Anaemia in patients with self-reported use of iron supplements in the BAriatric surgery SUbstitution and nutrition study: A prospective cohort study.

BACKGROUND AND AIMS: After bariatric surgery, micronutrient deficiencies may lead to anaemia. To prevent post-operative deficiencies, patients are recommended lifelong micronutrient supplementation. Studies investigating the effectiveness of supplementation to prevent anaemia after bariatric surgery are scarce. This study aimed to investigate the relationship between nutritional deficiencies and anaemia in patients who report use of supplementation two years after bariatric surgery versus patients who do not. METHODS AND RESULTS: Obese (BMI≥35 kg/m2) individuals (n = 971) were recruited at Sahlgrenska University Hospital in Gothenburg, Sweden between 2015 and 2017. The interventions were Roux-en-Y gastric bypass (RYGB), n = 382, sleeve gastrectomy (SG), n = 201, or medical treatment (MT), n = 388. Blood samples and self-reported data on supplements were collected at baseline and two years post treatment. Anaemia was defined as haemoglobin <120 g/L for females and <130 g/L for males. Standard statistical methods, including a logistic regression model and a machine learning algorithm, were used to analyse data. The frequency of anaemia increased from baseline in patients treated with RYGB (3·0% vs 10·5%; p < 0·05). Neither iron-dependent biochemistry nor frequency of anaemia differed between participants who reported use of iron supplements and those who did not at the two-year follow-up. Low preoperative level of haemoglobin and high postoperative percent excessive BMI loss increased the predicted probability of anaemia two years after surgery. CONCLUSION: The results from this study indicate that iron deficiency or anaemia may not be prevented by substitutional treatment per current guidelines after bariatric surgery and highlights there is reason to ensure adequate preoperative micronutrient levels. TRIAL REGISTRATION: March 03, 2015; NCT03152617.

Teriparatide treatment in severe osteoporosis - a controlled 10-year follow-up study.

BACKGROUND: Teriparatide was the first anabolic agent recommended for the treatment of osteoporosis. Long-term real-world, controlled studies are not available. The purpose was to evaluate the long-term effects of treatment with teriparatide on fractures and Health Related Quality of Life in subjects with established osteoporosis in comparison with placebo treated patients with osteoporosis and the general population. METHODS: A 10-year follow-up was performed after a prospective, open-labelled study with teriparatide 20 µg given subcutaneously daily for a mean of 18 months (range 14-24 months) in 40 women, mean age 69 years, with osteoporosis and vertebral compression. Placebo treated women, n = 25, mean age 60 years, from a randomized, double-blind, placebo-controlled growth hormone trial with daily subcutaneous injections for 18 months, with osteoporosis were used as controls. Dual energy x-ray absorptiometry and questionnaires were performed at start, after 18 months, after 36 months and after 10 years. Women, n = 233, of similar age from a random population sample, also served as controls and were followed in parallel. All fractures were X-ray verified. RESULTS: Fractures decreased from 100 to 35% in the teriparatide treated patients (p < 0.0001) to similar levels as in the population sample, 25 to 28% at start and after 10 years, respectively. Bone mineral density increased on teriparatide but returned to levels at treatment start after 10 years. Health Related Quality of Life was lower in the teriparatide group than in the population (p < 0.001) before and, after treatment and at 10 years. CONCLUSIONS: Anabolic hormonal treatment with teriparatide reduced fracture prevalence to similar levels as in the general population at 10 years' follow-up. Health Related Quality of Life was low in osteoporosis and unaffected by bone specific treatment.

Vitamin D-Binding Protein and the Free Hormone Hypothesis for Vitamin D in Bio-Naïve Patients with Psoriasis.

