Helena Filipsson Nyström

University of Gothenburg, Goeteborg, Västra Götaland, Sweden

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Publications (20)55.35 Total impact

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    ABSTRACT: Objective: Quality of life (QoL) is impaired in hypopituitary patients and in patients with primary adrenal insufficiency. The aim of this study was to analyze the impact of glucocorticoid (GC) replacement on QoL. The main hypothesis was that ACTH insufficient patients experience a dose dependent deterioration in QoL. Design, patients and methods: This was a retrospective analysis of data obtained from KIMS (Pfizer International Metabolic Database). Data from 2,737 adult growth hormone deficient (GHD) hypopituitary patients were eligible for analysis. Thirty-six percent were ACTH sufficient and 64% ACTH insufficient receiving a mean ±SD hydrocortisone equivalent (HCeq) dose of 22.3±8.7 mg (median 20.0). QoL at baseline and one year after commencement of GH replacement was assessed by the QoL-assessment of GHD in adults. Results: At baseline no significant difference in QoL was observed between ACTH sufficient and insufficient patients. Increasing HC dose was associated with worse QoL. Patients on HCeq ≤10 mg had the best and patients receiving ≥25 mg demonstrated poorest QoL. At one year of GH replacement therapy the mean improvement in QoL did not differ between ACTH sufficient and insufficient patients and no association was observed between HC dose and QoL-improvement.. Conclusion: Adult hypopituitary patients with untreated GH deficiency receiving GC replacement have similar QoL as ACTH sufficient patients. Among ACTH insufficient patients there is a dose-dependent association between increasing dose and impaired QoL. This association may be explained by supraphysiological GC exposure although it remains plausible that clinicians may have increased GC doses in order to address otherwise unexplained QoL deficits.
    European journal of endocrinology / European Federation of Endocrine Societies. 08/2014;
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    ABSTRACT: Objective: The number of studies on the incidence of pituitary adenomas (PA) is limited. The aim of this study was to evaluate the standardized incidence rate (SIR) of PA in western Sweden. Design, Subjects and Methods: Data from adult patients diagnosed with PA in 2001-2011, living in the Västra Götaland County, were collected from the Swedish Pituitary Registry (SPR). In addition, medical records on all patients diagnosed with PA at the six hospitals in the region were reviewed. In total, 592 patients were included in the study. Age standardised incidence rate, given as rate/100,000 inhabitants (95% CI), was calculated using the WHO 2000 standard population as a reference. Results: The total SIR for PA was 3.9/100,000 (3.6-4.3), 3.3/100,000 (2.9-3.7) for men and 4.7/100,000 (4.1-5.3) for women. In men, SIR increased with age, while in women SIR peaked at 25-34 years, mainly due to prolactinomas. Non-functioning PA (NFPA) was the most common PA (54%, 1.8/100,000 (1.6-2.0)) followed by prolactinomas 32%, 1.6/100,000 (1.3-1.9)), acromegaly (9%, 0.35/100,000 (0.25-0.45)), Cushing's disease (4%, 0.18/100,000 (0.11-0.25)) and TSH-producing PA (0.7%, 0.03/100,000 (0.00-0.05)). The proportion of macroadenomas for NFPA was 82%, prolactinomas 37%, GH-producing PA 77%, ACTH-producing PA 28%, and TSH-producing PA 100%. The lifetime risk for PA was 0.27% (0.24-0.31) in men and 0.29% (0.26-0.33) in women. Conclusion: This study provides a reliable estimate on the overall incidence of PAs and confirms an increased incidence of PA compared to studies conducted in the pre-MRI era. The lower proportion of prolactinomas compared to previous studies is probably explained by different criteria used.
