A 12-month phase 3 study of pasireotide in Cushing's disease.

BACKGROUND: Cushing's disease is associated with high morbidity and mortality. Pasireotide, a potential therapy, has a unique, broad somatostatin-receptor-binding profile, with high binding affinity for somatostatin-receptor subtype 5. METHODS: In this double-blind, phase 3 study, we randomly assigned 162 adults with Cushing's disease and a urinary free cortisol level of at least 1.5 times the upper limit of the normal range to receive subcutaneous pasireotide at a dose of 600 µg (82 patients) or 900 µg (80 patients) twice daily. Patients with urinary free cortisol not exceeding 2 times the upper limit of the normal range and not exceeding the baseline level at month 3 continued to receive their randomly assigned dose; all others received an additional 300 µg twice daily. The primary end point was a urinary free cortisol level at or below the upper limit of the normal range at month 6 without an increased dose. Open-label treatment continued through month 12. RESULTS: Twelve of the 82 patients in the 600-µg group and 21 of the 80 patients in the 900-µg group met the primary end point. The median urinary free cortisol level decreased by approximately 50% by month 2 and remained stable in both groups. A normal urinary free cortisol level was achieved more frequently in patients with baseline levels not exceeding 5 times the upper limit of the normal range than in patients with higher baseline levels. Serum and salivary cortisol and plasma corticotropin levels decreased, and clinical signs and symptoms of Cushing's disease diminished. Pasireotide was associated with hyperglycemia-related adverse events in 118 of 162 patients; other adverse events were similar to those associated with other somatostatin analogues. Despite declines in cortisol levels, blood glucose and glycated hemoglobin levels increased soon after treatment initiation and then stabilized; treatment with a glucose-lowering medication was initiated in 74 of 162 patients. CONCLUSIONS: The significant decrease in cortisol levels in patients with Cushing's disease who received pasireotide supports its potential use as a targeted treatment for corticotropin-secreting pituitary adenomas. (Funded by Novartis Pharma; ClinicalTrials.gov number, NCT00434148.).

iASPP: a novel protein involved in pituitary tumorigenesis?

Pituitary tumors can be morphologically classified as microadenomas (diameter<1 cm) or macroadenomas (>1 cm), which can be enclosed, invasive and/or expansive. Functionally, they are classified as secreting tumors and clinically non-secreting or 'non-functioning' tumors. Several molecular mechanisms have been studied acting in uncontrolled cell proliferation and the acquisition of resistance to apoptosis. A potential mechanism related to apoptosis control has been found following the isolation and characterization of the ASPP proteins family. All these proteins share sequence similarities in their C-termini, which contains their signature sequences of Ankyrin repeats, SH3 domain and proline-rich region. Recent investigations reported that the expression of iASPP mRNA and protein was increased in non-transformed cells induced to undergo apoptosis and inhibition of iASPP expression in these cells by siRNA reduced apoptosis. Thus, modulation of iASPP expression seems to be an integral part of the apoptotic response. The ASPP proteins family binds to proteins that are key players in controlling apoptosis (P53 and NFkappaB p65 subunit). It has been speculated that the iASPP protein product induces apoptosis by blocking NFkappaB or inhibits apoptosis by blocking P53. By either mechanism, the gene could influence the survival of precancerous lesions.

Role for postoperative cortisol response to desmopressin in predicting the risk for recurrent Cushing's disease.

