| 21. |
- Nyström, Helena Filipsson, 1966, et al.
(författare)
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The metabolic consequences of thyroxine replacement in adult hypopituitary patients.
- 2012
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Ingår i: Pituitary. - : Springer Science and Business Media LLC. - 1573-7403 .- 1386-341X. ; 15:4, s. 495-504
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Tidskriftsartikel (refereegranskat)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.
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| 22. |
- Olivius, C., et al.
(författare)
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Prevalence and treatment of central hypogonadism and hypoandrogenism in women with hypopituitarism
- 2018
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Ingår i: Pituitary. - : Springer Science and Business Media LLC. - 1386-341X .- 1573-7403. ; 21:5, s. 445-453
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 23. |
- Olsson, Daniel S, 1983, et al.
(författare)
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Time trends of mortality in patients with non-functioning pituitary adenoma : a Swedish nationwide study
- 2017
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Ingår i: Pituitary. - : Springer-Verlag New York. - 1386-341X .- 1573-7403. ; 20:2, s. 218-224
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: Patients with non-functioning pituitary adenomas (NFPA), especially women, have increased mortality. The aim of this study was to investigate whether mortality in NFPA patients has changed during the last two decades.METHODS: This was a nationwide population-based study including 2795 patients (1502 men, 1293 women) diagnosed with NFPA between 1997 and 2011. Patients were identified and followed in Swedish National Health Registries. Standardized mortality ratios (SMRs) with 95 % confidence intervals were calculated for three time periods at first NFPA diagnosis using the general population as reference.RESULTS: Mean (±SD) age at NFPA diagnosis was 58.9 ± 16.8 years. Mean (range) follow-up time was 8.3 (0-18) years, resulting in 20,517 patient-years at risk. Surgical treatment and radiotherapy were used in 53 and 5 %, respectively. The prevalence of hypopituitarism was 64 % during the first time period of diagnosis and then declined gradually during the study period (P value for trend <0.0001). The use of pituitary surgery and radiotherapy remained stable. In women, mortality was increased for patients diagnosed between 1997 and 2006 but not for those diagnosed between 2007 and 2011. The SMR in men remained stable throughout the study and did not differ from the general population. During the last time period, 2007-2011, the SMR between men and women did not differ.CONCLUSIONS: While mortality in men with NFPA remains normal and stable during the last two decades, mortality in women has declined. Decreasing prevalence of pituitary insufficiency may be a plausible explanation for this positive development.
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| 24. |
- Papakokkinou, Eleni, et al.
(författare)
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Prevalence of Nelson's syndrome after bilateral adrenalectomy in patients with cushing's disease: a systematic review and meta-analysis
- 2021
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Ingår i: Pituitary. - : Springer Science and Business Media LLC. - 1386-341X .- 1573-7403.
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Tidskriftsartikel (refereegranskat)abstract
- Purpose Bilateral adrenalectomy (BA) still plays an important role in the management of Cushing's disease (CD). Nelson's syndrome (NS) is a severe complication of BA, but conflicting data on its prevalence and predicting factors have been reported. The aim of this study was to determine the prevalence of NS, and identify factors associated with its development. Data sources Systematic literature search in four databases. Study Selection Observational studies reporting the prevalence of NS after BA in adult patients with CD. Data extraction Data extraction and risk of bias assessment were performed by three independent investigators. Data synthesis Thirty-six studies, with a total of 1316 CD patients treated with BA, were included for the primary outcome. Pooled prevalence of NS was 26% (95% CI 22-31%), with moderate to high heterogeneity (I-2 67%, P < 0.01). The time from BA to NS varied from 2 months to 39 years. The prevalence of NS in the most recently published studies, where magnet resonance imaging was used, was 38% (95% CI 27-50%). The prevalence of treatment for NS was 21% (95% CI 18-26%). Relative risk for NS was not significantly affected by prior pituitary radiotherapy [0.9 (95% CI 0.5-1.6)] or pituitary surgery [0.6 (95% CI 0.4-1.0)]. Conclusions Every fourth patient with CD treated with BA develops NS, and every fifth patient requires pituitary-specific treatment. The risk of NS may persist for up to four decades after BA. Life-long follow-up is essential for early detection and adequate treatment of NS.
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| 25. |
- Ragnarsson, Oskar, 1971, et al.
