Type 2 diabetes mellitus in women with polycystic ovary syndrome during a 24-year period: importance of obesity and abdominal fat distribution.

STUDY QUESTION: What are the predictive factors for later development of type 2 diabetes (T2DM) in women with polycystic ovary syndrome (PCOS)? SUMMARY ANSWER: Obesity and abdominal fat distribution in women with PCOS in the mid-fertile years were the major risk factors for T2DM development 24 years later when lifestyle factors were similar to controls. WHAT IS KNOWN ALREADY: Women with PCOS have an increased prevalence of T2DM. STUDY DESIGN SIZE DURATION: A longitudinal and cross-sectional study was performed. Women with PCOS were examined in 1992 and in 2016. Randomly selected, age-matched women from the general population served as controls. PARTICIPANTS/MATERIALS SETTING METHODS: Women with PCOS (n = 27), attending an outpatient clinical at a tertiary care centre for infertility or hirsutism were diagnosed in 1992 (mean age 30 years) and re-examined in 2016 (mean age 52 years). Women from the World Health Organization MONItoring of trends and determinants for CArdiovascular disease (WHO MONICA-GOT) 2008, aged 38-68 years, served as controls (n = 94), and they were previously examined in 1995. At both at baseline and at follow-up, women had blood samples taken, underwent a clinical examination and completed structured questionnaires, and the women with PCOS also underwent a glucose clamp test at baseline. MAIN RESULTS AND THE ROLE OF CHANCE: None of women with PCOS had T2DM at baseline. At the 24-year follow-up, 19% of women with PCOS had T2DM versus 1% of controls (P < 0.01). All women with PCOS who developed T2DM were obese and had waist-hip ratio (WHR) >0.85 at baseline. No difference was seen between women with PCOS and controls regarding use of high-fat diet, Mediterranean diet or amount of physical activity at follow-up at peri/postmenopausal age. However, women with PCOS had a lower usage of a high-sugar diet as compared to controls (P = 0.01). The mean increases in BMI and WHR per year were similar in women with PCOS and controls during the follow-up period. LIMITATIONS REASONS FOR CAUTION: The small sample size of women with PCOS and the fact that they were recruited due to infertility or hirsutism make generalization to women with milder forms of PCOS uncertain. WIDER IMPLICATIONS OF THE FINDINGS: Obesity and abdominal fat distribution, but not hyperandrogenism per se, in women with PCOS in the mid-fertile years were the major risk factors for T2DM development 24 years later when peri/postmenopausal. Lifestyle factors were similar to controls at that time. STUDY FUNDING/COMPETING INTERESTS: The study was financed by grants from the Swedish state under the agreement between the Swedish government and the country councils, the ALF-agreement (ALFGBG-718611), the Gothenburg Medical Association GLS 694291 and 780821, the Swedish Heart Lung Foundation and Hjalmar Svensson Foundation. The authors have no conflict of interest.

Hearing loss but not bone-regulating hormones predicts fractures in older women-a 17-year follow-up of the Gothenburg BEDA study.

High-frequency hearing loss and S-Ca, but not hormones related to bone structure and strength, or lifestyle factors, predicted incident fractures during 17 years of follow-up in women up to 97 years of age. INTRODUCTION: The fracture risk increases and inner ear function deteriorates with increasing age. The aim of this study was to investigate whether hearing loss was of greater importance than bone-regulating hormones for the risk of fracture in elderly women. METHODS: In 1997, a random population sample of 63-82-year-old women, n = 552, underwent a physical examination, audiometry and blood sampling for analyses of serum albumin-adjusted calcium (S-Ca), parathyroid hormone (PTH), 25(OH) vitamin D and insulin-like growth factor-1 (IGF-1). Data on medication, lifestyle, previous fractures, hearing, vision and dizziness were obtained using questionnaires. Data on subsequent fractures were retrieved, and censored at death, through December 2013. RESULTS: In 1997, 228 women (41%) reported a previous fracture, most commonly of the wrist (18%). During the following 17 years, 323 fractures occurred in 207 women (38%). Hip fractures were the most frequent, in 96 women (17%). In a Cox regression analysis adjusted for age and previous fractures, hearing loss, reflected by a high pure tone average ≥ 59 dB, almost doubled the risk of a subsequent fracture (hazard ratio (HR) 1.81, 95% CI 1.25; 2.61, p = 0.002). S-Ca (HR 1.21 (1.02; 1.44) p = 0.028) also predicted future fractures, whereas PTH, IGF-1, 25(OH) vitamin D, hormone replacement therapy, smoking, degree of physical activity, impaired vision and dizziness did not. CONCLUSION: Hearing loss and higher S-Ca, but not bone-regulating hormones, medication or lifestyle factors predicted incident fractures, mainly caused by falling, during 17 years of follow-up in women up to 97 years of age.

