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1.
Eur J Endocrinol ; 187(3): 373-381, 2022 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-35830276

RESUMO

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-QoL-score (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.


Assuntos
Nanismo Hipofisário , Histiocitose de Células de Langerhans , Hormônio do Crescimento Humano , Hipopituitarismo , Adulto , Criança , Estudos Transversais , Feminino , Histiocitose de Células de Langerhans/tratamento farmacológico , Terapia de Reposição Hormonal , Hormônio do Crescimento Humano/uso terapêutico , Humanos , Hipopituitarismo/tratamento farmacológico , Masculino , Qualidade de Vida
2.
J Clin Endocrinol Metab ; 107(7): 1906-1919, 2022 06 16.
Artigo em Inglês | MEDLINE | ID: mdl-35368070

RESUMO

CONTEXT: Data on long-term safety of growth hormone (GH) replacement in adults with GH deficiency (GHD) are needed. OBJECTIVE: We aimed to evaluate the safety of GH in the full KIMS (Pfizer International Metabolic Database) cohort. METHODS: The worldwide, observational KIMS study included adults and adolescents with confirmed GHD. Patients were treated with GH (Genotropin [somatropin]; Pfizer, NY) and followed through routine clinical practice. Adverse events (AEs) and clinical characteristics (eg, lipid profile, glucose) were collected. RESULTS: A cohort of 15 809 GH-treated patients were analyzed (mean follow-up of 5.3 years). AEs were reported in 51.2% of patients (treatment-related in 18.8%). Crude AE rate was higher in patients who were older, had GHD due to pituitary/hypothalamic tumors, or adult-onset GHD. AE rate analysis adjusted for age, gender, etiology, and follow-up time showed no correlation with GH dose. A total of 606 deaths (3.8%) were reported (146 by neoplasms, 71 by cardiac/vascular disorders, 48 by cerebrovascular disorders). Overall, de novo cancer incidence was comparable to that in the general population (standard incidence ratio 0.92; 95% CI, 0.83-1.01). De novo cancer risk was significantly lower in patients with idiopathic/congenital GHD (0.64; 0.43-0.91), but similar in those with pituitary/hypothalamic tumors or other etiologies versus the general population. Neither adult-onset nor childhood-onset GHD was associated with increased de novo cancer risks. Neutral effects were observed in lipids/fasting blood glucose levels. CONCLUSION: These final KIMS cohort data support the safety of long-term GH replacement in adults with GHD as prescribed in routine clinical practice.


Assuntos
Nanismo Hipofisário , Hormônio do Crescimento Humano , Hipopituitarismo , Doenças da Hipófise , Neoplasias Hipofisárias , Adolescente , Adulto , Criança , Nanismo Hipofisário/complicações , Nanismo Hipofisário/tratamento farmacológico , Nanismo Hipofisário/epidemiologia , Hormônio do Crescimento/uso terapêutico , Terapia de Reposição Hormonal/efeitos adversos , Hormônio do Crescimento Humano/efeitos adversos , Humanos , Hipopituitarismo/tratamento farmacológico , Hipopituitarismo/epidemiologia , Doenças da Hipófise/etiologia , Neoplasias Hipofisárias/tratamento farmacológico
3.
Eur J Endocrinol ; 182(3): 285-292, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31917681

RESUMO

OBJECTIVE: To examine all-cause mortality rates in patients with acromegaly on pegvisomant and identify pertinent risk factors, including insulin-like growth factor I (IGF-I). DESIGN: Retrospective cohort analysis of data from ACROSTUDY (global surveillance study of patients with acromegaly treated with pegvisomant). METHODS: Kaplan-Meier analyses and Cox regression techniques were used to examine survival rates. Standardized mortality ratios (SMR) with reference to general population (WHO GBD 2016) were estimated. Multiplicative multiple Poisson regression models were used to characterize the association between SMR, IGF-I, and other risk factors associated with mortality risk. RESULTS: The study consisted of 2077 subjects who were followed for a median interval of 4.1 years, contributing to 8957 patient-years. Higher on-treatment IGF-I (P = 0.0035), older attained age (P < 0.0001), and longer duration of acromegaly (>10 years) before starting pegvisomant (P = 0.05) were associated with higher mortality rates. In reference to general population rates, higher SMR (1.10, 1.42, and 2.62, at attained age 55 years) were observed with higher serum IGF-I category (SMR trend: 1.44 (44%)/per fold level of IGF-I/ULN (95% CI: 1.10, 1.87), P = 0.0075). SMR increased per year of younger attained age (1.04 (1.02-1.04), P < 0.0001) and were higher for longer disease duration (>10 years) before starting pegvisomant (1.57 (1.02, 2.43), P = 0.042). Serum IGF-I levels within the normal range during pegvisomant therapy were associated with all-cause mortality rates that were indistinguishable from the general population. CONCLUSIONS: Higher on-treatment IGF-I, older attained age, and longer duration of acromegaly before starting pegvisomant are associated with higher all-cause mortality rates. Younger patients with uncontrolled acromegaly have higher excess all-cause mortality rates in comparison with older patients.