UNLABELLED: In the early postoperative period of Cushing's disease patients, desmopressin may stimulate ACTH secretion in the remnant corticotrophic tumour, but not in nontumour suppressed cells. OBJECTIVE: The aim of this study is to evaluate the serum cortisol responses to desmopressin after pituitary surgery, establishing an optimal cut-off for absolute increment (Delta) of serum cortisol (F) suitable to predict recurrence risk. DESIGN: Retrospective case record study. PATIENTS: Fifty-seven Cushing's disease patients submitted to pituitary surgery and desmopressin stimulation in the early postoperative with a long-term follow-up (20-161 months) were studied. METHODS AND MEASUREMENTS: Serum cortisol levels after desmopressin test (10 microg i.v.) 15-30 days after adenomectomy were used to determine DeltaF (absolute increment of F: F peak - F baseline). Sensitivity and specificity of DeltaF were calculated and a ROC curve was performed to establish an optimal cut-off for DeltaF to predict recurrence risk. RESULTS: Fifteen patients had immediate postoperative failure (basal F > 165 nmol/l; 6 microg/dl) and one patient was lost during the follow-up. Forty-one patients achieved initial remission and were followed-up. Five of 11 patients who recurred had DeltaF > 193 nmol/l (7 microg/dl), but none of 30 patients who remained in prolonged remission showed DeltaF > 193 nmol/l after postoperative desmopressin stimulation. CONCLUSIONS: Persistence of cortisol response (DeltaF > 193 nmol/l) to desmopressin in the early postoperative period can help to identify Cushing's disease patients with initial remission who present risk for later recurrence.

[Exogenous Cushing's syndrome and glucocorticoid withdrawal]. / Síndrome de Cushing exógena e retirada de glicocorticóides.

Glucocorticoids are widely used in clinical practice to control the activity of autoimmune, inflammatory, allergic diseases and other nosological entities. Therapeutic doses of glucocorticoids are often administered inappropriately and it is a particular problem because chronic therapy has many side effects, ranging from suppression of the hypothalamic-pituitary-adrenal axis and Cushing's syndrome to infections and changes in mental status. Factors influencing both the therapeutic and adverse effects of glucocorticoids include the pharmacokinetic properties of the glucocorticoid, daily dosage, individual differences in steroid metabolism and the duration of treatment. When used to control the activity of these diseases, four aspects of glucocorticoid withdrawal deserve special attention. First, the illness treated by steroids may relapse. Second, the hypothalamic-pituitary-adrenal axis may remain suppressed for a long time. Third, psychological dependence to these hormones often develops. Fourth, a nonspecific withdrawal syndrome may develop even while patients are receiving physiological replacement doses of glucocorticoids. The severity of the withdrawal syndrome depends on the phase and degree of dependence and includes many symptoms as anorexia, nausea, emesis, weight loss, fatigue, myalgias, arthralgias, headache, abdominal pain, lethargy, postural hypotension, fever, and skin desquamation.

[Pseudo-Cushing states]. / Estados de pseudo-Cushing.

Pseudo-Cushing syndromes are a heterogeneous group of disorders, including alcoholism, anorexia nervosa, visceral obesity, and depression, which share many of the clinical and biochemical features of Cushing's syndrome. The mechanisms responsible for the genesis of pseudo-Cushing's syndrome are poorly understood. It has been suggested that hypercortisolism of pseudo-Cushing syndrome may be the result of increased hypothalamic corticotrophin-releasing hormone (CRH) secretion in the context of a hypothalamic-pituitary-adrenal axis that is otherwise normally constituted. The substantial overlap in clinical and biochemical features among several patients with Cushing syndrome and those with pseudo-Cushing syndromes can make the differential diagnosis difficult. Distinguishing between pseudo-Cushing's syndrome and true Cushing's syndrome is critical for preventing the unnecessary and potentially harmful treatment of such patients. This brief review summarizes the main pathophysiological events of pseudo-Cushing syndromes and provides a useful strategy for differential diagnosis.

Ectopic ACTH syndrome: our experience with 25 cases.

