Endocrine Complications of Cystic Fibrosis

Abstract

Endocrine comorbidities have become increasingly important medical considerations as improving cystic fibrosis (CF) care increases life expectancy. Although the underlying pathophysiology of CF-related diabetes remains elusive, the use of novel technologies and therapeutics seeks to improve both CF-related outcomes and quality of life. Improvements in the overall health of those with CF have tempered concerns about pubertal delay and short stature; however, other comorbidities such as hypogonadism and bone disease are increasingly recognized. Following the introduction of highly effective modulator therapies there are many lessons to be learned about their long-term impact on endocrine comorbidities.

Keywords: Body composition; Bone accrual; Cystic fibrosis bone disease; Cystic fibrosis-related diabetes; Diabetes management; Diabetes technologies; Dual X-ray absorptiometry; Growth.

Fig. 1.

Pathogenesis of CFRD arises largely from insulin secretion defects.

Fig. 2.

Plasma glucose (A) and insulin secretory rates (B) in response to the mixed-meal tolerance test (MMTT) in subjects with pancreatic insufficient CF (PI-CF). Individuals were categorized based on a preceding oral glucose tolerance test (NGT, normal glucose tolerance; EGI, early glucose intolerance (plasma glucose at 1 hour > 155 mg/dL and plasma glucose at 2 hours < 140 mg/dL; IGT, impaired glucose tolerance; CFRD, CF-related diabetes). Significant decline in beta-cell secretory capacity is evident in PI-EGI. Reprinted under STM Permissions Guidelines from “Beta-cell secretory defects are present in pancreatic insufficient cystic fibrosis with 1-h oral glucose tolerance test glucose >/ = 155 mg/dL”. (From Nyirjesy SC, Sheikh S, Hadjiliadis D, De Leon DD, Peleckis AJ, Eiel JN, Kubrak C, Stefanovski D, Rubenstein RC, Rickels MR, Kelly A. β-Cell secretory defects are present in pancreatic insufficient cystic fibrosis with 1-hour oral glucose tolerance test glucose ≥155 mg/dL. Pediatr Diabetes. 2018 Nov;19(7):1173–1182.)

Fig. 3.

Example of continuous glucose monitoring (CGM) usage. (From Marks BE, Wolfsdorf JI. Monitoring of Pediatric Type 1 Diabetes. Front Endocrinol (Lausanne). 2020 Mar 17;11:128.)

Fig. 4.

Baby Observational and Nutrional Study (BONUS) Cohort and Historic Infant Cohort z Scores for Growth During the First Year of Life. (A) Weight for age, ( B) Length for age. (From Leung DH, Heltshe SL, Borowitz D, Gelfond D, Kloster M, Heubi JE, Stalvey M, Ramsey BW; Baby Observational and Nutrition Study (BONUS) Investigators of the Cystic Fibrosis Foundation Therapeutics Development Network. Effects of Diagnosis by Newborn Screening for Cystic Fibrosis on Weight and Length in the First Year of Life. JAMA Pediatr. 2017 Jun 1;171(6):546–554.)