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2.
Pituitary ; 22(3): 212-219, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31020506

RESUMO

PURPOSE: Traumatic brain injury (TBI) is a major worldwide cause of disability, often burdening young people with serious lifelong health problems. A frequent clinical complication is post-traumatic hypopituitarism (PTHP) manifesting in several hypothalamus-pituitary axes. The head trauma-induced mechanisms underlying PTHP remain largely unknown. Several hypotheses have been proposed including direct damage to the pituitary gland and hypothalamus, vascular events and autoimmunity. This review aims to provide a summary of the currently limited number of studies exploring hypothalamus-pituitary dysfunction in experimental animal TBI models. RESULTS: Although the impact of different forms of TBI on a number of hypothalamus-pituitary axes has been investigated, consequences for pituitary tissue and function have only scarcely been described. Moreover, mechanisms underlying the endocrine dysfunctions remain under explored. CONCLUSIONS: Studies on TBI-induced pituitary dysfunction are still scarce. More research is needed to acquire mechanistic insights into the pathophysiology of PTHP which may eventually open up the horizon toward better treatments, including pituitary-regenerative approaches.


Assuntos
Lesões Encefálicas Traumáticas/metabolismo , Hipopituitarismo/metabolismo , Doenças da Hipófise/metabolismo , Hipófise/metabolismo , Animais , Lesões Encefálicas Traumáticas/patologia , Humanos , Hipopituitarismo/patologia , Modelos Animais , Doenças da Hipófise/patologia , Hipófise/patologia
3.
Pituitary ; 22(3): 229-235, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30825117

RESUMO

PURPOSE: To estimate the total number of articles on traumatic brain injury (TBI)-related hypopituitarism and patients (including children and adolescents) with such disorder that were published until now, particularly after the author's review published on April 2000. METHODS: Review of the literature retrievable on PubMed. RESULTS: TBI-related hypopituitarism accounts for 7.2% of the whole literature on hypopituitarism published during the 18 years and half between May 2000 and October 2018. As a result, the total number of patients with TBI-related hypopituitarism now approximates 2200. A number of patients, both adults and children, continue to be published as case reports. Articles, including reviews and guidelines, have been published in national languages in order to maximize locally the information on TBI-related hypopituitarism. TBI-related hypopituitarism has been also studied in animals (rodents, cats and dogs). CONCLUSIONS: The interest for the damage suffered by anterior pituitary as a result of TBI continues to remain high both in the adulthood and childhood.


Assuntos
Lesões Encefálicas Traumáticas/patologia , Hipopituitarismo/patologia , Doenças da Hipófise/patologia , Hipófise/patologia , Animais , Lesões Encefálicas Traumáticas/metabolismo , Humanos , Hipopituitarismo/metabolismo , Doenças da Hipófise/metabolismo , Hipófise/metabolismo
4.
Pituitary ; 22(3): 220-228, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30734143

RESUMO

PURPOSE: This review aimed to evaluate the data underlying the pathophysiology of TBI-induced hypothalamo-pituitary dysfunction. METHODS: Recent literature about the pathophysiology of TBI-induced hypothalamo-pituitary dysfunction reviewed. RESULTS: Traumatic brain injury (TBI) is a worldwide epidemic that frequently leads to death; TBI survivors tend to sustain cognitive, behavioral, psychological, social, and physical disabilities in the long term. The most common causes of TBI include road accidents, falls, assaults, sports, work and war injuries. From an endocrinological perspective, TBIs are important, because they can cause pituitary dysfunction. Although TBI-induced pituitary dysfunction was first reported a century ago, most of the studies that evaluate this disorder were published after 2000. TBI due to sports and blast injury-related pituitary dysfunction is generally underreported, due to limited recognition of the cases. CONCLUSION: The underlying pathophysiology responsible for post-TBI pituitary dysfunction is not clear. The main proposed mechanisms are vascular injury, direct traumatic injury to the pituitary gland, genetic susceptibility, autoimmunity, and transient medication effects.


Assuntos
Lesões Encefálicas Traumáticas/metabolismo , Lesões Encefálicas Traumáticas/patologia , Doenças da Hipófise/metabolismo , Doenças da Hipófise/patologia , Animais , Humanos , Hipófise/metabolismo , Hipófise/patologia
5.
Pituitary ; 22(3): 283-295, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30746590

RESUMO

PURPOSE: It is estimated that approximately 69 million individuals worldwide will sustain a TBI each year, which accounts for substantial morbidity and mortality in both children and adults. TBI may lead to significant neuroendocrine changes, if the delicate pituitary is ruptured. In this review, we focus on the anterior pituitary hormonal changes in the acute post-TBI period and we present the evidence supporting the need for screening of anterior pituitary function in the early post-TBI time along with current suggestions regarding the endocrine assessment and management of these patients. METHODS: Original systematic articles with prospective and/or retrospective design studies of acute TBI were included, as were review articles and case series. RESULTS: Although TBI may motivate an acute increase of stress hormones, it may also generate a wide spectrum of anterior pituitary hormonal deficiencies. The frequency of post-traumatic anterior hypopituitarism (PTHP) varies according to the severity, the type of trauma, the time elapsed since injury, the study population, and the methodology used to diagnose pituitary hormone deficiency. Early neuroendocrine abnormalities may be transient, but additional late ones may also appear during the course of rehabilitation. CONCLUSIONS: Acute hypocortisolism should be diagnosed and managed promptly, as it can be life-threatening, but currently there is no evidence to support treatment of acute GH, thyroid hormones or gonadotropins deficiencies. However, a more comprehensive assessment of anterior pituitary function should be undertaken both in the early and in the post-acute phase, since ongoing hormone deficiencies may adversely affect the recovery and quality of life of these patients.


