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1.
Endocrine ; 84(2): 670-676, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38194218

RESUMO

PURPOSE: Data regarding the presence of a prolactin (PRL) threshold above which a pituitary magnetic resonance imaging (MRI) is mandatory in patients with hyperprolactinemia (hyperPRL) are controversial and derived primarily from studies focused on female populations. Aim of our study was to evaluate in a cohort of patients of both sexes with confirmed hyperPRL, the possible correlation between PRL values and the presence of pituitary abnormalities. METHODS: We retrospectively analyzed data from patients who underwent serial PRL sampling at our Division between January 2015 and December 2022. Patients diagnosed with monomeric hyperPRL at serial sampling and with subsequent contrast-enhanced MRI results available for the pituitary region were included in the study. Exclusion criteria were prior pituitary disease, severe renal insufficiency, liver cirrhosis, uncompensated primary hypothyroidism and ongoing therapy with hyperprolactinemic drugs. Physiological causes of hyperPRL were also ruled out. RESULTS: Out of the 1253 patients who underwent serial PRL sampling, 139 patients (101 women and 38 men) met the inclusion criteria: 106 (76.3%) patients had some form of pituitary disease, with microlesions observed in 69.8%, macrolesions in 25.5% and other findings in 4.7% of subjects. PRL values showed a modest accuracy in predicting the presence of a pituitary abnormality and the best cut-offs identified were >25 µg/L (AUC 0.767, p = 0.003) and >44.2 µg/L (AUC 0.697, p < 0.001) in men and women, respectively; however, if only patients with PRL values > 500 µg/L were excluded from the analysis, as they were already supposed to harbor a macroprolactinoma, PRL levels were not able to predict the presence of a macrolesion neither in men nor women. CONCLUSION: Given the high prevalence of pituitary abnormalities in patients of both sexes with hyperPRL at serial sampling, performing a pituitary imaging in all cases of hyperPRL, even if mild, appears to be a cautious choice.


Assuntos
Hiperprolactinemia , Imageamento por Ressonância Magnética , Prolactina , Humanos , Hiperprolactinemia/sangue , Hiperprolactinemia/etiologia , Feminino , Masculino , Prolactina/sangue , Adulto , Estudos Retrospectivos , Pessoa de Meia-Idade , Hipófise/diagnóstico por imagem , Hipófise/patologia , Adulto Jovem , Doenças da Hipófise/sangue , Doenças da Hipófise/diagnóstico por imagem , Doenças da Hipófise/diagnóstico , Idoso , Neoplasias Hipofisárias/sangue , Neoplasias Hipofisárias/complicações , Neoplasias Hipofisárias/diagnóstico por imagem , Adolescente
2.
Clin Biochem ; 97: 48-53, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34437886

RESUMO

BACKGROUND: Sellar masses (SM) frequently present with insidious hormonal dysfunction. We previously showed that, by utilizing a combined reflex/reflecting approach involving a laboratory clinician (LC) on common endocrine test results requested by non-specialists, and subsequently adding further warranted tests, previously undiagnosed pituitary disorders can be identified. However, manually employing these strategies by an LC is not feasible for wider screening of pituitary disorders. OBJECTIVE: The aim of this study was to compare the accuracy and financial impact of an Artificial Intelligence (AI) based, fully computerized reflex protocol with manual reflex/reflective intervention protocol led by an LC. METHODS: We developed a proof-of-concept AI-based framework to fully computerize multi-stage reflex testing protocols for pituitary dysfunction using automated reasoning methods. We compared the efficacy of this AI-based protocol with a reflex/reflective protocol based on manually curated retrospective data in identifying pituitary dysfunction based on 12 months of laboratory testing. RESULTS: The AI-based reflex protocol, as compared with the manual protocol, would have identified laboratory tests for add-on that either directly matched or included all manual add-on tests in 92% of cases, and recommended a similar specialist referral in 90% of the cases. The AI-based protocol would have issued 2.8 times the total number of manual add-on laboratory tests at an 85% lower operation cost than the manual protocol when considering marginal test costs, technical staff and specialist salary. CONCLUSION/DISCUSSION: Our AI-based reflex protocol can successfully identify patients with pituitary dysfunction, with lower estimated laboratory cost. Future research will focus on enhancing the protocol's accuracy and incorporating the AI-based reflex protocol into institutional laboratory and hospital information systems for the detection of undiagnosed pituitary disorders.


Assuntos
Inteligência Artificial , Diagnóstico por Computador/métodos , Doenças da Hipófise/diagnóstico , Análise Química do Sangue , Procedimentos Clínicos , Diagnóstico por Computador/economia , Diagnóstico Precoce , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Doenças da Hipófise/sangue , Gravidez , Estudo de Prova de Conceito , Estudos Retrospectivos
3.
J Clin Endocrinol Metab ; 106(12): e5147-e5155, 2021 11 19.
Artigo em Inglês | MEDLINE | ID: mdl-34254637

