RESUMO
Cushing's syndrome (CS) is a rare disorder, once exogenous causes have been excluded. However, when diagnosed, the majority of cases are adrenocorticotropic hormone (ACTH)-dependent, of which a substantial minority are due to a source outside of the pituitary, ectopic ACTH syndrome (EAS). Differentiating among pituitary-dependent CS, Cushing's disease (CD) and an ectopic source can be problematic. Because non-invasive tests in the evaluation of CS patients often lack adequate sensitivity and specificity, bilateral inferior petrosal sinus sampling (BIPSS), a minimally invasive procedure performed during the investigation of ACTH-dependent CS, can be extremely helpful. BIPSS is considered to be the gold standard for differentiating CD from the EAS. Furthermore, although such differentiation may indeed be challenging, BIPSS is itself a complex investigation, especially in recent times due to the widespread withdrawal of corticotrophin-releasing hormone and its replacement by desmopressin. We review current published data on this investigation and, in the light of this and our own experience, discuss its appropriate use in diagnostic algorithms.
Assuntos
Síndrome de ACTH Ectópico , Hormônio Adrenocorticotrópico , Síndrome de Cushing , Amostragem do Seio Petroso , Humanos , Diagnóstico Diferencial , Síndrome de Cushing/diagnóstico , Síndrome de ACTH Ectópico/diagnóstico , Hormônio Adrenocorticotrópico/sangue , Hipersecreção Hipofisária de ACTH/diagnósticoRESUMO
Pediatric procedure-related pain management is often incompletely understood, inadequately addressed, and critical in influencing a child's lifelong relationship with the larger health care community. We highlight the evolution of ethics and expectations around optimizing periprocedural pain management as a fundamental human right. We investigate the state-of-the-art of topical anesthetics, reviewing their mechanisms of action and providing comparisons of their relative safety and efficacy data to help guide clinical selection. In total, this two-part review offers a combination of conventional approaches and innovative techniques that should be used multimodally-in series and in parallel-to help optimize pain management and provide alternatives to sedation medication and general anesthesia.
Assuntos
Anestésicos Locais , Manejo da Dor , Humanos , Anestésicos Locais/uso terapêutico , Manejo da Dor/métodos , Manejo da Dor/ética , Criança , Dor Processual/prevenção & controle , Pediatria/éticaRESUMO
Pediatric procedure-related pain management is often incompletely understood, inadequately addressed, and critical in influencing a child's lifelong relationship with the larger healthcare community. We present a comprehensive review of infiltrative anesthetics, including a comparison of their mechanisms of action and relative safety and efficacy data to help guide clinical selection. We also describe the multimodal utilization of adjunct therapies-in series and in parallel-to support the optimization of pediatric periprocedural pain management, enhance the patient experience, and provide alternatives to sedation medication and general anesthesia.
Assuntos
Anestésicos Locais , Manejo da Dor , Humanos , Criança , Manejo da Dor/métodos , Anestésicos Locais/uso terapêutico , Anestésicos Locais/administração & dosagem , Dor Processual/prevenção & controle , Dor Processual/etiologiaRESUMO
BACKGROUND: Cushing's syndrome (CS) poses diagnostic challenges, particularly in distinguishing pituitary-dependent Cushing's syndrome, Cushing's disease (CD), from the ectopic ACTH syndrome (EAS). This study evaluated the diagnostic value of the desmopressin stimulation test (DST) in patients with ACTH-dependent CS in helping this discrimination. METHODS: Twenty-three ACTH-dependent CS patients underwent sequential DST, bilateral inferior petrosal sinus sampling (BIPSS), and transsphenoidal surgery (TSS). Two definitions of a positive DST results were applied. Diagnostic performance was assessed using sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and likelihood ratios. To avoid bias from predetermined criteria, we generated univariate receiver-operating characteristic (ROC) curves, plotting sensitivity against 1-specificity at various percentage cortisol and ACTH response levels. RESULTS: Against BIPSS, DST demonstrated robust sensitivity (Definition 1: 90.0%, Definition 2: 76.2%) and overall accuracy (Definition 1: 87.0%, Definition 2: 73.9%). PPV was high (Definition 1: 95.0%, Definition 2: 94.1%), but NPV indicated potential false negatives. Compared to TSS, DST showed good sensitivity (Definition 1: 90.9-77.3%) and PPV (100.0%) but limited NPV (16.7%). The likelihood ratios emphasized the diagnostic value of the test. Notably, against TSS, DST showed perfect discriminatory power (AUC 1.000 for percent ACTH, 0.983 for percent cortisol). CONCLUSION: The desmopressin test shows promise in accurately identifying the underlying cause of ACTH-dependent CS, potentially reducing the reliance on invasive procedures and providing a practical solution for managing complex cases. Further research with larger cohorts is required to validate the utility of the DST in routine clinical practice.
