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To evaluate the outcome of medical and surgical treatment of 10 young women with congenital adrenal hyperplasia (CAH), final height, weight, body proportions and body hair growth as well as aspect and functionality of the external genitalia were assessed. The final height was below-2 SD of the target height in 55%, though the body proportions were in the normal range. Only 3 patients were menstruating regularly. Scores for 'hormonal' body hair growth were in a higher range. Gynaecological examination revealed that in 5 out of 9 patients, the genitalia were functionally acceptable. This pilot study stresses that from birth into adulthood of female patients with CAH there is a need for a combined therapeutic approach by a paediatric endocrinologist, a surgeon and a psychologist. This will improve the physical and psychosocial well-being of these patients.

Testicular adrenal-like tissue (TALT) have been observed in patients with congenital adrenal hyperplasia, and is usually associated with 21-hydroxylase deficiency; in 3 cases with 11 beta-hydroxylase deficiency. We report a case of male pseudohermaphroditism with 17 alpha-hydroxylase deficiency (17OHD) who also had TALT. To our knowledge, this is the first report about the association of 17OHD and TALT. Also, the patient had high levels of serum aldosterone--an unusual finding in patients with 17OHD. A possible pathogenic mechanism is discussed.

Two neonates, one female and one male, with congenital adrenal hyperplasia due to 21-hydroxylase deficiency are described. The inheritance of this disease is autosomal recessive. It is of interest that these two babies were non-identical twins. 21-hydroxylase deficiency is briefly discussed and some relevant aspects of the hormonal control of the development of morphological or phenotypic sex are presented. Some of the difficulties encountered following the diagnosis of this condition in Papua New Guinea are mentioned.

The articles includes eight cases of congenital atresia of the vagina seen and studied at the Pediatric Surgery Department. All cases were congenital five of them corresponded to the Mayer-Rokitansky-Kuster-Hauser Syndrome an the remaining three to congenital adrenal hyperplasia. No other malformations were associated to any of the cases. The karyotype, hormones and secondary sexual characteristics were normal in those cases of Mayer-Rokitansky-Kuster-Hauser Syndrome. In the other three cases of congenital adrenal hyperplasia the karyotype was found to be 46XX, the 17-ketosteroids and pregnanediol were high and the patients were found to have hirsutism and were virilized. The ultrasonography, CAT and magnetic resonance scans showed excellent anatomical information on the congenital vaginal atresia and the intrapelvic organs. No other invasive study was needed to confirm its existence. Six of the patients were operated using the McIndoe and Bannister technique while on the other two the Tobin and Day technique was used. Post-surgical complications included vaginal stenosis in two cases within the first three months. The article includes an analysis of the complications and both the anatomical and functional results obtained.

To determine the presence of structural abnormalities of the adrenal in late-onset adrenal hyperplasia, four consecutive patients were studied by MRI before beginning glucocorticoid replacement therapy. Three women were diagnosed as 21-hydroxylase deficient late-onset adrenal hyperplasia by a 17-OHP level greater than 1,000 ng/dL 30 minutes after acute adrenal stimulation, and one patient was diagnosed as 11-hydroxylase deficient late-onset adrenal hyperplasia when her 11-deoxycortisol level was threefold the upper 95th percentile of normal. Two patients with 21-hydroxylase deficient late-onset adrenal hyperplasia had normal adrenal glands on MRI. Another 21-hydroxylase deficient late-onset adrenal hyperplasia patient was noted to have a 2.5 x 3.3-cm left adrenal nodule, which had been documented some 4 years earlier on CT scan and had not changed in size during that interval. This patient was 40 years of age when the diagnosis of late-onset adrenal hyperplasia was established. The patient with 11-hydroxylase deficient late-onset adrenal hyperplasia demonstrated a diffuse enlargement of the left adrenal gland consistent with hyperplasia, with no focal lesions. In conclusion, although patients with late-onset adrenal hyperplasia may often demonstrate nodular or diffuse adrenocortical hyperplasia on MRI, not all patients with endocrinologically evident disease demonstrate such abnormalities, consistent with a lesser degree of ACTH stimulation compared with women with classical congenital adrenal hyperplasia.

