Characterization of sporadic somatotropinomas with high GIP receptor expression.

PURPOSE: To analyze the expression of glucose-dependent insulinotropic polypeptide receptor (GIPR) in somatotropinomas specimens and compare clinical, biochemical, radiological, therapeutic, molecular, and pathological data among those who overexpressed (GIPR +) and those who did not overexpress (GIPR - ) GIPR. METHODS: Clinical, biochemical, radiological, molecular, and pathological data were collected. GNAS1 sequencing was performed with the Sanger method. Protein expression of somatostatin receptor subtypes 2 and 5 and CAM 5.2 were analyzed by immunohistochemistry. Quantitative real-time PCR was performed to analyze the mRNA expression of GIPR with the TaqMan® method. Positive expression was considered when the fold change (FC) was above 17.2 (GIPR +). RESULTS: A total of 74 patients (54% female) were included. Eighteen tumors (24%) were GIPR + . Gsp mutation was detected in 30 tumors (40%). GIPR + tumors were more frequently densely granulated adenomas (83% vs 47%, p = 0.028). There was no difference in clinical, biochemical, radiological, therapeutic (surgical cure or response to medical therapy), or other pathological features between GIPR + and GIPR -  tumors. Twenty-eight out of 56 (50%) GIPR -  tumors harbored a gsp mutation, whereas two out of 18 (11%) GIPR + tumors harbored a gsp mutation (p = 0.005). CONCLUSION: We described, for the first time, that GIPR + and gsp mutations are not mutually exclusive, but gsp mutations are less common in GIPR + tumors. GIPR + and GIPR -  tumors have similar clinical, biochemical, radiological, therapeutic, and pathological features, with the exception of a high frequency of densely granulated adenomas among GIPR + tumors.

Approach to the Patient: Differential Diagnosis of Cystic Sellar Lesions.

Cystic lesions arising in the sellar region are not uncommon and encompass cystic pituitary adenomas, Rathke cleft cysts, craniopharyngiomas, and arachnoid cysts. Their clinical presentation may be similar, including headache, visual field defects, and anterior pituitary hormone deficits, which makes differential diagnosis challenging. On the other hand, imaging features may indicate certain pathologies. In this approach to the patient, we describe the case of a patient who presented with right temporal hemianopsia and a sellar/suprasellar cystic lesion, which was determined to be Rathke cleft cyst. We discuss the imaging characteristics that may suggest a particular diagnosis between Rathke cleft cyst, cystic pituitary adenoma, craniopharyngioma, and arachnoid cyst and propose a flowchart for aiding in the imaging differential diagnosis.

Pituitary MRI Standard and Advanced Sequences: Role in the Diagnosis and Characterization of Pituitary Adenomas.

Pituitary adenomas (PAs) represent the most frequently found lesions in the sellar region; however, several other lesions may be encountered in this region, such as meningiomas, craniopharyngiomas, and aneurysms. High-quality imaging is fundamental for diagnosis, characterization, and guidance of treatment planning of PAs. Sellar magnetic resonance imaging (MRI) is considered the imaging modality of choice for the evaluation of lesions in the sella turcica. The sellar MRI standard protocol includes coronal and sagittal T1-weighted spin-echo sequencing with and without gadolinium-based contrast agent and coronal T2-weighted (T2w) fast-spin echo sequencing. A systematic MRI approach to the pituitary region generally provides information that includes the size and shape of the PA, the presence of cysts or hemorrhage within the tumor, its relationship with the optic pathways and surrounding structures, potential cavernous sinus invasion, sphenoid sinus pneumatization type, and differential diagnosis with other sellar lesions. The standard protocol is sufficient for the evaluation of most cases; however, some advanced techniques (susceptibility imaging, diffusion-weighted imaging, 3D T2w high-resolution sequences, magnetic resonance elastography, perfusion-weighted imaging) may render additional information, which may be important for some cases. In this "approach to the patient" manuscript, we will discuss the use of standard and advanced MRI sequences in the diagnosis and characterization of PAs, including MRI features associated with treatment response that may aid in presurgical evaluation and planning, and red flags that may point to an alternative diagnosis.

