Neoplasia endócrina múltipla tipo 2A: relato de caso / Multiple endocrine neoplasia type 2A: a case report / Neoplasia endocrina múltiple tipo 2A: reporte de caso

As neoplasias endócrinas múltiplas (NEM) são síndromes genéticas autossômicas dominantes implicadas no desenvolvimento de neoplasias benignas ou malignas, envolvendo ao menos duas glândulas endócrinas. Entre seus subtipos, está a NEM2A, que consiste em carcinoma medular de tireoide (CMT), feocromocitoma e hiperparatireoidismo. Este texto apresente o relato de caso de um paciente de 40 anos, previamente hígido, que passou a apresentar episódios de cefaleia associada a sudorese profusa, vômitos e taquicardia. Evoluiu com distensão abdominal intensa após alimentação por via oral, perda ponderal, desnutrição, astenia, obstipação, humor deprimido e picos pressóricos. Exames laboratoriais evidenciaram alterações dos hormônios tireoidianos, PTH e hormônios da adrenal. Foi levantada a suspeita clínica de NEM2A, posteriormente corroborada pelos diagnósticos anatomopatológicos de feocromocitoma e CMT, associados à presença de hiperparatireoidismo. Foi possível concluir que, a despeito de sua baixa prevalência na população geral, a NEM é uma síndrome clínica de grande relevância, tendo em vista os impactos para os pacientes e famílias acometidas. Dessa forma, é necessário que os profissionais de saúde tenham conhecimento acerca da síndrome e que o Sistema Único de Saúde (SUS) esteja apto a assistir aos pacientes portadores de NEM, possibilitando diagnóstico precoce e tratamento adequado.

Multiple endocrine neoplasias (MEN) are dominant autosomal genetic syndromes involved in the development of benign or malignant tumors in at least two endocrine glands. MEN2A is one of its subtypes, which consists of medullary thyroid carcinoma (MTC), pheochromocytoma, and hyperparathyroidism. This study reports the case of a healthy 40-year-old male patient presenting with episodes of headache associated with profuse sweating, vomiting, and tachycardia. The patient evolved with severe abdominal distension after oral feeding, weight loss, malnutrition, asthenia, constipation, depressed mood, and pressure peaks. Laboratory tests showed abnormalities in thyroid, parathyroid (PTH), and adrenal hormones ­ thus raising the hypothesis of MEN2A, which was later corroborated by the histological diagnosis of pheochromocytoma and MTC, associated with hyperparathyroidism. The results indicate that, despite its low prevalence in the general population, MEN has a great impact on affected patients and families, thus being a relevant clinical syndrome. For enabling early diagnosis and adequate treatment, health professionals must be familiarized with such a condition, and the Brazilian Unified Health System (SUS) must be able to assist affected patients.

Las neoplasias endocrinas múltiples (NEM) son síndromes genéticos autosómicos dominantes involucrados en el desarrollo de neoplasias benignas o malignas, que afectan al menos dos glándulas endocrinas. Entre sus subtipos se encuentra NEM2A, que consiste en carcinoma medular de tiroides (CMT), feocromocitoma e hiperparatiroidismo. Este es un reporte de caso de un paciente de 40 años de edad, previamente sano, que comenzó a presentar episodios de cefalea asociada a sudoración profusa, vómitos y taquicardia. Evolucionó con distensión abdominal severa después de alimentarse, pérdida de peso, desnutrición, astenia, estreñimiento, estado de ánimo deprimido y picos de presión. Las pruebas de laboratorio mostraron alteraciones en las hormonas tiroideas, PTH y hormonas suprarrenales. Se planteó la hipótesis de MEN2A, posteriormente corroborada por el diagnóstico anatomopatológico de feocromocitoma y CMT, asociado a hiperparatiroidismo. Se pudo concluir que, a pesar de su baja prevalencia en la población general, el NEM es un síndrome clínico de gran relevancia, dado el impacto que tiene en los pacientes y familiares afectados. Por tanto, es necesario que los profesionales sanitarios tengan conocimiento sobre el síndrome y que el Sistema Único de Salud (SUS) sea capaz de asistir a los pacientes con NEM, posibilitándoles diagnóstico precoz y tratamiento adecuado.