A mechanistic linkage between oral lichen planus and autoimmune thyroid disease.

OBJECTIVE: To determine the levels of antithyroid antibodies and thyroid hormones in the sera of patients with oral lichen planus (OLP), and to quantify the expression of thyroid proteins in OLP lesions. SUBJECTS AND METHODS: Venous blood samples were drawn from 110 patients with OLP who had no history of thyroid disease or levothyroxine supplementation (OLP+/LT4 -). A random population sample of 657 healthy subjects was used as the control group. Two additional groups were used as comparators. Immunohistochemical and qPCR analyses were performed on tissue specimens collected from the patients with OLP and thyroid disease and healthy subjects. RESULTS: No association was found between the presence of antithyroid antibodies and OLP. More patients in the OLP+/LT4 - group showed high levels of thyroid-stimulating hormone and low levels of free thyroxine than were seen in the control group. Thyroid-stimulating hormone receptor was more highly expressed in the OLP lesions of patients with thyroid disease than in the healthy oral mucosa. CONCLUSIONS: A significant number of patients with OLP who are not previously diagnosed with thyroid disease have thyroid parameters that are compatible with hypothyroidism. The expression of thyroid-stimulating hormone receptor in OLP lesions suggests that mechanisms related to autoimmune thyroid disease are involved in the aetiology of OLP.

Case report: fast reversal of severe osteoporosis after correction of excessive levothyroxine treatment and long-term follow-up.

This case report describes a 38-year-old woman, who presented with bilateral femoral stress fractures and osteoporosis after years of excessive levothyroxine treatment. Her bone health was restored rapidly and long-lasting with the reduction of levothyroxine dosage. No bone-active treatment was warranted. INTRODUCTION: Hyperthyroidism is a known risk factor for osteoporosis and fractures. Recent studies on patients with serum thyrotropin-suppressive therapy have not, however, indicated adverse effects on bone during long-term follow-up. METHODS: This case report describes long-term follow-up data of a clinically euthyreoid patient, who developed symptomatic osteoporosis due to excessive levothyroxine treatment. RESULTS: After correction of levothyroxine dosage, her bone mineral density (BMD) and previously elevated serum osteocalcin levels normalized rapidly and she remained free from fractures during 23 years of follow-up over menopause. CONCLUSION: Excessive TSH suppression contributed to the secondary osteoporosis in this patient; BMD normalized after dose reduction of levothyroxine and no fractures occurred during 23 years' follow-up. Some patients develop severe osteoporosis if they are over-substituted with levothyroxine, and decent follow-up of patients with levothyroxine supplementation is mandatory.

Serum IGF-1 is higher in patients with idiopathic normal pressure hydrocephalus than in the population.

BACKGROUND: Hypopituitarism has been reported in patients with idiopathic normal pressure hydrocephalus (iNPH), which could enhance characteristic symptoms like impaired wakefulness, gait, body balance, and subcortical cognitive deterioration. PURPOSE: To compare basal serum levels of pituitary and sex hormones and serum insulin-like growth factor-1 (S-IGF-1) in patients with iNPH and an age-matched control population, and to correlate the preoperative hormone levels with symptoms and signs pre-operatively and three months after surgery. METHODS: A cross-sectional case control design was used. Patients diagnosed with iNPH, n=108 (65 men and 43 women, mean age 72.3 years), were consecutively included during 2006-2011 at Sahlgrenska University Hospital, Gothenburg, Sweden. S-TSH, S-free T4, S-FSH, S-LH, S-prolactin, plasma ACTH, S-testosterone, S-oestradiol and S-IGF-1 were examined. Symptoms and signs were scored using the iNPH scale score. Population controls, n=146, were recruited from the WHO MONICA project, Gothenburg in 2008. RESULTS: Men and women with iNPH had higher S-IGF-1 than controls (p<0.001). Women with iNPH had lower S-TSH (p=0.016) than controls, but the frequency of levothyroxine substitution was similar. Among men, a higher level of S-IGF-1 was associated with milder symptoms, while higher levels of S-FSH and S-LH were associated with more severe symptoms. CONCLUSIONS: Patients with iNPH did not have lower levels of pituitary or sex hormones but presented with higher levels of S-IGF-1, compared with healthy, age-matched controls. Higher S-IGF-1 in men was related to milder mental and physical symptoms and signs.

