| 1. |
- Arlien-Soborg, Mai C., et al.
(författare)
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Acromegaly management in the Nordic countries: A Delphi consensus survey
- 2024
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Ingår i: Clinical Endocrinology. - : WILEY. - 0300-0664 .- 1365-2265.
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Tidskriftsartikel (refereegranskat)abstract
- ObjectiveAcromegaly is associated with increased morbidity and mortality if left untreated. The therapeutic options include surgery, medical treatment, and radiotherapy. Several guidelines and recommendations on treatment algorithms and follow-up exist. However, not all recommendations are strictly evidence-based. To evaluate consensus on the treatment and follow-up of patients with acromegaly in the Nordic countries.MethodsA Delphi process was used to map the landscape of acromegaly management in Denmark, Sweden, Norway, Finland, and Iceland. An expert panel developed 37 statements on the treatment and follow-up of patients with acromegaly. Dedicated endocrinologists (n = 47) from the Nordic countries were invited to rate their extent of agreement with the statements, using a Likert-type scale (1-7). Consensus was defined as >= 80% of panelists rating their agreement as >= 5 or <= 3 on the Likert-type scale.ResultsConsensus was reached in 41% (15/37) of the statements. Panelists agreed that pituitary surgery remains first line treatment. There was general agreement to recommend first-generation somatostatin analog (SSA) treatment after failed surgery and to consider repeat surgery. In addition, there was agreement to recommend combination therapy with first-generation SSA and pegvisomant as second- or third-line treatment. In more than 50% of the statements, consensus was not achieved. Considerable disagreement existed regarding pegvisomant monotherapy, and treatment with pasireotide and dopamine agonists.ConclusionThis consensus exploration study on the management of patients with acromegaly in the Nordic countries revealed a relatively large degree of disagreement among experts, which mirrors the complexity of the disease and the shortage of evidence-based data.
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| 2. |
- Arlien-Soborg, Mai C., et al.
(författare)
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Acromegaly management in the Nordic countries: A Delphi consensus survey
- 2024
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Ingår i: CLINICAL ENDOCRINOLOGY. - : WILEY. - 0300-0664 .- 1365-2265.
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Tidskriftsartikel (refereegranskat)abstract
- ObjectiveAcromegaly is associated with increased morbidity and mortality if left untreated. The therapeutic options include surgery, medical treatment, and radiotherapy. Several guidelines and recommendations on treatment algorithms and follow-up exist. However, not all recommendations are strictly evidence-based. To evaluate consensus on the treatment and follow-up of patients with acromegaly in the Nordic countries.MethodsA Delphi process was used to map the landscape of acromegaly management in Denmark, Sweden, Norway, Finland, and Iceland. An expert panel developed 37 statements on the treatment and follow-up of patients with acromegaly. Dedicated endocrinologists (n = 47) from the Nordic countries were invited to rate their extent of agreement with the statements, using a Likert-type scale (1-7). Consensus was defined as >= 80% of panelists rating their agreement as >= 5 or <= 3 on the Likert-type scale.ResultsConsensus was reached in 41% (15/37) of the statements. Panelists agreed that pituitary surgery remains first line treatment. There was general agreement to recommend first-generation somatostatin analog (SSA) treatment after failed surgery and to consider repeat surgery. In addition, there was agreement to recommend combination therapy with first-generation SSA and pegvisomant as second- or third-line treatment. In more than 50% of the statements, consensus was not achieved. Considerable disagreement existed regarding pegvisomant monotherapy, and treatment with pasireotide and dopamine agonists.ConclusionThis consensus exploration study on the management of patients with acromegaly in the Nordic countries revealed a relatively large degree of disagreement among experts, which mirrors the complexity of the disease and the shortage of evidence-based data.
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| 3. |
- Brabant, Georg, et al.
