| 1. |
- Falhammar, Henrik, et al.
(författare)
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Bone Mineral Density, Bone Markers, and Fractures in Adult Males with Congenital Adrenal Hyperplasia.
- 2013
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Ingår i: European journal of endocrinology / European Federation of Endocrine Societies. - 1479-683X. ; 168, s. 331-341
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: 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 versus overtreatment, and early versus late (>36 months) diagnosis were studied. Bone mineral density (BMD) measured by dual-energy x-ray absorptiometry (DXA) and markers of bone metabolism and androgens/17-hydroxyprogesterone levels were investigated. RESULTS: All, including older (>30 yrs), CAH patients had lower BMD in all measured sites compared to 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 to 32% in controls (≥30 yrs). Fracture frequency was similar, osteocalcin lower, and fewer patients than controls had vitamin D insufficiency. IGF-I was elevated in the milder genotypes. In patients, total body BMD was positively correlated to weight, BMI, total lean body mass, 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 versus late diagnosis. CONCLUSIONS: 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.
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| 2. |
- Falhammar, Henrik, et al.
(författare)
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Cardiovascular risk, Metabolic Profile, and Body Composition in Adult Males with Congenital Adrenal Hyperplasia due to 21-Hydroxylase Deficiency.
- 2011
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Ingår i: European journal of endocrinology. - 1479-683X. ; 164:1, s. 285-293
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Life-long 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. Subjects and Methods: 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 (DXA), lipids, liver function tests, homocysteine, lipoprotein(a), glucose and insulin during an oral glucose tolerance test (OGTT), urine albumin, adrenal hormones, and 24h ambulatory blood pressure measurements were studied. Results: 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. Gamma-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 compared to prednisolone. Urinary epinephrine was lower in all groups of patients except in I172N. Conclusions: 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.
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| 3. |
- Falhammar, Henrik, et al.
(författare)
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Fertility, Sexuality and Testicular Adrenal Rest Tumors in Adult Males with Congenital Adrenal Hyperplasia.
- 2012
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Ingår i: European journal of endocrinology. - 1479-683X. ; 166, s. 441-449
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Fertility in males with congenital adrenal hyperplasia (CAH) is reported from normal to severely impaired. We therefore investigated fertility/fecundity, social/sexual situation, and pituitary- gonadal function in CAH males.Subjects and methods: The patient cohort comprised 30 males with 21-hydroxylase deficiency, 19-67 yr. 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), I2splice (milder salt wasting), and I172N (simple virilizing) were also studied. Patients underwent testicular ultrasound examination (n=21), and semen analysis (n=14).Results: Fertility was impaired in CAH males compared to 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 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 tumours (TARTs) were found in 86% (18/21). Functional testicular volume correlated positively with the testosterone/estradiol ratio, sperm concentration and inhibin B. Patients with pathological semen had increased fat mass and indications of increased cardiometabolic risk.Conclusions: Fertility/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.
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| 4. |
- Falhammar, Henrik, et al.
(författare)
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Increased liver enzymes in adult women with congenital adrenal hyperplasia due to 21-hydroxylase deficiency.
- 2009
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Ingår i: Endocrine journal. - 1348-4540. ; 56:4, s. 601-8
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Tidskriftsartikel (refereegranskat)abstract
- The aims were assessing liver function tests (LFT) in women with congenital adrenal hyperplasia (CAH) on glucocorticoids. Sixty-one women with genetically verified CAH due to 21-hydroxylase deficiency, aged 18-63 years were compared to 61 controls. Serum alkaline phosphatase (ALP), alanine aminotransferase (ALT), aspartate aminotransferase (AST) and gamma-glutamyl transpeptidase (GGT), anthropometry and fat mass (dual energy X-ray absorptiometry) were measured. ALT and GGT were higher in the entire patient group (p=0.01 and 0.002); AST, GGT and ALP in patients > or =30 years (p=0.007-0.045); all LFT in salt-wasting (p<0.001-0.042); GGT in simple virilizing (p=0.008); ALT, GGT and ALP in Null/Null genotype (p=0.018-0.040); ALT and GGT in I2splice genotype (p<0.001 and 0.011). Using a recently proposed cut-off level for ALT (>0.317 microkat/L), 54% of patients vs 23% of controls had elevated levels (p=0.028). In patients, GGT and ALP correlated with waist circumference and with total body and trunk fat (r=0.274-0.406, p=0.001-0.043). However, ALT, GGT and ALP were increased even in non-obese patients (waist circumference < or =88 cm and body mass index <30 kg/m(2)) (p=0.012-0.045) mainly attributed to the patients > or =30 years who also demonstrated elevated insulin levels and HOMA-indices. In conclusion, compared with controls, women with CAH have higher LFT, in particular patients > or =30 years and those with severe forms, probably reflecting a higher lifetime glucocorticoid exposure. LFT were positively correlated to measurements of body fat. These women might have increased frequency of NAFLD. The finding of higher LFT also in non-obese patients suggests that not only central obesity but also glucocorticoids per se may influence.