    European journal of endocrinology / European Federation of Endocrine Societies. 08/2014;
  • Henrik Falhammar, Helena Filipsson Nyström, Marja Thorén
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    ABSTRACT: To determine quality of life (QoL) in adult males with congenital adrenal hyperplasia (CAH). CAH males with 21-hydroxylase deficiency (n = 30), 19-67 years old, were compared with controls (n = 32). QoL was assessed using questionnaires on general living conditions and sexual issues, and the psychological well-being index (PGWB) form. Fewer CAH males than controls were students (3 vs. 25 %, P = 0.028) and more had blue-collar work (57 vs. 33 %, P = 0.023). Patients were less interested in sports (47 vs. 72 %, P = 0.034) and art/literature/film (10 vs. 47 %, P = 0.004). PGWB total score was 82.7 ± 13.7 versus 87.0 ± 11.1 (P = NS), but hydrocortisone/cortisone acetate treated scored lower than controls and prednisolone treated. Glucocorticoid over-treated had lower QoL than those with poor control (PGWB total score 77.1 ± 13.5 vs. 92.4 ± 11.1, P = 0.026) and controls (P = 0.025). Total PGWB score was positively correlated with adrenal androgens and steroid precursors. Subscale scores indicated that patients with late diagnosis were more depressive (12.1 ± 2.8 vs. 13.9 ± 1.4, P = 0.011) and had a lower self-control (11.3 ± 3.6 vs. 13.1 ± 1.0, P = 0.019) compared with controls. Sexual satisfaction was similar in spite of more patients being sexually inactive (27 vs. 6 %, P = 0.040). Adult CAH males differed from controls with respect to type of occupation and spare time interests but had similar QoL despite being less sexually active. Optimizing glucocorticoid therapy might further improve QoL. Some disadvantages found in patients diagnosed late will hopefully not be seen in patients diagnosed by neonatal screening, but this has yet to be studied.
    Endocrine 01/2014; · 1.42 Impact Factor
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    ABSTRACT: Growth hormone deficiency (GHD) in adults is associated with decreased extracellular water volume (ECW). In response to GH replacement therapy (GHRT), ECW increases and blood pressure (BP) reduces or remains unchanged. Our primary aim was to study the association between polymorphisms in genes related to renal tubular function with ECW and BP before and 1 year after GHRT. The ECW measures using bioimpedance analysis (BIA) and bioimpedance spectroscopy (BIS) were validated against a reference method, the sodium bromide dilution method (Br-).
    PLoS ONE 01/2014; 9(8):e105754. · 3.53 Impact Factor
  • Eric Mohlin, Helena Filipsson Nyström, Mats Eliasson
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    ABSTRACT: Objective To investigate the long-term prognosis of patients with Graves' disease (GD) after antithyroid drug (ATD) treatment and follow-up outside of highly specialized care.Design and methodsMedical records of all patients diagnosed with first-time GD 2000-2010 with at least 6 months ATD treatment at a central hospital and follow up in primary health care in the county of Norrbotten in northern Sweden were retrospectively reviewed. Patients were followed for relapse until 31 December 2012. We included 219 patients (mean age 46 years, 82.5% women) with follow-up of maximum 10 years and 829 observed patient years. Data were analysed using Kaplan-Meier estimates and log-rank test.ResultsDuring the observation period, 43.5% of the patients had relapsed into active GD. Cumulative relapse rates were 22.6%, 30.2%, 36.9%, and 41.5% after 6 months, 1 year, 3 years, and 5 years, respectively. The presence of goitre (p=0.014) predicted relapse. Previous smoking was protective against relapse (p=0.003). The levels of fT4 or fT3, age, gender, current smoking, and ophthalmopathy did not predict relapse. Agranulocytosis was found in 1.7% (95% CI 0.7-4.0%).ConclusionA long-term remission of 56.5%, in an iodine-sufficient area where ATD is offered to most patients in the real world of central and district hospitals, is higher than in most studies. Relapse was most common during the first years, and prognosis was excellent after four years without relapse. The protective effect of previous smoking merits further research.
