Transient remission of hyperparathyroidism after fine-needle aspiration biopsy.

Primary hyperparathyroidism (PHPT) is the unregulated overproduction of parathyroid hormone (PTH), resulting in abnormal calcium homeostasis. PHPT is most commonly caused by a single adenoma of the parathyroid gland, which can have an intrathyroid location in rare cases. The measurement of intact PTH in the washout fluid obtained by ultrasound (US)-guided fineneedle aspiration (FNA) can be useful in clarifying the aetiology of these lesions. This study presented a 48-year-old man with a background history of symptomatic renal stone disease who was diagnosed with PHPT and referred to our Endocrinology department. A neck US revealed a thyroid nodule with a size of 21 mm in the right lobe. The patient underwent US-guided FNA of the lesion. The measurement of PTH in the washout fluid was significantly elevated. Following the procedure, he reported neck pain and noticed distal paraesthesias in the upper limbs. Blood test results showed significant hypocalcaemia and supplementation with calcium and calcitriol was started. The patient was closely monitored. Recurrence of hypercalcaemia was later observed, and the patient was submitted to surgery. We present a case of FNAinduced transitory remission of PHPT in a patient with an intrathyroid parathyroid adenoma. We conjecture that intra-nodular haemorrhage might have occurred, which temporarily affected the viability of the autonomous parathyroid tissue. A few similar cases of spontaneous or induced remission of PHPT after FNA have been previously described in the literature. This remission can be transitory or permanent, depending on the degree of cellular damage thus follow-up of these patients is recommended.

Microscopic extrathyroid extension in papillary thyroid carcinoma: impact on response to therapy.

Objectives Evaluate the impact of microscopic extrathyroid extension (MEE) on outcome and therapy response in patients with cT1 and cT2 papillary thyroid carcinoma (PTC). Subjects and methods Retrospective study of 970 consecutive patients, who underwent surgery for PTC between 2000 and 2016. All patients had: tumours ≤ 4 cm, apparent complete tumour resection, without clinically apparent lymph node or distant metastasis at diagnosis and nonaggressive histologic variant. Results Based on the finding of MEE, 175 (18.0%) patients were upstaged to T3. They were older (53.9 versus 50.6 years; P = 0.004) and were more prone to have multifocal tumours (38.2% versus 24.8%; P = 0.001). Radioiodine ablation therapy (RAI) was administered more often to MEE patients (92% versus 40.5%; P < 0.001), as well as prophylactic lymph node resection (35.4% versus 28.6%, P = 0.048). They were more likely to have biochemical incomplete response (4% versus 0.3%; P = 0.03) at the end of the follow-up period. There was no significant association between MEE and recurrence rate, persistence of disease or disease-specific mortality. Conclusion These results support the changes made to the latest edition of the TNM staging system, regarding MEE. Although incomplete biochemical response is more common in these patients, it does not seem to affect their prognosis.

Lymph Node Metastases of Medullary Thyroid Cancer: Role of Calcitonin in the Washout Fluid of Fine-Needle Aspiration.

INTRODUCTION: The diagnostic value of calcitonin (CT) measurement in fine-needle aspirate washout (FNA-CT) for medullary thyroid cancer (MTC) lymph node (LN) metastases remains to be determined. It may increase the diagnostic sensitivity, but data on this subject is sparse. OBJECTIVE: Our study aimed to evaluate the utility of FNA-CT in the diagnosis of LN metastases of MTC. METHODS: We retrospectively investigated, in our institutional database, 69 consecutive FNA LN cytology from 42 patients who underwent FNA cytology and CT measurement in needle washout for suspicious LN between 2012 and 2017. RESULTS: From the total of 69 FNA, 30 (43.4%) were performed in patients with personal history of MTC. MTC was detected in 19 FNA cytology (27.5%), and CT was detectable in needle washout in 23 cases (median = 2014 pg/mL; interquartile range = 490-15111 pg/mL). Based on the combined results of FNA-CT and FNA cytology, LN surgical resection was performed in 33 cases (47.8%). Histology reported MTC LN metastases in 21 lesions (63.6%). Regarding the diagnosis of MTC LN metastases, FNA cytology showed sensitivity of 81.8% and specificity of 97.9%, and FNA-CT demonstrated sensitivity of 100% and specificity of 97.9%. We determined through ROC analysis an optimal FNA-CT cut-off value of 23 pg/mL for the diagnosis of LN metastases (sensitivity 100%; specificity 100%). CONCLUSIONS: FNA-CT may be a valuable diagnostic tool for detection of MTC LN metastases, along with FNA cytology, and it should be included in the clinical workup of neck adenopathies in patients with MTC or with thyroid nodules.

