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Background Sporadic Adrenal Medullary hyperplasia (AMH) has been little described in the literature, being most often diagnosed during a genetic syndrome screening or the evaluation of an adrenal incidentaloma. Case report A 51-year-old female patient presented with progressive attacks of tachycardia, headache, nausea and mild paroxysmal hypertension, which started in December 2020. She had a history of smoking and she also presented Takotsubo syndrome in 2018. She denied other comorbidities. In March 2021, she was submitted to laboratorial testing which demonstrated indeterminate plasma fractionated metanephrines by HPLC/MS: metanephrines 0.3 nmol/L (n< 0.5) and normetanephrines 1.2 nmol/L (n< 0.9) and normal serum chromogranin A level: 82 ng/mL (n Conclusion Adrenal Medullary hyperplasia is a rare condition, which usually presents in a milder form and is often associated with pheochromocytoma or genetic syndromes. However it should be considered in symptomatic patients without a personal or family history of PHEO/PGL, allowing an early diagnosis and treatment. Presentation: No date and time listed

In recent years the immunomodulatory actions of vitamin D, a steroid hormone, have been extensively studied. In 2020, due to the COVID-19 pandemic, the question arose as to 25(OH)D status would be related to susceptibility to SARS-CoV-2 infection, since several studies pointed out a higher prevalence and severity of the disease in populations with low levels of 25(OH)D. Thus, we investigated the 25(OH)D levels in adults “Detected” positive for SARS CoV-2 by RT-PCR (reverse transcriptase polymerase chain reaction) test, and in negative controls, “not Detected”, using the Fleury Group's examination database, in Sao Paulo, Brazil. Of a total of 14.692 people with recent assessments of 25(OH)D and RT-PCR tests for COVID-19, 2.345 were positive and 11.585 were negative for the infection. The groups did not differ in the percentage of men and women, or in the age distribution. There were no differences in the distribution of 25(OH)D between the two groups (p = 0.08); mean 25(OH)D of 28.8 ± 21.4 ng/mL and 29.6 ± 18.1 ng/mL, respectively. In the specific population studied, clinical, environmental, socioeconomic and cultural factors should have greater relevance than 25(OH)D in determining the susceptibility to COVID-19.

Background Different pathogenic germline mutations in the RET oncogene are identified in MEN 2, a hereditary syndrome characterized by medullary thyroid carcinoma (MTC) and other endocrine tumors. Although genetic predisposition is recognized, not all RET mutation carriers will develop the disease during their lifetime or, likewise, RET mutation carriers belonging to the same family may present clinical heterogeneity. It has been suggested that a single germline mutation might not be sufficient for development of MEN 2-associated tumors and a somatic bi-allelic alteration might be required. Here we investigated the presence of somatic second hit mutation in the RET gene in MTC. Methods We integrated Multiplex Ligation-dependent Probe Amplification (MLPA) and whole exome sequencing (WES) to search for copy number alteration (CNA) in the RET gene in MTC samples and medullary thyroid cell lines (TT and MZ-CR-1). We next found reads spanning exon-exon boundaries on RET, an indicative of retrocopy. We subsequently searched for RET retrocopies in the human reference genome (GRCh37) and in the 1000 Genomes Project data, by looking for reads reporting joined exons in the RET locus or distinct genomic regions. To determine RET retrocopy specificity and recurrence, DNA isolated from sporadic and MEN 2-associated MTC (n = 37), peripheral blood (n = 3) and papillary thyroid carcinomas with RET fusion (n = 10) samples were tested using PCR-sequencing methodology. Results Through MLPA we have found evidence of CNA in the RET gene in MTC samples and MTC cell lines. WES analysis reinforced the presence of the CNA and hinted for a retroposed copy of RET not found in the human reference genome and 1.000 Genomes Project. Extended analysis confirmed the presence of a somatic MTC-related retrocopy of RET in both sporadic and hereditary tumors. We further unveiled a recurrent (28%) novel point mutation (p.G548 V) found exclusively in the retrocopy of RET. The mutation was also found in cDNA of mutated samples, suggesting it might be functional. Conclusion We here report a somatic specific RET retroposed copy in MTC samples and cell lines. Our results support the idea that generation of retrocopies in somatic cells is likely to contribute to MTC genesis and progression. Electronic supplementary material The online version of this article (10.1186/s12920-019-0552-1) contains supplementary material, which is available to authorized users.

