Blood pressure and Turner syndrome.

INTRODUCTION: Elevated blood pressure (BP) is an important predictor of morbidity and mortality from cardiovascular disease. Patients with Turner syndrome (TS) have a higher morbidity and mortality in middle age than the normal population. As BP in childhood or early adulthood is predictive of BP later in adult life, we assessed manual and 24 h ambulatory BP in patients with TS to determine whether the BP pattern is altered at an early stage in these patients who are known to be at risk of cardiovascular disease. PATIENTS AND METHODS: We studied manual and 24 h ambulatory BP profiles in 75 girls with Turner syndrome, age range 5.4-22.4 years. A monitor with an oscillometric device (SpaceLabs model 90207) and an appropriate sized cuff was used. BP was measured during the day-time (0800-2000 h) and the night-time periods (2200-0800 h). The BP measured were compared with population standards. The effect of different growth promoting agents on BP was also evaluated. RESULTS: Mean manual and 24 h ambulatory BP measurements were 118/77 mmHg (range 95/60-140/102) and 115/70 mmHg (range 93/57-154/99), respectively. There was minimal difference between the two methods with a positive bias of 2.4 mmHg for diastolic BP and a negative bias of 2.1 mmHg for systolic BP. The mean standard deviation scores (SDS) corresponding to the mean BP recordings were 24 h systolic + 0. 81 (range - 1.26 to + 4.45), 24 h diastolic + 0.43 (range - 0.85 to + 3.42), day-time systolic + 1.08 (range - 0.95 to + 4.72), day-time diastolic + 0.70 (range - 0.94 to + 3.71), night-time systolic + 0. 22 (range -2.2 to + 3.64) and night-time diastolic - 0.18 (range -2. 0 to + 2.43). The SDS for both the mean 24 h and day-time systolic and diastolic BP were shifted to the right of the normal distribution. 57% of the girls had less than the normal 10% reduction in nocturnal systolic blood pressure. 17% had diastolic and 21% had systolic blood pressure above the 95th percentile for age and sex. There was no significant difference in the BP SDS between girls on no treatment and those receiving treatment. CONCLUSION: Over 50% of girls with Turner syndrome have an abnormal BP circadian rhythm, which is similar to adult patients with secondary hypertension. Patients with Turner syndrome have higher blood pressure measurements compared to published population standards, as evidenced by the shift to the right of both the systolic and diastolic BP SDS. These findings suggest that girls with Turner syndrome should be carefully monitored in childhood and adulthood for blood pressure and other cardiovascular risk factors.

The influence of renal and cardiovascular abnormalities on blood pressure in Turner syndrome.

INTRODUCTION: Patients with Turner syndrome (TS) are at an increased risk of morbidity and mortality from cardiovascular disease. This study was undertaken to establish the prevalence of hypertension in patients with TS and to establish to what extent cardiovascular or renal abnormalities contribute to the measured blood pressure. PATIENTS AND METHODS: 62 patients with TS, age 5.4-22.4 years, had 24 h-ABPM (ambulatory blood pressure monitoring), echocardiography, renal imaging and measurement of recumbent plasma renin activity (PRA). Blood pressure was compared with population standards. RESULTS: 21% of the TS study population had mean systolic and 17% mean diastolic 24 h-ABPM measurements above the 95th percentile for age and sex (i.e. mild hypertension). Borderline blood pressure (i.e. 90th to 95th percentile) was found in another 17% of the patients. 57% of the patients had a blunted (i.e. less than 10%) fall in the night-time blood pressure. 24% of the patients had a detectable cardiac abnormality, 42% a detectable renal abnormality and 52% were found to have raised plasma renin activity. The presence of a cardiac or renal abnormality had no significant effect on blood pressure. Blood pressure of patients on growth and/or pubertal therapy was not different from those patients on no such treatment. CONCLUSION: Over 30% of patients with Turner syndrome were found to be mildly hypertensive and over 50% had an abnormal diurnal blood pressure profile. In this study we were unable to demonstrate that the presence of renal or cardiac abnormalities had an effect on recorded blood pressure. The use of growth hormone and oestrogen to manage growth failure and pubertal delay did not seem to affect blood pressure. This study suggests that there is a high prevalence of raised blood pressure in Turner syndrome patients. The 24 h-ambulatory blood pressure monitoring profile suggests that this may be secondary in origin, but we were unable to demonstrate an underlying mechanism with the renal and cardiac investigations performed.

Gonadotrophin pulsatility in girls with the Turner syndrome: modulation by exogenous sex steroids.