Assuntos
Acromegalia/tratamento farmacológico , Hormônio do Crescimento Humano/análogos & derivados , Mortalidade , Receptores da Somatotropina/antagonistas & inibidores , Acromegalia/metabolismo , Adulto , Fatores Etários , Idoso , Causas de Morte , Estudos de Coortes , Feminino , Hormônio do Crescimento Humano/uso terapêutico , Humanos , Fator de Crescimento Insulin-Like I/metabolismo , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo , Tempo para o Tratamento
4.
Eur J Endocrinol ; 181(6): 629-638, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31590143

RESUMO

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 three study periods (1994-1999 (P1), 2000-2004 (P2), and 2005-2012 (P3)) using the KIMS (Pfizer's International Metabolic) database. METHODS: Data were retrieved for a total of 6069 patients with adult-onset 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 proportions with hypertension and diabetes increased. The lag time from diagnosis of pituitary disease to start of GH treatment 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 radiotherapy, 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 patients with co-morbidities and diabetes were considered for GH replacement therapy, possibly reflecting increased knowledge and confidence in GH therapy gained with time.


Assuntos
Nanismo Hipofisário/tratamento farmacológico , Nanismo Hipofisário/epidemiologia , Nanismo Hipofisário/patologia , Hormônio do Crescimento/uso terapêutico , Adulto , Bélgica/epidemiologia , Feminino , Alemanha/epidemiologia , Glucocorticoides/uso terapêutico , Terapia de Reposição Hormonal , Humanos , Masculino , Pessoa de Meia-Idade , Países Baixos/epidemiologia , Espanha/epidemiologia , Suécia/epidemiologia , Reino Unido/epidemiologia
5.
Neuroendocrinology ; 109(2): 131-140, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30844796

RESUMO

BACKGROUND/AIMS: It is unknown whether long-term growth hormone replacement therapy (GHRT) affects body composition in an age- or sex-dependent manner. We aimed to study the effects of 4 years of GHRT on body composition in a large cohort of patients with hypopituitarism compared to a reference population matched by age and sex. METHODS: A total of 964 GH-deficient adults from KIMS (Pfizer International Metabolic Database) with adult-onset hypopituitarism, adequately replaced with all pituitary hormones except for GH at baseline were included. A random sample of the general population (2,301 subjects) from a similar time period was used as reference. Patients and controls were grouped by sex in 5 age cohorts of 10 years. Main outcome measures were changes in BMI and waist circumference after 4 years of GHRT. RESULTS: In younger patients (28-47 years), 4 years of GHRT resulted in a BMI increase similar to that observed in the reference population, but older patients (48-67 years) had significantly less BMI increase than age-matched healthy controls. Significant differences were seen in waist circumference in patients of all age cohorts who showed virtually no change after 4 years of GHRT compared to approximately 4 cm of increase in the reference population. CONCLUSION: Four years of GHRT resulted in improvements in BMI and waist circumference in patients with adult-onset hypopituitarism compared to age-matched controls observed during the same follow-up time. Despite these beneficial effects on body composition, BMI and waist circumference remained higher in patients on GHRT compared to healthy controls.


Assuntos
Composição Corporal/efeitos dos fármacos , Terapia de Reposição Hormonal , Hormônio do Crescimento Humano/administração & dosagem , Hipopituitarismo/tratamento farmacológico , Adulto , Idoso , Estudos de Casos e Controles , Estudos de Coortes , Bases de Dados Factuais , Feminino , Hormônio do Crescimento Humano/deficiência , Humanos , Hipopituitarismo/metabolismo , Hipopituitarismo/fisiopatologia , Masculino , Pessoa de Meia-Idade , Fatores de Tempo , Resultado do Tratamento
6.
Endocr Connect ; 7(5): 653-662, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29661785

RESUMO

BACKGROUND: Adult-onset growth hormone deficiency (AO-GHD) is associated with an increased prevalence of the metabolic syndrome (MetS). AIM: To determine the effect of GH replacement on the prevalence of MetS in AO-GHD and to study the impact of MetS on the incidence of cardiovascular events during GH replacement. PATIENTS AND METHODS: 1449 AO-GHD patients (males 48.9%; mean age 48.9 ± 12.8 year) were retrieved from KIMS (Pfizer International Metabolic Database). The prevalence of MetS (using International Diabetes Federation criteria) and its components were calculated at baseline and after one year of GH replacement. The relative risk to develop cardiovascular events according to the presence of MetS at baseline was assessed in another group of 3282 patients after prolonged GH replacement. RESULTS: The prevalence of MetS was 46.9% at baseline and 48.2% after one year of GH replacement (P = NS). The percentage of patients with abnormal waist circumference decreased significantly (80.3 vs 77.4%; P < 0.001), but impaired glucose metabolism (17.1 vs 23.3%; P < 0.001) increased and HDL cholesterol (48.2 vs 50.9%; P = 0.011) decreased. Switch from MetS to NoMS (18.5%) and from NoMS to MetS (18.8%) occurred. All patients showed a significant and comparable amelioration of quality of life. During seven years of GH replacement patients with MetS had a 66% higher risk (P = 0.0016) to develop a new coronary disease compared to NoMS. CONCLUSION: MetS prevalence remains unchanged in AO-GHD during one year of GH replacement whereas its components are differentially affected. Besides GH replacement, consequent pharmacotherapy of all risk factors and endorsement of lifestyle intervention appears to be of uttermost importance together with early GHD diagnosis to prevent cardiovascular disease during prolonged treatment.