Obstetric outcomes in women with Turner karyotype.

CONTEXT: Women with Turner syndrome (TS) have high risk of cardiovascular complications and hypertensive disorders. Few studies have analyzed obstetric outcome in women with TS. OBJECTIVE: This study compared obstetric outcome in women with TS karyotype with women in the general population. DESIGN: The Swedish Genetic Turner Register was cross-linked with the Swedish Medical Birth Register between 1973 and 2007. Obstetric outcome in singletons was compared with a reference group of 56,000 women from the general population. Obstetric outcome in twins was described separately. RESULTS: A total of 202 singletons and three sets of twins were born to 115 women with a TS karyotype that was unknown in 52% at time of pregnancy. At first delivery, TS women of singletons were older than controls (median 30 vs. 26 yr, P < 0.0001). Preeclampsia occurred in 6.3 vs. 3.0% (P = 0.07). Aortic dissection occurred in one woman. Compared with the general population, the gestational age was shorter in children born by TS women (-6.4 d, P = 0.0067), and median birth weight was lower (-208 g, P = 0.0012), but sd scores for weight and length at birth were similar. The cesarean section rate was 35.6% in TS women and 11.8% in controls (P < 0.0001). There was no difference in birth defects in children of TS women as compared with controls. CONCLUSIONS: Obstetric outcomes in women with a TS karyotype were mostly favorable. Singletons of TS women had shorter gestational age, but similar size at birth, adjusted for gestational age and sex. Birth defects did not differ between TS and controls.

High serum total cholesterol is a long-term cause of osteoporotic fracture.

SUMMARY: Risk factors for osteoporotic fractures were evaluated in 1,396 men and women for a period of 20 years. Serum total cholesterol was found to be an independent osteoporotic fracture risk factor whose predictive power improves with time. INTRODUCTION: The purpose of this study was to evaluate long-term risk factors for osteoporotic fracture. METHODS: A population random sample of men and women aged 25-64 years (the Gothenburg WHO MONICA project, N = 1,396, 53% women) was studied prospectively. The 1985 baseline examination recorded physical activity at work and during leisure time, psychological stress, smoking habits, coffee consumption, BMI, waist/hip ratio, blood pressure, total, HDL and LDL cholesterol, triglycerides, and fibrinogen. Osteoporotic fractures over a period of 20 years were retrieved from the Gothenburg hospital registers. Poisson regression was used to analyze the predictive power for osteoporotic fracture of each risk factor. RESULTS: A total number of 258 osteoporotic fractures occurred in 143 participants (10.2%). As expected, we found that previous fracture, smoking, coffee consumption, and lower BMI each increase the risk for osteoporotic fracture independently of age and sex. More unexpectedly, we found that the gradient of risk of serum total cholesterol to predict osteoporotic fracture significantly increases over time (p = 0.0377). CONCLUSIONS: Serum total cholesterol is an independent osteoporotic fracture risk factor whose predictive power improves with time. High serum total cholesterol is a long-term cause of osteoporotic fracture.

Women who gave birth to girls with Turner syndrome: maternal and neonatal characteristics.

