RESUMO
X-linked acrogigantism (X-LAG) is the most severe form of pituitary gigantism and is characterized by aggressive growth hormone (GH)-secreting pituitary tumors that occur in early childhood. X-LAG is associated with chromosome Xq26.3 duplications (the X-LAG locus typically includes VGLL1, CD40LG, ARHGEF6, RBMX, and GPR101) that lead to massive pituitary tumoral expression of GPR101, a novel regulator of GH secretion. The mechanism by which the duplications lead to marked pituitary misexpression of GPR101 alone was previously unclear. Using Hi-C and 4C-seq, we characterized the normal chromatin structure at the X-LAG locus. We showed that GPR101 is located within a topologically associating domain (TAD) delineated by a tissue-invariant border that separates it from centromeric genes and regulatory sequences. Next, using 4C-seq with GPR101, RBMX, and VGLL1 viewpoints, we showed that the duplications in multiple X-LAG-affected individuals led to ectopic interactions that crossed the invariant TAD border, indicating the existence of a similar and consistent mechanism of neo-TAD formation in X-LAG. We then identified several pituitary active cis-regulatory elements (CREs) within the neo-TAD and demonstrated in vitro that one of them significantly enhanced reporter gene expression. At the same time, we showed that the GPR101 promoter permits the incorporation of new regulatory information. Our results indicate that X-LAG is a TADopathy of the endocrine system in which Xq26.3 duplications disrupt the local chromatin architecture forming a neo-TAD. Rewiring GPR101-enhancer interaction within the new regulatory unit is likely to cause the high levels of aberrant expression of GPR101 in pituitary tumors caused by X-LAG.
Assuntos
Acromegalia , Doenças Genéticas Ligadas ao Cromossomo X , Gigantismo , Neoplasias Hipofisárias , Acromegalia/complicações , Acromegalia/genética , Acromegalia/patologia , Pré-Escolar , Cromatina/genética , Comunicação , Proteínas de Ligação a DNA/genética , Doenças Genéticas Ligadas ao Cromossomo X/genética , Gigantismo/complicações , Gigantismo/genética , Gigantismo/patologia , Humanos , Neoplasias Hipofisárias/genética , Receptores Acoplados a Proteínas G/genética , Fatores de Transcrição/genéticaRESUMO
OBJECTIVES: Skin changes in acromegaly are often the first sign of the disease. The aim of this study was to describe the cutaneous findings in patients with acromegaly. In addition, a secondary aim was to investigate the possible association of these findings with remission status and concomitant endocrinopathies. DESIGN, PATIENTS, AND MEASUREMENTS: In this prospective multicenter study, 278 patients over the age of 18 years with acromegaly who were followed up in 14 different tertiary healthcare institutions were included. These patients, who were followed up by the Endocrinology Department, were then referred to a dermatologist for dermatological examination. The frequency of skin lesions was investigated by detailed dermatologic examination. Dermatological diagnosis is reached by clinical, dermatological and/or dermoscopic examination, and rarely skin punch biopsy examinations in suspicious cases. The possible association of the skin findings between remitted and nonremitted patients and with concomitant endocrinopathies were evaluated. RESULTS: The most common skin findings in patients with acromegaly in our study were skin tags (52.5%), cherry angiomas (47.4%), seborrhoea (37%), varicose veins (33%), acneiform lesions (28.8%), hyperhidrosis (26.9%) and hypertrichosis (18.3%). Hypertrichosis was significantly more prevalent in patients nonremitted (p: .001), while xerosis cutis was significantly more prevalent in patients remitted (p: .001). The frequency of diabetes mellitus and hypothyroidism was significantly higher in patients with varicose veins and seborrhoeic keratosis than those without. Additionally, the coexistence of hypothyroidism, hyperthyroidism and galactorrhea was significantly higher in patients with Cherry angioma than in those without Cherry angioma (p-values: .024, .034 and .027, respectively). The frequency of hypogonadism in those with xerosis cutis was significantly higher than in those without (p: .035). CONCLUSIONS: Cutaneous androgenization findings such as skin tag, seborrhoea, acne and acanthosis nigricans are common in patients with acromegaly. Clinicians should be aware that skin findings associated with insulin resistance may develop in these patients. It can be said that the remission state in acromegaly has no curative effect on cutaneous findings. Only patients in remission were less likely to have hypertrichosis. This may allow earlier review of the follow-up and treatment of acromegaly patients presenting with complaints of hypertrichosis. Additionally, it can be said that patients with skin findings such as cherry angioma may be predisposed to a second endocrinopathy, especially hypothyroidism. Including dermatology in a multidisciplinary perspective in acromegaly patient management would be beneficial to detect cutaneous findings earlier.
