Adherence to glucocorticoid treatment guidelines improved, but risk for adrenal failure remains

Despite increased adherence to glucocorticoid stress dosing guidelines, patients with adrenal insufficiency are still at risk for acute adrenal failure, according to data published in the Journal of Pediatrics.

Patients with adrenal insufficiency not only require daily glucocorticoid therapy, but they must also receive higher doses during stress, researchers from Sainte-Justine Hospital in Montreal wrote. The Lawson Wilkins Pediatric Endocrine Society (LWPES) developed guidelines to address these needs, yet few studies have described the effect of the recommendations.

“When the LWPES published its guidelines on stress coverage in adrenal failure and I tried to find evidence to support what they recommended — and what they also have been doing in our center for more than 30 years — there were very little data in the literature. In particular, we could find very little documentation of what happens in the hospital with these patients and if what we do, or do not do, with [glucocorticoid] stress coverage makes a difference,” Cheri L. Deal, PhD, MD, president of the Canadian Society of Endocrinology and Metabolism, told Endocrine Today.

This lack of information, as well as the death of a patient with septo-optic dysplasia and panhypopituitarism from septicemia at their center, prompted Deal and colleagues to investigate the degree to which these guidelines are followed and what role inappropriate care may play in acute adrenal failure.

Hospitalizations

The researchers conducted a retrospective study involving 102 patients with primary adrenal insufficiency and 34 patients with secondary adrenal insufficiency seen at their hospital from 1973 to 2007. None of the patients had a history of central nervous system tumors or other malignancy. Analysis was divided into three periods: before 1990; 1990 to 1997; and 1998 to 2007. Each period represented progress made in hospital and patient care.

Of 247 total hospitalizations, 201 occurred in patients with primary adrenal insufficiency and 46 in those with secondary adrenal insufficiency. Sixty-four percent of hospitalizations were classified as urgent, with no sex-related differences appearing for patients with either primary or secondary adrenal insufficiency, according to the researchers. Approximately one-third of all admissions were elective.

Trends in treatment

Before hospitalization, only 31.2% of patients received increased glucocorticoid doses at home, despite the guidelines and physician recommendations to the contrary. In addition, the glucocorticoids were injected intramuscularly in only five cases resulting in urgent hospitalization. However, the number of parents using glucocorticoid stress doses before urgent hospitalization increased from 17.5% during 1973 to 1989 to 47% during 1998 to 2007.

“It is important to indicate that we did not collect data about home management or management in the ED when no hospitalization followed, so that this is, we hope, a worse-case scenario of stress dose usage by caregivers,” Deal said.

Results also revealed “a striking improvement” in administration of glucocorticoid stress doses in the ED after 1989, the researchers said, with the proportion of stress doses received by patients escalating from 40% before 1990 to 67.6% during 1990 to 1997 and 65.2% during 1998 to 2007. The researchers also noted, however, that evidence of acute adrenal failure was present in 36.9% of the 157 urgent hospitalizations in the ED.

“In some cases, decompensation probably occurred too quickly for the parents to react, as another smaller study by Japanese investigators recently pointed out,” Deal said.

In 23.5% of all hospitalizations, health care professionals did not follow stress protocol for glucocorticoid treatment. In 27 cases, the endocrine service was not consulted. Morbidity, as defined by clinical evidence of acute adrenal failure after delayed or missed doses, was minimal, with only two cases of acute adrenal failure that were managed clinically without sequelae.

“Our study documents an improvement in patient care with the introduction of more formal protocols for stress management in patients with adrenal failure, although affected individuals still show morbidity, which is occasionally fatal.

“Some of this morbidity may be eliminated with a more conscientious application of glucocorticoid stress doses, but there is still a subset of patients at higher risk because of their underlying pathology, such as in the case of septo-optic dysplasia, or because of immunologic and/or genetic factors influencing glucocorticoid bioavailability, metabolism and action,” Deal said. – by Melissa Foster

For more information:

• Leblicq C. J Pediatr. 2011;158:492-498.

Disclosure: Dr. Deal and colleagues report no relevant financial disclosures.

Janet H. Silverstein

The article by Leblicq et al highlights the fact that despite clear, well-publicized protocols for stress-management of patients with adrenal insufficiency, a significant percentage of patients still remain under-treated when hospitalized for illness or surgery. This literature review was prompted by the death of a young child with central adrenal insufficiency. In this case, there was insufficient glucocorticoid administration due to a lack of venous access when the child was febrile.

This case, however, is not an isolated one, and underscores the need to repeatedly educate all medical personnel, particularly those who are the first responders such as the ED staff and hospital physicians about the need for immediate treatment with high-dose glucocorticoid administration for all patients ill enough to require ED or hospital care. Endocrinologists are generally careful to stress the importance of providing parents of children with adrenal insufficiency handouts and written instructions on how to manage vomiting or other stressors and to train them in the use of parenteral glucocorticoids if the child is unable to take medications orally. However, too often, treatment in the hospital is delayed because medications aren’t ordered promptly, because IV access is not available or because there is a long delay in transfer from the ED to the wards. It is, therefore, extremely important that no child with adrenal insufficiency be admitted to the hospital from the ED without first receiving stress doses of glucocorticoids.

– Janet H. Silverstein, MD

Endocrine Today Editorial Board Member

Disclosure: Dr. Silverstein reports no disclosures.