Hydroxychloroquine with azithromycin in patients hospitalized for mild and moderate COVID-19.

OBJECTIVES: To assess the efficacy of hydroxychloroquine in combination with azithromycin in terms of clinical and biochemical outcomes in adult patients with COVID-19 hospitalized for acute respiratory distress syndrome (ARDS), and to describe the occurrence of adverse events. METHOD: Retrospective comparative study, based in a quaternary private hospital in Rio de Janeiro, Brazil, involving 193 adult patients hospitalized for mild and moderate COVID-19 related ARSD, analyzing treatment efficacy based on clinical and biochemical outcomes. RESULTS: The active group comprised 101 (52.3%) patients using hydroxychloroquine associated with azithromycin and the control group 92 (47.7%) patients who did not take these medications. Median age was 59 (47-70) in the active group and 65 (47-77) in the control group (p < 0.05). Patients in the control group had greater extent of pulmonary involvement on baseline chest CT scans (p < 0.05). All other baseline variables (BMI, comorbidities, previous use of medications and biochemical assessments) were similar between groups. In the medication group, 25% (25 out of 101) were admitted to the ICU, compared to 21% (19 out of 92) in the control group (p > 0.05). No difference in mortality, duration of non-invasive oxygen use or duration of hospitalization was seen between groups. The therapeutic regimen was well tolerated, with only eight (7.9%) patients presenting gastrointestinal symptoms and eight (7.9%) patients withdrawn treatment due to QTc prolongation. CONCLUSIONS: Patients treated with hydroxychloroquine combined with azithromycin and the control group had similar clinical outcomes. This therapeutic regimen was considered ineffective in hospitalized patients with mild to moderate COVID-19 related ARDS and was associated with few non-severe adverse events.

Telomerase expression in clinically non-functioning pituitary adenomas.

PURPOSE: Non-functioning pituitary adenomas (NFPA) are benign tumors, however, some are agressive. We aimed to assess if human telomerase reverse transcriptase (hTERT) is present in NFPA and if it can be used as a marker of aggressiveness and proliferation. METHODS: Consecutive patients operated for NFPA whose fresh frozen tumors were available were included. We analyzed tumor's aggressiveness (based on radiological progression) and proliferation (based on Ki-67), as well as hTERT mRNA by quantitative real-time polymerase chain reaction (RT-qPCR). RESULTS: We included 109 samples from 86 patients followed for a median period of 60 months (5-120 months). Aggressive tumors were present in 66% cases and proliferative tumors in 47.7%. Seven (6.4%) samples expressed hTERT: 3 (42.8%) had aggressive and proliferative tumors, 2 (28.6%) only exhibited aggressiveness and the remaining 2 (28.6%) only proliferation. From the aggressive and proliferative tumors, 14% and 16%, respectively, expressed hTERT. From the non-aggressive and non-proliferative tumors, 9% and 6%, respectively, expressed hTERT. CONCLUSION: hTERT expression is present in a minority of NFPA and does not seem to be related to aggressiveness or proliferation in NFPA.

Hydroxychloroquine with azithromycin in patients hospitalized for mild and moderate COVID-19