Assuntos
Acromegalia , Dermatopatias , Humanos , Acromegalia/complicações , Acromegalia/patologia , Feminino , Masculino , Pessoa de Meia-Idade , Adulto , Estudos Prospectivos , Dermatopatias/patologia , Dermatopatias/epidemiologia , Doenças do Sistema Endócrino/complicações , Doenças do Sistema Endócrino/epidemiologia , Idoso , Pele/patologia , Adulto Jovem , Hipertricose/patologia , Hipertricose/epidemiologia , Hiperidrose/epidemiologia , Hiperidrose/complicações , Hiperidrose/etiologia , Hemangioma/complicações , Hemangioma/patologiaRESUMO
CONTEXT: Epidemiological studies involving patients with acromegaly have yielded conflicting results regarding cancer incidence and causes of mortality in relation to control of growth hormone (GH) excess. OBJECTIVE: The objective of this retrospective cohort study is to clarify these questions and identify goals for treatment and monitoring patients. METHODS: We studied 1845 subjects from the UK Acromegaly Register (1970-2016), obtaining cancer standardised incidence rates (SIR) and all causes standardised mortality rates (SMR) from UK Office for National Statistics, to determine the relationship between causes of mortality-age at diagnosis, duration of disease, post-treatment and mean GH levels. RESULTS: We found an increased incidence of all cancers (SIR, 1.38; 95% CI: 1.06-1.33, p < .001), but no increase in incidence of female breast, thyroid, colon cancer or any measure of cancer mortality. All-cause mortality rates were increased (SMR, 1.35; 95% CI: 1.24-1.46, p < .001), as were those due to vascular and respiratory diseases. All-cause, all cancer and cardiovascular deaths were highest in the first 5 years following diagnosis. We found a positive association between post-treatment and mean treatment GH levels and all-cause mortality (p < .001 and p < .001), which normalised with posttreatment GH levels of <1.0 µg/L or meantreatment GH levels of <2.5 µg/L. CONCLUSION: Acromegaly is associated with increased incidence of all cancers but not thyroid or colon cancer and no increase in cancer mortality. Excess mortality is due to vascular and respiratory disease. The risk is highest in the first 5 years following diagnosis and is mitigated by normalising GH levels.
Assuntos
Acromegalia , Hormônio do Crescimento Humano , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem , Acromegalia/sangue , Acromegalia/complicações , Acromegalia/terapia , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/complicações , Hormônio do Crescimento Humano/sangue , Hormônio do Crescimento Humano/metabolismo , Incidência , Neoplasias/complicações , Sistema de Registros , Doenças Respiratórias/complicações , Estudos Retrospectivos , Reino Unido , Doenças Vasculares/complicaçõesRESUMO
BACKGROUND: Growth hormone (GH) positive pituitary neuroendocrine tumors do not always cause acromegaly. Approximately one-third of GH-positive pituitary tumors are classified as non-functioning pituitary tumors in clinical practice. They typically have GH and serum insulin-like growth factor 1 (IGF-1) levels in the reference range and no acromegaly-like symptoms. However, normal hormone levels might not exclude the underlying hypersecretion of GH. This is a rare and paradoxical case of pituitary tumor causing acromegaly-associated symptoms despite normal GH and IGF-1 levels. CASE PRESENTATION: We report a case of a 35-year-old woman with suspicious acromegaly-associated presentations, including facial changes, headache, oligomenorrhea, and new-onset diabetes mellitus and dyslipidemia. Imaging found a 19 × 12 × 8 mm pituitary tumor, but her serum IGF-1 was within the reference, and nadir GH was 0.7ng/ml after glucose load at diagnosis. A thickened skull base, increased uptake in cranial bones in bone scan, and elevated bone turnover markers indicated abnormal bone metabolism. We considered the pituitary tumor, possibly a rare subtype in subtle or clinically silent GH pituitary tumor, likely contributed to her discomforts. After the transsphenoidal surgery, the IGF-1 and nadir GH decreased immediately. A GH and prolactin-positive pituitary neuroendocrine tumor was confirmed in the histopathologic study. No tumor remnant was observed three months after the operation, and her discomforts, glucose, and bone metabolism were partially relieved. CONCLUSIONS: GH-positive pituitary neuroendocrine tumors with hormonal tests that do not meet the diagnostic criteria for acromegaly may also cause GH hypersecretion presentations. Patients with pituitary tumors and suspicious acromegaly symptoms may require more proactive treatment than non-functioning tumors of similar size and invasiveness.
Assuntos
Acromegalia , Tumores Neuroendócrinos , Neoplasias Hipofisárias , Humanos , Feminino , Adulto , Acromegalia/diagnóstico , Acromegalia/complicações , Acromegalia/etiologia , Tumores Neuroendócrinos/complicações , Tumores Neuroendócrinos/diagnóstico , Tumores Neuroendócrinos/patologia , Neoplasias Hipofisárias/complicações , Neoplasias Hipofisárias/diagnóstico , Neoplasias Hipofisárias/patologia , Adenoma Hipofisário Secretor de Hormônio do Crescimento/complicações , Adenoma Hipofisário Secretor de Hormônio do Crescimento/patologia , Adenoma Hipofisário Secretor de Hormônio do Crescimento/diagnóstico , Hormônio do Crescimento Humano/sangue , Hormônio do Crescimento Humano/metabolismo , Fator de Crescimento Insulin-Like I/metabolismo , Doenças Ósseas/etiologia , Doenças Ósseas/diagnóstico , Doenças Ósseas/patologiaRESUMO
PURPOSE: Insulin sensitivity (Si) and its role in glucose intolerance of acromegaly has been extensively evaluated. However, data on insulin secretion is limited. We aimed to assess stimulated insulin secretion using an intravenous glucose tolerance test (IVGTT) in active acromegaly. METHODS: We performed an IVGTT in 25 patients with active acromegaly (13 normal glucose tolerance [NGT], 6 impaired glucose tolerance [IGT] and 6 diabetes mellitus [DM]) and 23 controls (8 lean NGT, 8 obese NGT and 7 obese IGT). Serum glucose and insulin were measured at 20 time points along the test to calculate Si and acute insulin response (AIRg). Medical treatment for acromegaly or diabetes was not allowed. RESULTS: In acromegaly, patients with NGT had significantly (p for trend < 0.001) higher AIRg (3383 ± 1082 pmol*min/L) than IGT (1215 ± 1069) and DM (506 ± 600). AIRg was higher in NGT (4764 ± 1180 pmol*min/L) and IGT (3183 ± 3261) controls with obesity than NGT (p = 0.01) or IGT (p = 0.17) acromegaly. Si was not significantly lower in IGT (0.68 [0.37, 0.88] 106*L/pmol*min) and DM (0.60 [0.42, 0.84]) than in NGT (0.81 [0.58, 1.55]) patients with acromegaly. NGT (0.33 [0.30, 0.47] 106*L/pmol*min) and IGT (0.37 [0.21, 0.66]) controls with obesity had lower Si than NGT (p = 0.001) and IGT (p = 0.43) acromegaly. CONCLUSION: We demonstrated that low insulin secretion is the main driver behind glucose intolerance in acromegaly. Compared to NGT and IGT controls with obesity, patients with NGT or IGT acromegaly had higher Si. Together, these findings suggest that impaired insulin secretion might be a specific mechanism for glucose intolerance in acromegaly.
