RESUMO

PURPOSE: To evaluate clinical, laboratory, radiological, therapeutic, and prognostic characteristics of patients with acromegaly according to the size of the growth hormone (GH)-secreting pituitary adenoma at diagnosis. METHODS: Observational, retrospective, single-center study of patients with acromegaly followed at a tertiary center. Data were collected regarding clinical presentation, characteristics of the adenoma in the magnetic resonance imaging, GH and IGF-1 levels, and disease control after surgery or adjuvant treatment (normal IGF-1 levels). Patients were divided according to the adenoma size at diagnosis in: group I < 10 mm; II 10-19 mm; III 20-29 mm; IV 30-39 mm; and V ≥ 40 mm. Comparisons were made between the groups, and correlations of tumor size with disease parameters, ROC curves, and logistic regression analyses were performed to investigate tumor size and confounding factors that could impact the outcomes. RESULTS: 117 patients were studied [59 women, age at diagnosis 43 ± 13 years; group I = 11 patients (9%); group II 54 (46%); group III 34 (29%); group IV 10 (9%); group V 8 (7%)]. Hypopituitarism, cavernous sinus invasion, GH levels, and use of somatostatin receptor ligands had their prevalence increased according to the adenoma size. Age showed a negative correlation with tumor size. A tumor diameter around 20 mm was the best predictor for the presence of hypopituitarism, invasiveness, need of adjuvant therapies, and poorer disease control. CONCLUSION: Adenomas < 20 mm showed lower morbidity and better therapeutic response in acromegaly, while those ≥ 20 mm had similar clinical, therapeutic, and prognostic behavior.

RESUMO

CONTEXT: Paltusotine is a nonpeptide selective somatostatin receptor 2 agonist in development as once-daily oral treatment for acromegaly. OBJECTIVE: To evaluate the efficacy and safety of paltusotine in the treatment of patients with acromegaly previously controlled with injected somatostatin receptor ligands (SRLs). METHODS: This phase 3, randomized, double-blind, placebo-controlled trial enrolled adults with acromegaly who had insulin-like growth factor I (IGF-I) ≤1.0 times the upper limit of normal (×ULN) while receiving a stable dose of depot octreotide or lanreotide. Patients were switched from injected SRLs and randomized to receive paltusotine or placebo orally for 36 weeks. The primary endpoint was proportion of patients maintaining IGF-I ≤1.0×ULN. Secondary endpoints were change in IGF-I level, change in Acromegaly Symptom Diary (ASD) score, and maintenance of mean 5-sample growth hormone (GH) <1.0 ng/mL. RESULTS: The primary endpoint was met: 83.3% (25/30) of patients receiving paltusotine and 3.6% (1/28) receiving placebo maintained IGF-I ≤1.0×ULN (odds ratio: 126.53; 95% CI: 13.73, >999.99; P<.0001). Paltusotine was also superior to placebo for all secondary endpoints: mean (±SE) change in IGF-I of 0.04±0.09×ULN versus 0.83±0.1×ULN (P<.0001); mean (±SE) change in ASD score of -0.6±1.5 versus 4.6±1.6 (P=.02); mean GH maintained at <1.0 ng/mL in 20/23 (87.0%) versus 5/18 (27.8%) patients (odds ratio: 16.61; 95% CI: 2.86, 181.36; P=.0003). The most common adverse events were acromegaly symptoms and gastrointestinal effects characteristic of SRLs. CONCLUSION: Replacement of injected SRLs by once-daily oral paltusotine was effective in maintaining both biochemical and symptom control in patients with acromegaly and was well tolerated.