Cases of sexual immaturity and male pseudohermaphroditism due to disorders such as androgen resistance, 5 alpha-reductase deficiency, cholesterol desmolase deficiency, 3 beta-hydroxysteroid dehydrogenase deficiency, and testicular and ovary dysgenesis can easily be distinguished from 17 alpha-OHD. None of these disturbances result in hypertension. In the only other form of juvenile hypertension due to congenital adrenal hyperplasia, 11 beta-OHD, androgen excess leads to female pseudohermaphroditism and precocious puberty in the male patient. Patients with dexamethasone-suppressible hyperaldosteronism present with no sexual abnormalities. A diagnosis of 17 alpha-OHD can be readily assumed in the female patient with primary amenorrhea, hypertension, and hypokalemia. The absence of aldosterone, a measurement that is readily available, establishes this diagnosis even without the measurement of DOC.

We have studied a male patient who presented with secondary infertility. His eldest daughter suffers from late onset congenital adrenal hyperplasia. Based on his hormonal profile, adrenal and gonadal stimulation tests, semen analyses and testicular biopsy he was diagnosed as suffering from the same disease as his daughter. Steroid treatment yielded improvement in all the parameters mentioned above. Four months later his wife became pregnant and he fathered a child. Suppression of gonadotropin secretion due to overproduction of adrenal androgens would appear to be the reason for the failure of testicular maturation and spermatogenesis in this patient. We conclude: 1) glucocorticoid treatment is indicated in infertile males suffering from nonclassical 21-hydroxylase deficiency; 2) Late onset congenital adrenal hyperplasia should be suspected in any male infertility of unknown origin.

We have investigated gonadal development and growth in 4 individuals (3 with 46,XY and 1 with 46,XX karyotype) with P450scc deficiency. One patient died at 2 months of age from adrenal insufficiency, while the remaining 3 individuals were healthy and developed normally (age at follow-up: 18, 10 and 8 years). In the surviving individuals, the diagnosis was established during the first 2-4 months of life by extensive endocrine studies of blood and urine. In the remaining patient, the diagnosis was made on the basis of karyotype (46,XY), anatomy of internal and external genitalia and adrenal pathology. Gonadectomy was performed in the 2 surviving 46,XY individuals at the age of 7 years, and histological examination showed normal testicular morphology but very few germ cells. Postmortem examination of the testes of the 2-month-old subject showed normal testicular histology, and quantitative analysis revealed a normal number of germ cells. Ultrasound of the 46,XX individual showed normal internal female genitalia including ovaries with follicles. The 3 surviving patients grew along the 75th (46,XY), the 90th (46,XY) and the 50th percentile (46,XX), respectively. The oldest girl experienced normal breast and pubic hair development after oral estrogen replacement and topical testosterone administration. The glucocorticoid and mineralocorticoid replacement was adjusted in accordance with repeated measurements of serum sodium and serum potassium, plasma renin concentration and blood pressure. No attempts were made to normalize serum ACTH. We conclude that prenatal testicular maturation and development of female internal genitalia may take place in the absence of normal steroid hormone production. Normal growth and development may be obtained in P450scc-deficient individuals with adequate hormone replacement.

