A multivariable prediction model for pegvisomant dosing: monotherapy and in combination with long-acting somatostatin analogues.


BACKGROUND:Effective treatment of acromegaly with pegvisomant (PEGV), a growth hormone receptor antagonist, requires an appropriate dose titration. PEGV doses vary widely among individual patients, and various covariates may affect its dosing and pharmacokinetics. OBJECTIVE:To identify predictors of the PEGV dose required to normalize insulin-like growth factor I (IGF-I) levels during PEGV monotherapy and in combination with long-acting somatostatin analogues (LA-SSAs). DESIGN:Two retrospective cohorts (Rotterdam + Liège Acromegaly Survey (LAS), total n = 188) were meta-analyzed as a form of external replication to study the predictors of PEGV dosing in addition to LA-SSA, the LAS (n = 83) was used to study the predictors of PEGV monotherapy dosing. Multivariable regression models were used to identify predictors of the PEGV dose required to normalize IGF-I levels. RESULTS:For PEGV dosing in combination with LA-SSA, IGF-I levels, weight, height and age, were associated with the PEGV normalization dosage (P ≤ 0.001, P ≤ 0.001, P = 0.028 and P = 0.047 respectively). Taken together, these characteristics predicted the PEGV normalization dose correctly in 63.3% of all patients within a range of ±60 mg/week (21.3% within a range of ±20 mg/week). For monotherapy, only weight was associated with the PEGV normalization dose (P ≤ 0.001) and predicted this dosage correctly in 77.1% of all patients within a range of ±60 mg/week (31.3% within a range of ±20 mg/week). CONCLUSION:In this study, we show that IGF-I levels, weight, height and age can contribute to define the optimal PEGV dose to normalize IGF-I levels in addition to LA-SSA. For PEGV monotherapy, only the patient's weight was associated with the IGF-I normalization PEGV dosage.


Eur J Endocrinol


Franck SE,Korevaar TIM,Petrossians P,Daly AF,Chanson P,Jaffrain-Réa ML,Brue T,Stalla GK,Carvalho D,Colao A,Hána V,Delemer B,Fajardo C,van der Lely AJ,Beckers A,Neggers SJCMM




Has Abstract


2017-04-01 00:00:00














  • Bone microarchitecture and estimated bone strength in men with active acromegaly.

    abstract:CONTEXT:Both acromegaly and adult growth hormone deficiency (GHD) are associated with increased fracture risk. Sufficient data are lacking regarding cortical bone microarchitecture and bone strength, as assessed by microfinite element analysis (µFEA). OBJECTIVE:To elucidate both cortical and trabecular bone microarchi...

    journal_title:European journal of endocrinology

    pub_type: 杂志文章


    authors: Silva PPB,Amlashi FG,Yu EW,Pulaski-Liebert KJ,Gerweck AV,Fazeli PK,Lawson E,Nachtigall LB,Biller BMK,Miller KK,Klibanski A,Bouxsein M,Tritos NA

    更新日期:2017-11-01 00:00:00

  • Variation in the gene encoding Krüppel-like factor 7 influences body fat: studies of 14 818 Danes.

    abstract:OBJECTIVE:KLF7 encodes Krüppel-like factor (KLF) 7, a member of the KLF family of transcription factors, initially shown to play important roles in cellular development and differentiation, and reported to be specifically involved in adipogenesis. Several single nucleotide polymorphisms (SNPs) have been identified in K...

    journal_title:European journal of endocrinology

    pub_type: 杂志文章


    authors: Zobel DP,Andreasen CH,Burgdorf KS,Andersson EA,Sandbaek A,Lauritzen T,Borch-Johnsen K,Jørgensen T,Maeda S,Nakamura Y,Eiberg H,Pedersen O,Hansen T

    更新日期:2009-04-01 00:00:00

  • The metabolic syndrome and its components in 178 patients treated for craniopharyngioma after 16 years of follow-up.

    abstract:OBJECTIVE:Patients with craniopharyngioma are at an increased risk for cardio- and cerebrovascular mortality. The metabolic syndrome (MetS) is an important cardiometabolic risk factor, but barely studied in patients with craniopharyngioma. We aimed to investigate the prevalence of and risk factors for the MetS and its ...

    journal_title:European journal of endocrinology

    pub_type: 杂志文章


    authors: Wijnen M,Olsson DS,van den Heuvel-Eibrink MM,Hammarstrand C,Janssen JAMJL,van der Lely AJ,Johannsson G,Neggers SJCMM

