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Cushing's Disease (CD), hypercortisolism due to pituitary ACTH secreting neuroendocrine neoplasm, is associated with increased morbidity and, if untreated, mortality in about half of the affected individuals. Consequently, the timely initiation of effective treatment is mandatory. Neurosurgery is the first line and the only potentially curative treatment; however, 30% of patients will have persistent disease post-surgery. Furthermore, a small percentage of those initially controlled will develop hypercortisolism during long-term follow- up. Therefore, patients with persistent or recurrent disease, as well as those considered non-eligible for surgery, will need a second-line therapeutic approach, i.e., pharmacotherapy. Radiation therapy is reserved as a third-line therapeutic option due to its slower onset of action and its unfavorable profile regarding complications. During the past few years, the understanding of molecular mechanisms implicated in the physiology of the hypothalamus-pituitary-adrenal axis has evolved, and new therapeutic targets for CD have emerged. In the present review, currently available treatments, compounds currently tested in ongoing clinical trials, and interesting, potentially new targets emerging from unraveling molecular mechanisms involved in the pathophysiology of Cushing's disease are discussed.
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Hipersecreción de la Hormona Adrenocorticotrópica Pituitaria (HACT) , Humanos , Hipersecreción de la Hormona Adrenocorticotrópica Pituitaria (HACT)/tratamiento farmacológico , AnimalesRESUMEN
N-of-1 trials can serve as useful tools in managing rare disease. We describe a patient presenting with a typical clinical picture of Cushing's Syndrome (CS). Further testing was diagnostic of ectopic Adrenocorticotropic Hormone (ACTH) secretion, but its origin remained occult. The patient was offered treatment with daily pasireotide at very low doses (300 mg bid), which resulted in clinical and biochemical control for a period of 5 years, when a pulmonary typical carcinoid was diagnosed and dissected. During the pharmacological treatment period, pasireotide was tentatively discontinued twice, with immediate flare of symptoms and biochemical markers, followed by remission after drug reinitiation. This is the first report of clinical and biochemical remission of an ectopic CS (ECS) with pasireotide used as first line treatment, in a low-grade lung carcinoid, for a prolonged period of 5 years. In conclusion, the burden of high morbidity caused by hypercortisolism can be effectively mitigated with appropriate pharmacological treatment, in patients with occult tumors. Pasireotide may lead to complete and sustained remission of hypercortisolism, until surgical therapy is feasible. The expression of SSTR2 from typical carcinoids may be critical in allowing the use of very low drug doses for achieving disease control, while minimizing the risk of adverse events.
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Adenoma , Tumor Carcinoide , Síndrome de Cushing , Neoplasias Pulmonares , Tumores Neuroendocrinos , Humanos , Síndrome de Cushing/etiología , Hormona Adrenocorticotrópica , Tumores Neuroendocrinos/complicaciones , Neoplasias Pulmonares/complicaciones , Tumor Carcinoide/complicaciones , Adenoma/complicacionesRESUMEN
INTRODUCTION: Tyrosine kinase inhibitors (TKIs) have been used in patients with advanced medullary thyroid carcinoma (MTC); however, data on their effectiveness and safety are limited. The aim of this systematic review and meta-analysis was to document clinical response and toxicities of TKIs in advanced MTC. METHODS: We systematically searched major databases for articles or abstracts on TKI use in MTC patients until May 2018. Objective response (OR), defined as the sum of complete + partial response, expressed as percentage, was our primary endpoint, while disease stability, disease progression (DP), median progression-free survival (PFS), and drug discontinuation rate due to adverse events (AEs) were secondary endpoints. Pooled percentages, PFS time, and 95% CIs were reported. RESULTS: Thirty-three publications were finally included in the analysis: 1 phase IV, 2 phase III trials evaluating vandetanib and cabozantinib, respectively, 20 phase I or II studies, and the remaining 10 studies of retrospective-observational nature. OR was documented in 28.6% (95% CI 25.9-31.9) of patients. Stable disease was recorded in 46.2% (95% CI 43.3-49.1). Overall, DP was observed in 22.9% (95% CI 20.4-27.6). Grade 3 or more AEs occurred in 48.5% (95% CI 45.5-51.5) of patients, and drug discontinuation was reported in 44.7% (95% CI 41.7-47.6). In general, use of TKIs conferred a PFS of 23.3 months (95% CI 21.07-25.5). In particular, vandetanib induced an OR in 33.8% (95% CI 29.6-38.0) of patients and cabozantinib in 27.7% (95% CI 22.05-33.4). DP occurred in 23.7% (95% CI 19.9-27.6) with vandetanib use and in 22.6% (95% CI 17.4-27.9) in cabozantinib-treated patients. Sorafenib, the third most frequently studied drug, showed intermediate efficacy, but higher discontinuation rates. CONCLUSION: Treatment with TKIs in MTC patients with progressive disease is associated with a moderate therapeutic benefit, with achievement of either disease stability or partial response in 73%. The toxicity of these drugs is not negligible, but it is, nonetheless, manageable.