Steroid-secreting tumors of the testis have generally been considered to be of Leydig cell origin. Testicular tumors in patients with congenital adrenal hyperplasia have been thought to be adrenal rests, but no conclusive evidence supporting the hypothesis has been presented. We report a morphological and biochemical analysis of a patient with 21-hydroxylase deficiency who developed bilateral nodular hyperplasia of steroid-secreting tissue within the testis, despite suppression therapy with both exogenous glucocorticoids and testosterone. The tissue was formed of confluent nodules of homogenous cells. Electron microscopy showed the cells to have abundant smooth endoplasmic reticulum, well developed Golgi apparatus, and mitochondria with predominantly tubular cristae, features characteristic of steroid-secreting cells of adrenocortical origin. Crystals of Reinke were not observed. Functional studies in vivo showed a marked response to ACTH infusion, with 17-hydroxyprogesterone rising from 56 to 13,500 ng/mL, cortisol from less than 2 to 19 micrograms/dL, and testosterone from 369 to 629 ng/dL, with an attendant increase in testicular size and pain over 48 h. Receptor studies in vitro revealed no gonadotropin receptors, but abundant angiotensin-II receptors. Enzyme activity analysis in vitro showed undetectable 21-hydroxylase activity and an enzyme profile consistent with adrenocortical cells rather than Leydig cells. Based on these morphological and biochemical findings, we conclude that the nodular steroidogenic tissue that replaced this patient's testes was of adrenal origin. The study documents for the first time the development of adrenocortical tumors from adrenal rest tissue within the testis.

We present a modified technique for feminization genitoplasty, which combines the main features of the Hendren and Crawford pull-through operation and the Kogan reduction clitoroplasty. The unique features of the operation are the use of a flap of preputial skin to construct the vestibule and the anterior vaginal wall, and the universal use of the urogenital sinus to form the distal urethra, which avoids creation of female hypospadias. The new introitus is ample and, because there is no cut-back of the urogenital sinus, we avoid accidental incision of the urethral sphincter and the potential for urinary incontinence. There is no pull-through of the vagina because the introitus is created by mobilization of anterior and posterior skin flaps. The clitoris and the neourethra are exteriorized through the folded preputial skin, which simulates the normal female anatomy. The cosmetic and functional results in 9 children who have undergone this procedure have been excellent.

Two adult males are described with congenital adrenal hyperplasia (21-hydroxylase deficiency). Patient 1 was receiving therapy with cortisone acetate and presented with clinical features of glucocorticoid excess and uncontrolled adrenal androgen activity. It was established that the short-acting steroid which the patient was receiving was cleared so rapidly that endogenous ACTH secretion was not inhibited. Patient 2 presented with enlarged and painful testes in association with poor compliance with corticosteroid therapy. The histologic picture of the testis was compatible with 'Leydig cell hyperplasia'. However, successful response to dexamethasone therapy suggests that the testes harboured an adrenal rest. These observations highlight the need for careful follow-up and treatment of adult male patients with congenital adrenal hyperplasia.

A combination of the following malformations in a boy of 6 months is described: a salt-losing form of the adrenogenital syndrome, true hermaphroditism (external genitalia of the male type, the Fallopian and tissue of the embryonal ovary found in the abdominal cavity), left-side uretherohydronephrosis and microgyria of the right parietooccipital area of the brain.

Rare carcinoid-like ACTH-active tumour of the thymus in a woman of 40 is described. The tumour was of a solid-trabecular structure with rosette-like figures and consisted of spindle, polyhedral and roundish cells containing electron-dense granules of the neurosecretory type. Hormonal activity of the tumour was manifested in a pronounced hypercorticism with a marked adrenal hyperplasia, atrophy of sex organs and general virilization, skeletal muscle atrophy, osteoporosis, signs of diabetes mellitus, lipid hepatosis and other symptoms of a grave Itsenko-Cushing' syndrome followed by a fever. In spite of the absence of metastasis tumour was characterised by a rapid expansive growth with the compression of neck veins and venous stasis in both mediastinal organs and the tumour itself with the necrosis in its central parts. The cause of death was the thromboembolism of lung arteries from the thrombotic veins of the lower limbs.

The case of a 14-month-old girl presenting with precocious breast development due to adrenal hyperplasia is reported. The endocrine studies revealed a slight elevation of the plasma progesterone, 17 alpha-hydroxyprogesterone, testosterone and oestrone levels, and an increased urinary oestrogen excretion. The findings of the ultrasound examination and the evidence that the oestradiol concentration in the left adrenal vein was higher than in the right adrenal vein confirmed the diagnosis of left adrenal hyperfunction. Surgical exploration revealed unilateral hyperplasia of the adrenal cortex. After adrenalectomy the plasma hormone levels and urinary oestrogen excretion fell to normal, with concomitant regression of breast tissue. The girl shows no signs of recurrence of the disorder in a 2 year follow-up. This adrenal hyperplasia might be a benign adrenal disorder causing precocious breast development.

