RESUMO
PURPOSE: Acromegaly and neuroendocrine tumors are rare diseases that, under certain conditions, can be treated with somatostatin analogs. The aim was to determine the prescription patterns of somatostatin analogs in a group of patients with acromegaly and neuroendocrine tumors affiliated with the Colombian Health System. METHODS: A retrospective study. A cohort of patients from a drug dispensing database that collected all prescriptions of long-acting somatostatin analogs (octreotide, lanreotide, pasireotide). Sociodemographic variables, clinical variables (diagnosis and comorbidities) and pharmacological therapy variables (dose, changes, persistence of use, comedications) were considered. RESULTS: A total of 213 patients were identified, including 139 (65.3%) with acromegaly and 74 (34.7%) with neuroendocrine tumors. There was a predominance of women (58.7%) and a mean age of 59.7 ± 14.5 years. The most commonly used medications were lanreotide autogel (n = 107; 50.2%), octreotide LAR (n = 102; 47.9%) and pasireotide LAR (n = 4; 1.9%). During follow-up, 11.3% of patients experienced modifications of therapy, with a mean duration from the beginning of treatment to the change in medication of 25 ± 15.9 months. A total of 48.9% of the patients with acromegaly and 87.1% of individuals with neuroendocrine tumors received maximum approved doses of the drug. CONCLUSION: Patients with acromegaly and neuroendocrine tumors in Colombia are mainly women and are most frequently treated with lanreotide autogel for acromegaly and with octreotide LAR for neuroendocrine tumors. In addition, a high proportion are managed with maximum doses of long-acting somatostatin analogs.
Assuntos
Acromegalia , Tumores Neuroendócrinos , Peptídeos Cíclicos , Somatostatina , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Acromegalia/tratamento farmacológico , Acromegalia/induzido quimicamente , Tumores Neuroendócrinos/tratamento farmacológico , Octreotida/uso terapêutico , Peptídeos Cíclicos/uso terapêutico , Estudos Retrospectivos , Somatostatina/análogos & derivadosRESUMO
OBJECTIVE: We aimed to evaluate the awareness and perspectives of acromegaly patients in the diagnosis and treatment processes and to evaluate basic clinical and demographic features. METHODS: This cross-sectional study was conducted at the Endocrinology Department of Yildirim Beyazit University between March 2019 and April 2020. A total of 58 acromegalic patients were enrolled. All patients were identified from our database and called for a clinical visit and filling the questionnaire forms. RESULTS: A total of 58 patients were included in this study (41.4% female). The mean age of the patients was 52±10.8 years. Median year from symptom to diagnosis (min-max) was 2 (1-12). Notably, 55.2% of the patients did not graduate from high school. Of the 58 patients, 30 (51.7%) patients had knowledge about the etiology of their disease. While 12 (20.7%) patients identified their initial symptoms themselves, 75% of the patients reported their symptoms during the clinical history taken by a health care professional. The majority of patients were diagnosed by an endocrinologist (69%). Acromegaly did not affect social life but affected work life and caused early retirement. Transsphenoidal surgery was performed as primary treatment in 96.6% of the patients (n=56). In all, 46 (79.3%) patients received medical treatment with somatostatin receptor ligands (e.g., octreotide or lanreotide long-acting release [LAR]) with or without cabergoline. Overall disease control was achieved in 38 (65.5%) patients. CONCLUSIONS: Acromegaly is usually detected incidentally by clinicians. The diagnosis of acromegaly is delayed in most patients and disease-related complications have already developed at the time of diagnosis. Therefore, increasing the awareness of the society and health care professionals will reduce both disease-related comorbidities and the economic burden on the health system.
Assuntos
Acromegalia , Acromegalia/induzido quimicamente , Acromegalia/diagnóstico , Acromegalia/terapia , Adulto , Estudos Transversais , Preparações de Ação Retardada/uso terapêutico , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Octreotida/efeitos adversosRESUMO
Pharmacogenetics aims to maximize the beneficial effects of a medical therapy by identifying genetic finger prints from responders and non-responders and, thereby improving safety and efficacy profile of the drug. Most subjects who are deficient in growth hormone (GHD) are candidates for recombinant human GH (rhGH) therapy. To date, it is well established that even after adjustments for several clinical variables, such as age, gender, body composition and the age at onset of the GHD, response to rhGH treatment is highly variable among individuals, part of which is believed to be due to genetic factors within the GH system. As the first genetic variant to potentially influence the individual response to rhGH therapy in children with growth disorders, polymorphism in the GH receptor (GHR) has attracted a great interest as a target for pharmacogenetics. Studies have been conducted to compare the functional and molecular effects of the full-length GHR (fl-GHR) isoform with the exon 3 deleted (d3-GHR) isoform in children and adults treated with rhGH therapy. Additionally, the impact of the GHR polymorphism has been investigated in relation to the clinical status and response to medical treatment in acromegaly, especially to the GHR antagonist drug pegvisomant. We have performed a narrative review of the studies performed to date on the association of GHR polymorphism with rhGH response in children and adults, and its potential influence in the medical management of acromegaly. In addition, data from studies on the general population and in other chronic diseases examining a role of this genetic variant in the regulation of growth and metabolism are summarized.