OBJECTIVE: Ectopic ACTH syndrome (EAS) occurs in about 5-10% of all patients with ACTH-dependent hypercortisolism with most of them caused by intrathoracic neoplasms. It may be associated with overt malignancies or with occult and indolent tumors. We assessed the accuracy of dynamic tests, inferior petrosal sinus sampling (IPSS) using desmopressin, and imaging in the work-up diagnosis of EAS. DESIGN AND SUBJECTS: Tumor markers, imaging, and outcome data from 25 patients (13F/12M) aged 18-72 years. High dexamethasone suppression test (HDDST), desmopressin test, GHRP-6 test, corticotropin-releasing hormone (CRH) test, IPSS, computed tomography (CT), magnetic resonance imaging (MRI), and (111)In-pentetreotide scintigraphy were revised. RESULTS: In 5 out of 20 patients HDDST was positive. In 13 patients who underwent desmopressin test, ACTH- and cortisol-positive responses were seen in six and five patients respectively. GHRP-6 test was positive in two out of three cases. Two patients underwent CRH test with negative response. In the seven patients submitted to IPSS using desmopressin in six of them, none had ACTH gradients. CT was positive in 15 out of 21 patients and MRI in 8 out of 17 cases. (111)In-pentetreotide scintigraphy was positive in three out of five patients. Fourteen patients had intrathoracic tumors, five had pheochromocytomas, three had pancreatic tumors, one had a glomic tumor, and had three occult tumors. Six out of 11 patients with metastasis died and 3 others without metastasis died. CONCLUSIONS: IPSS with desmopressin was helpful for differential diagnosis. Patients initially harboring occult carcinoids may also exhibit severe hypercortisolism and those harboring tymic carcinoids had poor prognoses when compared with bronchial carcinoids and pheocromocytomas.

Cushing's disease arising from a clinically nonfunctioning pituitary adenoma.

A 49-yr-old woman with a large pituitary tumor leading to visual loss and galactorrhea- amenorrhea was submitted to transcranial pituitary surgery, when a clinically nonfunctioning pituitary adenoma was partially removed. Histopathology and immunohistochemistry confirmed the diagnosis of "non-secreting atypical adenoma." At that time, serum and urinary free cortisol were normal, with low T4 levels and hyperprolactinemia. The patient was discharged on thyroxine and bromocriptine and treated with conventional radiotherapy. Two years later, she presented high free urinary cortisol levels and a positive ACTH response to desmopressin testing on dexametasone 2 mg overnight. A pituitary biopsy confirmed aggressive growth as well as positive immunoreactivity for ACTH, p53, Ki-67, and c-erb-B2. The patient was then treated with radiosurgery on ketoconazole therapy. The overall clinical, laboratory, and pathological data suggest a transition from a clinically nonfunctioning to a hypersecreting ACTH-producing tumor. Putative mechanisms of tumor transformation and the possibility of a silent corticotropinoma evolving into clinical Cushing s syndrome are discussed.

[TSH-secreting pituitary tumors: two case reports and literature review]. / Tumores hipofisários secretores de TSH: relato de dois casos e revisão da literatura.

INTRODUCTION: TSH-secreting pituitary adenomas are rare pituitary functioning tumors accounting for less than 2% of the pituitary adenomas. The clinical feature consists of thyrotoxicosis occasionally associated to tumoral symptoms due to mass effect. The biochemical feature consists of elevated thyroid hormones levels and normal or high TSH concentrations. This disease is often wrongly diagnosed as Grave's disease, and the ablative therapy is frequently conducted prior to the diagnosis. OBJECTIVE: To report two cases followed in the Neuroendocrine Unit of Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo and to review the literature aiming at the management of this affection. CONCLUSION: In the presence of elevated thyroid hormone levels associated with inappropriate normal or increased TSH levels, the possibility of a TSH-secreting pituitary adenoma should be considered for the proper medical treatment.

Severe hyperprolactinemia associated with internal carotid artery aneurysm: differential diagnosis between prolactinoma and hypothalamic-pituitary disconnection.

Sellar and parasellar masses blocking inhibitory hypothalamic dopaminergic tonus can produce hyperprolactinemia. One of these conditions, seldom reported, is internal carotid artery aneurysm causing pituitary stalk compression and hyperprolactinemia, the majority of which is related to small increases in serum prolactin levels. The aim of this study is to report the case of a patient with an internal carotid aneurysm and severe hiperprolactinemia. A 72 years old female patient, on oncology follow-up for clinically controlled cervical carcinoma, was evaluated due to worsening chronic headaches. During the investigation, computed tomography and magnetic resonance imaging (MRI) showed a sellar mass associated with high prolactin level (1.403 microg/L) that initially was considered a macroprolactinoma, and treated with bromocriptine. However, subsequent pituitary MRI suggested an internal carotid aneurysm, which was confirmed by an angioresonance imaging of cerebral vessels. On low bromocriptine dose (1.25 mg/day), there was a prompt normalization of prolactin levels with a great increase (> 600 microg/L) after withdrawal, which was confirmed several times, suggesting HPD. We report a patient with internal carotid artery aneurysm with severe hyperprolactinemia never reported before in patients with HPD, and the need for a differential diagnosis with macroprolactinomas even considering high prolactin levels.