High levels of vitamin D-binding protein (DBP) have been reported in patients with psoriasis and the possibility of DBP as a marker of inflammation has been discussed. Furthermore, high DBP levels might negatively affect free 25(OH)D concentrations. According to the free hormone hypothesis, only the free fraction of a steroid hormone is capable of exerting biological action. Thus, free 25(OH)D level could be a better biomarker of vitamin D status than total 25(OH)D level. The objectives of this study were to identify the strongest determinants for DBP levels and to test the free hormone hypothesis for vitamin D in psoriasis. Additionally, we also aimed to investigate correlations between directly measured free 25(OH)D levels in serum and psoriasis disease severity compared to total 25(OH)D levels. This was a retrospective cross-sectional study including 40 bio-naïve patients with mild to severe plaque psoriasis. Psoriasis disease severity was evaluated using high sensitivity C-reactive protein (hsCRP), Psoriasis Area Severity Index (PASI) and visual analogue scale (VAS). Vitamin D metabolites including directly measured free 25(OH)D and serum DBP levels were measured. DBP levels were higher in patients with self-reported arthropathy than those without irrespective of confounding factors like sex, age and body weight. Total and free 25(OH)D levels correlated well (ρ = 0.77, p < 0.0001) and both were inversely correlated to intact parathyroid hormone (iPTH) (ρ = -0.33, p = 0.038 for total 25(OH)D and ρ = -0.40, p = 0.010 for free 25(OH)D). Only total 25(OH)D correlated to serum calcium levels (ρ = 0.32, p = 0.047). No correlations between any of the vitamin D metabolites and psoriasis disease severity were observed. In conclusion, DBP might be a new inflammatory biomarker in psoriasis, especially in psoriatic arthritis. Total 25(OH)D was a reliable measure for vitamin D status in this psoriasis cohort. However, evaluation of free 25(OH)D in patients with psoriatic disease and multiple co-morbidities and/or ongoing biologic treatment should be considered.

Health-related quality of life in hypothyroidism-A population-based study, the WHO MONICA Project.

OBJECTIVE: To explore health-related quality of life (HRQoL) among subjects with hypothyroidism compared to subjects without hypothyroidism in the general population. HRQoL is important in clinical practice. Hypothyroidism is prevalent, mainly found in women, and increasing with age. DESIGN: Cohort study of random population sample. PATIENTS: Women and men, n = 414 (39-78 years) from the WHO MONICA project, Gothenburg, Sweden, participated. Hypothyroidism was defined as subjects having levothyroxine supplementation or serum thyroid-stimulating hormone (S-TSH) >4.2 mU/L. MEASUREMENTS: Health-related quality of life was measured with Psychological General Well-Being Index (PGWB), Nottingham Health Profile (NHP), Short Form 36 Health Survey (SF-36) and a single item self-rated health scale (0-100), and stress was rated 1-6. The results were adjusted for age, sex and comorbidity using analysis of covariance (ANCOVA). RESULTS: Hypothyroidism was found in 70 subjects (17%). They scored worse HRQoL than controls regarding Sleep (p < .001), Social isolation (p = .01) and Total NHP (p < .05), and had more medication in general 2.7 ± 2.5 vs. 1.8 ± 2.1, p < .05. Subjects with levothyroxine (n = 40) showed similar results as the total hypothyroid group. Subjects unaware of their newly detected elevated STSH (n = 30) showed lower HRQoL in Sleep (p < .01) and Pain (p < .05) in NHP. HRQoL was similar in subjects with and without positive thyroperoxidase antibodies (TPO-Ab) either in those with hypothyroidism (44% TPO-Ab) or controls (9% TPO-Ab). CONCLUSION: Men and women with hypothyroidism in the general population reported having more issues with Sleep and Social isolation than those without hypothyroidism irrespective of TPO-Ab. Scores were similar in all of the other HRQoL domains measuredAQ5.

Impact of Etanercept on Vitamin D Status and Vitamin D-binding Protein in Bio-naïve Patients with Psoriasis.