Assuntos
Lesões Encefálicas Traumáticas/metabolismo , Lesões Encefálicas Traumáticas/patologia , Animais , Lesões Encefálicas/metabolismo , Lesões Encefálicas/patologia , Humanos , Hipopituitarismo/metabolismo , Hipopituitarismo/patologia , Doenças da Hipófise/metabolismo , Doenças da Hipófise/patologia , Qualidade de Vida
6.
Medicine (Baltimore) ; 98(2): e13853, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30633157

RESUMO

RATIONALE: Langerhans cell histiocytosis (LCH) is characterized by clonal proliferation of immature dendritic cells, mainly affects children. LCH in adult sellar region is extremely rare. In literature, optimal treatments remain unclear and only a few cases of LCH were treated using surgery. Here, we present a rare case of isolated hypothalamic-pituitary LHC in female adult. We focused on elucidating the clinical manifestations and immunohistochemical features of LCH, and exploring the proper treatment in adults. PATIENT CONCERNS: A 50-year-old woman was admitted to our hospital, presenting with polydipsia and polyuria for over 3 months. DIAGNOSES: Radiological studies revealed lesions (0.5 × 0.9 × 0.4 cm) on posterior pituitary and enlarged pituitary stalk, which was moderately enhanced on contrast magnetic resonance imaging (MRI) of sellar region. In biopsy, pathological examination of Langerhans cells were observed with positive S-100 protein and Ki-67 antigen markers, findings were sufficient to establish a diagnosis of central nervous system (CNS) LCH. INTERVENTIONS: The patient with LCH restricted in the sellar region received both surgery and chemotherapy. Gamma knife radiosurgery was performed after diagnosed as central diabetes insipidus (CDI) induced by pituitary lesion. And tumorectomy was performed 5 years later. However, in the latest MRI in 2017, the nodular shadow became larger (about 1.4 cm), chemotherapy and further systemic therapy were given. OUTCOMES: At 12-month follow-up, no local reoccurrence was noticed. LESSONS: For LCH, though difficult to be diagnosed and none defined standard therapeutic approach to adults, surgery should be considered if there are neurological symptoms or histological diagnosis. The present study showed that some manifestations can be meaningful when central nervous system (CNS) is involved. For complex diseases in the sellar region, multi-disciplinary team (MDT) model of diagnosis and treatment should be helpful for better clinical efficacy.


Assuntos
Histiocitose de Células de Langerhans/diagnóstico , Histiocitose de Células de Langerhans/terapia , Doenças da Hipófise/diagnóstico , Doenças da Hipófise/terapia , Terapia Combinada , Diagnóstico Diferencial , Feminino , Histiocitose de Células de Langerhans/metabolismo , Histiocitose de Células de Langerhans/patologia , Humanos , Pessoa de Meia-Idade , Doenças da Hipófise/metabolismo , Doenças da Hipófise/patologia , Hipófise/diagnóstico por imagem , Hipófise/metabolismo , Hipófise/patologia
7.
Endocrinology ; 159(12): 4043-4055, 2018 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-30395240

RESUMO

Ca2+ influx through voltage-gated Ca2+ channels (VGCCs) plays a key role in GH secretion. In this review, we summarize the current state of knowledge regarding the physiology and molecular machinery of VGCCs in pituitary somatotrophs. We next discuss the possible involvement of Ca2+ channelopathies in pituitary disease and the potential use of Ca2+ channel blockers to treat pituitary disease. Various types of VGCCs exist in pituitary cells. However, because L-type Ca2+ channels (LTCCs) contribute the major component to Ca2+ influx in somatotrophs, lactotrophs, and corticotrophs, we focused on these channels. An increasing number of studies in recent years have linked genetic missense mutations in LTCCs to diseases of the human cardiovascular, nervous, and endocrine systems. These disease-associated genetic mutations occur at homologous functional positions (activation gates) in LTCCs. Thus, it is plausible that similar homologous missense mutations in pituitary LTCCs can cause abnormal hormone secretion and underlying pituitary disorders. The existence of LTCCs in pituitary cells opens questions about their sensitivity to dihydropyridines, a group of selective LTCC blockers. The dihydropyridine sensitivity of pituitary cells, as with any other excitable cell, depends primarily on two parameters: the pattern of their electrical activity and the dihydropyridine sensitivity of their LTCC isoforms. These two parameters are discussed in detail in relation to somatotrophs. These discussions are also relevant to lactotrophs and corticotrophs. High dihydropyridine sensitivity may facilitate their use as drugs to treat pituitary oversecretion disorders such as acromegaly, hyperprolactinemia, and Cushing disease.


