Management of paediatric thyroid carcinoma: recent experience with recombinant human thyroid stimulating hormone in preparation for radioiodine therapy

Background: Thyroid carcinoma in children is rare and raises unique management issues. Although metastatic disease is more common in this age group, prognosis remains good with appropriate treatment. The aim of the study was to report recent experience in the management of differentiated thyroid carcinoma in children, especially in the use of radioiodine after recombinant human thyroid stimulating hormone (rhTSH) stimulation. Methods: Eight patients, aged 5–17 years (five were boys) presented following total thyroidectomy for thyroid carcinoma between May 2003 and June 2005. Seven had papillary carcinoma and one had follicular carcinoma. Five had known lymph node metastases and one had pulmonary metastases at presentation. Four patients had previously received therapeutic irradiation for malignancy. All eight underwent diagnostic iodine scans, seven with rhTSH stimulation. Seven went on to receive radioiodine treatment as hospital inpatients, comanaged by the paediatric and nuclear medicine units. The dosage of ¹³¹I ranged from 1.5 to 3.7 × 10⁹ Bq. All except one were prepared by rhTSH stimulation. Results: Seven of eight patients had significant uptake in the neck on diagnostic scan and two had pulmonary abnormalities. Six of seven evaluable patients achieved complete thyroid ablation. Both patients with pulmonary abnormalities had scan resolution, although one of them only after a second radioiodine treatment. All patients had thyroxine replacement in doses to suppress TSH and all remain alive and well at time of carrying out this study. Conclusion: Optimal management of paediatric thyroid carcinoma necessitates a multidisciplinary approach. Radioiodine therapy under rhTSH is an effective and safe adjuvant treatment in this special subgroup.     

Diagnostic and therapeutic use of recombinant human TSH (rhTSH) in differentiated thyroid cancer

The introduction of rhTSH into clinical practice has changed dramatically the monitoring and treatment of differentiated thyroid cancer patients. In particular, the post-surgical thyroid ablation with radio-iodine and the periodical follow-up are more and more routinely based on the use of rhTSH as the method of choice for patient preparation. Therapeutic results and sensitivity of follow-up when using rhTSH are not inferior to conventional thyroid hormone withdrawal and, in some regard, are superior if one considers the preservation of quality of life. The latter aspect is very well exemplified by the constant observation that patients who have experienced rhTSH will never accept going back to thyroid hormone withdrawal.

• the issue of ultrasensitive measures of serum Tg in basal condition versus rhTSH-stimulated serum Tg

• prospective clinical trial of rhTSH-aided RAI therapy for metastatic disease

• definition of the best activity of radio-iodine to be used for post-surgical thyroid remnant ablation