RESUMO
Primary aldosteronism (PA), a significant and curable cause of secondary hypertension, is seen in 5-10% of hypertensive patients, with its prevalence contingent upon the severity of the hypertension. The principal aetiologies of PA include bilateral idiopathic hypertrophy (BIH) and aldosterone-producing adenomas (APAs), while the less frequent causes include unilateral hyperplasia, familial hyperaldosteronism (FH) types I-IV, aldosterone-producing carcinoma, and ectopic aldosterone synthesis. This condition, characterised by excessive aldosterone secretion, leads to augmented sodium and water reabsorption alongside potassium loss, culminating in distinct clinical hallmarks: elevated aldosterone levels, suppressed renin levels, and hypertension. Notably, hypokalaemia is present in only 28% of patients with PA and is not a primary indicator. The association of PA with an escalated cardiovascular risk profile, independent of blood pressure levels, is notable. Patients with PA exhibit a heightened incidence of cardiovascular events compared to counterparts with essential hypertension, matched for age, sex, and blood pressure levels. Despite its prevalence, PA remains frequently undiagnosed, underscoring the imperative for enhanced screening protocols. The diagnostic process for PA entails a tripartite assessment: the aldosterone/renin ratio (ARR) as the initial screening tool, followed by confirmatory and subtyping tests. A positive ARR necessitates confirmatory testing to rule out false positives. Subtyping, achieved through computed tomography and adrenal vein sampling, aims to distinguish between unilateral and bilateral PA forms, guiding targeted therapeutic strategies. New radionuclide imaging may facilitate and accelerate such subtyping and localisation. For unilateral adrenal adenoma or hyperplasia, surgical intervention is optimal, whereas bilateral idiopathic hyperplasia warrants treatment with mineralocorticoid antagonists (MRAs). This review amalgamates established and emerging insights into the management of primary aldosteronism.
Assuntos
Adenoma Adrenocortical , Hiperaldosteronismo , Hipertensão , Humanos , Aldosterona , Hiperplasia , Renina , Hipertensão/complicações , Hiperaldosteronismo/diagnóstico , Hiperaldosteronismo/epidemiologiaRESUMO
5-hydroxyindole acetic acid, a metabolite of serotonin, is used in the diagnosis and monitoring of patients with neuroendocrine tumours, in particular patients with small intestinal neuroendocrine tumours associated with the carcinoid syndrome. Analysis of 5-hydroxyindole acetic acid was commonly performed in urine, but blood-based assays are now becoming available. The objective of this study was to assess how 5-hydroxyindole acetic acid compares in plasma and serum as a biochemical marker of neuroendocrine tumours. Twenty-four-hour urine, plasma and serum samples were obtained from 80 patients with neuroendocrine tumours and 30 healthy volunteers. We developed a liquid chromatography tandem mass spectrometry assay for plasma and serum 5-hydroxyindole acetic acid. Comparison was made between them, and their cut-off was determined using a receiver-operating characteristic curve. A close correlation was shown between plasma and serum 5-hydroxyindole acetic acid. At a cut-off of 135 nmol/l, a sensitivity of 91.2% with a specificity of 61.9% was obtained for both compared to the urinary assay. A statistically significant agreement was shown when plasma and serum 5-hydroxyindole acetic acid were compared with the currently used urine assay in patients with neuroendocrine tumours; κ = 0.675 (95% CI 0.49 to 0.86), p < 0.001 and healthy volunteers; 0.967 (95% CI 0.828 to 0.999), p = <0.001. In conclusion, 5-hydroxyindole acetic acid in plasma and serum were comparable, hence either sample type can be used interchangeably.
