State of the Art: Endocrinology in Cystic Fibrosis
Brennan AL, Blackman SM (eds.) State of the Art: Endocrinology in Cystic Fibrosis. J Cyst Fibros 2019; 18, Suppl
Purpose and Background
People with cystic fibrosis are at risk for a number of endocrine disorders that impact the quality and duration of life. Many endocrine complications of CF occur more frequently at older ages or in the context of late-stage complications, such as organ transplantation. Thus, these endocrine complications of CF are increasingly relevant as people with CF are living longer lives.
The Emerging Leaders in CF Endocrinology (EnVision) program is a three-year training program to increase clinical and research expertise in CF endocrinology. Adult and pediatric endocrinologists from the first EnVision cohort, along with EnVision mentors and other content experts worldwide, coauthored the Journal of Cystic Fibrosis Supplement, State of the Art: Endocrinology in Cystic Fibrosis. The supplement is comprised of 15 topic-driven articles reviewing the pathogenesis, diagnosis, and management of CF endocrine disorders. This executive summary highlights key content from the articles.
Articles in State of the Art: Endocrinology in Cystic Fibrosis cover many important endocrine topics relevant to CF, including:
- CF-related diabetes (CFRD).
- CF associated bone disease.
- Puberty, growth and nutrition, including obesity.
- Male and female reproductive health.
- Adrenal insufficiency.
- Endocrine complications after lung transplant.
Disease pathophysiology, epidemiology, diagnosis, and management are addressed. Diagnostic algorithms and clinical decision trees are provided when appropriate, and, where available, CF Foundation clinical practice guidelines are referenced. Key contents of each article are highlighted below.
|CF-related diabetes and Hypoglycemia|
|CFRD: Pathophysiology, screening and diagnosis||
Pathophysiology of CFRD
Screening and diagnosis of CFRD and alternative screening methods
|CFRD Medical management||
Discusses unique aspects of CFRD management including:
Use of non-insulin therapies in CFRD
|CFRD: nutrition and growth considerations||
Growth and nutrition issues in CFRD including:
|Hypoglycemia in cystic fibrosis: Prevalence, impact, and treatment||
Hypoglycemia classification and neuroendocrine protective mechanisms
Prevalence and impact of hypoglycemia in patients with and without CFRD
Pathophysiology and management of hypoglycemia in CF
|Continuous glucose monitoring in cystic fibrosis — a practical guide||
Overview of commercially available continuous glucose monitors (CGM)
CGM in screening and evaluation of CFRD
CGM in management of CFRD, including step-by-step instructions for CGM interpretation
|CF-Associated Bone Disease|
|Cystic fibrosis bone disease: pathophysiology, assessment, and prognostic implications||
Pathophysiology of cystic fibrosis bone disease
Definition of osteoporosis by age group and menopausal status
Evaluation of CFBD using dual energy X-ray absorptiometry (DEXA) and alternative imaging modalities
|Cystic fibrosis bone disease treatment: Current knowledge and future directions||
Screening for CF bone disease and defining at risk populations
Pharmacologic and non-pharmacologic management of CF bone disease
|Puberty and Reproduction|
|Puberty in cystic fibrosis||
Normal physiology and timing of puberty
Evaluation and management of pubertal disorders
Sequelae of delayed puberty in CF: short stature, low bone mineral density, and psychosocial distress
|Female reproductive health in cystic fibrosis||
Pathophysiology, evaluation, and management of female reproductive health in CF including:
|Male reproductive health in cystic fibrosis||
Pathophysiology, evaluation, and management of infertility in CF, including the use of assistive reproductive technology
Presentation, evaluation, and management of male hypogonadism in CF including:
|Growth and Nutrition|
|Energy balance and obesity in individuals with cystic fibrosis||
Prevalence of overweight and obesity in CF
Pathophysiology of increased energy expenditure in CF and the impact of CFTR modulation on energy metabolism
Complications and management of obesity in CF patients
|Growth failure and treatment in cystic fibrosis||
Pathophysiology of disordered growth in cystic fibrosis
Management of short stature in CF with recombinant human growth hormone therapy and other therapies
|Vitamin D deficiency and its treatment in cystic fibrosis||
Pathophysiology of vitamin D metabolism and evaluation of vitamin D deficiency in CF
Clinical impact of vitamin D deficiency on skeletal health, inflammation, pulmonary disease, and diabetes
Management of vitamin D deficiency
|Adrenal function in cystic fibrosis||Pathophysiology, clinical presentation, diagnosis, and management of iatrogenic adrenal insufficiency in CF
Causes of iatrogenic adrenal insufficiency including oral glucocorticoids, inhaled glucocorticoids, itraconazole, and megestrol acetate
|Endocrine complication after solid organ transplant in cystic fibrosis||
Prevalence, presentation, mechanisms, and management of endocrine complications of solid organ transplant including:
- Identification and treatment of CF-related endocrine disease are needed to optimize the quality and duration of life for people living with CF.
