RESUMO
"What's in a name? That which we call a rose/By any other name would smell as sweet." (Juliet, from Romeo and Juliet by William Shakespeare). Shakespeare's implication is that a name is nothing but a word and it therefore represents a convention with no intrinsic meaning. Whilst this may be relevant to romantic literature, disease names do have real meanings, and consequences, in medicine. Hence, there must be a very good rational for changing the name of a disease that has a centuries-old historical context. A working group of representatives from national and international endocrinology and pediatric endocrine societies now proposes changing the name of "diabetes insipidus" to "Arginine Vasopressin Deficiency (AVP-D)" for central etiologies, and "Arginine Vasopressin Resistance (AVP-R)" for nephrogenic etiologies. This editorial provides both the historical context and the rational for this proposed name change.
Assuntos
Arginina Vasopressina , Diabetes Insípido , Humanos , Arginina Vasopressina/deficiência , Diabetes Insípido/classificação , Diabetes Mellitus , Sociedades MédicasRESUMO
OBJECTIVE: Surgery is a stressor that can be categorized by duration and severity and induces a systemic stress response that includes increased adrenal cortisol production. However, the precise impact of surgical stress on the cortisol response remains to be defined. DESIGN: We performed a systematic review and meta-analysis to assess the cortisol stress response induced by surgery and to stratify this response according to different parameters. METHODS: We conducted a comprehensive search in several databases from 1990 to 2016. Pairs of reviewers independently selected studies, extracted data and evaluated the risk of bias. Cortisol concentrations were standardized, pooled in meta-analysis and plotted over time. RESULTS: We included 71 studies reporting peri-operative serum cortisol measurements in 2953 patients. The cortisol response differed substantially between moderately/highly invasive and minimally invasive surgical procedures. Minimally invasive procedures did not show a peri-operative cortisol peak, whereas more invasive surgeries caused a cortisol surge that was more pronounced in older subjects, women and patients undergoing open surgery and general anaesthesia. The duration of the procedure and the use of etomidate for induction of anaesthesia did not affect the cortisol response. CONCLUSIONS: The peri-operative cortisol stress response is dynamic and influenced by patient-specific, surgical and anaesthetic features. However, the available evidence is derived from highly heterogeneous studies, with only two of 71 studies measuring cortisol by mass spectrometry, which currently prevents a precise and reproducible definition of this response.
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Hidrocortisona/sangue , Complicações Pós-Operatórias/sangue , Feminino , Humanos , Masculino , Espectrometria de MassasRESUMO
PURPOSE: Non-functioning pituitary adenomas (NFPAs) are benign pituitary neoplasms that do not cause a hormonal hypersecretory syndrome. An improved understanding of their epidemiology, clinical presentation and diagnosis is needed. METHOD: A literature review was performed using Pubmed to identify research reports and clinical case series on NFPAs. RESULTS: They account for 14-54% of pituitary adenomas and have a prevalence of 7-41.3/100,000 population. Their standardized incidence rate is 0.65-2.34/100,000 and the peak occurence is from the fourth to the eighth decade. The clinical spectrum of NFPAs varies from being completely asymptomatic to causing significant hypothalamic/pituitary dysfunction and visual field compromise due to their large size. Most patients present with symptoms of mass effect, such as headaches, visual field defects, ophthalmoplegias, and hypopituitarism but also hyperprolactinaemia due to pituitary stalk deviation and less frequently pituitary apoplexy. Non-functioning pituitary incidentalomas are found on brain imaging performed for an unrelated reason. Diagnostic approach includes magnetic resonance imaging of the sellar region, laboratory evaluations, screening for hormone hypersecretion and for hypopituitarism, and a visual field examination if the lesion abuts the optic nerves or chiasm. CONCLUSION: This article reviews the epidemiology, clinical behaviour and diagnostic approach of non-functioning pituitary adenomas.