Microscopic extrathyroid extension in papillary thyroid carcinoma: impact on response to therapy

ABSTRACT Objectives Evaluate the impact of microscopic extrathyroid extension (MEE) on outcome and therapy response in patients with cT1 and cT2 papillary thyroid carcinoma (PTC). Subjects and methods Retrospective study of 970 consecutive patients, who underwent surgery for PTC between 2000 and 2016. All patients had: tumours ≤ 4 cm, apparent complete tumour resection, without clinically apparent lymph node or distant metastasis at diagnosis and nonaggressive histologic variant. Results Based on the finding of MEE, 175 (18.0%) patients were upstaged to T3. They were older (53.9 versus 50.6 years; P = 0.004) and were more prone to have multifocal tumours (38.2% versus 24.8%; P = 0.001). Radioiodine ablation therapy (RAI) was administered more often to MEE patients (92% versus 40.5%; P < 0.001), as well as prophylactic lymph node resection (35.4% versus 28.6%, P = 0.048). They were more likely to have biochemical incomplete response (4% versus 0.3%; P = 0.03) at the end of the follow-up period. There was no significant association between MEE and recurrence rate, persistence of disease or disease-specific mortality. Conclusion These results support the changes made to the latest edition of the TNM staging system, regarding MEE. Although incomplete biochemical response is more common in these patients, it does not seem to affect their prognosis.

Surveillance of succinate dehydrogenase gene mutation carriers: Insights from a nationwide cohort.

OBJECTIVE: Mutations in the genes coding for succinate dehydrogenase (SDHx) are the most frequent germline alterations in pheochromocytomas and paragangliomas. Evidence for the advantages associated with presymptomatic screening for SDHx mutation carriers is scarce. This study describes a nationwide cohort of these mutation carriers and aims to compare patients with clinical manifestations of the disease and those diagnosed through genetic screening. DESIGN: Cross-sectional study. PATIENTS: SDHx mutation carriers (n = 118) followed through the Portuguese Oncology referral centres: 41 probands and 77 nonprobands. MEASUREMENTS: All participants were subjected to biochemical and body imaging examinations for a complete assessment of the extent and spread of disease. Clinical data obtained this way were further analysed. RESULTS: The mean age of this cohort was 44.5 ± 17.4 years, and more than half carried the same founder SDHB mutation. About 50.8% of the mutation carriers developed pheochromocytomas or paragangliomas. Compared to patients diagnosed through genetic screening, those diagnosed clinically were characterized by larger tumours (P < .001), more frequent metastases (P = .024), were more frequently subjected to surgery (P = .011) and radiotherapy (P = .013), and had worse outcomes, such as macroscopic positive margins (P = .034). Persistent and/or unresectable disease and disease-related mortality were also more frequent in symptomatic patients compared to those diagnosed through genetic screening (P = .014). CONCLUSIONS: In this nationwide cohort study, a large proportion of mutation carriers were found to develop SDHx-related neoplasia. Genetic testing and subsequent follow-up resulted in the diagnosis of smaller and nonmetastatic tumours, fewer treatment procedures, fewer complications and greater number of disease-free patients.

Metabolomic Urine Profile: Searching for New Biomarkers of SDHx-Associated Pheochromocytomas and Paragangliomas.