ABSTRACT Objectives: To assess the efficacy of hydroxychloroquine in combination with azithromycin in terms of clinical and biochemical outcomes in adult patients with COVID-19 hospitalized for acute respiratory distress syndrome (ARDS), and to describe the occurrence of adverse events. Method: Retrospective comparative study, based in a quaternary private hospital in Rio de Janeiro, Brazil, involving 193 adult patients hospitalized for mild and moderate COVID-19 related ARSD, analyzing treatment efficacy based on clinical and biochemical outcomes. Results: The active group comprised 101 (52.3%) patients using hydroxychloroquine associated with azithromycin and the control group 92 (47.7%) patients who did not take these medications. Median age was 59 (47-70) in the active group and 65 (47−77) in the control group (p < 0.05). Patients in the control group had greater extent of pulmonary involvement on baseline chest CT scans (p < 0.05). All other baseline variables (BMI, comorbidities, previous use of medications and biochemical assessments) were similar between groups. In the medication group, 25% (25 out of 101) were admitted to the ICU, compared to 21% (19 out of 92) in the control group (p > 0.05). No difference in mortality, duration of non-invasive oxygen use or duration of hospitalization was seen between groups. The therapeutic regimen was well tolerated, with only eight (7.9%) patients presenting gastrointestinal symptoms and eight (7.9%) patients withdrawn treatment due to QTc prolongation. Conclusions: Patients treated with hydroxychloroquine combined with azithromycin and the control group had similar clinical outcomes. This therapeutic regimen was considered ineffective in hospitalized patients with mild to moderate COVID-19 related ARDS and was associated with few non-severe adverse events.

Acromegaly: Update on Management and Long-Term Morbidities.

Acromegaly is a systemic disease associated with great morbidity and increased mortality if not adequately treated. In the past decades much improvement has been achieved in its treatment and in the knowledge of its comorbidities. We provide an update of acromegaly management with current recommendations. We also address long-term comorbidities emphasizing the changing face of the disease in more recent series, with a decrease of cardiovascular disease severity and an increased awareness of comorbidities like bone disease, manifested mainly as vertebral fractures and the change in the main cause of death (from cardiovascular disease to cancer in more recent series).

Collision sellar lesions: coexistence of pituitary adenoma and Rathke cleft cyst-a single-center experience.

PURPOSE: Collision sellar lesions represent the coexistence of distinct histopathological lesions found in the sella turcica. They are uncommon entities and have mainly been reported as pituitary adenoma (PA) associated to Rathke cleft cyst (RCC). Pre- and perioperative diagnosis is difficult, since most of the cases appear clinically, radiologically, and macroscopically as solitary cystic sellar lesion. METHODS: A retrospective study of histological reports from patients operated for PA from 2013 to 2018 in a single neurosurgery reference center was performed. Patients who also exhibited RCC in the histological sections were included. Clinical and biochemical data were collected from medical files. MRI scans and histopathological slides were also reviewed. RESULTS: Among 554 PA, five patients (0.9%) presented the association of PA and RCC. At diagnosis, patients had median age of 60 years (33-78) with, at least, one pituitary dysfunction, and visual field loss and/or headache. There was a female predominance (n = 3). All patients had nonfunctioning PA. MRI studies showed a predominantly cystic lesion and were unable to distinguish both lesions. The definitive diagnosis was made by histopathology. CONCLUSION: The association of PA and RCC is extremely rare. On MRI, they appear as a solid-cystic or cystic sellar tumors. RCC can rupture causing granulomatous reaction with cholesterol crystal formation, which can be mistaken for craniopharyngiomas during surgery. Therefore, collision sellar lesion must be included in the differential diagnosis of cystic sellar lesions. The definitive diagnosis is made by histological study.

Accuracy of microcystic aspect on T2-weighted MRI for the diagnosis of silent corticotroph adenomas.

INTRODUCTION: A single study suggested that silent corticotropinomas (SCAs) have a different imaging phenotype, with microcystic aspect on T2-weighted sequence of magnetic resonance imaging (T2-MRI). This study only analysed manifest and silent corticotropinomas and nonfunctioning gonadotroph adenomas. Therefore, the prevalence of microcystic patterns of other tumours is not known. AIM: To analyse frequency of microcystic patterns on T2-MRI in all subtypes of pituitary adenomas and determine accuracy of this radiological finding for diagnosing SCA. METHODS: Consecutive pituitary adenoma patients who underwent surgery between 2013 and 2016 at a single centre were included. T2-MRIs were evaluated by a radiologist and an endocrinologist blinded to histological diagnosis. RESULTS: A total of 143 patients (52% female) with median age of 49 years (14-80) were included. Clinically, there were 90 nonfunctioning pituitary adenomas (NFPAs), 32 somatotropinomas, 13 corticotropinomas, five prolactinomas and three TSH-secreting adenomas. Of the patients with NFPA, 12 (13%) were SCAs, 73 (79%) were gonadotropinomas and five (6%) were positive for prolactin (three) or TSH (two). A microcystic pattern was observed in 16 tumours (11%): one somatotropinoma, one corticotropinoma, seven SCAs and seven gonadotropinomas, and in no prolactinomas or TSH-secreting adenomas. It was more common in SCAs than in other tumours (58.3% vs 6.9%, respectively, P < .001) and had a sensitivity of 58%, a specificity of 93% and an accuracy of 90% to define an SCA. CONCLUSION: Microcystic aspect on T2-MRI is able to define SCA with a good accuracy and can be a useful tool, considering the more aggressive behaviour of these tumours.