Association between tumoral GH-releasing peptide receptor type 1a mRNA expression and in vivo response to GH-releasing peptide-6 in ACTH-dependent Cushing's syndrome patients.

OBJECTIVE: GH secretagogues (GHS) produce exaggerated ACTH and cortisol responses in Cushing's disease (CD) patients, attributable to their direct action on GH-releasing peptide receptor type 1a (GHSR-1a). However, there are no studies correlating the in vivo response to GHS and GHSR-1a mRNA expression in ACTH-dependent Cushing's syndrome (CS) patients. The aim of this study is to correlate the patterns of ACTH and cortisol response to GH-releasing peptide-6 (GHRP-6) to GHSR-1a expression in ACTH-dependent CS patients. DESIGN: Prospective study in a tertiary referral hospital center. Fifteen CD patients and two ectopic ACTH syndrome (EAS) patients were studied. METHODS: Tumor fragments were submitted to RNA extraction, and GHSR-1a expression was studied through real-time qPCR and compared with normal tissue samples. The patients were also submitted to desmopressin test and vasopressin receptor type 1B (AVPR1B) mRNA analysis by qPCR. RESULTS: GHSR-1a expression was similar in normal pituitary samples and in corticotrophic tumor samples. GHSR-1a expression was higher in patients (CD and EAS) presenting in vivo response to GHRP-6. Higher expression of AVPR1B was observed in the EAS patients responsive to desmopressin, as well as in corticotrophic tumors, as compared with normal pituitary samples, but no correlation between AVPR1B expression and response to desmopressin was observed in the CD patients. CONCLUSIONS: Our results revealed a higher expression of GHSR-1a in the ACTH-dependent CS patients responsive to GHRP-6, suggesting an association between receptor gene expression and in vivo response to the secretagogue in both the CD and the EAS patients.

The role of desmopressin in bilateral and simultaneous inferior petrosal sinus sampling for differential diagnosis of ACTH-dependent Cushing's syndrome.

OBJECTIVE: Bilateral inferior petrosal sinus sampling (BIPSS) with corticotrophin-releasing hormone (CRH) stimulation is currently the gold standard test for the differential diagnosis of ACTH-dependent Cushing's syndrome. Reports on the use of desmopressin in this approach are limited. The aim of this study was to evaluate the use of desmopressin during BIPSS in a cohort of patients with ACTH-dependent Cushing's syndrome. DESIGN: A retrospective case-record study. PATIENTS: Fifty-six patients with confirmed ACTH-dependent Cushing's syndrome underwent BIPSS with desmopressin stimulation when presenting negative pituitary tumour imaging. MEASUREMENTS: Central to peripheral (CEN:PER) ACTH gradient, lateralization of the ACTH source and surgical tumour confirmation were evaluated. RESULTS: A CEN:PER ACTH gradient was found in 40 patients under basal conditions (CEN:PER >or= 2) and in 47 patients after desmopressin stimulation (CEN:PER >or= 3). Ectopic ACTH-producing tumours (three lung carcinoid tumour, one thymus carcinoid tumour and one thymus hyperplasia) were confirmed in five out of nine patients without the CEN:PER ACTH gradient, and four cases were false negative for Cushing's disease. Lateralization (IPS:IPS >or= 1.4) was observed in 80.8% of patients under basal conditions (38/47) and in 97.8% after desmopressin (46/47), and it was surgically confirmed in 78.7%. There were no false-positive cases. Sensitivity and specificity were 92.1% and 100%, respectively. CONCLUSIONS: Desmopressin improves the differential diagnosis of ACTH-dependent Cushing's syndrome by amplifying the CEN:PER and IPS:IPS ACTH gradients, and is therefore a useful ACTH secretagogue in BIPSS.

Medical management of pituitary adenomas: the special case of management of the pregnant woman.