BACKGROUND: The aim was to identify maternal risk factors in women giving birth to girls with Turner syndrome (TS) and to describe the characteristics of newborns with TS. METHODS: The Swedish Genetic Turner Register was cross-linked with the Swedish Medical Birth Register. Between 1973 and 2005, 494 children with TS were born. Maternal age, parity, height, smoking habits and neonatal characteristics; mode of delivery, gestational age, size at birth and Apgar score, were compared with women in the general population who gave birth to girls during the same period. RESULTS: More women with advanced maternal age (40+) delivered girls with TS, 3.2% when compared with 1.8% in the general population [OR 1.83, 95% confidence interval (CI) 1.09-3.08, after adjustment for year of birth]. Maternal height was inversely associated with TS pregnancies (P = 0.005). Late preterm birth occurred in newborns with TS in 10.5% when compared with 4.8% in the general population (OR 2.23; 95% CI: 1.67-2.97, after adjustment for year of birth and maternal age). Newborns with TS had birthweight less than -2SD in 17.8% and birth length less than -2SD in 21.0% when compared with 3.5 and 3.4%, in the general population (OR 6.55; 95% CI: 5.12-8.38 and OR 8.69; 95% CI: 6.89-10.97, after adjustment for year of birth and maternal age). CONCLUSION: Advanced maternal age and short stature were risk factors for giving birth to a girl with TS. More TS girls were born late preterm and were smaller for gestational age than non-TS girls in the general population.

Male risk factors for hip fracture-a 30-year follow-up study in 7,495 men.

SUMMARY: Risk factors for hip fracture were studied in 7,495 randomly selected men during 30 years; 451 men had a hip fracture. High degree of leisure-time, but not work-related, physical activity, high occupational class, and high body mass index (BMI) protected against hip fracture. Smoking, tall stature, interim stroke, and dementia increased the risk. PURPOSE: The purpose was to prospectively study risk factors for hip fracture in men. METHODS: We studied midlife determinants of future hip fractures in 7,495 randomly selected men aged 46-56 years in Gothenburg, Sweden. The subjects were investigated in 1970-1973 and followed for over 30 years. Questionnaires were used regarding lifestyle factors, psychological stress, occupational class, and previous myocardial infarction, stroke, and diabetes mellitus. Alcohol problems were assessed with the aid of registers. Using the Swedish hospital discharge register, data were collected on intercurrent stroke and dementia diagnoses and on first hip fractures (X-ray-verified). RESULTS: Four hundred fifty-one men (6%) had a hip fracture. Age, tall stature, low occupational class, tobacco smoking, alcoholic intemperance, and interim stroke or dementia were independently associated with the risk of hip fracture. There were inverse associations with leisure-time physical activity, BMI, and coffee consumption. The gradient of risk for one standard deviation of multivariable risk decreased with time since measurement yet was a good alternative to dual energy X-ray absorptiometry measurements. CONCLUSIONS: High degree of leisure-time physical activity, high occupational class, and high BMI protected against hip fracture. However, work-related physical activity was not protective. Smoking, tall stature, and interim stroke or dementia increased the risk.

Effect of climate therapy at Gran Canaria on vitamin D production, blood glucose and lipids in patients with psoriasis.

BACKGROUND: Climate therapy (heliotherapy) of psoriasis is an effective and natural treatment. Ultraviolet radiation (UVB) from the sun improves psoriasis and induces vitamin D(3) synthesis. OBJECTIVE: The aim of the study was to investigate the effect of climate therapy on vitamin D(3) synthesis, blood glucose, lipids and vitamin B12 in psoriasis patients. METHODS: Twenty Caucasian patients (6 women and 14 men; mean age, 47.2 years; range, 24-65) with moderate to severe psoriasis [mean Psoriasis Area and Severity Index (PASI) score 9.8; range, 3.8-18.8] received climate therapy at the Gran Canarias for 3 weeks. Blood samples were drawn before and after 15 days of sun exposure. In addition, the patients' individual skin UV doses based on UV measurements were estimated. RESULTS: Sun exposure for 15 days lead to a 72.8% (+/- 18.0 SD) reduction in the PASI score in psoriasis patients. Although no direct correlation was observed between PASI score improvement and UVB dose, the sun exposure improved the vitamin D, lipid and carbohydrate status of the patients. The serum concentrations of 25-hydroxyvitamin D [25(OH)D] increased from 57.2 +/- 14.9 nmol/L before therapy to 104.5 +/- 15.8 nmol/L (P < 0.0001) after 15 days of sun exposure; the serum levels of 1,25-dihydroxyvitamin D [1,25(OH)(2)D] increased from 146.5 +/- 42.0 to 182.7 +/- 59.1 pmol/L (P = 0.01); the ratio of low-density lipoprotein cholesterol and high-density lipoprotein cholesterol decreased from 2.4 to 1.9 (P < 0.001); and the haemoglobin A(1)c (HbA(1)c) levels decreased from 5.6 +/- 1.7% to 5.1 +/- 0.3% (P < 0.0001). CONCLUSION: Climate therapy with sun exposure had a positive effect on psoriasis, vitamin D production, lipid and carbohydrate status.