Background: The thyroid storm is a rare disorder characterized by multisystem involvement and high mortality rates. A high index of suspicion should be maintained in patients with thyrotoxicosis associated with evidence of systemic decompensation. Case Presentation: A 25 year old male was referred to an endocrine clinic with the diagnose of Graves disease, complained about 34kg weight loss, goiter, diarrhea, palpitation and exophthalmia, his hormonal profile showed TSH 7.77 ng/dl (0.7-1.8), TRAb 25.2 UI/L, T3>651,0 ng/dl; Methimazole 20mg/day, and Propanolol 120mg/day were introduced at that appointment. After a month the patient was admitted at Santa Casa de São Paulo hospital as a result of orquiepididymitis and jaundice. He evolved 48hs after the admission with respiratory insufficiency, fever and tachycardia. Propylthiouracil 200mg 4/4hs, Lugol 8/8hs, dexamethasone, Tazocin, Meropenem, Vancomicine were introduced by the internal medicine team. The laboratory profile showed: total bilirubin 11.4, direct 10.4, RNI 2.06, AST 40, ALT 46, hemoglobin 10.7, hematocrit 33.4, leucocytes 7800 (86,7% neutrophils), plaques 128.000. Transthoracic echocardiogram revealed diffuse hypokinemia, mainly antero-septal, FE=38%, moderated left ventricle eccentric hypertrophy. After 48hs the endocrine team discontinued thionamide drugs, lithium and plasmapheresis was indicated. The patient did 3 session of plasmapheresis, the day after the first section he was extubated, and his hormonal scan revealed TSH 0.01 (0.4-5.8), T4l 1.04 (0.7-1.8), at that day. After recovering from the infection a total thyroidectomy was performed, and levothyroxine 1.0mcg/kg/day was introduced. The patient had post-operative hypoparathyroidism and is takin calcitriol, calcium carbonate and cholecalciferol. Conclusion: A multimodality treatment approach should be used. Therapeutic plasma exchange (TPE) is a potential therapeutic option for thyroid storm, but its indication is not well established. The literature contains few reported cases and no clear guidelines about indication criteria and best time to start. When there are threatening symptoms, TPE should be done early, without waiting for the efficiency of conventional treatment. It’s effect can be explained by the rapid decline of plasma hormones and antibodies responsible for Graves’ disease. It is a relatively safe therapy, although it has a high cost. Monitoring the thyroid hormones is interesting, but clinical improvements are often dissociated from the hormonal levels and must be mainly judged on the patient’s condition.

Background: Insulinoma is the most common functioning pancreatic neuroendocrine tumor. It’s an important endocrine etiology of obesity, which is characterized by a hyperinsulinemic hypoglycemia (HH). Case reports: Case 1: A 23 years old woman developed hypoglycemia symptoms and weight gain (13kg in 6 months). The prolonged fasting test (PFT) was performed: plasma glucose 29 mg/dL, C-peptide 2,6ng/mL (< 0,6 ng/mL), plasma insulin 29,9 μU/mL (< 3,0 μU/mL), showing a HH. Abdominal CT showed a 1.3 cm hypervascularity nodule, next to the distal portion of the pancreatic tail close to the vein and splenic artery. A successful partial pancreatectomy and splenectomy were performed and she remains asymptomatic. Case 2: A 41 years old man, with severe obesity Body Mass Index (BMI) 65 kg/m2 and impaired fasting glucose presented HH (glucose 41 mg/dL, C-peptide 27,3 ng/mL, insulin 637 μU/mL) and weight gain. MRI showed a 3,0 cm hypervascularity nodule between the body and pancreas tail. Octreotide, diazoxide, dextrose continuous infusion pump and hydrochlorothiazide were prescribed to control hypoglycemia. Partial pancreatectomy and splenectomy were performed but in the postoperative period, patient developed renal failure, sepsis, acute respiratory distress syndrome and death. Case 3: A 21 years old woman with severe obesity (BMI 60 kg/m2), after using intragastric balloon for 6 months, developed hypoglycemic symptoms, including seizures. The PFT showed plasma glucose 44 mg/dl, plasma insulin 47 μU/mL, C-peptide 3,2 ng/mL. MRI showed a 1.9 cm hypervascularity nodule in the cephalic portion of the pancreas, very close to cava vein. Diazoxide was prescribed with improvement of hypoglycemia. Due to the high surgical risk given the location of the tumor and obesity, an endoscopic ultrasound (EUS) guided ethanol ablation was performed. After the procedure, diazoxide was discontinued and two months later she had no hypoglycemia and is still loosing weight. Antiinsulin antibodies were negative and all biopsies confirmed insulinoma. Conclusion: Insulinomas can be a challenging diagnose and management. Once, most of the patients are overweight, the surgical treatment became a threat , therefore advanced techniques are an important advance for reducing mortality.

