medwireNews: High doses of fludrocortisone in the absence of salt supplements can provoke hypertension in infants with congenital adrenal hyperplasia (CAH), research shows.

Speaking to medwireNews, Caroline Brain, a consultant paediatric endocrinologist from Great Ormond Street Hospital and University College London Hospital, UK, who was not involved in the study, said the findings are “an important warning to others.”

The children in the study were not receiving salt supplements, despite the risk of salt wasting being most marked during infancy.

“It is a classic mistake to keep pushing up the fludrocortisone dose to maintain normal sodium and potassium when the infants are total body sodium depleted and the fludrocortisone can therefore not work efficiently,” she said. “Hence the dose becomes artificially high and the blood pressure is pushed up.”

In the study, Walter Bonfig and Hans Peter Schwarz, from Ludwig Maximilian Universität, Munich, Germany, identified systolic hypertension in 30.3% of 33 children at the age of 3 months and 39.4% at age 6 months. The rate peaked at the age of 18 months, at 57.6%, and fell thereafter, to 9.1% at the end of the 4-year study period.

The team attributes the fall to increasing mineralocorticoid sensitivity as the children age. However, Brain noted that the children would have moved onto weaning diets at 1–2 years of age, which would raise their salt levels, increasing the effectiveness of fludrocortisone treatment.

In three children, hypertension persisted at the age of 4 years despite fludrocortisone dose reduction and no apparent vascular, cardiac or renal cause, with one child requiring calcium channel-blocker treatment.

As reported in Clinical Endocrinology, the researchers found that the average dose of fludrocortisone in patients who developed hypertension was about double that in those who did not, and plasma renin activity was significantly lower. They therefore suggest that overtreatment with fludrocortisone resulted in excessive suppression of plasmin renin activity, leading to hypertension.

The average daily fludrocortisone dose used in all patients was 0.11 mg in children aged 3–6 months, 0.09 mg in those aged 12–18 months and 0.05 to 0.06 mg in older children.

However, Brain described these doses as “very high”, saying that her starting daily dose for a newborn would be about 25 µg (0.25 mg). “For a 3-month-old to be on 100 [µg] is a huge amount.”

The researchers’ caution that high doses of fludrocortisone result in hypertension is “perfectly valid”, said Brain. But she stressed that “it’s missing the point of why they’re having to give such high doses of fludrocortisone; I think that’s because they’ve not been salt-replacing them adequately.”

By Eleanor McDermid, Senior medwireNews Reporter

Clin Endocrinol 2014; Advance online publication

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