Congenital adrenal hyperplasia: management during critical illness

BACKGROUND—Little is known of the optimal dose and administration schedule of hydrocortisone in critically ill patients with congenital adrenal hyperplasia (CAH) caused by 21-hydroxylase deficiency.
AIM—To determine plasma cortisol concentrations after intravenous administration of hydrocortisone in children with CAH and to relate these to plasma cortisol concentrations achieved by endogenous secretion in the stress of critical illness in previously healthy children.
METHODS—Plasma cortisol concentrations were measured in 20 patients with classical CAH (median age 11.2 years, range 6.1-16.4) following intravenous administration of hydrocortisone 15 mg/m²; and in 60 critically ill mechanically ventilated children (median age 2.5 years, range 0.25-16.3) on admission to the paediatric intensive care unit and for 24 hours thereafter.
RESULTS—In the CAH patients, plasma cortisol reached a mean peak of 1648.3 nmol/l (SD 511.9) within 10 minutes of the intravenous bolus, and fell rapidly thereafter; levels remained greater than 450 nmol/l for 2.5 hours only. In critically ill children, mean plasma cortisol on admission to the intensive care unit was 727nmol/l (SD 426.1). Cortisol concentrations remained raised during the first 24hours.
CONCLUSIONS—Critically ill patients with classical CAH may be best managed with a single intravenous hydrocortisone bolus followed by a constant rate infusion of hydrocortisone.

     

Congenital adrenal hyperplasia.

Congenital Adrenal Hyperplasia is reviewed under the basic concepts of pathophysiology, the modes of clinical presentation and treatment principles. With the recent advances in the understanding of the genetics, prenatal diagnosis and interventional prenatal treatment may offer hope to subsequent afflicted generations.     

Congenital adrenal hyperplasia: experience at Calcutta.

Eight patients (7 females, 1 male) with congenital adrenal hyperplasia (CAH), were seen over a 24-month period beginning from March 1988. Seven patients had 21 hydroxylase (21-OH) deficiency while one had 11 beta hydroxylase deficiency. Of the 7 patients with 21-OH deficiency, 3 were of the salt losing (SL-CAH), and 4 were of the non-salt losing (NSL-CAH) type. The patients with NSL-CAH were diagnosed by their elevated 17-hydroxyprogesterone (17-OHP) levels. The 3 cases with SL-CAH were diagnosed on the basis of ambiguous external genitalia, typical electrolyte picture, normal female internal genitalia, sex chromatin and response to steroids. In one patient post-ACTH 17 OHP was alter measured. All 3 patients with SL-CAH were assigned the male sex. Sex reassignment was advised for two children; one accepted the advice and the child is doing well; one family did not accept sex reassignment and the child died. One patient died due to non-availability of fludrocortisone. Six patients are under follow-up. All are doing well except one patient with NSL-CAH who started treatment late. We conclude that a high index of suspicion, early diagnosis and meticulous patient education are the key features of successful management of CAH in India.     

Congenital adrenal hyperplasia: Renin and steroid values during treatment

Plasma renin activity (PRA), aldosterone (Aldo), 17-hydroxyprogesterone (17-OHP) and testosterone (T), together with urine sodium, pregnanetriol, 17-oxosteroids and the 11-oxygenation index (11-OH) were estimated in 23 patients (age 5.7–18 yrs.) with congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency during glucocorticoid treatment.Elevated PRA levels (1400–17200 ng Al/l/hr) were found in 13 out of 15 patients with a history of salt loss. Three non-salt losers showed high PRA levels and in the remaining 5 the levels were in the upper normal range (540–900 ng Al/l/hr). Plasma Aldo levels were normal (25–620 pmol/l) in 18 patients and slightly elevated (690–2360 pmol/l) in 5. While these results indicate persistent impairment of sodium homeostasis in CAH patients, no significant correlations between log. PRA, log. Aldo and urinary sodium excretion were found.Mid-day 17-OHP levels ranged from 9 to 117 nmol/l and T from 0.3 to 18.0 nmol/l. Neither the 17-OHP nor the T results correlated well with the clinical assessment of therapeutic control. The results of the urinary steroid determinations showed better agreement with the clinical assessment of treatment and the 17-oxosteroid, pregnanetriol and 11-OH index results appeared to be better discriminants between good and poor control.Twelve of the patients with a history of early salt loss were reinvestigated after one month's treatment with oral 9-flurohydrocortisone (0.05 mg/day). PRA was reduced in 7 patients and 17-OHP fell in 10 patients. No consistent changes were found in Aldo, T, or urinary sodium and steroid excretion during this low-dose mineralocorticoid treatment.     