Objective: Multiple endocrine neoplasia type 1 (MEN1) has an estimated incidence in the general population of 0.01 to 2.5 cases per 1,000 individuals. Here we report on the case of a 36-year-old female patient with some uncommon aspects of MEN1.Methods: The patient was admitted with primary hyperparathyroidism (PHPT) and suspicion of parathyroid carcinoma, demanding additional exams. Abdominal resonance imaging revealed a left adrenal mass, three pancreatic tumors, and hepatic lesions. Diagnostic work-up revealed hypergastrinemia and autonomous production of corticosteroids.Results: The patient was subjected to multiple surgeries: subtotal parathyroidectomy, left adrenalectomy, subtotal pancreatectomy associated with enucleation of a tumor lesion in the pancreatic head, and resection of a hepatic metastasis. The patient's DNA sequencing analysis revealed a frameshift mutation in exon 3 of the MEN1 gene. Her daughter was found to be affected by the same mutation.Conclusion: This case presents three uncommon aspects in MEN1: (1) suspicion of PHPT due to parathyroid carcinoma, (2) the presence of a functioning adrenal adenoma producing Cushing syndrome, and (3) pancreatic location and malignancy of the gastrinoma.Abbreviations: MEN1 = multiple endocrine neoplasia type 1; PHPT = primary hyperparathyroidism; PTH = parathyroid hormone

Introduction Surgery has been the standard treatment for Cushing's disease. Currently, the endoscopic endonasal approach (EEA) is the most widely used technique. However, among some endocrinologists and neurosurgeons used to the microscope assisted technique, there are still questions about the effectiveness and safety of transitioning to the EEA. We aim to show our initial experience with such transition. Method Retrospective review of medical records of patients, who underwent EEA in our center as a first treatment for Cushing's disease, and with a minimum 18 months of follow-up, from March 2004 to March 2014 Results Our cohort had 16 patients (14 females and 2 males), with a mean age of 33.7 years. The mean follow-up was 52.0 months. Magnetic resonance imaging (MRI) identified an adenoma in 93.8% of the patients (56.2% microadenomas and 37.5% macroadenomas). Postoperative cerebrospinal fluid (CSF) leak was observed in two patients (12.5%). No new neurological deficits were present after surgery. The early remission and sustained remission rates after a single procedure were 87.5 and 68.75%, respectively. Weight reduction, improved control of blood pressure, and lower serum glucose levels were documented in 68.75, 60, and 55.5% of patients, respectively, after remission. Conclusion Despite the need for specialized training, equipment and team building by ENT (Ear, Nose and Throat) and neurosurgery, the transition from microscope assisted pituitary surgery to endoscopic endonasal approach is possible and safe. The clinical outcomes, even in the early years, are similar to the previous microscope assisted treatment, and over time, with greater experience and knowledge, there is a tendency for improvement.

Treatment of advanced medullary thyroid carcinoma (MTC) was recently improved with the approval of vandetanib and cabozantinib. However, there is still a need to explore sequential therapy with more than one tyrosine kinase inhibitor (TKI) and to explore alternative therapies when vandetanib and cabozantinib are not available. This study reports the authors' experience with sorafenib as a treatment for advanced MTC.This is a retrospective longitudinal study of 13 patients with progressive metastatic MTC treated with sorafenib 400 mg twice daily between December 2011 and January 2015. The primary endpoints were to evaluate response and progression-free survival (PFS) in patients treated with sorafenib outside a clinical trial. The secondary endpoint was an assessment of the toxicity profile. One patient was excluded because of a serious allergic skin rash one week after starting sorafenib.The analysis included 12 patients with metastatic MTC (median age 48 years), 10 with sporadic and 2 with hereditary disease. The median duration of treatment was 11 months, and the median follow-up was 15.5 months. At data cutoff, 2/12 (16%) patients were still on treatment for 16 and 34 months. According to Response Evaluation Criteria in Solid Tumors analysis, 10 (83.3%) patients showed stable disease, and two (16.6%) had progression of disease; no partial response was observed. The median PFS was nine months. However, three patients with extensive and rapidly progressive disease died within three months of sorafenib treatment. The median PFS excluding these three patients was 12 months. Adverse events (AE) occurred in nine (75%) patients. The main AEs were skin toxicity, weight loss, and fatigue. Five (41.6%) patients needed dose reduction, and one patient discontinued treatment because of toxicity.Treatment with sorafenib in progressive metastatic MTC is well tolerated and resulted in disease control and durable clinical benefit in 75% of patients. Sorafenib treatment could be considered when vandetanib and cabozantinib are not available or after failing these drugs.