(författare)
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Clinical implications of residual growth hormone (GH) response to provocative testing in adults with severe GH deficiency
- 2007
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Ingår i: Journal of Clinical Endocrinology and Metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 92:7, s. 2604-2609
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Tidskriftsartikel (refereegranskat)abstract
- Context: The diagnosis of GH deficiency (GHD) in adults is based on provocative tests of GH release, all influenced by clinical factors. It is unknown whether the amount of residual GH reserve under the cutoff value has any physiological implication. Objectives: We used a large pharmacoepidemiological database of adult GHD (KIMS) and tested the impact of confounding factors on GH release of no greater than 3 µg/liter after an insulin tolerance test (ITT) and evaluated its potential physiological role. Design, Settings, and Patients: A total of 1098 patients fulfilled the criteria of having a GH peak of no greater than 3 µg/liter during ITT as well as documented IGF-I levels. Outcomes: The impact of underlying hypothalamic-pituitary disease, age, gender, body weight, as well as treatment modalities such as irradiation on peak GH level to ITT was evaluated, and the correlations between GH peak and targets of GH action were analyzed. Results: The GH response to ITT was regulated by gender, age, and the number of additional pituitary deficiencies. In a multivariate evaluation, the extent of hypothalamic-pituitary dysfunction was the most important single predictor of GH peak in ITT. GH peaks in ITT were positively related to IGF-I levels and high-density lipoprotein-cholesterol, as well as inversely to triglycerides. Conclusions: Even in adult severe GHD, GH release appears to be regulated by factors defined to play an important role in normal GH secretion. The impact of very low GH release on IGF-I and lipid parameters indicates a persistent physiological role of low GH concentrations in severely affected patients with GHD.
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| 4. |
- Feldt-Rasmussen, Ulla, et al.
(författare)
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Response to GH treatment in adult GH deficiency is predicted by gender, age, and IGF1 SDS but not by stimulated GH-peak
- 2013
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Ingår i: European Journal of Endocrinology. - 0804-4643 .- 1479-683X. ; 168:5, s. 733-743
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Tidskriftsartikel (refereegranskat)abstract
- Objective: We studied whether the severity of GH deficiency (GHD) defined as i) GH-peak on stimulation tests (insulin tolerance test (ITT), arginine, and glucagon), ii) number of additional pituitary deficits, or iii) baseline IGF1 SDS could impact the response to GH treatment. We further explored whether iv) IGF1 SDS after 24 months of GH replacement or v) Delta IGF1 SDS from baseline to 24 months was related to the phenotypic response to GH treatment. Design, patients, and measurements: The patient cohort (n=1752; 50% women) was obtained from KIMS (Pfizer International Metabolic Database). The patients were divided into three groups of approximately equal size (tertiles) according to the stimulated GH-peak values and baseline IGF1 SDS and were studied at baseline, 12, and 24 months of GH therapy. Results: Lower baseline IGF1 SDS predicted better response in weight, BMI, total cholesterol, and triglycerides, while IGF1 SDS after 24 months was associated with reduction in waist/hip ratio, total cholesterol, and improved quality of life (QoL). Age-correlated negatively with the response in body weight, BMI, waist, IGF1 SDS, and total and LDL-cholesterol. Response in weight and BMI was greater in men than in women, whereas women showed greater improvement in QoL than men. Patients with more severe GHD as assessed by lower GH-peaks and more pituitary hormone deficiencies had a greater increase in IGF1 SDS. The increase in IGF1 SDS was associated with a reduction in waist/hip ratio and an increase in weight, BMI, and triglycerides. There was no correlation with other lipids, blood pressure, or glucose. Conclusion: Our findings indicate that baseline and 24 months, IGF1 and its degree of increase during GH replacement were more important than stimulated peak GH to predict the phenotypic response.
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| 5. |
- Toogood, Andy, et al.
(författare)
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Similar Clinical Features Among Patients With Severe Adult Growth Hormone Deficiency Diagnosed With Insulin Tolerance Test Or Arginine Or Glucagon Stimulation Tests
- 2012
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Ingår i: Endocrine Practice. - 1530-891X .- 1934-2403. ; 18:3, s. 325-334
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To determine whether the ITT, arginine (AST) and glucagon stimulation tests (GST) identify patients who have similar features of GH deficiency using a diagnostic threshold of 3 μg/l.Patients and Methods: 5453 tests were available from 4,867 patients registered in the KIMS database (49.9% females, ITT = 3111, AST = 1390, GST = 952). Comparisons were made for GH peak, BMI, lipids, waist circumference, waist:hip ratio and quality of life (QoL-AGHDA questionnaire).Results.There were significant (p<0.0001) intra-individual correlations between the GH peaks for the ITT vs AST (r = 0.655), ITT vs GST (r = 0.445) and AST vs GST (r = 0.632). GH peaks in response to all tests were negatively correlated to the number of additional pituitary hormone deficiencies, and positively correlated to IGF-I SDS. BMI had a negative influence on all three tests.Comparing GHD patients according to the diagnostic test used, most clinical variables did not differ between the groups. The only exceptions showing any difference were BMI being slightly higher in the AST and GST groups, triglyceride levels increased in the GST group, and IGF-I SDS was lower in the ITT and AST than in the GST group. Waist circumference was larger and quality of life was worse in the GST group than in the other groups.Conclusions.This study demonstrates that the ITT, AST and GST produce similar GH peaks, are influenced by similar clinical factors and identify patients with similar features of GH deficiency at a diagnostic threshold of 3 μg/L.
