Svend Juul

Morbidity in Turner Syndrome

Turner syndrome afflicts approximately 50 per 100,000 females and is characterized by retarded growth, gonadal dysgenesis, and infertility. Much attention has been focused on growth and growth promoting therapies, while less is known about the natural course of the syndrome, especially in adulthood. We undertook this study to assess the incidence of diseases relevant in the study of Turner syndrome. The study period was from January 1, 1984 to December 31, 1993, and the study base was all women living in Denmark during the study period. We used data from the Danish Cytogenetic Central Register and the Danish National Registry of Patients to assess morbidity. This study supports several earlier studies reporting increased morbidity and confirms results of a recent study on cancer in Turner syndrome. Women with Turner syndrome seem to have an increased incidence of fractures, osteoporotic fractures in adulthood, and non-osteoporotic fractures in childhood. Furthermore, diabetes mellitus, both NIDDM and IDDM, was found with a markedly increased incidence in Turner syndrome, as well as ischemic heart disease, hypertension, and stroke. The risk of cancer, except cancer of the large bowel, does not seem to be elevated in Turner syndrome. Our data suggest that patients with Turner syndrome are extraordinarily prone to abnormalities constituting the metabolic syndrome (e.g., hypertension, dyslipidaemia, NIDDM, obesity, hyperinsulinemia and hyperuricemia). The present data may help to explain the decreased life span found in patients with Turner syndrome.

Screening for abdominal aortic aneurysms: single centre randomised controlled trial

Abstract Objective To determine whether screening Danish men aged 65 or more for abdominal aortic aneurysms reduces mortality. Design Single centre randomised controlled trial. Setting All five hospitals in Viborg County, Denmark. Participants All 12 639 men born during 1921-33 and living in Viborg County. In 1994 we included men born 1921-9 (64-73 years). We also included men who became 65 during 1995-8. Interventions Men were randomised to the intervention group (screening by abdominal ultrasonography) or control group. Participants with an abdominal aortic aneurysm > 5 cm were referred for surgical evaluation, and those with smaller aneurysms were offered annual scans. Outcome measures Specific mortality due to abdominal aortic aneurysm, overall mortality, and number of planned and emergency operations for abdominal aortic aneurysms. Results 4860 of 6333 men were screened (attendance rate 76.6%). 191 (4.0% of those screened) had abdominal aortic aneurysms. The mean follow-up time was 52 months. The screened group underwent 75% (95% confidence interval 51% to 91%) fewer emergency operations than the control group. Deaths due to abdominal aortic aneurysms occurred in nine patients in the screened group and 27 in the control group. The number needed to screen to save one life was 352. Specific mortality was significantly reduced by 67% (29% to 84%). Mortality due to non-abdominal aortic aneurysms was non-significantly reduced by 8%. The benefits of screening may increase with time. Conclusion Mass screening for abdominal aortic aneurysms in Danish men aged 65 or more reduces mortality.

