Prospective study of surgery for primary hyperparathyroidism (HPT) in multiple endocrine neoplasia-type 1 and Zollinger-Ellison syndrome: long-term outcome of a more virulent form of HPT

BACKGROUND: Primary hyperparathyroidism (HPT) in multiple endocrine neoplasia type 1 (MEN1) patients with Zollinger-Ellison syndrome (ZES) is caused by parathyroid hyperplasia. Surgery for parathyroid hyperplasia is tricky and difficult. Long-term outcome in ZES/MEN1/HPT is not well known. METHODS: Eighty-four consecutive patients (49 F/35 M) with ZES/MEN1/HPT underwent initial parathyroidectomy (PTX) and were followed at 1- to 3-year intervals. RESULTS: Age at PTX was 36 +/- 2 years. Mean follow-up was 17 +/- 1 years. Before PTX, mean Ca = 2.8 mmol/L (normal level (nl <2.5), PTH i = 243 pg/mL (nl <65), and gastrin = 6950 pg/mL (nl < 100). Sixty-one percent had nephrolithiasis. Each patient had parathyroid hyperplasia. Fifty-eight percent of patients had 4 parathyroid glands identified. Nine of 84 (11%) had 4 glands removed with immediate autograft, 40/84 (47%) 3 to 3.5 glands, whereas 35/84 (42%) <3 glands removed. Persistent/recurrent HPT occurred in 42%/48% of patients with <3 glands, 12%/44% with 3 to 3.5 glands, and 0%/55% with 4 glands removed. Hypoparathyroidism occurred in 3%, 10%, and 22%, respectively. The disease-free interval after surgery was significantly longer if >3 glands were removed. After surgery to correct the HPT, each biochemical parameter of ZES was improved and 20% of patients no longer had laboratory evidence of ZES. CONCLUSIONS: HPT/MEN1/ZES is a severe form of parathyroid hyperplasia with a high rate of nephrolithiasis, persistent and recurrent HPT. Surgery to correct the hypercalcemia significantly ameliorates the ZES. Removal of less than 3.5 glands has an unacceptably high incidence of persistent HPT (42%), whereas 4-gland resection and transplant has a high rate of permanent hypoparathyroidism (22%). More than 3-gland resection has a longer disease-free interval. The surgical procedure of choice for patients with HPT/MEN1/ZES is 3.5-gland parathyroidectomy. Careful long-term follow-up is necessary as a significant proportion will develop recurrent HPT.     

Squamous cell carcinoma arising in a papillary carcinoma of the thyroid: a case report

BACKGROUND: primary squamous cell carcinoma (scc) of the thyroid is a rare malignant tumor that needs to be distinguished from other neoplasms. Cases of papillary carcinoma merging in association with squamous cell carcinoma are extremely rare. AIM: the characteristics of such association will be studied herein through a review of literature. CASE REPORT: we report a case of an 87-year-old patient presented with an enlarged right lobe of the thyroid. Thyroid scintigraphy revealed a cold nodule. Clinically, malignancy was suspected. Histopathologic diagnosis was a well-differentiated scc associated with areas of papillary carcinoma. Exhaustive clinical, endoscopic and radiological examinations did not reveal any primary site of scc or any contiguous spread from neighboring structures. Surgery was followed by radiotherapy, but the patient died 6 months later. CONCLUSION: the coexistence of epidermoide and papillary carcinomas in the thyroid gland must be known because of its prognostic impact.     

Engagement of CD160 receptor by HLA-C is a triggering mechanism used by circulating natural killer (NK) cells to mediate cytotoxicity

Circulating human natural killer (NK) lymphocytes have been functionally defined by their ability to exert cytotoxic activity against MHC class I-negative target cell lines, including K562. Therefore, it was proposed that NK cells recognized the "missing self." We show here that the Ig-like CD160 receptor expressed by circulating CD56(dim+) NK cells or IL-2-deprived NK cell lines is mainly involved in their cytotoxic activity against K562 target cells. Further, we report that HLA-C molecules that are constitutively expressed by K562 trigger NK cell lysis through CD160 receptor engagement. In addition, we demonstrate, with recombinant soluble HLA-Cw3 and CD160 proteins, direct interaction of these molecules. We also find that CD158b inhibitory receptors partially interfere with CD160-mediated cytotoxicity, whereas CD94CD159a and CD85j have no effect on engagement with their respective ligands. Thus, CD160HLA-C interaction constitutes a unique pathway to trigger NK cell cytotoxic activity.     

Anti-thyroid-stimulating hormone receptor antibodies determined by second-generation assay.

BACKGROUND: The aim of our study was to determine the frequency of anti-thyroid-stimulating hormone (TSH) receptor antibodies (TRAb) in Tunisian patients with Graves' disease (GD) and to compare the validity of TRAb to that of thyroperoxidase (TPO-Ab) and thyroglobulin antibodies (TG-Ab). METHODS: ELISA was used to determine the frequency of TRAb, TPO-Ab and TG-Ab in sera of 190 patients with GD. Patients were divided into four groups: those with untreated active GD (group A, n=71), those receiving treatment with anti-thyroid drugs (group B, n=85), those in relapse (group C, n=15) and those in remission (group D, n=19). Sera of 100 healthy blood donors served as controls. RESULTS: The sensitivity of TRAb for the diagnosis of GD (95.8%) was significantly higher than that of TPO-Ab (73.2%) and TG-Ab (42.2%) (p=0.0005 and p<10(-7), respectively). The positive rate for TRAb was lower in group B than in group A (70.6% and 95.8%, respectively; p=0.0001). The levels of TRAb were significantly higher in group A than in group B (mean 30.1 and 14.2 IU/L, respectively; p=0.006). CONCLUSIONS: TRAb, but neither TPO-Ab nor TG-Ab, is valuable in the diagnosis and management of patients with GD.     