RESUMO

CONTEXT: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a severe chronic illness that reduces the quality of life. A potential role of neuroendocrine autoimmune dysfunction has been hypothesized. OBJECTIVE: This work aims to investigate the occurrence of antipituitary (APA) and antihypothalamic (AHA) antibodies and possible related hypothalamic/pituitary dysfunctions in ME/CSF patients. METHODS: This is a case-control study conducted in a university hospital setting (Stanford, California, USA; and Naples, Italy). Thirty women with ME/CSF (group 1) diagnosed according to Fukuda, Canadian, and Institute of Medicine criteria, at Stanford University, were enrolled and compared with 25 age-matched healthy controls. APA and AHA were detected by immunofluorescence; moreover, we investigated hormonal secretions of anterior pituitary and respective target glands. APA and AHA titers both were assessed and the prevalence of pituitary hormone deficiencies was also investigated. RESULTS: Patients in group 1 showed a high prevalence of AHA (33%) and APA (56%) and significantly lower levels of adrenocorticotropin (ACTH)/cortisol, and growth hormone (GH) peak/insulin-like growth factor-1 (IGF-1) vs controls (all AHA/APA negative). Patients in group 1A (13 patients positive at high titers, ≥ 1:32) showed ACTH/cortisol and GH peak/IGF-1 levels significantly lower and more severe forms of ME/CFS with respect to patients in group 1B (7 positive at middle/low titers, 1:16-1:8) and 1C (10 antibody-negative patients). CONCLUSION: Both AHA and/or APA at high titers were associated with hypothalamic/pituitary dysfunction, suggesting that hypothalamic/pituitary autoimmunity may play an important role in the manifestations of ME/CFS, especially in its more severe forms.


Assuntos
Autoanticorpos/sangue , Doenças Autoimunes/epidemiologia , Biomarcadores/sangue , Síndrome de Fadiga Crônica/fisiopatologia , Hipotálamo/patologia , Doenças da Hipófise/epidemiologia , Hormônio Adrenocorticotrópico/sangue , Adulto , Autoanticorpos/imunologia , Doenças Autoimunes/sangue , Doenças Autoimunes/imunologia , Doenças Autoimunes/patologia , Estudos de Casos e Controles , Feminino , Seguimentos , Hormônio do Crescimento Humano/sangue , Humanos , Hipotálamo/imunologia , Hipotálamo/metabolismo , Fator de Crescimento Insulin-Like I/análise , Doenças da Hipófise/sangue , Doenças da Hipófise/imunologia , Doenças da Hipófise/patologia , Prognóstico , Estados Unidos/epidemiologia , Adulto Jovem
4.
J Urol ; 205(3): 871-878, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33080146

RESUMO

PURPOSE: We aimed to identify predictor variables associated with pituitary abnormalities in hypogonadal men with mild hyperprolactinemia. We also sought to develop a decision-making aid to select patients for evaluation with pituitary magnetic resonance imaging. MATERIALS AND METHODS: We retrospectively examined men with mild hyperprolactinemia (15.1-50.0 ng/ml) who presented with symptoms of hypogonadism and underwent pituitary magnetic resonance imaging. Demographics, laboratory values and clinical data were obtained from the electronic medical record. Selected predictor variables were included in multivariable logistic regression and partitioning models. Cost avoidance analysis was performed on models achieving sensitivities ≥90%. RESULTS: A total of 141 men were included in the study, of whom 40 (28%) displayed abnormalities on pituitary magnetic resonance imaging. Patients with pituitary abnormalities exhibited higher prolactin (p=0.01), lower testosterone (p=0.0001) and lower luteinizing hormone (p=0.03) levels than those with normal anatomy, as well as higher prolactin-to-testosterone ratios (p <0.0001) and lower luteinizing hormone-to-follicle-stimulating hormone ratios (p=0.0001). These serological variables were identified as the best performing predictor variables. The partition incorporating a prolactin-to-testosterone ratio cutoff of 0.10 and prolactin cutoff of 25 ng/ml achieved 90% sensitivity and 48% specificity, and reduced diagnostic expenses by 28%. CONCLUSIONS: Hypogonadal men presenting with mild hyperprolactinemia and pituitary abnormalities declare themselves via endocrine studies routinely ordered to evaluate these conditions. The prolactin-to-testosterone ratio is the best independent predictor of finding a pituitary abnormality on magnetic resonance imaging, although sensitivity improves by referencing additional serological parameters. Significant cost avoidance may result from screening this population prior to ordering pituitary magnetic resonance imaging.


Assuntos
Hipogonadismo/sangue , Doenças da Hipófise/sangue , Prolactina/sangue , Testosterona/sangue , Adulto , Biomarcadores/sangue , Hormônio Foliculoestimulante/sangue , Humanos , Hormônio Luteinizante/sangue , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Doenças da Hipófise/diagnóstico por imagem , Valor Preditivo dos Testes , Estudos Retrospectivos , Sensibilidade e Especificidade
5.
PLoS One ; 15(8): e0238223, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32853260

RESUMO

Being delivered as a low birthweight (LBW) infant is a risk factor for elevated blood pressure and future problems with cardiovascular and cerebellar diseases. Although premature babies are reported to have low numbers of nephrons, some unclear questions remain about the mechanisms underlying elevated blood pressure in full-term LBW infants. We previously reported that glucocorticoids increased miR-449a expression, and increased miR-449a expression suppressed Crhr1 expression and caused negative glucocorticoid feedback. Therefore, we conducted this study to clarify the involvement of pituitary miR-449a in the increase in blood pressure caused by higher glucocorticoids in LBW rats. We generated a fetal low-carbohydrate and calorie-restricted model rat (60% of standard chow), and some individuals showed postnatal growth failure caused by growth hormone receptor expression. Using this model, we examined how a high-fat diet (lard-based 45kcal% fat)-induced mismatch between prenatal and postnatal environments could elevate blood pressure after growth. Although LBW rats fed standard chow had slightly higher blood pressure than control rats, their blood pressure was significantly higher than controls when exposed to a high-fat diet. Observation of glomeruli subjected to periodic acid methenamine silver (PAM) staining showed no difference in number or size. Aortic and cardiac angiotensin II receptor expression was altered with compensatory responses. Blood aldosterone levels were not different between control and LBW rats, but blood corticosterone levels were significantly higher in the latter with high-fat diet exposure. Administration of metyrapone, a steroid synthesis inhibitor, reduced blood pressure to levels comparable to controls. We showed that high-fat diet exposure causes impairment of the pituitary glucocorticoid negative feedback via miR-449a. These results clarify that LBW rats have increased blood pressure due to high glucocorticoid levels when they are exposed to a high-fat diet. These findings suggest a new therapeutic target for hypertension of LBW individuals.