Assuntos
Adenoma/diagnóstico , Adenoma/epidemiologia , Neoplasias Hipofisárias/diagnóstico , Neoplasias Hipofisárias/epidemiologia , Adenoma/patologia , Animais , Humanos , Hipopituitarismo/diagnóstico , Hipopituitarismo/epidemiologia , Hipopituitarismo/patologia , Neoplasias Hipofisárias/patologiaRESUMO
Acromegaly is a rare condition necessitating large population studies for the generation of reliable epidemiological data. In this review, we systematically analysed the epidemiological profile of this condition based on recently published population studies from various geographical areas. The total prevalence ranges between 2.8 and 13.7 cases per 100,000 people and the annual incidence rates range between 0.2 and 1.1 cases/100,000 people. The median age at diagnosis is in the fifth decade of life with a median diagnostic delay of 4.5-5 years. Acral enlargement and coarse facial features are the most commonly described clinical manifestations. At the time of detection, most of the tumors are macroadenomas possibly relating to diagnostic delays and posing challenges in the surgical management. Increased awareness of acromegaly amongst the medical community is of major importance aiming to reduce the adverse sequelae of late diagnosis and treatment, improve patient outcomes and, hopefully, reduce the burden on the health care system.
Assuntos
Acromegalia/epidemiologia , Acromegalia/diagnóstico , Distribuição por Idade , Feminino , Humanos , Incidência , Masculino , Prevalência , Distribuição por SexoRESUMO
OBJECTIVE: Steroid 11ß-hydroxylase (CYP11B1) deficiency (11OHD) is the second most common form of congenital adrenal hyperplasia. Nonclassic or mild 11OHD appears to be a rare condition. Our study assessed the residual CYP11B1 function of detected mutations, adding to the spectrum of mild 11OHD, and illustrates the variability of the clinical presentation of 11OHD. PATIENTS AND METHODS: Five patients presented with mild to moderate 11OHD. Two women presented with mild hirsutism and in one case with secondary amenorrhoea. Two men presented with precocious pseudopuberty, gynaecomastia and elevated blood pressure. One 46,XX female patient was diagnosed with virilization of the external genitalia 2 years after birth. Direct DNA sequencing was carried out to perform CYP11B1 mutation analysis. The CYP11B1 mutations were functionally characterized using an in vitro expression system. RESULTS: CYP11B1-inactivating mutations were detected in all patients. Two novel missense mutations (p.P42L and p.A297V) and the previously characterized p.R143W mutation had residual CYP11B1 activities between 10% and 27%. A novel p.L382R and the previously uncharacterized p.G444D mutation both caused complete loss of CYP11B1 enzymatic activity. CONCLUSION: Mutations causing partial impairment of 11ß-hydroxylase activity (residual activity of 10% or above) are associated with a less severe clinical presentation of 11OHD, which can be classified as a nonclassic form. Our data demonstrate that patients with nonclassic 11OHD can present with androgen excess, precocious pseudopuberty and increased blood pressure. Timely diagnosis of nonclassic 11OHD and consequently initiation of personalized treatment is essential to prevent co-morbidities caused by androgen excess and hypertension.
Assuntos
Hiperplasia Suprarrenal Congênita/genética , Esteroide 11-beta-Hidroxilase/genética , Adulto , Feminino , Humanos , Masculino , Mutação , Adulto JovemRESUMO
OBJECTIVE: The frequency and the degree of recovery of anterior pituitary hormone deficits in patients with macroprolactinoma responsive to cabergoline are not clear. Our aim was to evaluate pituitary function in these patients with particular reference to an assessment of the possible restoration of pituitary deficits. SUBJECTS AND METHODS: The records of all subjects prospectively presenting to our Department with macroprolactinomas treated with cabergoline over a 2-year period were reviewed. Pituitary function was assessed at diagnosis and, if abnormal, for three consecutive years for the GH, FSH/LH and ACTH axes, and at 3 years for the TSH axis. RESULTS: Twelve patients were included. Severe GH deficiency was found in 83% at diagnosis and did not resolve in any patient at last assessment. Gonadotrophin deficiency was found in 90% at diagnosis and in 50% at last evaluation (showing reversal in 44% of deficient patients, all achieved within 1 year). ACTH deficiency was found in 17% at diagnosis and it did not reverse in any patient at last assessment. TSH deficiency was found in 36% at diagnosis and in 27% at last assessment (reversal in 25% of deficient patients). CONCLUSIONS: In our study, in a group of patients with macroprolactinoma systematically assessed at intervals, pituitary dysfunction in response to cabergoline was found to be mostly irreversible, except for the gonadotroph axis which showed restoration in a subset of subjects following achievement of normoprolactinaemia. It would appear that the reversibility of pituitary axes may be less common than previously thought.
