Patients with classic congenital adrenal hyperplasia due to 21-hydroxylase deficiency can achieve their target height: the Leipzig experience.

BACKGROUND: Despite treatment, the mean final height (FH) of patients with classic congenital adrenal hyperplasia (CAH) is below the mean height of a normal population. AIMS: To show that CAH patients can achieve their target height (TH), 39 adult subjects, whose therapy had started in infancy, were studied in a retrospective analysis. All height SDS were corrected so that they related to TH SDS. PATIENTS: Group 1: patients born before 1975 (n = 13) had received prednisolone, at doses equivalent to hydrocortisone 39.4 +/- 15.6 mg/m2 BSA daily, together with DOCA in the first 2 years of life. Group 2: patients born from 1975 to 1986 (n = 26) received at this age lower hydrocortisone doses (16.4 +/- 6.9 mg/m2 BSA daily, divided 8 hourly; p < 0.001) combined with fludrocortisone, had outpatient visits every 3 months and bone age (BA) estimation every 6 months. RESULTS: Patients of group 1 (FH SDS -1.2 +/- 1.0) had a poor outcome, whereas patients of group 2 (FH SDS 0.1 +/- 0.9; p = 0.01) achieved their TH. CONCLUSION: Combined corticoid administration adjusted quarterly to keep height, BMI, blood pressure and BA within normal limits resulted in FH close to TH in patients with classic CAH.

Blood pressure in patients with congenital adrenal hyperplasia due to 21-hydroxylase deficiency.

BACKGROUND: In patients with congenital adrenal hyperplasia (CAH) recording of blood pressure (BP) must be included in monitoring treatment to detect hypertension. AIM: To investigate the BP patterns in patients with CAH. METHODS: Twenty-three children and adolescents (age 6-17 years) and 11 adult patients (age 18-26 years) were studied (21 females, 13 males; 28 salt-wasting patients). In the whole group BP in the outpatient clinic was compared with BP under hospitalisation and in 11 of the children and adolescents also with 24-hour ambulatory blood pressure monitoring (ABPM). RESULTS: BP in the ward in children and adolescents but not in adults was significantly higher than BP in the outpatient clinic, where BP was in the upper normal range. There was also a significant difference between BP in the outpatient clinic and the lower ABPM in the 11 patients tested. Atrial natriuretic peptide (ANP) in blood serum showed normal values. CONCLUSIONS: BP measured in outpatients in a relaxed and calm atmosphere meets the requirements for monitoring of treatment. Measurement of BP on the ward leads to falsely high results. ABPM is not necessary. Estimation of ANP provides no additional information.

Pregnancies in patients with congenital adrenal hyperplasia with complete or almost complete impairment of 21-hydroxylase activity.

OBJECTIVE: To show that, with appropriate therapy, women with classic congenital adrenal hyperplasia (CAH) can become pregnant. DESIGN: Observational clinical study. SETTING: University hospital. PATIENT(S): Adult young women with CAH: three with the salt-wasting form and four patients with simple virilizing CAH due to severe homozygous or compound heterozygous mutations of the CYP21B gene (deletions, I172N in exon 4 and nt656A/C-->G in intron 2) who wished to become pregnant. INTERVENTION(S): After confirmation in the first patient of the beneficial effect of additional treatment with fludrocortisone in lowering 17alpha-hydroxyprogesterone (17-OHP) levels, five other patients were treated with hydrocortisone as three daily doses at 8-hour intervals and fludrocortisone 0.1-0.2 mg daily divided into two to three doses. One patient received glucocorticoid alone. MAIN OUTCOME MEASURE(S): Treatment was controlled on the basis of morning salivary 17-OHP estimates and plasma renin concentrations. RESULT(S): Nine pregnancies occurred in six women. The course of the pregnancies (except one spontaneous abortion) was normal without any other modification of therapy. Only the women treated with hydrocortisone alone did not become pregnant. CONCLUSION(S): When treated with a combination of glucocorticoids and mineralocorticoids, sexually active patients with the classic phenotype of CAH can become pregnant.