Assuntos
Pressão Sanguínea/fisiologia , Retroalimentação Fisiológica/fisiologia , Glucocorticoides/sangue , Doenças da Hipófise/sangue , Doenças da Hipófise/fisiopatologia , Hipófise/fisiologia , Animais , Peso ao Nascer/efeitos dos fármacos , Peso ao Nascer/fisiologia , Pressão Sanguínea/efeitos dos fármacos , Corticosterona/sangue , Dieta Hiperlipídica/efeitos adversos , Feminino , Humanos , Hipertensão/sangue , Hipertensão/fisiopatologia , Recém-Nascido de Baixo Peso/sangue , Recém-Nascido de Baixo Peso/fisiologia , Recém-Nascido , Masculino , Metirapona/uso terapêutico , Doenças da Hipófise/tratamento farmacológico , Hipófise/efeitos dos fármacos , Gravidez , Efeitos Tardios da Exposição Pré-Natal/sangue , Efeitos Tardios da Exposição Pré-Natal/fisiopatologia , Ratos , Ratos Wistar
6.
J Vet Intern Med ; 34(3): 1350-1356, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32255541

RESUMO

BACKGROUND: Determination of plasma adrenocotrophic hormone (ACTH) concentration (endogenous or thyrotropin-releasing hormone [TRH] stimulation test) is the most commonly used diagnostic test for pituitary pars intermedia dysfunction (PPID) in horses. Because ACTH is unstable, samples often are frozen to be shipped to laboratories or to allow for batch analysis of research samples. However, the effect of multiple freeze-thaw cycles on equine ACTH is unknown. OBJECTIVE: To determine the effects of multiple freeze-thaw cycles on immunoreactive ACTH concentration. ANIMALS: Twenty-eight horses ranging from 10 to 27 years of age were used. METHODS: Prospective study. Horses were divided into 4 groups: group 1, PPID-negative, without TRH stimulation; group 2, PPID-negative, with TRH stimulation; group 3, PPID-positive, without TRH stimulation; and group 4, PPID-positive, with TRH stimulation. Whole blood was collected from each horse at baseline or 30 minutes after TRH stimulation. Immunoreactive plasma ACTH concentration was determined using a chemiluminescence assay. Plasma samples then were frozen at -80°C >24 hours, thawed at 4°C and reanalyzed for 5 freeze-thaw cycles. Changes in plasma ACTH concentration were analyzed using a linear mixed-effect model. RESULTS: Significant effects of freeze-thaw cycles (P = .001) and PPID status (P = .04) on plasma ACTH concentration were observed, but no significant effect of TRH stimulation was identified. CONCLUSIONS AND CLINICAL IMPORTANCE: The plasma ACTH concentration is altered by freeze-thaw cycles, and the effect is observed sooner in horses with PPID. To diagnose PPID, multiple freeze-thaw cycles should be avoided when measuring plasma ACTH concentration.


Assuntos
Hormônio Adrenocorticotrópico/sangue , Congelamento/efeitos adversos , Doenças dos Cavalos/diagnóstico , Doenças da Hipófise/veterinária , Manejo de Espécimes/veterinária , Animais , Testes Diagnósticos de Rotina , Feminino , Doenças dos Cavalos/sangue , Cavalos , Medições Luminescentes/veterinária , Masculino , Doenças da Hipófise/sangue , Doenças da Hipófise/diagnóstico , Estudos Prospectivos , Manejo de Espécimes/métodos , Hormônio Liberador de Tireotropina/administração & dosagem
7.
Artigo em Inglês | MEDLINE | ID: mdl-32132974

RESUMO

Purpose: To detect the presence of antipituitary (APA) and antihypothalamus antibodies (AHA) in subjects treated for brain cancers, and to evaluate their potential association with pituitary dysfunction. Methods: We evaluated 63 patients with craniopharyngioma, glioma, and germinoma treated with surgery and/or radiotherapy and/or chemotherapy at a median age of 13 years. Forty-one had multiple pituitary hormone deficiencies (MPHD), six had a single pituitary defect. GH was the most common defect (65.1%), followed by AVP (61.9%), TSH (57.1%), ACTH (49.2%), and gonadotropin (38.1%). APA and AHA were evaluated by simple indirect immunofluorescence method indirect immunofluorescence in patients and in 50 healthy controls. Results: Circulating APA and/or AHA were found in 31 subjects (49.2%) and in none of the healthy controls. In particular, 25 subjects out of 31 were APA (80.6%), 26 were AHA (83.90%), and 20 were both APA and AHA (64.5%). Nine patients APA and/or AHA have craniopharyngioma (29%), seven (22.6%) have glioma, and 15 (48.4%) have germinoma. Patients with craniopharyngioma were positive for at least one antibody in 39.1% compared to 33.3% of patients with glioma and to 78.9% of those with germinoma with an analogous distribution for APA and AHA between the three tumors. The presence of APA or AHA and of both APA and AHA was significantly increased in patients with germinoma. The presence of APA (P = 0.001) and their titers (P = 0.001) was significantly associated with the type of tumor in the following order: germinomas, craniopharyngiomas, and gliomas; an analogous distribution was observed for the presence of AHA (P = 0.002) and their titers (P = 0.012). In addition, we found a significant association between radiotherapy and APA (P = 0.03). Conclusions: Brain tumors especially germinoma are associated with the development of hypothalamic-pituitary antibodies and pituitary defects. The correct interpretation of APA/AHA antibodies is essential to avoid a misdiagnosis of an autoimmune infundibulo-neurohypophysitis or pituitary hypophysitis in patients with germinoma.