7.
J Clin Endocrinol Metab ; 103(2): 523-531, 2018 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-29228199

RESUMO

Context: Data on the association between growth hormone (GH) replacement in patients with GH deficiency (GHD) after malignancies and new neoplasms show conflicting results. Objective: To clarify the incidence of new malignant neoplasm in childhood-onset (CO) and adult-onset (AO) adult cancer survivors (CSs). Design: Retrospective comparison of CO-CS and AO-CS with CO idiopathic GHD (IGHD) and AO nonfunctioning pituitary adenoma (NFPA) patients and with the general population [standardized incidence ratio (SIR)]. Setting: Data from the Pfizer International Metabolic Database study (KIMS). Patients: CO-CS [n = 349; 50.4% females; mean baseline (MBL) IGF-I standard deviation score (SDS), -2.4], IGHD (n = 619; 35.7% females; MBL IGF-I SDS, -3.4), AO-CS (n = 174; 42.5% females; MBL IGF-I SDS, -1.4), and NFPA (n = 2449; 38.1% females; MBL IGF-I SDS, -1.0). Main Outcome Measures: SIRs of malignant neoplasms. Results: After a median follow-up of 5.9 years (2192 patient-years), 15 CO-CS (4.3%) had developed 16 new neoplasms. The SIR was 10.4 [95% confidence interval (CI), 5.9 to 16.9] and 6.5 (95% CI, 3.0 to 12.4) after exclusion of seven patients with skin cancers. In IGHD, three malignant neoplasms (0.5%) were observed after a median follow-up of 5.4 years (3908 patient-years; SIR, 0.47; 95% CI, 0.09 to 1.37). New malignant neoplasms occurred in three AO-CS (1.7%; SIR, 1.1; 95% CI, 0.2 to 3.2) and 146 NFPA patients (153 cases, 6.0%; SIR, 1.1; 95% CI, 0.9 to 1.2) after a median follow-up of 4.9 (1024 patient-years) and 5.6 years (15,215 patient-years). Conclusions: The risk of second malignant neoplasms was increased in CO-CS but not in AO-CS, which illustrates the need to closely follow patients on GH replacement because of a prior malignancy.


Assuntos
Adenoma/complicações , Hormônio do Crescimento Humano/uso terapêutico , Hipopituitarismo/tratamento farmacológico , Hipopituitarismo/etiologia , Segunda Neoplasia Primária/epidemiologia , Neoplasias Hipofisárias/complicações , Adenoma/tratamento farmacológico , Adenoma/epidemiologia , Adolescente , Adulto , Sobreviventes de Câncer/estatística & dados numéricos , Criança , Bases de Dados Factuais , Feminino , Seguimentos , Terapia de Reposição Hormonal/efeitos adversos , Hormônio do Crescimento Humano/efeitos adversos , Humanos , Hipopituitarismo/epidemiologia , Masculino , Pessoa de Meia-Idade , Segunda Neoplasia Primária/induzido quimicamente , Neoplasias Hipofisárias/tratamento farmacológico , Neoplasias Hipofisárias/epidemiologia , Estudos Retrospectivos , Adulto Jovem
8.
J Clin Endocrinol Metab ; 103(2): 768-777, 2018 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-29029108

RESUMO

Context: In adults, craniopharyngioma (CP) of either childhood-onset (CO-CP) or adult-onset (AO-CP) is associated with increased morbidity and mortality, but data on the relative risks (RRs) of contributing factors are lacking. Objective: To assess the RRs of factors contributing to morbidity and mortality in adults with CO-CP and AO-CP. Methods: Data on 1669 patients with CP from KIMS (Pfizer International Metabolic Database) were analyzed using univariate and multiple Poisson and Cox regression methods. Results: When CO-CP and AO-CP groups were combined, history of stroke and hyperlipidemia increased cardiovascular risk, higher body mass index (BMI) and radiotherapy increased cerebrovascular risk, and increased waist circumference increased the risk of developing diabetes mellitus (DM). Compared with patients with CO-CP, patients with AO-CP had a threefold higher risk of tumor recurrence, whereas being female and previous radiotherapy exposure conferred lower risks. Radiotherapy and older age with every 10 years from disease onset conferred a 2.3- to 3.5-fold risk for developing new intracranial tumors, whereas older age, greater and/or increasing BMI, history of stroke, and lower insulinlike growth factor I (IGF-I) standard deviation score measured at last sampling before death were related to increased all-cause mortality. Compared with the general population, adults with CP had 9.3-, 8.1-, and 2.2-fold risks of developing DM, new intracranial tumors, and early death, respectively. Conclusion: Conventional factors that increase the risks of cardio- and cerebrovascular diseases and DM and risks for developing new intracranial tumors contributed to excess morbidity and mortality. In addition, lower serum IGF-I level measured from the last sample before death was inversely associated with mortality risk in patients with CP.