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In postmenopausal women, osteoporosis may coexist with other metabolic diseases, including, but not limited to, obesity, diabetes, nonalcoholic fatty liver disease (NAFLD), dyslipidemia and cardiovascular disease (CVD). This association may lie beyond simple coincidence owing to high prevalence of all these diseases, especially in the aging population, as common pathogenetic mechanisms between them and osteoporosis may exist. In this context, anti-osteoporotic medications may affect the pathogenesis of some of these metabolic diseases; this is an important consideration when selecting the most appropriate medication for osteoporotic patients with coexistent metabolic diseases. Conversely, some current or emerging medications for metabolic diseases adversely affect bone metabolism and, if possible, should be avoided in women with postmenopausal osteoporosis. The main aim of this review is to summarize the evidence on anti-osteoporotic treatment in postmenopausal women with concomitant metabolic diseases, i.e. obesity, diabetes, NAFLD, dyslipidemia and CVD. The secondary aim is to present data on the effect of current or emerging medication for metabolic diseases on bone metabolism of postmenopausal women. Deeper understanding of the underlying links between osteoporosis and metabolic diseases may have clinical implications. However, mechanistic studies are needed to elucidate the potential pathophysiological links, as well as clinical trials in women with postmenopausal osteoporosis coexisting with specific metabolic diseases; these may guide clinical practice in the future for the selection of the best anti-osteoporotic medication for each patient with specific metabolic diseases.
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Enfermedades Metabólicas/complicaciones , Osteoporosis Posmenopáusica/complicaciones , Animales , Enfermedades Cardiovasculares/complicaciones , Enfermedades Cardiovasculares/terapia , Femenino , Humanos , Enfermedades Metabólicas/terapia , Enfermedad del Hígado Graso no Alcohólico/complicaciones , Enfermedad del Hígado Graso no Alcohólico/terapia , Obesidad/complicaciones , Obesidad/terapia , Osteoporosis Posmenopáusica/terapiaRESUMEN
INTRODUCTION: Hajdu-Cheney Syndrome (HCS) is a rare genetic autosomal dominant disorder, characterized by distinctive facial features, acroosteolysis, and severe osteoporosis. Very rarely HCS is associated with polycystic kidney disease, splenomegaly or Crohn's disease (CD). It is caused by gain-of-function mutations in NOTCH2 gene. Treatment with bisphosphonates or denosumab is reported to result in BMD increase. OBJECTIVE: We report a mutation in exon 34 of NOTCH2 gene, in a Greek pedigree, with diverse phenotypes among members. DESCRIPTION OF THE PEDIGREE: The 48-year-old mother had a history of a T12 vertebral fracture, postpartum at the age of 21 and two subsequent uneventful full-term pregnancies and never received treatment. Her 29-year-old son, presented with severe osteoporosis and multiple morphological vertebral fractures. Her 21-year-old daughter had recurrent vertebral fractures starting at 10 years of age. At 17 years, she developed severe CD, resistant to treatment with biologic agents, and functional hypothalamic hypogonadism. One male pedigree died of cystic fibrosis. All subjects bore the typical facial characteristics and acroosteolysis, while none had splenomegaly or renal defects. Zoledronate infusion led to BMD increase. GENETIC TESTING: Mutation in c.6758 G > A (NM_008163.1), leading to a Trp2253Ter replacement. This mutation has been reported as possibly pathogenic (SCV000620308), but not in association with HCS. CONCLUSIONS: Bone involvement can present with diverse severity in the same pedigree, ranging from low BMD to multiple fragility fractures. Antiresorptive therapy improves BMD, but its anti-fracture efficacy remains to be shown. The presence of CD might indicate the significant role of NOTCH2 signaling in different tissues.