Heterotopic glial tissue was seen within the lungs of a newborn with a cranial malformation and anterior spina bifida. Histological examination of the lung showed solid islands of glial tissue intermingled with pulmonary structures. Well developed bronchioles that were in continuity with the main bronchial tree could be identified within the nodules. The central cystic cavity of the nodules is a bronchial lumen probably dilated by the respiratory movements. Several hypotheses have been elaborated to explain the heterotopic glial tissue in lung. The presence of an anterior spina bifida suggests a migratory mechanism to explain the embryogenesis of this case.

In order to evaluate the diagnostic significance of vaginal smears in endocrinopathies associated with menstrual disorders, the cytologic pattern of vaginal smears was examined in 703 patients who had a well-established diagnosis of the disorder's origin. The patients were classified into four groups according to their menstrual disorders: primary amenorrhea (159 patients), secondary amenorrhea (116 patients), primary oligomenorrhea (214 patients) and secondary oligomenorrhea (214 patients). Using the maturation index and the maturation value, three cytologic patterns of vaginal smears were distinguished: parabasal cell pattern, intermediate cell pattern and superficial cell pattern. The frequency with which the cytologic patterns occurred in the groups of patients and their subdivisions are presented. As a whole, the 703 patients showed 25.2% with a parabasal cell pattern, 58.3% with an intermediate cell pattern and 16.5% with a superficial cell pattern. Although the cytohormonal pattern of vaginal smears in endocrinopathies with associated menstrual disorders is not diagnostic of a specific endocrinopathy, the cellular patterns may prove helpful in suggesting a range of diagnoses or in excluding some possibilities.

The authors report about 3 cases of the congenital adreno-genital syndrome in first-born children with a high weight at birth (3900, 3600, and 4200 g) who perished in early infancy. One child, who was considered to be a boy, died of septic postoperative complications; during the operation the uterus, ovaries, tubes, phenomena of pseudofemale hemaphroditis were observed. The considerably enlarged adrenals were gyral, goffered and their cortex consisted of cells of the fetal zone. Two other boys, who perished at the age of 3 1/2 and 2 1/2 months, were sick from the birth. In the clinical picture there prevailed anorexia, dehydration, regurgitation, periodic vomiting, convulsions, clonic spasms, Hyponatrema, hyperkalemia, sudden arrest of the heart, rose no suspicion in pediatricians with respect to the salt-losing form of the adreno-genital syndrome. Post-mortem examination revealed congenital hyperplasia of the adrenals, whose cortex consisted of the fetal zone cells.

Non-iatrogenic Cushing's syndrome has been associated primarily with three entities: pituitary-dependent processes due to pituitary adenomas or microadenomas causing adrenal hyperplasia; pituitary-independent primary adrenal causes, predominantly unilateral adenomas, rarely multiple adenomas or adrenal carcinoma; ectopic sources of adrenocorticotropic hormone (ACTH) production. Although non-neoplastic bilateral adrenal disease generally has been ascribed to extra-adrenal stimulation, a rare cause of Cushing's syndrome that involves bilateral adrenal nodule formation independent of pituitary stimulation has been identified. Nodular adrenal diseases represent a confusion of terms in the literature, but one subgroup of Cushing's syndrome has most frequently--and, perhaps, most appropriately--been designated primary adrenocortical nodular dysplasia. A case of this unusual entity is presented, and previous case reports pertaining to this confusing area of adrenal hyperfunction are reviewed. The characteristic manifestations that separate this diagnosis from other types of nodular adrenal disease are also discussed. Recognition of this diagnosis, although rare, is important, as bilateral adrenalectomy in the treatment of choice.