Assuntos
Craniofaringioma/tratamento farmacológico , Craniofaringioma/epidemiologia , Hormônio do Crescimento Humano/uso terapêutico , Neoplasias Hipofisárias/tratamento farmacológico , Neoplasias Hipofisárias/epidemiologia , Adolescente , Adulto , Criança , Pré-Escolar , Craniofaringioma/complicações , Feminino , Terapia de Reposição Hormonal , Humanos , Hipopituitarismo/tratamento farmacológico , Hipopituitarismo/epidemiologia , Hipopituitarismo/etiologia , Masculino , Pessoa de Meia-Idade , Morbidade , Mortalidade , Neoplasias Hipofisárias/complicações , Estudos Retrospectivos , Risco , Fatores de Risco , Adulto Jovem
9.
J Clin Endocrinol Metab ; 102(3): 1051-1058, 2017 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-28359095

RESUMO

CONTEXT: De novo brain tumors developing after treatment of pituitary/sellar lesions have been reported, but it is unknown whether this is linked to any of the treatment modalities. OBJECTIVE: To study the occurrence of malignant brain tumors and meningiomas in a large cohort of patients treated for pituitary/sellar lesions, with special emphasis on the role of radiotherapy (RT). PATIENTS AND METHODS: Patients (n = 8917) who were hypopituitary due to pituitary adenomas, craniopharyngiomas, and other sellar tumors followed in KIMS (Pfizer International Metabolic Database) from 1994 to 2012 were included. Treatment consisted of surgery and/or medical therapy in 4927 patients, RT alone, or with surgery in 3236 patients; data were missing in 754. Incidence rate ratios (RRs) were analyzed through Poisson regression methods with internal comparisons. RESULTS: During 53,786 patient-years, 17 cases of malignant brain tumors (13 exposed to RT) and 27 meningiomas (22 exposed to RT) were reported. RR for RT vs no RT was 3.34 [95% confidence interval (CI), 1.06 to 10.6] for malignant brain tumors, and 4.06 (95% CI, 1.51 to 10.9) for meningiomas. The risk of developing a malignant brain tumor increased by 2.4-fold (P = 0.005) and meningioma by 1.6-fold with every 10 years of younger age at RT (P = 0.05). Incidence rates were similar in patients treated with conventional RT compared with stereotactic RT. CONCLUSION: RT of pituitary tumors is associated with increased risk of developing malignant brain tumors and meningiomas, especially when given at younger ages. In balancing risks and benefits of RT, our findings emphasize that special consideration should be given to the age of the patient.


Assuntos
Adenoma/terapia , Neoplasias Encefálicas/epidemiologia , Irradiação Craniana , Craniofaringioma/terapia , Glioma/epidemiologia , Neoplasias Meníngeas/epidemiologia , Meningioma/epidemiologia , Neuroblastoma/epidemiologia , Neoplasias Hipofisárias/terapia , Adenoma/complicações , Adolescente , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Astrocitoma/epidemiologia , Criança , Pré-Escolar , Craniofaringioma/complicações , Feminino , Glioblastoma/epidemiologia , Hormônio do Crescimento/uso terapêutico , Humanos , Hipopituitarismo/etiologia , Hipopituitarismo/terapia , Incidência , Masculino , Pessoa de Meia-Idade , Procedimentos Neurocirúrgicos , Oligodendroglioma/epidemiologia , Neoplasias Hipofisárias/complicações , Distribuição de Poisson , Radiocirurgia , Análise de Regressão , Estudos Retrospectivos , Fatores de Risco , Adulto Jovem
10.
Fertil Steril ; 104(5): 1210-7.e1, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26256649

RESUMO

OBJECTIVE: To study pregnancies in a large group of patients with growth hormone deficiency and hypopituitarism; and to investigate potential factors determining pregnancy outcomes and pregnancy complications. DESIGN: We analyzed pregnancies reported in KIMS, the Pfizer International Metabolic Database, of adult patients with growth hormone deficiency treated with growth hormone. SETTING: Outpatient clinics. PATIENT(S): A total of 201 pregnancies were reported: 173 in female patients and 28 in partners of male patients. INTERVENTION(S): Growth hormone replacement therapy (GHRT) was prescribed according to the local clinical practice. MAIN OUTCOME MEASURE(S): Pregnancy outcomes (live births, gestational week at delivery, and birth weight), pregnancy complications, and their relationship to use of GHRT during pregnancy were analyzed with regression models. RESULT(S): Two-thirds of women underwent fertility treatment to achieve pregnancy. Growth hormone replacement therapy was stopped before pregnancy in 7.5% of the female patients, as soon as pregnancy was confirmed in 40.1%, and at the end of the second trimester in 24.7% of the patients, whereas 27.6% continued GHRT throughout pregnancy. Birth of a healthy child was reported in 79% of the female pregnancies, nonelective abortions occurred mainly in the first trimester, and one fetal malformation (cystic hygroma) was diagnosed in the second trimester. Pregnancy outcomes and pregnancy complications were not related to GHRT treatment patterns, method of conception, or number of additional pituitary deficiencies. CONCLUSION(S): These data on pregnancy outcomes in a large group of women with hypopituitarism revealed no relationship between GHRT regimens and pregnancy outcomes.


Assuntos
Hormônio do Crescimento Humano/deficiência , Hipopituitarismo/complicações , Resultado da Gravidez , Adolescente , Adulto , Biomarcadores/sangue , Peso ao Nascer , Bases de Dados Factuais , Esquema de Medicação , Europa (Continente) , Feminino , Idade Gestacional , Terapia de Reposição Hormonal/efeitos adversos , Hormônio do Crescimento Humano/administração & dosagem , Hormônio do Crescimento Humano/efeitos adversos , Hormônio do Crescimento Humano/sangue , Humanos , Hipopituitarismo/sangue , Hipopituitarismo/diagnóstico , Hipopituitarismo/tratamento farmacológico , Nascido Vivo , Masculino , Pessoa de Meia-Idade , Gravidez , Complicações na Gravidez/etiologia , Estudos Prospectivos , Técnicas de Reprodução Assistida , Fatores de Risco , Fatores de Tempo , Estados Unidos , Adulto Jovem
11.
Eur J Endocrinol ; 172(4): 371-81, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25583905

