Endocrine Society updates 21-hydroxylase deficiency CAH guidelines

By Eleanor McDermid
J Clin Endocrinol Metab 2018; doi:10.1210/jc.2018-01865
01 November 2018

medwireNews: The Endocrine Society has released updated guidelines for the management of congenital adrenal hyperplasia (CAH) due to steroid 21-hydroxylase deficiency.

The guidelines, which are published in The Journal of Clinical Endocrinology & Metabolism, contain several changes from the preceding version, published in 2010.

Two of these changes are based on meta-analyses specially commissioned to support the guideline-making process, both led by M Hassan Murad (Mayo Clinic, Rochester, Minnesota, USA), and looking at cardiovascular and metabolic outcomes and genital reconstructive surgery in female patients.

For the latter, Murad and team reviewed the results of 29 observational studies involving 1178 patients who were aged an average of 2.7 years at the time of surgery.

They found the majority of patients had a female gender identity and were satisfied with their surgical outcomes, but sexual function was often impaired, with intercourse uncomfortable for around half of the patients and many reporting poor clitoral sensitivity. The researchers also noted that there was very little information on the patients’ quality of life.

Based on this information, the guidelines contain three ungraded good practice recommendations:

  • To inform parents of surgical options, including observation until the child is older.
  • To initiate early discussions about surgical repair of the urogenital sinus in severely virilised girls.
  • That “all surgical decisions remain the prerogative of families” with support from experienced surgeons.

And there is one graded recommendation: the preferred surgical approach is vaginoplasty using urogenital mobilisation, with neurovascular-sparing clitoroplasty for severe clitoromegaly when applicable.

“Our goals have been consistently directed at preserving functional anatomy and fertility”, write guideline author Phyllis Speiser (Cohen Children’s Medical Center of New York, USA) and colleagues.

The second meta-analysis includes information from 416 CAH patients in 20 observational studies. This revealed significantly higher blood pressure and insulin resistance in these patients relative to healthy controls, and greater carotid intima-media thickness, which is a surrogate marker of atherosclerotic risk.

However, almost all research focused on these surrogate markers rather than on hard cardiac outcomes, the quality of the evidence was low, and measures of glucose metabolism and blood lipids did not significantly vary between patients and controls.

The guideline authors therefore “recommend that individuals with CAH should be monitored according to conventional guidelines for monitoring CAH-unaffected children, adolescents, and adults.”

Other changes to the latest guidelines encompass diagnosis, treatment during pregnancy, stress dosing, transitional care and mental health.

For diagnosis, the guidelines now state that gestational age should be accounted for when interpreting 17-hydroxyprogesterone assay results. These tests should be first tier for newborn CAH screening, with liquid chromatography–tandem mass spectrometry the preferred second-tier test.

Regarding treatment, the guideline writers have responded to data raising concerns about the effects of prenatal exposure to glucocorticoids, and now advise against the use of any that can cross the placenta, such as dexamethasone, during pregnancy. Also, the recommendations for stress dosing have been adjusted to advocate a “more moderate” approach during minor illness or minor surgery.

Finally, the authors stress the need for smooth transition of CAH patients from paediatric to adult care, and that patients and their parents can benefit from mental health evaluation and monitoring.

“Clinicians should be aware that individuals with congenital adrenal hyperplasia may be at risk for developing mental health problems and should have a low threshold for referral to psychological or psychiatric treatment”, says the team.

They stress that “mental health support is a valuable complement to endocrinological and surgical management”.

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