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Síndrome de Hajdu-Cheney , Osteoporosis , Receptor Notch2 , Femenino , Grecia , Síndrome de Hajdu-Cheney/diagnóstico por imagen , Síndrome de Hajdu-Cheney/tratamiento farmacológico , Síndrome de Hajdu-Cheney/genética , Humanos , Masculino , Mutación , Fenotipo , Embarazo , Receptor Notch2/genéticaRESUMEN
The hypothalamic-pituitary axis is responsible for the neuroendocrine control of several organ systems. The anterior pituitary directly affects the functions of the thyroid gland, the adrenal glands, and gonads, and regulates growth and milk production. The posterior hypophysis, through nerve connections with the hypothalamic nuclei, releases vasopressin and oxytocin responsible for water balance and social bonding, sexual reproduction and childbirth, respectively. Pituitary gland hormonal excess or deficiency results in dysregulation of metabolic pathways and mechanisms that are important for the homeostasis of the organism and are associated with increased morbidity and mortality. Cardiovascular (CV) disorders are common in pituitary disease and have a significant impact on survival. Hormonal imbalance is associated with CV complications either through direct effects on the heart structure and function and vasculature or indirectly by altering the metabolic profile. Optimal endocrine control can prevent or reverse CV defects and preserve survival and quality of life. In this review, we discuss the effects of pituitary hormone excess and deficiency on the CV system. Specifically, we assess the impact of Somatotroph, Corticotroph, Gonadotroph, and Lactotroph anterior pituitary axes on the CV system. The effect of posterior pituitary function on the CV system is also explored.
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Enfermedades Cardiovasculares , Humanos , Hipotálamo , Calidad de Vida , Glándula TiroidesRESUMEN
An amendment to this paper has been published and can be accessed via a link at the top of the paper.
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BACKGROUND AND AIMS: Nonalcoholic fatty liver disease (NAFLD) is highly prevalent in patients with type 2 diabetes mellitus (T2DM). There is currently no approved treatment for NAFLD. The main aim was the evaluation of the effect of glucagon-like peptide-1 receptor agonists (GLP-1 RA) vs. dipeptidyl peptidase-4 inhibitor (DPP-4i) treatment on noninvasive indices of hepatic steatosis and fibrosis in patients with T2DM. METHODS: In this retrospective study, three noninvasive indices of hepatic steatosis [HSI, NAFLD ridge score, and triglycerides (TG) to high-density lipoprotein cholesterol (HDL-C) ratio] and five of fibrosis (APRI, FIB-4, NAFLD fibrosis score, BAAT and BARD) were calculated before and after (6-18 months) the addition of a DPP-4i (n = 152) or a GLP-1 RA (n = 37) in patients with T2DM. RESULTS: Regarding steatosis indices, NAFLD ridge score was significantly decreased in the GLP-1 RA group (baseline: 0.90 ± 0.34, follow-up: 0.67 ± 0.24; p = 0.001), but not in the DPP-4i group (p = 0.25); the difference for group∗time interaction was significant (p = 0.02). HSI showed a trend between groups, being significantly different at baseline and follow-up (p < 0.001) with no significant difference in group∗time interaction. Indices of fibrosis were not essentially changed within or between groups. CONCLUSIONS: NAFLD ridge score was significantly decreased after the addition of GLP-1 RA in patients with T2DM. This study warrants further prospective clinical trials.
