Graves'-related ophthalmopathy: [A] study of proinflammatory serum cytokines profile and peripheral blood T-cell subsets in relation to clinical status and orbital ultrasonography

Aim: Graves'-related ophthamopathy [GRO] is an organ -specific autoimmune disease passing into two stages, the stage of active inflammatory disease, which is treated conservatively by anti-inflammatory drugs or radiotherapy, and the inactive fibrotic stage, which is treated surgically. It is rather difficult to distinguish inflammatory from noninflammatory stages. The aim of the present work was to study some proinflammatory cytokines as sICAM, IL-2, and IFN-gamma serum levels, and peripheral blood T-cell subsets, together with orbital Ultrasonography in patients with GRO and their relation to clinical activity score [CAS] and relevant clinical parameters. Subjects and Fourty patients with GRO were enrolled, 30 of whom had inactive GRO and 10 cases had active GRO according to the clinical activity score, in addition to 10 healthy volunteers as a control group. Thorough clinical evaluation and orbital ulttrasonography were done for all patients. Laboratory work included measurement of sICAM, IL-2, IFN-gamma in serum and T-cell subsets in peripheral blood for patients and control. It was found that age, sex, smoking habit, or thyroid hormone status are not different in patients having active compared to inactive GRO, while the duration of the disease was significantly different, being shorter in those having active GRO. Extraocular muscle hyporeflectivity, as shown by orbital ultra-sonography, was significantly correlated with clinical activity score [P <0.01]. Serum sICAM-1, IL-2, and IFN-gamma levels were high in patients compared to controls [40.4=/=5 pg/ml versus 10.4 +/- 3.08 pg/ml, 440 +/- 187.6 pg/ml versus 65.8'24.3 pg/ml, and 479=/=160.3 pg/ml versus 116.4 +/- 24.0 pg/ml, respectively], and those having active GRO showed higher levels compared to those with inactive GRO [46.2 +/- 4.6 pg/ml versus 38.4 +/- 3.4 pg/ml, 707 +/- 149 pg/ml versus 351 +/- 87.6 pg/ml and 705.3 +/- 108.2 pg/ml versus 404.2 +/- 86.5 pg/ml, respectively]. T-cell subsets studied [CD3, CD4, and CD8] in peripheral blood were not different in patients with active GRO compared to those with inactive GRO [75.5 +/- 6.19% versus 71.8 +/- 5.53%, 58.4 +/- 4.62% versus 53.7+7.26%, and 14.8'6.05% versus 14.8 +/- 3.18%, respectively]. Conclusions: It is concluded that the duration of the eye disease and orbital utrasonography added to the clinical activity score could help distinguish patients with active Graves'-related ophthalmopathy, while serum levels of slCAM-1, IL-2, and IFN-gamma as single measurements, or peripheral blood T-cell subset pattern are of little help in this respect

Outcome of drug treatment in patients with prolactinoma

Aim: Prolactinoma is the most common pituitary adenoma, accounting for about one third of patients with pituitary tumors. Therapeutic options include drug treatment, pituitary surgery, and radiotherapy. However, medical therapy is the preferred initial therapy for most patients with prolactinoma. The aim of the present work was to study patients with prolactinoma attending the Mansoura University Hospital from the clinical, biochemical and radiologic aspects, and to assess the efficacy and outcome of drugs used [bromocriptine and quinagolide] in their treatment. Subjects and A series of 29 cases with prolactinoma attending the Endocrinology outpatient clinic and inpatient department at the Mansoura University Hospital, during the period from 1998 to 2001, were analyzed retrospectively. Patients were followed up for a mean of 6 months to one year. Diagnosis of prolactinoma was made on the basis of high serum prolactin levels with pituitary mass lesion, after exclusion of high GH and high TSH serum levels. Patients had full sheets of clinical data, together with biochemical profile including serum prolactin level, TSH, basal GH. Magnetic resonance imaging [MRI] was done at diagnosis and at follow up. Fundus examination and field of vision were done for patients with macroprolactinoma, at diagnosis and follow up. Bromocriptine [B] was given to 21 patients [15 with microprolactinoma and 6 with macroprolactinoma] in a dose of 7.5-15 mg/day in divided doses, while quinagolide [Q] was given to 8 cases [4 with micro-and 4 with macroprolctinoma] in a dose of 1.5-3 mg once a day. Follow up was made for 6-12 months with clinical, biochemical and MRI assessment. It was found that about 2/3 of prolactinoma patients were females. Microprolactinoma was more prevalent in women while macroprolactinoma was more prevalent in men, and in general, microprolactinoma was more prevalent than macroprolactinoma. The clinical presentation was mainly related to hypogonadism in the form of amenorrhea-galactorrhea in women and sexual impotence and infertility in men. Serum prolactin level was significantly higher in macroprolactinoma compared to microprolactinoma. Visual field defects were found in 5 out of 10 patients harboring macro-prolactinoma. There was no significant difference in efficacy between bromocriptine and quinagolide. Normalized serum prolactin was achieved in 14 out of 15 patients with microprolactinoma in the B treated group versus 4 out of 4 patients in the Q treated group, and 4 out of 6 patients with macroprolactinoma in the B treated group versus 3 out of 4 patients in the Q treated group. Microprolactinoma disappeared in 6 cases out of 15 patients in the B treated group versus 3 out of 4 patients in the Q treated group. More than 50% reduction in tumor dimensions was achieved in 6 out of 15 patients in the B treated group versus 3 out of 4 patients in the Q treated group, and less than 50% reduction in tumor dimensions was achieved in 3 patients in the B treated group. Response to both drugs was not statistically different. For macroprolactinomas there was also a nonsignificant difference in the response to both drugs used. More than 50% reduction in tumor dimensions was achieved in 4 out of 6 patients in the B treated group versus 2 out of 4 patients in the Q treated group, while less than 50% reduction in tumor dimensions was achieved in one patient in the B treated group versus 2 patients in the Q treated group. One patient with macroprolactinoma was resistant to bromocriptine without change in adenoma dimensions. Visual field defects improved in 4 macroprolactinoma cases with prior field defects with the exception of the failed case in the B treated group. Drug side effects were more severe in bromocriptine-treated patients than quinagolide, and three patients of the series were switched to quinagolide because of bromocriptine intolerance. Conclusions: It can be concluded that prolactinoma is more prevalent in females predominantly microprolactinoma. When males are affected macroprolactima predominates due to delayed diagnosis. Patients with prolactinoma respond well to medical treatment in terms of normalization of excess prolactin level and reduction or disappearance of the tumor mass. Both bromocriptine and quinagolide are similarly effective, but quinagolide has fewer side effects