Assuntos
Agonistas de Dopamina/uso terapêutico , Ergolinas/uso terapêutico , Hipopituitarismo/tratamento farmacológico , Neoplasias Hipofisárias/tratamento farmacológico , Prolactinoma/tratamento farmacológico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Cabergolina , Feminino , Humanos , Hipopituitarismo/fisiopatologia , Masculino , Pessoa de Meia-Idade , Prolactina/sangue , Estudos ProspectivosRESUMO
OBJECTIVE: We investigated the control of GH and IGF1 in acromegaly in routine clinical practice in the UK on and off medical treatment. DESIGN: The UK Acromegaly Register collected routine biochemical and clinical data on patients with acromegaly from 31 UK centres with GH data covering >30y. PATIENTS: We identified 2572 patients. Somatostatin analogues (SMS) were used in 40·6% and dopamine agonists (DA) in 41·4%. MEASUREMENTS: We identified 29,181 GH records linked to data on IGF1, surgery, radiotherapy and medical treatment and derived data on 9900 distinct Periods of Care including 4206 courses of medical treatment. We considered GH controlled when ≤2 µg/l. RESULTS: Control of GH and IGF1 improved over time, particularly on medical treatment. Control on medical treatment was better after prior surgery and/or radiotherapy. On long-term SMS, GH was controlled in 75%, IGF1 in 69% and both in 55%; on long-term DA, GH control was similar but IGF1 worse (77%/55%/45%). Responses to long-term treatment with octreotide LAR and lanreotide autogel were broadly similar, but we noted a failure to escalate SMS to maximal effective dose. Increasing precourse GH levels were associated with a decreasing proportion who achieved control, despite greater suppression from baseline. CONCLUSIONS: Control of acromegaly in the UK is improving, but 'safe' GH levels are still only achieved in 75% on long-term medical treatment, with GH and IGF1 both normalized in no more than 55% on SMS and 36% on cabergoline. It remains unclear whether the control of GH, but not IGF1, observed in many patients is sufficient to restore long-term morbidity and mortality to normal.
Assuntos
Acromegalia/sangue , Acromegalia/tratamento farmacológico , Agonistas de Dopamina/uso terapêutico , Hormônio do Crescimento/sangue , Fator de Crescimento Insulin-Like I/metabolismo , Somatostatina/análogos & derivados , Somatostatina/uso terapêutico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
OBJECTIVE: Non-functioning pituitary adenomas (NFA) may be associated with significant morbidity. Published data on the quality of life (QoL) of patients with NFA are scarce and conflicting. In view of the discordant findings and the advances in the management of these subjects, we aimed to evaluate the QoL in patients with NFA followed up in a tertiary endocrine UK referral centre. SUBJECTS AND METHODS: All consecutive patients with NFA attending the outpatient clinic in the Department of Endocrinology in Oxford over a 6-month period (n = 193) were offered 3 health-related QoL questionnaires [Short Form 36 (SF36), Nottingham Health Profile (NHP), European Quality of Life Scale (EuroQoL)] to complete. Patient outcomes (response rate 93.3%) were compared with age-related UK reference values. RESULTS: None of the QoL scores in the SF-36 or the 5 dimensions of health in the EuroQoL was different from the reference values. The visual analogue scale (VAS) score (EuroQoL) was slightly compromised (P = 0.041). In the NHP questionnaire, males had no parameter significantly affected, whereas females performed worse in 1/6 areas (energy levels). Tumour recurrence was an independent predictor for compromised VAS score and for anxiety/depression (EuroQoL), and visual field defects for more frequent problems with interests/hobbies (NHP). CONCLUSIONS: Overall, the health-related QoL and perception of subjective health in patients with NFA was not compromised to any major extent suggesting that we can now offer the prospect of treatment and replacement, which will provide a normal or near-normal QoL. Specific groups are affected in various dimensions, necessitating measures to compensate for predisposing factors.
Assuntos
Neoplasias Hipofisárias/metabolismo , Qualidade de Vida , Hormônio Adrenocorticotrópico/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Tireotropina/metabolismoRESUMO
Acute adrenal crisis is an important condition to consider in any shocked patient presenting to the acute medical unit. This article aims to highlight the key aspects of initial management, focussing on the importance of rapid recognition and prompt initiation of steroid treatment.