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| 6. |
- Abrams, Pascale, et al.
(författare)
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GH replacement in hypopituitarism improves lipid profile and quality of life independently of changes in obesity variables
- 2008
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Ingår i: European Journal of Endocrinology. - 0804-4643 .- 1479-683X. ; 159:6, s. 825-832
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Tidskriftsartikel (refereegranskat)abstract
- Objective: GH deficiency (GHD) in adults is characterized by elevated body mass index (BMI), increased waist girth (WG) and increased fat mass (FM). Information about how these indicators of obesity affect the lipid profile and quality of life (QoL) of GHD subjects is scarce. It is also unclear how changes in these indicators brought about by GH replacement influence lipids and QoL. Design and methods: Adult GHD Subjects from the Pfizer International Metabolic Database were grouped according to BMI (n = 291 with BMI < 25 kg/m(2), n = 372 with BMI 25-30 kg/m(2), n = 279 with BMI > 30 kg/m(2)), WG (n = 508 with normal WG, n = 434 with increased WG) and FM (n = 357) and according to changes in these variables after 1 year of GH replacement. Serum IGF-1 concentrations, lipid concentrations and QoL using the QoL Assessment of GHD in Adults questionnaire were assessed at baseline and after 1 year of treatment. Results: At baseline, total and low-density lipoprotein (LDL) cholesterol were similarly elevated in the BMI and WG groups, but high-density lipoprotein (HDL) cholesterol decreased and triglycerides increased with increasing BMI and WG. QoL was progressively poorer with increasing BMI and WG. After 1 year of GH replacement, total and LDL cholesterol and QoL improved in all BMI, WG and FM groups. Conclusions: Variables of obesity adversely affect the already unfavourable lipid profile in GHD Subjects by decreasing HDL cholesterol, but do not counteract the positive effect of GH replacement on LDL cholesterol. Similarly, QoL is influenced by obesity, but responds equally well to GH treatment independent of BMI, WG and FM.
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| 7. |
- Abs, Roger, et al.
(författare)
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Determinants of cardiovascular risk in 2589 hypopituitary GH-deficient adults - a KIMS database analysis.
- 2006
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Ingår i: European Journal of Endocrinology. - : Oxford University Press (OUP). - 0804-4643 .- 1479-683X. ; 155:1, s. 79-90
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Tidskriftsartikel (refereegranskat)abstract
- Objective: The aim of the present study was to clarify the relationship between GH deficiency (GHD) andsome cardiovascular risk factors and to analyse the effect of GH replacement therapy in a large numberof patients over a prolonged period of time.Design: Data for analysis were retrieved from KIMS (Pfizer International Metabolic Database). Serumconcentrations of total cholesterol, high-density lipoprotein (HDL)-cholesterol, low-density lipoprotein(LDL)-cholesterol and triglycerides were obtained from 2589 patients at baseline and from 1206patients after 1 and 2 years of GH replacement therapy. Body mass index (BMI), waist and hip, restingblood pressure and body composition were also measured.Results: At baseline, the unfavourable effects of GHD were most obvious in the lipid profiledemonstrating elevated mean total and LDL-cholesterol, in the increased waist circumference and theelevated BMI. The cholesterol concentration, BMI and body composition were significantly adverselyaffected by a number of factors, including age, sex and the use of anti-epileptic drugs. The therapeuticeffect of GH was essentially uniform across the whole population. GH replacement reduced significantlythe mean total and LDL-cholesterol, the waist circumference and the fat mass and was maintainedduring 2 years.Conclusions: This analysis of a large number of patients confirmed that GHD adults present with anincreased cardiovascular risk. The sustained improvement of the adverse lipid profile and bodycomposition suggests that GH replacement therapy may reduce the risk of cardiovascular disease andthe premature mortality seen in hypopituitary patients with untreated GHD.