Cardiac malformations and hypertension, but not metabolic risk factors, are common in Turner syndrome.

Turner syndrome (TS) is caused by an X chromosome aberration and is characterized by endogenous estrogen deficiency secondary to ovarian dysgenesis and short stature. Our aim was to study the prevalence of cardiovascular malformations and cardiovascular risk factors (blood pressure, blood lipids and glucose, coagulation factors, social factors, smoking habits) in adults with Turner syndrome in comparison with a female random population sample. One hundred women with Turner syndrome (aged 16-71 yr) underwent physical examination, echocardiography, electrocardiography, and blood sampling. Seventy-one of them were matched for age [mean age, 33.7 +/- 11 yr (range, 25-64)] with a random population sample (n = 213) of women [mean age, 34.8 +/- 9 yr (range, 25-64)] from the World Health Organization's Monitoring of Trends and Determinants in Cardiovascular Diseases Project, Göteborg. Six percent of Turner syndrome women were smokers compared with 25% in the population (P < 0.001). Turner syndrome women were relatively heavier and had a lower degree of leisure time physical activity than controls (P < 0.001). Diabetes and treatment for hypertension were present in 3 and 22% among Turner syndrome women vs. 2% (not significant) and 3% (P < 0.001) in controls, respectively. Cardiovascular malformations were found among 17% in Turner syndrome women (45,X dominated) vs. 0.5% in controls (P < 0.001). Systolic but not diastolic blood pressure was higher in Turner syndrome women. No differences were seen in serum total cholesterol, high- or low-density lipoprotein cholesterol, triglycerides, lipoprotein (a), or plasma fibrinogen concentrations between patients and controls. Diabetes or hypertension was not related to karyotype. In conclusion, congenital cardiovascular malformations were frequent. Most cardiovascular risk factors (glucose and lipid levels, fibrinogen, smoking habits) were not increased, but hypertension was more common in Turner syndrome women.

Recommendations for the diagnosis and management of Turner syndrome.

Comprehensive recommendations on the diagnosis of Turner syndrome (TS) and the care of affected individuals were published in 1994. In the light of recent advances in diagnosis and treatment of TS, an international multidisciplinary workshop was convened in March 2000, in Naples, Italy, in conjunction with the Fifth International Symposium on Turner Syndrome to update these recommendations. The present paper details the outcome from this workshop. The genetics and diagnosis of the syndrome are described, and practical treatment guidelines are presented.

Ear and hearing in relation to genotype and growth in Turner syndrome.

Hearing loss, auricular anomalies and middle ear infections are common findings in many genetic disorders, but the mechanisms have remained unknown. We studied ear and hearing problems in Turner's syndrome (TS) in relation to the degree of X chromosome loss (i.e. degree of mosaicism) and growth. One hundred and nineteen girls and women with TS were studied regarding audiometry, fluorescent in situ hybridisation, serum concentration of insulin-like growth factor-1 (IGF-1) and body height. It was found that sensorineural hearing loss and occurrence of auricular anomalies were significantly increased the greater the proportion of 45,X cells in a particular individual (P<0.05 and P<0.001, respectively). Middle ear infections and sensorineural hearing loss were negatively correlated with IGF-1 (P<0.05 and P<0.001, respectively). Hearing correlated positively with height (P<0.01) and IGF-1 independently of age (P<0.05). Height correlated positively with IGF-1 (P<0.001). Auricular malformations, middle ear infections and hearing impairment in TS were interpreted as due to growth disturbances during development. A new hypothesis on the pathophysiology of external, middle and inner ear disorders due to a delayed cell cycle caused by chromosomal aberrations per se and not only to the specific X chromosome deletion is presented.

Calcaneal ultrasound measurements are determined by age and physical activity. Studies in two Swedish random population samples.