RESUMO

OBJECTIVE: Prevalence of GH deficiency (GHD) caused by traumatic brain injury (TBI) is highly variable. Short-term studies show improvement in quality of life (QoL) during GH replacement (GHR), but long-term data are lacking. The aim of this study was to analyse the clinical characteristics of post-traumatic hypopituitarism and the QoL effects of long-term GHR. DESIGN/METHODS: Pfizer International Metabolic Database patients with GHD caused by TBI and by non-functioning pituitary adenoma (NFPA) were compared regarding: clinical characteristics at baseline and 1-year of GHR, and QoL response up to 8-years of GHR (QoL-AGHDA total scores and dimensions) in relationship with country-specific norms. RESULTS: TBI patients compared with NFPA patients were younger, diagnosed with GHD 2.4 years later after primary disease onset (P<0.0001), had a higher incidence of isolated GHD, higher GH peak, a more favourable metabolic profile and worse QoL, were shorter by 0.9 cm (1.8 cm when corrected for age and gender; P=0.004) and received higher GH dose (mean difference: 0.04 mg/day P=0.006). In TBI patients, 1-year improvement in QoL was greater than in NFPA (change in QoL-AGHDA score 5.0 vs 3.5, respectively, P=0.04) and was sustained over 8 years. In TBI patients, socialisation normalised after 1 year of GHR, self-confidence and tenseness after 6 years and no normalisation of tiredness and memory was observed. CONCLUSION: Compared with NFPA, TBI patients presented biochemically with less severe hypopituitarism and worse QoL scores. GHR achieved clinically relevant, long-term benefit in QoL.


Assuntos
Lesões Encefálicas/complicações , Lesões Encefálicas/tratamento farmacológico , Hormônio do Crescimento Humano/deficiência , Hormônio do Crescimento Humano/uso terapêutico , Hipopituitarismo/tratamento farmacológico , Hipopituitarismo/etiologia , Qualidade de Vida , Adenoma/complicações , Adenoma/tratamento farmacológico , Adenoma/epidemiologia , Adenoma/psicologia , Adulto , Lesões Encefálicas/epidemiologia , Lesões Encefálicas/psicologia , Bases de Dados Factuais , Feminino , Terapia de Reposição Hormonal , Humanos , Hipopituitarismo/epidemiologia , Hipopituitarismo/psicologia , Masculino , Pessoa de Meia-Idade , Neoplasias Hipofisárias/complicações , Neoplasias Hipofisárias/tratamento farmacológico , Neoplasias Hipofisárias/epidemiologia , Neoplasias Hipofisárias/psicologia
12.
Eur J Endocrinol ; 171(5): 571-9, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25127712

RESUMO

OBJECTIVE: Quality of life (QoL) is impaired in hypopituitary patients and patients with primary adrenal insufficiency. The aim of this study was to analyse 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 from KIMS (Pfizer International Metabolic Database). Data from 2737 adult GH-deficient (GHD) hypopituitary patients were eligible for analysis. Thirty-six per cent were ACTH sufficient and 64% ACTH insufficient receiving a mean±s.d. hydrocortisone equivalent (HCeq) dose of 22.3±8.7 mg (median 20.0). QoL at baseline and 1 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 HCeq dose was associated with worse QoL. Patients on HCeq≤10 mg had the best and patients receiving ≥25 mg demonstrated the poorest QoL. At 1 year of GH replacement, the improvement in QoL did not differ between ACTH-sufficient and -insufficient patients, and no association was observed between HCeq dose and QoL improvement. CONCLUSION: Adult hypopituitary patients with untreated GHD 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.


Assuntos
Glucocorticoides/uso terapêutico , Terapia de Reposição Hormonal , Hipopituitarismo/tratamento farmacológico , Qualidade de Vida , Doença de Addison/tratamento farmacológico , Doença de Addison/epidemiologia , Doença de Addison/etiologia , Adenoma/complicações , Adenoma/tratamento farmacológico , Adenoma/epidemiologia , Adulto , Feminino , Humanos , Hipopituitarismo/epidemiologia , Hipopituitarismo/etiologia , Masculino , Pessoa de Meia-Idade , Neoplasias Hipofisárias/complicações , Neoplasias Hipofisárias/tratamento farmacológico , Neoplasias Hipofisárias/epidemiologia , Estudos Retrospectivos
13.
J Clin Endocrinol Metab ; 99(6): 2018-29, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24694339

RESUMO

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.