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| 8. |
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| 9. |
- Astradsson, Arnar, et al.
(författare)
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Cerebral infarction after fractionated stereotactic radiation therapy of benign anterior skull base tumors
- 2019
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Ingår i: Clinical and Translational Radiation Oncology. - : Elsevier BV. - 2405-6308. ; 15, s. 93-98
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Tidskriftsartikel (refereegranskat)abstract
- Background: The purpose of this study was to examine the occurrence of cerebral infarction (ischemic stroke), in a large combined cohort of patients with anterior skull base meningiomas, pituitary adenomas and craniopharyngiomas, after fractionated stereotactic radiation therapy (FSRT). Material and Methods: All patients, 18 years and older, with anterior skull base meningiomas, pituitary adenomas and craniopharyngiomas, treated with fractionated stereotactic radiation, in our center, from January 1999 to December 2015 were identified. In total 169 patients were included. The prescription dose to the tumor was 54 Gy for 164 patients (97%) and 46.0–52.2 Gy for 5 patients (3%). Cases of cerebral infarctions subsequent to FSRT were identified from the Danish National Patient Registry and verified with review of case notes. The rate of cerebral infarction after FSRT was compared to the rate in the general population with a one sample t-test after standardization for age and year. We explored if age, sex, disease type, radiation dose and dose per fraction was associated with increased risk of cerebral infarction using univariate Cox models. Results: At a median follow-up of 9.3 years (range 0.1–16.5), 7 of the 169 patients (4.1%) developed a cerebral infarction, at a median 5.7 years (range 1.2–11.5) after FSRT. The mean cerebral infarction rate for the general population was 0.0035 and 0.0048 for the FSRT cohort (p = 0.423). Univariate cox models analysis showed that increasing age correlated significantly with the cerebral infarction risk, with a hazard ratio of 1.090 (p = 0.013). Conclusion: Increased risk of cerebral infarction after FSRT of anterior skull base tumors was associated with age, similar to the general population. Our study revealed that FSRT did not introduce an excess risk of cerebral infarction.
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| 10. |
- Chantzichristos, Dimitrios, 1976, et al.
(författare)
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Identification of human glucocorticoid response markers using integrated multi-omic analysis from a randomized crossover trial.
- 2021
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Ingår i: eLife. - 2050-084X. ; 10
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Tidskriftsartikel (refereegranskat)abstract
- Glucocorticoids are among the most commonly prescribed drugs, but there is no biomarker that can quantify their action. The aim of the study was to identify and validate circulating biomarkers of glucocorticoid action.In a randomized, crossover, single-blind, discovery study, 10 subjects with primary adrenal insufficiency (and no other endocrinopathies) were admitted at the in-patient clinic and studied during physiological glucocorticoid exposure and withdrawal. A randomization plan before the first intervention was used. Besides mild physical and/or mental fatigue and salt craving, no serious adverse events were observed. The transcriptome in peripheral blood mononuclear cells and adipose tissue, plasma miRNAomic, and serum metabolomics were compared between the interventions using integrated multi-omic analysis.We identified a transcriptomic profile derived from two tissues and a multi-omic cluster, both predictive of glucocorticoid exposure. A microRNA (miR-122-5p) that was correlated with genes and metabolites regulated by glucocorticoid exposure was identified (p=0.009) and replicated in independent studies with varying glucocorticoid exposure (0.01 ≤ p≤0.05).We have generated results that construct the basis for successful discovery of biomarker(s) to measure effects of glucocorticoids, allowing strategies to individualize and optimize glucocorticoid therapy, and shedding light on disease etiology related to unphysiological glucocorticoid exposure, such as in cardiovascular disease and obesity.The Swedish Research Council (Grant 2015-02561 and 2019-01112); The Swedish federal government under the LUA/ALF agreement (Grant ALFGBG-719531); The Swedish Endocrinology Association; The Gothenburg Medical Society; Wellcome Trust; The Medical Research Council, UK; The Chief Scientist Office, UK; The Eva Madura's Foundation; The Research Foundation of Copenhagen University Hospital; and The Danish Rheumatism Association.NCT02152553.
