Congenital Adrenal Hyperplasia Males Research Articles

7955 Increased occurrence of psychiatric disorders and use of psychiatric-related medication in patients with congenital adrenal hyperplasia

Abstract Disclosure: M. Lind-Holst: None. D. Hansen: None. K.M. Main: None. A. Juul: None. M. Andersen: None. M. Dunø: None. Å.K. Rasmussen: None. N. Jørgensen: None. C.H. Gravholt: None. A. Berglund: None. Background: Clinical studies on psychiatric morbidity, quality of life and cognition in patients with congenital adrenal hyperplasia (CAH) imply impaired mental health. Epidemiological studies on psychiatric morbidity in CAH are, however, scarce. Methods: A registry study of hospital diagnoses and prescribed medication related to psychiatric disorders in a national cohort of patients (n=462) diagnosed with CAH from 1943 to 2018 compared to 100 randomly selected sex- and age-matched controls (n=44,527) from the general population. Psychiatric hospital diagnoses were available for in-patient contacts from 1968 and out-patient contacts from 1994. Medication data were available from 1995. Outcomes: CAH was associated with an increased risk of hospital contacts related to any psychiatric diagnosis (incidence rate ratio (IRR)=2.73, 95% CI 1.85-4.04), and this applied to both males (IRR=2.48, 95% CI 1.57-3.91) and females (IRR=3.20, 95% CI 1.58-6.50). Psychiatric disorders due to psychoactive substance use were more common among CAH males (IRR=3.55, 95% CI 1.58-7.96) and females (IRR=3.81, 95% CI 1.71-8.48). Males with CAH also had an increased risk of suicidal behaviour (IRR=10.66, 95% CI 3.74-30.42). By the age of 30 years, 23% of CAH females and 21% of CAH males had at least one diagnosis related to a psychiatric disorder while this was the case in 14% of female controls and 15% of male controls. Stratifying by sex and CAH phenotype there were important differences among groups. Prescription of medication related to psychiatric disorders was increased for CAH overall (HR=1.73, 95% CI 1.48-2.03) and males (HR=1.80, 95% CI 1.35-2.38) and females (HR=1.70, 95% CI1.36-2.38), separately. Age at the first prescription of any psychiatry-related medication was significantly earlier for patients than for controls (HR males=1.67, 95% CI 1.2-2.3; HR females=1.48, 95% CI 1.2-1.8). Thirty-five per cent (157/448) of CAH patients and 24% of controls had at least one prescription related to a psychiatric disorder within the study period. Interpretation: An increased risk of psychiatric morbidity, psychoactive substance use and use of medication related to poor mental health was seen in both males and females with CAH. The risk of suicidal behaviour was increased for patients with CAH, yet only significantly in CAH males. The study underlines the need for more attention and extension of psychological care and support for patients with CAH. Presentation: 6/1/2024

7955 Increased occurrence of psychiatric disorders and use of psychiatric-related medication in patients with congenital adrenal hyperplasia