Assuntos
Transtornos do Crescimento/tratamento farmacológico , Terapia de Reposição Hormonal/efeitos adversos , Hormônio do Crescimento Humano/deficiência , Hormônio do Crescimento Humano/uso terapêutico , Variantes Farmacogenômicos , Polimorfismo Genético , Receptores da Somatotropina/genética , Acromegalia/induzido quimicamente , Acromegalia/genética , Acromegalia/metabolismo , Acromegalia/terapia , Adulto , Criança , Resistência a Medicamentos , Éxons , Deleção de Genes , Transtornos do Crescimento/etiologia , Transtornos do Crescimento/genética , Transtornos do Crescimento/metabolismo , Hormônio do Crescimento Humano/efeitos adversos , Hormônio do Crescimento Humano/análogos & derivados , Hormônio do Crescimento Humano/genética , Humanos , Fragmentos de Peptídeos/efeitos adversos , Fragmentos de Peptídeos/genética , Fragmentos de Peptídeos/metabolismo , Fragmentos de Peptídeos/uso terapêutico , Isoformas de Proteínas/efeitos adversos , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo , Isoformas de Proteínas/uso terapêutico , Receptores da Somatotropina/agonistas , Receptores da Somatotropina/antagonistas & inibidores , Receptores da Somatotropina/metabolismo , Proteínas Recombinantes/efeitos adversos , Proteínas Recombinantes/metabolismo , Proteínas Recombinantes/uso terapêuticoRESUMO
BACKGROUND: Craniofacial, hand, foot and somatic growth depend on normal GH secretion. Acromegalic features have been described in children with GH insensitivity after IGF-I treatment. We observed patients with acromegalic features such as increase of foot size, nose and jaw enlargement among our cases with GH deficiency, treated with standard recombinant (rh)GH doses. The aim of our study was to analyse the possible factors involved in the development of acromegalic features in these patients. PATIENTS: We evaluated 21 patients, 17 with combined pituitary hormone deficiency and four with isolated GH deficiency treated with rhGH (0.05-0.15 U/kg/day, sc, at night) for 2-12 years who achieved final height. IGF-I and IGFBP-3 were measured before and every 6 months during therapy and bone age was evaluated yearly. At the end of therapy, patients' hand and foot sizes and height were measured and plotted on nomograms for hand according to height and age, and foot size according to height. Lateral radiographs of the face were performed to obtain the linear measurement of the lower jaw length. RESULTS: Foot size was greater than 97th percentile in 8/21 patients and lower jaw length was greater than +2SD in 4/21 patients. Patients were classified in two groups: group 1 (with foot size greater than 97th percentile and/or lower jaw length greater than +2SD) consisted of 11 patients (six females); nine had combined pituitary hormone deficiency (six associated to hypogonadotrophic hypogonadism) and three had isolated GH deficiency; group 2 (with foot size smaller than 97th percentile and lower jaw length less than +2SD) consisted of 10 patients (seven boys); nine had combined pituitary hormone deficiency (six associated to hypogonadotrophic hypogonadism) and one with isolated GH deficiency. During treatment, IGF-I levels ranged from < or = 3 to +2SD and IGFBP-3 levels ranged from -3 to +2SD, in both groups. We observed no statistically significant differences between the two groups regarding chronological age, bone age, height at the beginning and at the end of therapy, pubertal development, duration of rhGH treatment and IGF-I and IGFBP-3 levels (P > 0.05). Foot size percentile exceeded final height percentile in 11/21 patients (seven girls). CONCLUSION: Long-term rhGH treatment with standard doses might be associated with acromegalic features (increased foot size and lower jaw measurements) in patients with GH deficiency who achieved final height, especially in girls. Neither the clinical nor the hormonal parameters, IGF-I and IGFBP-3 levels, were useful to predict the development of these features. Further studies are necessary to analyse the frequency of this side-effect and how to prevent it.