(författare)
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The incidence of Cushing’s disease : a nationwide Swedish study
- 2019
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Ingår i: Pituitary. - : Springer. - 1386-341X .- 1573-7403. ; 22:2, s. 179-186
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Tidskriftsartikel (refereegranskat)abstract
- Background: Studies on the incidence of Cushing’s disease (CD) are few and usually limited by a small number of patients. The aim of this study was to assess the annual incidence in a nationwide cohort of patients with presumed CD in Sweden.Methods: Patients registered with a diagnostic code for Cushing’s syndrome (CS) or CD, between 1987 and 2013 were identified in the Swedish National Patient Registry. The CD diagnosis was validated by reviewing clinical, biochemical, imaging, and histopathological data.Results: Of 1317 patients identified, 534 (41%) had confirmed CD. One-hundred-and-fifty-six (12%) patients had other forms of CS, 41 (3%) had probable but unconfirmed CD, and 334 (25%) had diagnoses unrelated to CS. The mean (95% confidence interval) annual incidence between 1987 and 2013 of confirmed CD was 1.6 (1.4–1.8) cases per million. 1987–1995, 1996–2004, and 2005–2013, the mean annual incidence was 1.5 (1.1–1.8), 1.4 (1.0–1.7) and 2.0 (1.7–2.3) cases per million, respectively. During the last time period the incidence was higher than during the first and second time periods (P < 0.05).Conclusion: The incidence of CD in Sweden (1.6 cases per million) is in agreement with most previous reports. A higher incidence between 2005 and 2013 compared to 1987–2004 was noticed. Whether this reflects a truly increased incidence of the disease, or simply an increased awareness, earlier recognition, and earlier diagnosis can, however, not be answered. This study also illustrates the importance of validation of the diagnosis of CD in epidemiological research.
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| 26. |
- Siegel, Sonja, et al.
(författare)
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Coping strategies have a strong impact on quality of life, depression, and embitterment in patients with Cushing's disease
- 2016
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Ingår i: Pituitary. - : Springer Science and Business Media LLC. - 1386-341X .- 1573-7403. ; 19:6, s. 590-600
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Tidskriftsartikel (refereegranskat)abstract
- Quality of life (QoL) and psychosocial well-being are substantially impaired in patients with Cushing's disease (CD), not only at the acute illness stage but also after therapy; however, the reason for these impairments remains unclear. In this cross-sectional, patient-reported outcome study, we conducted a postal survey on psychosocial impairment and coping strategies in patients after surgical treatment of CD in three large tertiary referral centers. In total, 176 patients with CD completed a compilation of self-assessment inventories pertaining to depression (Hospital Anxiety and Depression Scale, HADS), QoL (Short Form SF-36, Tuebingen CD; Tuebingen CD-25), coping style (Freiburg questionnaire on coping with illness, FKV-LIS), and embitterment (Bern Embitterment Inventory), on average 6.8 +/- 6.66 years after surgery. Regression analyses were performed to identify predictors of psychosocial impairment. At the time of the study, 21.8 % of patients suffered from anxiety, 18.7 % experienced an above-average feeling of embitterment, and 13.1 % suffered from depression. Maladaptive coping styles (FKV-LIS subscales depressive coping and minimizing importance) emerged as robust and strong predictors of psychosocial impairment in all inventories; while age, sex, and hydrocortisone intake failed to explain the variance in these measures. Similar to several studies in non-pituitary patient cohorts (e.g., patients with multiple sclerosis or lower back pain), our results indicate that psychosocial impairment in CD is significantly influenced by how the patient deals with the illness. Therefore, psychological training of positive coping styles could be a helpful complementary therapy in the overall treatment strategy of CD.
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| 27. |
- Smith, Casey Jo Anne, et al.
(författare)
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Intermediate lobe immunoreactivity in a patient with suspected lymphocytic hypophysitis
- 2014
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Ingår i: Pituitary. - : Springer Science and Business Media LLC. - 1386-341X .- 1573-7403. ; 17:1, s. 22-29
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Tidskriftsartikel (refereegranskat)abstract
- Lymphocytic hypophysitis is an organ-specific autoimmune disease characterised by destruction of pituitary hormone-secreting cells due to attack by self-reactive T lymphocytes. The spectrum of pituitary autoantibodies characterised by indirect immunofluorescence (IF) in these patients has not been substantially defined. The purpose of this study was to determine the spectrum of pituitary autoantibodies in 16 lymphocytic hypophysitis patients. Pituitary sections were prepared from guinea pigs and sera from 16 lymphocytic hypophysitis patients (13 biopsy proven and 3 suspected cases) and 13 healthy controls were evaluated for immunoreactivity to the pituitary tissue by immunofluorescence. A single patient was found to have high titre pituitary autoantibodies against guinea pig pituitary tissue. Immunoreactivity was directed against cells of the intermediate lobe. We present the case report of the patient who is a 24 year old woman that presented with headaches, polyuria and polydipsia. A uniformly enlarged pituitary mass was visible on MRI and a diagnosis of suspected lymphocytic hypophysitis was made. Based on our IF study, we postulate this patient has an autoimmune process directed towards the major cell type in the intermediate lobe, the melanotroph. Pre-adsorption with peptides representing adrenocorticotropic hormone, alpha-melanocyte stimulating hormone or beta-endorphin did not affect the IF signal suggesting our patient's pituitary autoantibodies may target some other product of Proopiomelanocortin (POMC) processing, such as corticotrophin-like intermediate peptide or gamma-lipoprotein. Alternatively, the autoantibodies may target a peptide completely unrelated to POMC processing.