Abstract Disclosure: M. Lind-Holst: None. D. Hansen: None. K.M. Main: None. A. Juul: None. M. Andersen: None. M. Dunø: None. Å.K. Rasmussen: None. N. Jørgensen: None. C.H. Gravholt: None. A. Berglund: None. Background: Clinical studies on psychiatric morbidity, quality of life and cognition in patients with congenital adrenal hyperplasia (CAH) imply impaired mental health. Epidemiological studies on psychiatric morbidity in CAH are, however, scarce. Methods: A registry study of hospital diagnoses and prescribed medication related to psychiatric disorders in a national cohort of patients (n=462) diagnosed with CAH from 1943 to 2018 compared to 100 randomly selected sex- and age-matched controls (n=44,527) from the general population. Psychiatric hospital diagnoses were available for in-patient contacts from 1968 and out-patient contacts from 1994. Medication data were available from 1995. Outcomes: CAH was associated with an increased risk of hospital contacts related to any psychiatric diagnosis (incidence rate ratio (IRR)=2.73, 95% CI 1.85-4.04), and this applied to both males (IRR=2.48, 95% CI 1.57-3.91) and females (IRR=3.20, 95% CI 1.58-6.50). Psychiatric disorders due to psychoactive substance use were more common among CAH males (IRR=3.55, 95% CI 1.58-7.96) and females (IRR=3.81, 95% CI 1.71-8.48). Males with CAH also had an increased risk of suicidal behaviour (IRR=10.66, 95% CI 3.74-30.42). By the age of 30 years, 23% of CAH females and 21% of CAH males had at least one diagnosis related to a psychiatric disorder while this was the case in 14% of female controls and 15% of male controls. Stratifying by sex and CAH phenotype there were important differences among groups. Prescription of medication related to psychiatric disorders was increased for CAH overall (HR=1.73, 95% CI 1.48-2.03) and males (HR=1.80, 95% CI 1.35-2.38) and females (HR=1.70, 95% CI1.36-2.38), separately. Age at the first prescription of any psychiatry-related medication was significantly earlier for patients than for controls (HR males=1.67, 95% CI 1.2-2.3; HR females=1.48, 95% CI 1.2-1.8). Thirty-five per cent (157/448) of CAH patients and 24% of controls had at least one prescription related to a psychiatric disorder within the study period. Interpretation: An increased risk of psychiatric morbidity, psychoactive substance use and use of medication related to poor mental health was seen in both males and females with CAH. The risk of suicidal behaviour was increased for patients with CAH, yet only significantly in CAH males. The study underlines the need for more attention and extension of psychological care and support for patients with CAH. Presentation: 6/1/2024

Brain activity during visuospatial working memory in congenital adrenal hyperplasia.

Patients with congenital adrenal hyperplasia (CAH) require life-long replacement of cortisol. Problems with cognitive function, especially working memory, have previously been identified, but the long-term effects of this disease on brain function are unknown. We investigate brain activity during working memory in CAH compared to controls. Twenty-nine individuals with CAH (17 females) and 40 healthy controls (24 females), 16-33 years, from a single research institute, underwent functional magnetic resonance imaging while doing a verbal and visuospatial working memory task. Individuals with CAH responded faster on the verbal task. Although we found no differences in BOLD response over the whole group, there were significant interactions with sex: CAH males had increased activity in the bilateral lateral superior occipital cortex, left supramarginal and angular gyri, left precuneus, left posterior cingulate cortex and bilateral cerebellum during decoding of the visuospatial task, while females showed decreased activity in these regions. Long-term cortisol imbalances do not seem to have a major impact on the functional brain responses during working memory in CAH. However, activity of the left dorsal visual stream in particular might be affected depending on sex. As the task employed may have been relatively easy, larger studies using more complex tasks are needed to further investigate this.

Challenges in the treatment of late-identified untreated congenital adrenal hyperplasia due to CYP11B1 deficiency: Lessons from a developing country.

Congenital Adrenal Hyperplasia (CAH) due to CYP11B1 is a rare autosomal recessive adrenal disorder that causes a decrease in cortisol production and accumulation of adrenal androgens and steroid precursors with mineralocorticoid activity. Clinical manifestations include cortisol deficiency, ambiguous genitalia in females (differences of sex development (DSD)), and hypertension. Medical treatment recommendations are well defined, consisting of glucocorticoid treatment to substitute glucocorticoid deficiency and consequently normalize adrenal androgen and precursors levels. Current guidelines also emphasize the need for specialized multidisciplinary DSD teams and psychosocial support. In many developing countries, care for DSD patients, especially when caused by an adrenal disease, is challenging due to the lack of infrastructure, knowledge, and medication. The study aims to report the conflicting decision-making process of medical treatment and sex assignment in late-identified CAH patients in developing countries. We describe the clinical and biochemical findings and the psychological assessment of five affected but untreated family members with CAH due to CYP11B1 deficiency. All patients had a 46,XX karyotype, ambiguous genitalia, low cortisol levels, and hypertension. Two identified as males, two as females, and one had undecided gender. The patients were counselled that refusing treatment will lead to infertility and the potential risk of developing Addisonian crisis and severe hypertension. However, all 46,XX CAH males refused treatment with glucocorticoids due to the expected lowering of adrenal androgens as their main source of testosterone. None of the patients developed Addisonian crisis, probably due to some residual cortisol activity and glucocorticoid activity of elevated adrenal steroid precursors. Medical treatment and sex assignment in late-identified 46,XX CAH patients in Indonesia may often depend on local and cultural factors. The management of DSD conditions may have to be individualized and integrated into the psychological and social context of the affected family.