Inappropriate ACTH secretion with bilateral diffuse or macronodular adrenal hyperplasia is the most common cause of Cushing's syndrome. This report describes a patient with Cushing's syndrome and feminization due to ACTH-independent bilateral macronodular adrenal hyperplasia. A 47-yr-old black man presented with Cushingoid features, diabetes mellitus, hypertension, impotence, and gynecomastia. Urinary cortisol and 17-hydroxycorticosteroid excretion were 94 nmol/mmol creatinine (normal, less than 32) and 5.8 mumol/mmol creatinine (normal, 0.6-3.6), respectively. Both decreased by less than 30% after administration of dexamethasone (8 and 16 mg/day), and urinary 17-hydroxycorticosteroid excretion did not increase after metyrapone (750 mg, orally, every 4 h for six doses). Plasma ACTH was undetectable (less than 1 pmol/L) and was not stimulated by administration of metyrapone or ovine CRH. Serum testosterone was 5.2 nmol/L (normal, 7-30), FSH was 5 U/L (normal, 3-18), LH was 2.8 U/L (normal, 1.5-9.2), and estrone was 767 pmol/L (normal, 55-240). Both adrenal glands were enlarged, with a total weight of 86 g (normal, 8-10), and contained multiple nodules (diameter, greater than 0.5 cm) composed of two active cell types, one of which was also observed between the nodules. Cushing's syndrome with feminization due to ACTH-independent bilateral macronodular adrenal hyperplasia is an unusual process of unknown etiology that should be included with the other known causes of Cushing's syndrome.

An adrenal size index (ASI) was specifically designed to improve ultrasound evaluation of adrenal size in the 1st year of life. In 84 newborns and infants, ASI and plasma dehydroepiandrosterone sulphate (DHEA-S) concentrations were determined to study in vivo changes in adrenal size and cortical zonal composition. ASI was higher (P less than 0.0001) in the first 2 postnatal weeks (median 60.5 mm2) than in the rest of the first year (median 39.6 mm2) and showed a negative correlation with chronological age (r = -0.41). A positive correlation existed between DHEA-S concentrations and ASI (r = 0.29) as well as ASI relative to body weight (r = 0.57). These data and changes in gland echogenicity are consistent with histopathological observations that the early decrease in adrenal size is due to involution of the fetal zone. In four patients with congenital adrenal hyperplasia (CAH) due to 21-hydroxylase (21-OHase) deficiency, ASI and plasma concentrations of pre-defect steroid were determined. Two patients with severe salt loss had markedly elevated ASI, which returned to normal during treatment. Two patients without severe salt loss had pretreatment ASI in the upper normal range, which decreased with treatment. Our findings indicate that ASI is useful in assessing physiological changes in adrenal size and, in conjunction with DHEA-S determinations, in adrenal cortex composition. ASI may aid in the early diagnosis of the salt-losing variety of 21-OHase deficiency. ASI is an instantaneously available tool which, in addition to biochemical and clinical data, can be used to monitor treatment of 21-OHase deficiency.

Studies in 18 Jewish families from Morocco, Tunis, Turkey and Iran revealed 26 patients with congenital adrenal hyperplasia due to 11 beta-hydroxylase deficiency. The clinical expression of androgen excess varied widely in affected females, and range from solely enlarged clitoris in the mildest forms to severely hypertrophied clitoris with penile urethra and fused labial-scrotal folds in the most extreme forms of masculinization. Intermediate degrees of severity were manifested by ambiguous genitalia. There was no correlation between the degree of virilization and the signs of mineralocorticoid excess. Severe volume-induced hypertension leading to vascular accidents and death were also observed in severe as well as in mildly virilized patients, while completely masculinized females were sometime normotensive. Overt hypokalemia was present in 6 patients but was not a constant feature of hypertensives. However, all affected individuals, except for 2 infants, had very low levels of plasma renin activity suggesting that a state of volume expansion was indeed present in the majority of cases, even though changes in blood pressure did not always occur. The clinical expression of this disorder is characterized by a wide range of variability in the signs of both androgen and mineralocorticoid excess, which do not necessarily correlate with the quantity of hormones secreted.