The development of efficacious surgical and medical therapies for pituitary adenomas as well as the improvement of hormone therapy for ovulation induction has made pregnancy possible for women harboring pituitary tumors. However, gestational risks due to the possibility of tumor growth during pregnancy, mainly in women with macroadenomas, raise a concern. Bromocriptine has a well-established role for prolactinoma treatment before and during pregnancy, even when a symptomatic tumor increase occurs. It can also be used in acromegaly, despite its poorer results. Somatostatin analogs have been used in acromegaly even during pregnancy with uneventful outcomes, but their safety in pregnancy is not well established, yet. The largest experience with medical treatment for Cushing's disease during pregnancy involves metyrapone, a steroidogenesis inhibitor, without descriptions of congenital abnormalities. Concerning clinically non-functioning pituitary tumors, ovulation induction or even in vitro fertilization are frequently needed. The purpose of this review is to provide an update on therapeutic strategies to restore fertility as well as gestational and post-gestational management of patients with pituitary adenomas, focusing mainly on the role of medical treatment for different tumor types.

Tumores hipofisários secretores de TSH: relato de dois casos e revisão da literatura / TSH-secreting pituitary tumors: two case reports and literature review

INTRODUÇÃO: Tumores hipofisários secretores de hormônio estimulante da tireoide (TSH), tireotropinomas, são raros e correspondem a menos de 2 por cento de todos os adenomas da hipófise. Manifestam-se clinicamente com sintomas e sinais de tireotoxicose, eventualmente associados a sintomas compressivos, sobretudo visuais, devido ao efeito de massa do tumor. Esses tumores se caracterizam pela presença de níveis séricos elevados de hormônios tireoidianos e níveis séricos elevados, ou inapropriadamente normais, de TSH. Frequentemente, ao diagnóstico, há relato de tratamento prévio cirúrgico, medicamentoso e/ou ablativo, por hipótese de hipertireoidismo primário por doença de Graves. OBJETIVO: Relatar dois casos de tireotropinomas acompanhados na Unidade de Neuroendocrinologia do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (HC-FMUSP) e revisar a literatura visando ao manejo desta afecção. CONCLUSÃO: Na presença de hormônios tireoidianos elevados e níveis de TSH inapropriadamente normais ou elevados, a possibilidade de adenoma hipofisário produtor de TSH deve ser considerada com vistas à realização da terapia adequada.

INTRODUCTION: TSH-secreting pituitary adenomas are rare pituitary functioning tumors accounting for less than 2 percent of the pituitary adenomas. The clinical feature consists of thyrotoxicosis occasionally associated to tumoral symptoms due to mass effect. The biochemical feature consists of elevated thyroid hormones levels and normal or high TSH concentrations. This disease is often wrongly diagnosed as Grave's disease, and the ablative therapy is frequently conducted prior to the diagnosis. OBJECTIVE: To report two cases followed in the Neuroendocrine Unit of Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo and to review the literature aiming at the management of this affection. CONCLUSION: In the presence of elevated thyroid hormone levels associated with inappropriate normal or increased TSH levels, the possibility of a TSH-secreting pituitary adenoma should be considered for the proper medical treatment.

Severe hyperprolactinemia associated with internal carotid artery aneurysm: differential diagnosis between prolactinoma and hypothalamic-pituitary disconnection / Hiperprolactinemia severa associada a aneurisma interno da artéria carótida: diagnóstico diferencial entre prolactinoma e desconexão hipotálamo-hipofisária

Sellar and parasellar masses blocking inhibitory hypothalamic dopaminergic tonus can produce hyperprolactinemia. One of these conditions, seldom reported, is internal carotid artery aneurysm causing pituitary stalk compression and hyperprolactinemia, the majority of which is related to small increases in serum prolactin levels. The aim of this study is to report the case of a patient with an internal carotid aneurysm and severe hiperprolactinemia. A 72 years old female patient, on oncology follow-up for clinically controlled cervical carcinoma, was evaluated due to worsening chronic headaches. During the investigation, computed tomography and magnetic resonance imaging (MRI) showed a sellar mass associated with high prolactin level (1.403 µg/L) that initially was considered a macroprolactinoma, and treated with bromocriptine. However, subsequent pituitary MRI suggested an internal carotid aneurysm, which was confirmed by an angioresonance imaging of cerebral vessels. On low bromocriptine dose (1.25 mg/day), there was a prompt normalization of prolactin levels with a great increase (> 600 µg/L) after withdrawal, which was confirmed several times, suggesting HPD. We report a patient with internal carotid artery aneurysm with severe hyperprolactinemia never reported before in patients with HPD, and the need for a differential diagnosis with macroprolactinomas even considering high prolactin levels.