Sexuality in Males With Congenital Adrenal Hyperplasia Resulting From 21-Hydroxylase Deficiency.

PurposeAlthough sexuality has been reported to be impaired in females with congenital adrenal hyperplasia (CAH) resulting from 21-hydroxylase deficiency, sexuality in males with CAH so far has remained largely unconsidered.PatientsOne of the largest European male cohorts of patients with CAH in which sexuality in male patients with CAH was assessed.MethodsSexuality was evaluated in 91 sexually active male patients with CAH using questionnaires investigating sexual orientation, age at sexual initiation, sexual activity, satisfaction with sex life, and sexual problems, such as fears or dislike of sexual activity, lack or excessive sexual desire, difficulties getting aroused or reaching an orgasm, premature ejaculation, and no or incomplete erection.ResultsSexuality in male patients with CAH was similar to European reference populations. If sexuality problems were present, they were less frequently reported by the most severely affected CAH males. Adducing a holistic perspective, sexual problems showed substantial association to psychological problems, such as anxiety and depression.ConclusionsSexuality in male patients with CAH in general was unaffected and sexuality problems seemed to be associated in particular with psychological problems. Because sexual health is a key factor of general health, we recommend that sexuality as well as psychological issues explicitly should be addressed in health care of patients with a CAH diagnosis, independent of sex.

Cognitive function in children with classic congenital adrenal hyperplasia.

Studies of cognitive function in patients with congenital adrenal hyperplasia (CAH) are few and controversial. This study aimed to investigate general intelligence and specific cognitive functions in children with salt wasting (SW) form of CAH and their relationship to demographic, clinical, and laboratory variables. This study included 36 children with classic 21 hydroxylase deficiency SW type of CAH (males = 12; females = 24; mean age = 15.6 ± 2.3years). Intelligence quotient (IQ) and cognition were assessed using Wechsler Intelligence Scale for Children 3rd edition (WISC-III) and Stanford Binet Subsets Test version 4 (SBST4). Compared to controls, patients had lower mean full-scale (FS) IQ (P = 0.01) score, particularly performance IQ score (P = 0.001), and comprehension, pattern analysis, quantitation, bead memory, and memory for sentences of SBST4 (P = 0.05, P = 0.014, P = 0.001, P = 0.002, and P = 0.05, respectively). Lower IQ was observed in poorly controlled compared with well-controlled patients on medical treatment. Significant correlations were observed between FSIQ with age (r = - 0.810; P = 0.001), duration of treatment (r = - 0.887; P = 0.01), dose of glucocorticoids (r = - 0.463; P = 0.01), 17-OHP (r = - 0.543; P = 0.01) and testosterone (r = - 0.462; P = - 0.006) levels, and number of hyponatremic episodes (r = - 0.350; P = 0.05). In multivariate analysis, the independent risks of low FSIQ were the dose of glucocorticoids (OR = 1.14; 95% CI = 1.08-1.23, P = 0.0001), 17-OHP levels (OR = 2.25; 95% CI = 1.19-2.85, P = 0.01), and number of hyponatremic episodes (OR = 4.34; 95% CI = 2.05-5.15, P = 0.01).Conclusion: Patients with SW form of CAH may have lower IQ and cognitive deficits which may be related to the dose of glucocorticoids, androgen excess, and number of hyponatremic episodes. What is Known: • Congenital adrenal hyperplasia (CAH) is a group of inherited impairment of cortisol biosynthesis. • Studies of cognitive function in patients with congenital adrenal hyperplasia (CAH) are few and controversial. What is New: • Children with CAH may have lower intelligent quotient (IQ) and cognitive deficits. • Early hyponatremic episodes, overtreatment with glucocorticoids, and high androgen levels may be possible causative factors for the cognitive deficits.