High levels of serum vitamin D-binding protein have been shown previously in patients with psoriasis compared with healthy controls; a possible role in inflammation is implied. The primary objective of this study was to investigate the impact of 24-week etanercept treatment on vitamin D status and vitamin D-binding protein in patients with psoriasis. The secondary aim was to explore whether pre-treatment vitamin D levels could predict the treatment effect. A prospective observational study was performed, including 20 patients with psoriasis and 15 controls. Serum samples were analyzed for, among others, vitamin D metabolites, vitamin D-binding protein and highly sensitive C-reactive protein. Baseline levels of vitamin D-binding protein were higher in patients with self-reported arthropathy than in those without. After 24 weeks' treatment, an improvement in psoriasis was noted, as was a decrease in highly sensitive C-reactive protein. Vitamin D-binding protein decreased in those with self-reported arthropathy. Higher baseline levels of vitamin D were associated with faster and greater improvement in psoriasis. Vitamin D-binding protein may have an inflammatory biomarker role.

Case report: acromegaly and breast cancer in a woman with turner syndrome.

PURPOSE: To present a case with a woman with Turner syndrome (TS) with acromegaly and breast cancer, in her medical history. METHOD: A descriptive case report of a single patient. RESULTS: The woman had short stature and lack of puberty and was not treated with hormones. When she was 36-year-old, acromegaly was diagnosed. She was treated with transsphenoidal surgery, followed by external radiation on the adenoma, without any affection on the pituitary gland. Annual controls revealed ordinary pituitary axes during 40 years' follow-up. She was treated for hypertension, had an aortic dilatation and started menopausal hormone therapy (MHT),1 mg estradiol and 0.5 mg norethisterone acetate daily, at the age of 50, due to osteoporosis. At the age of 60, she was diagnosed with breast cancer at the mammography screening. After, mastectomy, neoadjuvant radiation, and treatment with tamoxifen citrate were given due to the tubular breast cancer. CONCLUSIONS: Despite a possible growth hormone (GH) resistance and lack of endogenous estradiol in women with TS, this patient was diagnosed with acromegaly and breast cancer. This case demonstrates the potential for co-occurring two hormonally active tumors in a woman with TS with monosomy karyotype.

Hyperparathyroidism in men - morbidity and mortality during 21 years' follow-up.

Hyperparathyroidism (HPT), including normocalcaemic, vitamin D sufficient (Serum (S)-25(OH)D ≥ 50 nmol/L) hyperparathyroidism (nHPT), has increasingly been diagnosed in the last few decades due to the more common use of the serum parathyroid hormone (S-PTH) assay. We investigated if men with HPT had higher morbidity and mortality than men without HPT during 21 years' follow-up.A random population sample of 750 men, all 50 years of age, was examined in 1993. Endpoints were retrieved 21 years later at 71 years of age.Albumin-corrected serum (S) calcium, S-25-hydroxyvitamin D and S-PTH were assessed along with data on cardiovascular risk factors and medication. Outcome data on fractures, stroke, myocardial infarction, cancer and death were retrieved in 2014; 21 years after primary assessment. The prevalence of HPT at 50 years of age was 9.3%; nHPT 2.8%, primary HPT 0.4%, secondary HPT 0.4%, and HPT with vitamin D insufficiency 6%. Fracture rate, myocardial infarction, stroke, cancer and death occurred similarly in men with or without HPT, as well as in men with nHPT as compared with men without calcium/PTH aberrations during 21 years' follow-up. S-PTH was evenly distributed in the univariable analyses for each outcome. Cox regression analyses showed no increase in serious morbidity or in mortality in men with HPT, irrespective of cause, compared with men with normal S-PTH over a 21-year period. None had HPT at a S-25(OH)D level of 100 nmol/L.

Higher menopausal age but no differences in parity in women with polycystic ovary syndrome compared with controls.

INTRODUCTION: To address the question of whether women with polycystic ovary syndrome (PCOS) reach menopause later than age-matched controls, we conducted a follow-up cohort study of women with well-characterized PCOS that was diagnosed 24 years ago. The hypothesis was that women with PCOS would reach menopause later than non-PCOS women. Parity during these 24 years was also studied. MATERIAL AND METHODS: Twenty-seven women diagnosed with PCOS in 1992 (mean age 29.5 years) were re-examined in 2016 (mean age 52.4 years). Randomly selected women, n = 94 (mean age 52.4 years), from the same geographic area included in the World Health Organization MONICA study, Gothenburg, Sweden, served as controls. RESULTS: The mean menopausal age in women with PCOS was higher than in controls (53.3 ± 2.2 years vs 49.3 ± 3.5 years, P < 0.01). Serum-follicle stimulating hormone levels were lower in the PCOS women than in controls (31.0 ± 28.1 IU/L vs 52.3 ± 37.7 IU/L, P = 0.01). There was no difference in parity between women with PCOS (1.9 ± 1.3 children, range 0-4) and controls (1.7 ± 1.0, range 0-4 children). CONCLUSIONS: Women with PCOS reached menopause 4 years later and had lower serum-follicle stimulating hormone compared with age-matched controls. Neither parity nor nulliparity differed between women with PCOS and controls.