Assuntos
Autoanticorpos/sangue , Neoplasias Encefálicas/epidemiologia , Sobreviventes de Câncer/estatística & dados numéricos , Hipotálamo/imunologia , Doenças da Hipófise/epidemiologia , Hipófise/imunologia , Adolescente , Adulto , Idade de Início , Doenças Autoimunes/sangue , Doenças Autoimunes/epidemiologia , Doenças Autoimunes/etiologia , Neoplasias Encefálicas/sangue , Neoplasias Encefálicas/imunologia , Neoplasias Encefálicas/terapia , Estudos de Casos e Controles , Criança , Pré-Escolar , Craniofaringioma/sangue , Craniofaringioma/epidemiologia , Craniofaringioma/imunologia , Craniofaringioma/terapia , Feminino , Seguimentos , Germinoma/sangue , Germinoma/epidemiologia , Germinoma/imunologia , Germinoma/terapia , Glioma/sangue , Glioma/epidemiologia , Glioma/imunologia , Glioma/terapia , Humanos , Masculino , Doenças da Hipófise/sangue , Doenças da Hipófise/imunologia , Doenças da Hipófise/terapia , Neoplasias Hipofisárias/sangue , Neoplasias Hipofisárias/epidemiologia , Neoplasias Hipofisárias/imunologia , Neoplasias Hipofisárias/terapia , Adulto Jovem
8.
Vet Immunol Immunopathol ; 221: 110013, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32058159

RESUMO

Similarly to aged humans, senior horses (≥20 years) exhibit chronic low-grade inflammation systemically, known as inflamm-aging. Inflamm-aging in the senior horse has been characterized by increased circulating inflammatory cytokines as well as increased inflammatory cytokine production by lymphocytes and monocytes in response to a mitogen. Little is currently known regarding underlying causes of inflamm-aging. However, senior horses are also known to present with muscle wasting and often the endocrinopathy pituitary pars intermedia dysfunction (PPID). Despite the concurrence of these phenomena, the relationships inflamm-aging may have with measures of body composition and pituitary function in the horse remain unknown. Furthermore, nutrition has been a focus of research in an attempt to promote health span as well as life span in senior horses, with some nutrients, such as omega-3 fatty acids, having known anti-inflammatory effects. Thus, an exploratory study of a population of n = 42 similarly-managed senior horses was conducted to determine relationships between inflamm-aging and measures of circulating nutrients, body composition, age, and PPID. Serum was collected to determine vitamin, mineral, and fatty acid content. Peripheral blood mononuclear cells were also isolated to determine inflammatory cytokine production of interferon-γ (IFN-γ) and tumor necrosis factor-α (TNF-α) following stimulation with a mitogen, as well as to determine gene expression of interleukin(IL)-1ß, IL-6, IL-10, IFN-γ, and TNF-α. Serum IL-6 and C-reactive protein were determined by enzyme-linked immunosorbent assay. Whole blood was collected for hematological and biochemical analysis. Body composition was evaluated via ultrasound and muscle scoring for all 42 horses as well as by deuterium oxide dilution for a subset of n = 10 horses. Pituitary function was evaluated by measuring basal adrenocorticotropin hormone concentrations as well as by thyrotropin releasing hormone stimulation testing (to determine PPID status). Results showed various relationships between inflammatory markers and the other variables measured. Most notably, docosadienoic acid (C22:2n6c), docosapentaenoic acid (C22:5n3c), and folate were positively associated with numerous inflammatory parameters (P ≤ 0.05). Although no relationships were found between inflamm-aging and PPID, being positive for PPID was negatively associated with vitamin B12 (P ≤ 0.01). No relationships between inflammation and body composition were found. Even within this senior horse population, age was associated with multiple parameters, particularly with numerous inflammatory cytokines and fatty acids. In summary, inflamm-aging exhibited relationships with various other parameters examined, particularly with certain fatty acids. This exploratory study provides insights into physiological changes associated with inflamm-aging in the senior horse.


Assuntos
Envelhecimento/imunologia , Composição Corporal , Doenças dos Cavalos/sangue , Inflamação , Doenças da Hipófise/veterinária , Adeno-Hipófise Parte Intermédia/patologia , Animais , Citocinas/sangue , Feminino , Ácido Fólico/sangue , Cavalos , Masculino , Nutrientes , Doenças da Hipófise/sangue
9.
J Vet Intern Med ; 33(6): 2746-2751, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31617618

RESUMO

BACKGROUND: Diseases associated with insulin dysregulation (ID), such as equine metabolic syndrome and pituitary pars intermedia dysfunction, are of interest to practitioners because of their association with laminitis. Accurate insulin concentration assessment is critical in diagnosing and managing these diseases. HYPOTHESIS/OBJECTIVES: To determine the effect of time, temperature, and collection tube type on insulin concentrations in horses at risk of ID. ANIMALS: Eight adult horses with body condition score >6/9. METHODS: In this prospective study, subjects underwent an infeed oral glucose test 2 hours before blood collection. Blood samples were divided into ethylenediaminetetraacetic acid, heparinized, or serum tubes and stored at 4 or 20°C. Tubes were centrifuged and analyzed for insulin by a chemiluminescent assay over 8 days. Changes in insulin concentrations were compared with a linear mixed effects model. RESULTS: An overall effect of time, tube type and temperature was identified (P = .01, P = 0.001, and P = 0.001, respectively). Serum and heparinized samples had similar concentrations for 3 days at 20°C and 8 days at 4°C; however, after 3 days at 20°C, heparinized samples had significantly higher insulin concentrations (P = .004, P = .03, and P = .03 on consecutive days). Ethylenediaminetetraacetic acid samples had significantly lower insulin concentrations regardless of time and temperature (P = .001 for all comparisons). CONCLUSIONS AND CLINICAL IMPORTANCE: These results suggest an ideal protocol to determine insulin concentrations involves using serum or heparinized samples with analysis occurring within 3 days at 20°C or 8 days at 4°C.