Assuntos
Canais de Cálcio/metabolismo , Canalopatias/terapia , Terapia de Alvo Molecular , Doenças da Hipófise/terapia , Adeno-Hipófise/metabolismo , Somatotrofos/metabolismo , Acromegalia/etiologia , Acromegalia/terapia , Animais , Cálcio/fisiologia , Canalopatias/etiologia , Canalopatias/metabolismo , Humanos , Hiperprolactinemia/etiologia , Hiperprolactinemia/terapia , Terapia de Alvo Molecular/métodos , Terapia de Alvo Molecular/tendências , Hipersecreção Hipofisária de ACTH/etiologia , Hipersecreção Hipofisária de ACTH/terapia , Doenças da Hipófise/etiologia , Doenças da Hipófise/metabolismo , Adeno-Hipófise/patologia , Somatotrofos/patologia
8.
Endocr J ; 65(9): 935-942, 2018 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-29952338

RESUMO

Diagnosis of adrenal insufficiency requires evaluation by dynamic stimulation tests. The insulin tolerance test (ITT) is accepted as the gold-standard test for the evaluation of hypothalamo-pituitary-adrenal (HPA) axis but the test is unpleasant and dangerous. Although it takes more time, glucagon stimulation test (GST) is a good alternative to ITT. The primary aim of this study was to compare the ITT and GSTs in the evaluation of HPA axe in patients with pituitary disorders. We conducted a prospective study in which ITT and GST were performed within 7 days in 81 patients. Serum cortisol was measured. We divided our population in Group 1 (G1): Adrenal Insufficiency (Peak cortisol under ITT <200 ng/mL) and Group 2 (G2): normal response (Peak cortisol under ITT >200 ng/mL). Receiver-operating characteristic (ROC) analysis was performed to identify the thresholds for GST. The mean peak of cortisol under GST was not significantly different from that obtained after ITT in the whole cohort (182.67 ± 89.07 ng/mL vs. 179.75 ± 79.01 ng/mL), and it was significantly reduced in patients of G1 (p < 10-3). ROC curve analysis showed that the best diagnostic accuracy was obtained with a peak cortisol cut-off to GST of 167 ng/mL (sensitivity, 89%; specificity, 79%). Using this cut-off, 86.4% of the patients were correctly classified. In our prospective series, GST is a potential accurate and safe alternative test for the assessment HPA. Test-specific cut-offs should be applied to avoid misinterpretation.


Assuntos
Insuficiência Adrenal/diagnóstico , Glucagon/farmacologia , Hidrocortisona/sangue , Sistema Hipotálamo-Hipofisário/efeitos dos fármacos , Testes de Função Adreno-Hipofisária/normas , Sistema Hipófise-Suprarrenal/efeitos dos fármacos , Adolescente , Insuficiência Adrenal/sangue , Adulto , Criança , Estudos de Coortes , Feminino , Humanos , Hidrocortisona/normas , Sistema Hipotálamo-Hipofisário/fisiologia , Masculino , Pessoa de Meia-Idade , Doenças da Hipófise/diagnóstico , Doenças da Hipófise/metabolismo , Testes de Função Adreno-Hipofisária/métodos , Sistema Hipófise-Suprarrenal/fisiologia , Padrões de Referência , Estimulação Química , Adulto Jovem
9.
Endocr Rev ; 39(4): 440-488, 2018 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-29684108

RESUMO

Neuroendocrinology of bone is a new area of research based on the evidence that pituitary hormones may directly modulate bone remodeling and metabolism. Skeletal fragility associated with high risk of fractures is a common complication of several pituitary diseases such as hypopituitarism, Cushing disease, acromegaly, and hyperprolactinemia. As in other forms of secondary osteoporosis, pituitary diseases generally affect bone quality more than bone quantity, and fractures may occur even in the presence of normal or low-normal bone mineral density as measured by dual-energy X-ray absorptiometry, making difficult the prediction of fractures in these clinical settings. Treatment of pituitary hormone excess and deficiency generally improves skeletal health, although some patients remain at high risk of fractures, and treatment with bone-active drugs may become mandatory. The aim of this review is to discuss the physiological, pathophysiological, and clinical insights of bone involvement in pituitary diseases.