AIM: To present reference values and correlations with body composition, blood variables and lifestyle factors. SUBJECTS: Two random population samples from Göteborg, Sweden, one comprising 184 men and 455 women aged 25-64 years (MONICA) and the other 860 women aged 55-82 years (BEDA) were studied. METHODS: Calcaneal ultrasound measurement (LUNAR Achilles) and bioimpedance were measured. Smoking habits, coffee consumption, physical activity, psychological stress, education and marital status, as well as blood lipids, blood pressure, and fractures were studied. RESULTS: Broadband ultrasound attenuation and stiffness were higher in men than in women (P < 0. 001), but speed of sound did not differ between sexes. Speed of sound, broadband ultrasound attenuation and stiffness decreased with age (P < 0.001). In both sexes speed of sound, broadband ultrasound attenuation and stiffness correlated positively to body size variables, and negatively with smoking in women after adjustment for age. Speed of sound, broadband ultrasound attenuation and stiffness were positively related to physical activity in both sexes, and these relationships were the only ones that remained in multivariate analyses in addition to age (negative). Osteoporotic fractures increased with age. Speed of sound, broadband ultrasound attenuation and stiffness were lower amongst women with osteoporotic fractures. CONCLUSION: Speed of sound, broadband ultrasound attenuation and stiffness decreased with age and increased with physical activity, but body weight and height were not correlated in multivariate analyses. Osteoporotic fractures increased with age and were associated with lower calcaneal ultrasound values.

Postmenopausal osteoporosis is more related to hormonal aberrations than to lifestyle factors.

OBJECTIVE: Serum insulin-like growth factor-1 (IGF-1) decreases with increasing age and this process is more pronounced in women after the menopause in parallel with the increasing prevalence of osteoporosis. This study was designed to compare IGF-1 concentrations, vitamin D, intact parathyroid hormone (PTH) and lifestyle factors in postmenopausal, osteoporotic women with and without oestrogen replacement therapy (HRT), with an age-matched random population sample of women. DESIGN: Case control study. PATIENTS: Postmenopausal, osteoporotic women, n = 128, mean age 59 +/- 6 years, were compared with a female random population sample matched for age, n = 227, mean age 59 +/- 5 years, from the WHO MONICA Project, Göteborg, Sweden. Osteoporotic fractures had occurred in 56% of the patients compared with 4% of the controls (P < 0.001). MEASUREMENTS: Anthropometry, occupation, smoking habits, physical activity, blood pressure, IGF-1, vitamin D, intact PTH, blood lipids. RESULTS: There were no differences in occupational class, current or previous smoking habits, degree of physical activity during occupational or leisure time between the patients and controls. Osteoporotic women had lower body weight and body mass index than the controls (P < 0.001). Height, waist/hip ratio and osteocalcin were similar. 25(OH) vitamin D and 1,25(OH)2 vitamin D were lower (P < 0.05 and P < 0.01, respectively), PTH was higher (P < 0.001) and IGF-1 lower (P < 0.01) in osteoporotic women compared with the controls. IGF-1 was lower (P < 0.05), in spite of similar bone mineral density, in osteoporotic women without HRT than in those with HRT, who had IGF-1 concentrations similar to those of the population sample, of whom fewer than 10% had HRT. Among patients, IGF-1 did not correlate with serum oestradiol or bone mineral density. PTH correlated negatively to bone mineral density at the femoral site (r = - 0.29; P = 0.003). CONCLUSION: Osteoporosis in postmenopausal women is more related to hormonal aberrations than to lifestyle factors.

Osteoporosis and fractures in Turner syndrome-importance of growth promoting and oestrogen therapy.