    European Journal of Endocrinology 12/2013; · 3.14 Impact Factor
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    ABSTRACT: Growth hormone (GH) deficient (GHD) adults have reduced serum concentrations of insulin-like growth factor I (IGF-I). GH replacement therapy increases serum IGF-I concentrations, however, the interindividual variation in treatment response is large and likely influenced by genetic factors. This study was designed to test the hypothesis that single-nucleotide polymorphisms (SNPs) in genes within the GH signaling pathway influence the serum IGF-I response to GH replacement. 313 consecutive GHD adults (58.1 % men; mean age 49.7 years) were studied before and after 1 week, 6 months and 1 year of GH treatment. GH dose was individually titrated to normalize serum IGF-I levels. Six SNPs in the GH receptor (GHR) and the GH signaling pathway (JAK2, STAT5B, SOCS2 and PIK3CB) genes were selected for genotyping. The GHR exon 3 deleted/full-length (d3/fl) polymorphism was analyzed using tagSNP rs6873545. After 1 week of GH replacement, homozygotes of the fl-GHR showed a better IGF-I response to GH than carriers of the d3-GHR (p=0.016). Conversely, homozygotes of the minor allele of PIK3CB SNP rs361072 responded better than carriers of the major allele (p=0.025). Compared to baseline, both SNPs were associated with the IGF-I response at 6 months (p=0.041 and p=0.047, respectively), and SNP rs6873545 was further associated with the IGF-I response at 1 year (p=0.041). Our results indicate that common genetic variants in the GH signaling pathway may be of functional relevance to the response to GH replacement in GHD adults.
    European Journal of Endocrinology 10/2013; · 3.14 Impact Factor
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    ABSTRACT: OBJECTIVE: Congenital adrenal hyperplasia (CAH) is an autosomal recessive inherited disorder in which the lack of 21-hydroxylase results in cortisol and aldosterone insufficiency and an overproduction of adrenal androgens. High levels of androgens in women may cause virilization of the larynx and a masculine voice. The purpose of the present study was to investigate subjective voice problems due to virilization in women with CAH. DESIGN/PATIENTS: Participants were 42 women with CAH between 25 and 71 years of age, and 43 age-matched female healthy control subjects. All patients, but two, were in good disease control. MEASUREMENTS: A validated Swedish version of the Voice Handicap Index (VHI) and questions related to voice virilization were used. Endocrine data were obtained from medical files. RESULTS: Patients scored significantly higher on VHI when the results were divided into no/mild, moderate and severe voice handicap as compared with the control subjects. They rated significantly higher for "dark voice" and for "being perceived as a man on the phone" compared to controls. Seven percent of the women with CAH had voice problems clearly related to voice virilization. High ratings of dark voice were significantly associated with long periods of under-treatment with glucocorticoids and higher bone mineral density but not with severity of mutation. CONCLUSION: Subjective voice problems due to voice virilization may occur in women with CAH. This further emphasizes the importance of avoiding long periods of increased androgen levels to prevent irreversible voice changes. For these patients we recommend referral to voice assessment and treatment. This article is protected by copyright. All rights reserved.
    Clinical Endocrinology 04/2013; · 3.40 Impact Factor
  • Helena Filipsson Nyström, Svante Jansson, Gertrud Berg
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    ABSTRACT: OBJECTIVES: To study hyperthyroidism in long-term iodine sufficiency (IS), as iodine supply affects its occurrence. DESIGN: Prospective descriptive study PATIENTS: In 2003-2005, all referred cases of subclinical (SH) and overt hyperthyroidism (OH) were registered at diagnosis from a population (n=631239) in Gothenburg, Sweden. MEASUREMENTS: Information on age, gender, smoking, thyroid associated ophthalmopathy (TAO), thyroid hormones and TSH receptor antibodies (TRab) was collected. Incidences were calculated. SH and OH cases with Graves' disease (GD), toxic multinodular goiter (TMNG) and solitary toxic adenoma (STA) were compared. In GD, TRab+ and TRab- cases and patients with (TAO+) and without TAO (TAO-) were compared. RESULTS: The total incidence (n/100000/year) of hyperthyroidism was 27.6; OH 23.8; SH 3.8; GD 21.4; TMNG 4.3; and STA 1.8. SH was more common among TMNG (40.2%) and STA (45.7%) than in GD (5.9%). SH-GD patients were older, more often smokers and had lower TRab levels than OH-GD patients. FreeT4 and T3 levels in GD were higher than in TMNG and STA. FreeT4, T3 and TRab decreased with age in GD patients, p<0.0001. TRab- patients had lower T3 than TRab+ patients, p<0.001. TRab was positively correlated to FreeT4, p<0.0001. TAO occured in 20% of GD patients. TAO+ patients were younger than TAO- patients. Smokers did not have more TAO. CONCLUSION: The total incidence of hyperthyroidism was low. GD dominated with an age-related decline of thyroid hormones and TRab levels. The spectrum of hyperthyroidism in this long-term IS area may represent the future situation for countries with shorter history of IS. © 2012 Blackwell Publishing Ltd.