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| 11. |
- Delgrange, Etienne, et al.
(författare)
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Giant prolactinomas in women
- 2014
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Ingår i: European Journal of Endocrinology. - 1479-683X. ; 170:1, s. 31-38
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To characterise distinctive clinical features of giant prolactinomas in women. Design: A multicentre, retrospective case series and literature review. Methods: We collected data from 15 female patients with a pituitary tumour larger than 4 cm and prolactin levels above 1000 mu g/l and identified 19 similar cases from the literature; a gender-based comparison of the frequency and age distribution was obtained from a literature review. Results: The initial PubMed search using the term 'giant prolactinomas' identified 125 patients (13 women) responding to the inclusion criteria. The female: male ratio was 1:9. Another six female patients were found by extending the literature search, while our own series added 15 patients. The median age at diagnosis was 44 years in women compared with 35 years in men (P<0.05). All cases diagnosed before the age of 15 years were boys. In women (n=34), we observed a minor peak incidence during the third decade of life and a major peak during the fifth decade. Amenorrhoea was a constant feature with seven cases of primary amenorrhoea. In eight women with onset of secondary amenorrhoea before the age of 40 years, the diagnosis was made 2-31 years later (median 9 years) and in all but one because of tumour pressure symptoms. The prolactin levels were above 10 000 mu g/l in 15/34 and misdiagnosis due to 'hook effect' occurred in two of them. Eighteen patients were treated with cabergoline; standard doses (<2.0 mg/week) were able to normalise prolactin in only 4/18 patients, and 7/18 patients were resistant to weekly doses ranging from 3.0 to 7.0 mg. Conclusion: Giant prolactinomas are rare in women, often resistant to dopamine agonists and seem to be distributed in two age groups, with a larger late-onset peak.
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| 12. |
- Granfors, Michaela, 1972-
(författare)
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Hypothyroidism and Pregnancy
- 2015
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Hypothyroidism is a common endocrine disorder affecting women of reproductive age. On a global level, iodine deficiency is still the most common cause of hypothyroidism. Also genetic variations, in particular SNP rs4704397 in the PDE8B gene, are responsible for a significant proportion of TSH variations. Untreated hypothyroidism has significant adverse effects on pregnancy and fetal outcome. Most international guidelines suggest targeted thyroid testing in pregnant women with risk factors for thyroid disturbances.In a case-control study, an association between homozygous A/A as well as homozygous G/G carriers of SNP rs 4704397 in PDE8B and recurrent miscarriage was found. The explanation for this association is unknown.In a nationwide survey, all guidelines for thyroid testing and management of hypothyroidism during pregnancy in Sweden were collected and compared with international guidelines. The local guidelines were variable and poorly compliant with the international guidelines.In a follow-up in one district, 5,254 pregnant women were included for subsequent review of their medical reports. We found a targeted thyroid testing rate of 20.1% in clinical practice, with an overall frequency of women with trimester-specific elevated TSH of 18.5%. More disturbingly, half of the women who were on levothyroxine treatment at the time of conception had an elevated TSH level at thyroid testing.In a subsequent cohort study of the 5,254 women, we found the prevalence of trimester-specific elevated TSH and overt hypothyroidism to be equal in targeted thyroid tested and untested women.In a cross-sectional study, a median urinary iodine concentration (UIC) of 98 μg/l was found in the study population. According to WHO/UNICEF/IGN criteria, the population-based median UIC during pregnancy should be 150-249 μg/l.In conclusion, genetic variations may contribute to adverse pregnancy outcomes. In clinical practice, thyroid testing and the management of hypothyroidism during pregnancy is unsatisfactory, regarding the whole chain from development of local guidelines to their implementation and to targeted thyroid testing. Moreover, our results indicate insufficient iodine status in the pregnant population of Sweden.
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| 13. |
- Höybye, Charlotte, et al.