Assuntos
Fraturas Ósseas , Osteoporose , Doenças da Hipófise , Animais , Fraturas Ósseas/diagnóstico , Fraturas Ósseas/tratamento farmacológico , Fraturas Ósseas/etiologia , Fraturas Ósseas/metabolismo , Humanos , Osteoporose/diagnóstico , Osteoporose/tratamento farmacológico , Osteoporose/etiologia , Osteoporose/metabolismo , Doenças da Hipófise/complicações , Doenças da Hipófise/diagnóstico , Doenças da Hipófise/tratamento farmacológico , Doenças da Hipófise/metabolismo
10.
Exp Clin Endocrinol Diabetes ; 126(6): 349-356, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29475205

RESUMO

INTRODUCTION: Endocrine disorders of the pituitary axes are frequent in patients with hemodialysis (CKD5D). The aim of this multicenter study (Leipzig (L), Quedlinburg and Blankenburg in the Harz region (Hz)) in CKD5D patients was to evaluate influences of CKD5D related factors, morphological and biochemical parameters, and serum iodine and prolactin concentrations on the pituitary-thyroid axis. PATIENTS AND METHODS: 170 patients (L n=58; Hz n=112) were included in this prospective, non-interventional, cross-sectional study. Mann-Whitney-U-test and bivariate correlation analyses with Spearman-Rho test (r correlation coefficient) were used in statistical analysis. RESULTS: TSH was higher in patients with prolactin concentrations>370 mIU/l (p=0.013), in patients with high flux membranes (p=0.0013) and in patients with longer dialysis vintage (p=0.04). Median iodine serum concentrations were slightly elevated in the Leipzig cohort (p=0.001) and correlated with fT4 (p<0.001, r=0.43) and albumin (p=0.001, r=0.245) but not with morphological signs. Albumin was correlated with fT3 (p<0.001, r=0.339) and fT4 (p<0.001, r=0.421). Prolactin was correlated with residual excretion rate (p=0.001, r=- 0.303) and thyroid volume (p=0.027, r=0.217). CONCLUSIONS: In the assessment of the thyroid status in CKD5D patients, the synopsis of the clinical and nutritional status, comorbidities, ultrasound of the thyroid gland and laboratory results is necessary for further intervention with hormone replacement. Standardized reference values of the pituitary-thyroid axis should be critically evaluated and are still lacking in CKD5D.


Assuntos
Falência Renal Crônica , Hipófise/fisiopatologia , Prolactina/metabolismo , Diálise Renal , Glândula Tireoide/fisiopatologia , Idoso , Idoso de 80 Anos ou mais , Estudos Transversais , Doenças Endêmicas , Feminino , Alemanha/epidemiologia , Humanos , Falência Renal Crônica/epidemiologia , Falência Renal Crônica/metabolismo , Falência Renal Crônica/fisiopatologia , Falência Renal Crônica/terapia , Masculino , Pessoa de Meia-Idade , Doenças da Hipófise/complicações , Doenças da Hipófise/epidemiologia , Doenças da Hipófise/metabolismo , Testes de Função Hipofisária , Hipófise/metabolismo , Diálise Renal/estatística & dados numéricos , Doenças da Glândula Tireoide/complicações , Doenças da Glândula Tireoide/epidemiologia , Doenças da Glândula Tireoide/metabolismo , Testes de Função Tireóidea , Glândula Tireoide/metabolismo
11.
Medicine (Baltimore) ; 97(2): e9084, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29480822

RESUMO

Pituitary stalk interruption syndrome (PSIS) is associated with simultaneous or subsequent pituitary hormone deficiencies (PHDs). Although the clinical features of multiple PHDs are well known, the status of the thyrotrophic axis in PSIS has not been thoroughly investigated.The clinical data of 89 PSIS patients and 34 Sheehan syndrome (SS) patients were retrospectively analyzed.The prevalence of central hypothyroidism in the PSIS patients and the SS patients was 79.8% and 70.6%, respectively. The thyroid-stimulating hormone (TSH) levels in the PSIS patients were significantly higher in comparison with the SS patients (5.13 ±â€Š3.40 vs 1.67 ±â€Š1.20 mU/L, P < .05). TSH elevation (8.79 ±â€Š3.17 mU/L) was noticed in 29 of 71 (40.85%) hypothyroid PSIS patients but not in the 24 hypothyroid SS patients. The TSH levels in the hypothyroid PSIS patients were significantly higher in comparison with the euthyroid PSIS patients (5.42 ±â€Š3.67 vs 3.66 ±â€Š1.50 mU/L). Thyroid hormone replacement significantly reduced the TSH levels in the PSIS patients with elevated TSH levels from 7.24 ±â€Š0.98 to 1.67 ±â€Š1.51 mU/L (P < .05). The logistic regression analysis suggested that TSH level was not significantly associated with pituitary stalk status and height of the anterior pituitary gland.PSIS is a newly recognized cause of central hypothyroidism. The proportion and amplitude of TSH elevations are higher in PSIS than in other causes of central hypothyroidism.