CONTEXT: Metabolomic studies of pheochromocytoma and paraganglioma tissue showed a correlation between metabolomic profile and presence of SDHx mutations, especially a pronounced increase of succinate. OBJECTIVE: To compare the metabolomic profile of 24-hour urine samples of SDHx mutation carriers with tumors (affected mutation carriers), without tumors (asymptomatic mutation carriers), and patients with sporadic pheochromocytomas and paragangliomas. METHODS: Proton nuclear magnetic resonance spectroscopic profiling of urine samples and metabolomic analysis using pairwise comparisons were complemented by metabolite set enrichment analysis to identify meaningful patterns. RESULTS: The urine of the affected SDHx carriers showed substantially lower levels of seven metabolites than the urine of asymptomatic mutation carriers (including, succinate and N-acetylaspartate). The urine of patients with SDHx-associated tumors presented substantially higher levels of three metabolites compared with the urine of patients without mutation; the metabolite set enrichment analysis identified gluconeogenesis, pyruvate, and aspartate metabolism as the pathways that most probably explained the differences found. N-acetylaspartate was the only metabolite the urinary levels of which were significantly different between the three groups. CONCLUSIONS: The metabolomic urine profile of the SDHx mutation carriers with tumors is different from that of asymptomatic carriers and from that of patients with sporadic neoplasms. Differences are likely to reflect the altered mitochondria energy production and pseudohypoxia signature of these tumors. The urinary levels of N-acetylaspartate and succinate contrast with those reported in tumor tissue, suggesting a defective washout process of oncometabolites in association with tumorigenesis. The role of N-acetylaspartate as a tumor marker for these tumors merits further investigation.

Gastric neuroendocrine neoplasm with late liver metastasis.

Gastric neuroendocrine neoplasms (GNENs) are classified into three types according to their aetiology. We present a clinical case of a female patient of 66 years and a well-differentiated (grade 2), type 3 GNEN with late liver metastasis (LM). The patient underwent surgical excision of a gastric lesion at 50 years of age, without any type of follow-up. Sixteen years later, she was found to have a neuroendocrine tumour (NET) metastatic to the liver. The histological review of the gastric lesion previously removed confirmed that it was a NET measuring 8 mm, pT1NxMx (Ki67 = 4%). 68Ga-DOTANOC PET/CT reported two LM and a possible pancreatic tumour/gastric adenopathy. Biopsies of the lesion were repeatedly inconclusive. She had a high chromogranin A, normal gastrin levels and negative anti-parietal cell and intrinsic factor antibodies, which is suggestive of type 3 GNEN. She underwent total gastrectomy and liver segmentectomies (segment IV and VII) with proven metastasis in two perigastric lymph nodes and both with hepatic lesions (Ki67 = 5%), yet no evidence of local recurrence. A 68Ga-DOTANOC PET/CT was performed 3 months after surgery, showing no tumour lesions and normalisation of CgA. Two years after surgery, the patient had no evidence of disease. This case illustrates a rare situation, being a type 3, well-differentiated (grade 2) GNEN, with late LM. Despite this, it was possible to perform surgery with curative intent, which is crucial in these cases, as systemic therapies have limited efficacy. We emphasise the need for extended follow-up in these patients. LEARNING POINTS: GNENs have a very heterogeneous biological behaviour.Clinical distinction between the three types of GNEN is essential to plan the correct management strategy.LMs are rare and more common in type 3 and grade 3 GNEN.Adequate follow-up is crucial for detection of disease recurrence.Curative intent surgery is the optimal therapy for patients with limited and resectable LM, especially in well-differentiated tumours (grade 1 and 2).

Invasive thyroid angiosarcoma with a favorable outcome.