Assuntos
Insuficiência Adrenal/diagnóstico , Insuficiência Adrenal/tratamento farmacológico , Anti-Inflamatórios/administração & dosagem , Hidrocortisona/administração & dosagem , Doença Aguda , Doença de Addison/diagnóstico , Doença de Addison/tratamento farmacológico , Hormônio Adrenocorticotrópico/sangue , Adulto , Algoritmos , Serviços Médicos de Emergência , Hidratação , Humanos , Hidrocortisona/sangue , MasculinoRESUMO
Rathke's cleft cysts (RCCs) are benign, sellar and/or suprasellar lesions originating from the remnants of Rathke's pouch. Although a common finding in routine autopsies (12-33% of normal pituitary glands), symptomatic cases are rare and comprise 5-15% of all surgically resected sellar lesions. Small, asymptomatic RCC do not require surgical intervention, and their natural history is not clear. In series of nonoperated presumed RCCs, 26-94% did not progress during follow-up periods up to 9 years. In symptomatic ones, surgery is indicated, aiming to drain the cyst content and safely remove as much of the capsule as possible. Following surgical intervention, headaches and visual field defects improve or resolve in a significant number of patients (40-100% and 33-100%, respectively) and partial hypopituitarism recovers in 14-50%. Data on relapse rates published in the last 15 years are based on variable follow-up periods and show wide variation (between 0% and 33%). The lowest relapse rates have been described in reports with relatively short mean observation periods (<3 years), whereas in those with longer follow-up the relapse rates increase. Most of the relapses occur within 5-6 years, suggesting that follow-up is required for at least 5 years after surgery. Risk factors for relapse include the presence of squamous metaplasia in the cyst wall, cyst size and the presence of inflammation. Long-term sufficiently powered studies aiming to clarify the natural history of asymptomatic RCCs and of those relapsing postoperatively are required.
Assuntos
Cistos do Sistema Nervoso Central/terapia , Cistos do Sistema Nervoso Central/complicações , Cistos do Sistema Nervoso Central/diagnóstico , Humanos , RecidivaRESUMO
Importance: Previous studies have suggested an association between surgical volume and patient outcomes for parathyroid surgery. However, most previous studies are relatively small and the literature is dominated by studies form the US, which might not be readily generalizable to other settings. Objective: To investigate volume-outcome associations for parathyroid surgery in England. Design, Setting, and Participants: Cohort study that included all National Health Service hospital trusts in England with secondary analysis of administrative data using International Statistical Classification of Diseases and Related Health Problems, Tenth Revision (ICD-10). Participants included all adult, elective hospital admissions for parathyroid surgery without a diagnosis of multiple endocrine neoplasia, parathyroid cancer, or kidney disease over a 5-year period (April 2014-March 2019 inclusive). Exposures: The number of procedures conducted in the year prior to the index procedure by each surgeon and each hospital trust. Main Outcomes and Measures: Repeat parathyroid surgery within 1 year of the index procedure. Results: This study included data for 17â¯494 participants who underwent parathyroidectomies conducted across 125 hospital trusts. The median (IQR) age of patients was 62 (53-71) years, and 13â¯826 were female (79.0%). Across the period, the number of surgeons conducting parathyroid surgery changed little (280 in 2014-2015 and 2018-2019), although the number of procedures conducted rose from 3331 to 3848 per annum. Repeat parathyroid surgery at 1 year was significantly associated with surgeon volume (odds ratio [OR], 0.99; 95% CI, 0.98-0.99), but not trust volume, in the previous 12 months. Extended length of stay (OR, 0.98; 95% CI, 0.98-0.99), hypoparathyroidism/calcium disorder (OR, 1.0; 95% CI, 0.99-1.0), and postprocedural complications (OR, 0.99; 95% CI, 0.99-1.0) were also associated with lower surgeon volume. Conclusions and Relevance: In this cohort study, higher surgeon annual volume was associated with decreased rates of repeat parathyroid surgery. A minimum volume threshold of 20 procedures per annum should improve patient outcomes, although possible negative effects on access to services should be monitored.
