Biomedical subjects

Kam-Tsun Tang

Publications and source records attributed to Kam-Tsun Tang.

10 recordsLinked to original sources

PubMed2006

Clinical features and morphological characterization of 10 patients with noninsulinoma pancreatogenous hypoglycaemia syndrome (NIPHS).

OBJECTIVE: Noninsulinoma pancreatogenous hypoglycaemia syndrome (NIPHS), characterized by postprandial neuroglycopaenia, negative prolonged fasts and negative perioperative localization studies for insulinoma, but positive selective arterial calcium stimulation tests and nesidioblastosis in the gradient-guided resected pancreas, is a rare hypoglycaemic disorder of undetermined aetiology. We analysed the clinical, morphological and immunohistological features to further clarify the aetiology and pathogenesis of this rare disease. PATIENTS: Ten consecutive patients with NIPHS (nine men and one woman, aged 29-78 years) were included in the study. Six of the 10 received a gradient-guided subtotal (70%) or distal (50%) pancreatectomy. In the remaining four patients, diazoxide treatment was initiated and the precise mechanism of its action was assessed by meal tests. RESULTS: All of the patients showed a combination of postprandial neuroglycopaenia, negative prolonged fasts (except one patient) and negative localization studies for insulinoma, but positive calcium stimulation tests and nesidioblastosis in the gradient-guided resected pancreas. Immunohistological studies of the resected pancreatic tissues revealed neither an increased rate of proliferation of beta-cells nor an abnormal synthesis and/or processing of either proinsulin or amylin. Evidence of overexpression of the two pancreatic differentiation factors, PDX-1 and Nkx-6.1, as well as the calcium sensing receptor (CaSR) was absent. Nevertheless, abnormal expression of islet neogenesis-associated protein (INGAP), a human cytokine expressed only in the presence of islet neogenesis, in ducts and/or islets, was identified in three of the five patients studied. All of the six patients who received a surgical operation were relieved of further neuroglycopaenic attacks, but one patient who received a subtotal pancreatectomy developed diabetes. In the remaining four patients who received diazoxide treatment, hypoglycaemic episodes were satisfactorily controlled with an attenuated response of beta-cell peptides to meal stimulation. CONCLUSIONS: Our results strengthen the existence of this unique clinical hypoglycaemic syndrome from beta-cell hyperfunction as well as the value of the selective arterial calcium stimulation test in its correct diagnosis and localization. The mechanisms underlying beta-cell hyperfunction and release of insulin to calcium, however, remain poorly characterized. Nevertheless, in a subset of patients with NIPHS, there exists some, as yet undefined, pancreatic humoral/paracrine factor(s) other than proinsulin, amylin, PDX-1, Nkx-6.1 and possibly glucagon-like peptide-1 (GLP-1) that are capable of inducing the INGAP gene and, if activated, will initiate ductal proliferation and islet neogenesis. As for the treatment, we recommend that diazoxide be tried first in each patient and, should it fail, a gradient-guided subtotal or distal pancreatectomy be attempted.

Adult↗

PubMed2005

TGF-beta induced hyaluronan synthesis in orbital fibroblasts involves protein kinase C betaII activation in vitro.

Graves' ophthalmopathy is accompanied by hyaluronan (HA) accumulation in the orbital space and infiltration of immunocompetent cells and cytokines, including IFN-gamma, IL-1beta, and TGF-beta. We examined the signal transduction pathways by which TGF-beta induces HA synthesis in normal orbital fibroblasts, orbital fibroblasts from patients with Graves' ophthalmopathy, and abdominal fibroblasts. Calphostin C inhibited the stimulation of HA synthesis by TGF-beta. Phorbol 12-myristate 13-acetate (PMA) activation of PKC stimulated HA production. The effects of TGF-beta and PMA were not synergistic. Stimulation by TGF-beta and PMA were dependent on protein synthesis and their effects were inhibited by cycloheximide. Since TGF-beta-induced HA synthesis was inhibited by BAPTA or by PKC inhibitors, a calcium-dependent PKC was most likely involved. The PKA inhibitor H-89 enhanced TGF-beta- and PMA-induced HA synthesis, thus showing that communication between the PKA and PKC pathways was evident. TGF-beta stimulated the translocation of PKCbetaII to the cell membrane. PKCbetaII, a key enzyme in the regulation of HA synthesis by TGF-beta, might be an appropriate target for therapeutic compounds to be used to treat Graves' ophthalmopathy accompanied by inflammation.