Comorbidity and health-related quality of life in Somali women living in Sweden.

Objective: To explore the relationship between low serum vitamin D levels and comorbidity in Somali women, immigrants to Sweden. Design and setting: Cohort study in a Primary Health Care Center and a University Hospital. Subjects: Somali women skin type V, n = 114, aged 18-56 years, from latitude 0-10○ N, living in Sweden, latitude 57○ N > 2 years were compared with women from a population sample, skin type II-III, n = 69, aged 38-56 years, the WHO MONICA study, Gothenburg, Sweden. Main outcome measures: Serum (S)-25(OH)D, S-parathyroid hormone (PTH), comorbidity and Health-Related Quality of Life (HRQoL) using the Short Form-36 (SF-36) and part of the EQ-5D questionnaires. All calculations were corrected for age. Results: Vitamin D deficiency (S-25(OH)D < 25 nmol/l) was found in 73% of the Somali women and in 1% of the controls (p < .0001). S-PTH was elevated (>6.9 pmol/l) in 26% and 9%, respectively (p < .004). Somali women used less medication, 16% vs. 55%, p < .0001) but more allergy medication, 11% vs. 7% (p = .006), had fewer fractures, 2% vs. 28% (p < .0001) and lower HRQoL in 7 out of 9 scales (p < .05-.001), than native controls. There were no differences in the prevalence of diabetes mellitus, hypothyroidism, positive thyroid peroxidase antibodies, vitamin B12 deficiency, celiac disease or hypertension. Conclusions: Vitamin D deficiency was common in Somali women living in Sweden, 73%, but comorbidity was low. Both mental, and especially physical HRQoL scores were lower in the Somali women. The effects of long-lasting deficiency are unknown. Key points The aim was to explore the relationship between vitamin D deficiency (S-25(OH)D < 25 nmol/l) and comorbidity in immigrants. Vitamin D deficiency was common in Somali women living in Sweden, 73%, but comorbidity of hypothyroidism, diabetes mellitus, hypertension, fractures and use of medications was low. Both mental, and especially physical, Health-Related Quality of Life were lower in the Somali women than in native Swedish women. The effects of long-lasting deficiency are unknown.

Prevalence and treatment of central hypogonadism and hypoandrogenism in women with hypopituitarism.

PURPOSE: Women with hypopituitarism have increased morbidity and mortality, and hypogonadism has been suggested to be a contributing mechanism. The purpose of this study was to investigate the prevalence of central hypogonadism and hypoandrogenism in women with hypopituitarism at a single Swedish center. METHODS: All consecutive women (n = 184) who commenced growth hormone (GH) replacement therapy at Sahlgrenska University Hospital in Gothenburg between 1995 and 2015 were included. In accordance with the Endocrine Society Clinical Practice Guidelines, strict criteria, based on menstrual history combined with laboratory measurements, were used to define central hypogonadism. Hypoandrogenism was defined as subnormal levels of dehydroepiandrosterone sulfate and/or androstenedione. RESULTS: Central hypogonadism was present in 78% of the women, in 75% of those ≤ 52 years and in 82% of those > 52 years of age. Hypoandrogenism was found in 61% of all the women and in 92% of those with adrenocorticotropic hormone (ACTH) deficiency. The estrogen substitution rate in hypogonadal women ≤ 52 years was lower than the hormonal substitution rate in the other pituitary hormone axes (74% versus 100%, P < 0.001). The use of estrogen substitution tended to decrease between 2000 and 2016. Few women received androgen treatment. CONCLUSIONS: In this first study of hypogonadism in women with hypopituitarism, using stringent diagnostic criteria for hypogonadism, the prevalence of central hypogonadism and low androgen levels was high and estrogen substitution was insufficient. Further studies are needed to elucidate the importance of hypogonadism and insufficient sex steroid replacement for the increased morbidity in hypopituitary women.