OBJECTIVES: The endocrine manifestation of puberty, nocturnal pulsatile secretion of gonadotrophins precedes the physical manifestations by 2 years. Whether gonadal steroids and inhibin have a role to play in the regulation of pulsatile gonadotrophin release is unclear. The agonadal model, girls with Turner's syndrome (TS), has been used to determine the role of the hypothalamic pulse generator in the ontogeny of gonadotrophin secretion in man. We evaluated the ontogeny of gonadotrophin secretion in TS girls with respect to amplitude and frequency and compared these results to those obtained in a group of normal girls. The effects of treatment with ethinyloestradiol (EE2) or oxandrolone (OX) on parameters of gonadotrophin secretion were also evaluated. PATIENTS: We studied 32 girls with TS, aged 4.3-12.4 years. All were prepubertal at the start of the study and longterm follow up revealed that none entered spontaneous puberty. The pulse amplitude and frequency was evaluated and compared to the results obtained in 23 normal girls, aged 4.9-12.8 years who acted as controls. MEASUREMENTS: Samples were taken at 20 minute intervals for 24 h for the measurement of serum concentrations of luteinising (LH) and follicle stimulating (FSH) hormones. The girls were than randomized to receive EE2 or OX and were then re-admitted 6 months into the course of the treatment for a repeat 24 h serum profile of LH and FSH levels. RESULTS: The girls with TS showed a clearly defined dominant pulse periodicity of 180 min and that in the normal cohort was 160-220 min. The girls with TS had an increased oscillatory activity between 120 and 260 min compared to the normal. Mean 24 h serum gonadotrophin concentration in TS girls was always higher than in the normal cohort. The inflection points of the fitted polynomial regression equation relating sex hormone concentration with age was similar for the two groups. EE2 lead to a significant change in pulse periodicity in TS girls but OX had no significant effect on the pulse periodicity. CONCLUSION: These results demonstrate that girls with Turner syndrome have gonadotrophin pulse periodicity in the prepubertal years similar to those of normal girls. The oscillatory activity was much greater in girls with Turner syndrome at all ages in the prepubertal years, suggesting a role for the ovary in modulating gonadotrophin secretion in the prepubertal years. Our data confirm that in girls with Turner syndrome the normal pattern of gonadotrophin secretion evolving with time is preserved.

Cytogenetic and molecular investigations of Y chromosome sequences and their role in Turner syndrome.

It has been proposed that all live born females with Turner syndrome carry a cell line containing two sex chromosomes, which may be present at a low level of mosaicism (Hook & Warburton, 1983; Hassold et al. 1985; 1988; Connor & Loughlin, 1989). If the second sex chromosome is a Y, these patients are at risk of developing gonadoblastoma. In this study, 50 patients found to have a 45,X karyotype by conventional cytogenetic analysis, were screened by the polymerase chain reaction (PCR), for the presence of Y chromosome sequences. Two patients were positive for six of the eight Y chromosome loci tested and additional cytogenetic analysis confirmed the presence of a marker chromosome, in 8% and 3% of cells respectively. Fluorescence in situ hybridization (FISH) was used to confirm that the markers were of Y chromosome origin and helped to elucidate their structure. In addition, four other patients were found to have a Y chromosome by initial routine cytogenetic analysis. FISH, in conjunction with PCR, elucidated the structure of the Y chromosomes. This study illustrates the value of using a combination of cytogenetic and molecular techniques, to identify Y chromosome sequences in Turner syndrome.

Bacterial colonisation of leg ulcers and its effect on the success rate of skin grafting.

There is little information on the immediate and long-term results of skin grafting to chronic lower limb ulcers. Our experience in their management had led us to analyse, retrospectively, the results of split thickness skin grafts applied to lower limb ulcers in 88 consecutive patients. Graft take has been related to bacterial growth from ulcer swabs taken on admission, preoperatively and postoperatively. Follow-up was for a median of 18 months. Initial graft take varied from 20% to 100% (median 85%). Bacterial flora grown from the ulcer swabs varied with the duration of the ulcer and the treatment. Analysis by bacterial type has shown that Staphylococcus aurcus and Pseudomonas significantly reduced skin graft healing. Overall, 90% of these ulcers had healed with a median of 6 weeks' in-patient treatment. Examination of the swab results from the 8 ulcers that were slow to heal postoperatively and the 8 ulcers that recurred 6 days to 8 months after discharge from hospital revealed that 15 out of 16 (94%) grew S. aurcus; none had Pseudomonas isolated from them. After eighteen months 8% of these ulcers remain active. Aetiology appears important as this figure is 6% for limbs affected by venous disease only, 13.3% for limbs with arterial disease only and 13.6% for limbs with both venous and arterial disease.