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| 5. |
- Falhammar, Henrik, et al.
(författare)
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Metabolic profile and body composition in adult women with congenital adrenal hyperplasia due to 21-hydroxylase deficiency.
- 2007
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Ingår i: The Journal of clinical endocrinology and metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 92:1, s. 110-6
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Tidskriftsartikel (refereegranskat)abstract
- CONTEXT: The chronic, often supraphysiological glucocorticoid doses used in congenital adrenal hyperplasia (CAH) might increase morbidity in cardiovascular disease and diabetes. OBJECTIVE: Our aim was to assess risk factors for cardiovascular disease and diabetes in CAH women. SUBJECTS, METHODS, AND DESIGN: We compared 61 women, 18-63 yr, with CAH due to 21-hydroxylase deficiency with 61 age- and sex- matched controls. Twenty-seven were younger than 30 yr, and 34 were 30 yr or older. Anthropometry, fat and lean mass measured by dual-energy x-ray absorptiometry, serum lipids, insulin, and adrenocortical steroids were studied. MAIN OUTCOME MEASURE: Body composition and cardiovascular risk factors were the main outcome measures. RESULTS: Younger patients and controls had similar waist to hip ratio, lean and fat mass, and insulin. Older patients had higher waist to hip ratio, lean mass, and insulin than controls. Fat mass was similar to controls but higher than in younger patients. Lipid profiles were slightly more favorable in older patients than controls. Gestational diabetes was more common in patients (21% of pregnancies vs. 0, P < 0.026). Few older patients had hypertension, cardiovascular disease, or diabetes. Despite moderate glucocorticoid doses, most patients had suppressed androgens. CONCLUSIONS: No clear evidence of unfavorable cardiovascular risk factors were found. Increased fat mass and higher insulin levels were, however, found in patients older than 30 yr. High frequency of gestational diabetes is a risk marker for future diabetes. Lifelong follow-up, lifestyle modifications, and attempts to adjust and reduce the glucocorticoid doses seem important.
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| 6. |
- Falhammar, Henrik, et al.
(författare)
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Quality of life, social situation, and sexual satisfaction, in adult males with congenital adrenal hyperplasia.
- 2014
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Ingår i: Endocrine. - : Springer Science and Business Media LLC. - 1559-0100 .- 1355-008X. ; 47:1, s. 299-307
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 7. |
- Frisén, Lars, et al.
(författare)
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Gender role behavior, sexuality, and psychosocial adaptation in women with congenital adrenal hyperplasia due to CYP21A2 deficiency
- 2009
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Ingår i: J Clin Endocrinol Metab. - : The Endocrine Society. ; 94:9, s. 3432-9
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Tidskriftsartikel (refereegranskat)abstract
- CONTEXT: Gender-atypical behavior has been described in young girls as well as in women with congenital adrenal hyperplasia (CAH) due to a CYP21A2 deficiency. OBJECTIVE: The aim of the study was to assess health-related, psychosexual, and psychosocial parameters and correlate the results to CYP21A2 genotype. DESIGN AND PARTICIPANTS: Sixty-two Swedish women with CAH and age-matched controls completed a 120-item questionnaire and a validated quality of life instrument [psychological general well-being (PGWB) formula] to identify psychosexual and psychosocial parameters. The patients were divided into four CYP21A2 genotype groups. RESULTS: The women with CAH held more male-dominant occupations (30%) compared to controls (13%) (P = 0.04), especially those in the null genotype group (55%) (P = 0.006). They also reported a greater interest in rough sports (74%) compared to controls (50%) (P = 0.007). Eight women with CAH (14%) reported a prime interest in motor vehicles, compared to none of the controls (P = 0.002). Non-heterosexual orientation was reported by 19% of women with CAH (P = 0.005), 50% in the null genotype group (P = 0.0001), 30% in I2 splice (NS), and 5% in I172N (NS). PGWB total score did not differ between patients and controls. CONCLUSION: We identified increased gender-atypical behavior in women with CAH that could be correlated to the CYP21A2 genotype. This speaks in favor of dose-dependent effects of prenatal androgens on the development of higher brain functions. The impact of the disease on upbringing and interpersonal relationships did not correlate with disease severity, indicating that other factors, such as coping strategies, are important for psychosocial adaptation. This illustrates the need for psychological support to parents and patients.