Assuntos
Tumores Neuroendócrinos , Humanos , Ácido Hidroxi-Indolacético , Cromatografia Líquida/métodos , Biomarcadores/urina , AcetatosRESUMO
OBJECTIVE: Thyroid status in the months following radioiodine (RI) treatment for Graves' disease can be unstable. Our objective was to quantify frequency of abnormal thyroid function post-RI and compare effectiveness of common management strategies. DESIGN: Retrospective, multicentre and observational study. PATIENTS: Adult patients with Graves' disease treated with RI with 12 months' follow-up. MEASUREMENTS: Euthyroidism was defined as both serum thyrotropin (thyroid-stimulating hormone [TSH]) and free thyroxine (FT4) within their reference ranges or, when only one was available, it was within its reference range; hypothyroidism as TSH ≥ 10 mU/L, or subnormal FT4 regardless of TSH; hyperthyroidism as TSH below and FT4 above their reference ranges; dysthyroidism as the sum of hypo- and hyperthyroidism; subclinical hypothyroidism as normal FT4 and TSH between the upper limit of normal and <10 mU/L; and subclinical hyperthyroidism as low TSH and normal FT4. RESULTS: Of 812 patients studied post-RI, hypothyroidism occurred in 80.7% and hyperthyroidism in 48.6% of patients. Three principal post-RI management strategies were employed: (a) antithyroid drugs alone, (b) levothyroxine alone, and (c) combination of the two. Differences among these were small. Adherence to national guidelines regarding monitoring thyroid function in the first 6 months was low (21.4%-28.7%). No negative outcomes (new-onset/exacerbation of Graves' orbitopathy, weight gain, and cardiovascular events) were associated with dysthyroidism. There were significant differences in demographics, clinical practice, and thyroid status postradioiodine between centres. CONCLUSIONS: Dysthyroidism in the 12 months post-RI was common. Differences between post-RI strategies were small, suggesting these interventions alone are unlikely to address the high frequency of dysthyroidism.
Assuntos
Doença de Graves , Oftalmopatia de Graves , Hipertireoidismo , Hipotireoidismo , Adulto , Antitireóideos/uso terapêutico , Doença de Graves/radioterapia , Humanos , Hipertireoidismo/radioterapia , Hipotireoidismo/tratamento farmacológico , Radioisótopos do Iodo/uso terapêutico , Estudos Retrospectivos , Tireotropina , Tiroxina/uso terapêuticoRESUMO
The tumour microenvironment (TME) includes a variety of non-neoplastic cells and non-cellular elements such as cytokines, growth factors and enzymes surrounding tumour cells. The TME emerged as a key modulator of tumour initiation, progression and invasion, with extensive data available in many cancers, but little is known in pituitary tumours. However, the understanding of the TME of pituitary tumours has advanced thanks to active research in this field over the last decade. Different immune and stromal cell subpopulations, and several cytokines, growth factors and matrix remodelling enzymes, have been characterised in pituitary tumours. Studying the TME in pituitary tumours may lead to a better understanding of tumourigenic mechanisms, identification of biomarkers useful to predict aggressive disease, and development of novel therapies. This review summarises the current knowledge on the different TME cellular/non-cellular elements in pituitary tumours and provides an overview of their role in tumourigenesis, biological behaviour and clinical outcomes.