Base Sequence↗

PubMed2005

Diffuse soft tissue emphysema in anorexia nervosa: a case report.

OBJECTIVE: Anorexia nervosa (AN) is an eating disorder that occurs mainly among young females and its prevalence has increased in recent decades. METHODS: We reported a patient with AN with spontaneous diffuse soft tissue emphysema and bicytopenia, both of which are very rare complications of AN. Our patient, a 20-year-old woman, had lost 41.6% of her previous body weight within 9 months. Her body mass index was 10.8 and amenorrhea had persisted for 5 months. RESULTS: After admission, she was diagnosed with AN-restrictive subtype. She was noted to have crunching sounds in the neck and upper chest wall during hospitalization. A chest X-ray and chest computed tomography scan both revealed diffuse soft tissue emphysema including subcutaneous emphysema, pneumomediastinum, and pneumoretroperitoneum. DISCUSSION: Diffuse soft tissue emphysema improved gradually and completely resolved on the 21st day of hospitalization. This condition seems to be benign and only a short period of hospitalization is required.

Adult↗

PubMed2005

Severe hypoglycemic coma due to insulin autoimmune syndrome.

Insulin autoimmune syndrome, characterized by the presence of insulin-binding autoantibodies and fasting or late postprandial hypoglycemia, is a rare cause of hypoglycemia. We report a patient with pulmonary tuberculosis who developed recurrent spontaneously post-absorptive hyperinsulinemic hypoglycemia after treatment with anti-tuberculous drugs. Imaging studies of the pancreas were unremarkable, and selective intra-arterial calcium stimulation with hepatic venous sampling for insulin failed to show a gradient, thus almost completely excluding the possibility of occult insulinoma or nesidioblastosis. Examinations of sera, however, disclosed a high titer of polyclonal insulin-binding autoantibodies containing at least 2 classes of binding sites, 1 with high affinity but low capacity, and the other with low affinity but high capacity. An oral glucose tolerance test revealed high serum levels of total insulin associated with relatively low levels of free insulin, but not of C-peptide, suggesting binding of the released insulin to autoantibodies. Regretfully, shortly after the withdrawal of isoniazid, the patient died of respiratory failure unrelated to hypoglycemia, and whether these antibodies were induced by isoniazid remains unknown. We recommend that insulin autoimmune syndrome be one of the differential diagnoses in patients with hyperinsulinemic hypoglycemia.

Aged↗

PubMed2004

Primary hypothalamic lymphoma with panhypopituitarism presenting as stiff-man syndrome.

We report an unusual case of primary hypothalamic lymphoma with hypopituitarism presenting as Stiff-man syndrome (SMS). A 64-year-old man was hospitalized due to a 3-week history of general weakness, anorexia, vomiting, weight loss, and muscle pain and spasms precipitated by motion and tactile stimuli resulting in muscle stiffness and difficulty in mobility. Physical examination revealed normal sensorimotor function and reflexes, except for bitemporal visual field defect. Routine laboratory and gastrointestinal examinations provided no remarkable clues. Endocrine assessment revealed low levels of morning cortisol, thyroxine, and anterior pituitary hormones but an increase in prolactin level. The patient's muscle pain and stiffness improved dramatically within 2 days after hydrocortisone therapy and thyroxine replacement. Magnetic resonance imaging (MRI) of the brain confirmed an 18-mm enhancing hypothalamic tumor with optic chiasm involvement, which proved to be a B-cell lymphoma. The results of the extensive studies for systemic lymphoma were negative, suggesting a primary hypothalamic lymphoma. The tumor regressed completely and was invisible on MRI scan after adjuvant radiotherapy. The patient's condition was satisfactory and there was no recurrence of SMS during the 2-year follow-up period. This case demonstrated that primary hypothalamic lymphoma complicated with adrenal insufficiency may manifest as SMS. Early diagnosis and prompt intervention can lead to a favorable outcome and reduce morbidity.

Adrenal Insufficiency↗

PubMed2003

Intra-arterial calcium stimulation test for detection of insulinomas: detection rate, responses of pancreatic peptides, and its relationship to differentiation of tumor cells.