RESUMO

Hypopituitarism is a rare endocrine disorder characterized by insufficient hormone secretion from the pituitary gland. This condition leads to deficient production of one or more pituitary hormones, including growth hormone (GH), thyroid-stimulating hormone (TSH), luteinizing hormone (LH), follicle-stimulating hormone (FSH), adrenocorticotropic hormone (ACTH), and antidiuretic hormone (ADH), also called arginine vasopressin (AVP). Symptoms vary widely and are often not, late recognized.Diagnosis typically involves a thorough clinical evaluation, hormone level assessments, and neuroimaging studies to identify underlying causes. Treatment aims to replace deficient hormones and address the underlying cause and related complications when possible. In this special issue we address diagnosis, comorbidities, and management of hypopituitarism. We hope that it will help healthcare professionals to manage their patients.

Assuntos

RESUMO

BACKGROUND: The trabecular bone score (TBS) indirectly estimates bone quality and predicts low-impact fractures independently of bone mineral density (BMD). However, there is still a paucity of data linking bone and heart diseases, mainly with gaps in the TBS analysis. METHODS: In this cross-sectional study, we evaluated TBS, BMD, and fractures in patients with heart failure with reduced ejection fraction (HFrEF) and in sex-, BMI- and age-matched controls, and we assessed the fracture probability using the FRAX tool, considering active search for fractures by vertebral fracture assessment (VFA) and the adjustment for the TBS. RESULTS: TBS values were 1.296 ± 0.14 in 85 patients (43.5% women; age 65 ± 13 years) and 1.320 ± 0.11 in 142 controls (P = 0.07), being reduced (< 1.31) in 51.8% and 46.1% of them, respectively (P = 0.12). TBS was lower in patients than in the controls when BMD was normal (P = 0.04) and when the BMI was 15-37 kg/m2 (P = 0.03). Age (odds ratio [OR] 1.05; P = 0.026), albumin (OR 0.12; P = 0.046), statin use (OR 0.27; P = 0.03), and energy intake (OR 1.03; P = 0.014) were associated with reduced TBS. Fractures on VFA occurred in 42.4% of the patients, and VFA and TBS adjustment increased the fracture risk by 16%-23%. CONCLUSION: Patients with HFrEF had poor bone quality, with a better discriminating impact of the TBS assessment when BMD was normal, and BMI was suitable for densitometric analysis. Variables related to the prognosis, severity, and treatment of HFrEF were associated with reduced TBS. VFA and TBS adjustment increased fracture risk.

Assuntos

RESUMO

BACKGROUND: The management of antidiabetic therapy in people with type 2 diabetes (T2D) has evolved beyond glycemic control. In this context, Brazil and Portugal defined a joint panel of four leading diabetes societies to update the guideline published in 2020. METHODS: The panelists searched MEDLINE (via PubMed) for the best evidence from clinical studies on treating T2D and its cardiorenal complications. The panel searched for evidence on antidiabetic therapy in people with T2D without cardiorenal disease and in patients with T2D and atherosclerotic cardiovascular disease (ASCVD), heart failure (HF), or diabetic kidney disease (DKD). The degree of recommendation and the level of evidence were determined using predefined criteria. RESULTS AND CONCLUSIONS: All people with T2D need to have their cardiovascular (CV) risk status stratified and HbA1c, BMI, and eGFR assessed before defining therapy. An HbA1c target of less than 7% is adequate for most adults, and a more flexible target (up to 8%) should be considered in frail older people. Non-pharmacological approaches are recommended during all phases of treatment. In treatment naïve T2D individuals without cardiorenal complications, metformin is the agent of choice when HbA1c is 7.5% or below. When HbA1c is above 7.5% to 9%, starting with dual therapy is recommended, and triple therapy may be considered. When HbA1c is above 9%, starting with dual therapyt is recommended, and triple therapy should be considered. Antidiabetic drugs with proven CV benefit (AD1) are recommended to reduce CV events if the patient is at high or very high CV risk, and antidiabetic agents with proven efficacy in weight reduction should be considered when obesity is present. If HbA1c remains above target, intensification is recommended with triple, quadruple therapy, or even insulin-based therapy. In people with T2D and established ASCVD, AD1 agents (SGLT2 inhibitors or GLP-1 RA with proven CV benefit) are initially recommended to reduce CV outcomes, and metformin or a second AD1 may be necessary to improve glycemic control if HbA1c is above the target. In T2D with HF, SGLT2 inhibitors are recommended to reduce HF hospitalizations and mortality and to improve HbA1c. In patients with DKD, SGLT2 inhibitors in combination with metformin are recommended when eGFR is above 30 mL/min/1.73 m2. SGLT2 inhibitors can be continued until end-stage kidney disease.