Assuntos
Paratireoidectomia , Medicina Estatal , Adulto , Idoso , Estudos de Coortes , Inglaterra/epidemiologia , Feminino , Hospitais , Humanos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/epidemiologiaRESUMO
'What's in a name? That which we call a rose/By any other name would smell as sweet.' (Juliet, from Romeo and Juliet by William Shakespeare). Shakespeare's implication is that a name is nothing but a word and it therefore represents a convention with no intrinsic meaning. Whilst this may be relevant to romantic literature, disease names do have real meanings, and consequences, in medicine. Hence, there must be a very good rationale for changing the name of a disease that has a centuries-old historical context. A working group of representatives from national and international endocrinology, nephrology and pediatric societies now proposes changing the name of 'diabetes insipidus' to 'arginine vasopressin deficiency (AVP-D)' for central etiologies and 'arginine vasopressin resistance (AVP-R)' for nephrogenic etiologies. This editorial provides both the historical context and the rationale for this proposed name change.
Assuntos
Diabetes Insípido , Diabetes Mellitus , Arginina , Arginina Vasopressina , Criança , Diabetes Insípido/terapia , HumanosRESUMO
'What's in a name? That which we call a rose/By any other name would smell as sweet' (Juliet, from Romeo and Juliet by William Shakespeare). Shakespeare's implication is that a name is nothing but a word, and it therefore represents a convention with no intrinsic meaning. While this may be relevant to romantic literature, disease names do have real meanings, and consequences, in medicine. Hence, there must be a very good rationale for changing the name of a disease that has a centuries-old historical context. A working group of representatives from national and international endocrinology, and pediatric endocrine societies now proposes changing the name of 'diabetes insipidus' to 'arginine vasopressin deficiency (AVP-D)' for central etiologies, and 'arginine vasopressin resistance (AVP-R)' for nephrogenic etiologies. This article provides both the historical context and the rationale for this proposed name change.
RESUMO
Objective: There is growing recognition of morbidity and mortality that can occur in patients with cranial diabetes insipidus (CDI) during hospitalisation, due to prescribing errors and dysnatraemia, often related to confusion between CDI and diabetes mellitus among non-specialists. We aimed to investigate this. Methods: Data for each hospitalisation in patients with CDI attending Oxford University Hospital (OUH) were collected retrospectively. The same cohort were invited to complete a questionnaire by telephone. Results: One hundred and nine patients were included, median age was 42 (range: 6-80) years. Route of desmopressin was tablet, melt and nasal spray in 74%, 7% and 17% of patients, respectively, while two patients used a combination of tablet and nasal spray. There were 85 admissions to OUH by 38 patients between 2012 and 2021. Daily measurement of serum sodium was performed in 39% of admissions; hyponatraemia and hypernatraemia occurred in 44 and 15% of admissions, respectively. Endocrine consultation was sought in 63% of admissions post-2018. Forty-five of 78 patients (58%) self-reported ≥1 admission to any hospital since diagnosis. Of these, 53% felt their medical team did not have a good understanding of the management of CDI during hospital admission. Twenty-four per cent reported delay in administration of desmopressin, while 44% reported confusion between CDI and diabetes mellitus, often leading to unnecessary blood glucose monitoring. Conclusion: Dysnatraemia is common in hospitalised patients with CDI. More than half of patients perceived their medical team's understanding of CDI to be poor when admitted with intercurrent illness. A coordinated approach, including early consultation of specialists, frequent serum sodium monitoring, and education of hospital specialists is needed to address this.