    Clinical Endocrinology 02/2013; · 3.40 Impact Factor
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    ABSTRACT: Context:TSH-secreting pituitary adenomas (TSHomas) are rare. Epidemiological data are scant and there are no reports on national incidence.Objective:The objective of the study was to estimate the national Swedish incidence and prevalence of TSHomas.Design:This was an observational study.Setting:The study was conducted at tertiary referral centers.Patients:The Swedish Pituitary Registry and World Health Organization International Statistical Classification of Diseases and Related Health Problems coding at all university hospitals were used to identify patients diagnosed with TSHomas 1990-2010. The identified patients' medical records were studied until the latest follow-up [median 5.0 years (range < 1-20 years)].Main Outcome Measurements:Incidence, prevalence, demographics, tumor characteristics, treatment outcome, and thyroid hormone level at diagnosis were measured.Results:The age-standardized national incidence of 28 TSHoma patients was 0.15 per 1 million inhabitants per year, with an increasing incidence over time (0.05 per 1 million per year in 1990-1994 to 0.26 per 1 million per year in 2005-2009). The national prevalence in 2010 was 2.8 per 1 million inhabitants, in which 0.85 per 1 million had active disease. Most patients (n = 22) underwent pituitary surgery, 5 had radiotherapy, and 6 had somatostatin analogues. Eighteen patients were considered cured at the latest follow-up; 25% remained uncontrolled. Subjects treated for putative primary hyperthyroidism prior to diagnosis had TSH levels more than double those with intact thyroid at diagnosis (P = .013). The median time to diagnosis was longer for women than men (4 vs < 1 year, P = .026). More women than men were treated surgically (94.1% vs 54.5%, P = .022).Conclusion:This is the first estimate of a national incidence of TSHoma. Additional epidemiological studies are needed to compare these results with other geographical areas. This study suggests an increased incidence of TSHomas, in agreement with reports on other pituitary adenomas.
    The Journal of clinical endocrinology and metabolism 01/2013; · 6.50 Impact Factor
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    ABSTRACT: Context: Adult GH deficiency (GHD) is associated with impaired quality of life (QoL) and increased cardiovascular risk. Continued long-term efficacy in terms of QoL and cardiovascular risk factors has been indicated in open surveillance studies. Objectives: The aim was to study the impact of discontinuation of long-term GH replacement on QoL, body composition, and metabolism. Design and Setting: We conducted a randomized, double-blind, placebo-controlled 4-month crossover trial in a referral center. Patients: Sixty adult hypopituitary patients with GHD and more than 3 yr of continuous GH replacement therapy (mean treatment duration, 10 yr) participated in the study. Intervention: Patients received GH or placebo. Main Outcome Measurements: We measured QoL using validated questionnaires; body composition using computer tomography, dual-energy x-ray absorptiometry, and bioelectrical impedance spectroscopy; and insulin sensitivity using the short insulin tolerance test. Results: Mean serum IGF-I decreased from 168 ± 52 to 98 ± 47 μg/liter during the placebo period (P < 0.001). Two QoL domains (emotional reactions and positive well-being) in the Nottingham Health Profile and Psychological General Well-Being questionnaires deteriorated during placebo, compared with GH treatment (P < 0.05). Waist circumference and sc and visceral fat mass increased, and extracellular water and muscle area decreased during the placebo period (all P < 0.05). C-reactive protein and total-, low-density lipoprotein-, and high-density lipoprotein-cholesterol increased, and insulin sensitivity improved during placebo, compared to GH treatment (P < 0.05). Conclusion: After more than 3 yr of GH replacement therapy, a 4-month period of placebo treatment caused self-perceived deterioration in QoL and increased abdominal fat accumulation. Moreover, markers of systemic inflammation and lipid status deteriorated, whereas insulin sensitivity improved. Long-term continuous GH replacement is needed to maintain therapeutic effects of GH on QoL and cardiovascular risk factors.