    更新日期:2018-01-01 00:00:00

  • Withdrawn: Case detection, diagnosis, and treatment of patients with primary aldosteronism: an Endocrine Society clinical practice guideline.

    abstract::Ahead of Print article withdrawn by publisher. ...

    journal_title:European journal of endocrinology

    pub_type: 杂志文章


    authors: Funder J,Carey R,Fardella C,Gomez-Sanchez C,Mantero F,Stowasser M,Young W,Montori VM

    更新日期:2009-09-30 00:00:00

  • The relationship between plasma osmolality and plasma vasopressin concentration is altered in old male Lewis rats.

    abstract::Kidney dysfunction has been observed in aged humans and rats, the primary cause of which may reside in the kidney itself or in the hypothalamus. The latter possibility is suggested by the increased release of AVP in response to salt infusion in humans. The effect of age on the relationship between plasma osmolality an...

    journal_title:European journal of endocrinology

    pub_type: 杂志文章


    authors: Terwel D,Jolles J

    更新日期:1994-07-01 00:00:00

  • Preoperative diagnosis of insulinoma: low body mass index, young age, and female gender are associated with negative imaging by endoscopic ultrasound.

    abstract:OBJECTIVE:Endoscopic ultrasound (EUS) is a highly reliable procedure to localize insulinomas preoperatively. It has been considered to be important in planning surgical strategy, especially considering a minimal invasive approach. However, even under ideal conditions experienced examiners miss about 10-20% of insulinom...

    journal_title:European journal of endocrinology

    pub_type: 杂志文章


    authors: Kann PH,Ivan D,Pfützner A,Forst T,Langer P,Schaefer S

    更新日期:2007-08-01 00:00:00

  • Long-term treatment of acromegaly with the slow-release somatostatin analogue lanreotide.

    abstract::Thirteen patients with active acromegaly despite previous surgery were treated with 30 mg lanreotide im twice a month for 9 months. In 10 subjects the treatment continued to 19 months. GH serum levels of all patients decreased significantly from an initial value of 32.0 (29.4) micrograms/l [median (standard error of m...

    journal_title:European journal of endocrinology

    pub_type: 杂志文章


    authors: Marek J,Hána V,Krsek M,Justová V,Catus F,Thomas F

    更新日期:1994-07-01 00:00:00

  • Modulation by retinoic acid of insulin-like growth factor (IGF) and IGF binding protein expression in human SK-N-SH neuroblastoma cells.

    abstract::Growth in neuroblastoma cells is regulated by insulin-like growth factors (IGFs) whose action is modulated by IGF binding proteins (IGFBPs). In this study, SK-N-SH neuroblastoma cells were shown to produce IGF-II, IGFBP-2, IGFBP-4 and small quantities of IGFBP-6. We have studied the effects of a natural morphogen, ret...

    journal_title:European journal of endocrinology

    pub_type: 杂志文章


    authors: Babajko S,Binoux M

    更新日期:1996-04-01 00:00:00

  • Lipid accumulation product as a marker of cardiometabolic susceptibility in women with different phenotypes of polycystic ovary syndrome.

    abstract:OBJECTIVE:There are limited data on cardiometabolic risk factors and the prevalence of metabolic syndrome (MetS) across the different PCOS phenotypes in Caucasian population. Lipid accumulation product (LAP) is a clinical surrogate marker that could be used for evaluation of MetS in clinical practice. The aim of the st...

    journal_title:European journal of endocrinology

    pub_type: 杂志文章


    authors: Božić-Antić I,Ilić D,Bjekić-Macut J,Bogavac T,Vojnović-Milutinović D,Kastratovic-Kotlica B,Milić N,Stanojlović O,Andrić Z,Macut D

    更新日期:2016-12-01 00:00:00

  • Association of the type 2 deiodinase Thr92Ala polymorphism with type 2 diabetes: case-control study and meta-analysis.

    abstract:OBJECTIVE:The type 2 deiodinase (D2) is a key enzyme for intracellular triiodothyronine (T(3)) generation. A single-nucleotide polymorphism in D2 (Thr92Ala) has been associated with increased insulin resistance in nondiabetic and type 2 diabetes (DM2) subjects. Our aim was to evaluate whether the D2 Thr92Ala polymorphi...