Assuntos
Doenças dos Cavalos/sangue , Insulina/sangue , Síndrome Metabólica/veterinária , Doenças da Hipófise/veterinária , Adeno-Hipófise Parte Intermédia , Animais , Coleta de Amostras Sanguíneas/veterinária , Feminino , Cavalos , Insulina/metabolismo , Masculino , Doenças da Hipófise/sangue
10.
J Vet Intern Med ; 33(5): 2249-2256, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31498947

RESUMO

BACKGROUND: The thyrotropin-releasing hormone (TRH) stimulation test and the 2-step insulin sensitivity test are commonly used methods to diagnose, respectively, pituitary pars intermedia dysfunction (PPID) and insulin dysregulation (ID). OBJECTIVES: To investigate the diagnostic value of combining the TRH stimulation test and the 2-step insulin sensitivity test to diagnose PPID and ID simultaneously. ANIMALS: Twenty-seven adult horses, 10 control horses without PPID or ID, 5 horses with PPID only, 5 horses with ID only, and 7 horses with PPID and ID. METHODS: Randomized prospective study. Horses underwent a TRH stimulation test alone, a 2-step insulin sensitivity test alone, and combined testing with simultaneous TRH and insulin injection in the same syringe. Data were compared by 2-way repeated measures analysis of variance and 2 1-sided tests to demonstrate equivalence. Bland-Altman plots were generated to visualize agreement between combined and independent testing. RESULTS: The effect of combined testing on plasma adrenocorticotropic hormone, blood glucose concentration, or percentage decrease in blood glucose concentration was not significantly different from the effect obtained with independent testing. One control horse appeared falsely positive for PPID, 2 PPID-only horses appeared falsely positive for ID, and 1 PPID and ID horse appeared falsely negative for ID when tests were performed simultaneously. Bland-Altman plots supported the agreement between combined and independent testing. CONCLUSIONS AND CLINICAL IMPORTANCE: Combining the TRH stimulation test and the 2-step insulin sensitivity test appears to be a useful diagnostic tool for equine practitioners in the field, allowing testing of a horse for both PPID and ID simultaneously.


Assuntos
Hormônio Adrenocorticotrópico/sangue , Doenças dos Cavalos/diagnóstico , Resistência à Insulina , Doenças da Hipófise/veterinária , Animais , Glicemia , Feminino , Doenças dos Cavalos/sangue , Doenças dos Cavalos/metabolismo , Cavalos , Masculino , Doenças da Hipófise/sangue , Doenças da Hipófise/diagnóstico , Adeno-Hipófise Parte Intermédia/patologia , Estudos Prospectivos , Distribuição Aleatória , Hormônio Liberador de Tireotropina/administração & dosagem , Hormônio Liberador de Tireotropina/farmacologia
11.
Eur J Endocrinol ; 181(4): R155-R171, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31370006

RESUMO

INTRODUCTION: The transition age is the period between childhood to adulthood; it refers to a broad set of physical, cognitive and sociocultural modifications, arbitrarily defined as starting in late puberty and ending with full adult maturation. Pituitary disorders in adolescence represent a challenge that requires careful management during the transition to adult care. METHODS: Given the complexity of care of pituitary disorders in the transition age, we have reviewed the relevant medical literature focusing on aetiology, clinical manifestations, treatment strategies of GH deficiency (GHD), hypogonadotrophic hypogonadism (HH) in male and female adolescents, central hypothyroidism (CH), central adrenal insufficiency (CAI) and cranial diabetes insipidus (CDI) at this time. The objective of the present review is to provide an up-to-date evaluation of the transition period to evaluate the specific needs of adolescents with chronic pituitary disease in order to optimise their management. RESULTS: We provide an overview of current clinical management of GHD, HH, CH, CAI and CDI in the transition age. CONCLUSIONS: Specific changes occur in pituitary function during the transition period. A holistic approach including discussion of patients' concerns and emotional support should constitute a key component of managing pituitary disorders in adolescence. Special transition clinics where paediatric and adult endocrinologists work together, should be increasingly created and strengthened to bridge care, to promote continuity and adherence to treatment and to limit potential negative development, metabolic, skeletal and cardiovascular sequelae of discontinuity of care among adolescents with pituitary disorders.


Assuntos
Transferência de Pacientes/métodos , Doenças da Hipófise/diagnóstico , Doenças da Hipófise/terapia , Maturidade Sexual/fisiologia , Adolescente , Fatores Etários , Criança , Hormônio do Crescimento Humano/sangue , Humanos , Transferência de Pacientes/tendências , Doenças da Hipófise/sangue , Adulto Jovem
12.
BMJ Case Rep ; 12(7)2019 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-31289170

RESUMO

Diencephalic syndrome is one of the rare causes of failure to thrive in infants and young children. It is caused by a tumour in diencephalon (thalamus and hypothalamus), characterised by profound emaciation with uniform loss of body weight despite normal or slightly decreased appetite, locomotor hyperactivity, euphoria and visual symptoms. Anaesthetic considerations due to decreased body fat include positioning to avoid pressure necrosis, measures to avoid hypothermia, proper drug dosing, treating electrolyte imbalances and delayed recovery. We report successful anaesthetic management of a child with diencephalic syndrome scheduled for an endoscopic biopsy of suprasellar space occupying lesion under general anaesthesia.