Assuntos
Tumores Neuroendócrinos/patologia , Neoplasias Hipofisárias/patologia , Microambiente Tumoral/fisiologia , Animais , Citocinas/metabolismo , Humanos , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Invasividade Neoplásica , Tumores Neuroendócrinos/diagnóstico , Tumores Neuroendócrinos/metabolismo , Tumores Neuroendócrinos/terapia , Neoplasias Hipofisárias/diagnóstico , Neoplasias Hipofisárias/metabolismo , Neoplasias Hipofisárias/terapia , Terapias em Estudo/métodos , Terapias em Estudo/tendênciasRESUMO
Prolactinomas are the most frequent type of pituitary tumors, which represent 10-20% of all intracranial neoplasms in humans. Prolactinomas develop in mice lacking the prolactin receptor (PRLR), which is a member of the cytokine receptor superfamily that signals via Janus kinase-2-signal transducer and activator of transcription-5 (JAK2-STAT5) or phosphoinositide 3-kinase-Akt (PI3K-Akt) pathways to mediate changes in transcription, differentiation and proliferation. To elucidate the role of the PRLR gene in human prolactinomas, we determined the PRLR sequence in 50 DNA samples (35 leucocytes, 15 tumors) from 46 prolactinoma patients (59% males, 41% females). This identified six germline PRLR variants, which comprised four rare variants (Gly57Ser, Glu376Gln, Arg453Trp and Asn492Ile) and two low-frequency variants (Ile76Val, Ile146Leu), but no somatic variants. The rare variants, Glu376Gln and Asn492Ile, which were in complete linkage disequilibrium, and are located in the PRLR intracellular domain, occurred with significantly higher frequencies (P < 0.0001) in prolactinoma patients than in 60 706 individuals of the Exome Aggregation Consortium cohort and 7045 individuals of the Oxford Biobank. In vitro analysis of the PRLR variants demonstrated that the Asn492Ile variant, but not Glu376Gln, when compared to wild-type (WT) PRLR, increased prolactin-induced pAkt signaling (>1.3-fold, P < 0.02) and proliferation (1.4-fold, P < 0.02), but did not affect pSTAT5 signaling. Treatment of cells with an Akt1/2 inhibitor or everolimus, which acts on the Akt pathway, reduced Asn492Ile signaling and proliferation to WT levels. Thus, our results identify an association between a gain-of-function PRLR variant and prolactinomas and reveal a new etiology and potential therapeutic approach for these neoplasms.
Assuntos
Suscetibilidade a Doenças , Prolactinoma/etiologia , Prolactinoma/metabolismo , Receptores da Prolactina/genética , Receptores da Prolactina/metabolismo , Alelos , Sequência de Aminoácidos , Substituição de Aminoácidos , Everolimo/farmacologia , Feminino , Genótipo , Humanos , Janus Quinases/metabolismo , Masculino , Mutação , Prolactinoma/patologia , Inibidores de Proteínas Quinases/farmacologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , Receptores da Prolactina/química , Fatores de Transcrição STAT/metabolismo , Transdução de SinaisRESUMO
The classification of adenohypophysial neoplasms as "pituitary neuroendocrine tumors" (PitNETs) was proposed in 2017 to reflect their characteristics as epithelial neuroendocrine neoplasms with a spectrum of clinical behaviors ranging from small indolent lesions to large, locally invasive, unresectable tumors. Tumor growth and hormone hypersecretion cause significant morbidity and mortality in a subset of patients. The proposal was endorsed by a WHO working group that sought to provide a unified approach to neuroendocrine neoplasia in all body sites. We review the features that are characteristic of neuroendocrine cells, the epidemiology and prognosis of these tumors, as well as further refinements in terms used for other pituitary tumors to ensure consistency with the WHO framework. The intense study of PitNETs has provided information about the importance of cellular differentiation in tumor prognosis as a model for neuroendocrine tumors in different locations.
Assuntos
Tumores Neuroendócrinos/classificação , Tumores Neuroendócrinos/patologia , Neoplasias Hipofisárias/classificação , Neoplasias Hipofisárias/patologia , HumanosRESUMO
The literature on COVID-19-related thyroid complications has accumulated over the past year or so as the pandemic has accelerated throughout the world. In particular, several recent case reports have been published describing a possible correlation between COVID-19 disease and subacute thyroiditis (SAT). In this review, we briefly present one of our own patients and review the current published literature in this area up to January 2021, including analyses of major series of thyroid function tests in patients with significant COVID-19 infection. We conclude that while the great majority of patients with severe COVID-19 infection may show manifestations of the sick euthyroid syndrome, clinicians should be aware of the possibility of SAT, especially in the early weeks and months following even mild COVID-19 infection.