Assuntos
Acromegalia , Intolerância à Glucose , Resistência à Insulina , Humanos , Acromegalia/complicações , Acromegalia/metabolismo , Glicemia , Diabetes Mellitus , Glucose , Intolerância à Glucose/metabolismo , Teste de Tolerância a Glucose , Insulina , Resistência à Insulina/fisiologia , Secreção de Insulina , ObesidadeRESUMO
PURPOSE: Cardiac abnormalities are common in patients with acromegaly, contributing to the increased morbidity and mortality. Cardiac magnetic resonance (CMR) is the gold standard for measuring cardiac morpho-functional changes. This study aims to detect cardiac alterations in acromegaly through CMR, even when the disease is adequately controlled. METHODS: In this, multicentre, case-control study, we compared consecutive patients with acromegaly, cured after surgery or requiring medical treatment, with matched controls recruited among patients harbouring non-functioning adrenal incidentalomas. RESULTS: We included 20 patients with acromegaly (7 females, mean age 50 years) and 17 controls. Indexed left ventricular-end-diastolic volume (LV-EDVi) and LV-end-systolic volume (LV-ESVi) were higher in patients than in controls (p < 0.001), as were left ventricular mass (LVMi) (p = 0.001) and LV-stroke volume (LV-SVi) (p = 0.028). Right ventricle (RV) EDVi and ESVi were higher, whereas RV-ejection fraction (RV-EF) was lower (p = 0.002) in patients than in controls (p < 0.001). No significant differences were observed in the prevalence of cardiometabolic comorbidities, including hypertension, glucose and lipid metabolism impairment, obstructive sleep apnoea syndrome, and obesity. IGF1 x upper limit of normal significantly predicted LVMi (b = 0.575; p = 0.008). Subgroup analysis showed higher LVMi (p = 0.025) and interventricular septum thickness (p = 0.003) in male than female patients, even after adjusting cardiac parameters for confounding factors. CONCLUSIONS: The CMR analysis reveals a cluster of biventricular structural and functional impairment in acromegaly, even when the biochemical control if achieved. These findings appear specifically triggered by the exposure to GH-IGF1 excess and show sex-related differences advocating a possible interaction with sex hormones in cardiac disease progression.
Assuntos
Acromegalia , Imageamento por Ressonância Magnética , Humanos , Feminino , Acromegalia/diagnóstico por imagem , Acromegalia/patologia , Acromegalia/complicações , Masculino , Pessoa de Meia-Idade , Estudos de Casos e Controles , Adulto , Idoso , Coração/diagnóstico por imagem , Coração/fisiopatologiaRESUMO
OBJECTIVES: To explore the role of conventional X-ray imaging in detecting vertebral fractures (VFs) in patients with acromegaly, both at diagnosis of disease and at the last clinical visit. The risk factors for VFs were also evaluated. DESIGN AND METHODS: A retrospective cohort study was conducted on 60 consecutive patients with acromegaly, in a tertiary referral centre. Thoracolumbar spine radiography (X-spine) was performed at the last clinical visit during the follow-up in order to detect VFs. Routine chest radiograph, performed as a part of the general evaluation at diagnosis of acromegaly, were retrospectively analysed to screen for baseline VFs. RESULTS: At diagnosis of acromegaly, chest X-ray revealed that 10 (17%) patients had VFs. Of the 50 patients without VFs at diagnosis of acromegaly, 33 (66%) remained unfractured at the last clinical visit (median [IQR] time, 144 [96-192] months after the diagnosis of acromegaly), whereas 17 (34%) had VFs. Overall, 22 patients (37%) had novel VFs detected on X-spine including five patients with previous VFs. Risk factor for incident VFs was the presence of hypogonadism at diagnosis of acromegaly (p = 0.016). CONCLUSIONS: In acromegaly patients, conventional X-rays can detect vertebral fractures early at diagnosis of acromegaly. They can also reveal incident VFs, which may occur several years later even in patients without VFs at diagnosis, above all in relation to hypogonadism.