Assuntos
Diabetes Insípido Neurogênico , Diabetes Insípido , Diabetes Mellitus , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Glicemia , Automonitorização da Glicemia , Criança , Desamino Arginina Vasopressina/uso terapêutico , Diabetes Insípido/terapia , Diabetes Insípido Neurogênico/epidemiologia , Diabetes Insípido Neurogênico/terapia , Diabetes Mellitus/epidemiologia , Humanos , Pessoa de Meia-Idade , Sprays Nasais , Percepção , Estudos Retrospectivos , Sódio , Comprimidos , Adulto JovemRESUMO
All endocrine glands are susceptible to neoplastic growth, yet the health consequences of these neoplasms differ between endocrine tissues. Pituitary neoplasms are highly prevalent and overwhelmingly benign, exhibiting a spectrum of diverse behaviors and impact on health. To understand the clinical biology of these common yet often innocuous neoplasms, we review pituitary physiology and adenoma epidemiology, pathophysiology, behavior, and clinical consequences. The anterior pituitary develops in response to a range of complex brain signals integrating with intrinsic ectodermal cell transcriptional events that together determine gland growth, cell type differentiation, and hormonal production, in turn maintaining optimal endocrine health. Pituitary adenomas occur in 10% of the population; however, the overwhelming majority remain harmless during life. Triggered by somatic or germline mutations, disease-causing adenomas manifest pathogenic mechanisms that disrupt intrapituitary signaling to promote benign cell proliferation associated with chromosomal instability. Cellular senescence acts as a mechanistic buffer protecting against malignant transformation, an extremely rare event. It is estimated that fewer than one-thousandth of all pituitary adenomas cause clinically significant disease. Adenomas variably and adversely affect morbidity and mortality depending on cell type, hormone secretory activity, and growth behavior. For most clinically apparent adenomas, multimodal therapy controlling hormone secretion and adenoma growth lead to improved quality of life and normalized mortality. The clinical biology of pituitary adenomas, and particularly their benign nature, stands in marked contrast to other tumors of the endocrine system, such as thyroid and neuroendocrine tumors.
Assuntos
Adenoma , Neoplasias Hipofisárias , Humanos , Neoplasias Hipofisárias/complicações , Qualidade de Vida , Adenoma/genética , Adenoma/complicações , Adenoma/metabolismo , Biologia , HormôniosRESUMO
BACKGROUND: Central diabetes insipidus is a rare neuroendocrine condition. Data on treatment-associated side-effects, psychological comorbidities, and incorrect management are scarce. The aim of this study was to investigate patients' perspectives on their disease. METHODS: This study used a cross-sectional, web-based, anonymous survey, developed by endocrinologists and patient representatives, to collect the opinions of patients with central diabetes insipidus on management and complications of their disease, psychological comorbidities, degree of knowledge and awareness of the condition among health-care professionals, and renaming the disease to avoid confusion with diabetes mellitus (diabetes). FINDINGS: Between Aug 23, 2021, and Feb 7, 2022, 1034 patients with central diabetes insipidus participated in the survey. 91 (9%) participants were children and adolescents (37 [41%] girls and 54 [59%] boys; median age 10 years [IQR 6-15]) and 943 (91%) were adults (757 [80%] women and 186 [20%] men]; median age 44 years [34-54]). 488 (47%) participants had isolated posterior pituitary dysfunction and 546 (53%) had combined anterior and posterior pituitary dysfunction. Main aetiologies were idiopathic (315 [30%] of 1034 participants) and tumours and cysts (pre-surgical 217 [21%]; post-surgical 254 [25%]). 260 (26%; 95% CI [0·23-0·29]) of 994 patients on desmopressin therapy had hyponatraemia leading to hospitalisation. Patients who routinely omitted or delayed desmopressin to allow intermittent aquaresis had a significantly lower prevalence of hyponatraemia compared with those not aware of this approach (odds ratio 0·55 [95% CI 0·39-0·77]; p=0·0006). Of patients who had to be hospitalised for any medical reason, 71 (13%; 95% CI 0·10-0·16) of 535 patients did not receive desmopressin while in a fasting state (nil by mouth) without intravenous fluid replacement and reported symptoms of dehydration. 660 (64%; 0·61-0·67) participants reported lower quality of life, and 369 (36%; 0·33-0·39) had psychological changes subjectively associated with their central diabetes insipidus. 823 (80%; 0·77-0·82) participants encountered a situation where central diabetes insipidus was confused with diabetes mellitus (diabetes) by health-care professionals. 884 (85%; 0·83-0·88) participants supported renaming the disease; the most favoured alternative names were vasopressin deficiency and arginine vasopressin deficiency. INTERPRETATION: This is the largest survey of patients with central diabetes insipidus, reporting a high prevalence of treatment-associated side-effects, mismanagement during hospitalisation, psychological comorbidities, and a clear support for renaming the disease. Our data are the first to indicate the value of routinely omitting or delaying desmopressin. FUNDING: Swiss National Science Foundation, Swiss Academy of Medical Sciences, and G&J Bangerter-Rhyner-Foundation.