Massas selares e parasselares podem produzir hiperprolactinemia por bloquear o tônus inibitório hipotalâmico de dopamina. Uma destas condições, raramente reportada, é o aneurisma de artéria carótida interna causando compressão da haste hipofisária e hiperprolactinemia, a maioria com pequenas elevações da prolactina. O objetivo deste estudo é descrever o caso de uma paciente com aneurisma de carótida interna e grave hiperprolactinemia. Paciente feminina, 72 anos, em acompanhamento oncológico por carcinoma de colo de útero clinicamente controlado, avaliada por causa da piora de cefaléia crônica. Durante investigação, tomografia computadorizada e ressonância magnética (RM) de hipófise mostraram massa selar associada com altos níveis de prolactina (1.403 µg/L), sendo avaliado como macroprolactinoma e tratado com bromocriptina. Entretanto, RM subseqüente sugeriu aneurisma de carótida interna que foi confirmado por angiorressonância de vasos cerebrais. Em uso de baixas doses de bromocriptina (1,25 mg/dia), houve pronta normalização da prolactina com grande elevação (> 600 µg/L) após a retirada do medicamento, sendo confirmado por várias vezes sugerindo DHH. Reporta-se uma paciente com aneurisma de artéria carótida interna com grave hiperprolactinemia, nunca descrita anteriormente em pacientes com DHH, e a necessidade do diagnóstico diferencial com macroprolactinoma, mesmo considerando altos níveis de prolactina.

Síndrome de Cushing exógena e retirada de glicocorticóides: [revisão] / Exogenous Cushing's syndrome and glucocorticoid withdrawal: [review]

Glicocorticóides são amplamente utilizados na prática clínica para o controle da atividade de doenças auto-imunes, inflamatórias, alérgicas e outras entidades nosológicas. Doses terapêuticas de glicocorticóides são muita vezes administradas inapropriadamente e isto é um problema particular, pois a terapia crônica tem muitos efeitos colaterais que se estendem desde a supressão do eixo hipotálamo-hipofisário-adrenal e síndrome de Cushing até infecções e alterações do status mental. Fatores que influenciam tanto nos efeitos adversos quanto nos terapêuticos dos glicocorticóides incluem propriedades farmacocinéticas do glicocorticóide, dose diária, diferenças individuais no metabolismo esteróide e duração do tratamento. Quando utilizados para o controle da atividade destas doenças, quatro aspectos da retirada de glicocorticóide merecem atenção especial. Primeiro, a doença tratada pelo esteróide pode recorrer. Segundo, o eixo hipotálamo- hipófise-adrenal pode permanecer suprimido por um longo período. Terceiro, muitas vezes desenvolve-se dependência psicológica a esses hormônios. Quarto, uma síndrome de retirada inespecífica pode desenvolver mesmo enquanto os pacientes estão recebendo doses de reposição fisiológica de glicocorticóides. A gravidade da síndrome de retirada depende da fase e o grau de dependência e inclui sintomas tais como anorexia, náusea, vômitos, perda de peso, fadiga, mialgias, artralgias, cefaléia, dor abdominal, letargia, hipotensão postural, febre e descamação da pele.