(författare)
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Change in baseline characteristics over 20 years of adults with growth hormone (GH) deficiency on GH replacement therapy
- 2019
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Ingår i: European Journal of Endocrinology. - 0804-4643 .- 1479-683X. ; 181:6, s. 629-638
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Clinical observations over time of adults with growth hormone (GH) deficiency (GHD) have indicated a shift in patient characteristics at diagnosis. The objective of this study was to compare baseline characteristics of patients diagnosed with adult-onset GHD naive to GH replacement during t hree study periods (1994-1999 (P1), 2000-2004 (P2), and 2005-2012 (P3)) using the KIMS (Pfizer's International Metab olic) database. Methods: Data were retrieved for a total of 6069 patients with adult-on set GHD from six countries (Belgium, Germany, Netherlands, Spain, Sweden, and UK): P1 (n = 1705), P2 (n = 2397), and P3 (n = 1967). Results: The proportions of patients with pituitary/hypothalamic tumors and patients with multiple pituitary hormone deficiencies decreased per entry year period, while the proporti ons with hypertension and diabetes increased. The lag time from diagnosis of pituitary disease to start of GH treatme nt decreased by 2.9 years over the entry year periods. IGF-1 increased by 0.1 standard deviation score per entry year period. Maximum GH following various stimulation tests, BMI, and waist circumference increased. The use of radio therapy, glucocorticoid replacement doses, and the proportion of women >50 years on estrogen replacement therapy decreased. The effects of 1 year of GH replacement were similar over the entry year periods despite changes in the patients' baseline characteristics. An expected increase in fasting blood glucose was seen after 1 year of GH treatment. Conclusions: The degree of confirmed GHD became less pronounced and more pat ients with co-morbidities and diabetes were considered for GH replacement therapy, possibly r eflecting increased knowledge and confidence in GH therapy gained with time.
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| 14. |
- Höybye, Charlotte, et al.
(författare)
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Clinical features of GH deficiency and effects of 3 years of GH replacement in adults with controlled Cushing's disease.
- 2010
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Ingår i: European journal of endocrinology / European Federation of Endocrine Societies. - 1479-683X. ; 162:4, s. 677-84
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Patients in remission from Cushing's disease (CD) have many clinical features that are difficult to distinguish from those of concomitant GH deficiency (GHD). In this study, we evaluated the features of GHD in a large cohort of controlled CD patients, and assessed the effect of GH treatment. DESIGN AND METHODS: Data were obtained from KIMS, the Pfizer International Metabolic Database. A retrospective cross-sectional comparison of background characteristics in unmatched cohorts of patients with CD (n=684, 74% women) and nonfunctioning pituitary adenoma (NFPA; n=2990, 39% women) was conducted. In addition, a longitudinal evaluation of 3 years of GH replacement in a subset of patients with controlled CD (n=322) and NFPA (n=748) matched for age and gender was performed. RESULTS: The cross-sectional study showed a significant delay in GHD diagnosis in the CD group, who had a higher prevalence of hypertension, fractures, and diabetes mellitus. In the longitudinal, matched study, the CD group had a better metabolic profile but a poorer quality of life (QoL) at baseline, which was assessed with the disease-specific questionnaire QoL-assessment of GHD in adults. After 3 years of GH treatment (mean dose at 3 years 0.39 mg/day in CD and 0.37 mg/day in NFPA), total and low-density lipoprotein cholesterol decreased, while glucose and HbAlc increased. Improvement in QoL was observed, which was greater in the CD group (-6 CD group versus -5 NFPA group, P<0.01). CONCLUSION: In untreated GHD, co-morbidities, including impairment of QoL, were more prevalent in controlled CD. Overall, both the groups responded similarly to GH replacement, suggesting that patients with GHD due to CD benefit from GH to the same extent as those with GHD due to NFPA.
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| 15. |
- Marina, Djordje, et al.