Carotid Intima-Media Thickness Is Associated with Increased Androgens in Adolescents and Young Adults with Classical Congenital Adrenal Hyperplasia

Background/Aims: Youth with congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency develop cardiovascular disease (CVD) risk factors of obesity and hypertension. Carotid intima-media thickness (CIMT), a marker of CVD risk, is increased in CAH young adults. We examined CIMT and its relationship with androgens and obesity in adolescents/young adults with CAH. Methods: Twenty CAH subjects (age 16 ± 3.3 years, 50% female) and 20 matched controls were studied cross-sectionally. Eight additional obese patients with CAH were included in within-group comparisons. CIMT by high-resolution ultrasound, androgens, anthropometry, bone age (BA), and metabolic/inflammatory markers were assessed. Results: Within the CAH group, CIMT correlated with 17-hydroxyprogesterone (r = 0.48, p < 0.05) and androstenedione (r = 0.46, p < 0.05), and was greater in obese subjects. CIMT was greater in CAH males than females, but similar among CAH females with advanced BA, CAH males with normal BA, and control males. There was no difference in CIMT between CAH and controls, although high-density lipoprotein was inversely correlated with CIMT in both groups. Conclusion: CIMT is associated with increased androgens in CAH adolescents and young adults, with loss of sex differences in CAH females with excess androgen exposure. Our findings highlight the importance of hormonal control for CVD prevention in CAH.

Increased mortality in patients with congenital adrenal hyperplasia due to 21-hydroxylase deficiency.

Reports on mortality in patients with congenital adrenal hyperplasia (CAH) are lacking. This study sought to study mortality and causes of death in CAH. We studied patients with CAH (21-hydroxylase deficiency, n = 588; CYP21A2 mutations known, >80%), and compared them with controls (n = 58 800). Data were derived through linkage of national population-based registers. Mortality and causes of death. Mean age of death was 41.2 ± 26.9 years in patients with CAH and 47.7 ± 27.7 years in controls (P < .001). Among patients with CAH, 23 (3.9%) had deceased compared with 942 (1.6%) of controls. The hazard ratio (and 95% confidence interval) of death was 2.3 (1.2-4.3) in CAH males and 3.5 (2.0-6.0) in CAH females. Including only patients born 1952-2009, gave similar total results but only patients with salt wasting (SW) or with unclear phenotype had an increased mortality. The causes of death in patients with CAH were adrenal crisis (42%), cardiovascular (32%), cancer (16%), and suicide (10%). There were seven additional deaths in CAH individuals with incomplete or reused personal identification number that could not be analyzed using linkage of registers. Of the latter, all except one were deceased before the introduction of neonatal screening in 1986, and most of them in the first weeks of life, probably in an adrenal crisis. CAH is a potentially lethal condition and was associated with excess mortality due to adrenal crisis. The SW phenotype also seemed to have worse outcome in children and adults due to adrenal crisis and not only before the introduction of neonatal screening.

New studies of second and fourth digit ratio as a morphogenetic trait in subjects with congenital adrenal hyperplasia

Congenital adrenal hyperplasia (CAH) is a disease that occurs during fetal development and can lead to virilization in females or death in newborn males if not discovered early in life. Because of this there is a need to seek morphological markers in order to help diagnose the disease. In order to test the hypothesis that prenatal hormones can affect the sexual dimorphic pattern 2D:4D digit ratio in individual with CAH, the aim of this study was to compare the digit ratio in female and male patients with CAH and control subjects. The 2D:4D ratios in both hands of 40 patients (31 females-46, XX, and 9 males-46, XY) were compared with the measures of control individuals without CAH (100 males and 100 females). Females with CAH showed 2D:4D ratios typical of male controls (0.950 and 0.947) in both hands (P < 0.001). In CAH males the left hand 2D:4D ratio (0.983) was statistically different from that of male controls (P < 0.05). These finding support the idea that sexual dimorphism in skeletal development in early fetal life is associated with differences between the exposure to androgens in males and females, and significant differences associated with adrenal hyperplasia. Although the effects of prenatal androgens on skeletal developmental are supported by numerous studies, further investigation is yet required to clarify the disease and establish the digit ratio as a biomarker for CAH.