Autoimmune polyglandular syndrome (APS) type 1 and candida onychomycosis.

A 21-year-old female presented at age 2 years with a chronic mucocutaneous candidiasis and at age 3 alopecia totalis. Later, chronic hypoparathyroidism and autoimmune adrenal insufficiency appeared. In addition, malabsorption syndrome and signs of pernicious anaemia occurred. The onychomycosis totally improved under systemic treatment with fluconazole (Diflucan), endocrine and organ failure with replacement therapy. The autoimmune polyglandular syndrome (APS 1) is a rare autosomal recessive inherited disease. Chronic mucocutaneous candidiasis (CMC) generally presents very early in life and is the most frequent of the three main diseases of APS type 1 (chronic hypoparathyroidism, autoimmune Addison's disease). It can be considered as a precocious marker of APS type 1. Consequently, all patients affected by isolated CMC, especially children, should be evaluated and carefully followed up by immunological, biochemical, and clinical tests to recognize signs and symptoms of imminent or ongoing endocrine glandular failure.

Re-assessment of growth hormone secretion in young adult patients with childhood-onset growth hormone deficiency.

OBJECTIVE: Patients with childhood-onset GH deficiency (coGHD) need retesting in late adolescence or young adulthood to verify whether they need to continue GH treatment. For this purpose the Growth Hormone Research Society (GRS) recommends the insulin tolerance test (ITT), or as an alternative the arginine + growth hormone releasing hormone test (ARG + GHRH test) as a diagnostic tool in adolescents and adults. However, there are no standardized cut-off levels based on normal GH secretion for determining GHD vs. GH sufficiency in young adults for the ITT, the ARG + GHRH test or the pyridostigmine + GHRH (PD + GHRH) test, a further new GH stimulation test. PATIENTS AND MEASUREMENTS: We studied 43 patients (28 with organic coGHD, 15 with idiopathic coGHD; 30 males, 13 females; aged 20.4 years, range 16.2-25.4; body mass index 23.5, range 16.3-35.8) using the ARG [0.5 g/kg intravenously (i.v.)] + GHRH (1 micro g/kg i.v.) test, the PD (120 mg orally) + GHRH (1 micro g/kg i.v.) test and the ITT (0.1 IU/kg i.v.) and compared these data with the results of 40 healthy age- and weight-matched volunteers. RESULTS: The GH response in patients was significantly lower than in healthy controls: ARG + GHRH test, 0.8 micro g/l (interquartile range 0.3-2.6) vs. 51.8 micro g/l (32.6-71.2) in controls (P < 0.0001); PD + GHRH test, 0.9 micro g/l (0.3-1.9) vs. 40.4 micro g/l (27.1-54.4) in controls (P < 0.0001); ITT, 0.1 micro g/l (0.0-0.8) vs. 20.3 micro g/l (14.7-31.7) in controls (P < 0.0001). In the ARG + GHRH test we found a diagnostic sensitivity of 100% and a specificity of 97.5% for a cut-off range from 15.1 to 20.3 micro g/l, in the PD + GHRH test a sensitivity of 100% and a specificity of 97% (cut-off range 9.1-13.1 micro g/l) and in the ITT a sensitivity and specificity of 100% each within a cut-off range from 2.7 to 8.8 micro g/l. CONCLUSION: There were no marked differences in sensitivity and specificity in young adults among ARG + GHRH test, PD + GHRH test and the ITT in assessing GH secretion. Because of the lack of side-effects, the ARG + GHRH test is the recommended method for re-evaluation of coGHD in young adults when pituitary GHD is suspected. Furthermore, in adult patient groups where organic pituitary coGHD is common, the ITT may be completely replaced by the ARG + GHRH test. Because of the predominance of hypothalamic GHD in childhood, the ITT is commonly performed for the re-evaluation of patients with childhood-onset GHD because of its mechanism of GH stimulation. The present results confirm the high discriminatory capability of the ITT in young adults.