Assuntos
Acromegalia , Hipogonadismo , Fraturas da Coluna Vertebral , Humanos , Acromegalia/complicações , Acromegalia/diagnóstico por imagem , Estudos Retrospectivos , Raios X , Seguimentos , Fraturas da Coluna Vertebral/diagnóstico por imagem , Fraturas da Coluna Vertebral/epidemiologia , Radiografia , Densidade Óssea , Hipogonadismo/complicaçõesRESUMO
BACKGROUND: Acne vulgaris is a prevalent skin condition. We have found that some acromegaly patients have acne. However, no study has examined the relationship between acromegaly and acne. OBJECTIVE: To explore prevalence and correlation of adult acne in patients with acromegaly. METHODS: For this cross-sectional study, we collected questionnaires, clinical information, and laboratory test results of acromegaly patients from January 2022 to December 2022 at Huashan Hospital. Of the 133 questionnaires returned, 123 had valid responses. RESULTS: Of the 123 patients with acromegaly enrolled in this study, 54.5% had adult acne. No statistically significant difference was found in prevalence between male and female patients. 61.2% of adult acne patients reported late-onset acne. Late-onset acne patients first developed acne years before acromegaly diagnosis (mean of 5.6 years for male and 4.5 years for female patients). Some acne patients have received traditional anti-acne treatment. Moreover, 31% of the patients reported no improvement, and only 3.5% of patients claimed complete resolution of acne after treatment. Before acromegaly treatment, the prevalence of adult acne was 51.2%, with mild acne accounting for 73.0%, moderate acne accounting for 23.8%, and severe acne accounting for 3.2%. After acromegaly treatment, the prevalence of adult acne was significantly decreased to 37.4% (P = 0.007). An overall decrease in acne severity was noted, with 93.5%, 6.5%, and 0% having mild, moderate, and severe acne, respectively. A total of 83.6% of the patients had self-assessed acne remission, and 33.3% of the patients reported complete acne resolution. However, 9.0% of patients reported that their condition had worsened after acromegaly treatment. After treatment, GH, IGF-1, IGF-1 index, insulin levels, and HOMA-IR decreased significantly in all patients with acromegaly (P < 0.05). Acne remission correlated positively with IGF-1 levels, but not with GH levels. The relationship between acromegaly and acne remains to be elucidated. CONCLUSIONS: Our findings provide preliminary evidence of the high prevalence of adult acne in acromegaly patients, and a high rate of late-onset acne as well. Traditional anti-acne treatments are less effective. Acne could be considerably relieved by treating acromegaly. Acne remission positively correlated with IGF-1 decline as well, which revealed the correlation between acne and IGF-1.
Assuntos
Acne Vulgar , Acromegalia , Humanos , Acne Vulgar/epidemiologia , Acromegalia/epidemiologia , Acromegalia/sangue , Acromegalia/terapia , Acromegalia/complicações , Masculino , Feminino , Estudos Transversais , Adulto , Estudos Retrospectivos , Prevalência , Pessoa de Meia-Idade , Adulto Jovem , IdosoRESUMO
PURPOSE: Sexual dysfunctions are often experienced by male patients with acromegaly, due to a combination of hypogonadism and other comorbidities, but are a scarcely investigated complication. Erectile dysfunction is also closely related to cardiovascular diseases through endothelial dysfunction. Therefore, this project aimed to assess the prevalence of erectile dysfunction in a population of acromegalic men and evaluate its association with cardio-metabolic disorders, also exploring associations with androgen and estrogen receptor gene polymorphisms. METHODS: Sexually active men aged 18-65 with previous diagnosis of acromegaly were recruited. Clinical and laboratory data were retrospectively collected. Each patient also provided a blood sample for AR and ERß gene polymorphisms analyses and filled out the IIEF-15 questionnaire. RESULTS: Twenty men with previous diagnosis of acromegaly (mean age 48.4 ± 10.0 years) were recruited. 13/20 subjects (65%) had erectile dysfunction, but only four had a concurrent biochemical hypogonadism, with no significant correlation with IIEF-15 scores. Total testosterone negatively correlated with sexual intercourse satisfaction domain (ρ = - 0.595; p = 0.019) and general satisfaction domain (ρ = - 0.651; p = 0.009). IGF-1 levels negatively correlated with biochemical hypogonadism (ρ = - 0.585; p = 0.028). The number of CAG and CA repeats in AR and ERß receptors genes was not significantly associated with IIEF-15 scores or with GH/IGF-1 levels, but a negative correlation between CA repeats and the presence of cardiomyopathy (ρ = - 0.846; p = 0.002) was present. CONCLUSIONS: Men with acromegaly have a high prevalence of erectile dysfunction, but it does not appear to be correlated with treatments, testosterone levels and AR/ER-beta signaling. Nonetheless, a shorter CA polymorphic trait (ERbeta) is associated with the presence of cardiomyopathy. If confirmed, these data may suggest an association between an incorrect hormonal balance and increased cardiovascular risk in acromegaly subjects.