    journal_title:European journal of endocrinology

    pub_type: 杂志文章,meta分析


    authors: Dora JM,Machado WE,Rheinheimer J,Crispim D,Maia AL

    更新日期:2010-09-01 00:00:00

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    abstract:OBJECTIVE:Platinum-based chemotherapy (PBC) is the most effective cytotoxic treatment for advanced adrenocortical carcinoma (ACC). Excision repair cross complementing group 1 (ERCC1) plays a critical role in the repair of platinum-induced DNA damage. Two studies investigating the role of ERCC1 immunostaining as a predi...

    journal_title:European journal of endocrinology

    pub_type: 杂志文章


    authors: Laufs V,Altieri B,Sbiera S,Kircher S,Steinhauer S,Beuschlein F,Quinkler M,Willenberg HS,Rosenwald A,Fassnacht M,Ronchi CL

    更新日期:2018-02-01 00:00:00

  • ENDOCRINE TUMORS: BRAF V600E mutations in papillary craniopharyngioma.

    abstract::Papillary craniopharyngioma (PCP) is an intracranial tumor that results in high levels of morbidity. We recently demonstrated that the vast majority of these tumors harbor the oncogenic BRAF V600E mutation. The pathologic diagnosis of PCP can now be confirmed using mutation specific immunohistochemistry and targeted g...

    journal_title:European journal of endocrinology

    pub_type: 杂志文章,评审


    authors: Brastianos PK,Santagata S

    更新日期:2016-04-01 00:00:00

  • Etiology, baseline characteristics, and biochemical diagnosis of GH deficiency in the adult: are there regional variations?

    abstract::Previous work has examined potential links between the etiology of GH deficiency (GHD) and the baseline characteristics of the patients including biochemical and psychometric parameters. Using an update of the KIMS pharmaco-epidemiological database (Pfizer International Metabolic Database), we addressed the question h...

    journal_title:European journal of endocrinology

    pub_type: 杂志文章


    authors: Brabant G,Poll EM,Jönsson P,Polydorou D,Kreitschmann-Andermahr I

    更新日期:2009-11-01 00:00:00

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    abstract::Fibrous dysplasia/McCune-Albright Syndrome (FD/MAS), arising from gain-of-function mutations in Gαs, and cutaneous skeletal hypophosphatemia syndrome (CSHS), arising from gain-of-function mutations in the Ras/MAPK pathway, are strikingly complex, mosaic diseases with overlapping phenotypes. Both disorders are defined ...

    journal_title:European journal of endocrinology

    pub_type: 杂志文章,评审


    authors: de Castro LF,Ovejero D,Boyce AM

    更新日期:2020-05-01 00:00:00

  • Association of antiepileptic drug usage, trace elements and thyroid hormone status.

    abstract:BACKGROUND:Levels of thyroid hormone (TH) and trace elements (copper (Cu) and selenium (Se)) are important for development and function of the brain. Anti-epileptic drugs (AEDs) can influence serum TH and trace element levels. As the relationship between AEDs, THs, and trace elements has not yet been studied directly, ...

    journal_title:European journal of endocrinology

    pub_type: 杂志文章


    authors: Zevenbergen C,Korevaar TI,Schuette A,Peeters RP,Medici M,Visser TJ,Schomburg L,Visser WE

    更新日期:2016-04-01 00:00:00

  • MANAGEMENT OF ENDOCRINE DISEASE: Personalized medicine in the treatment of acromegaly.

    abstract::Acromegaly is associated with high morbidity and elevated mortality when not adequately treated. Surgery is the first-line treatment for most patients as it is the only one that can lead to immediate cure. In patients who are not cured by surgery, treatment is currently based on a trial-and-error approach. First-gener...

    journal_title:European journal of endocrinology

    pub_type: 杂志文章,评审


    authors: Kasuki L,Wildemberg LE,Gadelha MR

    更新日期:2018-03-01 00:00:00

  • Sleep-wake and melatonin pattern in craniopharyngioma patients.

    abstract:OBJECTIVE:To assess the influence of craniopharyngioma or consequent surgery on melatonin secretion, and the association with fatigue, sleepiness, sleep pattern and sleep quality. DESIGN:Cross-sectional study. METHODS:A total of 15 craniopharyngioma patients were individually matched to healthy controls. In this stud...

    journal_title:European journal of endocrinology

    pub_type: 杂志文章


    authors: Pickering L,Jennum P,Gammeltoft S,Poulsgaard L,Feldt-Rasmussen U,Klose M