Determinants of morbidities and mortality in acromegaly

ABSTRACT Acromegaly is a systemic disease associated with increased morbidity, presenting cardiovascular, metabolic, respiratory, neoplastic, endocrine, articular and bone complications. Most of these comorbidities can be prevented or delayed with adequate disease treatment and, more recent studies with the use of modern treatments of acromegaly, have shown a change in the severity and prevalence of these complications. In addition, acromegaly is associated with increased mortality, but recent studies (especially those published in the last decade) have shown a different scenario than older studies, with mortality no longer being increased in adequately controlled patients and a change in the main cause of death from cardiovascular disease to malignancy. In this review, we discuss this changing face of acromegaly summarizing current knowledge and evidence on morbimortality of the disease. Arch Endocrinol Metab. 2019;63(6):630-7

Determinants of morbidities and mortality in acromegaly.

Acromegaly is a systemic disease associated with increased morbidity, presenting cardiovascular, metabolic, respiratory, neoplastic, endocrine, articular and bone complications. Most of these comorbidities can be prevented or delayed with adequate disease treatment and, more recent studies with the use of modern treatments of acromegaly, have shown a change in the severity and prevalence of these complications. In addition, acromegaly is associated with increased mortality, but recent studies (especially those published in the last decade) have shown a different scenario than older studies, with mortality no longer being increased in adequately controlled patients and a change in the main cause of death from cardiovascular disease to malignancy. In this review, we discuss this changing face of acromegaly summarizing current knowledge and evidence on morbimortality of the disease. Arch Endocrinol Metab. 2019;63(6):630-7.

Eosinophilic fasciitis

Abstract Eosinophilic fasciitis is a rare sclerodermiform syndrome of unknown etiology. It is characterized by the thickening of the muscular fascia and subcutaneous tissue, with a variable infiltration of eosinophils. Peripheral eosinophilia, poly or monoclonal hypergammaglobulinemia and increased erythrocyte sedimentation rate can be seen. Clinical features begin acutely, with local edema and a painful and symmetrical stiffening of the limbs, progressing rapidly to fibrosis, which can limit joint movements. Some cases have a history of strenuous physical exercise or trauma. The diagnosis is confirmed by a deep skin biopsy. Glucocorticoids in high doses is the treatment of choice. We report a typical eosinophilic fasciitis case with peripheral eosinophilia and dramatic response to pulse therapy with methylprednisolone.

Eosinophilic fasciitis.

Eosinophilic fasciitis is a rare sclerodermiform syndrome of unknown etiology. It is characterized by the thickening of the muscular fascia and subcutaneous tissue, with a variable infiltration of eosinophils. Peripheral eosinophilia, poly or monoclonal hypergammaglobulinemia and increased erythrocyte sedimentation rate can be seen. Clinical features begin acutely, with local edema and a painful and symmetrical stiffening of the limbs, progressing rapidly to fibrosis, which can limit joint movements. Some cases have a history of strenuous physical exercise or trauma. The diagnosis is confirmed by a deep skin biopsy. Glucocorticoids in high doses is the treatment of choice. We report a typical eosinophilic fasciitis case with peripheral eosinophilia and dramatic response to pulse therapy with methylprednisolone.