Assuntos
Acromegalia , Cardiomiopatias , Disfunção Erétil , Hipogonadismo , Humanos , Masculino , Adulto , Pessoa de Meia-Idade , Androgênios , Disfunção Erétil/epidemiologia , Disfunção Erétil/genética , Acromegalia/complicações , Acromegalia/genética , Fator de Crescimento Insulin-Like I/genética , Estudos Retrospectivos , Receptor beta de Estrogênio/genética , Testosterona , Hipogonadismo/complicações , Hipogonadismo/epidemiologia , Hipogonadismo/genética , Polimorfismo Genético , EstrogêniosRESUMO
AIM: Acromegaly is a rare chronic disease, caused by the over-secretion of growth hormone (GH), that creates a pro-inflammatory state, but the exact mechanisms by which GH or insulin-like growth factor 1 (IGF-1) act on inflammatory cells are not fully understood. Aim of the study was to evaluate Interleukin-33 (IL33) and the skin perfusion of hands in patients with acromegaly (AP) and healthy controls (HC). METHODS: IL33 have been assessed in 40 AP and 40 HC. IL 33 was determined and skin perfusion of hands was assessed by laser speckle contrast analysis (LASCA) in both populations. RESULTS: IL33 was significantly higher in AP compared to HC [45.72 pg/ml (IQR 28.74-60.86) vs 14 pg/ml (IQR 6.5535); p < 0.05]. At LASCA, peripheral blood perfusion (PBP) was significantly lower in AP compared to HC [53.39 pU (IQR 40.94-65.44) vs 87 pU (IQR 80-98) p < 0.001]. The median values of ROI1, ROI2 and ROI3 were significantly lower in AP compared to HC [97.32 pU (IQR 50.89-121.69) vs 131 pU (IQR 108-135); p < 0.001], [58.68 pU (IQR 37.72-84.92) vs 83 pU (IQR 70-89), p < 0.05] and HC [52.16 (34.47-73.78) vs 85 (78-98), p < 0.001], respectively. The proximal-distal gradient (PDG) was observed in 18 of 40 (45%) AP. CONCLUSION: Serum IL33 is higher in AP compared to HC; conversely a reduction of PBP of hands was present in AP compared to HC, probably due to endothelial dysfunction, strictly dependent on acromegaly and are not influenced by the choice of treatment.
Assuntos
Acromegalia , Inflamação , Interleucina-33 , Humanos , Acromegalia/metabolismo , Acromegalia/sangue , Acromegalia/complicações , Acromegalia/patologia , Masculino , Feminino , Pessoa de Meia-Idade , Interleucina-33/sangue , Interleucina-33/metabolismo , Inflamação/metabolismo , Adulto , Estudos de Casos e Controles , Microvasos/patologia , Microvasos/metabolismo , Pele/irrigação sanguínea , Pele/patologia , Pele/metabolismo , Biomarcadores/sangue , Doença Crônica , Hormônio do Crescimento Humano/sangue , Hormônio do Crescimento Humano/metabolismo , Imagem de Contraste de Manchas a Laser/métodos , Estudos de Coortes , Mãos , Fator de Crescimento Insulin-Like I/metabolismo , Fator de Crescimento Insulin-Like I/análiseRESUMO
Acromegaly is a rare systemic syndrome induced by the overproduction of growth hormone (GH) and insulin-like growth factor type one (IGF1). It is responsible for changes in the skeletal and soft tissue systems and it almost always occurs because of a pituitary adenoma. Amongst the skin complications related to acromegaly, cutis verticis gyrate (CVG) is occasionally found. It is a skin condition characterized by excessive growth of the skin of the scalp, resulting in furrows and folds. Only a few cases of this uncommon association have been reported in the literature. The present clinical case illustrates typical CVG associated with acromegaly. Imaging revealed a pituitary macroadenoma lesion and hormonal evaluation revealed elevated IGF1 and hypopituitarism. The patient underwent a transsphenoidal resection of the pituitary adenoma and the histopathological examination confirmed the diagnosis. The diagnosis of CVG is clinical, so radiologic assessments are generally not necessary. The management of acromegaly associated with CVG depends on controlling the serum levels of GH and IGF1. In some cases, specific injections or surgery can be used to minimize CVG.
Assuntos
Acromegalia , Adenoma , Fator de Crescimento Insulin-Like I , Neoplasias Hipofisárias , Dermatoses do Couro Cabeludo , Humanos , Acromegalia/complicações , Acromegalia/etiologia , Dermatoses do Couro Cabeludo/complicações , Dermatoses do Couro Cabeludo/patologia , Dermatoses do Couro Cabeludo/etiologia , Adenoma/complicações , Adenoma/cirurgia , Adenoma/patologia , Neoplasias Hipofisárias/complicações , Neoplasias Hipofisárias/cirurgia , Fator de Crescimento Insulin-Like I/metabolismo , Fator de Crescimento Insulin-Like I/análise , Couro Cabeludo/patologia , Masculino , Pessoa de Meia-Idade , FemininoRESUMO
Acromegaly is a chronic systemic disease caused by excess levels of growth hormone and insulin-like growth factor-1 and is associated with numerous complications. Significantly, there is a lack of longitudinal data on kidney complications in patients with acromegaly. As such, we investigated the risk of end-stage kidney disease (ESKD) (stage 5D, 5T) in these patients with nationwide data obtained from the National Health Information Database of the National Health Insurance Service in Republic of Korea. A retrospective cohort study was conducted of 2.187 patients with acromegaly and 10,935 age- and sex-matched (1:5) control subjects without acromegaly over a mean follow-up period of 6.51 years. The study outcomes were analyzed using Cox proportional hazards regression analysis controlling for age, sex, household income, residential area, type 2 diabetes, hypertension, dyslipidemia, urolithiasis, congestive heart failure, myocardial infarction, stroke, and atrial fibrillation. The incidence (per 1,000 person-years) ESKD was 2.00 among patients with acromegaly but only 0.46 among controls, (hazard ratio 4.35 (95% confidence interval 2.63-7.20)) implicating a significantly higher risk. After adjustment for covariates, the risk of ESKD (2.36 (1.36-4.12)) was still significantly higher in patients with acromegaly than that in controls. Among the covariates, diabetes and hypertension were significant facilitators between acromegaly and ESKD in mediation analysis. Pituitary surgery and somatostatin analogues did not significantly change these associations. Thus, acromegaly may be linked with a higher risk for ESKD both independently and through mediators such as diabetes and hypertension.