    The Journal of clinical endocrinology and metabolism 07/2012; 97(9):3185-95. · 6.50 Impact Factor
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    ABSTRACT: GH deficiency (GHD) in adults is associated with an altered serum lipid profile that responds to GH replacement therapy (GHRT). This study evaluated the influence of polymorphisms in genes related to lipid metabolism on serum lipid profile before and after 1 year of GHRT in adults. In 318 GHD patients, total cholesterol (TC) serum concentrations, LDL-C, HDL-C, and triglycerides (TG) were assessed. Using a candidate gene approach, 20 single nucleotide polymorphisms (SNPs) were genotyped. GH dose was individually titrated to obtain normal serum IGF1 concentrations. At baseline, the minor alleles of cholesteryl ester transfer protein (CETP) gene SNPs rs708272 and rs1800775 were associated with higher serum TC and apolipoprotein E (APOE) gene SNP rs7412 with lower TC concentrations; CETP SNPs rs708272, rs1800775, and rs3764261 and apolipoprotein B (APOB) gene SNP rs693 with higher serum HDL-C; APOE SNP rs7412, peroxisome proliferator-activated receptor gamma (PPARG) gene SNP rs10865710 with lower LDL-C, and CETP SNP rs1800775 with higher LDL-C; and APOE/C1/C4/C2 cluster SNP rs35136575 with lower serum TG. After treatment, APOB SNP rs676210 GG genotype was associated with larger reductions in TC and LDL-C and PPARG SNP rs10865710 CC genotype with greater TC reduction. All associations remained significant when adjusted for age, sex, and BMI. In GHD adults, multiple SNPs in genes related to lipid metabolism contributed to individual differences in baseline serum lipid profile. The GH treatment response in TC and LDL-C was influenced by polymorphisms in the APOB and PPARG genes.
    European Journal of Endocrinology 06/2012; 167(3):353-62. · 3.14 Impact Factor
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    Marie Hansson, Helena Filipsson Nyström, Svante Jansson, Jukka Lausmaa, Gertrud Berg
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    ABSTRACT: Patients with Graves' disease can be medically prepared before surgery in different ways, which may have various effects on iodine stores. Thyroid specimens were collected at surgery from two patients pretreated with propylthiouracil (PTU) and stable iodine, respectively. A quantitative analysis of iodine content was performed using X-ray fluorescence (XRF) in frozen tissue and a qualitative analysis of aldehyde-fixed material with Time-of-Flight Secondary Ion Mass Spectrometry (TOF-SIMS). Iodine concentrations were 0.9 mg/mL and 0.5 mg/mL in the thyroid tissue from the patients treated with PTU and stable iodine respectively. TOF-SIMS showed iodine in the follicle lumina in both. However, in the PTU case, iodine was also seen within the thyrocytes indicating accumulation of iodinated compounds from uninhibited hormone release. XRF and TOF-SIMS can be used to follow iodine distribution within the thyroid and the intricate processes following the different medical treatment alternatives in Graves' disease.
    Case reports in endocrinology. 01/2012; 2012:842357.