Congenital lipoid adrenal hyperplasia results in deficient virilization of genetic male infants, indicating that gonadal testosterone biosynthesis is impaired in such patients. In order to better define the characteristics of the gonadal lesion, we studied a Japanese genetic male infant with congenital lipoid adrenal hyperplasia who underwent bilateral orchiectomy at 14 months of age. The basal serum testosterone was low before and after orchiectomy (6.6 +/- 1.1 vs. 9.5 +/- 1.3 ng/dl), though it was higher at 9 days of age (30 ng/dl). A stimulation test with human chorionic gonadotropin at 12 months of age yielded no testosterone response (7----less than 5 ng/dl). At the time of the surgical intervention, the external genitalia were completely female but Wolffian duct derivatives (epididymides and vasa deferentia) were well developed. The microscopic examination of the testes revealed an increased number of Leydig cells which were filled with abundant lipoid material.- The above data demonstrate that the fetus produced a sufficient amount of testicular testosterone for a male Wolffian duct development. This indicates a quantitative difference in androgen requirements for the male sexual development of the external genitalia and the Wolffian ducts.

Adrenal tumors accidently detected by CT scan are increasingly seen in patients without clinical signs of adrenal diseases. We studied whether enhanced adrenal stimulation is of importance in the development of adrenal tumors. For this purpose 22 patients with adrenogenital syndrome (AGS) were studied by CT scan. One of these patients suffered from C-11 beta-hydroxylase-, one from C-3 beta-hydroxy steroid dehydrogenase-, and 20 from C-21-hydroxylase deficiency. The average adrenal size of these patients was 506 +/- 79 mm2 as compared to 132 +/- 8 mm2 in the controls (P less than 0.001). Only two patients with the late onset form revealed adrenal glands of normal size. There was a significant correlation between adrenal size and patients' age (P less than 0.01). Females with the simple virilizing form revealed adrenal glands larger than those of the late onset form (640 +/- 169 vs 308 +/- 56 mm2). Eighteen patients with AGS exhibited one (n = 11) or several (n = 7) adrenal tumors, the size of which was 5-9 mm in diameter in 9, 10-20 mm in 7, and more than 50 mm in 2 patients. There was a significant correlation between adrenal hyperplasia and tumor diameter (P less than 0.001). No correlation was found between tumor size and plasma concentrations of testosterone or 17-hydroxyprogesterone, patients' age at the time of diagnosis, or clinical signs of androgenization. Again, tumors were larger in females suffering from the simple virilizing form of AGS than in those with the late onset form (14.8 +/- 5.5 vs 7.7 +/- 0.8 mm).(ABSTRACT TRUNCATED AT 250 WORDS)

A comparative study of adrenal morphology between normal fetuses and those with anencephaly or congenital adrenal hyperplasia (CAH) was performed in order to examine the hypothesis that fetal adrenal mass and structure are adrenocorticotrophin (ACTH)-dependent throughout gestation. Combined adrenal weight in 102 normal fetuses was used to establish a reference range for the gestational ages of 15-27 weeks. During this period, mean adrenal weight showed a 6-fold linear increase. In 38 anencephalic fetuses of similar gestation age, adrenal weight was below the normal range and did not show a rise. Three fetuses with CAH (18, 22 and 30 weeks gestation) had adrenal weights considerably above the normal range. Adrenal cortical thickness was significantly increased in CAH fetuses, largely as a consequence of cell hypertrophy, whereas decreased cortical thickness in the anencephalic group represented cellular hypoplasia. Conspicuous secretory granules in the cytoplasm was the electron-micrographic feature of the adrenal gland in the 22-week fetus with CAH. These observations are consistent with close dependency of fetal adrenal growth and development upon fetal pituitary function from an early age, mediated primarily through ACTH.