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Diabetes Mellitus Tipo 2/complicaciones , Inhibidores de la Dipeptidil-Peptidasa IV/uso terapéutico , Receptor del Péptido 1 Similar al Glucagón/agonistas , Cirrosis Hepática/tratamiento farmacológico , Enfermedad del Hígado Graso no Alcohólico/tratamiento farmacológico , Anciano , Biomarcadores/metabolismo , Femenino , Estudios de Seguimiento , Humanos , Cirrosis Hepática/etiología , Cirrosis Hepática/metabolismo , Cirrosis Hepática/patología , Masculino , Persona de Mediana Edad , Enfermedad del Hígado Graso no Alcohólico/etiología , Enfermedad del Hígado Graso no Alcohólico/metabolismo , Enfermedad del Hígado Graso no Alcohólico/patología , Pronóstico , Estudios RetrospectivosRESUMEN
Thyroid hormones are crucial for hepatic lipid and glucose metabolism. Non-alcoholic fatty liver disease (NAFLD), a very common and potentially serious disease of modern society, shares common clinical features with hypothyroidism, such as obesity, insulin resistance and dyslipidemia. Furthermore, in certain studies, increased prevalence of hypothyroidism was observed in patients with NAFLD. However, whether there is a linear relationship between thyroid hormone levels, including values within or in proximity to the reference range and NAFLD incidence and severity remains a contradictory subject in the literature. On the other hand, attempts to treat NAFLD with thyromimetic drugs remain at an early stage. In this review, data derived from observational studies along with evidence on possible treatment with thyroid hormone analogues are presented.
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Enfermedad del Hígado Graso no Alcohólico/complicaciones , Enfermedades de la Tiroides/complicaciones , Humanos , Enfermedad del Hígado Graso no Alcohólico/sangre , Enfermedad del Hígado Graso no Alcohólico/tratamiento farmacológico , Estudios Observacionales como Asunto , Enfermedades de la Tiroides/sangre , Enfermedades de la Tiroides/tratamiento farmacológico , Hormonas Tiroideas/sangre , Hormonas Tiroideas/uso terapéuticoRESUMEN
INTRODUCTION: Irisin is a myokine/adipokine induced by the exercise in mice and humans, which is proposed to induce "browning" of white adipose tissue, its primary target, thus increasing thermogenesis and energy expenditure. Since its identification, irisin has been linked to favorable effects on metabolic diseases, including obesity, type 2 diabetes mellitus (T2DM), lipid metabolism and cardiovascular disease (CVD), nonalcoholic fatty liver disease (NAFLD), polycystic ovary syndrome (PCOS), and metabolic bone diseases. Generally, despite the promising profile of irisin in rodents, its effects on human are less recognized. REVIEW: Most, but not all studies show a positive association between irisin and indices of adiposity. In T2DM, NAFLD, and CVD, most observational studies reported lower irisin levels in patients than controls. Regarding metabolic bone diseases, irisin is positively associated with bone mineral density and strength in athletes, and inversely associated with osteoporotic fractures in postmenopausal osteoporosis. In PCOS, data remain largely conflicting. Irisin does not seem to be further reduced when two metabolic diseases, e.g., T2DM and NAFLD, or obesity and NAFLD exist though more data are needed. Furthermore, it seems that diverse confounders may have affected the results of different clinical studies. CONCLUSION: Irisin remains an appealing molecule from a pathophysiological point of view and an appealing therapeutic target for metabolic diseases, albeit much research is still needed.