Quality of life, social situation, and sexual satisfaction, in adult males with congenital adrenal hyperplasia

To determine quality of life (QoL) in adult males with congenital adrenal hyperplasia (CAH). CAH males with 21-hydroxylase deficiency (n = 30), 19-67 years old, were compared with controls (n = 32). QoL was assessed using questionnaires on general living conditions and sexual issues, and the psychological well-being index (PGWB) form. Fewer CAH males than controls were students (3 vs. 25 %, P = 0.028) and more had blue-collar work (57 vs. 33 %, P = 0.023). Patients were less interested in sports (47 vs. 72 %, P = 0.034) and art/literature/film (10 vs. 47 %, P = 0.004). PGWB total score was 82.7 ± 13.7 versus 87.0 ± 11.1 (P = NS), but hydrocortisone/cortisone acetate treated scored lower than controls and prednisolone treated. Glucocorticoid over-treated had lower QoL than those with poor control (PGWB total score 77.1 ± 13.5 vs. 92.4 ± 11.1, P = 0.026) and controls (P = 0.025). Total PGWB score was positively correlated with adrenal androgens and steroid precursors. Subscale scores indicated that patients with late diagnosis were more depressive (12.1 ± 2.8 vs. 13.9 ± 1.4, P = 0.011) and had a lower self-control (11.3 ± 3.6 vs. 13.1 ± 1.0, P = 0.019) compared with controls. Sexual satisfaction was similar in spite of more patients being sexually inactive (27 vs. 6 %, P = 0.040). Adult CAH males differed from controls with respect to type of occupation and spare time interests but had similar QoL despite being less sexually active. Optimizing glucocorticoid therapy might further improve QoL. Some disadvantages found in patients diagnosed late will hopefully not be seen in patients diagnosed by neonatal screening, but this has yet to be studied.

Increased Psychiatric Morbidity in Men With Congenital Adrenal Hyperplasia due to 21-Hydroxylase Deficiency

Reports on psychiatric morbidity in males with congenital adrenal hyperplasia (CAH) are lacking. The aim was to study psychiatric disorders in CAH males. We studied males with CAH (21-hydroxylase deficiency, n = 253; CYP21A2 mutations known, n = 185), and compared them with controls (n = 25 300). Data were derived through linkage of national population-based registers. We assessed the subgroups of CYP21A2 genotype separately (null, I2splice, I172N, P30L, and NC), as well as outcomes before and after the introduction of national neonatal screening in 1986. Psychiatric disorders including attempted and completed suicide (suicidality) were reviewed. Psychiatric disorders (suicidality not included), suicidality, and alcohol misuse were increased in CAH males compared with controls (odds ratios, 1.5, 2.3, and 1.9; 95% confidence intervals, 1.1-2.2, 1.1-5.0, and 1.0-3.5, respectively). In the null genotype group, no increased rates were seen; in the I2splice group, psychiatric disorders, personality disorders, and alcohol misuse were increased; in the I172N group, suicide attempt and drug misuse were increased; and in the P30L and NC groups, psychotic disorders were increased. In CAH males born before the neonatal screening, the rates of psychiatric disorders and suicidality were increased, but only psychotic disorders increased in those born afterward. There was no increased risk for any neurodevelopmental disorder. CAH males have an increased psychiatric morbidity. Psychiatric morbidity was not raised in the most severe genotype group. Late diagnosis of CAH may explain some of the findings. Those born before the introduction of neonatal screening were more affected, which may be explained by the higher age.

Bone mineral density, bone markers, and fractures in adult males with congenital adrenal hyperplasia

The aim of this study was to determine bone mineral density (BMD), markers of bone metabolism, fractures, and steroids reflecting hormonal control in adult males with congenital adrenal hyperplasia (CAH). SUBJECTS, METHODS, AND DESIGN: We compared CAH males with 21-hydroxylase deficiency (n=30), 19-67 years old, with age- and sex-matched controls (n=32). Subgroups of CYP21A2 genotypes, age, glucocorticoid preparation, poor control vs overtreatment, and early vs late (>36 months) diagnosis were studied. BMD measured by dual energy X-ray absorptiometry and markers of bone metabolism and androgens/17-hydroxyprogesterone levels were investigated. All, including older (>30 years), CAH patients had lower BMD in all measured sites compared with control subjects. The null group demonstrated lower BMD in more locations than the other groups. Osteoporosis/osteopenia was present in 81% of CAH patients compared with 32% in controls (≥30 years). Fracture frequency was similar, osteocalcin was lower, and fewer patients than controls had vitamin D insufficiency. IGF1 was elevated in the milder genotypes. In patients, total body BMD was positively correlated to weight, BMI, total lean body mass, and triglycerides, and negatively to prolactin. Patients on prednisolone had lower BMD and osteocalcin levels than those on hydrocortisone/cortisone acetate. Patients with poor control had higher femoral neck BMD. There were no differences in BMD between patients with an early vs late diagnosis. CAH males have low BMD and bone formation markers. BMD should be monitored, adequate prophylaxis and treatment established, and glucocorticoid doses optimized to minimize the risk of future fractures.