RESUMO

The association between growth hormone (GH) and carcinogenesis has long been postulated. The rationale for this association is that several components of the GH axis play an important role in the regulation of cell proliferation, differentiation, apoptosis, and angiogenesis and have been tested as targets for cancer therapy. Epidemiological and clinical studies have examined the association between height, growth patterns, and insulin-like growth factor 1 (IGF1) levels with the most common types of malignancies, while genome-wide association studies have revealed several height-associated genes linked to cancer and/or metastasis-driving pathways. In this context, a permissive role of the GH-IGF signaling system in the link between height and cancer risk has also been investigated. In animal and human models, genetic defects associated with GH deficiency or resistance are associated with protection from tumor development, while the risk of malignancies in acromegaly or in patients exposed to recombinant GH therapy has long been a matter of concern and scrutiny. In this review, we present a narrative and historical review covering the potential relations among height, growth patterns, GH axis, and cancer.

Assuntos

RESUMO

PURPOSE: A systematic literature review was conducted to assess the use of home injections (self/partner/healthcare provider [HCP]-administered) of somatostatin analogs (SSAs) as an alternative to healthcare-setting injections in patients with acromegaly and neuroendocrine tumors (NETs). METHODS: MEDLINE/Embase/the Cochrane Library (2001-September 2021), key congresses (2019-2021), and bibliographies of relevant systematic reviews were searched. Eligible studies reported on efficacy/effectiveness, safety, adherence, patient-reported outcomes (PROs), and economic outcomes in populations receiving home injections of SSAs. RESULTS: Overall, 12 studies were included, all reporting on SSAs (lanreotide Autogel/Depot or octreotide long-acting release) in acromegaly or NETs. Across four studies, home injection was associated with similar disease control in patients with acromegaly/NETs compared with healthcare-setting administration. High rates of treatment adherence were shown in two studies of patients with acromegaly receiving lanreotide injections at home. Two studies reported non-serious adverse events; incidence of adverse reactions was similar in both the home and healthcare administration settings. Preference for injection setting varied between studies and indications; nonetheless, higher satisfaction/convenience (>75% patients) was reported for home injections. Self- or partner-injection was associated with economic savings compared with administration in the healthcare setting across five studies. CONCLUSION: Efficacy/effectiveness, adherence, and safety outcomes of SSAs in the home injection setting were similar to those in the healthcare setting, with high reported satisfaction and convenience. Self/partner injection also resulted in cost savings. These findings provide a basis to understand outcomes related to home injection and encourage healthcare providers to discuss optimal treatment choices with their patients.

Assuntos

Assuntos

Assuntos

RESUMO

PURPOSE: To make a systematic review and meta-analysis of studies evaluating the effect of cabergoline (CBG) in the treatment of non-functioning pituitary adenomas (NFPAs). METHODS: The primary outcome was tumor shrinkage, using as cut-off a reduction of at least 20% of the NFPA size from baseline. The secondary outcomes were prevention of tumor progression, clinically required additional interventions and adverse events (AE). Search strategies were applied to MEDLINE, EMBASE, LILACS and CENTRAL. Independent reviewers assessed the study eligibility, extracted data, and evaluated risk of bias. Random meta-analysis for the proportion of tumor shrinkage, prevention of tumor progression, clinically required additional interventions and frequency of AE were conducted. RESULTS: Five studies were included. The meta-analysis of proportion was 19% for tumor shrinkage (95% CI 8-38%, 4 studies, 108 participants), 50% for prevention of tumor progression (95% CI 35-64%, 5 studies, 187 participants), 14% for clinically required additional interventions (95% CI 6-30%, 4 studies, 128 participants) and 2% for adverse events (95% CI 1-6%, 3 studies, 157 participants). CONCLUSIONS: Effect of CBG to promote tumor shrinkage in NFPAs was low, while prevention of tumor progression after surgery was seen in half of the cases, with a low frequency of adverse events. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42020206778.