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    ABSTRACT: Fertility in males with congenital adrenal hyperplasia (CAH) is reported from normal to severely impaired. Therefore, we investigated fertility/fecundity, social/sexual situation, and pituitary-gonadal function in CAH males. The patient cohort comprised 30 males, aged 19-67 years, with 21-hydroxylase deficiency. Their fertility was compared with age-matched national population data. For the evaluation of social/sexual factors and hormone status, age-matched controls were recruited (n = 32). Subgroups of different ages (<30 years and older) and CYP21A2 genotypes (null (severe salt-wasting (SW)), I2splice (milder SW), and I172N (simple virilizing)) were also studied. Patients underwent testicular ultrasound examination (n = 21) and semen analysis (n = 14). Fertility was impaired in CAH males compared with national data (0.9 ± 1.3 vs 1.8 ± 0.5 children/father, P<0.001). There were no major differences in social and sexual factors between patients and controls apart from more fecundity problems, particularly in the I172N group. The patients had lower testosterone/estradiol (E(2)) ratio and inhibin B, and higher FSH. The semen samples were pathological in 43% (6/14) of patients and sperm concentration correlated with inhibin B and FSH. Testicular adrenal rest tumors (TARTs) were found in 86% (18/21). Functional testicular volume correlated positively with the testosterone/E(2) ratio, sperm concentration, and inhibin B. Patients with pathological semen had increased fat mass and indications of increased cardiometabolic risk. Fertility/fecundity was impaired in CAH males. The frequent occurrence of TARTs resulting in testicular insufficiency appears to be the major cause, but other factors such as elevated fat mass may contribute to a low semen quality.
    European Journal of Endocrinology 12/2011; 166(3):441-9. · 3.14 Impact Factor
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    ABSTRACT: The metabolic consequences of thyroxine replacement in patients with central hypothyroidism (CH) need to be evaluated. The aim was to examine the outcome of thyroxine replacement in CH. Adult hypopituitary patients (n = 1595) with and without CH from KIMS (Pfizer International Metabolic Database) were studied before and after 2 years of GH replacement. CH patients (CH, n = 1080) were compared with TSH sufficient patients (TSHsuff n = 515) as one group and divided by thyroxine dose/kg/day into tertiles (CHlow-mid-high). Anthropometry, fasting glucose, glycosylated haemoglobin (HbA1c), blood pressure, lipids, IGF-I SDS, quality of life and morbidity were studied. Analyses were standardized for gender, age, number and types of pituitary insufficiencies, stimulated GH peak, age at GH deficiency onset, aetiologies and, when appropriate, for weight and GH dose. At baseline, TSHsuff patients did not differ from CH or CHmid in any outcome. CHlow (≤1.18 μg thyroxine/kg/day) had increased weight, BMI and larger waist circumference (WC), CHhigh (≥1.58 μg thyroxine/kg/day) had lower weight, BMI, WC and IGF-I than TSHsuff and compared to their predicted weights, BMIs and WCs. For every 0.1 μg/kg/day increase of thyroxine dose, body weight decreased 1.0 kg, BMI 0.3 kg/m(2), and WC 0.65 cm. The GH sensitivity of the CH group was higher (0.76 ± 0.56 SDS/mg GH) than that of TSHsuff patients (0.58 ± 0.64 SDS/mg GH), P < 0.001. The middle thyroxine dose (1.19-1.57 μg/kg/day) seems to be the most physiological. This is equivalent to 70, 100, 125 μg thyroxine/day for hypopituitary patients of 50, 70 or 90 kg weight, respectively.