不同放射性活度131I清除分化型甲状腺癌患者残留甲状腺的荟萃分析

目的 使用荟萃分析方法汇总所有的随机对照研究,比较不同放射性活度131I清除术后残留甲状腺(清甲)的成功率,明确最佳的清甲剂量.方法 以‘thyroid’+‘cancer or carcinoma’+‘ablat$’(包括了ablation、ablative和ablate)为关键词检索2014年3月前Cochrane Library、MEDLINE、EMBASE和SCOPUS等数据库评估不同放射性活度”1 I清甲成功率的随机对照研究文献,并用Google学术查找相关文献.用RevMan 5.2进行统计学分析,依据Cochrane质量评价标准进行文献质量评估.纳入标准如下:(1)已发表的比较不同剂量131I对分化型甲状腺癌(DTC)清甲成功率的研究.(2)患者均行甲状腺切除术.(3)均为术后首次131I治疗.(4)服131I后3～12个月行清甲成功率评估.(5)服131I剂量为888 ～4 440 MBq(24～120 mCi).本研究定义低剂量为888～1 443 MBq(24～39 mCi)、中剂量为1 480～2 923 MBq(40 ～79 mCi)、高剂量为2 960～4 440 MBq(80～120 mCi).当研究间存在异质性时(I2＞50％)、采用随机效应模型进行荟萃分析,否则采用固定效应模型进行荟萃分析.结果 共纳入17个随机对照研究,包括3 737例患者(低剂量1 514例、中剂量811例、高剂量1 412例).5项研究比较了低剂量与中剂量的成功率,研究间有异质性(I2 =67％,P=0.02)、采用随机效应模型,荟萃分析结果显示两组的清甲成功率差异无统计学意义[风险比(RR) =0.89(0.80～1.00),P=0.06].7项研究比较了中剂量与高剂量的成功率,研究间无异质性(I2=34％,P=0.17),采用固定效应模型,荟萃分析结果显示两组剂量的清甲成功率差异无统计学意义[RR =0.94(0.89～1.00),P=0.05].11项研究比较了低剂量与高剂量的成功率,研究间有异质性(I2=70％,P=0.0002),采用随机效应模型,荟萃分析结果显示高剂量的清甲成功率显著高于低剂量[RR=0.89(0.81 ～0.97),P=0.008].结论 对于术后DTC患者,低剂量与中剂量131I以及中剂量与高剂量131I的清甲成功率无明显差异,但高剂量131I的清甲成功率显著高于低剂量.     

Cervical lymph node metastases in papillary thyroid cancer: Preoperative staging with ultrasound and/or computed tomography

Preoperative screening of potential risk of lymph node metastasis is necessary for thyroidectomy plus lymph node dissection. The 2015 American thyroid association management guidelines do not recommend prophylactic cervical lymph node resection without clinical evidence of metastasis. Ultrasound is recommended imaging method and routine computed tomography is not recommended by the 2015 American thyroid association management guidelines for screening of lymph node metastasis. The objective of the study was to compare the diagnostic performance of ultrasound against that of computed tomography for screening cervical lymph node metastasis of patients with papillary thyroid cancer before thyroidectomy plus lymph node dissection.Data regarding preoperative neck ultrasound, neck computed tomography, and physical examination of the head and neck and postoperative pathological results of a total of 185 patients (age > 18 years) with a diagnosis of papillary thyroid cancer who had suspicious lymph nodes on preoperative imaging and treated by thyroidectomy plus lymph node dissection for the therapeutic purpose were collected and analyzed.Sensitivity (78.09% vs 75.28%, P < .0001) and accuracy (77.29% vs 75.13%, P = .0004) of neck computed tomography scanning to detect cervical lymph node metastasis were higher than those of neck ultrasound scanning. Sensitivity, accuracy, positive clinical utility, and negative clinical utility for neck ultrasound scanning plus neck computed tomography scanning to detect cervical lymph node metastasis were higher among all index tests (P < .05 for all) and were statistically the same as those of surgical pathology (P > .05 for all). The working areas for decision-making of thyroidectomy plus lymph node dissection of the physical examination, neck ultrasound, the neck computed tomography, and the neck ultrasound scanning plus the neck computed tomography scanning were 0 to 0.691 diagnostic confidence/lesion, 0 to 0.961 diagnostic confidence/lesion, 0 to 0.944 diagnostic confidence/lesion, and 0 to 0.981 diagnostic confidence/lesion, respectively.Besides the neck ultrasound, the neck computed tomography scanning can be used as a complementary imaging method to detect cervical lymph node metastasis of patients with papillary thyroid cancer before thyroidectomy plus lymph node dissection.Level of evidence: III.Technical efficacy stage: 2.     