Assuntos
Acromegalia/terapia , Terapia de Reposição Hormonal , Hormônio do Crescimento Humano/uso terapêutico , Hipopituitarismo/tratamento farmacológico , Acromegalia/epidemiologia , Adulto , Idoso , Bases de Dados Factuais/estatística & dados numéricos , Feminino , Seguimentos , Terapia de Reposição Hormonal/efeitos adversos , Terapia de Reposição Hormonal/estatística & dados numéricos , Hormônio do Crescimento Humano/deficiência , Humanos , Hipopituitarismo/epidemiologia , Hipopituitarismo/etiologia , Masculino , Pessoa de Meia-Idade , Indução de Remissão , Estudos Retrospectivos , Resultado do Tratamento , Adulto Jovem
14.
Eur J Endocrinol ; 168(3): 297-305, 2013 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-23211573

RESUMO

OBJECTIVE: GH deficiency (GHD) in adults is characterized by a tendency toward obesity and an adverse body composition with visceral fat deposit and may thus predispose to the development of type 2 diabetes mellitus. The aim of this study was to assess the observed prevalence proportion (PP) and observed PP over expected PP ratio (standardized prevalence proportion ratio, SPR) of diabetes according to International Diabetes Federation criteria in a large cohort of GH-untreated adult-onset GHD patients. DESIGN AND METHODS: Associations between baseline variables and diabetes prevalence in 6050 GHD patients from KIMS (Pfizer International Metabolic Database) were studied and robust Poisson-regression analyses were performed. Comparisons between baseline status and HbA1c categories in the nondiabetic patients were done with covariance analysis. P values <0.05 were considered statistically significant. RESULTS: PP was 9.3% compared with the expected 8.2%. SPR was 1.13 (95% confidence intervals (95% CIs), 1.04-1.23), which was significantly increased in females (1.23; 95% CI, 1.09-1.38%) but not in males (SPR 1.04; 95% CI, 0.92-1.17%). PP increased significantly by age, familial diabetes, country selection, BMI, waist circumference, number of pituitary deficiencies, and GHD etiology. SPR decreased significantly by age and increased significantly by BMI, waist circumference, and IGF1 SDS. Multiple regression model showed that the most important impact on SPR was from age and BMI. HbA1c values of 6.0-6.5% were found in 9.5% of nondiabetic patients and were associated with higher BMI and waist circumference. CONCLUSIONS: GHD is associated with an increased prevalence of diabetes, largely to be explained by the adverse body composition. These data urge toward early initiation of lifestyle modification measures.


Assuntos
Diabetes Mellitus Tipo 2/etiologia , Hormônio do Crescimento Humano/deficiência , Hipopituitarismo/fisiopatologia , Adulto , Idade de Início , Idoso , Índice de Massa Corporal , Estudos de Coortes , Diabetes Mellitus Tipo 2/epidemiologia , Europa (Continente)/epidemiologia , Feminino , Hemoglobinas Glicadas/análise , Humanos , Hipopituitarismo/sangue , Hipopituitarismo/complicações , Masculino , Pessoa de Meia-Idade , Sobrepeso/complicações , Distribuição de Poisson , Prevalência , Fatores Sexuais , Estados Unidos/epidemiologia , Adulto Jovem
15.
Eur J Endocrinol ; 166(6): 1069-77, 2012 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-22457236

RESUMO

OBJECTIVE: Hypopituitarism is associated with an increased mortality rate but the reasons underlying this have not been fully elucidated. The purpose of this study was to evaluate mortality and associated factors within a large GH-replaced population of hypopituitary patients. DESIGN: In KIMS (Pfizer International Metabolic Database) 13,983 GH-deficient patients with 69,056 patient-years of follow-up were available. METHODS: This study analysed standardised mortality ratios (SMRs) by Poisson regression. IGF1 SDS was used as an indicator of adequacy of GH replacement. Statistical significance was set to P<0.05. RESULTS: All-cause mortality was 13% higher compared with normal population rates (SMR, 1.13; 95% confidence interval, 1.04-1.24). Significant associations were female gender, younger age at follow-up, underlying diagnosis of Cushing's disease, craniopharyngioma and aggressive tumour and presence of diabetes insipidus. After controlling for confounding factors, there were statistically significant negative associations between IGF1 SDS after 1, 2 and 3 years of GH replacement and SMR. For cause-specific mortality there was a negative association between 1-year IGF1 SDS and SMR for deaths from cardiovascular diseases (P=0.017) and malignancies (P=0.044). CONCLUSIONS: GH-replaced patients with hypopituitarism demonstrated a modest increase in mortality rate; this appears lower than that previously published in GH-deficient patients. Factors associated with increased mortality included female gender, younger attained age, aetiology and lower IGF1 SDS during therapy. These data indicate that GH replacement in hypopituitary adults with GH deficiency may be considered a safe treatment.


Assuntos
Terapia de Reposição Hormonal , Hormônio do Crescimento Humano/efeitos adversos , Hormônio do Crescimento Humano/deficiência , Hipopituitarismo/mortalidade , Adulto , Idoso , Feminino , Terapia de Reposição Hormonal/efeitos adversos , Hormônio do Crescimento Humano/administração & dosagem , Humanos , Hipopituitarismo/tratamento farmacológico , Hipopituitarismo/etiologia , Fator de Crescimento Insulin-Like I/metabolismo , Masculino , Pessoa de Meia-Idade , Distribuição de Poisson
16.
Diabetes Care ; 35(1): 57-62, 2012 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-22074727