Assuntos
Anestesia/métodos , Diencéfalo/patologia , Doenças Hipotalâmicas/patologia , Doenças da Hipófise/patologia , Anestésicos/administração & dosagem , Biópsia , Criança , Insuficiência de Crescimento/etiologia , Humanos , Doenças Hipotalâmicas/diagnóstico por imagem , Doenças Hipotalâmicas/metabolismo , Unidades de Terapia Intensiva Pediátrica/normas , Cuidados Intraoperatórios , Masculino , Doenças da Hipófise/sangue , Doenças da Hipófise/diagnóstico por imagem , Cuidados Pré-Operatórios , Prognóstico , Tomografia Computadorizada por Raios X , Derivação Ventriculoperitoneal/métodos
13.
Rheumatol Int ; 39(8): 1467-1476, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31203400

RESUMO

GPA with pituitary involvement is a rare condition which is prone to be misdiagnosed. The aim of this study was to summarize clinical features of pituitary involvement in GPA and facilitate early diagnosis. Twelve GPA patients were retrospectively analyzed at a single hospital between 2000 and 2017. A literature review was conducted to compare previous findings with our clinical results. The incidence rate of pituitary involvement in GPA was 3.9% (12/304) without sexual predilection. Other impairments included ear, nose and throat (n = 12), oculi (n = 10), lung (n = 6), meninges (n = 4), kidney (n = 3), and skin (n = 2). Antineutrophil cytoplasmic antibodies (ANCA) were positive in all patients with lung or kidney involvement (n = 6/6), while ANCA were negative in almost all patients without lung or kidney involvement (n = 5/6). Endocrine abnormalities included central diabetes insipidus (CDI, n = 11/12) hypogonadotropic hypogonadism (n = 6/11), adrenocorticotropic hormone deficiency (n = 4/7), thyroid-stimulating hormone deficiency (n = 5/11), and growth hormone deficiency (n = 3/9). Enlarged pituitary gland (n = 6), absence of posterior hyperintense signal on T1-weighed images (n = 11) and hypertrophic cranial pachymeningitis (n = 4) were common radiological manifestations. After treatment, nine patients experienced remission but one died. Pituitary images of 3/4 patients showed size of pituitary lesions decreased. CDI was not alleviated and hypopituitarism remained in two patients. Pituitary involvement in GPA can occur at any time throughout the course of disease, including at the initial presentation. GPA could not be excluded based on negative-ANCA in patients with pituitary abnormality alone. CDI and hypogonadotropic hypogonadism are dominant endocrine abnormalities. Systemic diseases may alleviate and pituitary images may improve after treatment, though the recovery of pituitary function is rare.


Assuntos
Granulomatose com Poliangiite , Doenças da Hipófise , Adulto , Anticorpos Anticitoplasma de Neutrófilos/sangue , Biomarcadores/sangue , Biópsia , Desamino Arginina Vasopressina/uso terapêutico , Feminino , Granulomatose com Poliangiite/sangue , Granulomatose com Poliangiite/diagnóstico por imagem , Granulomatose com Poliangiite/tratamento farmacológico , Granulomatose com Poliangiite/patologia , Terapia de Reposição Hormonal , Hormônios/sangue , Humanos , Imunossupressores/uso terapêutico , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Doenças da Hipófise/sangue , Doenças da Hipófise/diagnóstico por imagem , Doenças da Hipófise/tratamento farmacológico , Doenças da Hipófise/patologia , Indução de Remissão , Estudos Retrospectivos , Tiroxina/uso terapêutico , Tomografia Computadorizada por Raios X , Resultado do Tratamento , Adulto Jovem
14.
J Vet Diagn Invest ; 31(4): 585-587, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31246158

RESUMO

Plasma adrenocorticotropic hormone (ACTH) concentration is used in the diagnosis of pituitary pars intermedia dysfunction (PPID) in horses. We enrolled 10 horses, 5 PPID-positive and 5 PPID-negative, in our study, September 20-22, 2016. On day 0, 5 mL of whole blood was collected into each of 6 EDTA tubes and immediately placed in a refrigerator at 7°C. One tube was centrifuged within 15 min of collection, followed by centrifugation of one tube from each horse at 4, 8, 12, 24, and 36 h following collection. At each time, centrifuged plasma was pipetted into 1.5-mL polypropylene tubes and stored at -80°C. None of the plasma samples were turbid, hemolyzed, or icteric. Plasma was shipped frozen with cold packs overnight to the Animal Health Diagnostic Center of Cornell University (Ithaca, NY) for analysis. The percent change from baseline (PCFB) was reported to standardize the data given that baseline values differed. The mean PCFB was 2.8 (95% confidence interval: -2.9%, 7.0%). Neither refrigeration of whole blood for up to 36 h prior to centrifugation nor freezing affected plasma ACTH concentrations significantly.


Assuntos
Hormônio Adrenocorticotrópico/sangue , Centrifugação/veterinária , Doenças dos Cavalos/sangue , Doenças da Hipófise/veterinária , Adeno-Hipófise Parte Intermédia/patologia , Animais , Doenças dos Cavalos/diagnóstico , Cavalos , Doenças da Hipófise/sangue , Doenças da Hipófise/diagnóstico
15.
Endocrine ; 64(1): 118-121, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30868414

RESUMO

INTRODUCTION: Persistent elevation of thyroid-stimulating hormone (TSH) is common in endocrinology practice in patients undergoing replacement or suppression therapy with levothyroxine sodium (LT4). After examining the causes of this condition, LT4 absorption test is recommended. In this report, we wanted to share our results of LT4 absorption test in patients with elevated TSH levels. MATERIALS-METHODS: The files of patients who presented to our clinic between 2015 and 2018, whose TSH elevation continued despite high-dose LT4 therapy, and who underwent absorption test were reviewed retrospectively. RESULTS: Levothyroxine sodium absorption test was applied to five patients. Absorption test revealed LT4 malabsorption in two patients and pseudomalabsorption in the other three patients. DISCUSSION: When all published pseudomalabsorption cases were considered, it has been stated that at least 2.5 times increase in basal fT4 level may exclude malabsorption. The formula we used has been implemented by Cleveland Clinic since 2014. CONCLUSION: In cases where TSH normalization is not achieved despite high doses of LT4 therapy, LT4 absorption test is an easy test for administration and interpretation and prevents unnecessary medical treatments and examinations.