Assuntos
Acromegalia , Diabetes Mellitus Tipo 2 , Hipertensão , Falência Renal Crônica , Humanos , Acromegalia/complicações , Acromegalia/epidemiologia , Estudos de Coortes , Diabetes Mellitus Tipo 2/complicações , Hipertensão/complicações , Falência Renal Crônica/diagnóstico , Falência Renal Crônica/epidemiologia , Falência Renal Crônica/etiologia , Estudos Retrospectivos , Fatores de Risco , Masculino , FemininoRESUMO
OBJECTIVE: Although atherosclerosis-related macrovascular complications are well known in acromegaly, studies on endothelial function and arteriolar level are contradictory. In order to test the hypothesis, microvascular changes associated with macrovascular changes in acromegaly, we aimed to evaluate microvascular changes in nailfold capillaries and carotid intima-media thickness (CIMT) in patients with acromegaly. DESIGN: In this cross-sectional observation study, of total 70 patients with acromegaly [ten (14.3 %) were active acromegaly (AA), 60 (85.7 %) were controlled acromegaly (CA)] and 74 healthy controls were enrolled. Microvascular structure was evaluated using the nailfold video capillaroscopy, and CIMT was measured using ultrasonography. RESULTS: The median number of capillaries was less [10 no./mm (min-max: 5-16) vs. 11 no./mm (min-max: 9-15); p = 0.001] in the acromegaly group than in the controls. Capillaries below 6-8 per/mm was more common in the acromegaly patients [six (8.6 %) vs. one (1.4 %); p = 0.046]. All capillaroscopic parameters were similar among the patients with CA or AA. CIMT levels were higher in the acromegaly group than in the control group [0.60 mm (0.43-0.86) vs. 0.38 mm (0.27-0.59); p < 0.001], and AA patients had higher CIMT than CA patients (p = 0.037). None of the clinical or laboratory parameters including growth hormone and IGF-1 were related to capillaroscopic parameters or CIMT. CONCLUSION: Decreased capillary number was the major capillaroscopic finding in acromegaly and there was no significant difference between active and controlled cases, but CIMT was found to be higher in the active group. Increased CIMT levels in acromegaly were not associated with capillary changes. Large-scale, prospective studies are needed to make a definite conclusion about the effect of the disease activity on nailfold capillaries and its association with macrovascular changes.
Assuntos
Acromegalia , Humanos , Acromegalia/diagnóstico , Acromegalia/complicações , Capilares , Espessura Intima-Media Carotídea , Estudos Transversais , Estudos de Casos e Controles , Angioscopia Microscópica , Unhas/irrigação sanguíneaRESUMO
In this national cohort study, the patients with acromegaly had significantly higher risks of clinical vertebral (HR 2.09 [1.58-2.78]) and hip (HR 2.52 [1.61-3.95]) fractures than the controls. The increased fracture risk in patients with acromegaly was time-dependent and was observed even during the early period of follow-up. PURPOSE: Acromegaly is characterized by the overproduction of growth hormone (GH) and insulin-like growth factor-1 (IGF-1), both play important roles in regulating bone metabolism. We investigated the risk of vertebral and hip fractures in patients with acromegaly compared to age- and sex-matched controls. METHODS: This nationwide population-based cohort study included 1,777 patients with acromegaly aged 40 years or older in 2006-2016 and 8,885 age- and sex-matched controls. A Cox proportional hazards model was used to estimate the adjusted hazard ratio (HR) [95% confidence interval]. RESULTS: The mean age was 54.3 years and 58.9% were female. For approximately 8.5 years of follow-up, the patients with acromegaly had significantly higher risks of clinical vertebral (HR 2.09 [1.58-2.78]) and hip (HR 2.52 [1.61-3.95]) fractures than the controls in the multivariate analyses. There were significant differences in the risks of clinical vertebral (P < 0.0001) and hip (P < 0.0001) fractures between the patients with acromegaly and the controls in the Kaplan-Meier survival analysis. The multivariable-adjusted HRs for clinical vertebral fractures comparing the patients with acromegaly with controls during and excluding the first 7 years of observation were 1.69 [1.15-2.49] and 2.70 [1.75-4.17], respectively. The HRs for hip fractures during and excluding the first 7 years of observation were 2.29 [1.25-4.18] and 3.36 [1.63-6.92], respectively. CONCLUSIONS: The patients with acromegaly had a higher risk of hip fractures as well as clinical vertebral fractures than the controls. The increased fracture risk in patients with acromegaly was time-dependent and was observed even during the early period of follow-up.