Effect of recombinant human growth hormone treatment on insulin-like growth factor (IGF-I) levels in insulin-dependent diabetic patients

Basal and recombinant human growth hormone (rhGH)-stimulated insulin-like growth factor (IGF-I) levels were studied in 19 insulin-dependent diabetic patients and 4 healthy subjects. Diabetic patients were divided according to glucagon test result into CpN (10 patients without residual beta cell activity) and CpP (9 patients with preserved beta-cell activity) groups, and according to age into three groups (A=21–30 years; B=31–40 years; C=41–50 years). All control subjects belonged to group B. Blood glucose and growth hormone were measured at hourly intervals and IGF-I every 6 h during 24 h before and after 7 days treatment with 4 IU of rhGH given subcutaneously at 8 p.m. The age-related decrease in basal IGF-I levels was evident in both CpN and CpP groups of diabetic patients. IGF-I net increase with rhGH treatment was variable and insignificant in comparison with basal value without age-related differences in CpN diabetics. Progressively larger age-related increases in IGF-I concentrations were observed in CpP diabetic patients. This study indicates impairment of hepatic IGF-I generation capacity in diabetic patients without residual beta-cell activity and the importance of simultaneous actions of portal insulin and GH on hepatic IGF-I production.     

Clustered incidence of acute promyelocytic leukemia during gefitinib treatment for non-small-cell lung cancer: experience at a single institution

Although gefitinib, an epidermal growth factor receptor tyrosine kinase inhibitor, has been shown a significant activity for recurrent non-small-cell lung cancer (NSCLC), its long-term adverse effect with its continuous usage has hitherto not been clearly elucidated. Subjects were 108 consecutive NSCLC cases who were treated with gefitinib between November 2001 and December 2004 at our single institution. A crude incidence rate ratio was calculated by ratio of crude incidence rate in our subject to population-based incident rate of all leukemia (ICD: C91-95) in the same region. The 95% confidence intervals (CIs) were calculated based upon a Poisson distribution. Three cases of acute promyelocytic leukemia (APL) occurred during gefitinib treatment, and these patients' past treatment histories are presented herein. No other malignancy was identified. All of the cases were diagnosed at the stage of mild-to-moderate cytopenia, especially thrombocytopenia, without disseminated intravascular coagulation. All presented a normal karyotype with positive PML-RARalpha in RT-PCR, indicating submicroscopic translocation. They responded well to APL treatments, including all-trans-retinoic acid. The crude incident rate ratio was 639.9 (95% confidence interval: 131.6-1,878.9, P < 0.0001) when the APL incidence in this cohort was compared to all leukemia cases in the general population in the same district in Japan. Thus we had three cases of secondary APL patients within the gefitinib-treated NSCLC cohort. Although we cannot exclude an effect of past exposure of other cytotoxic agents and radiotherapy as a cause of APL, APL inducibility of gefitinib should be clarified in the further study.     

Minimally invasive resection for colorectal cancer: perioperative and medium-term results in an unselected patient group at a single institution

Background The use of laparoscopy for colorectal cancer resection is still controversial. Methods We prospectively analyzed the outcome of minimally invasive resection for colorectal cancer, performed at our institution from 1998, when laparoscopic surgery became the treatment of choice for colorectal cancer, until 2004. All patients undergoing elective resection were assessed in terms of perioperative results (duration of surgery, number of lymph nodes removed, length of specimen, rate of conversion, complications) and survival. Patients were assessed yearly with follow-up visits and telephone interviews. Results In the study period, 302 patients (mean age 66.1 years; range, 32–93 years) underwent 114 left hemicolectomies, 108 low anterior resections, 61 right hemicolectomies, 12 Miles procedures, 4 subtotal colectomies, and 3 transverse colon resections. Surgery took an average of 226 minutes (SD=71 min). The number of lymph nodes removed was 14±8. The conversion rate was 10%; most of the conversions were due to locally advanced cancer (15 cases) and bowel distension (7 cases). Fifteen anastomotic leaks were observed (5%). Twenty patients needed reoperation and two died: one of septic shock due to an anastomotic leak; the other of electrolyte imbalance and dehydration after peritonitis due to a bowel loop injury. Follow-up was available for 91% of patients. Cancer-related survival curves showed a 90% survival for stage II, 85% for stage III, and 10% for stage IV disease, 30 months after surgery. Conclusions Minimally invasive laparoscopic resection for colorectal cancer enables an oncologically adequate resection with complication and survival rates that are no worse than are to be expected after traditional open surgery. Locally advanced tumor and bowel distension are the most frequent reasons for conversion to open surgery. An erratum to this article is available at .     