High androgen levels protect against hypothyroidism.

INTRODUCTION: Hypothyroidism is a common disorder, appearing mainly in women although less frequently found in women with polycystic ovary syndrome (PCOS). The objective was to test the hypothesis that hyperandrogenism might protect against hypothyroidism. MATERIAL AND METHODS: The data from three prospective follow-up studies (up to 21 years) and one register study were compared: women with PCOS (Rotterdam criteria), n = 25, women with Turner syndrome, n = 217, a random population sample of women, n = 315, and men, n = 95 (the WHO MONICA study). Findings were to be verified or rejected in all females, n = 553 716, from the same region. The proportion of hypothyroidism was calculated and thyroid peroxidase antibodies (TPO) in serum were measured. RESULTS: Hypothyroidism at >50 years of age was found in 8% of women with PCOS, 4% in men (PCOS vs. men; ns), 43% of women with Turner syndrome, irrespective of karyotype (p < 0.001 vs. PCOS), and in 17% of postmenopausal women in the population (p < 0.01 vs. PCOS). Elevated TPO were similar in PCOS and women and men in the population but higher in Turner syndrome. Hypothyroidism increased with age in all groups except PCOS women and men. In the register study, hypothyroidism was less common in women with PCOS >25 years (5.5%) than in women without PCOS (6.8%) from the same region (p < 0.01). CONCLUSIONS: Hypothyroidism was less frequently seen in women with PCOS and in men compared with women in the general population and among women with Turner syndrome. This was not explained by altered autoimmunity or the Y-chromosome. Androgens seem to protect against hypothyroidism.

Acute effects of physical exercise on the serum insulin-like growth factor system in women with fibromyalgia.

BACKGROUND: Increased Serum insulin-like growth factor-1 (S-IGF-1) has been noted after physical activity in healthy subjects, while the acute release of S-IGF-1 in relation to exercise has not previously been studied in women with fibromyalgia (FM). S-IGF-1 and its binding protein (S-IGFBP-3) are mediated by growth hormone and have anabolic effects on the skeletal muscle. Aim of the study was to investigate acute release of IGF-1 after aerobic exercise in women with FM. METHODS: The acute effect of physical exercise on S-IGF-1 and S-IGFBP-3 were studied in 22 women with FM and in 27 healthy controls during moderate and high-intensity cycling (i.e. ratings 12-13 and 15-17, on Borg's perceived exertion scale (RPE), respectively). Self-reported pain and fatigue were recorded. Differences within and between the two groups were analyzed. RESULTS: After 15 min of bicycling, S-IGF-1 and S-IGFBP-3 increased both within the group with FM and in the healthy controls (p < 0.01). The increases in S-IGF-1 did not significantly differ between the women with FM and the healthy control group (mean increase 11 ± 10 vs. 11 ± 15 ng/ml and 13 ± 10 vs. 19 ± 22 ng/ml) when bicycling at moderate or high intensity, respectively. Self-reported pain and fatigue during exercise, irrespective of intensity, were higher in women with FM compared with healthy controls (p < 0.001). CONCLUSIONS: Fifteen minutes bicycling at moderate intensity was sufficient to acutely mobilise S-IGF-1 in women with FM similarly to healthy controls in spite of higher score of fatigue and pain in women with FM. Hence, patients with FM were able to activate their skeletal muscle metabolism during a short, moderate bout of exercise and were not resistant to training effects. The result is important for encouraging clinical rehabilitation of patients with FM who commonly exercise at a moderate, rather than at a high-intensity level. TRIAL REGISTRATION: ClinicalTrials.govNCT01592916 , May 4, 2012.