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| 8. |
- Nordenskjöld, Agneta, et al.
(författare)
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Type of mutation and surgical procedure affect long-term quality of life for women with congenital adrenal hyperplasia.
- 2008
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Ingår i: The Journal of clinical endocrinology and metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 93:2, s. 380-6
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Tidskriftsartikel (refereegranskat)abstract
- CONTEXT: In congenital adrenal hyperplasia (CAH) caused by different mutations, feminizing surgery is mostly performed in childhood, and many patients are lost to follow-up. OBJECTIVE/PATIENTS: A follow-up study on 62 CAH women aged 18-63 yr and 62 age-matched controls to correlate findings of both operative method and mutation was performed. DESIGN: Semistructured interviews were performed in cases and controls, as well as a gynecological examination in the cases. The results were correlated with disease-causing mutations and earlier surgical procedures if performed. SETTING: The study was conducted at university hospital referral clinics. MAIN OUTCOME MEASURES: Gynecological examination in all cases correlated to previous surgery (n = 49), type of mutation, and questionnaire responses. RESULTS: Half of the CAH women claimed that the disease affected their sex life. The women were less satisfied with their genitals, whether operated or not. Clitoris size and functions were affected by the surgical method. Five women had a clinically evident vaginal stenosis on examination. However, almost half of patients experienced a narrow vagina. The overall psychosexual aspects of life were affected in these patients with later sexual debut, fewer pregnancies and children, and an increased incidence of homosexuality. These quality of life factors were correlated to the severity of the mutations. CONCLUSIONS: The overall quality of life in adult women with CAH is affected both by the type of mutation and operative procedure. Indications for clitoroplasty should be restrictive. Medical, surgical, and psychological treatment should be centralized.
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| 9. |
- Nordenström, Anna, et al.
(författare)
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Sexual function and surgical outcome in women with congenital adrenal hyperplasia due to CYP21A2 deficiency: clinical perspective and the patients' perception.
- 2010
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Ingår i: The Journal of clinical endocrinology and metabolism. - : The Endocrine Society. - 1945-7197 .- 0021-972X. ; 95:8, s. 3633-40
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Tidskriftsartikel (refereegranskat)abstract
- CONTEXT: Females with congenital adrenal hyperplasia (CAH) due to a CYP21A2 deficiency are exposed to androgens during fetal development, resulting in virilization of the external genitalia. Little is known about how these women feel that the disease has affected their lives regarding surgery and psychosexual adaptation. OBJECTIVE: Our objective was to investigate the correlation between the surgical results, the self-perceived severity of the disease, and satisfaction with sexual life and relate the results to the CYP21A2 genotype. DESIGN AND PARTICIPANTS: Sixty-two Swedish women with CAH and age-matched controls completed a 120-item questionnaire, and a composite score for sexual function was constructed. The surgical outcome, including genital appearance and clitoral sensitivity, was evaluated by clinical examination. The patients were divided into four CYP21A2 genotype groups. RESULTS: The sexual function score, but not for genital appearance, was higher in the patients satisfied with their sexual life. This was also true of the patients who were satisfied with the surgical result. There were discrepancies between the patients' perception of the impact of the condition on their sexual life and what health professionals would assume from clinical examination. The patients in the null genotype group scored lower on sexual function and satisfaction with their sexual life and had more surgical complications, also compared with the slightly less severe I2-splice genotype group. CONCLUSION: Our data show that the null genotype group was considerably more affected by the condition than the other groups and should be regarded as a subgroup, both psychologically and from a surgical perspective. Genotyping adds clinically valuable information.
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