Assuntos
Acromegalia , Fraturas do Quadril , Fraturas da Coluna Vertebral , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Acromegalia/complicações , Estudos de Coortes , Fraturas do Quadril/epidemiologia , Fraturas do Quadril/etiologia , Fatores de Risco , Fraturas da Coluna Vertebral/epidemiologia , Fraturas da Coluna Vertebral/etiologia , Coluna Vertebral , AdultoRESUMO
BACKGROUND: Acromegaly is a disease of growth hormone excess that results in enlargement of extremities, abnormal glucose and lipid metabolism, and gonadal disruption. Manifestations of the disease are insidious and typically lead to a diagnostic delay of 7-10 years. Classically the polycystic ovary syndrome (PCOS) phenotype is described in women with irregular menses, clinical or biochemical evidence of androgen excess, and/or multiple ovarian follicles on pelvic ultrasonography. Women with acromegaly may present with some or all of these symptoms. Our objective was to evaluate the prevalence of PCOS in patients with acromegaly and to determine if diagnosis of PCOS results in a delay in diagnosing acromegaly. METHODS: Using patient databases at two academic health centers, we identified 97 premenopausal women aged 18-49 years old presenting with acromegaly. Data were collected regarding pelvic sonography and reproductive history, including the diagnosis of PCOS. Patients carrying the diagnosis of PCOS before their diagnosis of acromegaly were identified and the remaining patients were screened using the Rotterdam criteria to identify additional patients meeting the criteria for PCOS prior to their diagnosis of acromegaly. RESULTS: Mean age of the population (n = 97) at the time of diagnosis of acromegaly was 33.4 ± 7.5 years (SD). Thirty-three percent of patients (n = 32) either carried a diagnosis of PCOS or met diagnostic criteria for PCOS before their diagnosis of acromegaly. In the subset of patients in whom data on symptom onset were available, those who met criteria for PCOS were diagnosed with acromegaly a median of 5 years [4, 9] after the onset of symptoms compared to 2 years [0.92, 3] (p = 0.006) in the patients who did not meet criteria for PCOS. CONCLUSIONS: Our data demonstrate a high prevalence of signs and symptoms of PCOS in reproductive-aged women with acromegaly and a longer time to diagnosis in women who meet the clinical criteria for PCOS. As screening for acromegaly is relatively simple and done with measurement of a random, non-fasting IGF-1 level that can be drawn at any time during the menstrual cycle, screening patients with PCOS for acromegaly may lessen the delay in diagnosis for reproductive-aged women with this disease.
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Acromegalia , Síndrome do Ovário Policístico , Feminino , Humanos , Acromegalia/complicações , Acromegalia/diagnóstico , Diagnóstico Tardio , Síndrome do Ovário Policístico/complicações , Síndrome do Ovário Policístico/diagnóstico , Síndrome do Ovário Policístico/epidemiologia , Reprodução , Estudos Retrospectivos , AdultoRESUMO
BACKGROUND: Acromegaly is characterized by impaired bone quality and increased fracture risk. However, due to the pathophysiology of acromegalic osteopathy, bone mineral density (BMD) does not represent a reliable predictor for fragility fractures in this setting. Trabecular bone score (TBS) has been recently evaluated as an alternative index of skeletal fragility in acromegalic patients. However, no conclusive data are still available in this regard. METHODS: PubMed/Medline, EMBASE, Cochrane Library, Ovid, and CINAHL databases were systematically searched until June 2022 for studies reporting data either about the comparison of TBS values between acromegalic patients and non-acromegalic controls or about the relationship - within acromegalic patients - between TBS values and fracture risk. Effect sizes were pooled through a random-effect model. RESULTS: Eight studies were eligible for inclusion in the meta-analysis, encompassing 336 acromegalic patients and 490 non-acromegalic controls. Overall, TBS was significantly lower in acromegalic patients compared to controls (-0.089, 95% CI: [-0.111, -0.067], p < 0.01), irrespective of acromegaly disease activity and gonadal status. With respect to fracture risk, TBS was significantly lower in acromegalic patients with vertebral fractures than in those without (-0.099, 95% CI: [-0.166, -0.032], p < 0.01). CONCLUSION: In this meta-analysis, we specifically assessed the role of TBS as an index of bone quality and fracture risk in patients with acromegaly. Our results support the notion that TBS could be of value in the assessment and management of skeletal fragility in acromegalic patients, especially in light of the poor information provided in this setting by BMD.
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Acromegalia , Osso Esponjoso , Humanos , Osso Esponjoso/diagnóstico por imagem , Acromegalia/complicações , Absorciometria de Fóton , Vértebras Lombares , Densidade Óssea/fisiologiaRESUMO
BACKGROUND: Pregnancy in acromegaly is uncommon and still in debate for fear of tumor progression or potential threat to both mother and fetus's health. Besides, the data for pregnancy complications in uncontrolled acromegaly is limited. Thus, the objective of this study was to summarize pregnancy safety and disease courses after pregnancy in acromegalic patients and review their clinical characteristics based on disease activity in the literature. METHODS: An evaluation of eight acromegalic women from Peking Union Medical College Hospital (PUMCH) with 11 pregnancies was conducted. We also summarized a literature review of 82 disease-active pregnancies and 63 disease-controlled pregnancies with acromegaly. A second analysis was conducted to compare pregnancy courses and outcomes in different disease activities. RESULTS: Before pregnancy, all patients had macroadenomas and underwent pituitary surgery. Pregnancy occurred at a median of 6 years (4-10) after the diagnosis of acromegaly. Assisted reproductive therapy was needed in 42.9% of participants. No cases had a premature birth or congenital malformations. Biochemical control was achieved in 50% of females before pregnancy and 75% at the last follow-up after delivery. Data analysis showed no differences in the prevalence of gestational diabetes mellitus (GDM) or pregnancy-induced hypertension (PIH) between acromegaly-active or acromegaly-controlled groups. The GDM prevalence in patients diagnosed during pregnancy (33.3%) was higher than that in patients diagnosed before pregnancy (4.8%) (p = 0.001). CONCLUSION: Pregnancy without biochemical control in acromegaly and receiving medical treatment during pregnancy are not rare and generally safe for the fetus. There could be a higher prevalence of PIH in acromegalic pregnancies. The treatment of acromegaly and related complications can be managed with regular follow-up after pregnancy.