Assuntos

RESUMO

Objective: Evaluating the prevalence of sarcopenia in women submitted to bariatric surgery - Roux-en-Y gastric bypass. Design: Observational, cross-sectional study. Subjects and methods: Women (18-65 years old) who underwent bariatric surgery (BG) ≥ 2 years and reached stable weight ≥ 6 months, were investigated. Control group (CG) comprised non-operated matched women with obesity. Body composition was determined through dual-energy X-ray absorptiometry. Low lean mass (LLM) was defined as appendicular lean mass index (ALM kg/height m2) < 5.5 kg/m2. Physical strength was assessed through dynamometer and sit-to-stand test (SST), whereas performance was assessed through 4-m gait speed and Short Physical Performance Battery Tests (SPPB). Sarcopenia was diagnosed in the presence of LLM and low strength. Results: One-hundred and twenty women (60 in each group, 50 ± 9.7 years old) were investigated. All anthropometric and body composition parameters were lower in BG than in CG, whereas strength and performance were similar between groups. Women with reduced strength presented high total fat mass and low physical activity level (p < 0.005). LLM was observed in 35% of BG and in 18.3% of CG (p = 0.04), whereas sarcopenia was diagnosed in 28.3% of BG and in 16.6% of CG (p = 0.12). Sarcopenic women in BG had better performance both in SST (p = 0.001) and SPPB (p = 0.004). Total lean mass (OR:1.41, 95% CI [1.18; 1.69], p < 0.001) and obesity (OR: 38.2 [2.27; 644.12], p < 0.001) were associated with sarcopenia in the multivariate analysis. Conclusion: Despite great weight loss, sarcopenia prevalence did not increase in BG and its presence was influenced by total lean mass and obesity.

RESUMO

ABSTRACT Objective: Evaluating the prevalence of sarcopenia in women submitted to bariatric surgery - Roux-en-Y gastric bypass. Design: Observational, cross-sectional study. Subjects and methods: Women (18-65 years old) who underwent bariatric surgery (BG) ≥ 2 years and reached stable weight ≥ 6 months, were investigated. Control group (CG) comprised non-operated matched women with obesity. Body composition was determined through dual-energy X-ray absorptiometry. Low lean mass (LLM) was defined as appendicular lean mass index (ALM kg/height m2) < 5.5 kg/m2. Physical strength was assessed through dynamometer and sit-to-stand test (SST), whereas performance was assessed through 4-m gait speed and Short Physical Performance Battery Tests (SPPB). Sarcopenia was diagnosed in the presence of LLM and low strength. Results: One-hundred and twenty women (60 in each group, 50 ± 9.7 years old) were investigated. All anthropometric and body composition parameters were lower in BG than in CG, whereas strength and performance were similar between groups. Women with reduced strength presented high total fat mass and low physical activity level (p < 0.005). LLM was observed in 35% of BG and in 18.3% of CG (p = 0.04), whereas sarcopenia was diagnosed in 28.3% of BG and in 16.6% of CG (p = 0.12). Sarcopenic women in BG had better performance both in SST (p = 0.001) and SPPB (p = 0.004). Total lean mass (OR:1.41, 95% CI [1.18; 1.69], p < 0.001) and obesity (OR: 38.2 [2.27; 644.12], p < 0.001) were associated with sarcopenia in the multivariate analysis. Conclusion: Despite great weight loss, sarcopenia prevalence did not increase in BG and its presence was influenced by total lean mass and obesity.

