SummaryContext As a result of the introduction of treatment with glucocorticoids and mineralocorticoids, now 60 years ago, congenital adrenal hyperplasia has become a lifelong chronic disease. Whether long-term treatment of the disease leads to long-term side effects remains unknown. In this respect, especially cardiovascular risk seems to be important. Evidence synthesis We reviewed the reported prevalence of conventional cardiovascular risk factors, i.e. obesity, insulin resistance, high blood pressure and dyslipidaemia in patients with congenital adrenal hyperplasia. Overall, the studies suggest a tendency towards an increased body mass index and fat mass, the presence of insulin resistance and hypertension, although data are relatively scarce and obtained in heterogeneous populations. Conclusions Our findings suggest that adult CAH patients tend to have a cluster of metabolic risk factors, which are consistent with the metabolic syndrome. This notion may have consequences for the care for this group of patients.

In the human situation, treatment of insulin-resistant subjects with pioglitazone improves insulin sensitivity, whereas at the same time, sc adipocyte cell surface increases.

ObjectiveTreatment with glucocorticoids and mineralocorticoids has changed congenital adrenal hyperplasia (CAH) from a fatal to a chronic lifelong disease. Long-term treatment, in particular the chronic (over-)treatment with glucocorticoids, may have an adverse effect on the cardiovascular risk profile in adult CAH patients. The objective of this study was to evaluate the cardiovascular risk profile of adult CAH patients.DesignCase-control study.Patients and MeasurementsIn this case-control study the cardiovascular risk profile of 27 adult CAH patients and 27 controls, matched for age, sex and body mass index was evaluated by measuring ambulatory 24-hour blood pressure, insulin sensitivity (HOMA-IR), lipid profiles, albuminuria and circulating cardiovascular risk markers (PAI-1, tPA, uPA, tPA/PAI-1 complex, hsCRP, adiponectin, IL-6, IL-18 and leptin).Results24-Hour systolic (126.3 mmHg±15.5 vs 124.8 mmHg±15.1 in controls, P = 0.019) and diastolic (76.4 mmHg±12.7 vs 73.5 mmHg±12.4 in controls, P<0.001) blood pressure was significantly elevated in CAH patients compared to the control population. CAH patients had higher HDL cholesterol levels (P<0.01), lower hsCRP levels (P = 0.03) and there was a trend toward elevated adiponectin levels compared to controls. Other cardiovascular risk factors were similar in both groups.ConclusionAdult CAH patients have higher ambulatory blood pressure compared to healthy matched controls. Other cardiovascular risk markers did not differ, while HDL-cholesterol, hsCRP and adiponectin levels tended to be more favorable.

Context: Patients with congenital adrenal hyperplasia (CAH) are chronically treated with supraphysiological doses of glucocorticoids, which are known to induce insulin resistance. Thiazolidinediones might reverse this effect and improve insulin sensitivity. Objectives: To assess insulin sensitivity in CAH patients and the effect of pioglitazone treatment on insulin sensitivity in CAH patients. Secondary objectives were the effects of treatment with pioglitazone on blood pressure, body fat distribution, lipid, and steroid profiles. Design: Randomized placebo controlled crossover trial. Participants: Twelve CAH patients and 12 body mass and age-matched control subjects. Intervention: Sixteen-week treatment with pioglitazone (45 mg/day) or placebo. Main outcome measure: Insulin sensitivity measured by euglycemic clamp and oral glucose tolerance test. Further measures were 24-h blood pressure profiles, body fat distribution measured by magnetic resonance imaging, dual energy x-ray absorptiometry (DEXA) and bioimpedance procedures, liver fat by magnetic resonance spectroscopy, lipid, and steroid profiles. Results: CAH patients were insulin resistant compared with healthy controls. Treatment with pioglitazone significantly improved insulin sensitivity in CAH patients (glucose infusion rate (GIR) from 28.5G11.6 to 38.9G11.0 mmol/kg per min, PZ0.000, GIR in controls 46.2G23.4 mmol/kg per min, P!0.05 versus CAH). Treatment with pioglitazone decreased blood pressure (systolic: 124.0G13.6 vs 127.0G14.9 mmHg, P!0.001, diastolic: 72.8G11.5 vs 77.4G12.6 mmHg, P!0.001). No changes in body fat distribution, lipid, and steroid profiles were observed. Conclusions: CAH patients are insulin resistant compared with matched control subjects. Treatment with pioglitazone improves insulin sensitivity and decreases blood pressure in CAH patients.

Objective: To study the acute effect of epinephrine on hemodynamics of noninnervated normal and retinoic-acid-treated embryos. Design: Prospective interventional study design. Methods: A total of 190 stage 15 (50–55 h of incubation) chick embryos were randomly treated with 1 µg all-trans retinoic acid and reincubated. At stage 20 (day 3) and stage 24 (day 4), dorsal aortic flow velocities were measured with a 20-MHz pulsed Doppler velocity meter, in normal and retinoic-acid-treated embryos. Flow velocity waveforms were assessed both before and after the administration of epinephrine (5 or 10 µg). Results: Epinephrine caused a significant increase (p < 0.05) in heart rate, peak and mean velocities, peak acceleration, peak and mean blood flows, stroke volume and dorsal aortic area of both stage 20 and stage 24 normal and retinoic-acid-treated chick embryos. However, before epinephrine administration, stage 24 retinoic-acid-treated embryos displayed a significantly lesser increase in all outcome variables with the exception of dorsal aortic area. This was even observed after epinephrine administration. The effect of retinoic acid on cardiac output could not be compensated by epinephrine application. Conclusion: Epinephrine affects hemodynamics in both normal embryos and retinoic-acid-treated embryos prior to sympathetic innervation. A significant difference in hemodynamics exists between stage 24 normal and retinoic-acid-treated embryos. The underlying mechanism for the observed hemodynamic changes will need to be investigated.