OBJECTIVE: Turner syndrome (TS) is a chromosomal aberration (45,X) characterized by endogenous oestrogen deficiency and short stature. The aim was to study body composition, bone mineral density, fracture frequency, social and life style factors and biochemical bone markers, as well as hormones, in adults with TS in comparison with a female random population sample. PATIENTS: Seventy women with TS responded to questionnaires. They underwent physical examination, bone mineral density measurement with Dual Energy X-ray Absorptiometry (DEXA) and blood sampling. Mean age was 31 +/- 12 (range 16-71) years. A random population sample of women from the WHO MONICA Project, Göteborg (25-64 years) served as controls (n = 740). RESULTS: Women with TS were shorter than the controls and had lower body weight and lean body mass (P < 0.0001). Body mass index and waist/hip circumference ratio were higher in TS (P < 0.0001). Osteoporosis was present in seven TS women, six above 45 years of age. None of these had received oestrogen substitution continuously. Fractures (all types) were reported by 11 (16%) TS women (six (50%) above 45 years) compared with 5% in the population sample (P < 0. 001). Four TS women with fractures had osteoporosis, all above 45 years of age. Osteoporosis and fractures did not differ between women with the 45,X karyotype and those with mosaicism. Impaired hearing was reported by 40%, and 73% wore glasses. Six percent among TS were smokers compared with 25% in the population (P < 0.001). TS women reported a lower degree of leisure time physical activity than controls (P < 0.001). Parathyroid hormone and osteocalcin were higher among TS (P < 0.02 and 0.001). Insulin-like growth factor-I was similar. Ninety-one percent of all TS had oestrogen substitution and 96% of TS below 25 years of age had received growth hormone treatment. CONCLUSION: Osteoporosis and fractures were common above, but not below, 45 years of age in Turner syndrome. It is probable that modern therapy, including growth promoting and continuous oestrogen therapy, will prevent osteoporotic fractures in the future.

Increased fracture frequency in adult patients with hypopituitarism and GH deficiency.

Fracture frequency was studied in 107 hypopituitary patients with GH deficiency (GHD) (69 men, mean age 53 years, range 18-74 and 38 women, mean age 54 years, range 31-73). Routine hormonal replacement therapy was given, except GH. Five male patients and 15 female patients with untreated hypogonadism were allocated to a separate group. The mean duration of hypopituitarism was 13.4 years. The prevalence of a history of fractures was assessed using questionnaires. A subsample of the Göteborg WHO MONICA Project was used as a reference population (n = 323). The total fracture frequency was threefold higher (P < 0.001) in patients (24.1%) compared with controls (8.7%) (odds ratio 3.49) (1.85-6.56; 95% confidence intervals). In men (n = 64) the fracture frequency was 25.0%, compared with 7.8% among the controls (P < 0.001). In women (n = 23) the fracture frequency was 21.7%, compared with 9.5% among the controls (P = 0.08). The odds ratios for fracture frequency were 3.97 (1.81-8.40; 95% confidence intervals) and 2.64 (0.89-7.81; 95% confidence intervals) in men and women respectively. In conclusion, adult hypopituitary patients with GHD had a threefold increased fracture frequency compared with controls. Further studies are needed to ascertain whether long-term recombinant human GH treatment can reduce the fracture rate in hypopituitary patients with GHD.

Elevated fibrinogen levels decrease following treatment of acromegaly.

OBJECTIVE: Acromegaly is associated with increased morbidity and mortality from cardiovascular disease and from stroke in particular. Fibrinogen is an established risk factor for stroke and myocardial infarction and high levels of plasminogen activator inhibitor-1 (PAI-1) activity were predictive of a recurrent myocardial infarction. The aim of this study was to analyse fibrinogen and PAI-1 activity in patients with acromegaly before and after treatment. PATIENTS: Twenty patients with acromegaly were compared with healthy controls matched for sex (12 men, 8 women), age (mean 53 +/- 7 years), body mass index (mean 26.5 +/- 2.5 kg/m2) and smoking. Fibrinogen was also compared with a random population sample of men and women (n = 392), aged 25-64 years, from the WHO's MONICA Project, Göteborg, Sweden. RESULTS: The acromegalic patients had a higher lean body mass of 65 +/- 11 vs 59 +/- 11 kg (P < 0.05), lower body fat of 17 +/- 8 vs 25 +/- 10 kg (P < 0.01), higher plasma fibrinogen of 4.0 +/- 0.9 vs 2.4 +/- 0.5 g/l (P < 0.001) and plasma insulin of 15 +/- 14 vs 7 +/- 2 mU/l (P < 0.01), serum triglycerides of 1.5 +/- 0.5 vs 1.2 +/- 0.5 mmol/l (P < 0.05), as well as serum insulin-like growth factor-I (IGF-I) levels of 742 +/- 271 vs 168 +/- 51 micrograms/l (P < 0.001) compared with the matched controls. PAI-1 activity was similar, as was total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, fasting blood glucose and blood pressure for acromegalic patients compared with controls. All the acromegalic patients had higher fibrinogen levels (p < 0.001) than the population mean. Plasma fibrinogen correlated positively with serum IGF-I in acromegaly (r = 0.55, P < 0.05). Fibrinogen decreased to a mean value of 3.2 +/- 0.3 g/l on treatment. CONCLUSION: Acromegaly is associated with high fibrinogen levels which may be one explanation for the increased risk of cardiovascular events, and stroke in particular, in this disease. Fibrinogen levels decreased following treatment of acromegaly.