Assuntos
COVID-19 , Tireoidite Subaguda , Tireoidite , COVID-19/complicações , Humanos , Testes de Função Tireóidea , Tireoidite/virologia , Tireoidite Subaguda/virologiaRESUMO
The hypothalamo-pituitary-adrenal (HPA) axis is one of the main components of the stress system. Maintenance of normal physiological events, which include stress responses to internal or external stimuli in the body, depends on appropriate HPA axis function. In the case of severe cortisol deficiency, especially when there is a triggering factor, the patient may develop a life-threatening adrenal crisis which may result in death unless early diagnosis and adequate treatment are carried out. The maintenance of normal physiology and survival depend upon a sufficient level of cortisol in the circulation. Life-long glucocorticoid replacement therapy, in most cases meeting but not exceeding the need of the patient, is essential for normal life expectancy and maintenance of the quality of life. To enable this, the initial step should be the correct diagnosis of adrenal insufficiency (AI) which requires careful evaluation of the HPA axis, a highly dynamic endocrine system. The diagnosis of AI in patients with frank manifestations is not challenging. These patients do not need dynamic tests, and basal cortisol is usually enough to give a correct diagnosis. However, most cases of secondary adrenal insufficiency (SAI) take place in a gray zone when clinical manifestations are mild. In this situation, more complicated methods that can simulate the response of the HPA axis to a major stress are required. Numerous studies in the assessment of HPA axis have been published in the world literature. In this review, the tests used in the diagnosis of secondary AI or in the investigation of suspected HPA axis insufficiency are discussed in detail, and in the light of this, various recommendations are made.
Assuntos
Insuficiência Adrenal , Sistema Hipotálamo-Hipofisário , Insuficiência Adrenal/diagnóstico , Humanos , Hidrocortisona , Sistema Hipófise-Suprarrenal , Qualidade de VidaRESUMO
Cushing's disease (CD) is rare in paediatric practice but requires prompt investigation, diagnosis and therapy to prevent long-term complications. Key presenting features are a change in facial appearance, weight gain, growth failure, virilization, disturbed puberty and psychological disturbance. Close consultation with an adult endocrinology department is recommended regarding diagnosis and therapy. The incidence of CD, a form of ACTH-dependent Cushing's syndrome (CS), is equal to approximately 5% of that seen in adults. The majority of ACTH-secreting adenomas are monoclonal and sporadic, although recent studies of pituitary tumours have shown links to several deubiquitination gene defects. Diagnosis requires confirmation of hypercortisolism followed by demonstration of ACTH-dependence. Identification of the corticotroph adenoma by pituitary MRI and/or bilateral inferior petrosal sampling for ACTH may contribute to localisation before pituitary surgery. Transsphenoidal surgery (TSS) with selective microadenomectomy is first-line therapy, followed by external pituitary irradiation if surgery is not curative. Medical therapy to suppress adrenal steroid synthesis is effective in the short-term and bilateral adrenalectomy should be considered in cases unfit for TSS or radiotherapy or when urgent remission is needed after unsuccessful surgery. TSS induces remission of hypercortisolism and improvement of symptoms in 70-100% of cases, particularly when performed by a surgeon with experience in children. Post-TSS complications include pituitary hormone deficiencies, sub-optimal catch-up growth, and persisting excess of BMI. Recurrence of hypercortisolism following remission is recognised but infrequent, being less common than in adult CD patients. With experienced specialist medical and surgical care, the overall prognosis is good. Early referral to an experienced endocrine centre is advised.
