In male patients with congenital adrenal hyperplasia, testicular tumors, or so-called adrenal rest tumors, have been described, but their presence in well controlled patients is thought to be rare. In this study, the prevalence of testicular tumors in 17 adolescent and adult male patients with congenital adrenal hyperplasia (age, 16-40 yr) was investigated. In 16 of 17 patients, one or more testicular tumors, ranging in maximal length from 0.2-4.0 cm, were found on ultrasonography. In 6 patients, the testicular tumors were palpable. Undertreatment, defined as the presence of a salivary androstenedione level (mean of 6 saliva samples collected over 24 h with intervals of 4 h) above the upper reference morning level, was found in 5 of 17 patients at the time of investigation. The other 12 patients were treated adequately or even over treated at the time of investigation. Nevertheless, 11 of these 12 patients showed testicular tumors on ultrasonography. Neither the presence of undertreatment at the time of investigation nor characteristics of the therapeutic regimen (daily dose of hydrocortisone equivalents per body surface, the use of glucocorticoid medication either two or three times a day, or the time of taking the highest glucocorticoid dose either in the morning or the evening) could predict tumor size (maximal diameter of largest tumor). In patients who were heterozygous or homozygous for the deletion or conversion of the CYP21 gene, tumor size was significantly larger than in patients who did not have this genotype. Impairment of Leydig cell function as manifested by decreased plasma levels of T was found in 6 of 17 patients. Semen analysis in 11 patients revealed azoospermia in 3 patients and poor semen quality in 4 patients. We conclude that, when carefully sought for, testicular adrenal rest tumors are frequently present in adolescent and adult males with congenital adrenal hyperplasia and are often accompanied by impaired spermatogenesis and Leydig cell failure.

We measured bone mineral density (BMD) using dual-energy x-ray absorptiometry in 20 patients with Cushing's syndrome (CS) (14 preand 2 postmenopausal women, 4 men) before and in 18 of them also at regular intervals after surgical cure (median duration of follow-up, 36 months). In addition, in the premenopausal women with CS, fast ing blood samples and 2-h fasting urine samples for measurement of biochemical parameters of bone and collagen metabolism were col lected before and in 9 of them also at regular intervals during the first 2 yr after surgery. Marked osteopenia was present in'most patients with active CS (Z-scores: lumbar spine -1.45 ± 1,44 and femoral neck ~ 1.50 ± 1 .02; mean ± sd). No consistent change in BMD was observed at 3 and 6 months after surgery. Thereafter BMD increased consid erably in almost all patients. For the 15 patients with a follow-up of at least 1 yr, Z-scores at the last evaluation were -0.65 ± 1.27 for the lumbar spine and -0.98 ± 1.02 for the femoral neck (both/5 < 0.002 compared with pretreatment values). In the premenopausal patients, the increase in BMD both in the lumbar spine and in the femoral neck at 24 months was inversely correlated with age (r = -0.733, P < 0.03, and r ~ -0.667, P < 0.05, respectively). Serum levels of osteocalcin, bone alkaline phosphatase, carboxyterminal propeptide of type I pro

Congenital adrenal hyperplasia (CAH) is generally regarded as a paediatric endocrine disease, but nowadays nearly all patients reach adulthood as a result of improved diagnosis and treatment. It is now increasingly recognised that treatment goals shift during life: one of the major treatment goals in childhood and puberty, i.e. normal growth and development, is no longer relevant after childhood, whereas other aspects, such as fertility and side effects of longterm glucocorticoid treatment, become more important in adulthood. This paper focuses on fertility in male and female adult patients with CAH. In males with CAH the fertility rate is reduced compared with the normal population, the most frequent cause being testicular adrenal rest tumours. Development and growth of these tumours is assumed to be ACTH dependent and undertreatment may play an important role. If intensifying glucocorticoid treatment does not lead to tumour decrease, surgical intervention may be considered, but the effect on fertility is not yet known. In females with CAH the degree of fertility depends on the phenotype of the CAH. Most fertility problems are seen in the classic salt-wasting type. Age of menarche and regularity of the menstrual cycle depends on the degree of adrenal suppression. Not only adrenal androgens have to be normalised but also the levels of adrenal progestins (progesterone and

We investigated the effects of i.v. and intracerebroventricular (i.c.v) administration of increasing doses of recombinant human IL-1 beta, TNF alpha and IL-6 on plasma corticosterone (B) levels in rats. Rats were equipped with a jugular cannula for repeated blood sampling anda subgroup of rats also received an i.c.v implanted cannula. I.v. administration of IL-1 beta, TNF alpha or IL-6 and i.c.v administration of IL-1 beta and IL-6 induced a significant dose-dependent increase in plasma B levels, whereas i.c.v injection of TNF alpha in doses up to 1000 ng/rat was not effective. I.v. pretreatment of rats with anti-CRH antiserum had no significant overall effect on the plasma B response to i.v. administered IL-1 beta (500 and 3000 ng/rat), whereas the plasma B response to i.v. TNF alpha or IL-6 administration (3000 ng/rat) were significantly reduced. I.v. pretreatment of the animals with recombinant human IL-1 receptor antagonist (IL-1ra) significantly blocked the plasma B response to i.v. treatment with IL-1 beta, whereas the TNF alpha- and IL-6-induced increases in plasma B levels were not affected. Our data show that 1) i.v. administration of IL-beta, TNF alpha or IL-6 and i.c.v administration of IL-1 beta or IL-6 dose-dependently stimulate the HPA axis; 2) when given i.v. or i.c.v, IL-1 beta is more powerful than TNF alpha and IL-6 in activating the HPA axis; 3) endogenous CRH is involved in the activation of the HPA axis by acute i.v. administration of TNF alpha and IL-6. It is most likely that in case of i.v. treatment with IL-1 beta a CRH-independent mechanism is involved. This study provides no arguments for the involvement of endogenous IL-1 in TNF alpha- or IL-6-induced activation of the HPA axis.

In order to study male gonadal function in Noonan syndrome, clinical and laboratory data, including inhibin B, were gathered in nine pubertal males diagnosed with Noonan syndrome. Bilateral testicular maldescent was observed in four, and unilateral cryptorchidism occurred in two. Puberty was delayed in three patients. Luteinising hormone (LH) levels were normal in all patients in our series, while follicle stimulating hormone (FSH) levels were raised in seven. Inhibin B was low in six males and just above the lower limit of normal in two. Importantly, all three men with normal testicular descent displayed signs of Sertoli cell dysfunction, indicating, in contrast to earlier reports, that bilateral cryptorchidism does not seem to be the main contributing factor to impairment of testicular function in Noonan syndrome. These findings suggest different mechanisms of disturbance in male gonadal function, which is frequently associated with Sertoli dysfunction.