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| 28. |
- Takahashi, Y., et al.
(författare)
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Weekly somapacitan had no adverse effects on glucose metabolism in adults with growth hormone deficiency
- 2022
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Ingår i: Pituitary. - : Springer Science and Business Media LLC. - 1386-341X .- 1573-7403.
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Tidskriftsartikel (refereegranskat)abstract
- Purpose The long-term effects of long-acting growth hormone (LAGH) analogues on glucose metabolism in adult growth hormone deficiency (AGHD) are not known. We investigated the impact of LAGH somapacitan, administered once-weekly, on glucose metabolism in patients with AGHD. Methods In post hoc-defined analyses, we compared the effects of somapacitan with daily growth hormone (GH) and placebo on fasting plasma glucose (FPG), glycated hemoglobin (HbA1c), fasting insulin, homeostasis model assessment of insulin resistance (HOMA-IR) and beta-cell function (HOMA-beta) in patients with AGHD across a unique data set from three phase 3 randomized controlled trials (REAL 1, REAL 2 and REAL Japan). Results No new cases of diabetes mellitus were reported with somapacitan. Among GH-naive patients (n = 120 somapacitan, n = 119 daily GH), higher changes from baseline in FPG, HOMA-IR and fasting insulin levels were observed with daily GH versus somapacitan at 34 weeks, but not at 86 weeks. HbA1c and HOMA-beta did not differ between groups at either timepoint. Among treatment-naive patients, sex, age, fasting insulin, glucose tolerance status and body mass index did not influence changes in glucose metabolism. In previously treated patients (REAL 1 extension: n = 51 somapacitan, n = 52 daily GH; REAL 2: n = 61 and n = 31, respectively; REAL Japan: n = 46 and n = 16, respectively), the difference in changes from baseline were not statistically significant between somapacitan and daily GH for any glucose metabolism parameters. Conclusions Somapacitan, compared with daily GH, did not adversely affect glucose metabolism up to 86 weeks in a large cohort of treatment-naive or previously treated patients with AGHD. Trial registrations (date of registration): NCT02229851 (2 September 2014), NCT02382939 (3 March 2015), NCT03075644 (7 March 2017).
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| 29. |
- Tuy, Hoang, et al.
(författare)
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The Minimum Concave Cost Network Flow Problem with fixed numbers of sources and nonlinear arc costs
- 1995
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Ingår i: Journal of Global Optimization. - 0925-5001 .- 1573-2916. ; 6:2, s. 135-151
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Tidskriftsartikel (refereegranskat)abstract
- We prove that the Minimum Concave Cost Network Flow Problem with fixed numbers of sources and nonlinear arc costs can be solved by an algorithm requiring a number of elementary operations and a number of evaluations of the nonlinear cost functions which are both bounded by polynomials in r, n, m, where r is the number of nodes, n is the number of arcs and m the number of sinks in the network
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| 30. |
- Uvelius, Erik, et al.
(författare)
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An early post-operative ACTH suppression test can safely predict short- and long-term remission after surgery of Cushing’s disease
- 2018
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Ingår i: Pituitary. - : Springer Science and Business Media LLC. - 1386-341X .- 1573-7403. ; 21:5, s. 490-498
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: The present study evaluates the usefulness of an ACTH suppression test shortly after surgery, and to determine optimal cut-off values of included laboratory analyses, in predicting short- and long-term remission after surgery of Cushing’s disease. Methods: A 48 h suppression test with betamethasone 2 mg/day applied after 45 transphenoidal adenomectomies in 28 patients was evaluated. Receiver operating characteristic (ROC)-curves were created for the included assays: plasma cortisol, plasma adrenocorticotropic hormone (ACTH) and urinary free cortisol (UFC). Plasma levels of cortisol and ACTH were measured both at 24 and 48 h. Youden’s index was used to determine cut-off with the highest sensitivity and specificity in predicting short- (3 months) and long-term (5 years or longer) remission. The area under curve (AUC) illustrated the clinical accuracy of the different assays. Results: Plasma cortisol after 24 h with betamethasone was most accurate in predicting both short- and long-term remission. 3 months remission with cut-off 107 nmol/L: sensitivity 0.85, specificity 0.94, positive predictive value (PPV) 0.96 and AUC 0.92 (95% CI 0.85–1). 5 years remission with cut-off 49 nmol/L: sensitivity: 0.94, specificity 0.93, PPV 0.88, AUC 0.98 (95% CI 0.95–1). Analyses of ACTH or UFC did not improve diagnostic accuracy. Conclusions: A 48 h, 2 mg/day betamethasone suppression test after transphenoidal surgery of Cushing’s disease could predict short- and long-term remission with a high accuracy. Suppression of plasma cortisol after 24 h with betamethasone to values excluding Cushings disease in the diagnostic setting yielded the highest accuracy in predicting long-term remission.
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