Fertility, sexuality and testicular adrenal rest tumors in adult males with congenital adrenal hyperplasia

ObjectiveFertility in males with congenital adrenal hyperplasia (CAH) is reported from normal to severely impaired. Therefore, we investigated fertility/fecundity, social/sexual situation, and pituitary–gonadal function in CAH males.Subjects and methodsThe patient cohort comprised 30 males, aged 19–67 years, with 21-hydroxylase deficiency. Their fertility was compared with age-matched national population data. For the evaluation of social/sexual factors and hormone status, age-matched controls were recruited (n=32). Subgroups of different ages (<30 years and older) and CYP21A2 genotypes (null (severe salt-wasting (SW)), I2splice (milder SW), and I172N (simple virilizing)) were also studied. Patients underwent testicular ultrasound examination (n=21) and semen analysis (n=14).ResultsFertility was impaired in CAH males compared with national data (0.9±1.3 vs 1.8±0.5 children/father, P<0.001). There were no major differences in social and sexual factors between patients and controls apart from more fecundity problems, particularly in the I172N group. The patients had lower testosterone/estradiol (E2) ratio and inhibin B, and higher FSH. The semen samples were pathological in 43% (6/14) of patients and sperm concentration correlated with inhibin B and FSH. Testicular adrenal rest tumors (TARTs) were found in 86% (18/21). Functional testicular volume correlated positively with the testosterone/E2 ratio, sperm concentration, and inhibin B. Patients with pathological semen had increased fat mass and indications of increased cardiometabolic risk.ConclusionsFertility/fecundity was impaired in CAH males. The frequent occurrence of TARTs resulting in testicular insufficiency appears to be the major cause, but other factors such as elevated fat mass may contribute to a low semen quality.

Cardiovascular risk, metabolic profile, and body composition in adult males with congenital adrenal hyperplasia due to 21-hydroxylase deficiency

Lifelong glucocorticoid therapy in patients with congenital adrenal hyperplasia (CAH) or the disease per se may result in increased cardiovascular risk. We therefore investigated cardiovascular and metabolic risk profiles in adult CAH males. We compared CAH males (n = 30), 19-67 years old, with age- and sex-matched controls (n = 32). Subgroups of different ages (< 30 years or older) and CYP21A2 genotypes (null, I2splice, and I172N as the mildest mutation) were studied. Anthropometry, fat and lean mass measured by dual-energy X-ray absorptiometry, lipids, liver function tests, homocysteine, lipoprotein-(a), glucose and insulin during an oral glucose tolerance test (OGTT), urine albumin, adrenal hormones, and 24 h ambulatory blood pressure measurements were studied. CAH males were shorter. Waist/hip ratio and fat mass were higher in older patients and the I172N group. Heart rate was faster in older patients, the I2splice, and I172N groups. Insulin levels were increased during OGTT in all patients and in the I172N group. γ-glutamyl transpeptidase was increased in older patients and in the I172N group. Testosterone was lower in older patients. Homocysteine was lower in younger patients, which may be cardioprotective. The cardiovascular risk seemed higher with hydrocortisone/cortisone acetate than prednisolone. Urinary epinephrine was lower in all groups of patients except in I172N. Indications of increased risk were found in CAH males ≥ 30 years old and in the I172N group. In contrast, younger CAH males did not differ from age-matched controls. This is likely to reflect a better management in recent years.