Renal Papillary Necrosis Associated With Normocalcemic Primary Hyperparathyroidism.

OBJECTIVES: Renal papillary necrosis (RPN) occurring in primary hyperparathyroidism (PHPT) has not been reported. We present a 50-year-old woman who manifested RPN associated with hypercalciuria and normocalcemic PHPT. METHODS: The diagnosis of RPN was based on imaging studies (ultrasound and computed tomography [CT] scan). PHPT was diagnosed with high parathyroid hormone (PTH) and high/normal serum calcium. RESULTS: A 38-year-old woman was evaluated for hypercalcemia (serum calcium, 11.8 mg/dL; ionized calcium, 6.3 mg/dL; phosphorus, 1.8 mg/dL; intact PTH, 98 pg/mL; and 24-hour urine calcium, 543 mg). Renal ultrasound showed no nephrocalcinosis or nephrolithiasis. A parathyroid scan revealed a left parathyroid adenoma. The patient underwent parathyroidectomy, and she became normocalcemic with normal serum PTH levels postoperatively. One year later, she was diagnosed with a left-sided bronchial carcinoid tumor. Following surgery, a surveillance gallium68 positron emission tomography/CT scan performed 2 years later was negative for metastases. Twelve years later (aged 50 years), she presented for follow-up and reported no symptoms of hypercalcemia, fractures, nephrolithiasis, history of pyelonephritis, diabetes mellitus, analgesic drug use, or hypertension. Her serum calcium level was 9.1 mg/dL, PTH level was 82 pg/mL, 25-OH vitamin D level was 34 ng/mL, and 24-hour urine calcium level was 410 mg. However, renal ultrasound showed bilateral RPN that was confirmed by a CT scan. CONCLUSION: RPN may be associated with hypercalciuria and normocalcemic PHPT. Additional studies with a large number of patients are needed.

Identification of Occult Adenomas in Primary Hyperparathyroidism With 18F-fluorocholine PET/CT. / Identificación de adenomas ocultos en hiperparatiroidismo primario con PET-TC 18F-fluorocolina.

INTRODUCTION: Single parathyroid adenomas are the most common cause of primary hyperparathyroidism (PHP) in our population. Parathyroidectomy is still the only potentially curative treatment and requires preoperative localization imaging studies to perform selective surgery. In patients with negative results on conventional tests, PET/CT has demonstrated higher sensitivity rates. METHODS: A prospective cohort study was designed, including 34 patients diagnosed with PHP between 2017 and 2019, candidates for surgery with negative preoperative localization tests with scintigraphy and MIBI SPECT/CT. All patients underwent PET/CT with 18F-Fluorocholine. The clinical, biochemical and postoperative outcome results were compared with a control group of 30 patients with positive standard tests. RESULTS: Hyperfunctional parathyroid tissue was detected in 85% of the patients that had undergone choline PET/CT. The selective resection of the adenoma identified in these patients achieved curative criteria in 87% of the cases without undergoing bilateral cervical surgical exploration. The preoperative levels of PTH, calcemia and gland weight were significantly lower in this group compared to the control group. No differences were identified in cure criteria or approach between the 2groups. CONCLUSION: In our study, choline PET/CT showed higher detection rates compared to the gold standard. The increase provides the opportunity to perform unilateral selected adenoma resection, especially in patients with smaller adenomas associated with lower calcemia and PTH levels and patients with previous cervical surgery.

A clinical perspective of parathyroid hormone related hypercalcaemia.