Bone status in patients with hyperthyroidism: impact of the severity, duration, and etiology of hyperthyroidism on bone turnover markers and bone mineral density

Hyperthyroidism is accompanied by osteopenia or osteoporosis with higher incidence of fracture rates. There is paucity of data about the relation between the degree or duration of hyperthyroidism or its etiology and the resulting bone changes. The aim of the present work was to study bone status in patients with hyperthyroidism including biochemical markers of bone turnover and bone mineral density, and to elucidate the impact of severity, duration, and etiology of hyperthyroidism on biochemical markers of bone turnover and bone mineral density. Subjects and Thirty-six male patients with hyperthyroidism, 21 with Graves' disease and 15 with toxic multinodular goiter, with an age ranging from 23 to 65 years and a mean of 43 +/- 10 years, were included, together with 10 healthy men with matched age as a control group. In addition to full clinical examination, patients were subjected to radioisotope scanning and uptake of the thyroid gland with Tc 99,and DEXA scanning of the lower half of the left radius. Laboratory work up included serum free T3, free T4, TSH. Special assays done for patients and controls included serum total and B-ALP, serum OC, serum calcium, serum phosphorus urinary calcium, urinary DXP cross-links, urinary creatinine and calculated urinary DXP/urinary creatinine ratio. Biochemical markers of bone turnover were significantly higher in patients with Graves' disease compared to controls. Serum B-ALP was 9,5 +/- 5.6 KAU/I versus 2.2 +/- 0.8 KAU/I [P=0.00], serum OC was12.7 +/- 5 ng/dl versus 6.6 +/- 1.6 ng/dl [P=0.00], urinary calcium was 22.6 +/- 7.5 mg/dl versus15.5 +/- 5.1 mg/dl [P<0.05], and urinary DXP/urinary creatinine ratio was 12.6 +/- 5.5 versus 6.3 +/- 1.8 [P=0.00]. Biochemical markers of bone turnover were significantly higher in patients with toxic multinodular goiter compared to controls. Serum B-ALP was 4.3 +/- 2.6 KAU/I versus 2.2 +/- 0.8 KAU/I [P<0.05], serum OC was11.5 +/- 6.1 ng/dl versus 6.6 +/- 1.6 ng/dl [P<0.05], urinary calcium was 19.2 +/- 5 mg/dl versus15.5 +/- 5.1 mg/dl [P<0.05], and urinary DXP/urinary creatinine ratio was 13.5 +/- 7 versus 6.3 +/- 1.8 [P<0.05]. There was nonsignificant difference in the biochemical markers of turnover in patients with Graves' disease compared to those with toxic multinodualr goiter. Serum OC was 12.7 +/- 5 ng/d versus11.5 +/- 6.1 ng/dl, urinary calcium was 22.6 +/- 7.5 mg/dl versus 19.2 +/- 5 mg/dl, and urinary DXP/urinary creatinine ratio was 12.6 +/- 5.5 versus 13.5 +/- 7. However, serum B-ALP was higher in patients with Graves1 disease compared to those with multinodular goiter [9.5=/=5.6 KAU/I versus4.3 +/- 2.6 KAU/I [P< 0.05]. The Z -score at the lower half of the left radius in patients with Graves' disease [-1.7 +/- 0.5] was not significantly different from those with toxic multinodular goiter [-1.6 +/- 6]. Correlation between free T3 and biochemical markers of bone turnover revealed a significant positive correlation with all studied parameters: B-ALP [n= 0,37, P<0.05], serum OC [r= 0.62, P<0.05], urinary calcium [r=0.46, P<0.05], and urinary DXP/urinary creatinine ratio [r=0.52, P<0.05]. Correlation between free T4 and bone turnover markers revealed a significant positive correlation with B-ALP [r=0.43, P<0.05], serum OC [r=0.65, P<0.05], urinary calcium [r= 0.61, P<0.05], and urinary DXP/ urinary creatinine ratio [r=0.49, P< 0.05]. The duration of the thyrotoxic state did not correlate with the assessed bone turnover markers. However, the duration of the thyrotoxic state correlated significantly with the Z-score of the studied patients [r =0.68, P< 0.05]. The Z-score of the studied patients did not correlate with the free T3 and freeT4. Conclusions: It is concluded that men with hyperthyroidism have significant bone loss with higher biochemical markers of bone turnover. The severity of hyperthyroidism is directly related to the derangement of biochemical markers of bone turnover. Duration of the thyrotoxic state is related to the degree of bone loss. The etiology of the thyrotoxic state is not related to the degree of derangement in bone turnover markers or to the degree of bone loss