Assuntos
Doenças da Hipófise/metabolismo , Tireotropina/metabolismo , Adulto , Feminino , Terapia de Reposição Hormonal , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Doenças da Hipófise/diagnóstico por imagem , Doenças da Hipófise/tratamento farmacológico , Doenças da Hipófise/epidemiologia , Hipófise/diagnóstico por imagem , Hipófise/efeitos dos fármacos , Hipófise/metabolismo , Prevalência , Estudos Retrospectivos , Tireotropina/administração & dosagem , Adulto Jovem
12.
Horm Metab Res ; 50(4): 296-302, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29458219

RESUMO

Primary hypophysitis (PH) is a rare disease with a poorly-defined natural history. Our aim was to characterise patients with PH at presentation and during prolonged follow-up. Observational retrospective study of 22 patients was conducted from 3 centres. In 14 patients, PH was confirmed histologically and in the remaining 8 clinically, after excluding secondary causes of hypophysitis. All patients had hormonal and imaging investigations before any treatment. Median follow up was 48 months (25-75%: 3-60). There was a female predominance with a female/male ratio: 3.4:1. Eight out of 22 patients had another autoimmune disease. Headaches and gonadal dysfunction were the most common symptoms. Five patients presented with panhypopituitarism; 17 patients had anterior pituitary deficiency, and 7 had diabetes insipidus. At presentation, 9 patients were treated surgically, 5 received replacement hormonal treatment, and 8 high-dose glucocorticoids from whom 5 in association with other immunosuppressive agents. Six patients showed complete recovery of pituitary hormonal deficiencies while 6 showed a partial recovery during a 5-year follow-up period. No difference was found between patients treated with surgery and those treated medically. The overall relapse rate was 18%. PH can be manifested with a broad spectrum of clinical and hormonal disturbances. Long-term follow-up is required to define the natural history of the disease and response to treatment, since pituitary hormonal recovery or relapse may appear many years after initial diagnosis. We suggest that surgery and immunosuppressive therapy be reserved for exceptional cases.


Assuntos
Sistema Endócrino/fisiopatologia , Hipofisite/patologia , Imagem por Ressonância Magnética/métodos , Doenças da Hipófise/patologia , Hormônios Hipofisários/metabolismo , Acuidade Visual/fisiologia , Adulto , Terapia Combinada , Feminino , Humanos , Hipofisite/diagnóstico por imagem , Hipofisite/metabolismo , Hipofisite/terapia , Masculino , Pessoa de Meia-Idade , Doenças da Hipófise/diagnóstico por imagem , Doenças da Hipófise/metabolismo , Doenças da Hipófise/terapia , Estudos Retrospectivos
13.
Am J Vet Res ; 79(2): 199-210, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29359976

RESUMO

OBJECTIVE To identify signs of tissue-specific cortisol activity in samples of suspensory ligament (SL) and neck skin tissue from horses with and without pituitary pars intermedia dysfunction (PPID). SAMPLE Suspensory ligament and neck skin tissue samples obtained from 26 euthanized horses with and without PPID. PROCEDURES Tissue samples were collected from 12 horses with and 14 horses without PPID (controls). Two control horses had received treatment with dexamethasone; data from those horses were not used in statistical analyses. The other 12 control horses were classified as old horses (≥ 14 years old) and young horses (≤ 9 years old). Standard histologic staining, staining for proteoglycan accumulation, and immunostaining of SL and neck skin tissue sections for glucocorticoid receptors, insulin, 11ß hydroxysteroid dehydrogenase type 1, and 11ß hydroxysteroid dehydrogenase type 2 were performed. Findings for horses with PPID were compared with findings for young and old horses without PPID. RESULTS Compared with findings for old and young control horses, there were significantly more cells stained for glucocorticoid receptors in SL samples and for 11 ß hydroxysteroid dehydrogenase type 1 in SL and skin tissue samples from horses with PPID. Insulin could not be detected in any of the SL or skin tissue samples. Horses with PPID had evidence of SL degeneration with significantly increased proteoglycan accumulation. Neck skin tissue was found to be significantly thinner in PPID-affected horses than in young control horses. CONCLUSIONS AND CLINICAL RELEVANCE Results suggested that tissue-specific dysregulation of cortisol metabolism may contribute to the SL degeneration associated with PPID in horses.


Assuntos
Doenças dos Cavalos/metabolismo , Hidrocortisona/metabolismo , Ligamentos/patologia , Doenças da Hipófise/veterinária , Adeno-Hipófise Parte Intermédia/fisiopatologia , Animais , Dexametasona , Feminino , Doenças dos Cavalos/patologia , Cavalos , Ligamentos/metabolismo , Masculino , Doenças da Hipófise/metabolismo , Doenças da Hipófise/patologia , Adeno-Hipófise Parte Intermédia/metabolismo
14.
Pituitary ; 20(6): 624-634, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28822018

RESUMO

OBJECTIVE: The variation in reported prevalence of growth hormone deficiency (GHD) post subarachnoid haemorrhage (SAH) is mainly due to methodological heterogeneity. We report on the prevalence of GHD in a large cohort of patients following SAH, when dynamic and confirmatory pituitary hormone testing methods are systematically employed. DESIGN: In this cross-sectional study, pituitary function was assessed in 100 patients following SAH. Baseline pituitary hormonal profile measurement and glucagon stimulation testing (GST) was carried out in all patients. Isolated GHD was confirmed with an Arginine stimulation test and ACTH deficiency was confirmed with a short synacthen test. RESULTS: The prevalence of hypopituitarism in our cohort was 19% and the prevalence of GHD was 14%. There was no association between GHD and the clinical or radiological severity of SAH at presentation, treatment modality, age, or occurrence of vasospasm. There were statistically significant differences in terms of Glasgow Outcome Scale (GOS; p = 0.03) between patients diagnosed with GHD and those without. Significant inverse correlations between GH peak on GST with body mass index (BMI) and waist hip ratio (WHR) was also noted (p < 0.0001 and p < 0.0001 respectively). CONCLUSION: Using the current testing protocol, the prevalence of GHD detected in our cohort was 14%. It is unclear if the BMI and WHR difference observed is truly due to GHD or confounded by the endocrine tests used in this protocol. There is possibly an association between the development of GHD and worse GOS score. Routine endocrine screening of all SAH survivors with dynamic tests is time consuming and may subject many patients to unnecessary side-effects. Furthermore the degree of clinical benefit derived from growth hormone replacement in this patient group, remains unclear. Increased understanding of the most appropriate testing methodology in this patient group and more importantly which SAH survivors would derive most benefit from GHD screening is required.