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Adiposidad/fisiología , Fibronectinas/sangre , Enfermedades Metabólicas/sangre , Tejido Adiposo Blanco/metabolismo , Densidad Ósea , Humanos , Músculo Esquelético/metabolismoRESUMEN
PURPOSE: To compare denosumab-induced changes in lumbar spine (LS) and femoral neck (FN) bone mineral density (BMD), bone markers and free soluble receptor activator of nuclear factor kappaB ligand (sRANKL) between treatment naïve postmenopausal women with low bone mass (naïve group) and those who were previously treated with a single zoledronic acid infusion (post-Zol group). PROCEDURES: Procollagen type 1N-terminal propeptide (P1NP), C-terminal cross-linking telopeptide of type 1 collagen (CTx) and sRANKL levels were measured in serum samples obtained at baseline and 3, 6 and 12months after denosumab initiation. LS and FN BMD were measured at baseline and 12months. RESULTS: LS and FN BMD increased significantly in both naïve and post-Zol group (p<0.001 and p=0.025 vs. p<0.001 and p=0.017, respectively). Despite the higher P1NP and CTx levels in naïve patients at baseline (both p<0.001), denosumab caused comparable decreases in both groups at month 3, which returned to post-Zol group baseline levels at month 6 and 12 in all patients. Similarly, sRANKL levels decreased significantly at month 3 in both groups and returned to baseline levels at months 6 and 12. CONCLUSIONS: In patients previously treated with zoledronic acid, sequential denosumab treatment is effective in terms of BMD increases and bone turnover suppression. Despite the lower baseline levels in patients pre-treated with zoledronic acid, bone markers are similarly decreased in both groups following denosumab administration and maintain their reversibility. Denosumab reversibly suppresses endogenous free sRANKL levels in both naïve and zoledronic acid pre-treated patients.
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Conservadores de la Densidad Ósea/administración & dosificación , Densidad Ósea/efectos de los fármacos , Remodelación Ósea/efectos de los fármacos , Denosumab/administración & dosificación , Difosfonatos/uso terapéutico , Imidazoles/uso terapéutico , Osteoporosis Posmenopáusica/tratamiento farmacológico , Biomarcadores/sangre , Colágeno Tipo I/sangre , Difosfonatos/administración & dosificación , Esquema de Medicación , Femenino , Estudios de Seguimiento , Humanos , Imidazoles/administración & dosificación , Persona de Mediana Edad , Osteoporosis Posmenopáusica/sangre , Fragmentos de Péptidos/sangre , Péptidos/sangre , Posmenopausia/efectos de los fármacos , Procolágeno/sangre , Ligando RANK/sangre , Ácido ZoledrónicoRESUMEN
OBJECTIVE: The association of four single nucleotide polymorphisms in estrogen receptor alpha (ESR1) and beta (ESR2) genes with lipid levels and insulin resistance in men. DESIGN AND METHODS: Lipids, glucose, insulin and HOMA-IR were determined, in a population-based, cross-sectional, cohort of 170 apparently healthy middle-aged Greek men, along with body mass index (BMI), waist circumference (WC) and percentage of body fat content (%fat). Genotyping of ESR1 for PvuII and XbaI and ESR2 for RsaI and AluI polymorphisms was performed. RESULTS: Associations of AluI with LDL-Chol (mean ± SD, aa 4.3 ± 1.1 vs. Aa 3.7 ± 1.0 and ΑΑ 4.2 ± 1.1, p = 0.023) and RsaI with HOMA-IR [median (IQR), RR 1.55 (0.88-2.49) vs. Rr/rr 1.69 (0.72-2.29), p = 0.032] were found. Synergistic effects of RsaI and AluI of ESR2 gene on LDL-Chol levels, %fat and WC, as well as a synergistic effect of both ESR1 and ESR2 genes on levels of TChol (p = 0.01) and LDL-Chol (p = 0.027) were also shown. These findings remained significant after adjustment for potential confounders. Significant independent associations of PvuII with %fat (mean ± SD, pp 24.6 ± 5.3 vs Pp 22.4 ± 5.2 and PP 21.2 ± 6.7, p = 0.044), and RsaI with %fat (RR 22.6 ± 5.5 vs. Rr/rr 25.2 ± 6.3, p = 0.015) and WC (mean ± SD, RR 97.4 ± 10.4 vs. Rr/rr 102.6 ± 12.6, p = 0.013) were found. Synergistic effects on %fat, between the ESR1 polymorphisms (p = 0.004), between the ESR2 polymorphisms and among all four ESR polymorphisms studied were also present. CONCLUSIONS: ESR2 is associated with LDL-Chol levels and HOMA-IR in men independently of confounders. Body fat is affected by both genes. Furthermore, a synergistic effect of ESR1 and ESR2 on TChol, LDL-Chol and %fat, was shown.