Assuntos
Diabetes Insípido Neurogênico , Diabetes Insípido , Diabetes Mellitus , Hiponatremia , Adolescente , Adulto , Arginina , Criança , Estudos Transversais , Desamino Arginina Vasopressina/uso terapêutico , Diabetes Insípido/diagnóstico , Diabetes Insípido/etiologia , Diabetes Insípido Neurogênico/complicações , Diabetes Insípido Neurogênico/etiologia , Feminino , Humanos , Hiponatremia/complicações , Hiponatremia/etiologia , Internet , Masculino , Pessoa de Meia-Idade , Morbidade , Qualidade de VidaRESUMO
Graves' disease (GD) is a common autoimmune disease (AID) that shares many of its susceptibility loci with other AIDs. The thyroid stimulating hormone receptor (TSHR) represents the primary autoantigen in GD, in which autoantibodies bind to the receptor and mimic its ligand, thyroid stimulating hormone, causing the characteristic clinical phenotype. Although early studies investigating the TSHR and GD proved inconclusive, more recently we provided convincing evidence for association of the TSHR region with disease. In the current study, we investigated a combined panel of 98 SNPs, including 70 tag SNPs, across an extended 800 kb region of the TSHR to refine association in a cohort of 768 GD subjects and 768 matched controls. In total, 28 SNPs revealed association with GD (P < 0.05), with strongest SNP associations at rs179247 (chi(2) = 32.45, P = 8.90 x 10(-8), OR = 1.53, 95% CI = 1.32-1.78) and rs12101255 (chi(2) = 30.91, P = 1.95 x 10(-7), OR = 1.55, 95% CI = 1.33-1.81), both located in intron 1 of the TSHR. Association of the most associated SNP, rs179247, was replicated in 303 GD families (P = 7.8 x 10(-4)). In addition, we provide preliminary evidence that the disease-associated genotypes of rs179247 (AA) and rs12101255 (TT) show reduced mRNA expression ratios of flTSHR relative to two alternate TSHR mRNA splice variants.
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Doença de Graves/genética , Receptores da Tireotropina/genética , Estudos de Casos e Controles , Estudos de Coortes , Expressão Gênica , Doença de Graves/metabolismo , Haplótipos , Humanos , Íntrons , Desequilíbrio de Ligação , Polimorfismo de Nucleotídeo Único , Receptores da Tireotropina/metabolismo , População Branca/genéticaRESUMO
CONTEXT: The optimal duration of dopamine agonist (DA) therapy in prolactinoma is unknown. There are concerns that despite low recurrence rates in highly selected groups, high recurrence rates after DA withdrawal may occur in routine practice. OBJECTIVE: To explore recurrence of hyperprolactinaemia and predictive factors following DA withdrawal in patients with microprolactinoma and macroprolactinoma. DESIGN: A retrospective study on adult patients with confirmed prolactinoma attending the Oxford Endocrine Department. PATIENTS AND MEASUREMENTS: We identified patients with macroprolactinoma (n = 15) and microprolactinoma (n = 45) treated with DA therapy for >3 years, with a trial off DA therapy. None had other treatments. Measurements included recurrence of hyperprolactinaemia following DA withdrawal, tumour size (macroprolactinomas), duration of DA therapy, prolactin levels (baseline, during DA therapy, recurrence) and time to recurrence. Data were reported as mean (range). RESULTS: During DA therapy, prolactin levels suppressed to normal range in all patients with macroprolactinoma and microprolactinoma, and most macroprolactinomas (n = 14) had substantial tumour shrinkage. Hyperprolactinaemia recurred in 93% of macroprolactinomas (n = 14) at 8·8 months (3-36) and 64% of microprolactinomas (n = 29) at 4·8 months (3-12). Duration of DA therapy was 7·5 years (4-15) for macroprolactinomas and 4·1 years (3-10) for microprolactinomas. Prolactin levels during DA therapy were 144 mU/l (7-336) for macroprolactinomas and 278 mU/l (30-629) for microprolactinomas. For microprolactinomas, prolactin levels during DA therapy were less suppressed in those with recurrence than in those without recurrence (P < 0·05). CONCLUSIONS: In routine practice, hyperprolactinaemia recurs early in most macroprolactinomas (93%) and microprolactinomas (64%) following DA therapy discontinuation. For most macroprolactinomas, cessation of DA cannot be recommended even after 7 years of therapy.