Assuntos
Hormônio do Crescimento Humano/metabolismo , Hemorragia Subaracnóidea/epidemiologia , Hemorragia Subaracnóidea/patologia , Adulto , Estudos Transversais , Feminino , Hormônio do Crescimento Humano/deficiência , Humanos , Hipopituitarismo/epidemiologia , Hipopituitarismo/metabolismo , Hipopituitarismo/patologia , Masculino , Pessoa de Meia-Idade , Doenças da Hipófise/epidemiologia , Doenças da Hipófise/metabolismo , Doenças da Hipófise/patologia , Hipófise/metabolismo , Hipófise/patologia , Prevalência , Hemorragia Subaracnóidea/metabolismo
15.
Endocrine ; 57(3): 474-480, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28795329

RESUMO

BACKGROUND: Copeptin (pre-proAVP) secreted in equimolar amounts with vasopressin closely reflects vasopressin release. Copeptin has been shown to subtly mirror stress potentially mediated via corticotrophin-releasing hormone. To further test a potential direct interaction of corticotrophin-releasing hormone with copeptin release, which could augment vasopressin effects on pituitary function, we investigated copeptin response to corticotrophin-releasing hormone. PATIENTS AND METHODS: Cortisol, adrenocorticotropin and copeptin were measured in 18 healthy controls and 29 subjects with a history of pituitary disease during standard corticotrophin-releasing hormone test. RESULTS: Patients with previous pituitary disease were subdivided in a group passing the test (P1, n = 20) and failing (P2, n = 9). The overall copeptin response was higher in controls than in subjects with pituitary disease (area under the curve, p = 0.04 for P1 + P2) with a maximum increase in controls from 3.84 ± 2.86 to 12.65 ± 24.87 pmol/L at 30 min, p < 0.05. In contrast, both groups of pituitary patients lacked a significant copeptin response to corticotrophin-releasing hormone, and even in P1, where adrenocorticotropin concentrations increased fourfold (mean, 21.48 vs. 91.53 pg/mL, p < 0.01), copeptin did not respond (e.g., 4.35 ± 5.81 vs. 5.36 ± 6.79 pmol/L, at 30 min, p = ns). CONCLUSIONS: Corticotrophin-releasing hormone is able to stimulate copeptin release in healthy controls suggesting a direct interaction of corticotrophin-releasing hormone and vasopressin/vasopressin. Interestingly, this relation is altered already in the group of pituitary patients who pass the standard corticotrophin-releasing hormone test indicating (1) the corticotrophin-releasing hormone-adrenocorticotropin-cortisol response is largely independent from the vasopressin system, but (2) the corticotrophin-releasing hormone-vasopressin interaction reflected by copeptin may be much more sensitive to reveal subtle alterations in the regulation of pituitary function.


Assuntos
Hormônio Liberador da Corticotropina/metabolismo , Glicopeptídeos/metabolismo , Sistema Hipotálamo-Hipofisário/metabolismo , Doenças da Hipófise/metabolismo , Hipófise/metabolismo , Receptores de Hormônio Liberador da Corticotropina/agonistas , Transdução de Sinais , Córtex Suprarrenal/efeitos dos fármacos , Córtex Suprarrenal/metabolismo , Córtex Suprarrenal/fisiopatologia , Hormônio Adrenocorticotrópico/sangue , Hormônio Adrenocorticotrópico/metabolismo , Adulto , Biomarcadores/sangue , Hormônio Liberador da Corticotropina/genética , Hormônio Liberador da Corticotropina/farmacologia , Feminino , Glicopeptídeos/sangue , Humanos , Hidrocortisona/sangue , Hidrocortisona/metabolismo , Sistema Hipotálamo-Hipofisário/efeitos dos fármacos , Sistema Hipotálamo-Hipofisário/fisiopatologia , Imunoensaio , Cinética , Masculino , Pessoa de Meia-Idade , Doenças da Hipófise/sangue , Doenças da Hipófise/fisiopatologia , Hipófise/efeitos dos fármacos , Hipófise/fisiopatologia , Receptores de Hormônio Liberador da Corticotropina/metabolismo , Proteínas Recombinantes/metabolismo , Proteínas Recombinantes/farmacologia , Índice de Gravidade de Doença , Transdução de Sinais/efeitos dos fármacos , Estimulação Química
16.
BMC Endocr Disord ; 17(1): 49, 2017 Aug 04.
Artigo em Inglês | MEDLINE | ID: mdl-28778166

