Adrenal Gland Disorder Research Activities and Advances

Through its intramural and extramural organizational units, NICHD supports and conducts a broad range of research on adrenal gland disorders.

Much of this research is conducted through the Section on Genetics and Endocrinology, which is part of the NICHD Division of Intramural Research (DIR). Researchers in this Section study the genetic and molecular mechanisms leading to disorders that affect the adrenal cortex, with an emphasis on those disorders that are developmental, hereditary, and associated with adrenal hypoplasia or hyperplasia, multiple tumors, and abnormalities in other endocrine glands. Work supported by this Section includes:

• Studying congenital adrenal hypoplasia caused by triple A syndrome and several endocrine deficiencies; familial hyperaldosteronism; adrenocortical and thyroid cancer; pituitary tumors; multiple endocrine neoplasia syndromes affecting the pituitary, thyroid, and adrenal glands; and the Carney complex (CNC), a multisystem disease that is a combination of endocrine overactivity, spotty skin pigmentation, myxomas, and other tumors
• Identifying the chromosome on which the genes for CNC are located, and searching for other possible locations
• Investigating the relationship between these locations and CNC
• Using cell lines established from CNC patients to investigate the consequences of mutations of PRKAR1A, the gene responsible for most cases of CNC
• Using transgenic mouse models to study the role of the PRKAR1A gene
• Identifying novel genetic abnormalities in certain endocrine glands
• Identifying a new syndrome known as "paraganglioma and gastrointestinal stromal tumor syndrome" due to SDH gene mutations

Within the Section on Medical Neuroendocrinology, scientists conduct patient-oriented research into the causes, functions, genetics, diagnosis, location, and treatment of pheochromocytoma and paraganglioma. One recent study assessed whether the size of adrenal tumors plays a role in the development of metastatic disease (disease that moves or spreads from one organ or tissue to another) regardless of the genetic background of these tumors.¹ In another study, researchers discovered an alteration in the HIF2A gene that was associated with growth of pheochromocytomas in two patients. The finding could lead to information on how to hinder the growth of tumors and treat cancers associated with excessive production of red blood cells.²

Other units within the DIR focus on adrenal gland disorders and disorders of female reproduction. Researchers are evaluating the usefulness of basal cortisol and corticotrophin-releasing hormone testing for the prediction of recurrent Cushing's disease.

Within the DIR Developmental Endocrinology, Metabolism, Genetics & Endocrine Oncology, investigators aim to characterize the genotypes of parents of children with congenital adrenal hyperplasia (CAH) and to examine the structure and function of the adrenal glands in these patients. Research also has been conducted to assess complications linked to the disorder, such as hypoglycemia and insulin resistance, and to test new versions of medications intended for use as treatments.

The Pediatric Growth and Nutrition Branch (PGNB), within the Division of Extramural Research, supports research about genetic and molecular mechanisms of adrenal gland hyperplasia, prenatal screening for the disorder, and prenatal treatment of classic CAH with dexamethasone. The PGNB also has supported studies to characterize novel mutations in genes for enzymes involved in CAH.

In addition, the Developmental Biology and Congenital Anomalies Branch advances research with animal models to understand typical pituitary development, as well as growth of pituitary tumors, and investigates the genetic basis of tumor development.

• The biennial Conference on the Adrenal Cortex is for basic and clinical scientists and clinicians with specific interests in the adrenal cortex. Authorities in the field present current findings on topics related to the adrenal cortex. Co-sponsors include the NICHD Developmental Endocrine Oncology and Genetics Group in the DIR.
• The Pediatric Endocrinology Training Program 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's 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 RSDP, 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's syndrome.