Assuntos
Síndrome de Cushing , Hipersecreção Hipofisária de ACTH , Neoplasias Hipofisárias , Adulto , Criança , Síndrome de Cushing/etiologia , Humanos , Hipersecreção Hipofisária de ACTH/diagnóstico , Hipersecreção Hipofisária de ACTH/epidemiologia , Hipersecreção Hipofisária de ACTH/etiologia , Hipófise/cirurgia , Neoplasias Hipofisárias/cirurgia , Resultado do TratamentoRESUMO
BACKGROUND: The number of therapeutic options for patients with pancreatic neuroendocrine neoplasms (PNEN) has increased, but the optimal therapeutic algorithm has not been defined due to lack of randomised trials comparing different modalities. METHODS: We performed a retrospective study in patients with metastatic PNEN treated with ≥1 line of systemic therapy. The relationship between baseline characteristics, treatment type, and time to treatment failure (TTF), time to progression (TTP), and overall survival (OS) was analysed using the Kaplan-Meier method. Univariate and multivariate analyses were performed using the Cox proportional hazards model. RESULTS: Two hundred and fifty-five patients with metastatic PNEN had 491 evaluable lines of therapy. Independent predictors of TTF included treatment type, Ki-67, tumour grade, and chromogranin A. To reduce selection bias, a subgroup of 114 patients with grade 2 (G2) metastatic pancreatic neuroendocrine tumours (PNET) was analysed separately. These patients had received 234 lines of treatment (105 chemotherapy, 82 molecular targeted therapy, and 47 peptide receptor radionuclide therapy [PRRT]). In the G2 cohort, TTF and TTP were superior for PRRT compared with both chemotherapy and molecular targeted therapy. OS in the G2 cohort was also superior for those that had received PRRT compared with those that had not (median 84 vs. 56 months; HR 0.55, 95% CI: 0.31-0.98, p = 0.04). CONCLUSIONS: This study suggests that PRRT is associated with superior clinical outcomes relative to other systemic therapies for G2 metastatic PNET. Prospective studies are required to confirm these observations.
Assuntos
Algoritmos , Antineoplásicos/farmacologia , Terapia de Alvo Molecular , Tumores Neuroendócrinos/terapia , Avaliação de Resultados em Cuidados de Saúde , Neoplasias Pancreáticas/terapia , Radioterapia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Tumores Neuroendócrinos/secundário , Neoplasias Pancreáticas/secundário , Estudos Retrospectivos , Adulto JovemRESUMO
Reproductive function depends upon an operational hypothalamo-pituitary-gonadal (HPG) axis. Due to its role in determining survival versus reproductive strategies, the HPG axis is vulnerable to a diverse plethora of signals that ultimately manifest with Central Hypogonadism (CH) in all its many guises. Acquired CH can result from any pituitary or hypothalamic lesion, including its treatment (such as surgical resection and/or radiotherapy). The HPG axis is particularly sensitive to the suppressive effects of hyperprolactinaemia that can occur for many reasons, including prolactinomas, and as a side effect of certain drug therapies. Physiologically, prolactin (combined with the suppressive effects of autonomic neural signals from suckling) plays a key role in suppressing the gonadal axis and establishing temporary CH during lactation. Leptin is a further key endocrine regulator of the HPG axis. During starvation, hypoleptinaemia (from diminished fat stores) results in activation of hypothalamic agouti-related peptide neurons that have a dual purpose to enhance appetite (important for survival) and concomitantly suppresses GnRH neurons via effects on neural kisspeptin release. Obesity is associated with hyperleptinaemia and leptin resistance that may also suppress the HPG axis. The suppressibility of the HPG axis also leaves it vulnerable to the effects of external signals that include morphine, anabolic-androgenic steroids, physical trauma and stress, all of which are relatively common causes of CH. Finally, the HPG axis is susceptible to congenital malformations, with reports of mutations within >50 genes that manifest with congenital CH, including Kallmann Syndrome associated with hyposmia or anosmia (reduction or loss of the sense of smell due to the closely associated migration of GnRH with olfactory neurons during embryogenesis). Analogous to the HPG axis itself, patients with CH are often vulnerable, and their clinical management requires both sensitivity and empathy.