Vitamin D treatment in Somali women living in Sweden - Two randomized, placebo-controlled studies.

OBJECTIVE: There is limited information about the prevalence of vitamin D deficiency and the effects of treatment on immigrants. The effects of oral vitamin D intake and UVB treatment on vitamin D status in healthy Somali women living in Sweden were analysed. DESIGN: Two studies were carried out; a randomized, double-blind, placebo-controlled study, with oral drops of 800 IU and 1600 IU cholecalciferol and similar amounts of placebo given daily during 12 weeks and a single-blind, placebo-controlled study, using UVB (4·3-8·7 J/cm(2) ) or Woods lamp (placebo) on the upper body, or the face and hands. PATIENTS: One-hundred fourteen Somali women, mean age 34 years, latitude 0-10°N, living in Sweden >2 years, latitude 57°N, participated. MEASUREMENTS: Serum 25-hydroxyvitamin D (S-25(OH)D) was monitored before, every 6 weeks and at 3 months after treatment. RESULTS: The majority of the women (n = 83, 73%) were vitamin D-deficient, S-25(OH)D < 25 nmol/l at start. There was a dose-dependent increase in S-25(OH)D levels (P = 0·001, stratified Jonckheere-Terpstra test) with a mean increase after twelve weeks in women treated with 800 IU/day and women treated with 1600 IU/day of 18 nmol/l (95% CI: 6-29, median = 17) and 29 nmol/l (95% CI: 17-42, median = 34), respectively. S-25(OH)D decreased during follow-up but remained above baseline levels. The placebo group remained unchanged throughout the study. UVB treatment increased S-25(OH)D dose-dependently after 6 weeks (P = 0·03, Jonckheere-Terpstra test). CONCLUSIONS: Vitamin D deficiency was common in immigrants living at higher latitudes. Vitamin D treatment increased S-25(OH)D levels dose-dependently during 3 months. The effect was maintained for another 3 months. At least 1600 IU/day is recommended. The dropout rate was high.

Normocalcaemic, vitamin D-sufficient hyperparathyroidism - high prevalence and low morbidity in the general population: A long-term follow-up study, the WHO MONICA project, Gothenburg, Sweden.

OBJECTIVE: There is limited knowledge about the natural history of normocalcaemic, vitamin D-sufficient hyperparathyroidism (nHPT). The aim was to study the prevalence of nHPT and its relation to morbidity. DESIGN: Cross-sectional and retrospective study at the Sahlgrenska University Hospital, Gothenburg, Sweden. SUBJECTS: A random population of 608 men and women, age 25-64 years, was studied in 1995 as part of the WHO MONICA study and reinvestigated in 2008 (n = 410, of whom 277 were vitamin D sufficient). MEASUREMENTS: A serum intact parathyroid hormone (S-PTH) ≥60 ng/l was considered as HPT, S-calcium 2·15-2·49 mmol/l as normocalcaemia and S-25(OH)D ≥ 50 nmol/l as vitamin D sufficiency. Data on fractures, stroke and myocardial infarction were retrieved until 2013, that is a 17-year follow-up. RESULTS: The prevalence of nHPT was 2·0% in 1995 (age 25-64) and 11·0% in 2008 (age 38-79). S-PTH was positively correlated with age and BMI. After adjustment for these variables, a high S-PTH level (≥60 ng/l) at follow-up was associated with previously low S-25(OH)D, high osteocalcin, S-PTH and both past and presently treated hypertension. No relation was seen with creatinine, cystatin C, malabsorption markers, thyroid function, glucose, insulin, lipids, calcaneal quantitative ultrasound, fractures, myocardial infarction, stroke or death at follow-up. CONCLUSIONS: This small random population study showed that nHPT was common, 11% at follow-up. Only one individual developed mild hypercalcaemia in 13 years. Previous S-PTH was predictive of nHPT and hypertension was prevalent, but no increase in hard end-points was seen over a 17-year period.

Sex steroid levels in women with hypopituitarism: A case-controlled observational study.