The adrenals and kidney incretory structures (the juxtaglomerular apparatuses and renomedullary interstitial cells) were studied in 12 cases of a desalinization form of the adrenogenital syndrome in children who died at the age of 1-6 mos of acute water-electrolytic disturbances in order to assess function of the structures involved in the regulation of the water-salt equilibrium. The adrenals and kidneys from 7 children of the same age who died of mechanical asphyxia, were taken as controls. The depth of adrenocortical zones, volumes of nuclei and nucleoli in different cortical zones were determined; the juxtaglomerular index, cell count (including vacuolized cells), the area of the juxtaglomerular apparatus and mesangium were determined in the juxtaglomerular apparatus. The amount of cell lipid granules (the interstitial-cellular index), the mean granule volume and the total granule volume were counted in renomedullary interstitial cells. The results were statistically processed, and a paired correlation analysis of all the studied parameters was performed. In the desalinization form of the adrenogenital syndrome morphometric investigation of the glomerular and fascicular zones revealed compensatory processes, not of hyperplastic nature but mainly of hypertrophic nature; morphological and morphometric characteristics of the kidney incretory structures indicated tension of the renin-angiotensin system and probably a decrease in prostaglandin synthesis in salt and water loss. In the control group parameters of structures related to the regulation of the water-salt equilibrium, especially in the adrenal cortex, showed good correlation. In the desalinization form of the adrenogenital syndrome some other relationships between these structures developed.

The enzyme steroid 21-hydroxylase (21-OHase) plays a key role in adrenal steroidogenesis. Defects in this enzyme are responsible for one of the most common inborn errors of metabolism in humans. Duplicated genes for the enzyme are located in the class III region of the major histocompatibility complex (MHC), HLA. In the mouse, the genes encoding 21-OHase have been mapped to the homologous region of the H-2 complex. We previously described an H-2 recombinant haplotype aw18, in which the gene for the complement component C4 and one of the two genes for 21-OHase in the H-2 class III region have been deleted. We now report that newborn aw18 homozygous mice are deficient in 21-OHase activity, and that homozygosity for the aw18 haplotype directly causes death at the early postnatal stage. Morphological changes in the adrenal glands of newborn aw18 homozygotes are also observed. The aw18 recombinant haplotype is expected to serve as a useful and, thus far, unique experimental system to study adrenal steroidogenesis in vivo and as an animal model for the inherited human disease of congenital adrenal hyperplasia.

A case is presented of a seventeen-year-old phenotypic male with empty scrotum, hormonal studies consistent with adrenogenital syndrome, a 46,XX karyotype, and a normal prostate on rectal examination. Histochemical evidence of the true nature of the prostatic tissue is presented, and the developmental aspects of the case are discussed.

The concentration of 17-OH-progesterone was determined in second trimester amniotic fluid collected from 58 pregnancies at risk for fetal 21-hydroxylase deficiency. The prediction was incorrect in 1 male nonsalt-loser who had an increased plasma 17-OH-progesterone concentration at 3 months of age. All 11 infants predicted to be affected were salt-losers. The adrenals from 2 affected fetuses available for study were significantly enlarged in comparison with adrenal size in 84 normal fetuses from 15 to 26 weeks' gestation. Amniotic fluid steroid analysis reliably predicts the fetus with 21-hydroxylase deficiency most at risk in early infancy. There is no evidence from this study to indicate that ACTH is not the main trophic factor for fetal adrenal growth and steroidogenesis.

Peliosis most commonly affects the liver and spleen and has been associated with exogenous and endogenous steroid hormones, particularly of the anabolic type. The finding of peliosis of the parathyroid glands, as well as of the liver, in an infant with adrenogenital syndrome indicates that other organs may be affected.

