTH secretion [15].…”

“…The second time point (longer FU) was determined on the basis of the time when the adult patient (previous CMHI patient) completed the author's questionnaire. Answers to the questionnaire were obtained as previously described [14]. The patients were asked to indicate whether they had experienced a recurrence, whether they had a subsequent surgery, medical therapy, or pituitary radiotherapy, or were currently free of Cushing's syndrome.…”

“…increased midnight cortisol, the lack of suppression of cortisol during LDDST, and increased 24 h urinary free cortisol values, which recurred after successful treatment that resulted in clinical remission. Long-term remission was defined as previously described [14].…”