(författare)
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Truncated somatostatin receptor 5 may modulate therapy response to somatostatin analogues - Observations in two patients with acromegaly and severe headache
- 2015
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Ingår i: Growth Hormone & IGF Research. - : Elsevier BV. - 1096-6374 .- 1532-2238. ; 25:5, s. 262-267
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Tidskriftsartikel (refereegranskat)abstract
- Background: Somatotropinomas have unique "fingerprints" of somatostatin receptor (sst) expression, which are targets in treatment of acromegaly with somatostatin analogues (SSAs). However, a significant expression of sst is not always related to the biochemical response to SSAs. Headache is a common complaint in acromegaly and considered a clinical marker of disease activity. SSAs are reported to have an own analgesic effect, but the sst involved are unknown. Patients and methods: We investigated sst expression in two acromegalic patients with severe headache and no biochemical effects of octreotide, but a good response to pasireotide. We searched the literature for determinants of biochemical and analgesic effects of SSAs in somatotropinomas. Results: Case 1 had no biochemical or analgesic effects of octreotide, a semi-selective SSA, but a rapid and significant effect of pasireotide, a pan-SSA Case 2 demonstrated discordance between analgesic and biochemical effects of octreotide, in that headache disappeared, but without biochemical improvement. In contrast, pasireotide normalized insulin-like growth factor 1. Both adenomas were sparsely granulated and had strong membranous expressions of sst2a in 50-75% and sst5 in 75-100% of tumor cells. The truncated sst5 variant TMD4 (sst5TMD4) showed expression in 20-57% of tumor cells. Conclusions: A poor biochemical response to octreotide may be associated with tumor expression of a truncated sst5 variant, despite abundant sst2a expression, suggesting an influence from variant sst5 on common sst signaling pathways. Furthermore, unrelated analgesic and biochemical effects of SSAs supported a complex pathogenesis of acromegaly-associated headache. Finally, assessment of truncated sst5 in addition to full length sst could be important for a choice of postoperative SSA treatment in somatotropinomas.
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| 16. |
- 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 2years 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 (≤1.18μg thyroxine/kg/day) had increased weight, BMI and larger waist circumference (WC), CHhigh (≥1.58μg thyroxine/kg/day) had lower weight, BMI, WC and IGF-I than TSHsuff and compared to their predicted weights, BMIs and WCs. For every 0.1μg/kg/day increase of thyroxine dose, body weight decreased 1.0kg, BMI 0.3kg/m(2), and WC 0.65cm. 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 (1.19-1.57μg/kg/day) seems to be the most physiological. This is equivalent to 70, 100, 125μg thyroxine/day for hypopituitary patients of 50, 70 or 90kg weight, respectively.
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| 17. |
- Ragnarsson, Oskar, 1971, et al.
(författare)
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Comorbidity and cardiocascular risk factors in adult GH deficiency following treatment for Cushing´s disease or non-functioning pituitary adenomas during childhood.
- 2012
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Ingår i: European journal of endocrinology. - 0804-4643. ; 166:4, s. 593-600
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Tidskriftsartikel (refereegranskat)abstract
- Objective Cushing's disease (CD) and non-functioning pituitary adenoma (NFPA) are rare in paediatric patients. The aim of this study was to describe long-term consequences in adults with GH deficiency (GHD) treated for CD or NFPA during childhood. Design, patients and methods This was a retrospective analysis of data from KIMS (Pfizer International Metabolic Database). Background characteristics, anthropometry and comorbidity were studied in 47 patients diagnosed with childhood-onset (CO)-CD and 62 patients with CO-NFPA. Data from 100 ACTH-sufficient patients with CO-idiopathic hypopituitarism (CO-Idio) were used for comparison. Cardiovascular risk profile was analysed at baseline and at 1 year on GH treatment in a subgroup of patients (17 CO-CD, 24 CO-NFPA and 55 CO-Idio) not receiving GH treatment at study entry. Results The median age at diagnosis of pituitary tumour was 14.0 years (range 10–17) in patients with CO-CD and 13.7 years (range 8–17) in CO-NFPA. In addition to GHD, 41% of patients with CO-CD had three or four other pituitary hormone deficiencies compared with 78% of patients with CO-NFPA (P<0.001). Eighty-nine per cent of patients with CO-CD had height SDS lower than 0 compared with 61% of patients with CO-NFPA (P=0.002). Hypertension was more common in CO-CD compared with CO-Idio (23 vs 9%, P=0.018). At 1 year on GH treatment, total- and low-density lipoprotein-cholesterol decreased significantly in CO-CD but not in CO-NFPA. Conclusion Adult patients with GHD following treatment for paediatric CD and NFPA have long-term adverse consequences. Despite more severe hypopituitarism in CO-NFPA, patients with CO-CD have more frequently compromised final stature.