Congenital adrenal hyperplasia: an Indian experience

Aims: Data regarding the presentation and course of patients with congenital adrenal hyperplasia (CAH) is scarce in South Asia. We aimed to fill that gap by collating our experience with CAH and comparing it with findings from few other centres around the world for pertinent differences. Methods: We retrospectively analysed the records of 86 CAH patients seen at our tertiary care centre in Eastern‐India from 1996 to 2010. Results: Forty‐five patients (52.3%) had classic disease and 41 (47.7%) had non‐classic disease (NC CAH). In the classic CAH group, 18 (20.9%) had salt wasting CAH (SW CAH) while 27 (31.4%) had simple virilising disease (SV CAH). Ten (11.6%) had a 46,XY karyotype. Patients with SW CAH were diagnosed earlier in infancy at a median age of 0.5 year, than those with SV type, who were diagnosed at 9 years (P < 0.05). The NC CAH patients were diagnosed still later, at 20.4 years. In patients with SW CAH, boys were diagnosed at an earlier median age of 0.1 year than girls who were diagnosed at 6.4 years (P < 0.05). Sixteen girls (21% of the girls) underwent vaginoplasty of whom four required additional clitoroplasty. One girl needed bilateral laparoscopic adrenalectomy. One NC CAH patient had a successful assisted pregnancy. Hypothyroidism, found in seven (8.1%) was the commonest coexisting abnormality. Conclusion: The skewed male : female ratio suggested that a substantial proportion of males were being missed and consequently may die. Majority of the diagnosed patients (n= 55, 64%) have been lost to follow‐up. Remaining patients could be reasonably controlled with standard therapy.     

新生儿先天性肾上腺皮质增生症12例

目的探讨先天性肾上腺皮质增生症在新生儿期的诊断及治疗。方法分析新生儿先天性肾上腺皮质增生症12例的临床表现，结合血钠、钾、血17-羟孕酮(17-OHP)、睾酮(T)、雌二醇(E2)及肾素等检查进行诊断，并用激素替代治疗。结果诊断为21-羟化酶缺乏失盐型11例，单纯男性化1例。1例确诊后放弃治疗，余11例治疗好转出院；2例发生感染后出现失盐危象，第2次住院治疗；1例女性患儿病情稳定，2岁时行阴蒂短缩术。结论本病早期诊断及治疗可防止新生儿肾上腺危象、休克、后遗症发生及死亡。     

Congenital adrenal hyperplasia among peripubertal girls with hyperandrogenism.

Fifteen girls with severe hyperandrogenism were investigated by us during the last 6 years. Thirteen of these were cases of untreated congenital adrenal hyperplasia (CAH) and 2 were cases of tumoral (one sertoli leydig cell tumor of the ovary and one adrenal adenoma) hyperandrogenism. Here we present the clinical profile and laboratory data of those with congenital adrenal hyperplasia. All the girls had masculinization of genitalia (clitoromegaly alone 5, clitoromegaly with varying degree of posterior labial fusion 8). Eleven cases had hirsutism and 9 had short stature. Two patients underwent unilateral adrenelectomy with diagnosis of adrenal adenoma. Hormonal profile confirmed the diagnosis of CAH with 21 hydroxylase deficiency (elevated 17 OHP levels with exaggerated 17 OHP response to ACTH) in 12 cases and 3 beta hydroxy steroid dehydrogenase deficiency (elevated DHEAS and 17 pregnenelone levels and exaggerated DHEAS and 17 pregnenelone response to ACTH) in one case.