    Pituitary 10/2011; · 2.67 Impact Factor
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    ABSTRACT: The incidence of hyperthyroidism has been reported in various countries to be 23-93/100,000 inhabitants per year. This extended study has evaluated the incidence for ~40% of the Swedish population of 9 million inhabitants. Sweden is considered to be iodine sufficient country. All patients including children, who were newly diagnosed with overt hyperthyroidism in the years 2003-2005, were prospectively registered in a multicenter study. The inclusion criteria are as follows: clinical symptoms and/or signs of hyperthyroidism with plasma TSH concentration below 0.2 mIE/l and increased plasma levels of free/total triiodothyronine and/or free/total thyroxine. Patients with relapse of hyperthyroidism or thyroiditis were not included. The diagnosis of Graves' disease (GD), toxic multinodular goiter (TMNG) and solitary toxic adenoma (STA), smoking, initial treatment, occurrence of thyroid-associated eye symptoms/signs, and demographic data were registered. A total of 2916 patients were diagnosed with de novo hyperthyroidism showing the total incidence of 27.6/100,000 inhabitants per year. The incidence of GD was 21.0/100,000 and toxic nodular goiter (TNG=STA+TMNG) occurred in 692 patients, corresponding to an annual incidence of 6.5/100,000. The incidence was higher in women compared with men (4.2:1). Seventy-five percent of the patients were diagnosed with GD, in whom thyroid-associated eye symptoms/signs occurred during diagnosis in every fifth patient. Geographical differences were observed. The incidence of hyperthyroidism in Sweden is in a lower range compared with international reports. Seventy-five percent of patients with hyperthyroidism had GD and 20% of them had thyroid-associated eye symptoms/signs during diagnosis. The observed geographical differences require further studies.
    European Journal of Endocrinology 09/2011; 165(6):899-905. · 3.14 Impact Factor
  • Oskar Ragnarsson, Helena Filipsson Nyström, Gudmundur Johannsson
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    ABSTRACT: Patients with hypopituitarism have adverse cardiovascular morbidity and reduced bone mineral density (BMD). The objective of this study was to analyse the effects of glucocorticoid (GC) replacement on cardiovascular risk factors and BMD in patients with hypopituitarism. This was a cross-sectional study on 365 patients with hypopituitarism. Two-hundred and four patients (56%) were ACTH insufficient (ACTHins), receiving a mean ± SD hydrocortisone equivalent (HCeq) dose of 20·5 ± 5·8 mg/day. The difference in BMD and cardiovascular risk profile between ACTH sufficient (ACTHsuff) and ACTHins patients, before commencement of GH replacement, was analysed by multiple linear and logistic regression. ACTHins was independently associated with lower fasting glucose but not other cardiovascular risk factors. The mean HCeq dose per kg body weight was 15% higher in ACTHins women than in ACTHins men (P = 0·009). In women, ACTHins was independently associated with decreased BMD at the lumbar spine (P = 0·002) and femoral neck (P = 0·006) and the presence of osteopenia (P = 0·004). BMD was not different between ACTHins and ACTHsuff men. The current average HCeq dose of approximately 20 mg per day is not associated with an adverse metabolic profile, as compared with ACTHsuff patients with hypopituitarism. GC replacement in ACTHins women is independently associated with reduced BMD and higher prevalence of osteopenia.
    Clinical Endocrinology 07/2011; 76(2):246-52. · 3.40 Impact Factor
  • Henrik Falhammar, Helena Filipsson Nyström, Anna Wedell, Marja Thorén
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    ABSTRACT: Lifelong glucocorticoid therapy in patients with congenital adrenal hyperplasia (CAH) or the disease per se may result in increased cardiovascular risk. We therefore investigated cardiovascular and metabolic risk profiles in adult CAH males. We compared CAH males (n = 30), 19-67 years old, with age- and sex-matched controls (n = 32). Subgroups of different ages (< 30 years or older) and CYP21A2 genotypes (null, I2splice, and I172N as the mildest mutation) were studied. Anthropometry, fat and lean mass measured by dual-energy X-ray absorptiometry, lipids, liver function tests, homocysteine, lipoprotein-(a), glucose and insulin during an oral glucose tolerance test (OGTT), urine albumin, adrenal hormones, and 24 h ambulatory blood pressure measurements were studied. CAH males were shorter. Waist/hip ratio and fat mass were higher in older patients and the I172N group. Heart rate was faster in older patients, the I2splice, and I172N groups. Insulin levels were increased during OGTT in all patients and in the I172N group. γ-glutamyl transpeptidase was increased in older patients and in the I172N group. Testosterone was lower in older patients. Homocysteine was lower in younger patients, which may be cardioprotective. The cardiovascular risk seemed higher with hydrocortisone/cortisone acetate than prednisolone. Urinary epinephrine was lower in all groups of patients except in I172N. Indications of increased risk were found in CAH males ≥ 30 years old and in the I172N group. In contrast, younger CAH males did not differ from age-matched controls. This is likely to reflect a better management in recent years.