The selective intra-arterial calcium stimulation test has greatly facilitated the precise regionalization of insulinomas smaller than 2 cm, which noninvasive techniques (ultrasound [US], computed tomography [CT], magnetic resonance imaging [MRI]) often fail to localize. This study examined not only the role of the test in the localization of insulinomas, but also the responsiveness of 3 beta-cell peptides (insulin, C peptide, and proinsulin) and their relationship to the degree of differentiation of the tumor cells, using percentage decrease of both proinsulin/insulin (P/I) and proinsulin/C peptide (P/C) ratios after stimulation as indices. Ten consecutive surgically proven insulinoma patients each received an injection of calcium into the arteries supplying the pancreas after standard selective angiography and beta-cell peptide levels were measured in samples taken from the right hepatic vein before and 30, 60, 90, 120, and 180 seconds after each injection prior to operation. After surgery, the expressions of the calcium sensing receptor (CaSR) on the resected tumors were assessed by immunohistochemistry. Intra-arterial calcium stimulation with sampling either for insulin or for C peptide correctly predicted the site of insulinoma in 8 of 9 patients or in 7 of 8 patients if the 2 big malignant insulinomas were excluded; thus, the detection rate of this test was 89% and 88%, respectively. Calcium administration stimulated a marked and prompt release of insulin and C peptide simultaneously. Both peaked within 30 to 60 seconds, then declined gradually thereafter, remaining above the baseline at 180 seconds. The magnitude of increase correlated well with the corresponding percentage decrease of P/I and P/C ratios. The response of proinsulin was much less. Immunohistochemistry demonstrated variable membraneous staining for CaSR in normal pancreatic islets and in about 9% of the total normal beta cells, whereas staining in tumor cells was only minimally detectable. We conclude that selective intra-arterial calcium stimulation with hepatic venous sampling either for insulin or for C peptide is a highly sensitive method for the preoperative localization of small insulinomas. Calcium injection stimulates a brisk response of insulin, C peptide, and proinsulin simultaneously and the magnitude of increase of both insulin and C peptide appears to be correlated well with the degree of differentiation of the tumor cells. The exact mechanism by which calcium provokes the release of beta-cell peptides is less clear and whether the CaSR is involved in the mechanism of its action requires further study.

Adult↗

PubMed2003

Primary adrenal lymphoma manifestating as adrenal incidentaloma.

Although involvement of the adrenals by malignant lymphoma is common, primary adrenal lymphoma is extremely rare. Herein, we report a case of a 59-year-old woman with bilateral adrenal glands enlargement found incidentally on abdominal imaging. Despite of the huge size of the tumor, her adrenal function was intact. Ultrasound-guided biopsy disclosed a picture of malignant lymphoma, diffuse large B cell type. The patient received bilateral adrenalectomy and adjuvant chemotherapy, but succumbed 6 months later. We suggest that, although rare, primary adrenal lymphoma should be considered as a possible cause of bilateral adrenal incidentalomas.

Adrenal Gland Neoplasms↗

PubMed2002

The accuracy of fine-needle aspiration biopsy and frozen section in patients with thyroid cancer.

A total of 1076 patients with thyroid nodules were reviewed. The accuracy of fine needle aspiration biopsy (FNAB) and frozen section (FS) were compared and clinical risk factors were analyzed. Our results indicate that 67.9% are benign and 32.1% are malignant with the predominance of papillary thyroid cancer (75.1%). Overall diagnostic accuracy for FNAB and FS were 90.8%-91.2% and 89.1%-90.5%, respectively. There were no significant differences between the diagnostic accuracy on FNAB and FS in all tumors except the follicular adenoma and carcinoma. The diagnostic accuracy of FS was higher than FNAB in patients with follicular adenoma (89.3% vs. 58.9%, p < 0.001) and but lower than FNAB in patients with follicular carcinoma (46.2% vs. 92.3%, p < 0.001). In conclusion, FNAB is cost effective in the preoperative evaluation of thyroid nodule. FS could be eliminated in most cases except with follicular and Hürthle cell neoplasms. FS is valuable when result of FNAB is suspicious or unavailable. FS is more appropriate in deciding the extent of thyroidectomy in follicular neoplasm and FNAB is more reliable initial approach to surgery in patients with Hürthle cell neoplasm. Clinical risk factors may help in selecting patients for surgery but cannot exceed FS in deciding the extent of thyroidectomy in patients with follicular and Hürthle cell neoplasms.

Adolescent↗

PubMed2002

A reappraisal of the ovine corticotropin-releasing hormone stimulation test in the differential diagnosis of Cushing's syndrome: a comparison with the standard high-dose dexamethasone suppression test.