RESUMO

Several complications associated with active Cushing's disease may persist even years after complete and successful therapeutic remission of hypercortisolism. Growth hormone deficiency (GHD) shares many clinical features seen in patients with Cushing's disease, and its presence after disease remission (GHD-CR) might negatively influence and potentially worsen the systemic complications caused by previous hypercortisolism. GHD-CR is more prevalent in women, and compared to other causes of GHD, patients are younger at the onset of the pituitary disease, at diagnosis of GHD-CR and at start of GH therapy; prevalence of pituitary macroadenomas and visual abnormalities are lower, while prevalence of diabetes, hypertension, low bone mass, fractures, and worst quality of life, are higher. Serum IGF-1 levels are not useful for the diagnosis of GHD-CR and the application of GH stimulating tests requires some special attention in addition to the general recommendations for detecting GHD from other etiologies. In patients with active hypercortisolism, GH secretion is completely suppressed, but it may spontaneously and progressively recover over the years following successful therapy, meaning that GH testing may be performed at an appropriate time after remission for the correct diagnosis. Moreover, if the patient presents concomitant adrenal insufficiency, GH testing should only be carried out under adequate cortisol replacement therapy. GH therapy in children with GHD-CR improves adult height in the majority of patients, while GH therapy in adults has been associated with improvements in body composition, lipid profile and quality of life, but also with worsening of glucose metabolism.

Assuntos

RESUMO

Obesity is a chronic disease associated with impaired physical and mental health. A widespread view in the treatment of obesity is that the goal is to normalize the individual's body mass index (BMI). However, a modest weight loss (usually above 5%) is already associated with clinical improvement, while weight losses of 10%-15% bring even further benefits, independent from the final BMI. The percentage of weight reduction is accepted as a treatment goal since a greater decrease in weight is frequently difficult to achieve due to metabolic adaptation along with environmental and lifestyle factors. In this document, the Brazilian Society of Endocrinology and Metabolism (SBEM) and the Brazilian Society for the Study of Obesity and Metabolic Syndrome (ABESO) propose a new obesity classification based on the maximum weight attained in life (MWAL). In this classification, individuals losing a specific proportion of weight are classified as having "reduced" or "controlled" obesity. This simple classification - which is not intended to replace others but to serve as an adjuvant tool - could help disseminate the concept of clinical benefits derived from modest weight loss, allowing individuals with obesity and their health care professionals to focus on strategies for weight maintenance instead of further weight reduction. In future studies, this proposed classification can also be an important tool to evaluate possible differences in therapeutic outcomes between individuals with similar BMIs but different weight trajectories.

Assuntos

RESUMO

ABSTRACT Obesity is a chronic disease associated with impaired physical and mental health. A widespread view in the treatment of obesity is that the goal is to normalize the individual's body mass index (BMI). However, a modest weight loss (usually above 5%) is already associated with clinical improvement, while weight losses of 10%-15% bring even further benefits, independent from the final BMI. The percentage of weight reduction is accepted as a treatment goal since a greater decrease in weight is frequently difficult to achieve due to metabolic adaptation along with environmental and lifestyle factors. In this document, the Brazilian Society of Endocrinology and Metabolism (SBEM) and the Brazilian Society for the Study of Obesity and Metabolic Syndrome (ABESO) propose a new obesity classification based on the maximum weight attained in life (MWAL). In this classification, individuals losing a specific proportion of weight are classified as having "reduced" or "controlled" obesity. This simple classification - which is not intended to replace others but to serve as an adjuvant tool - could help disseminate the concept of clinical benefits derived from modest weight loss, allowing individuals with obesity and their health care professionals to focus on strategies for weight maintenance instead of further weight reduction. In future studies, this proposed classification can also be an important tool to evaluate possible differences in therapeutic outcomes between individuals with similar BMIs but different weight trajectories.