RESUMO

BACKGROUND: Acromegaly is a rare, slowly progressive disorder resulting from excessive growth hormone (GH) production by a pituitary somatotroph tumor. The objective of this study was to examine acromegaly treatment outcomes during long-term care at a specialized pituitary center in patients presenting with lack of biochemical control. METHODS: Data came from an acromegaly registry at the Cedars-Sinai Medical Center Pituitary Center (center). Acromegaly patients included in this study were those who presented biochemically-uncontrolled for care at the center. Biochemical control status, based on serum insulin-like growth factor-1 values, was determined at presentation and at study end. Patient characteristics and acromegaly treatments were reported before and after presentation by presenting treatment status and final biochemical control status. Data on long-term follow-up were recorded from 1985 through June 2013. RESULTS: Seventy-four patients presented uncontrolled: 40 untreated (54.1%) and 34 (45.9%) previously-treated. Mean (SD) age at diagnosis was 43.2 (14.7); 32 (43.2%) were female patients. Of 65 patients with tumor size information, 59 (90.8%) had macroadenomas. Prior treatments among the 34 previously-treated patients were pituitary surgery alone (47.1%), surgery and medication (41.2%), and medication alone (11.8%). Of the 40 patients without prior treatment, 82.5% achieved control by study end. Of the 34 with prior treatment, 50% achieved control by study end. CONCLUSIONS: This observational study shows that treatment outcomes of biochemically-uncontrolled acromegaly patients improve with directed care, particularly for those that initially present untreated. Patients often require multiple modalities of treatment, many of which are offered with the highest quality at specialized pituitary centers. Despite specialized care, some patients were not able to achieve biochemical control with methods of treatment that were available at the time of their treatment, showing the need for additional treatment options.


Assuntos
Acromegalia/terapia , Adenoma/terapia , Biomarcadores/metabolismo , Hormônio do Crescimento Humano/metabolismo , Doenças da Hipófise/terapia , Acromegalia/metabolismo , Adenoma/metabolismo , Adulto , Feminino , Seguimentos , Humanos , Fator de Crescimento Insulin-Like I/metabolismo , Masculino , Pessoa de Meia-Idade , Doenças da Hipófise/metabolismo , Centros de Atenção Terciária , Resultado do Tratamento
17.
Compr Physiol ; 7(3): 819-840, 2017 06 18.
Artigo em Inglês | MEDLINE | ID: mdl-28640444

RESUMO

Increasing prevalence of obesity and obesity-related conditions worldwide has necessitated a more thorough understanding of adipose tissue (AT) and expanded the scope of research in this field. AT is now understood to be far more complex and dynamic than previously thought, which has also fueled research to reevaluate how hormones, such as growth hormone (GH), alter the tissue. In this review, we will introduce properties of AT important for understanding how GH alters the tissue, such as anatomical location of depots and adipokine output. We will provide an overview of GH structure and function and define several human conditions and cognate mouse lines with extremes in GH action that have helped shape our understanding of GH and AT. A detailed discussion of the GH/AT relationship will be included that addresses adipokine production, immune cell populations, lipid metabolism, senescence, differentiation, and fibrosis, as well as brown AT and beiging of white AT. A brief overview of how GH levels are altered in an obese state, and the efficacy of GH as a therapeutic option to manage obesity will be given. As we will reveal, the effects of GH on AT are numerous, dynamic and depot-dependent. © 2017 American Physiological Society. Compr Physiol 7:819-840, 2017.


Assuntos
Tecido Adiposo/metabolismo , Hormônio do Crescimento/metabolismo , Tecido Adiposo/patologia , Animais , Hormônio do Crescimento/genética , Humanos , Obesidade/metabolismo , Obesidade/patologia , Doenças da Hipófise/metabolismo , Doenças da Hipófise/patologia , Transdução de Sinais
18.
Pituitary ; 20(5): 594-601, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28540625

RESUMO

PURPOSE: Granulomatosis with polyangiitis (GPA) is a multisystem disease, characterized by necrotizing small-vessel vasculitis, which mainly affects the respiratory tract and the kidneys. Pituitary involvement in GPA is rare, present in about 1% of all cases of GPA. To date, only case reports or small case series have been published. Herein we report clinical features, imaging findings, treatment and outcomes in three patients with GPA-related pituitary dysfunction (PD). METHODS: A retrospective analysis of three cases of GPA-related PD was conducted, followed by systematic review of the English medical literature using PubMed. RESULTS: The three cases include three women aged between 32 and 37 years. PD was the presenting feature in one and two developed PD in the course of the disease. All patients had a pituitary lesion on MRI. Conventional treatment with high doses of glucocorticoids and cyclophosphamide led to resolution or improvement of the MRI abnormalities, whereas it was not effective in restoring PD. A systematic review identified 51 additional patients, showing that GPA can lead to partial or global PD, either at onset or, during the course of the disease. Secondary hypogonadism is the predominant manifestation, followed by diabetes insipidus (DI). Sellar mass with central cystic lesion is the most frequent radiological finding. CONCLUSION: GPA should be carefully considered in patients with a sellar mass and unusual clinical presentation with DI and systemic disease. Although conventional induction-remission treatment improves systemic symptoms and radiological pituitary abnormalities, hormonal deficiencies persist in most of the patients. Therefore, follow-up should include both imaging and pituitary function assessment.