INTRODUCTION: Thyroid angiosarcoma is a malignant neoplasm, which usually shows local aggressive behavior and associated with a high recurrence rate. It was originally described in the Alpine region and extremely rare in other parts of the world. CASE PRESENTATION: An asymptomatic 61-year-old woman presented with a right lobe thyroid nodule with fine needle aspiration cytology indicating "suspicious for malignancy" was reported in our study. Histological examination revealed a vascular 35mm neoplasm with areas of necrosis. Immunohistochemistry staining had negative results for MNF, CAM5.2, CD34, thyroglobulin, and positive for CD31. The findings described were compatible with angiosarcoma diagnosis. Besides, a 4mm papillary microcarcinoma was found in the left lobe. Computerized tomography (CT) scan performed about two months after the operation, showed a right neck nodular lesion, conditioning tracheal deviation. At our institution, the study performed was consistent with local recurrence (angiosarcoma). Tumor excision was performed and invasion to larynx, trachea and esophagus was detected intraoperatively. Histopathologic examination confirmed tumor recurrence and the patient was submitted to radiotherapy (60 Gy), completed four years ago. There is not, so far, any evidence of tumor recurrence. CONCLUSIONS: We described a rare case of a usually aggressive thyroid angiosarcoma in a patient living in a non-Alpine region, with an unusual favorable outcome after the operation and radiotherapy.

Differential diagnosis of adrenocorticotropic hormone-independent Cushing syndrome: role of adrenal venous sampling.

OBJECTIVE: To outline the potential role for adrenal venous sampling in the diagnosis and management of adrenocorticotropic hormone (ACTH)-independent Cushing syndrome (CS). METHODS: We present a case description and discuss the management of a 59-year-old woman with an 8-year history of weight gain, centripetal obesity, a round plethoric face, skin thinning, easy bruising, hirsutism, and progressive muscle weakness. RESULTS: The patient reported a prior personal history of asthma, type 2 diabetes mellitus, hypertension, dyslipidemia, and bilateral leg ulcers, but she denied having any personal or family history of endocrinopathy and was not taking any corticosteroid medication. Elevated midnight serum cortisol, failure to suppress cortisol levels with a low-dose dexamethasone suppression test, and undetectable plasma ACTH all indicated ACTH-independent CS. Additional investigations including dynamic tests and adrenal imaging were supported by adrenal venous sampling in order to make a diagnosis and formulate a management plan. She was ultimately noted to have bilateral functioning adrenal nodules (adenoma and adenolipoma) and underwent successful bilateral laparoscopic adrenalectomy, with postoperative glucocorticoid and mineralocorticoid replacement. CONCLUSION: Adrenal venous sampling may be an important step in the differential diagnosis of CS and localization of the source of cortisol excess. It may distinguish pheochromocytoma or benign nonfunctioning adrenal nodules from cortisol-secreting adenomas and may avoid unnecessary bilateral adrenalectomy. It can also ensure that the correct operation is completed, if required, and thus avoid the increased morbidity and mortality associated with repeated surgical interventions.

[Primary amyloidosis associated with kappa light chain myeloma]. / Amiloidose primária associado a mieloma de cadeias leves kappa.

INTRODUCTION: The clinical spectrum of plasma cell dyscrasias includes primary amyloidosis and multiple myeloma. These two entities are present at the time of diagnosis in 10 percent of cases. CASE REPORT: A 72 years old female was admitted to our Institution with oligoanuric renal failure. Renal ultrasonography revealed normal kidney dimensions, with a slight decrease in the normal parenchyma-sinus differentiation. The complementary study identified free kappa light chains in urine (73,9 mg/dL) and bone marrow study fulfilled the criteria for multiple myeloma. Search for amyloid fibrils in abdominal subcutaneous fat was positive. The serum beta-2 microglobulin level was elevated (26 mg/L). Transthoracic echocardiogram did not reveal pathologic findings. Treatment initiation was complicated by hemodialysis catheter-associated Staphylococcus aureus infection. DISCUSSION: Primary amyloidosis associated with light chain myeloma is a rare, and often late, diagnosis with a dismal prognosis. Renal failure is a frequent initial presentation of the disease and infection an important cause of death.