Prenatal and postnatal prevalence of Turner's syndrome : a registry study

Abstract Objective: To study prevalence of Turners syndrome in Denmark and to assess validity of prenatal diagnosis. Design: Study of data on prenatal and postnatal Turners syndrome in Danish Cytogenetic Central Register. Subjects: All registered Turners syndrome karyotypes (100 prenatal cases and 215 postnatal cases) during 1970-93. Main outcome measures: Prevalence of Turners syndrome karyotypes among prenatally tested fetuses and Turners syndrome among liveborn infants. Results: Among infant girls, prevalence of Turners syndrome was 32/100000. Among female fetuses tested by amniocentesis, prevalence of Turners syndrome karyotypes was 176/100000 (relative risk of syndrome, 6.74 compared with prevalence among untested pregnancies). Among female fetuses tested by chorion villus sampling, prevalence of syndrome karyotypes was 392/100000 (relative risk, 16.8). We excluded prenatal tests referred because of results of ultrasound scanning: among fetuses tested by amniocentesis revised relative risk was 5.68, while revised relative risk among fetuses tested by chorion villus sampling was 13.3. For 29 fetuses with prenatal diagnosis of possible Turners syndrome, pregnancy was allowed to continue and 24 children were live born. Thirteen of these children were karyotyped postnatally, and diagnosis of Turners syndrome had to be revised for eight, seven being normal girls and one boy. This gives tentative predictive value of amniocentesis in diagnosing Turners syndrome of between 21% and 67%. There was no significant relation between mothers age and risk of Turners syndrome. Conclusions: Discrepancy between prenatal and postnatal prevalence of Turners syndrome challenges specificity of prenatal examination in diagnosing Turners syndrome. Key messages Key Messages We used data from the Danish Cytogenetic Central Register to try to estimate whether this reflected a true rise in the prevalence of Turners syndrome Karyotypes of Turners syndrome were diagnosed prenatally at a much higher rate than the observed postnatal rate of the syndrome Of 24 children who were live born after prenatal diagnosis of possible Turners syndrome, 13 were karyotyped postnatally and diagnosis of Turners syndrome had to be revised for eight, seven being normal girls and one a boy. Discrepancy between prenatal and postnatal prevalence of Turners syndrome challenges specificity of prenatal examination in diagnosing Turners syndrome

Vitamin B6 Level Is Associated with Symptoms of Depression

Background: A low level of vitamin B6 might theoretically cause depression as vitamin B6 is a cofactor in the tryptophan-serotonin pathway. In the present study, we examined the association between depression and the phosphate derivative of vitamin B6 in plasma, pyridoxal phosphate (PLP). Methods: In 140 individuals, symptoms of depression were evaluated by the Major Depression Inventory, and biochemical markers of vitamin B deficiency were measured. Results: We found that 18 (13%) individuals were depressed. A low plasma level of PLP was significantly associated with the depression score (p = 0.002). No significant association was found between depression and plasma vitamin B12 (p = 0.13), plasma methylmalonic acid (p = 0.67), erythrocyte folate (p = 0.77), and plasma total homocysteine (p = 0.16). Conclusion: Our study suggests that a low level of plasma PLP is associated with symptoms of depression. Randomized trials are now justified and needed in order to examine whether treatment with vitamin B6 may improve symptoms of depression.

Association between atopic dermatitis and insulin-dependent diabetes mellitus: a case-control study

BACKGROUND Up to two-thirds of children with atopic dermatitis have IgE-mediated allergic reactions and a Th2 immune reactivity pattern with low production of interferon gamma and high production of interleukin 4 after allergen stimulation of T lymphocytes. Insulin-dependent diabetes mellitus (IDDM) seems to be associated with a Th1 immune reactivity pattern. We therefore postulated that these diseases may be inversely associated. METHODS We designed a case-control study including 920 children with IDDM, registered in the Danish Registry for Childhood Diabetes, and a sample of 9732 non-diabetic children registered in the Danish Medical Birth Registry. The children were aged 3-15 years. Information on atopic dermatitis was obtained by questionnaires. FINDINGS The cumulative incidence of atopic dermatitis up to age 15 years was 13.1% among children with IDDM and 19.8% in non-diabetic children (p<0.0001). Among children who developed IDDM, the incidence of atopic dermatitis was significantly lower than in the controls before onset of IDDM (73 cases in 5314 person-months vs 1375 in 57432 person-months; odds ratio 0.49 [0.39-0.63]). After onset of IDDM, diabetic and non-diabetic groups did not differ in incidence of atopic dermatitis (1.36 [0.89-2.07]). INTERPRETATION Our findings may be explained by different acquired or inherited reactivity patterns associated with atopic dermatitis (Th2) and IDDM (Th1). The results do not allow us to find out whether early development of atopic dermatitis reduces the risk of IDDM, or a propensity for IDDM reduces the risk of early-onset atopic dermatitis.