Assuntos
Agonistas de Dopamina/uso terapêutico , Hiperprolactinemia/etiologia , Neoplasias Hipofisárias/tratamento farmacológico , Prolactinoma/tratamento farmacológico , Suspensão de Tratamento , Adulto , Agonistas de Dopamina/administração & dosagem , Feminino , Seguimentos , Humanos , Imageamento por Ressonância Magnética , Masculino , Neoplasias Hipofisárias/complicações , Neoplasias Hipofisárias/diagnóstico por imagem , Neoplasias Hipofisárias/patologia , Prolactinoma/complicações , Prolactinoma/diagnóstico por imagem , Prolactinoma/patologia , Radiografia , Recidiva , Estudos Retrospectivos , Fatores de Tempo , Carga TumoralRESUMO
BACKGROUND: Aggressive pituitary tumours are associated with substantial morbidity and mortality. Treatment options are often limited, and chemotherapy has been reserved as salvage therapy although historically results have often been disappointing. However, temozolomide, an oral alkylating agent, has recently demonstrated significant activity against these tumours. A DNA repair protein, 06-methylguanine-DNA methyltransferase (MGMT) has been suggested as a biomarker to predict response to temozolomide in pituitary tumours. MATERIALS AND METHODS: This paper will review the current literature on temozolomide and pituitary tumours and discuss the recent controversy surrounding the value of determining the MGMT status in this tumour group. A PubMed search was performed to retrieve articles, using the terms 'pituitary tumour' and 'temozolomide'. RESULTS: Overall, 24/40 (60%) of the published cases demonstrated a response to temozolomide therapy. The highest response rates were seen amongst prolactinomas (73%) and ACTH-secreting tumours (60%), whilst nonfunctioning pituitary tumours exhibit lower response rates (40%). Responsivity is typically evident in the first 3 months of therapy and may be dramatic and sustained. Low MGMT expression, as determined by immunohistochemistry, is associated with a high response rate (76%), whilst high MGMT expression has not been associated with responses. MGMT promoter methylation does not correlate with temozolomide response. CONCLUSIONS: Temozolomide is the first chemotherapeutic agent to show substantial response rates in aggressive pituitary tumours. MGMT immunohistochemistry, but not MGMT methylation analysis, shows promise as a predictive tool. Prospective clinical trials are now necessary to more accurately determine the efficacy of this agent in this patient group.
Assuntos
Adenoma/tratamento farmacológico , Antineoplásicos Alquilantes/uso terapêutico , Carcinossarcoma/tratamento farmacológico , Dacarbazina/análogos & derivados , O(6)-Metilguanina-DNA Metiltransferase/metabolismo , Neoplasias Hipofisárias/tratamento farmacológico , Adenoma/metabolismo , Biomarcadores Tumorais/metabolismo , Carcinossarcoma/metabolismo , Dacarbazina/uso terapêutico , Humanos , Neoplasias Hipofisárias/metabolismo , TemozolomidaRESUMO
Craniopharyngiomas are rare, mainly sellar/parasellar, epithelial tumors diagnosed during childhood or adult life. Histologically, two primary subtypes have been recognized (adamantinomatous and papillary) with an as yet, unclarified pathogenesis. They may present with a variety of manifestations (neurological, visual, and hypothalamo-pituitary). Despite their benign histological appearance, they often show an unpredictable growth pattern, which, combined with the lack of randomized studies, poses significant difficulties in the establishment of an optimal therapeutic protocol. This should focus on the prevention of recurrence(s), improvement of survival, reduction of the significant disease and treatment-related morbidity (endocrine, visual, hypothalamic, neurobehavioral, and cognitive), and preservation of the quality of life. Currently, surgical excision followed by external beam irradiation, in cases of residual tumor, is the main treatment option. Intracystic irradiation or bleomycin, stereotactic radiosurgery, or radiotherapy and systemic chemotherapy are alternative approaches; their place in the management plan remains to be assessed in adequately powered long-term trials. Apart from the type of treatment, the identification of clinical and imaging parameters that will predict patients with a better prognosis is difficult. The central registration of patients with these challenging tumors may provide correlates between treatments and outcomes and establish prognostic factors at the pathological or molecular level that may further guide us in the future.