Assuntos
Granulomatose com Poliangiite/metabolismo , Granulomatose com Poliangiite/patologia , Hipófise/metabolismo , Hipófise/patologia , Adulto , Ciclofosfamida/uso terapêutico , Diabetes Insípido/metabolismo , Diabetes Insípido/patologia , Feminino , Glucocorticoides/uso terapêutico , Granulomatose com Poliangiite/tratamento farmacológico , Humanos , Doenças da Hipófise/tratamento farmacológico , Doenças da Hipófise/metabolismo , Doenças da Hipófise/patologia , Hipófise/efeitos dos fármacos , Estudos Retrospectivos
19.
Pituitary ; 20(4): 471-476, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28528397

RESUMO

BACKGROUND: Silent corticotroph adenomas (SCAs) are characterized by strong ACTH immunostaining without clinical manifestations of hypercortisolism. Patients with SCAs often present with mechanical symptoms related to tumor growth. This study investigates the hypothalamic pituitary adrenal axis (HPA) characteristics after adenomectomy in patients with SCAs. METHODS: Biochemical parameters of HPA function were monitored frequently after surgical resection of non-functioning macroadenomas. Levels of ACTH, cortisol, DHEA and DHEA-S were measured frequently for 48 h after adenomectomy. HPA data of patients with SCAs (n = 38) were compared to others (Controls) with non-secreting, ACTH-negative immunostaining adenomas of similar age and gender distribution (n = 182) who had adenomectomy. RESULT: Plasma ACTH increased (P < 0.0001) equally in patients with SCA and controls reaching a peak at 3 h (238 ± 123 vs. 233 ± 96 ng/L, respectively) after extubation declining thereafter to baseline values 24-36 h. Similarly, serum cortisol levels increased (P < 0.0001) equally in both groups reaching a maximum at 7 h (36.8 ± 13.9 vs. 39.3 ± 13.3 ug/dL). Serum DHEA also increased (P < 0.001) equally in both groups in parallel to the rise in serum cortisol. Serum DHEA-S levels similarly increased (P < 0.001) from their respective baseline (105.9 ± 67.5 and 106.5 ± 58.7 ug/dL) reaching their peak (154.5 ± 69.5 and 153.5 ± 68.6 ug/dL; respectively) at 15 h after extubation. None of the patients acquired any hormone deficits. CONCLUSIONS: Under the maximal stimulation of the peri-operative stress, HPA function in patients with SCA behaved in an identical manner to others with ACTH-negative macroadenomas. Thus, despite the strong ACTH-positive immunostaining of these tumors, SCAs are truly non- functional.


Assuntos
Adenoma Hipofisário Secretor de ACT/sangue , Sistema Hipófise-Suprarrenal/metabolismo , Adenoma Hipofisário Secretor de ACT/fisiopatologia , Hormônio Adrenocorticotrópico/metabolismo , Feminino , Humanos , Sistema Hipotálamo-Hipofisário/efeitos dos fármacos , Sistema Hipotálamo-Hipofisário/metabolismo , Hipotálamo/citologia , Hipotálamo/efeitos dos fármacos , Masculino , Doenças da Hipófise/sangue , Doenças da Hipófise/metabolismo , Hipófise/metabolismo , Sistema Hipófise-Suprarrenal/efeitos dos fármacos
20.
Ann Endocrinol (Paris) ; 78(2): 80-82, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28495324

RESUMO

Normal growth requires that pituitary-secreted growth hormone (GH) bind to its specific receptor and activate a complex signaling cascade, leaving to production of insulin-like growth factor-I (IGF-I), which, in turn, activates its own receptor (IGF1R). The GH receptor (GHR) is preformed as a dimer and is transported in a nonligand bound state to the cell surface. Binding of GH to the GHR dimer, results in a conformational change of the dimer, activation of the intracellular Janus Kinase 2 (JAK2) and phosphorylation of signal transducer and activator of transcription (STAT) 5B. Phosphorylated STAT5B dimers are then translocated to the nucleus, where they transcriptionally activate multiple genes, including those for IGF-I, IGF binding protein-3 and the acid-labile subunit (ALS).


Assuntos
Somatotrofos/fisiologia , Hormônio do Crescimento Humano/genética , Hormônio do Crescimento Humano/metabolismo , Humanos , Fator de Crescimento Insulin-Like I/genética , Fator de Crescimento Insulin-Like I/metabolismo , Doenças da Hipófise/genética , Doenças da Hipófise/metabolismo , Receptor IGF Tipo 1/genética , Fatores de Transcrição STAT/genética , Somatotrofos/metabolismo
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