Assuntos
Síndrome de Kallmann/metabolismo , Animais , Gônadas/metabolismo , Humanos , Sistema Hipotálamo-Hipofisário/metabolismo , Síndrome de Kallmann/tratamento farmacológico , Síndrome de Kallmann/genética , Leptina/metabolismo , Prolactina/metabolismoRESUMO
BACKGROUND: Survival rates among childhood cancer survivors (CCSs) have significantly risen in the last 40 years due to substantial improvements in treatment protocols. However, this improvement has brought with it serious late effects that frequently involve the endocrine system. Of the endocrine disorders, GH deficiency (GHD) is the most common among CCSs as a consequence of a history of cancers, surgery, and/or radiotherapy involving the hypothalamo-pituitary region. METHODS: A comprehensive search of English language articles regardless of age was conducted in the MEDLINE database between December 2018 and October 2019. We selected all studies on GH therapy in CCSs during the transition age regarding the most challenging topics: when to retest; which diagnostic tests and cut-offs to use; when to start GH replacement therapy (GHRT); what GH dose to use; safety; quality of life, compliance and adherence to GHRT; interactions between GH and other hormonal replacement treatments. RESULTS: In the present review, we provide an overview of the current clinical management of challenges in GHD in cancer survivors in the transition age. CONCLUSIONS: Endocrine dysfunction among CCSs has a high prevalence in the transition age and increase with time. Many endocrine disorders, including GHD, are often not diagnosed or under-diagnosed, probably due to the lack of specialized centers for the long-term follow-up. Therefore, it is crucial that transition specialized clinics should be increased in terms of number and specific skills in order to manage endocrine disorders in adolescence, a delicate and complex period of life. A multidisciplinary approach, also including psychological counseling, is essential in the follow-up and management of these patients in order to minimize their disabilities and maximize their quality of life.
Assuntos
Sobreviventes de Câncer , Terapia de Reposição Hormonal , Hormônio do Crescimento Humano/deficiência , Hipopituitarismo/tratamento farmacológico , Neoplasias/terapia , Adolescente , Técnicas de Diagnóstico Endócrino , Hormônio do Crescimento Humano/metabolismo , Hormônio do Crescimento Humano/uso terapêutico , Humanos , Hipopituitarismo/diagnóstico , Fator de Crescimento Insulin-Like I/metabolismo , Proteínas Recombinantes , Adulto JovemRESUMO
Multiple endocrine neoplasia type 1 (MEN1) is an inherited tumour syndrome characterised by a predisposition to the development of endocrine tumours of the parathyroid glands, pituitary and pancreas: 30%-80% of patients with MEN1 develop pancreatic neuroendocrine tumours (pNETs), with metastatic tumours and/or their sequelae contributing to increased morbidity and early mortality. The optimal management of nonfunctioning (NF) pNETs in MEN1 remains controversial. Whilst pancreatic resection is widely recommended for tumours >2 cm, for smaller tumours (≤2 cm) a well-established consensus guiding the indications for surgical intervention does not exist. Although total pancreatectomy may be curative for some patients, both short- and long-term complications make this an unsatisfactory option for many patients. For small (<2 cm) MEN1 NF-pNETs, some clinicians advocate surveillance based largely on retrospective data that suggest 50%-80% of these lesions are stable over time and infrequently exhibit accelerated growth rates. It is increasingly recognised, however, that NF-pNETs exhibit unpredictable malignant behaviour that is not determined by tumour size alone, thereby prompting other clinicians to advocate surgery for all MEN1 NF-pNETs, irrespective of size. Such uncertainty poses clinical management challenges with regards to the timing and extent of surgery, which is further hindered by the inability to stratify patients based on predicted tumour behaviour. It is therefore critical that future MEN1 research initiatives include: (a) the discovery of biomarkers that better predict tumour behaviour; (b) the evaluation of medical therapies that may delay, or even prevent, the need for pancreatic surgery; and, ultimately, (c) improvement in the quality of life for individuals with MEN1. Here, based on the published literature, we address the Clinical Question, 'What is the management of NF-pNETs disclosed on screening in adult patients with MEN1?'.