BACKGROUND: We evaluated the diagnostic efficacy of the ovine corticotropin-releasing hormone (oCRH) stimulation test in the differential diagnosis of Cushing's syndrome and compared it with the standard high-dose dexamethasone suppression test. METHODS: Twelve healthy volunteers and 30 with Cushing's syndrome (12 Cushing's disease and 18 adrenal Cushing's syndrome) were enrolled. Plasma ACTH and cortisol levels were measured before and after an intravenous bolus of 100 microg oCRH. Plasma and urinary free cortisol were determined after standard 2-day high-dose dexamethasone suppression. RESULTS: Basal cortisol in 12 patients with Cushing's disease and 18 with adrenal Cushing's syndrome were higher than the control group (21.4 +/- 0.1 microg/dl vs. 22.3 +/- 0.5 microg/dl vs. 9.1 +/- 1.5 microg/dl; p < 0.01). In Cushing's disease, basal plasma ACTH value was significantly higher than those with adrenal disease (61.1 +/- 1.4 pg/ml vs. 6.2 +/- 4.5 pg/ml; p < 0.01). After oCRH, plasma ACTH and cortisol significantly increased, with a mean of 2.0 +/- 0.2-fold (range 1.0-2.4) and 1.6 +/- 0.1-fold (range 1.1-2.1), respectively over the basal values in patients with Cushing's disease, and 11 (90%) attained a significant ACTH (1.5-fold) or cortisol (1.2-fold) response. All except 2 (89%) with adrenal Cushing's showed no apparent change in response to oCRH. Dexamethsone suppressed urinary free cortisol by 90% in 8 (67%) with Cushing's disease, but all (100%) with adrenal Cushing's syndrome were resistant. No patient with Cushing's disease was refractory to oCRH and dexamethasone, while none with adrenal Cushing's syndrome was responsive to both. Combination of both tests could achieved a specificity of 100% for Cushing's disease and adrenal Cushing's, when these 2 tests gave concomitant positive or negative results, respectively. CONCLUSIONS: The oCRH test is a reliable examination in the differential diagnosis of Cushing's syndrome and is comparable to the high-dose dexamethasone test. A highest discrimination could be achieved when both are used.

ACTH Syndrome, Ectopic↗

PubMed2002

The relationship between morning serum cortisol and the short ACTH test in the evaluation of adrenal insufficiency.

BACKGROUND: Morning serum cortisol examinations and short corticotropin (ACTH) tests are popular screening tests for unstressed patients suspected of having adrenal insufficiency. However, the correlation between morning serum cortisol and the peak cortisol response in the short ACTH test after intravenous injection of ACTH has not been studied before. This retrospective study examined the relationship among the mean basal morning cortisol level, the single random morning cortisol level and the peak cortisol level in the short ACTH test in evaluation of adrenal insufficiency. METHODS: In this retrospective study, we examined the relationship among the mean basal morning cortisol level and the peak cortisol level stimulated by intravenous injection of 250 microg synthetic ACTH in 106 unstressed patients with proven or suspected hypothalamic-pituitary-adrenal disease. Plasma cortisol levels were determined by radioimmunoassay. The correlation of the basal morning cortisol to the short ACTH test was determined by linear regression analysis. The ACTH test was analyzed using the receiver operating characteristic (ROC) curve method, and the cut-off points for various sensitivity and specificity were calculated. RESULTS: The mean basal is highly correlated to peak cortisol response in the ACTH test (r = 0.7724, p < 0.0001). Iatrogenic Cushing's syndrome, caused by ingestion of herbs with illegal steroid additives, was the most common cause (60%) of adrenal insufficiency in the 52 patients with subnormal result. A mean basal morning serum cortisol of > or = 300 nmol/L excluded the possibility of adrenal insufficiency, and a level of < 110 nmol/L suggested adrenal insufficiency. A mean basal cortisol level of > or = 234 nmol/L predicted a normal cortisol response in the ACTH test with optimal sensitivity (80.6%) and specificity (91.4%). CONCLUSIONS: The mean morning cortisol level is a cost-effective screening test in predicting the results of the ACTH test. A mean morning cortisol level > or = 300 nmol/L in suspicious cases of adrenal insufficiency which are not due to acute central etiologies excludes the possibility of subnormal cortisol response to ACTH; whereas a level < 110 nmol/L is likely to have subnormal cortisol response to ACTH. The short ACTH test or insulin tolerance test should be performed in patients with a morning cortisol level 300 nmol/L or with clinical symptoms highly suggestive of adrenal insufficiency.

Adolescent↗