Assuntos
Hipotireoidismo/sangue , Doenças da Hipófise/sangue , Tireotropina/sangue , Tiroxina/uso terapêutico , Humanos , Hipotireoidismo/tratamento farmacológico , Doenças da Hipófise/tratamento farmacológico , Estudos Retrospectivos
16.
J Endocrinol Invest ; 42(2): 167-173, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29729005

RESUMO

PURPOSE: Osteocalcin (OCN), released from the bone matrix during the resorption phase, in its undercarboxylated form, stimulates testosterone (T) biosynthesis in mouse and a loss-of-function mutation of its receptor was associated with hypergonadotropic hypogonadism in humans. Nevertheless, when population-based studies have explored the OCN-T association, conflicting results have been reported. Hypothesizing that the evidence of a positive association between OCN and T could have been hindered by the preeminent role of a well-functioning hypothalamus-pituitary axis in promoting T biosynthesis, we explored this association in men with chronic spinal cord injury (SCI), exhibiting high prevalence of non-hypergonadotropic androgen deficiency. METHODS: Fifty-five consecutive men with chronic SCI underwent clinical/biochemical evaluations, including measurements of total T (TT), OCN and 25(OH)D levels. Free T (FT) levels were calculated by the Vermeulen formula. Comorbidity was scored by Charlson comorbidity index (CCI). RESULTS: A biochemical androgen deficiency (TT < 300 ng/dL) was observed in 15 patients (27.3%). TT was positively correlated with OCN, 25(OH)D and leisure time physical activity and negatively correlated with age, BMI and CCI. OCN was also positively correlated with calculated FT and negatively correlated with BMI and HOMA-IR. At the multiple linear regression analyses, a positive association of OCN with TT and calculated FT persisted after adjustment for confounders. CONCLUSIONS: The positive association here found between OCN and T levels in men with chronic SCI reinforces the notion that a bone-testis axis is also functioning in humans and suggests that it can be unmasked when the preeminent hypothalamic-pituitary regulation of T production is impaired.


Assuntos
Osteocalcina/sangue , Doenças da Hipófise/sangue , Traumatismos da Medula Espinal/sangue , Testosterona/sangue , Adulto , Idoso , Humanos , Masculino , Pessoa de Meia-Idade , Doenças da Hipófise/complicações , Traumatismos da Medula Espinal/complicações , Vitamina D/análogos & derivados , Vitamina D/sangue
17.
J Neurol Sci ; 395: 153-158, 2018 12 15.
Artigo em Inglês | MEDLINE | ID: mdl-30321796

RESUMO

INTRODUCTION: Current literature is poor with respect to well conducted prospective studies of hypothalamic pituitary axis (HPA) dysfunction in tubercular meningitis (TBM). As hormonal deficiencies are associated with poor clinical outcome in various neurological and non-neurological disorders, we prospectively evaluated the hypothalamic pituitary axis (HPA) dysfunction in TBM. PATIENTS AND METHODS: Present study included newly diagnosed drug naive TBM patients (n = 63) at a tertiary care centre in Northern India. All patients underwent detailed clinical, radiological evaluation (Gadolinium enhanced magnetic resonance imaging of brain) and HPA hormonal profiles (electrochemiluminescence assay) both at initial presentation and at six month follow up. All the data was recorded on a predesigned proforma. RESULTS: 77.8% patients had definite and 22.2% had highly probable TBM. 84.2% of patients had pituitary hormonal abnormalities at presentation. These included hyperprolactinemia (49.2%), secondary adrenal deficiency (42.9%), secondary hypogonadism (38.1%) and central hypothyroidism (9.5%). At follow up, 42.1% patients had HPA abnormalities [hyperprolactinemia (13.2%), secondary hypogonadism (15.8%), secondary adrenal deficiency (10.5%) and central hypothyroidism (10.5%)]. On multivariate logistic regression analysis, secondary hypocortisolism (Odd ratio: 4.042; 95% CI = 1.074-15.22; P = .039) was associated with poor outcome in TBM. CONCLUSION: Abnormalities of HPA are common in TBM. Patients with TBM should be evaluated for dysfunction of HPA and treated accordingly.


Assuntos
Doenças Hipotalâmicas/sangue , Doenças Hipotalâmicas/diagnóstico por imagem , Doenças da Hipófise/sangue , Doenças da Hipófise/diagnóstico por imagem , Tuberculose Meníngea/sangue , Tuberculose Meníngea/diagnóstico por imagem , Adulto , Antituberculosos/uso terapêutico , Biomarcadores/sangue , Biomarcadores/líquido cefalorraquidiano , Encéfalo/diagnóstico por imagem , Feminino , Seguimentos , Hormônios/sangue , Humanos , Doenças Hipotalâmicas/complicações , Índia , Masculino , Doenças da Hipófise/complicações , Estudos Prospectivos , Centros de Atenção Terciária , Resultado do Tratamento , Tuberculose Meníngea/complicações , Tuberculose Meníngea/tratamento farmacológico
18.
Andrologia ; 50(9): e13107, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30039560