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Colesterol/sangre , Receptor alfa de Estrógeno/genética , Receptor beta de Estrógeno/genética , Polimorfismo de Nucleótido Simple/genética , Composición Corporal , Índice de Masa Corporal , Estudios de Cohortes , Estudios Transversales , Genotipo , Grecia , Humanos , Resistencia a la Insulina/genética , Modelos Lineales , Masculino , Persona de Mediana Edad , Circunferencia de la Cintura , Adulto JovenRESUMEN
OBJECTIVE: An increased prevalence of thyroid autoimmunity has been observed after successful treatment of Cushing's syndrome. On the other hand, De Quervain's thyroiditis (DQT), in which autoimmunity is not a pathogenetic contributor, has not been reported during recovery from Cushing's syndrome. We describe 2 female patients with DQT coinciding with the resolution of hypercortisolism after treatment of Cushing's syndrome/disease. METHODS: The first patient had been diagnosed with Cushing's disease due to a corticotroph pituitary microadenoma, declined neurosurgery, and was receiving pharmacological treatment with pasireotide. Her hypercortisolism was optimally controlled with a minimum dose. The second patient had undergone unilateral adrenalectomy due to a cortisol-secreting adenoma and was on tapering doses of hydrocortisone due to a suppressed corticotroph axis. Both patients presented with clinical, functional, and imaging features of DQT at a time when their endogenous glucocorticoid levels were very low. RESULTS: Oral glucocorticoid treatment was administered in both cases, resulting in prompt recovery. CONCLUSIONS: The incidence of DQT following the resolution of hypercortisolism, either medical or surgical, has not been previously described. The exact pathogenetic mechanism can only be speculated on. Perhaps the relative or absolute glucocorticoid deficiency after effective treatment of hypercortisolism alters immunologic responses and renders patients more vulnerable to thyrolytic processes.
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Several studies have shown that acromegaly is associated with increased psychological morbidity. However, it is not known whether this is attributed to acromegaly per se or to its chronicity as a debilitating disease affecting quality of life (QoL). The aim of this study was to assess psychological profile in acromegalics compared with those suffering from other serious chronic diseases and healthy controls. Secondary end points were QoL assessment and its association with mood disturbances. Comparative, cross-sectional study conducted in Northern Greece (2011-2012). The Greek versions of the Profile of Mood States (POMS) and AcroQoL questionnaires were used to assess psychological status and QoL, respectively. Forty acromegalics, 40 age- and sex-matched people with other chronic diseases and 80 healthy controls were included. No significant differences were identified between acromegalics and those suffering from other chronic diseases, regarding tension, anger, depression, confusion, fatigue and vigor. Compared with healthy controls, acromegalics suffered more from depression and anger, which remained significant after controlling for age, gender and marital status (p = 0.003 and p = 0.048, respectively). Negative predictors were female gender, macroadenomas and radiotherapy. AcroQoL scores were negatively associated with POMS subscales. Males had better QoL than females. Other than a negative association between AcroQoL-relationships subscale and disease duration, no association with other parameters was observed. Acromegaly has a negative impact on psychological status, which is worse than that of general population, but comparable to other chronic diseases. Mood disturbances are associated with impaired QoL, mainly in females and those with longer disease duration.
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Acromegalia/psicología , Ira , Depresión/psicología , Salud Mental , Calidad de Vida/psicología , Acromegalia/complicaciones , Adulto , Enfermedad Crónica/psicología , Estudios Transversales , Fatiga/complicaciones , Fatiga/psicología , Femenino , Grecia , Estado de Salud , Encuestas Epidemiológicas , Humanos , Masculino , Persona de Mediana Edad , Encuestas y CuestionariosRESUMEN
BACKGROUND: Pituitary tumors, paragangliomas, and Cowden syndrome do not usually occur together. METHODS: The synchronous presentation of papillary thyroid carcinoma and neck paraganglioma was revealed in a 43-year-old woman who had been diagnosed with a microprolactinoma one decade before and now presented with a constellation of characteristics that are components of Cowden syndrome, specifically macrocephaly, multiple skin papules, fibrocystic mammary disease, and uterine leiomyofibroma. RESULTS: Germline mutation analysis of phosphatase and tensin homolog (PTEN), succinate dehydrogenase subunit B (SDHB), succinate dehydrogenase subunit C (SDHC), and succinate dehydrogenase subunit D (SDHD) was performed with revelation of 3 polymorphic sites in introns 1, 4, and 8 of the PTEN gene and 1 polymorphic site in exon 1 of the SDHB gene, but absence of known pathogenic mutations. CONCLUSION: The coexistence of Cowden-like syndrome, neck paraganglioma, and pituitary adenoma is described for the first time, and could represent a novel genetic syndrome with an as yet unidentified common genetic basis.