The clinical and pathological features of 40 cases in which testicular masses developed in patients with the adrenogenital syndrome are reviewed; this study was based on six personally observed cases and 34 other cases in the literature. The adrenal disorder was of the salt-losing form in two-thirds of the cases and the non-salt-losing form in the other third. Although the clinical diagnosis of the adrenogenital syndrome had been established prior to the discovery of the testicular lesion in most of the patients, in 18% of them the diagnosis was not made until or after the development of a testicular mass. Two-thirds of the masses were palpable (up to 10 cm); these cases were usually discovered in early adult life (average, 22.5 years). The remaining one-third were small (under 2 cm) and were usually found in children either at autopsy or on testicular biopsy. Eighty-three percent of the masses were bilateral. Eighty-six percent of the small lesions were located in the hilus. The larger lesions involved the testicular parenchyma in all but one case. They formed well-demarcated but unencapsulated brown-green masses, typically separated into lobules by prominent bands of fibrous tissue. Microscopical examination revealed sheets, nests, and (rarely) cords of cells with abundant eosinophilic cytoplasm separated by bands of fibrous tissue. Lipochrome pigment was identified in the cytoplasm in many cases, but crystals of Reinke were uniformly absent. The major pathological differential diagnosis is Leydig cell tumor; the associated clinical and laboratory features--including the high frequency of bilaterality and a decrease in the size of the tumor with corticosteroid therapy--are diagnostic of a testicular "tumor" of the adrenogenital syndrome. Although a variety of origins have been suggested for these lesions, in our opinion an origin from hilar pluripotential cells, which proliferate as a result of the elevated level of adrenocorticotropic hormone, is most likely.

Authors studied the surgically removed adrenals of a 16 year old girl with hyperandrogenism in tissue culture. The majority of cells in the initial culture was similar to the cells of the normal human adrenal. In the 6 weeks tissue culture the morphology of the cells has shown an alteration. The majority of them contained a small number of lipid droplets, abundant quantity of lysosomes and autophage vacuole. At this period in the media the progesterone level appeared to be elevated. Two months later in the tissue culture numerous transformed cells could be seen and the progesterone level of the media was low. It is believed that alteration of the biosynthesis of progesterone may have a role in the increased production of testosterone and in virilization.

Cushing's syndrome, a characteristic pattern of obesity with hypertension due to the hyperfunction of the adrenal cortex, is relatively rare in infancy. Thirty-six infants have been reported in world literature, most of whom have had adrenal tumours. There are only eight reported cases of infants under the age of 1 year with adrenal hyperplasia responsible for Cushing's syndrome. This is a report of an 8 month old child with bilateral nodular adrenal hyperplasia.

The child with testicular enlargement in the absence of gonadotrophin stimulation presents a difficult diagnostic dilemma. Leydig cell tumors, Leydig cell hyperplasia, and tumors of adrenal rest tissue are the primary etiologic considerations. Because of considerable overlap in clinical presentation, careful biochemical and histologic evaluations are necessary to make the diagnosis. These should include serum levels of testosterone, dehydroepiandosterone, androstenedione, 17-hydroxyprogesterone, and 11-desoxycortisol, as well as urinary levels of 17-ketosteroids. If diagnostic changes in the biochemical profile are not present, then testicular biopsy is indicated. Encapsulation, presence or absence of the crystalloids of Reinke, degree of seminiferous tubule maturation, and the site of any abnormal tissue are important observations in the examination of the tissue specimen. Once the diagnosis has been established, then appropriate and specific medical or surgical therapy can be instituted. With appropriate treatment, the long-term prognosis in each condition is good.

The human adrenal cortex in essential hypertension and in the salt-losing form of the adrenogenital syndrome and the adrenal cortex in spontaneously hypertensive rats were studied by morphometry. Under long-term functional loading hypertrophy of adrenocortical cells is the common way of increasing the mass of the cortex. The correlation between the morphological parameters of the adrenocortical structures increases in this condition. Hyperplasia along with hypertrophy has been found in man at an early age. The differences in the degree of hypertrophy of the nuclei and nucleoli may be connected with different intensity of adrenocortical function in different pathological conditions.

Dermatoglyphic findings were compared in 42 patients (32 females, 10 males) with Congenital Adrenal Hyperplasia (CAH) and 110 normal controls (70 females, 40 males). In CAH males, an excess of whorls (p less than 0.001), an increased total finger ridge count (p less than 0.05), and an increased frequency of patterns in the fourth interdigital area (p less than 0.025) was found. A main line A terminating high in the hypothenar area (p less than 0.05), and a missing c-triradius or an abortive main line C (p less than 0.05) was observed in CAH females. Both sexes displayed an increase in the frequency of small radially directed hypothenar patterns (p less than 0.05) and sydney lines (p less than 0.01).