Development of a novel diagnostic assay for insulin receptor autoantibodies based on a patient with autoimmune hypoglycaemia.

Differential diagnosis of hypoglycaemia can at times be challenging for patients who appear to be well. Here we identify the case of a 66-year-old Chinese man presenting with recurrent episodes of fasting hypoglycaemia and confusion without any other manifestations. He had no personal or family history of diabetes, nor was he on any hypoglycaemic drugs. The fasting insulin levels were elevated while the C-peptide and pro-insulin levels were slightly low or normal. Antibodies against insulin were negative and levels of insulin-like growth factors were normal. A series of imaging diagnosis excluded the presence of insulinoma or ectopic insulin-secreting neuroendocrine tumor. Ultimately, insulin receptor autoantibodies (IRAb) were detected by both immunoprecipitation assay and enzyme-linked immunosorbent assay (ELISA) developed in house. In a cell study, the immunoglobulins isolated from this patient exerted insulin-like effects on stimulation of post-insulin receptor signaling and glucose uptake as well as inhibited 125I-insulin binding with insulin receptors. Collectively, this patient was diagnosed with IRAb-induced autoimmune hypoglycaemia. Although this patient had no obvious immune disorders, several autoantibodies were identified in his plasma samples, suggesting the patient might have mild aberrant autoimmunity and therefore generated IRAb. IRAb-related disease is uncommon and possibly underdiagnosed or missed due to the lack of simple detection methods for IRAb. Our in-house user-friendly ELISA kit provides a valuable tool for diagnosis of this disease.

A novel mutation in pseudohypoparathyroidism type 1a in a Chinese woman and her son with hypocalcaemia.

Pseudohypoparathyroidism is a rare genetic disorder characterised by end-organ resistance to parathyroid hormone due to a defect of the guanine nucleotide-binding protein alpha that simulates activity of the polypeptide 1 (GNAS) gene. Patients with type 1a pseudohypoparathyroidism display different features of Albright's hereditary osteodystrophy as well as multi-hormone resistance. We describe a Chinese woman and her son, who presented with different symptoms of pseudohypoparathyroidism and clinically manifested different degree of Albright's hereditary osteodystrophy. Genetic study detected a mutation [NM_000516.4(GNAS):c682C>T (p.Arg228Cys)] in the GNAS gene.

Phaeochromocytoma in the Hong Kong Chinese population.

OBJECTIVE: To review the clinical manifestations of phaeochromocytoma in a Hong Kong Chinese population. DESIGN: Retrospective review. SETTING. Five public hospitals in Hong Kong. PATIENTS: Seventeen patients with operated phaeochromocytoma between 1994 and 2003 were reviewed retrospectively. RESULTS: Six patients (35%) were men, 11 (65%) were women. The mean age at presentation was 47 (range, 17-72) years. The diagnosis post-presentation was delayed by 1 to 132 months. Over 70% of the patients had hypertension. The most frequent symptoms were headache (53%), palpitations (53%), and sweating (41%); all these symptoms were present in 24% of the patients. Four (24%) had hereditary phaeochromocytoma/paraganglioma syndrome. The sensitivity of 24-hour urinary catecholamine measurements was 82%. Mean urinary adrenaline and noradrenaline concentrations were respectively 7- and 8-fold greater than the upper reference limits. Computed tomography and metaiodobenzylguanidine scintigraphy were the most widely used means for tumour localisation (sensitivity, 100% and 87% respectively). Approximately 65% of the patients had intra-adrenal tumours; 53% were on right side, 18% were bilateral. All the patients were prescribed phenoxybenzamine (dosage range, 20-120 mg/day) preoperatively. Two thirds of the patients had improved blood pressure 1 year after the operation. No malignancy was reported after a mean follow-up period of 7 years. CONCLUSION: Our series of patients with phaeochromocytomas commonly had a high frequency of normotension and extra-adrenal tumours. A high index of clinical suspicion and appropriate biochemical investigations are necessary to make the diagnosis, especially for patients manifesting adrenal incidentaloma and extra-adrenal lesion.

Incidence and progression of diabetic retinopathy in Hong Kong Chinese with type 2 diabetes mellitus.

OBJECTIVE: We conducted a cohort study to determine the incidence and progression of diabetic retinopathy (DR) in a Chinese population with type 2 diabetes mellitus in a district hospital in Hong Kong, and to identify the risk factors associated with the development and progression of DR over 4 years. RESEARCH DESIGN AND METHODS: A total of 413 type 2 diabetic patients who followed up in our diabetic clinic and had a diabetic complication screening performed in 2001 were studied. The final analysis included 354 subjects (85.7%) after a mean follow-up period of 4.2 years. The severity of DR was graded according to the modified Early Treatment Diabetic Retinopathy Study (ETDRS). The relationship between clinical variables and DR development and progression was determined. RESULTS: The baseline prevalence of DR was 39.2%. On 4-year follow-up, the incidence of DR was 20.3% (43 of 212). In those with baseline DR, 34.7% (42 of 121) progressed by >or=2 steps in ETDRS. On multivariate analysis, a high baseline glycosylated hemoglobin (HbA(1c)) was the only predictor of DR development, while macroalbuminuria and high mean HbA(1c) predicted progression. Regression of DR, defined by a >or=2-step decrement in ETDRS, occurred in 13.2% (12 of 91) of subjects and was associated with lower baseline HbA(1c) and absence of albuminuria. CONCLUSION: The incidence of DR in our study was similar to--but progression of DR was higher than--those reported in Caucasians. More frequent retinal screening should be offered to those with baseline DR, high HbA(1c), or albuminuria. Good glycemic control is important in order to prevent the development and progression of DR, and can lead to regression of DR.

Severe right heart failure in two patients with thyrotoxicosis.

Congestive heart failure is a recognised complication of uncontrolled thyrotoxicosis but isolated right heart failure is rarely seen in association with thyrotoxicosis. Two cases of right heart failure associated with thyrotoxicosis are presented. In a 45-year-old man with right heart failure, investigations for all common secondary causes of right heart failure were negative. The only concurrent disease identified was thyrotoxicosis. The right heart failure subsided after treatment of the thyrotoxicosis. In a 36-year-old woman, the right heart failure had two underlying causes, thyrotoxicosis and an atrial septal defect. Treatment of thyrotoxicosis alone resulted in improvement of pulmonary hypertension and right heart failure. Thyrotoxicosis should be considered as a possible cause of pulmonary hypertension or isolated right heart failure.