Insulin-like growth factor I levels during growth hormone (GH) replacement in GH-deficient adults: a gender difference

To evaluate the variation of serum IGF-1 levels during GH replacement and observe gender differences, 29 adults with GH deficiency (mean age 42.5 ± 10.1 year), were studied. Serum IGF-1 was assessed every 4 weeks during the titration period and afterwards every 3 months of GH therapy. At baseline 77.7% of women and 45.4% of men had serum baseline IGF-1 levels below the lower limit of normal age-related reference range. The time to reach the maintenance dose was lower in men than women (p < 0.05). There was an increase in IGF-1 levels after one year of GH therapy, significant only in men (p < 0.01). IGF-1 concentrations were higher in men than women (p < 0.05), at the 12th and 18th months of GH therapy. GH dose was reduced by 25% in men (p < 0.01). At the end of the study the mean GH dose was lower in men than in women (p < 0.05). The factor responsible for these findings is not known, however a possible role of androgens has been suggested.     

Clinical effects of cisplatin plus recombinant human endostatin (rh-endostatin) intratumoral injection on malignant central airway obstruction: a retrospective analysis of 319 cases

BackgroundPrimary lung cancer with severe central airway obstruction (CAO) is often life-threatening. In this study, we investigated the clinical efficacy and safety of cisplatin plus recombinant human endostatin (rh-endostatin) intratumoral injection in treatment of malignant central airway obstruction (MCAO) caused by primary squamous cell lung cancer.MethodsWe retrospectively analyzed patients with MCAO caused by primary squamous cell lung cancer treated with and without bronchoscopic intratumoral injection of cisplatin plus rh-endostatin between January 2007 and June 2016.ResultsA total of 206 patients received cisplatin plus rh-endostatin intratumoral injection, and 113 without injection. Dyspnea grade, degree of stenosis, quality of life and lung function of all patients were significantly improved at 1 week after treatment compared with baseline. Both groups achieved good airway patency (97.1% vs. 93.8%, P=0.156). Followed up at 2 months, all parameters were improved in the injection group compared with baseline, while no statistical differences were observed in the non-injection group (P>0.05). The injection group achieved airway patency in 155 (75.2%) of 206 patients, which was significantly superior to the non-injection group [20 (17.7%) of 113, P<0.001]. In addition, the restenosis rate of the injection group was lower compared with the non-injection group (22.5% vs. 81.1%, P<0.001, respectively). No serious complications were observed in two groups.ConclusionsCisplatin plus rh-endostatin intratumoral injection is effective and safe for the therapy of MCAO caused by primary squamous cell lung cancer.     

Primary ocular adnexal mucosa-associated lymphoid tissue lymphoma (MALT): single institution experience in a large cohort of patients

Extranodal marginal zone B-cell lymphoma is the most common orbital tumour. We conducted a retrospective analysis to examine: (i) the impact of initial presentation and staging on outcome and (ii) response to various treatment modalities and the effect of the latter on recurrence. Ninety patients with primary ocular adnexal marginal zone lymphoma (POAML) diagnosed at our institution between 1984 and 2009 were studied. POAML was associated with monoclonal gammopathy (13%) at presentation. Most POAML patients (86%) presented with Ann-Arbor stage I disease. Radiotherapy led to excellent local control, but relapses occurred in 18% of Ann-Arbor stage I patients during a median follow-up of 5 years. Local relapses, including secondary central nervous system (CNS) involvement, were observed in patients receiving radiation doses <30·6 Gy. No differences in relapse rate and survival were observed between patients who did or did not undergo staging bone marrow biopsy. Ann-Arbor stage II-IV disease and high lactate dehydrogenase levels were associated with shorter freedom from progression. In conclusion, POAML is an indolent lymphoma with continuous risk for relapse. Radiation doses of at least 30·6 Gy should be given in Ann-Arbor stage I disease, since lower doses may be more frequently associated with relapses, including CNS relapses.     