No effect of vitamin B-12 treatment on cognitive function and depression: a randomized placebo controlled study

BACKGROUND Associations between vitamin B-12 deficiency and impaired cognitive function and depression have been reported. METHODS A randomized placebo controlled study including 140 individuals with an increased plasma methylmalonic acid (0.40-2.00 micromol/l) not previously treated with vitamin B-12. Cognitive function was assessed by the Cambridge Cognitive Examination (CAMCOG), Mini-Mental State Examination (MMSE), and a 12-words learning test. Symptoms of depression were evaluated by the Major Depression Inventory. The main outcome measure was change in cognitive function and depression score from baseline to follow-up 3 months later. RESULTS At baseline 78 (56%) individuals had cognitive impairment judged from the CAMCOG score and 40 (29%) according to the MMSE; 18 (13%) individuals had symptoms of depression. No improvement was found in cognitive function comparing the treatment and placebo group (total CAMCOG score: P = 0.43), nor among individuals with only slightly impaired cognitive function (n = 44, total CAMCOG score: P = 0.42). The treatment group did not improve in depression score as compared to the placebo group (P = 0.18). LIMITATIONS The duration of impaired cognitive function was unknown. CONCLUSIONS A high proportion of individuals with an increased plasma methylmalonic acid had impaired cognitive function, and a rather high prevalence of depression was observed. However, vitamin B-12 treatment did not improve cognitive function or symptoms of depression within the 3-months study period.

The marker of cobalamin deficiency, plasma methylmalonic acid, correlates to plasma creatinine

Abstract. Hvas AM, Juul S, Gerdes LU, Nexø E (Aarhus University and Aarhus University Hospital, Aarhus, Denmark). The marker of cobalamin deficiency, plasma methylmalonic acid, correlates to plasma creatinine. J Intern Med 2000; 247: 507–512.

Frequent occurrence of pituitary apoplexy in patients with non-functioning pituitary adenoma

Background and objective  There is agreement in the literature that pituitary apoplexy is a rare disorder. As our experience differs from this view, we analysed the incidence in patients operated on for a nonfunctioning pituitary adenoma.

Atopic dermatitis is increased following vaccination for measles, mumps and rubella or measles infection.

The prevalence of atopic dermatitis increased markedly in the period 1960s to the 1990s. Earlier findings indicate that infections acquired in early life enhance or suppress the expression of atopic disease as a result of a change in immune reactivity. Our objectives were to examine the association between measles, mumps and rubella vaccination, measles infection and the risk of atopic dermatitis. A random sample of 9,744 children were followed up from birth to 3-15 years. Their parents responded to a questionnaire including highly structured questions on atopic dermatitis, measles, mumps and rubella vaccination and measles infection. Information on parental educational level was obtained from Statistics Denmark. The cumulative incidence of atopic dermatitis at age 14 was 19.7%. The confounder adjusted incidence ratio of atopic dermatitis among measles, mumps and rubella vaccinated children versus children not subjected to measles, mumps and rubella vaccination and measles infection was 1.86 (95% CI 1.25-2.79); the incidence ratio for measles-infected children was similar. The incidence of atopic dermatitis increased after measles, mumps and rubella vaccination and measles infection, which is surprising in view of the hygiene hypothesis. We suggest further study of the possible short-term and long-term effects of virus and bacteria on the immune responses and expression of atopic disease.

Retrospectively Sampled Time-to-Pregnancy Data May Make Age-Decreasing Fecundity Look Increasing

The retrospective study based on pregnancy samples is the most commonly used method for studying time to pregnancy. Using a simple Monte Carlo simulation, this note focuses on a particular selection bias problem associated with this design: even if each womans fecundity decreases with age, estimation of the effect of age may show the opposite trend. We recommend exercising increased caution in interpreting findings from pregnancy-based time-to-pregnancy studies.