In Cushing syndrome, the earlier treatment begins, the less harmful the disease is to the body. However, Cushing syndrome is complex and difficult to diagnose. It has a wide range of symptoms that mimic those of other conditions, and the severity of the syndrome can fluctuate. Through its numerous research projects, NICHD aims to improve understanding of Cushing syndrome and, ultimately, to bring faster diagnoses and more effective treatment.
Some NICHD research is aimed at devising new tests and tools to help health care providers screen and diagnose individuals with Cushing syndrome. Much of this research into tools and tests is supported through NICHD's Section on Reproductive Endocrinology (SRE), in the Division of Intramural Research (DIR). Work by the section includes:
- Establishing the corticotropin-releasing hormone test and inferior petrosal sinus sampling as major diagnostic tools for identifying pituitary adenomas causing Cushing syndrome.
- Improving understanding of how pregnancy affects a woman's circulating amount of both cortisol and ACTH and fine-tuning criteria used for interpreting diagnostic tests in pregnancy.
- Investigating widespread screening for Cushing syndrome in obese patients. Research demonstrated a high rate of false positives, which was used to advise against such screening. Researchers are now checking whether metabolic syndrome screening would be helpful.
- Improving understanding of cycling—disappearing and reappearing symptoms—which can disrupt attempts to diagnose Cushing syndrome. Researchers have found that cycling is prevalent in individuals with mild Cushing syndrome and recommend testing more than once, even after a negative result.
- Finding hidden adrenal tumors that are not identified by computed tomography (CT) scans and magnetic resonance imaging (MRI) tools in 30% to 50% of the cases of Cushing syndrome. Researchers are studying whether refinements to current tools or the use of other types of imaging studies can improve detection of these ectopic tumors.
Some people appear to be more likely to develop certain types of tumors. The NICHD's Section on Endocrinology and Genetics (SEGEN) is trying to identify genes that might be involved—and how that involvement unfolds—in several disorders of the adrenal and pituitary glands, as well as for multiple endocrine neoplasia syndromes that involve those glands.
Although identifying who has, or is more at risk for having, Cushing syndrome is key to successful treatment, researchers are also concerned with monitoring lingering effects from Cushing syndrome—even after cure. Researchers in many different parts of NICHD are examining the long-term impact of Cushing syndrome. Key research projects include the following:
- Cognition might be permanently affected by Cushing syndrome, so SEGEN researchers investigated memory impairment and depression in children. They found that children had declines in intelligence measures and school performance even after successful treatment of their Cushing syndrome.
- Tumors causing Cushing syndrome sometimes require radiation and chemotherapy. Researchers in DIR's Unit on Reproductive Endocrinology and Infertility are collaborating in investigations of how to preserve ovarian function in women and girls undergoing cancer treatment.
- Although cured of Cushing syndrome, some individuals do not recover as quickly as others, whether physically or mentally. SRE collaborated on research that found that the quality of life improves in the first 5 years after treatment but may remain subnormal for up to 15 years, suggesting the need for long-term monitoring of former patients.
- Chronic Cushing syndrome undermines bone strength, but treatment stops the bone weakening. To assess how bones of children are affected, NICHD researchers in the Unit on Hormones of Cancer (UHC) studied children before and after treatment and found vertebral bone mineral density was undermined more than femoral density.
To achieve its goals for Cushing syndrome research, NICHD supports a number of research and clinical training programs for physicians. These programs are part of NIH-wide or other collaborative efforts in which NICHD participates. Examples are listed below.
- The Pediatric Endocrinology Inter-Institute Training Program fellowship is a 3-year program accredited by the Accreditation Council for Graduate Medical Education. It provides comprehensive training in clinical patient management and guidance in the development of research skills. The fellowship is at NICHD and based at the NIH Clinical Center, which maintains clinical research protocols investigating the treatment of adrenal and pituitary tumors, Cushing syndrome, obesity, and other conditions.
- The Reproductive Scientist Development Program (RSDP) is a multidisciplinary, multi-institutional research career development program for obstetrician-gynecologists studying cell and/or molecular biology and genetics and related fundamental sciences. The program, sponsored jointly by NICHD's Fertility and Infertility (FI) Branch and other entities, helps academic obstetrics and gynecology departments increase research and discovery in the reproductive sciences.
- The National Centers for Translational Research in Reproduction and Infertility (NCTRI) (Formerly the Specialized Cooperative Centers Program in Reproduction and Infertility Research [SCCPIR]) is a national network of research-based centers, supported by the FI Branch, that aims to promote interactions between basic and clinical scientists with the goal of improving reproductive health. Several centers focus on diseases/disorders of the female reproduction system that may affect women who have undergone treatment for tumors in Cushing syndrome.