Pharmacokinetics of intravenous recombinant human granulocyte colony-stimulating factor (rhG-CSF) in children receiving myelosuppressive cancer chemotherapy: Clearance increases in relation to absolute neutrophil count with repeated dosing

Limited evidence suggests increased efficacy of rhG-CSF by subcutaneous (SQ) compared with intravenous (IV) administration. To examine the possibility that rapid elimination of IV rhG-CSF could substantially shorten the duration of systemic exposure and could explain a difference in pharmacodynamics, we characterized the pharmacokinetic profile of IV rhG-CSF for comparison to that previously reported for SQ administration. Twelve children were randomly assigned to receive 10 or more days of IV rhG-CSF at dosages of 5 or 10 μg/kg a day beginning 24 hr after chemotherapy. Enzyme-linked immunosorbent assay (ELISA) was used to measure rhG-CSF concentrations in timed serum samples on days 1 and 10. Pharmacokinetic parameters were estimated by nonlinear, least squares regression. All serum concentration-time profiles were best described by a two-compartment model of elimination. Mean t_1/2β values ranged from 3.68 ± 0.86 to 22.4 ± 12.0 hr. ANC was correlated with log CL_T (r = 0.72, P < 0.05), and inversely with log dose-adjusted AUC (r = −0.75, P < 0.05) and log dose-adjusted C_max (r = −0.65, P < 0.05). Estimated duration of serum rhG-CSF concentrations above 1 ng/ml exceeded 24 hr for all but the 5 μg/kg cohort on day 1. Pharmacokinetic parameters of IV rhG-CSF are similar to those previously reported for SQ administration in children treated with myelosuppressive cancer chemotherapy. Daily IV administration should be suitable alternative route of administration in this patient population. Am. J. Hematol. 54:124–130, 1997 © 1997 Wiley-Liss, Inc.     

Ablation of thyroid residues with 30 mCi (131)I: a comparison in thyroid cancer patients prepared with recombinant human TSH or thyroid hormone withdrawal

The aim of the study was to assess whether stimulation by recombinant human TSH (rhTSH) may be used in patients with differentiated thyroid carcinoma for postsurgical ablation of thyroid remnants using a 30-mCi standard dose of (131)I during thyroid hormone therapy. The rate of ablation was prospectively compared in three groups of patients consecutively assigned to one of three treatment arms: in the first arm, patients (n = 50) were treated while hypothyroid (HYPO); in the second arm, patients (n = 42) were treated while HYPO and stimulated in addition with rhTSH (HYPO + rhTSH); in the third arm, patients (n = 70) were treated while euthyroid (EU) on thyroid hormone therapy and stimulated with rhTSH (EU + rhTSH). The outcome of thyroid ablation was assessed by conventional HYPO (131)I scan performed in HYPO state 6-10 months after ablation. Basal serum TSH was elevated in the HYPO and HYPO + rhTSH groups. In the EU + rhTSH group, basal serum TSH was 1.3 +/- 2.5 micro U/ml (range, <0.005-11.9 micro U/ml). After rhTSH, serum TSH significantly increased in the HYPO + rhTSH group and the EU + rhTSH group. Basal 24-h radioiodine thyroid bed uptake was 5.8 +/- 5.7% (range, 0.2-21%) and 5.4 +/- 5.7% (range, 0.2-26%) in the HYPO and HYPO + rhTSH groups, respectively. In the HYPO + rhTSH group, mean 24-h thyroid bed uptake rose to 9.4 +/- 9.5% (range, 0.2-46%) after rhTSH (P < 0.0001). The 24-h uptake after rhTSH in the EU + rhTSH group was 2.5 +/- 4.3% (range, 0.1-32%), significantly lower (P < 0.0001) than that found in the HYPO and HYPO + rhTSH groups. The rate of successful ablation was similar in the HYPO and HYPO + rhTSH groups (84% and 78.5%, respectively). A significantly lower rate of ablation (54%) was achieved in the EU + rhTSH group. Mean initial dose rate (the radiation dose delivered during the first hour after treatment) was significantly lower in the EU + rhTSH group (10.7 +/- 12.6 Gy/h) compared with the HYPO + rhTSH group (48.5 +/- 43 Gy/h) and the HYPO group (27.1 +/- 42.5 Gy/h). In conclusion, our study indicates that by using stimulation with rhTSH, a 30-mCi standard dose of radioiodine is not sufficient for a satisfactory thyroid ablation rate. Possible reasons for this failure may be the low 24-h radioiodine uptake, the low initial dose rate delivered to the residues, and the accelerated iodine clearance observed in EU patients. Possible alternatives for obtaining a satisfactory rate of thyroid ablation with rhTSH may consist of increasing the dose of radioiodine or using different protocols of rhTSH administration producing more prolonged thyroid cells stimulation.     