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Predisposición Genética a la Enfermedad , Síndrome de Hamartoma Múltiple/diagnóstico , Neoplasias de Cabeza y Cuello/diagnóstico , Enfermedades Mitocondriales/diagnóstico , Neoplasias Primarias Múltiples/diagnóstico , Paraganglioma/diagnóstico , Neoplasias Hipofisarias/diagnóstico , Biopsia con Aguja , Femenino , Pruebas Genéticas , Mutación de Línea Germinal , Síndrome de Hamartoma Múltiple/genética , Síndrome de Hamartoma Múltiple/cirugía , Neoplasias de Cabeza y Cuello/genética , Neoplasias de Cabeza y Cuello/cirugía , Humanos , Inmunohistoquímica , Imagen por Resonancia Magnética/métodos , Persona de Mediana Edad , Enfermedades Mitocondriales/genética , Enfermedades Mitocondriales/cirugía , Neoplasias Primarias Múltiples/genética , Neoplasias Primarias Múltiples/cirugía , Paraganglioma/genética , Paraganglioma/cirugía , Neoplasias Hipofisarias/genética , Neoplasias Hipofisarias/cirugía , Enfermedades Raras , Tomografía Computarizada por Rayos X/métodos , Ultrasonografía DopplerRESUMEN
OBJECTIVE: Complete remission of acromegaly is associated with favourable changes in cardiovascular risk parameters. We evaluated the effects of suboptimal therapy on haemodynamic, metabolic, inflammatory and coagulation cardiovascular risk indices. DESIGN AND METHODS: Eighteen acromegalic patients on somatostatin analogues, with incomplete biochemical control, were evaluated at diagnosis and 6 months after treatment and compared to 15 healthy age- and body mass index (BMI)-matched controls. Measurements of blood pressure, GH, IGF-I, glucose, insulin, glycated haemoglobin (HbA1c), lipids, apolipoprotein A1 (apoA1), apoB, high-sensitivity C-reactive protein (hs-CRP), fibrinogen, plasminogen activator inhibitor 1 (PAI-1), tissue plasminogen activator (tPA) and circulating thrombomodulin were performed in all study participants, followed by an oral glucose tolerance test (OGTT). Insulin sensitivity (IS) was expressed by the Matsuda index (OGTT(ISI)). RESULTS: Partial control of acromegaly resulted in a significant reduction in systolic and diastolic blood pressure, glucose, insulin, HbA1c, total (T-C) and low density lipoprotein cholesterol (LDL-C) and triglyceride levels, and a significant increase in apoA1, high density lipoprotein cholesterol (HDL-C) and OGTT(ISI) compared to pretreatment levels. Plasma fibrinogen and PAI-1 levels fell significantly [respectively (mean +/- SEM), 11.04 +/- 0.41 vs. 10.12 +/- 0.34 micromol/l, P = 0.003 and 9.6 +/- 1.97 vs. 6.55 +/- 1.89 microg/l, P < 0.001]. However, a marked reduction in tPA [median (IQR) 5.1 (2.5-15) vs. 3.4 (2.4-8.6) microg/l, P = 0.031] and an increase in hs-CRP [median (IQR) 0.05 (0.03-0.11) vs. 0.1 (0.06-0.23) mg/l, P < 0.001] were also noted. On treatment, acromegalic patients were comparable to controls, except for OGTT(ISI), lipoprotein(a) [Lp(a)], fibrinogen and tPA and HDL-C levels. Thrombomodulin and apoB levels were not affected by treatment. CONCLUSIONS: Partial control in disease activity following somatostatin analogues results in significant improvement in a considerable number of cardiovascular risk markers in acromegaly.