Objective: The aim of this study was to evaluate the results of the endoscopic transsphenoidal technique for growth hormone (GH)-secreting adenomas. Methods: A retrospective analysis based on medical records of 23 acromegalic patients submitted to endoscopic transsphenoidal surgery. Biochemical control was defined as basal GH < 1ng/ml, nadir GH < 0.4ng/ml after glucose load and age-adjusted IGF-1 normal at the last follow-up. Results: The overall endocrinological remission rate was 39.1%. While all microademonas achieved a cure, just one third of macroadenomas went into remission. Suprasellar extension, cavernous sinus invasion and high GH levels were associated with lower rates of disease controlThe mos . t common complication was diabetes insipidus and the most severe was an ischemic stroke .Conclusion: The endoscopic transsphenoidal approach is a safe and effective technique to control GH-secreting adenomas. The transcavernous approach may increase the risk of complications. Suprasellar and cavernous sinus extensions may preclude gross total resection of these tumors.Keywords: acromegaly; growth hormone-secreting pituitary adenoma; endoscopy

Objetivo Descrever e analisar a técnica empregada para a cateterização bilateral dos seios petrosos inferiores (SPI) em nosso serviço, discutindo as dificuldades e as taxas de sucesso encontradas. Sujeitos e métodos Entre 2009 e 2012, foram submetidos ao cateterismo bilateral dos SPI 14 pacientes com suspeita de síndrome de Cushing, sendo descrita a técnica empregada para o cateterismo e para a análise hormonal. Resultados O procedimento foi bem tolerado por todos os pacientes, sendo alcançada a cateterização adequada dos SPI em 92,85% dos casos. O diagnóstico de doença de Cushing foi firmado em 10 casos, sendo o resultado do cateterismo dos SPI após estímulo com CRH coerente em todos, não havendo falso-negativos. Conclusão O cateterismo dos SPI, apesar de ser uma técnica invasiva, é um procedimento seguro. A sua realização pode ser feita de forma adequada na maioria dos casos e, quando bem indicada, permanece como padrão-ouro na distinção da forma hipofisária da ectópica na síndrome de Cushing. Objective To describe and analyze technique for bilateral catheterization of inferior petrosal sinus in our service, discussing the difficulties and success rates found. Subjects and methods Fourteen patients with suspected Cushing’s syndrome underwent bilateral inferior petrosal sinuses (IPS) catheterization between 2009 and 2012. The technique for catheterization and for hormone analysis were described. Results The procedure was well tolerated by all patients, and adequate catheterization was achieved in 92.85% of cases. The diagnosis of Cushing’s disease was confirmed in 10 cases. The result of IPS catheterization after CRH infusion was coherent in all cases, without false negatives. Conclusion The catheterization of IPS, despite being an invasive technique, is a safe procedure. The objectives can be done properly in most cases. When well indicated, this procedure remains the gold standard in distinguishing the ectopic form to pituitary source in Cushing’s syndrome.

To describe and analyze technique for bilateral catheterization of inferior petrosal sinus in our service, discussing the difficulties and success rates found.Fourteen patients with suspected Cushing's syndrome underwent bilateral inferior petrosal sinuses (IPS) catheterization between 2009 and 2012. The technique for catheterization and for hormone analysis were described.The procedure was well tolerated by all patients, and adequate catheterization was achieved in 92.85% of cases. The diagnosis of Cushing's disease was confirmed in 10 cases. The result of IPS catheterization after CRH infusion was coherent in all cases, without false negatives.The catheterization of IPS, despite being an invasive technique, is a safe procedure. The objectives can be done properly in most cases. When well indicated, this procedure remains the gold standard in distinguishing the ectopic form to pituitary source in Cushing's syndrome.