    更新日期:2014-06-01 00:00:00

  • Increased expression of tumor necrosis factor-alpha and decreased expression of thyroglobulin and thyroid peroxidase mRNA levels in the thyroids of iodide-treated BB/Wor rats.

    abstract::Several lines of evidence suggest that tumor necrosis factor-alpha (TNFalpha) may contribute to the pathogenesis of autoimmune thyroid disease. It is not known, however, whether increased thyroidal TNFalpha levels are associated with changes in thyroid function. The purpose of the present study was to utilize in situ ...

    journal_title:European journal of endocrinology

    pub_type: 杂志文章


    authors: Mori K,Mori M,Stone S,Braverman LE,DeVito WJ

    更新日期:1998-11-01 00:00:00

  • Unenhanced CT imaging is highly sensitive to exclude pheochromocytoma: a multicenter study.

    abstract:BACKGROUND:A substantial proportion of all pheochromocytomas is currently detected during the evaluation of an adrenal incidentaloma. Recently, it has been suggested that biochemical testing to rule out pheochromocytoma is unnecessary in case of an adrenal incidentaloma with an unenhanced attenuation value ≤10 Hounsfie...

    journal_title:European journal of endocrinology

    pub_type: 杂志文章,多中心研究


    authors: Buitenwerf E,Korteweg T,Visser A,Haag CMSC,Feelders RA,Timmers HJLM,Canu L,Haak HR,Bisschop PHLT,Eekhoff EMW,Corssmit EPM,Krak NC,Rasenberg E,van den Bergh J,Stoker J,Greuter MJW,Dullaart RPF,Links TP,Kerstens MN

    更新日期:2018-05-01 00:00:00

  • Neutrophil:lymphocyte ratio is positively related to type 2 diabetes in a large-scale adult population: a Tianjin Chronic Low-Grade Systemic Inflammation and Health cohort study.

    abstract:AIM:It is widely known that inflammation is related to type 2 diabetes (T2D), but few studies have shown a direct relationship between the immune system and T2D using a reliable biomarker. Neutrophil:lymphocyte ratio (NLR) is an easy-to-analyze inflammation biomarker, but few studies have assessed the relationship betw...

    journal_title:European journal of endocrinology

    pub_type: 杂志文章,随机对照试验


    authors: Guo X,Zhang S,Zhang Q,Liu L,Wu H,Du H,Shi H,Wang C,Xia Y,Liu X,Li C,Sun S,Wang X,Zhou M,Huang G,Jia Q,Zhao H,Song K,Niu K

    更新日期:2015-08-01 00:00:00

  • Endocrinology and Adolescence: aerobic exercise reduces insulin resistance markers in obese youth: a meta-analysis of randomized controlled trials.

    abstract:OBJECTIVE:The purpose of this meta-analysis was to examine the evidence for the effectiveness of aerobic exercise interventions on reducing insulin resistance markers in obese children and/or adolescents. A secondary outcome was change in percentage of body fat. METHODS:A computerized search was made from seven databa...

    journal_title:European journal of endocrinology

    pub_type: 杂志文章,meta分析


    authors: García-Hermoso A,Saavedra JM,Escalante Y,Sánchez-López M,Martínez-Vizcaíno V

    更新日期:2014-10-01 00:00:00

  • Possible delayed diagnosis and treatment of metastatic differentiated thyroid cancer by adopting the 2015 ATA guidelines.

    abstract:OBJECTIVE:According to the 2015 American Thyroid Association (ATA) guidelines, thyroid ablation by iodine-131 (I-131) therapy is absolutely recommended only in patients with high-risk differentiated thyroid cancer (DTC). Often distant metastases are not recognized early and they can stay silent for long time. The aim o...

    journal_title:European journal of endocrinology

    pub_type: 杂志文章


    authors: Albano D,Bertagna F,Bonacina M,Durmo R,Cerudelli E,Gazzilli M,Panarotto MB,Formenti AM,Mazziotti G,Giustina A,Giubbini R

    更新日期:2018-09-01 00:00:00

  • Increased reverse triiodothyronine is associated with shorter survival in independently-living elderly: the Alsanut study.

    abstract:OBJECTIVE:Increased reverse tritiodothyronine (T(3)) used to be described as a part of euthyroid sick syndrome (ESS). It was demonstrated to be associated with increased mortality in acutely ill patients. It can also be found with low or normal T(3) in non-severely ill subjects but its significance remains unclear. PA...