Glucocorticoids are widely used in clinical practice to control the activity of autoimmune, inflammatory, allergic diseases and other nosological entities. Therapeutic doses of glucocorticoids are often administered inappropriately and it is a particular problem because chronic therapy has many side effects, ranging from suppression of the hypothalamic-pituitary-adrenal axis and Cushing's syndrome to infections and changes in mental status. Factors influencing both the therapeutic and adverse effects of glucocorticoids include the pharmacokinetic properties of the glucocorticoid, daily dosage, individual differences in steroid metabolism and the duration of treatment. When used to control the activity of these diseases, four aspects of glucocorticoid withdrawal deserve special attention. First, the illness treated by steroids may relapse. Second, the hypothalamic-pituitary-adrenal axis may remain suppressed for a long time. Third, psychological dependence to these hormones often develops. Fourth, a nonspecific withdrawal syndrome may develop even while patients are receiving physiological replacement doses of glucocorticoids. The severity of the withdrawal syndrome depends on the phase and degree of dependence and includes many symptoms as anorexia, nausea, emesis, weight loss, fatigue, myalgias, arthralgias, headache, abdominal pain, lethargy, postural hypotension, fever, and skin desquamation.

Estados de pseudo-Cushing: [revisão] / Pseudo-Cushing states: [review]

Síndromes de pseudo-Cushing são um grupo heterogêneo de doenças, incluindo alcoolismo, anorexia nervosa, obesidade visceral e depressão, que compartilham muitas das características clínicas e bioquímicas da síndrome de Cushing. Os mecanismos responsáveis para a gênese da síndrome de pseudo-Cushing são fracamente compreendidos. Tem sido sugerido que o hipercortisolismo da síndrome de pseudo-Cushing pode ser resultante do aumento da secreção do hormônio liberador de corticotrofina (CRH) hipotalâmico no contexto de um eixo hipotálamo-hipofisário-adrenal que, de outra maneira, está normalmente constituído. A sobreposição substancial entre as características clínicas e laboratoriais entre muitos pacientes com síndrome de Cushing e aqueles com síndrome de pseudo-Cushing pode tornar o diagnóstico diferencial difícil. Distinguir entre síndrome de pseudo-Cushing e síndrome de Cushing verdadeira é crítico para se prevenir o tratamento desnecessário e potencialmente prejudicial de tais pacientes. Esta breve revisão sumariza os principais eventos patofisiológicos das síndromes de pseudo-Cushing e fornece uma estratégia útil para o seu diagnóstico diferencial.

Pseudo-Cushing syndromes are a heterogeneous group of disorders, including alcoholism, anorexia nervosa, visceral obesity, and depression, which share many of the clinical and biochemical features of Cushing's syndrome. The mechanisms responsible for the genesis of pseudo-Cushing's syndrome are poorly understood. It has been suggested that hypercortisolism of pseudo-Cushing syndrome may be the result of increased hypothalamic corticotrophin-releasing hormone (CRH) secretion in the context of a hypothalamic-pituitary-adrenal axis that is otherwise normally constituted. The substantial overlap in clinical and biochemical features among several patients with Cushing syndrome and those with pseudo-Cushing syndromes can make the differential diagnosis difficult. Distinguishing between pseudo-Cushing's syndrome and true Cushing's syndrome is critical for preventing the unnecessary and potentially harmful treatment of such patients. This brief review summarizes the main pathophysiological events of pseudo-Cushing syndromes and provides a useful strategy for differential diagnosis.

Alteracoes ecograficas tireoidianas em pacientes acromegalicos / Thyrods echographics alterations in acromegalics patients.

O proposito deste estudo e avaliar as alteracoes morfologicas da tireoide nos pacientes acromegalicos atraves da ultra-sonografia de alta resolucao, correlacionando-as com as dosagens hormonais da glandila. Os autores concluem que todos os acromegalicos apresentam aumento da tireoide, sendo que esta pode apresentar bocio tanto difusos quanto nodulares

MRI of congenital pituitary insuficiency

Foram analisadas as imagens obtidas em aparelho de 1,5 Tesla, 193 pacientes portadores de insuficiencia pituitaria congenita. Cento e trinta e nove pacientes eram portadores de deficit isolado de hormonio de crescimento e os outros 54 pacientes apresentavam multiplas deficiencias de hormonios pituitarios. Os lobos anterior e posterior da glandula pituitaria normal podem ser perfeitamente diferenciados a RM devido ao hipersinal caracteristico do lobo posterior em sequencias pesadas em T1...