Early androgen exposure modulates spatial cognition in congenital adrenal hyperplasia (CAH)

Major questions remain about the exact role of hormones in cognition. Furthermore, the extent to which early perturbation in steroid function affects human brain development continues to be a wide open area of research. Congenital adrenal hyperplasia (CAH), a genetic disorder of steroid dysfunction characterized in part by in utero over-production of testosterone, was used as a natural model for addressing this question. Here, CAH (n=54, mean age=17.53, 31 female) patients were compared to healthy age- and sex-matched individuals (n=55, mean age=19.02, 22 female) on a virtual equivalent of the Morris Water Maze task [Morris, R., 1984. Developments of a water-maze procedure for studying spatial learning in the rat. J. Neurosci. Methods 11, 47-60], an established measure of sex differences in spatial cognition in rodents. Findings revealed that females with CAH with the most severe form of the disease and expected highest level of in utero exposure to androgens were found to perform similarly to both healthy males and CAH males, whereas strong sex differences were apparent in milder forms of the disorder and in controls. Moreover, advanced bone age, an indicator of long-term childhood exposure to testosterone was correlated with improved performance. The results indicate that individuals exposed to both excess androgens prenatally and prolonged exposure during childhood may manifest long-lasting changes in cognitive function. Such finding suggests a pivotal role of hormonal function on brain development in humans, mirroring results from the animal literature.

Spatial ability and prenatal androgens: meta-analyses of congenital adrenal hyperplasia and digit ratio (2D:4D) studies.

Hormonal manipulations indicate that early androgens organize sex differences in spatial ability in laboratory rats. In humans, spatial ability is also sexually dimorphic, and information about the effects of prenatal androgens on spatial ability can be obtained from studies of congenital adrenal hyperplasia (CAH) and the ratio of the second and fourth finger lengths (2D:4D). CAH is characterized by prenatal overproduction of adrenal androgens and several lines of evidence suggest that 2D:4D reflects prenatal androgen exposure. Some studies have found that these proxy measures of prenatal androgens predict spatial ability, others have found no significant relationship, and yet others have obtained results in the opposite direction. In light of these mixed findings, we conducted meta-analyses of published literature and unpublished results to determine if, across studies, either of these indicators of prenatal androgens predicts performance on spatial tasks that show a male advantage. In addition, we applied a trim and fill analysis to the data in search of asymmetry that might be an indication of publication bias. Results indicated that females with CAH perform better on these spatial tasks, and CAH males perform worse, than do controls. Little or no relationship exists between 2D:4D and spatial ability. Implications for possible hormonal contributions and the developmental timing of sex differences in spatial cognition are discussed.

Bone mineral density and body composition in congenital adrenal hyperplasia.

The purpose of this study was to assess whether replacement doses of glucocorticoid hormones administered to patients with congenital adrenal hyperplasia (CAH) cause changes in body composition, including either generalized or regional osteoporosis. In 21 patients with 21-hydroxylase deficiency we measured height, body mass index, lean mass, fat mass, and whole body and regional bone mineral density (BMD). We measured the same parameters in 21 age- and sex-matched control patients. The CAH group (aged 8-32 yr) showed significantly reduced mean height compared with both standard data (P = 0.0015) and the control group (P = 0.009). There were no significant differences in mean body mass index between the CAH group and the standard data (P = 0.13) or the control group (P = 0.87). CAH males had significantly higher fat/lean mass ratios than control males (P = 0.005). There were no significant differences in whole body mean bone mineral apparent density values between the CAH and control groups (P = 0.39). There were, however, significant differences in whole body BMD z scores between the CAH and control groups and the reference data (P = 0.027 and P = 0.004, respectively). No significant differences were observed between the total CAH and control groups with respect to spinal bone mineral apparent density; however CAH males had significantly lower mean adjusted spinal BMD than the male controls (P = 0.02). We conclude that although replacement therapy with glucocorticoid and mineralocorticoid hormones in our group of CAH patients may not be optimal with regard to longitudinal growth, it is not deleterious in terms of general bone mineralization. It may decrease spinal BMD in CAH males. We also conclude that the relevance of Hologic reference data for BMD to an Australian population is uncertain, and there is a need for Australian standard data.

Dermatoglyphics in congenital adrenal hyperplasia (CAH).

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).