    journal_title:European journal of endocrinology

    pub_type: 杂志文章


    authors: Forestier E,Vinzio S,Sapin R,Schlienger JL,Goichot B

    更新日期:2009-02-01 00:00:00

  • Mass spectrometry and immunoassay: how to measure steroid hormones today and tomorrow.

    abstract::The recent onslaught of mass spectrometry (MS) to measurements of steroid hormones, including demands that they should be the only acceptable method, has confused clinicians and scientists who have relied for more than 40 years on a variety of immunoassay (IA) methods in steroid hormone measurements. There is little d...

    journal_title:European journal of endocrinology

    pub_type: 杂志文章,评审


    authors: Taylor AE,Keevil B,Huhtaniemi IT

    更新日期:2015-08-01 00:00:00

  • Short-term low-dose growth hormone administration in subjects with impaired glucose tolerance and the metabolic syndrome: effects on beta-cell function and post-load glucose tolerance.

    abstract:OBJECTIVE:Modest elevations in circulating IGF-I levels have been suggested to protect against the development of glucose intolerance in insulin-resistant subjects. To further understand the interactions of GH and IGF-I on beta-cell function and post-load glucose tolerance in glucose-intolerant subjects predisposed to ...

    journal_title:European journal of endocrinology

    pub_type: 临床试验,杂志文章,随机对照试验


    authors: Yuen K,Wareham N,Frystyk J,Hennings S,Mitchell J,Fryklund L,Dunger D

    更新日期:2004-07-01 00:00:00

  • Calcium mobilization is a prerequisite for the expression of phorbol ester-stimulated luteinizing hormone secretion from pituitaries of male and acutely ovariectomized rats.

    abstract::Ionomycin, which mobilizes Ca2+, and phorbol 12-myristate 13-acetate (PMA), which activates protein kinase C (PKC), were used to compare the effects/interactions of Ca2+ and PKC on luteinizing hormone (LH) secretion from pituitaries of intact male and acutely ovariectomized (72 h) rats. Quartered pituitaries from dono...

    journal_title:European journal of endocrinology

    pub_type: 杂志文章


    authors: Das S,Fahmy NW,Bourne GA

    更新日期:1994-02-01 00:00:00

  • Adrenal vein sampling in primary aldosteronism: concordance of simultaneous vs sequential sampling.

    abstract:OBJECTIVE:Many investigators believe that basal adrenal venous sampling (AVS) should be done simultaneously, whereas others opt for sequential AVS for simplicity and reduced cost. This study aimed to evaluate the concordance of sequential and simultaneous AVS methods. DESIGN AND METHODS:Between 1989 and 2015, bilatera...

    journal_title:European journal of endocrinology

    pub_type: 杂志文章


    authors: Almarzooqi MK,Chagnon M,Soulez G,Giroux MF,Gilbert P,Oliva VL,Perreault P,Bouchard L,Bourdeau I,Lacroix A,Therasse E

    更新日期:2017-02-01 00:00:00

  • The therapeutic outcome to intravenous steroid therapy for active Graves' orbitopathy is influenced by the time of response but not polymorphisms of the glucocorticoid receptor.

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    journal_title:European journal of endocrinology

    pub_type: 杂志文章


    authors: Vannucchi G,Covelli D,Campi I,Origo D,Currò N,Cirello V,Dazzi D,Beck-Peccoz P,Salvi M

    更新日期:2013-11-22 00:00:00

  • Regressive liver adenomatosis following androgenic progestin therapy withdrawal: a case report with a 10-year follow-up and a molecular analysis.

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    journal_title:European journal of endocrinology

    pub_type: 杂志文章


    authors: Svrcek M,Jeannot E,Arrivé L,Poupon R,Fromont G,Fléjou JF,Zucman-Rossi J,Bouchard P,Wendum D

    更新日期:2007-06-01 00:00:00

  • Iodine levels and thyroid hormones in healthy pregnant women and birth weight of their offspring.

    abstract:INTRODUCTION:The fetus is most vulnerable to severe iodine deficiency and hypothyroidism during pregnancy. The effects of mild iodine deficiency and subclinical hypothyroidism are poorly known. The present study assesses the association between thyroid hormones (TH)s and urinary iodine concentration (UIC) in healthy pr...

    journal_title:European journal of endocrinology

    pub_type: 杂志文章


    authors: Alvarez-Pedrerol M,Guxens M,Mendez M,Canet Y,Martorell R,Espada M,Plana E,Rebagliato M,Sunyer J

    更新日期:2009-03-01 00:00:00