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Acromegalia , Diabetes Gestacional , Gravidez , Humanos , Feminino , Lactente , Acromegalia/complicações , Acromegalia/epidemiologia , China/epidemiologia , Família , Análise de Dados , Diabetes Gestacional/epidemiologiaRESUMO
PURPOSE: Stereotactic radiosurgery (SRS) can be used in acromegaly patients to achieve endocrine remission. In this study we evaluate the biological effective dose (BED) as a predictor of SRS outcomes for acromegaly. METHOD: This retrospective, single-center study included patients treated with single-fraction SRS with growth hormone secreting pituitary adenomas and available endocrine follow-up. Kaplan-Meier analysis was used to study endocrine remission, new pituitary deficit, and tumor control. Cox analyses were performed using two models [margin dose (model 2) versus BED (model 1)]. RESULTS: Sixty-seven patients (53.7% male) with a median age of 46.8 years (IQR 21.2) were treated using a median dose of 25 Gy (IQR 5), and a median BED of 171.9Gy2.47 (IQR 66.0). Five (7.5%) were treated without stopping antisecretory medication. The cumulative probability of maintained endocrine remission off suppressive medications was 62.5% [47.9-73.0] at 3 years and 76.5% [61.0-85.9] at 5 years. IGF1i > 1.5 was a predictor of treatment failure [Hazard ratio (HR) 0.40 (0.21-0.79) in model 1, p = 0.00783]. Margin dose > 22 Gy [HR 2.33 (1.06-5.13), p = 0.03593] or a BED > 170Gy2.47 [HR 2.02 (1.06-3.86), p = 0.03370] were associated with endocrine remission. The cumulative probability of new hypopituitarism after SRS was 36.8% (CI 95% 22.4-45.9) at 3 years and 53.2% (CI 95% 35.6-66) at 5 years. BED or margin dose were not associated with new hypopituitarism. CONCLUSION: BED is a strong predictor of endocrine remission in patients treated with SRS. Dose planning and optimization of the BED to > 170Gy2.47 give a greater probability of endocrine remission in acromegalic patients.
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Acromegalia , Adenoma , Hipopituitarismo , Radiocirurgia , Feminino , Humanos , Masculino , Acromegalia/radioterapia , Acromegalia/cirurgia , Acromegalia/complicações , Adenoma/radioterapia , Adenoma/cirurgia , Adenoma/complicações , Seguimentos , Hipopituitarismo/etiologia , Radiocirurgia/efeitos adversos , Estudos Retrospectivos , Resultado do Tratamento , Pessoa de Meia-IdadeRESUMO
OBJECTIVE: To compare the incidence of cancer in patients with acromegaly with that of the local population in China and explore possible risk factors. METHODS: Data from 117 patients diagnosed with acromegaly at 2 centers between 2011 and 2022 were analyzed, and their cancer diagnoses were recorded. The cancer standardized incidence ratios (SIRs) and 95% confidence intervals (CIs) were calculated by comparison with those of the local population. The patients were divided into 2 groups, having cancer diagnosis or not. The relationships between cancer and sex, body mass index, age, growth hormone levels, diagnosis delay, tumor size, disease duration, treatment, disease status, and other comorbidities were analyzed. RESULTS: Eight (6.8%) of 117 patients were diagnosed with cancer. The incidence of overall (SIR = 3.29, 95% CI = 1.42-6.94), colorectal (SIR = 16.67, 95% CI = 4.45-42.67), and thyroid cancers (SIR = 14.29, 95% CI = 1.73-51.60) was increased, but that of lung cancer (SIR = 4.17, 95% CI = 0.50-15.05) was not. Diagnostic delay (10.1[8.6-14.3] vs 3.8[1.3-9.0]; P = .005) and duration of acromegaly (12.8[8.9-16.4] vs 5.6[2.3-10.9]; P = .008) were prolonged in the cancer group. Diabetes mellitus (odds ratio = 7.01, 95% CI = 1.23-39.99) was an independent risk factor for acromegaly with cancer. CONCLUSION: Acromegaly patients are at a higher risk of cancer and its association with diabetes mellitus. Considering the rarity of the disease, an Acromegaly Cancer Registry Center should be established in China as soon as possible.
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Acromegalia , Diabetes Mellitus , Hormônio do Crescimento Humano , Neoplasias da Glândula Tireoide , Humanos , Acromegalia/complicações , Acromegalia/epidemiologia , Diagnóstico Tardio , Diabetes Mellitus/epidemiologia , Fatores de RiscoRESUMO
PURPOSE: Bone is one of the main targets of hormones and endocrine diseases are frequent causes of secondary osteoporosis and fractures in real-world clinical practice. However, diagnosis of skeletal fragility and prediction of fractures in this setting could be a challenge, since the skeletal alterations induced by endocrine disorders are not generally captured by dual-energy X-ray absorptiometry (DXA) measurement of bone mineral density (BMD), that is the gold standard for diagnosis of osteoporosis in the general population. The aim of this paper is to review the existing evidence related to bone quality features in endocrine diseases, proposing assessment with new techniques in the future. METHODS: A comprehensive search within electronic databases was performed to collect reports of bone quality in primary hyperparathyroidism, hypoparathyroidism, hyperthyroidism, hypercortisolism, growth hormone deficiency, acromegaly, male hypogonadism and diabetes mellitus. RESULTS: Using invasive and non-invasive techniques, such as high-resolution peripheral quantitative computed tomography or DXA measurement of trabecular bone score (TBS), several studies consistently reported altered bone quality as predominant determinant of fragility fractures in subjects affected by chronic endocrine disorders. CONCLUSIONS: Assessment of skeletal fragility in endocrine diseases might take advantage from the use of techniques to detect perturbation in bone architecture with the aim of best identifying patients at high risk of fractures.