CONTEXT: Women with hypopituitarism remain at increased risk of morbidity and mortality. Insufficient replacement of sex steroids has been suggested as a contributing factor, but sex steroid levels in women with hypopituitarism have not been comprehensively mapped. OBJECTIVE: To quantify sex steroids in women with hypopituitarism by a high-sensitivity assay. METHODS: Using a combination of clinical and biochemical criteria, women with hypopituitarism (n = 104) who started growth hormone replacement 1995-2014 at a single center were categorized as eugonadal or having hypogonadotropic hypogonadism (HH). A population-based cohort of women (n = 288) served as controls. Eugonadal women and controls were categorized as pre-/postmenopausal and HH women as younger/older (≤ or >52 years). Dehydroepiandrosterone (DHEA), androstenedione, testosterone, dihydrotestosterone, progesterone, 17αOH-progesterone, estradiol and estrone were analyzed by a validated liquid chromatography-tandem mass spectrometry assay. RESULTS: Among both premenopausal/younger and postmenopausal/older women, women with HH had lower levels of sex steroid precursors (DHEA, androstenedione) and androgens (testosterone and dihydrotestosterone) than controls. Progesterone, 17αOH-progesterone, estrone and estradiol showed similar patterns. Women with HH and adrenocorticotropic hormone (ACTH) deficiency had markedly lower concentrations of all sex hormones than those without ACTH deficiency. CONCLUSION: This study demonstrates for the first time a broad and severe sex steroid deficiency in both younger and older women with HH, particularly in those with combined gonadotropin and ACTH deficiency. The health impact of low sex steroid levels in women with hypopituitarism requires further study and women with combined gonadotropin and ACTH deficiency should be a prioritized group for intervention studies with sex hormone replacement.

Autoimmune Disease in Turner Syndrome in Sweden: An up to 25 Years' Controlled Follow-up Study.

CONTEXT: Turner syndrome (TS) is the most common chromosomal aberration in women; it is the result of structural or numeric abnormalities in the X chromosome. Autoimmune hypothyroidism has been recognized as one of the more prominent disorders associated with TS. OBJECTIVE: This work aimed to study the prevalence of autoimmune diseases in TS. METHODS: A cross-sectional, longitudinal, 25-year follow-up study was conducted of patients from adult Turner centers at the University Hospitals, Sweden. During 1994 to 2020, a total of 503 women aged 16 to 71 years with TS were evaluated consecutively every fifth year according to national guidelines. A random population sample of women, n = 401, aged 25 to 44 years, from the World Health Organization Monitoring of Trends and Determinants for Cardiovascular Disease (MONICA) project served as controls. Serum thyrotropin, free thyroxine, vitamin B12, antithyroid peroxidase (anti-TPO), and antitransglutaminase antibodies were measured. RESULTS: Mean follow-up time (years) was 16 ± 7 for patients and 13 ± 1 for controls. From study start, the prevalence increased in TS for hypothyroidism 40% to 58%, vitamin B12 deficiency 5% to 12%, celiac disease 4% to 7%, positive anti-TPO 26% to 41%, and antitransglutaminase antibodies 6% to 8% (P < .0001 vs controls). Type 1 diabetes and Addison disease were rare. The only interrelationship was between hypothyroidism and vitamin B12 deficiency, both in TS and controls. No association between autoimmune disease and karyotype, antecedent growth hormone treatment, or ongoing estrogen hormone replacement, was seen in TS. CONCLUSION: In women with TS up to older than 80 years, more than half developed hypothyroidism, mainly autoimmune, during follow-up. Awareness of vitamin B12 deficiency and celiac disease throughout life is also recommended in women with TS.

Morbidity and mortality after childbirth in women with Turner karyotype.