- Endocrine disorder pathophysiology may involve direct CFTR effects, indirect effects of chronic inflammation and illness, or modifier genes. In most CF endocrine disorders, the relative contribution of these factors is poorly defined.
- CF endocrine disorders commonly coexist with, and are exacerbated by, declining lung function. Optimizing lung function is the initial treatment for many CF endocrine disorders.
- Few randomized controlled trials are available for treatment of CF-related endocrine disorders. Many treatment recommendations are based upon observational studies in CF or trials in the general population and reflect expert opinion. Insulin therapy for CFRD and bisphosphonates for CFBD are important exceptions.
- The degree to which CFTR modulators can prevent or reverse CF endocrine disorders is the largest unanswered question at the present time. In general, it is felt that direct CFTR effects may be reversible; whereas tissue damage due to altered development or chronic inflammation is less likely to be reversible. Evidence from ivacaftor-treated patients suggests a lower incidence of de-novo CFRD with CFTR modulator therapy.
- The impact of CFTR modulators on reproductive health in women with CF is not fully understood, though there is evidence of increased pregnancy rates. Studies on people taking highly effective CFTR modulators are needed.
- Although alternative screening methods for CFRD have garnered much interest, the optimal cutoffs for diagnosis remain uncertain. Whether insulin therapy benefits patients with milder dysglycemia that does not meet CFRD criteria also remains unknown. Whether increasing rates of obesity may increase the rate of type 2 diabetes in people with CF (possibly impacting treatment options) is unknown.
- The impact of improved longevity and higher rates of obesity in the CF population remains uncertain. Endocrine disorders associated with obesity may become more common in CF. It is uncertain whether CF patients will incur the same cardiometabolic risks of obesity as the general population.
- Sergeev V, Chou FY, Lam GY, Hamilton CM, Wilcox PG, Quon BS. The extrapulmonary effects of cystic fibrosis transmembrane conductance regulator modulators in cystic fibrosis. Ann Am Thorac Soc. 2020;17(2):147-154. doi:10.1513/AnnalsATS.201909-671CME
- Volkova N, Moy K, Evans J, et al. Disease progression in patients with cystic fibrosis treated with ivacaftor: Data from national US and UK registries. J Cyst Fibros. 2020;19(1):68-79. doi:10.1016/j.jcf.2019.05.015
- Aksit MA, Pace RG, Vecchio-Pagán B, et al. Genetic modifiers of cystic fibrosis-related diabetes have extensive overlap with type 2 diabetes and related traits. J Clin Endocrinol Metab. 2020;105(5):1401-1415. doi:10.1210/clinem/dgz102
- Kilberg MJ, Sheikh S, Stefanovski D, et al. Dysregulated insulin in pancreatic insufficient cystic fibrosis with post-prandial hypoglycemia. J Cyst Fibros. 2020;19(2):310-315. doi:10.1016/j.jcf.2019.07.006
- Sherwood JS, Jafri RZ, Balliro CA, et al. Automated glycemic control with the bionic pancreas in cystic fibrosis-related diabetes: A pilot study. J Cyst Fibros. 2020;19(1):159-161. doi:10.1016/j.jcf.2019.08.002
- Ubago-Guisado E, Cavero-Redondo I, Alvarez-Bueno C, et. al. Bone Health in Children and Youth with Cystic Fibrosis: A Systematic Review and Meta-Analysis of Matched Cohort Studies. J Pediatr. 2019; 215:178-186.e16. doi:10.1016/j.jpeds.2019.07.073
- Harindhanavudhi T, Wang Q, Dunitz J, Moran A, Moheet A. Prevalence and factors associated with overweight and obesity in adults with cystic fibrosis: A single-center analysis. J Cyst Fibros. 2020;19(1):139-145. doi:10.1016/j.jcf.2019.10.004
This executive summary was prepared by:
- Katherine Kutney, MD, (Rainbow Babies and Children's Hospital) and Scott M. Blackman, MD, PhD (Johns Hopkins University School of Medicine)