There are many causes of hypercalcaemia including hyperparathyroidism, drugs, granulomatous disorders and malignancy. Parathyroid hormone (PTH) related hypercalcaemia is most commonly caused by primary hyperparathyroidism (PHPT) and more rarely by familial hypocalciuric hypercalcaemia (FHH). Algorithms for diagnosis of PTH related hypercalcaemia require assessment of a 24-h urinary calcium and creatinine excretion to calculate calcium/creatinine clearance ratio and radiological investigations including ultrasound scan and 99mTc-sestamibi-SPECT/CT. To illustrate investigations and management of parathyroid-related hypercalcaemia, we present a selection of distinct cases of PHPT due to eutopic and ectopic parathyroid adenomas, as well as a case with a syndromic form of PHPT (multiple endocrine neoplasia type 1), and a case with FHH type 1 due to a CASR inactivating mutation. Additional cases with normocalcaemic hyperparathyroidism and secondary hyperparathyroidism are included for completeness of differential diagnosis. The common eutopic parathyroid adenomas are easily treated with parathyroidectomy while the less common ectopic parathyroid adenomas require more complex investigations and operative procedures such as video-assisted thoracoscopic surgery. On the other hand, the much less common FHH does not require treatment. Assessment of kin with FHH is important to identify members with this inherited condition in order to prevent unnecessary interventions.

Occurrence of paratesticular ganglioneuroma 18 years after concurrent adrenal ganglioneuroma and papillary thyroid carcinoma - a case report.

BACKGROUND: Ganglioneuromas (GNs) are composed of mature ganglion cells and Schwann cells with a fibrous stroma; GNs are most often observed in children and young adults. The majority of non-cranial GNs are located in the retroperitoneum and posterior mediastinum. Other reported rare sites include the adrenal gland, small intestine, colon and urinary bladder. However, para-testicular GNs are even more rare. CASE PRESENTATION: Herein, we report the case of a patient with concurrent adrenal GN and thyroid papillary carcinoma who developed paratesticular GN eighteen years later. CONCLUSIONS: We conclude that there is an association among papillary thyroid carcinoma, GN and MEN2 syndromes. This case report may provide important information for the proposed association. However, further studies are required.

A case of type 1 multiple endocrine neoplasia with esophageal stricture successfully treated with endoscopic balloon dilation and local steroid injection combined with surgical resection of gastrinomas.

BACKGROUND: In type 1 multiple endocrine neoplasia (MEN1), esophageal diseases association with excessive gastrin secretion in Zollinger-Ellison syndrome (ZES) sometimes develop. Here, we reported a case of MEN1/ZES, who developed dysphagia due to reflux esophagitis with severe esophageal stricture. Treatment for his esophageal stricture and ZES was discussed. CASE PRESENTATION: A 43-year-old man with progressive dysphagia and diarrhea was referred to the teaching hospital. He had a history of recurrent duodenojejunal perforations despite the anti-secretory medication. Blood examinations revealed elevated serum gastrin, calcium, and parathyroid hormone. Upper gastrointestinal endoscopy demonstrated a severe esophageal stricture, multiple gastroduodenal ulcer scars, and a duodenal submucosal tumor. Enhanced computed tomography showed multiple hypervascular tumors within the pancreas and duodenum, suggestive of MEN1. Genetic examination demonstrated a pathogenic MEN1 mutation. Repetitive endoscopic esophageal dilatation with intralesional corticosteroid injection, coupled with pancreatoduodenectomy were performed to improve the patient's symptoms and to treat pancreatic tumors. The histology of multiple tumors in the duodenum and pancreas were all consistent with neuroendocrine tumors. His hypergastrinemia subsided and he remained asymptomatic in his gastrointestinal tract after these treatments. CONCLUSION: For esophageal stenosis in case of MEN1/ZES, anti-secretory therapy and endoscopic dilatation with corticosteroid injection could be recommended. However, in refractory cases with repetitive and/or severe complications due to high acid secretion, surgical treatment could be considered as an option.