STUDY QUESTION: Do women with Turner karyotype have increased mortality and morbidity in the years after childbirth? SUMMARY ANSWER: No mortality occurred during pregnancy and follow-up in women with Turner karyotype, but a higher rate of circulatory and endocrine diseases and a high risk of aortic aneurysm were confirmed. WHAT IS KNOWN ALREADY: Pregnancies in women with Turner karyotype are high-risk pregnancies with an increased risk of maternal mortality from aortic dissection and morbidity from hypertensive disorders. STUDY DESIGN, SIZE, DURATION: A retrospective Swedish population-based registry study of 124 women with Turner karyotype born between 1957 and 1987 and who gave birth between 1973 and 2010. Women with Turner karyotype without childbirth (n = 378) were selected as controls. A second control group consisted of women from the Swedish Medical Birth Register (MBR) (n = 1230) matched for maternal age, number of children and year of birth of the first child. PARTICIPANTS/MATERIALS, SETTING AND METHODS: Women with Turner karyotype were identified in the Swedish Genetic Turner Register. Data were obtained by using the unique personal identification number with cross linkage to the Swedish MBR, the Cause of Death Register, the National Patient Register and the Swedish Cancer Register. Hazard ratio (HR) with 95% confidence interval (CI) was used in the analysis of morbidity. MAIN RESULTS AND THE ROLE OF CHANCE: No mortality occurred in women with Turner karyotype and childbirth. Diseases of the circulatory system occurred more often in women with Turner syndrome under the age of 40 years compared with the MBR control group (HR 4.59; 95% CI 2.75-7.66) but was similar at or above the age of 40 years. Morbidity from circulatory diseases was increased before pregnancy (HR 3.83; 95% CI 1.02-14.43) and during pregnancy or within 1 year after (HR 5.78; 95% CI 1.94-17.24), but was similar after 1 or more years after delivery (HR 1.91; 95% CI 0.74-4.96). Aortic aneurysm occurred in 11/502 (2.2%) women with Turner karyotype and in three women (2.4%) during pregnancy. The long-term follow-up showed that aortic dissection was a common cause of death in young women with Turner karyotype without childbirth. A thorough cardiac evaluation before pregnancy in women with Turner karyotype is of utmost importance. LIMITATIONS, REASONS FOR CAUTION: Although this was a population-based registry study performed over a period of more than 20 years, a much longer follow-up and larger series are needed to assess rare events. The study also lacks information on phenotype and mode of conception in women with Turner karyotype. Women who gave birth probably represent a selection of healthier women with Turner karyotype. WIDER IMPLICATIONS OF THE FINDINGS: The high risk of aortic aneurysm in young women with Turner karyotype is in agreement with the literature.

No difference in morbidity between perimenopausal women with PCOS with and without previous wedge resection.

OBJECTIVE: Polycystic ovary syndrome (PCOS), affecting more than every 10th woman of reproductive age, is associated with increased risk factors for cardiovascular disease (CVD). Most knowledge regarding longtime consequences concerning morbidity is based on women where ovarian wedge resection (WR) was used as a surgical treatment, a method not used today. The aim of this study was to compare women with PCOS who had and had not undergone WR, regarding risk factors for CVD. The hypothesis was that women who had undergone WR had a more severe PCOS phenotype, and that this cohort thus had more associated CVD risk factors compared with women diagnosed through non-invasive methods. STUDY DESIGN: A cross-sectional study was performed. A PCOS cohort who underwent WR in the 1950-60 s (n = 27) were compared with a PCOS cohort diagnosed by NIH-criterions in the 1990s without WR (n = 32). Both cohorts were examined at perimenopausal age. RESULTS: No differences were seen in prevalence of hypertension, obesity or type 2 diabetes mellitus (T2DM) between the women with PCOS with or without WR, respectively. The results were persistent irrespective of the lower mean BMI in the WR group, 26.4 vs. 30.7 kg/m2, p = 0.01. In the stratified group of overweight and obese, there was no difference in T2DM 27% vs 25% or hypertension 27% vs 25%, in WR and non-WR women with PCOS, respectively. The cohort diagnosed through WR had higher free androgen index (6.3 vs. 2.1, p < 0.01) and total testosterone (2.20 vs. 0.99 nmol/L, p < 0.01). CONCLUSION: No differences in CVD risk factors were found in perimenopausal women with PCOS with or without a previous WR, and irrespective of body weight. The results indicate that CVD morbidity and mortality from studies in women with PCOS who have undergone WR are generalizable to women with PCOS who have not undergone WR.