Comparison of high and low dose of cyclophosphamide in lupus nephritis patients: a long-term randomized controlled trial

To evaluate the outcome of low doses of cyclophosphamide (Cyclo) therapy in lupus nephritis (LN) patients, we studied 117 biopsy-proven, de novo LN WHO class IV patients double-blinded and randomized in December 1997 to receive Cyclo in different doses; Group I (n=73) received Cyclo 10 mg/kg monthly for six months then every two months for 12 months. Group II (n=44) received Cyclo 5 mg/kg monthly for six months then every two months for 36 months. The patients were followed-up till January 2007. Six months post-induction values for creatinine clearance were significantly higher in Group I (67.7 ± 28.6 mL/min) compared with Group II (55.1 ± 30.1 mL/min), P = 0.026. Serum C4 and ANA were not significantly different between the groups (P > 0.05). At the mean follow-up of 6.77 ± 3.3 years, the mean creatinine clearance was 44.74 ± 31.7 mL/min in Group I vs. 49.3 ± 38.8 in Group II. Urinary protein was 1.65 ± 1.8 g/dL in Group I vs. 1.02 ± 1.01 in Group II (P = 0.03). The survival curve showed that kidney survival overtime was comparable in both groups (P = 0.2). Complete remission was observed in 25 (34.2%) patients in Group I vs. 11 (25%) in Group II (P = 0.288), while partial remission was similar in both groups; 43 (58.9%) patients in Group I vs. 26 (59%) patients in Group II. End-stage renal disease was observed in 10 (13.7%) patients in Group I vs. 9 (20.4%) patients in Group II (P = 0.359). Side-effects were more frequent in Group I patients than in Group II patients; gonadal toxicity and malignancy were lower in Group II patients (P = 0.0000). Moreover, different infections occurred in 23 (31.3%) patients vs. six (13.6%), digital infarcts occurred in 1.35% vs. 0%, diabetes in 4.1% vs. 2.27%, and vasculitis in 4.1% vs. 2.27% in Group I vs. Group II, respectively. Sustained amenorrhea without pregnancy was observed in both groups; however, significantly more in Group I patients, P ≤ 0.05. We conclude that low-dose Cyclo therapy is sufficiently effective for WHO class IV LN patients with lower side-effects compared with standard dose.     

Screening for celiac disease in Tunisian patients with Graves' disease using anti-endomysium and anti-tissue transglutaminase antibodies

OBJECTIVE: Celiac disease (CD) can be associated with autoimmune thyroid diseases. The aim of this study was to screen for CD in patients with Graves' disease in Tunisia. PATIENTS AND METHODS: Sera from 161 patients with Graves' disease were tested for IgA class anti-endomysium antibodies (AEA) using indirect immunofluorescence on cryostat sections of human umbilical cord and for IgA class anti-human tissue transglutaminase antibodies (AtTG) by ELISA. RESULTS: AEA were positive in 6 out of 161 (3.7%) patients with Graves' disease and all 6 patients were also positive for AtTG. Four of these 6 patients with positive serological markers of CD underwent duodenal biopsy; three had marked villous atrophy, one has normal histological picture and two did not agree to undergo biopsy. The prevalence of biopsy confirmed CD in patients with Graves' disease was 1.86% (3/161). CONCLUSION: Patients with Graves' disease are at substantial risk of CD and therefore antibody screening for CD may be included in the work-up of these patients. Either AEA or AtTG may be used.     

Potentiation of NK cell-mediated cytotoxicity in human lung adenocarcinoma: role of NKG2D-dependent pathway

Natural cytotoxicity receptors and NKG2D correspond to major activating receptors involved in triggering of tumor cell lysis by human NK cells. In this report, we investigated the expression of NKG2D ligands (NKG2DLs), MHC class I-related chain (MIC) A, MICB and UL16-binding proteins 1, 2 and 3, on a panel of human non-small-cell lung carcinoma cell lines, and we analyzed their role in tumor cell susceptibility to NK cell lysis. Although adenocarcinoma (ADC) cells expressed heterogeneous levels of NKG2DLs, they were often resistant to NK cell-mediated killing. Resistance of a selected cell line, ADC-Coco, to allogeneic polyclonal NK cells and autologous NK cell clones correlated with shedding of NKG2DLs resulting from a matrix metalloproteinase (MMP) production. Treatment of ADC-Coco cells with a MMP inhibitor (MMPI) combined with IL-15 stimulation of autologous NK cell clones lead to a potentiation of NK cell-mediated cytotoxicity. This lysis is mainly NKG2D mediated, since it is abrogated by anti-NKG2D-neutralizing mAb. These results suggest that MMPIs, in combination with IL-15, may be useful for overcoming tumor cell escape from the innate immune response.