RESUMO

Growth hormone (GH) has been used for over 35 years, and its safety and efficacy has been studied extensively. Experimental studies showing the permissive role of GH/insulin-like growth factor 1 (IGF-I) in carcinogenesis have raised concerns regarding the safety of GH replacement in children and adults who have received treatment for cancer and those with intracranial and pituitary tumours. A consensus statement was produced to guide decision-making on GH replacement in children and adult survivors of cancer, in those treated for intracranial and pituitary tumours and in patients with increased cancer risk. With the support of the European Society of Endocrinology, the Growth Hormone Research Society convened a Workshop, where 55 international key opinion leaders representing 10 professional societies were invited to participate. This consensus statement utilized: (1) a critical review paper produced before the Workshop, (2) five plenary talks, (3) evidence-based comments from four breakout groups, and (4) discussions during report-back sessions. Current evidence reviewed from the proceedings from the Workshop does not support an association between GH replacement and primary tumour or cancer recurrence. The effect of GH replacement on secondary neoplasia risk is minor compared to host- and tumour treatment-related factors. There is no evidence for an association between GH replacement and increased mortality from cancer amongst GH-deficient childhood cancer survivors. Patients with pituitary tumour or craniopharyngioma remnants receiving GH replacement do not need to be treated or monitored differently than those not receiving GH. GH replacement might be considered in GH-deficient adult cancer survivors in remission after careful individual risk/benefit analysis. In children with cancer predisposition syndromes, GH treatment is generally contraindicated but may be considered cautiously in select patients.

Assuntos

RESUMO

The presence of a bidirectional risk for metachronous carcinomas among women with thyroid and breast cancer is well established. However, the underlying risk factors remain poorly understood. Two sisters developed papillary thyroid cancer (PTC) at age 32 and 34 years, followed by ductal carcinoma of the breast at 44 and 42 years. The 2 children of the younger sister developed ataxia-telangiectasia; the son also developed lymphoblastic lymphoma and his sister died secondary to acute lymphoblastic leukemia (ALL). They were found to be compound heterozygous for ataxia telangiectasia mutated (ATM) gene mutations (c.3848T>C, p.L1283P; and c.802C>T, p.Q268X). Exome sequencing of the 2 sisters (mother and aunt of the children with ataxia-telangiectasia) led to the detection of the pathogenic monoallelic ATM mutation in both of them (c.3848T>C; minor allele frequency [MAF] < 0.01) but detected no other variants known to confer a risk for PTC or breast cancer. The findings suggest that monoallelic ATM mutations, presumably in conjunction with additional genetic and/or nongenetic factors, can confer a risk for developing PTC and breast cancer.

RESUMO

PURPOSE: To evaluate the association between acromegaly and pregnancy in terms of disease activity, maternal and fetal outcomes. METHODS: This systematic review was conducted according to the Joanna Briggs Institute methodology for systematic reviews of etiology and risk. We focused on observational studies that included pregnant women with acromegaly. The outcomes were acromegaly activity, preterm birth, gestational diabetes, hypertension, eclampsia/preeclampsia, miscarriage, perinatal mortality, low birthweight, small for gestational age, and congenital malformations. Embase, Medline, LILACS, and CENTRAL were our source databases. To perform proportional meta-analyses, we used Stata Statistical Software 17. RESULTS: Nineteen studies were included encompassing a total of 273 pregnancies in 211 women with acromegaly. The overall frequency of control of acromegaly during pregnancy was 62%, and of tumor growth was 9%. No fetal or maternal deaths were reported. The overall frequency of worsening of previous diabetes or development of gestational diabetes was 9%, and of previous hypertension or preeclampsia/eclampsia was 6%. The overall frequency of premature labor was 9% [from 17 studies of 263 pregnancies; 95% confidence interval (CI), 5-13%]; of spontaneous miscarriage was 4% (from 19 studies of 273 pregnancies; 95% CI, 2-11%); of small for gestational age was 5% (from 15 studies of 216 newborns; 95% CI, 3-9%); and of congenital malformations was 1% (from 18 studies of 240 newborns; 95% CI, 0-7%). CONCLUSION: Pregnancy in women with acromegaly is frequently associated with disease control and is safe in relation to fetal and maternal outcomes, as in women without acromegaly.

Assuntos