RESUMO

OBJECTIVE: Growth hormone (GH) deficiency is associated with insulin resistance and diabetes. The aim of the current study was to determine incidence of diabetes during GH replacement therapy (GHRT) and the effect of GHRT on fasting plasma glucose concentrations and HbA(1c) in adult patients with GH deficiency. RESEARCH DESIGN AND METHODS: A total of 5,143 GH-deficient patients (male 49.9%; mean age ± SD, 49 ± 13 years; BMI 29.1 ± 5.9 kg/m(2)) were analyzed. Mean observation period was 3.9 years (range 0.01-13). Total number of patient-years was 20,106. Observed number of cases (O) was compared with expected number of cases (E). Reference rates were from Sweden, three additional European regions, and one U.S. region. RESULTS: Patients who developed diabetes (n = 523) were older; had higher BMI, waist circumference, triglyceride concentrations, and blood pressure; and had lower HDL-cholesterol concentrations (P < 0.0001) than those who did not develop diabetes. Diabetes incidence was 2.6 per 100 patient-years, equal in both sexes, and significantly increased compared with the Swedish reference (O/E = 6.02; P < 0.0001) as well as with the four other populations (O/E = 2.11-5.22). O/E increased with BMI and decreased with duration of GHRT (P < 0.0001). There was no significant association with GH dose (P = 0.74) or IGF-I SDS (P = 0.47). In subjects not developing diabetes, plasma glucose concentrations increased from 84.4 ± 0.9 mg/dL to 89.5 ± 0.8 mg/dL (0.70 mg/dL/year) and HbA(1c) increased from 4.74 ± 0.04% to 5.09 ± 0.13% (0.036%/year) after 6 years of GHRT. CONCLUSIONS: Diabetes incidence appears to be increased in GH-deficient patients receiving GHRT and exhibiting an adverse risk profile at baseline. Therefore, glucose homeostasis parameters should be monitored carefully in these patients.


Assuntos
Glicemia/metabolismo , Diabetes Mellitus Tipo 2/etiologia , Transtornos do Crescimento/tratamento farmacológico , Hormônio do Crescimento Humano/deficiência , Hormônio do Crescimento Humano/uso terapêutico , Adulto , Idoso , Diabetes Mellitus Tipo 2/epidemiologia , Feminino , Hemoglobinas Glicadas/metabolismo , Transtornos do Crescimento/sangue , Terapia de Reposição Hormonal , Humanos , Incidência , Masculino , Pessoa de Meia-Idade
17.
Eur J Endocrinol ; 165(6): 881-9, 2011 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-21969523

RESUMO

OBJECTIVE: An increased risk of cardiovascular morbidity and mortality in adult GH deficiency (GHD) may be related to hypopituitarism but also to the presence of the metabolic syndrome (MetS). Our objective was to investigate the characteristics and prevalence of MetS as well as its comorbidities in adult GHD. Design In KIMS (Pfizer International Metabolic Database) 2479 patients with severe adult-onset GHD, naïve to GH replacement, with complete information on all MetS components were found. MetS was defined according to the National Cholesterol Education Program's Adult Treatment Panel III (NCEP) and the International Diabetes Foundation (IDF). METHODS: The prevalence of MetS was calculated and compared with previously published data from the normal population. Associations were assessed between background variables, baseline variables, comorbidities, and MetS. RESULTS: MetS was present in 43.1% (NCEP) and in 49.1% (IDF) of patients, clearly higher than data from the normal population (20-30%). MetS prevalence was related to age, GHD duration, and body mass index (BMI), but not to GHD severity, extent of hypopituitarism, or etiology of pituitary disease. Adjusted for age, gender, and BMI, patients with MetS had a higher prevalence ratio for diabetes mellitus: 4.65 (95% confidence interval (CI): 3.29-6.58), for cardiovascular morbidity: 1.91 (95% CI: 1.33-2.75), and for cerebrovascular morbidity: 1.77 (95% CI: 1.09-2.87) than patients without MetS. CONCLUSIONS: MetS is highly prevalent in GHD and is associated with a higher prevalence ratio for comorbidities. The presence of MetS in GHD may therefore contribute to the increased risk of cardiovascular morbidity and mortality found in these patients.


Assuntos
Terapia de Reposição Hormonal , Hormônio do Crescimento Humano/deficiência , Hipopituitarismo/epidemiologia , Síndrome Metabólica/diagnóstico , Síndrome Metabólica/epidemiologia , Adulto , Fatores Etários , Estudos de Coortes , Feminino , Terapia de Reposição Hormonal/métodos , Hormônio do Crescimento Humano/sangue , Hormônio do Crescimento Humano/uso terapêutico , Humanos , Hipopituitarismo/sangue , Hipopituitarismo/diagnóstico , Masculino , Síndrome Metabólica/sangue , Pessoa de Meia-Idade , Prevalência
18.
J Clin Endocrinol Metab ; 95(9): 4449-54, 2010 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-20610598

RESUMO

CONTEXT: The association between IGFs and cancer in adults with GH deficiency (GHD) receiving GH replacement requires investigation. OBJECTIVE: The objective was to examine the association between IGF-I, IGF-binding protein 2 (IGFBP-2), and IGFBP-3 SD scores (SDSs) in GH-deficient adults receiving GH therapy and the occurrence of de novo malignancies. DESIGN: Serum IGF-I, IGFBP-2, and IGFBP-3 levels in GH-deficient patients who developed a malignancy since receiving GH were compared with patients with idiopathic GHD but without malignancy. Measurements were related to age-, sex-, and body mass index-specific SDS reference regions. SETTING: The setting included the KIMS (the Pfizer International Metabolic Database). PATIENTS: One hundred patients with de novo malignancy during GH therapy were compared with 325 patients with idiopathic GHD without malignancy. INTERVENTION(S): Serum samples were obtained as close as possible to the diagnosis of malignancy, or after approximately 2 yr of GH replacement in KIMS. MAIN OUTCOME MEASURES: Associations between relative risk (RR) of malignancy and IGF-I, IGFBP-2, and IGFBP-3 SDSs were assessed in multiple log-linear Poisson working regression models, controlling for age, sex, onset of GHD, and GH naivety at KIMS entry. RESULTS: No association between IGF-I SDSs and RR was observed (P = 0.48). Increasing IGFBP-2 and IGFBP-3 SDSs were associated with increasing RRs [18% per unit IGFBP-2 SDSs (95% confidence interval, 7-30%; P = 0.0006), 13% per unit IGFBP-3 SDS (2-26%; P = 0.01)]. CONCLUSIONS: IGF-I levels targeted to within normal age-related reference ranges during GH replacement were not associated with the occurrence of malignancies. Higher IGFBP-2 and/or IGFBP-3 SDSs may be associated with increased cancer risk.