Assuntos
Neoplasia Endócrina Múltipla Tipo 1/complicações , Neoplasias Pancreáticas/etiologia , Progressão da Doença , Feminino , Humanos , Masculino , Neoplasia Endócrina Múltipla Tipo 1/cirurgia , Tumores Neuroendócrinos/diagnóstico , Tumores Neuroendócrinos/etiologia , Tumores Neuroendócrinos/cirurgia , Neoplasias Pancreáticas/complicações , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/cirurgiaRESUMO
Neuroendocrine tumours (NETs) are being seen increasingly frequently, but to date only complete surgical resection is curative. However, among the various therapeutic options, peptide receptor radionuclide therapy, linking a radioactive moiety to an octreotide derivative, has been shown to be highly efficacious and a well-tolerated therapy, improving progression-free survival and probably overall survival. Nevertheless, the current radionuclides in use are beta particle emitters with non-optimal radiobiological properties. A new generation of alpha particle-emitting radionuclides is being developed, with advantages in terms of very high energy and a short path length, which should theoretically show higher efficacy. We survey the current developments in this field, emphasising the exciting potential of this novel form of therapy for NETs.
Assuntos
Partículas alfa/uso terapêutico , Tumores Neuroendócrinos/radioterapia , Radioisótopos/uso terapêutico , Receptores de Peptídeos/efeitos dos fármacos , Animais , HumanosRESUMO
At present there is no clinical guideline or standardised protocol for the treatment of metastatic or invasive phaeochromocytoma and paraganglioma (collectively known as PPGL) due to the rarity of the disease and the lack of prospective studies or extended national databases. Prognosis is mainly determined by genetic predisposition, tumour burden, rate of disease progression, and location of metastases. For patients with progressive or symptomatic disease that is not amenable to surgery, there are various palliative treatment options available. These include localised therapies including radiotherapy, radiofrequency, or cryoablation, as well as liver-directed therapies for those patients with hepatic metastases (e.g., transarterial chemoembolisation) and systemic therapies including chemotherapy or molecular targeted therapies. There is currently intense research interest in the value of radionuclide therapy for neuroendocrine tumours, including phaeochromocytoma and paraganglioma, with either iodine-131 (131I)-radiolabelled metaiodobenzylguanidine or very recently peptide receptor radionuclide therapy (PRRT), and the most important contemporary clinical studies will be highlighted in this review. The studies to date suggest that PRRT may induce major clinical, biochemical, and radiological changes, with 177Lu-DOTATATE being most efficacious and presenting less toxicity than 90Y-DOTATATE. Newer combination therapies with combined radioisotopes, or combinations with chemotherapeutic agents, also look promising. Given the favourable efficacy, logistic, and safety profiles, we believe that PRRT will probably become the standard treatment for inoperable metastatic PPGL in the near future, but we await data from definitive randomised controlled trials to understand its role.
Assuntos
Neoplasias das Glândulas Suprarrenais/radioterapia , Paraganglioma/radioterapia , Feocromocitoma/radioterapia , Radioisótopos/uso terapêutico , Receptores de Peptídeos/efeitos da radiação , Animais , Humanos , Invasividade Neoplásica , Metástase Neoplásica/radioterapiaRESUMO
Gastroenteropancreatic (GEP) neuroendocrine neoplasms (NEN) are classified based on morphology and graded based on their proliferation rate as either well-differentiated low-grade (G1 to G2) neuroendocrine tumors (NET) or poorly differentiated high-grade (G3) neuroendocrine carcinomas (NEC). Recently, a new subgroup of well-differentiated high-grade pancreatic tumors (NET G3) has been defined. The GEP NEN G3 group consisting of both NEC and NET G3 has recently been shown to be a quite heterogeneous patient group concerning prognosis and treatment benefit, depending on factors such as the primary tumor site, differentiation, proliferation rate, and molecular alterations. In this review we discuss the existing data on diagnostics, treatment, and biomarkers in this patient group, the unmet needs, and the future perspectives.