New drugs for colorectal cancer (irinotecan, oxaliplatin, raltitrexed) meet expectations in routine practice: a single center's experience before and after their introduction

Background and Aims: Treatment of metastatic colorectal cancer with new drugs (NDs) as oxaliplatin and irinotecan had improved response and survival. In order to check whether the promising achievements of the trials are obtained in routine clinical practice, we have reviewed retrospectively our results for two periods, before (period A: 1993–1995, n=63) and after (period B: 1998–2000 n=103) the introduction of these NDs. Patients characteristics, treatment modalities, survival, and prognostic factors were compared. Patients: There were 74 women and 92 men, aged 60.8 ±11.6 yr, 7 patients received best supportive care only, 91 had synchronous metastasis. Results: Period B patients were older, with WHO score >1 more often, more adjuvant treatment, more metachronous metastasis, and NDs used more frequently (24% vs 59%). Median survival was similar (16 vs 15 mo). But when looking at the population aged <75 years with WHO score <2, median survival was 13 mo (period A) vs 21 mo (period B); survival at 1,2, and 3 yr were respectively 59.5±8%, 16.2±6%, 13.5±6% vs 69.8±6%, 49.6±7%, 29.8±7%, p<0.01). In multiparametric analysis, factors correlated with survival were the absence of elevated serum alkaline phosphatase, a unique metastatic organ, and administration of NDs. Conclusion: In our routine clinical experience the use of NDs for metastatic CRC has allowed a significant improvement in survival among patients with unresectable tumors.     

Intraluminal high‐dose‐rate brachytherapy for palliation of dysphagia in cancer of the esophagus: initial experience at a single UK center