Sunlight increases serum 25(OH) vitamin D concentration whereas 1,25(OH)2D3 is unaffected. Results from a general population study in Göteborg, Sweden (The WHO MONICA Project).

OBJECTIVE: To determine serum 25-hydroxyvitamin D3 [25(OH)D3] and its 1-hydroxylated metabolite [1,25(OH)2D3] and relate them to anthropometric data, life-style habits, blood pressure and selected biochemical analytes. DESIGN: Random population samples of men and women. SETTING: Göteborg, Sweden, population size 450,000 inhabitants. The study was performed within the framework of the WHO MONICA Project. SUBJECTS: 2000 randomly selected subjects were invited to the main MONICA screening. Out of those 1421 (71%) participated. Fifty individuals in each of four age-groups, 25-64 years, were selected at random for the present analyses (184 men and 198 women). RESULTS: The concentration of 25(OH)D3 was similar in both sexes whereas 1,25(OH)2D3 concentration was higher in women than in men (P = 0.01). 25(OH)D3 correlated positively to sun exposure, physical activity and negatively to intact parathyroid hormone (PTH) in both sexes, and also negatively to blood pressure in men. The remaining significant relationship for 25(OH)D3, when age and sun exposure were taken into account in multivariate analyses, was a negative correlation to intact PTH in both sexes. 1,25(OH)2D3 correlated positively to intact PTH in both men and women, negatively to height in men, positively to fibrinogen in men and positively to psychological stress and osteocalcin in women. When all variables were included in multivariate analyses 1,25(OH)2D3 concentration correlated negatively to age and positively to intact PTH and osteocalcin in both sexes together. CONCLUSIONS: Sunlight was the only external factor that influenced 25(OH)D3 concentration whereas 1,25(OH)2D3 was unaffected by sun exposure. 1,25(OH)2D3 was not related to environmental or life style factors but declined by age and correlated positively to intact PTH and osteocalcin. SPONSORSHIP: Grants from the Swedish Medical Research Council and the Swedish Heart and Lung Foundation.

Serum intact parathyroid hormone in a random population sample of men and women: relationship to anthropometry, life-style factors, blood pressure, and vitamin D.

Intact parathyroid hormone (PTH) in serum was determined in a random population sample and was related to age, sex, body composition, life-style factors, blood pressure, blood lipids, plasma fibrinogen, and serum IGF-1, osteocalcin, and vitamin D. Within the framework of the WHO MONICA Project in the city of Göteborg, Sweden, 181 men and 166 women aged 25-64 years were studied. Intact PTH concentrations varied with age but were similar in both sexes (range 4-82 ng/liter) [mean (+/- SD) 23.8 +/- 10.4 ng/liter in men and 25.1 +/- 10.6 ng/liter in women]. Intact PTH concentrations increased with increasing age, body mass index, systolic blood pressure, and 1,25(OH)2D3 and decreased with increasing 25(OH)D3 in all subjects. Additionally, in men, intact PTH correlated positively to diastolic blood pressure and negatively to coffee consumption. In women, PTH also correlated negatively to smoking and IGF-1. In a multivariate analysis including all variables, age lost its significance. In both sexes there were independent positive relations between intact PTH and body mass index and 1,25(OH)2D3, and negative relations between PTH and smoking habits as well as 25(OH)D3; among men there was also negative relations between PTH and coffee consumption. The results indicate that life-style factors such as smoking and coffee consumption decrease the serum concentration of intact PTH, and the same effect is seen in individuals with low body mass index. Coffee intake, smoking, and low body mass index are also known to adversely affect bone mineral content, highlighting the relationship between PTH and bone metabolism.