Diagnosis and treatment of multiple insulinom / 中华普通外科杂志

Objective To summarize the diagnostic and therapeutic experiences for multiple insulinoma. Methods Clinical data of 34 cKsefl of multiple insulinoma treated in Peking Union Medical College Hospital between 1984 and 2007 were analyzed retrospectively. Results Multiple insulinoma was identified in these 34 cases for 37 instances.Malignant insulinoma was found in 2 cases.Three cases suffered from postoperative recurrent multipie tumors.35.3% cases belonged to MEN1;13.5% cases were of insulinoma combined with islet hyperplasia;43.2% cases had 3 or more than 3 insulinomas;Fifteen cases (40.5%)had had a misdiagnosis.45.2%tumors were smaller than 1 cm in diameter:88.9%multiple insulinonla located at the body and tail of the pancreas.Enucleation of multiple tumors was performed for 48.7 percent of cases. Conclusions Most multiple insulinomas were small,it was difficult for preoperative examination to locate all the tumors therefore.Being on the alert against multiple insulinoma and such measures as careful exploration,intraoperative blood glucose determination.fine needle aspiration biopsy,frozen sections helps to avoid missing multiple imuhnoma.

The Characteristics of Multiple Endocrine Neoplasia in Korean / 대한내분비외과학회지

PURPOSE: Multiple Endocrine Neoplasm (MEN) is a rare, complex and familial disease. There are MEN syndromes are inherited in an autosomal dominant fashion with high penetrance. The variations in the RET gene play an important role in the MEN syndromes. Recent advances in diagnosis, treatment and genetic study of patients with MEN in Korean are reviewed. METHODS: There were 79 cases and 20 families with MEN syndromes in Korea which based on my experiences and 27 published papers. According to subtypes, there were classified and analyzed. RESULTS: Mean age was 37.9±11.5 years old. Sex ratio was 1:2.6. There were 7 families and 23 cases with MEN type I in Korean. The clinical characteristics of MEN I in Korean are mostly not different from the previous reports except older age (mean=43.2 old-year) at diagnosis. The frequency of the MEN I germ-line mutation in Korean MEN I (80%) families was similar to those reported previously. There were 13 families and 52 cases with MEN type II A in Korean. Three-quarters (9/12) of the Korean patients with MEN IIa had RET mutations on codon 634 of exon 11 (4 patients, C634; 4 patients, C634Y; 1 patient, C634W), but a quarter (3/12) had mutations on codon 618 of exon 10 (2 patients, C618R; 1 patient, C618S). A small medullary carcinoma in a patient of MEN type II A family was detected by genetic mutation screening in SMC. MEN IIb was reported only 4 cases. A case showed a codon 918 mutation (M918T) at exon 16 of RET proto-oncogene. CONCLUSION: Multiple endocrine neoplasia is rare hereditary cancer syndromes expressing a variety of tumors. With understanding of the molecular and clinical pathology of MEN syndromes, genetic screening is now feasible, and treatments have become more individualized based on genetic information of Korean.

Clinical significance of molecular genetic changes in sporadic invasive pituitary adenomas

Several molecular and genetic changes have been found in pituitary adenomas. We looked for correlations between these changes and the degree of invasiveness of the tumors. The invasiveness of 11 pituitary adenomas was graded by Hardy classification. We examined the retinoblastoma gene (RB1.20 on chromosome 13q) and the region around the MEN1 locus (chromosome 11q13.1-5) for loss of heterozygosity. Also examined are p53 mutations using single strain conformation polymorphism, p53 protein overexpression using immuno cytochemistry, homozygous deletions of p15 and p16 by polymerase chain reaction, and cellular proliferative activity using MIB-1 antibody. Six tumors (54.5%) had an LOH at either RB1.20 or the MEN1 locus. LOHs were found more frequently in Grade 4 and stage E tumors (72% and 67%) than in Grade 3 and stage D tumors (25% and 40%). However, no mutation or overexpression of p53 was found. No homozygous deletions of p15 or p16 were identified. The cell proliferative index ranged from 0 to 3%. LOH at 11q13 and 13q may be valuable in predicting the invasiveness of pituitary adenomas.