    European Journal of Endocrinology 02/2011; 164(2):285-93. · 3.14 Impact Factor
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    ABSTRACT: Idiopathic pituitary insufficiency (IPI) is diagnosed in 10% of all hypopituitary patients. There are several known and unknown aetiologies within the IPI group. The aim of this study was to investigate an adult IPI population for genetic cause according a screening schedule. From files of 373 GH deficient (GHD) patients on GH replacement 50 cases with IPI were identified. Of the 39 patients that approved to the study, 25 patients were selected for genetic investigation according to phenotype and 14 patients were not further tested, as sporadic isolated GHD (n = 9) and GHD with diabetes insipidus (n = 5) have low probability for a known genetic cause. Genotyping of all coding exons of HESX1, LHX4, PROP1, POU1F1 and GH1 genes were performed according to a diagnostic algorithm based on clinical, hormonal and neuroradiological phenotype. Among the 25 patients, an overall rate of 8% of mutations was found, and a 50% rate in familial cases. Among two sibling pairs, one pair that presented with complete anterior pituitary insufficiency, had a compound heterozygous PROP1 gene mutation (codons 117 and 120: exon 3 p Phe 117 Ile (c349 T>A) and p Arg 120 Cys (c358 C>T)) with a phenotype of very late onset ACTH-insufficiency. In the other sibling pair and in the sporadic cases no mutation was identified. This study suggests that currently known genetic causes are rare in sporadic adult IPI patients, and that systematic genetic screening is not needed in adult-onset sporadic cases of IPI. Conversely, familial cases are highly suspect for genetic causes.
    Pituitary 12/2010; 14(3):208-16. · 2.67 Impact Factor
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    ABSTRACT: Sweden has had a salt iodination program since 1936. This first national surveillance study on iodine nutrition infers an adequate level of urinary iodine concentration (UIC 125 μg/l) and the aim is now to evaluate thyroid volume (Tvol) in the same national sample. A stratified probability proportionate to size cluster sampling was used to obtain a representative national sample of Swedish children aged 6-12 years. Median Tvol obtained ultrasonographically and the prevalence of enlarged thyroid glands were compared with an international reference standard. Regional differences were evaluated through comparisons of Tvol between coastal and inland areas, urban and rural regions, and former goitre and non-goitre regions. Tvol was correlated with age, body surface area (BSA), weight, height and body mass index for both sexes (P<0.0001) but not with UIC. The most important predictors for Tvol were age (girls: P<0.0001, boys: P=0.001) and BSA (girls: P<0.0001, boys: P<0.01). Median Tvol was higher in Sweden than in the reference study (P<0.0001). The prevalence of goitre was higher in Sweden (correlated to age 22.3%, BSA 15.7%, weight 17.6%, height 12.9%) than in the international reference (correlated to age 2.5%, BSA 2.5%, weight 2.5%, height 2.5%) (P<0.0001). Thyroids were larger in boys from urban and former non-goitre areas. Tvols were higher in Swedish school children than in the international reference study although iodine intake is considered optimal in Sweden. These findings underline the importance of regular monitoring of iodine intake, especially with regard to the decreased intake of table salt that is likely to follow initiation of health campaigns.
    European journal of clinical nutrition 11/2010; 64(11):1289-95. · 3.07 Impact Factor
  • Lakartidningen 109(3):90-3.

Publication Stats

60 Citations
55.35 Total Impact Points


  • 2010–2014
    • University of Gothenburg
      • Endocrinology Unit
      Goeteborg, Västra Götaland, Sweden
  • 2010–2013
    • Sahlgrenska University Hospital
      • Department of Cardiology
      Goeteborg, Västra Götaland, Sweden
  • 2011
    • Karolinska University Hospital
      Tukholma, Stockholm, Sweden
    • Karolinska Institutet
      • Institutionen för molekylär medicin och kirurgi
      Solna, Stockholm, Sweden