Assuntos
Hormônio do Crescimento Humano/uso terapêutico , Hipopituitarismo/tratamento farmacológico , Proteína 2 de Ligação a Fator de Crescimento Semelhante à Insulina/sangue , Proteína 3 de Ligação a Fator de Crescimento Semelhante à Insulina/sangue , Fator de Crescimento Insulin-Like I/análise , Neoplasias/etiologia , Adulto , Idoso , Estudos de Casos e Controles , Bases de Dados Factuais , Indústria Farmacêutica , Feminino , Terapia de Reposição Hormonal , Hormônio do Crescimento Humano/sangue , Hormônio do Crescimento Humano/deficiência , Humanos , Hipopituitarismo/sangue , Hipopituitarismo/complicações , Hipopituitarismo/epidemiologia , Cooperação Internacional , Masculino , Pessoa de Meia-Idade , Neoplasias/sangue , Neoplasias/epidemiologia , Risco
19.
J Pediatr ; 157(2): 265-70, 2010 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-20400105

RESUMO

OBJECTIVE: To assess the incidence of cancer in patients treated with growth hormone (GH) in KIGS - the Pfizer International Growth Database-without cancer or any other condition in medical history known to increase the risk of cancer. STUDY DESIGN: Data were analyzed from patients with growth disorders enrolled in an observational survey KIGS who had no known increased risk of developing cancer before starting recombinant human GH treatment. The incidence of cancer in this patient cohort (overall, site-specific, and according to etiology of growth disorder) was compared with the incidence in the general population by using the standardized incidence ratio (ie, relating the observed to expected number of cases with stratification for age, sex, and country). RESULTS: A total of 32 new malignant neoplasms were reported in 58 603 patients, versus the 25.3 expected (incidence, 16.4 per 100 000 patient-years; standardized incidence ratio, 1.26; 95% confidence interval, 0.86-1.78). No category of growth disorder showed a statistically significant difference in observed compared with the expected number of cases. CONCLUSION: There is no evidence in this series that GH treatment in young patients with growth disorders results in an increased risk of developing cancer relative to that expected in the normal population. However, surveillance for an extended time should continue to allow further assessment.


Assuntos
Transtornos do Crescimento/tratamento farmacológico , Hormônio do Crescimento Humano/efeitos adversos , Hormônio do Crescimento Humano/uso terapêutico , Neoplasias/induzido quimicamente , Adolescente , Criança , Pré-Escolar , Estudos de Coortes , Bases de Dados Factuais , Feminino , Humanos , Incidência , Masculino , Neoplasias/epidemiologia , Proteínas Recombinantes/efeitos adversos , Proteínas Recombinantes/uso terapêutico , Fatores de Risco , Resultado do Tratamento
20.
Eur J Endocrinol ; 161 Suppl 1: S51-64, 2009 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-19684056

RESUMO

Quality of life (QoL) has emerged as an important construct that has found numerous applications across healthcare-related fields, ranging from research and clinical evaluation of treatment effects to pharmacoeconomic evaluations and global healthcare policy. Impairment of QoL is one of the key clinical characteristics in adult GHD and has been extensively studied in the Pfizer International Metabolic Database (KIMS). We provide summarized evidence on GH treatment effects for both clinical and health economic applications based on the KIMS data. The primary focus is on those aspects of QoL research that cannot be investigated in the traditional clinical trial setting, such as specific patient subgroups, cross-country comparisons and long-term follow-up. First, the impact of age, gender, disease onset, primary aetiology, extent of hypopituitarism, previous radiotherapy and obesity on QoL before and during long-term GH replacement is discussed. Secondly, the studies on QoL in relation to country-specific normative values are reviewed. Finally, health economic data derived from KIMS including both burden of disease and utility assessment are evaluated. We conclude that the wide spectrum of analyses performed on the KIMS data allows for practical application of the results not only to research and clinical practice but also to health policy and global medical decision making.


Assuntos
Custos de Medicamentos , Hormônio do Crescimento Humano/deficiência , Hormônio do Crescimento Humano/uso terapêutico , Hipopituitarismo/tratamento farmacológico , Qualidade de Vida , Adulto , Fatores Etários , Idoso , Biomarcadores/sangue , Fatores de Confusão Epidemiológicos , Bases de Dados Factuais , Feminino , Recursos em Saúde/estatística & dados numéricos , Hormônio do Crescimento Humano/economia , Humanos , Hipopituitarismo/economia , Fator de Crescimento Insulin-Like I/metabolismo , Cooperação Internacional , Masculino , Pessoa de Meia-Idade , Fatores Sexuais
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