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| 18. |
- Touraine, Philippe, et al.
(författare)
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Pituitary function and the response to GH therapy in patients with Langerhans cell histiocytosis : analysis of the KIMS database
- 2022
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Ingår i: Yosetsu Gakkai Shi/Journal of the Japan Welding Society. - 0021-4787. ; 187:3, s. 373-381
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To analyze the effectiveness and safety of growth hormone (GH) replacement treatment in adult patients with Langerhans cell histiocytosis (LCH) and GH deficiency (GHD) enrolled in KIMS (Pfizer International Metabolic Database). Patients and methods: Patients with LCH and GHD were studied at baseline and some of them after 1 year of GH treatment. The effectiveness of GH is presented as change after 1 year of treatment (mean, 95% CI). The LCH population was compared to two other groups of patients enrolled in KIMS, granulomatous and lymphocytic hypophysitis. Results: At baseline, 81 adults with LCH (27 with childhood onset, 56% females), mean age at GHD onset of 29 (15) years were studied. Diabetes insipidus was diagnosed in 86% of patients. Analysis of 1 year of GH treatment was possible in 37 patients. One-year cross-sectional values for the GH dose were 0.39 (S.D. ± 0.21) mg and -0.5 (-1.2 to 0.2) for insulin-like growth factor-1 S.D. Total cholesterol decreased 0.9 (-1.5 to -0.3 (mmol/L); P < 0.05); AGHDA-QoLscore (n = 20) was improved by 2.8 points (-5.6 to 0.0; P < 0.05), while mean BMI increased 0.6 ± 3 kg/m2 (95% CI: -0.2 to 1.4). All these effects did not differ from the two other groups after adjusting for age, gender, and baseline values. In 20 of 77 patients included in the safety analysis, 36 serious adverse events were reported during 435 patient-years (82.8/1000); no new safety signals were reported. Conclusion: After 1 year of GH treatment in patients with LCH, metabolic variables and quality of life improved, with no new safety signals.
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- Tritos, Nicholas A, et al.
(författare)
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Effects of long-term growth hormone replacement in adults with growth hormone deficiency following cure of acromegaly : a KIMS analysis.
- 2014
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Ingår i: Journal of Clinical Endocrinology and Metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 99:6, s. 2018-2029
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Tidskriftsartikel (refereegranskat)abstract
- CONTEXT: GH deficiency (GHD) may occur in adults with cured acromegaly (acroGHD).OBJECTIVE: Our objective was to examine the effectiveness and safety of GH replacement in acroGHD.DESIGN: This study was a retrospective analysis of data from KIMS (Pfizer International Metabolic Database).SETTING: Data were extracted from a pharmaco-epidemiological survey of >16 000 GHD adults from 31 countries.PATIENTS: The effectiveness population included 115 adults with acroGHD and 142 age-, gender-, and body mass index-matched GHD adults with nonfunctioning pituitary adenoma (NFPA) followed up to 5 years on GH. The safety population included 164 adults with acroGHD and 2469 with NFPA, all GH-replaced. Both acroGHD and NFPA were compared with several cohorts from the general population (including the World Health Organization Global Burden of Disease).OUTCOME MEASURES: Outcome measures included quality of life (QoL-AGHDA), lipids, serious adverse events, and additional safety endpoints.RESULTS: Median GH dose was 0.3 mg/d in acroGHD and NFPA at 5 years. There were comparable improvements in QoL-AGHDA and total and low-density lipoprotein cholesterol in acroGHD and NFPA. High-density lipoprotein cholesterol increased only in acroGHD. Cardiovascular mortality was increased in acroGHD vs NFPA (standardized mortality ratio = 3.03, P = .02). All-cause mortality was similar in acroGHD (ratio between observed/expected cases [95% confidence interval] = 1.32 [0.70-2.25]) and lower in NFPA [observed/expected = 0.58 [0.48-0.70]) in comparison with the general population. There was no difference in incidence of all cancers, benign or malignant brain tumors, or diabetes mellitus between acroGHD and NFPA.CONCLUSIONS: GH replacement has comparable effects on quality of life and lipids in acroGHD and NFPA. Further investigation is needed to examine whether the increased cardiovascular mortality may be attributed to the history of previous GH excess in acroGHD.
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