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Thioamides antithyroid-drugs (ATDs) are important in hyperthyroid disease management. Identification of the susceptibility locus of ATD-induced agranulocytosis is important for clinical management. We performed a genome-wide association study (GWAS) involving 20 patients with ATD-induced agranulocytosis and 775 healthy controls. The top finding was further replicated. A single-nucleotide polymorphism (SNP), rs185386680, showed the strongest association with ATD-induced agranulocytosis in GWAS (odds ratio (OR) = 36.4; 95% confidence interval (CI) = 12.8-103.7; P = 1.3 × 10(-24)) and replication (OR = 37; 95% CI = 3.7-367.4; P = 9.6 × 10(-7)). HLA-B*38:02:01 was in complete linkage disequilibrium with rs185386680. High-resolution HLA typing confirmed that HLA-B*38:02:01 was associated with carbimazole (CMZ)/methimazole (MMI)-induced agranulocytosis (OR = 265.5; 95% CI = 27.9-2528.0; P = 2.5 × 10(-14)), but not associated with propylthiouracil (PTU). The positive and negative predictive values of HLA-B*38:02:01 in predicting CMZ/MMI-induced agranulocytosis were 0.07 and 0.999. Approximately 211 cases need to be screened to prevent one case. Screening for the risk allele will be useful in preventing agranulocytosis in populations in which the frequency of the risk allele is high.

SummaryWe report a case of elderly Chinese lady with neurofibromatosis type-1 presenting with longstanding palpitation, paroxysmal hypertension and osteoporosis. Biochemical testing showed mild hypercalcaemia with non-suppressed parathyroid hormone level suggestive of primary hyperparathyroidism, and mildly elevated urinary fractionated normetanephrine and plasma-free normetanephrine pointing to a catecholamine-secreting pheochromocytoma/paraganglioma. Further scintigraphic investigation revealed evidence of a solitary parathyroid adenoma causing primary hyperparathyroidism and a left pheochromocytoma. Resection of the parathyroid adenoma and pheochromocytoma resulted in normalization of biochemical abnormalities and hypertension. The rare concurrence of primary hyperparathyroidism and pheochromocytoma in neurofibromatosis type-1 is discussed.Learning points:All NF-1 patients who have symptoms suggestive of a pheochromocytoma/paraganglioma (PPGL), even remotely, should undergo biochemical testing.The initial biochemical tests of choice for PPGL in NF-1 are either plasma-free metanephrines or urinary fractionated metanephrines. Any elevations of metanephrines should be carefully evaluated for the presence of PPGLs in NF-1 patients.Primary hyperparathyroidism (PHPT) is described in subjects with NF-1. Due to the lack of epidemiological and functional studies, their association is yet to be substantiated. Meanwhile, PHPT may further exacerbate the metabolic bone defect in these patients and should be treated when present according to published guidelines.Coexistence of PPGL and PHPT can occur in subjects with NF-1, mimicking multiple endocrine neoplasia type 2 (MEN2).

AddressesPhaeochromocytoma or paraganglioma that exclusively secretes dopamine is very rare. This case illustrates its atypical presentation and the importance of interpretative reporting for urine catecholamines leading to the diagnosis and subsequent management of a patient with this condition. We report a 71-year-old Chinese woman with a large dopamine-secreting paraganglioma. She presented with low back pain for six months. On examination, a right abdominal mass was palpable incidentally. Her blood pressure was normal throughout. Serial 24-h urine collections for catecholamines showed enormous elevation of urine dopamine excretion to 80.7 mmol/day (normotensive: o2.6 mmol/day). However, the daily excretions of urine adrenaline and noradrenaline, as well as their metabolites were within their respective reference intervals. Good communication between chemical pathologists and physicians prompted the arrangement of the whole body 131 I-meta-iodobenzylguanidine (MIBG) scintigraphy, which showed a large signal in the right upper quadrant of the abdomen corresponding to a large extra-adrenal tumour detected by both ultrasonography and computerized tomography (CT) of the abdomen. Histological section of the tumour tissue revealed paraganglioma, which stained positive for chromogranin and neuron-specific enolase. After four months, the patient presented with chest symptoms and CT of the thorax revealed multiple nodules. Lung metastases were suspected. However, follow-up urine catecholamine and dopamine excretions were again within their respective normotensive reference intervals. A second MIBG scintigraphy was performed, but no specific uptake at either the thorax or the abdomen could be demonstrated. Fine-needle aspiration cytology using the thoracoscopic technique was performed and immunochemical staining of the biopsy specimen showed the presence of nonsmall-cell carcinoma of the lung. 2005; 42: 73-77 Ann Clin Biochem

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