Esophageal cancer tends to present with advanced disease, and the majority of patients are suitable only for palliative treatment at diagnosis. Dysphagia is the most common presenting symptom and significantly undermines quality of life. High‐dose‐rate intraluminal brachytherapy (ILBT) has been an option for the palliation of dysphagia for many years and has been used at our center since 2006. Experience was presented in terms of improvement of dysphagia and survival. Patients were identified from the local radiotherapy database. Original treatment sheets and clinical notes were reviewed retrospectively to obtain treatment details, pretreatment and post‐treatment dysphagia scores, and survival information. Between January 2006 and January 2010, 21 patients of median age 77 years with a mean pretreatment dysphagia score of 2.5 underwent ILBT for esophageal cancer. All received 12 Gy in a single fraction. Thirteen (62%) had adenocarcinoma and eight (38%) squamous cell carcinoma. Four (19%) tumors were in the mid‐esophagus and 17 (81%) in the lower esophagus. Eight had extension of tumor into the gastroesophageal junction. Seven patients (33%) received chemotherapy as first‐line treatment prior to brachytherapy. Nineteen patients had clear documentation of dysphagia scores both pretreatment and post‐treatment, and the improvement overall was significant (P= 0.04). Ten patients (53%) had an improvement in dysphagia score. Five of these (50%) went on to require further endoscopic intervention due to disease progression. Median duration of response was 4 months. Of the nonresponders, six (67%) went on to require further endoscopic intervention. No patients experienced documented toxicity aside from a short‐lived acute esophagitis. Median survival from date of diagnosis was 12 months and from treatment date was 5 months (1–32 months). In our series of elderly patients with significant dysphagia, ILBT was a well‐tolerated and effective treatment. It should be considered as a palliative option in esophageal cancer.     

The location and the regulation of the type I-iodothyronine 5′-monodeiodinase (type I-MD) in the rat thyroid: studies using a specific anti-type I-MD antibody

Type I-iodothyronine monodeiodinase (type I-MD) is abundant in thyroid tissue and contributes to the generation of T3 secreted by the gland. The availability of a specific antibody against rat type I-MD (type I-MD Ab) allowed us to directly identify this enzyme in rat thyroid glands, and in a differentiated strain of rat thyroid cells maintained in continuous culture (FRTL-5 cells). FRTL-5 cells maintain many differentiated functions of thyroid cells, including the expression of TSH receptor and thyroid peroxidase. Using an immunohistochemical technique on rat thyroid sections, a clear staining for type I-MD was demonstrated in follicular cells. The degree of immunoreactivity was greater in small follicles containing little amounts of colloid compared to large follicles lined by functionally inactive cells. Using immunofluorescence (IFL), a strong staining for type I-MD was observed in FRTL-5 cells grown in medium containing TSH. Both in vivo and in culture the staining for type I-MD was localised in the cytoplasm of thyroid cells, while nuclei were negative. Interestingly, no surface staining was shown when viable FRTL-5 cells were submitted to the same IFL procedure. TSH deprivation for 7 days was followed by the disappearance of type I-MD. Immunoreactivity for type I-MD was recovered by addition of TSH, forskolin or thyroid stimulating antibody (TSAb) to TSH-deprived FRTL-5 cells. The effect of TSH was prevented by cycloheximide. There was no induction of type I-MD when IGF-I was added to FRTL-5 cells. In conclusion, our results indicate that: (i) type I-MD is abundant in intracytoplasmic membranes of rat thyroid cells, both in vivo and in culture, while it is not expressed on the outer side of the plasma membrane; (ii) the synthesis of type I-MD is TSH-dependent through pathways that involve cAMP production, while it is not influenced by IGF-I which activates the tyrosine protein kinase pathway; (iii) TSAb mimics TSH in inducing the expression of type I-MD in FRTL-5 cells, and may thus influence the intrathyroidal generation of T3 in patients with Graves' disease.     

Treatment with recombinant human erythropoietin (rHuEpo) in a patient with paroxysmal nocturnal haemoglobinuria: evaluation of membrane proteins CD55 and CD59 with cytofluorometric assay

We describe a 28-year-old man with paroxysmal nocturnal haemoglobinuria (PNH) and a high transfusion requirement. Prior to and during therapy with recombinant human erythropoietin (rHuEpo), we evaluated the levels of 'decay-accelerating-factor', CD55, and 'membrane-inhibitor-of-reactive-lysis', CD59, as markers of the disease, whilst CD58, a marker present on leucocytes, was utilized to monitor normal haemopoietic activity.
The patient became transfusion independent 1 month after beginning rHuEpo and remains well. The analysis of CD55, CD59 and CD58 suggests that the efficacy of rHuEpo was due to a selective rHuEpo action on normal erythroid clones.