RESUMO

The aim of this study was to evaluate the hypothalamic-pituitary-gonadal axis functionality on a bodybuilding competitioner before, during and after the use of anabolic-androgenic steroids. A young healthy man was followed up for 4 months. The subject reported his drug administration protocol through periodic interviews and performed laboratory tests to monitor the function of his hypothalamic-pituitary-gonadal axis. Time 1 (before the steroids use) shows all hormones levels (follicle-stimulating hormone = 4,2 mUI/ml, luteinising hormone = 3,7 mUI/ml and total testosterone = 5,7 ng/ml) within reference values. In Time 2, after 8 weeks on steroids abuse, a complete hypothalamic-pituitary-gonadal axis derangement is evident with noticeable negative feedback (follicle-stimulating hormone = 1,47 mUI/ml, luteinising hormone = 0,1 mUI/ml and total testosterone = 1,47 ng/ml). At the third moment (40 days after Time 2), we can see a tendency to recovery, however, the serum levels of the investigated hormones were still considerably lower than the baseline values. At the end, we could conclude that the use of anabolic-androgenic steroids, at supraphysiological dosages, even for a short time (8 weeks), causes severe disorder in the hypothalamic-pituitary-gonadal axis. The endogenous testosterone synthesis was severely compromised by important decline in serum luteinising hormone levels.


Assuntos
Anabolizantes/efeitos adversos , Hormônio Foliculoestimulante/sangue , Hormônio Luteinizante/sangue , Congêneres da Testosterona/efeitos adversos , Testosterona/sangue , Anabolizantes/administração & dosagem , Humanos , Masculino , Doenças da Hipófise/sangue , Doenças da Hipófise/induzido quimicamente , Doenças Testiculares/sangue , Doenças Testiculares/induzido quimicamente , Congêneres da Testosterona/administração & dosagem , Adulto Jovem
19.
Clin Endocrinol (Oxf) ; 88(6): 908-919, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29566437

RESUMO

BACKGROUND: Bimagrumab is a human monoclonal antibody inhibitor of activin type II receptors (ActRII), with anabolic action on skeletal muscle mass by blocking binding of myostatin and other negative regulators of muscle growth. Bimagrumab is under evaluation for muscle wasting and associated functional loss in hip fracture and sarcopenia, and in obesity. Bimagrumab also blocks other endogenous ActRII ligands, such as activins, which act on the neurohormonal axes, pituitary, gonads and adrenal glands. AIM: To evaluate the effect of bimagrumab on the pituitary-gonadal and pituitary-adrenal axes in humans. METHODS: Healthy men and women, aged 55 to 75 years, received bimagrumab intravenously 10 mg/kg or placebo on Day 1 and Day 29. Pituitary-gonadal and pituitary-adrenal functions were evaluated with basal hormone measurement and standard gonadotropin-releasing hormone (GnRH) and adrenocorticotropic hormone (ACTH) stimulation tests at baseline, Week 8 and at the end of study (EOS)-Week 20. RESULTS: At Week 8, follicle-stimulating hormone (FSH) levels were reduced by 42.16 IU/L (P < .001) and luteinizing hormone (LH) levels were increased by 2.5 IU/L (P = .08) over placebo in response to bimagrumab in women but not in men. Effects that were reversible after bimagrumab was cleared. Gonadal and adrenal androgen levels were not affected by exposure to bimagrumab. CONCLUSION: Bimagrumab alters the function of pituitary gonadotroph cells, consistent with blockade of activin on local ActRII. This effect is reversible with clearance of bimagrumab. Bimagrumab did not impact gonadal and adrenal androgen secretion.


Assuntos
Receptores de Activinas Tipo II/metabolismo , Anticorpos Bloqueadores/uso terapêutico , Anticorpos Monoclonais/uso terapêutico , Hipófise/efeitos dos fármacos , Hipófise/metabolismo , Hormônio Adrenocorticotrópico/sangue , Idoso , Androgênios/sangue , Anticorpos Monoclonais Humanizados , Cromatografia Líquida , Método Duplo-Cego , Estradiol/sangue , Feminino , Voluntários Saudáveis , Humanos , Hidrocortisona/sangue , Masculino , Pessoa de Meia-Idade , Doenças da Hipófise/sangue , Doenças da Hipófise/tratamento farmacológico , Efeito Placebo , Pós-Menopausa , Espectrometria de Massas em Tandem , Testosterona/sangue
20.
Clin Biochem ; 54: 78-84, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29486187

RESUMO

OBJECTIVE: The clinical presentation of pituitary dysfunction is typically variable and may often be insidious, resulting in delayed diagnosis by up to decades. The complexity of presentation and difficulty in pattern recognition of first line hormone tests result in challenges in early diagnosis of this condition. The aim of this study was to determine the impact of reflective testing and interpretive commenting on the early detection and management of such cases from primary care. METHODS: Prospective audit over 12 months in which first line pituitary target organ hormones were identified via a reflex algorithm in the laboratory information system. Selected tests were reviewed by a laboratory clinician and decision made on reflective testing and interpretive commenting based on available clinical information and previous result trends. Patients who had a laboratory intervention were followed up to determine the clinical outcome. RESULTS: Out of 1099 patients identified, additional testing was made for 214. Interpretative comments were subsequently added to reports of 196 patients, 48 (25%) of whom were referred to endocrinology and 35 (73%) of these were directly related to the laboratory intervention. Eleven other patients had outcomes related to the intervention. Pituitary related conditions (insufficiency and/or adenoma) were found in 29 patients, 24 of which were identified as a result of laboratory intervention. CONCLUSIONS: This study highlights the clinical value of laboratory intervention in aiding early detection of pituitary dysfunction and may avoid the disease burden of delayed management.


Assuntos
Algoritmos , Sistemas de Informação em Laboratório Clínico , Auditoria Médica , Doenças da Hipófise/sangue , Doenças da Hipófise/diagnóstico , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Doenças da Hipófise/epidemiologia , Estudos Prospectivos
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