Ten-Year Follow-Up of a Randomized Clinical Trial of Total Thyroidectomy Versus Dunhill Operation Versus Bilateral Subtotal Thyroidectomy for Multinodular Non-toxic Goiter.

BACKGROUND: The aim of this study was to validate in a 10-year follow-up the initial outcomes of various thyroid resection methods for multinodular non-toxic goiter (MNG) reported in World J Surg 2010;34:1203-13. MATERIALS AND METHODS: Six hundred consenting patients with MNG were randomized to three groups of 200 patients each: total thyroidectomy (TT), Dunhill operation (DO), bilateral subtotal thyroidectomy (BST). Obligatory follow-up period of 60 months was extended up to 120 months for all the consenting patients. The primary outcome measure was the prevalence of recurrent goiter and need for revision thyroid surgery. The secondary outcome measure was the cumulative postoperative and post-revision morbidity rate. RESULTS: The primary outcomes were twice as inferior at 10 years when compared to 5-year results for DO and BST, but not for TT. Recurrent goiter was found at 10 years in 1 (0.6%) TT versus 15 (8.6%) DO versus 39 (22.4%) BST (p < 0.001), and revision thyroidectomy was necessary in 1 (0.6%) TT versus 5 (2.8%) DO versus 14 (8.0%) BST patients (p < 0.001). Any permanent morbidity at 10 years was present in 5 (2.8%) TT patients following initial surgery versus 7 (4.0%) DO and 10 (5.7%) BST patients following initial and revision thyroidectomy (nonsignificant differences). At 10 years, 23 (11.5%) TT versus 25 (12.5%) DO versus 26 (13.0%) BST patients were lost to follow-up. CONCLUSIONS: Total thyroidectomy can be considered the preferred surgical approach for patients with MNG, as it abolishes the risk of goiter recurrence and need for future revision thyroidectomy when compared to more limited thyroid resections, whereas the prevalence of permanent morbidity is not increased at experienced hands. REGISTRATION NUMBER: NCT00946894 ( http://www.clinicaltrials.gov ).

Prothymosin-alpha and Ki-67 expression in pituitary adenomas.

INTRODUCTION: Prothymosin alpha (PTMA), a nuclear oncoprotein involved in cell cycle regulation, is used as a prognostic marker in many cancers. The histopathology of pituitary carcinomas and locally invasive adenomas is indistinguishable from that of benign tumors. A new marker is needed to differentiate these lesions. We evaluated PTMA in pituitary adenomas to determine its usefulness as a prognostic factor of tumor proliferation. MATERIAL/METHODS: We conducted a retrospective analysis of a group of 27 patients, including 15 females (56%) and 12 males (44%) with a mean age of 58.6±12 years, who underwent pituitary tumor surgery between 2003 and 2012. The Ki-67 and PTMA-nuclear (PTMA-n) and PTMA-cytoplasmic (PTMA-c) indices were determined by immunohistochemical staining. We studied histopathological features, clinical symptoms, and magnetic resonance imaging or computed tomography performed before surgery and one year following surgery to evaluate tumor size and progression. RESULTS: The expression of Ki-67 was revealed in 77.8% of adenomas, PTMA-n in 81.5% and PTMA-c in 92.6%. The mean value of the Ki-67 index was 1.8%, PTMA-n was 1.84%, and PTMA-c was 35.6%. There was a significant positive correlation between Ki-67 and PTMA-n (p=0.009). We did not find any correlation between Ki-67, PTMA-c, and tumor progression. PTMA-n was found to be correlated with tumor size (p=0.045) and was higher in the case of gonadotropinomas (p=0.026). CONCLUSIONS: The positive nuclear expression of Ki-67 and PTMA was observed in the majority of pituitary adenomas. Neither the expression of Ki-67 nor that of PTMA-c was related to tumor recurrence or local invasion.

PTTG and Ki-67 expression in pituitary adenomas.

INTRODUCTION: The unpredictable biology of pituitary adenomas makes it a therapeutic challenge. Moreover ,histopathology of pituitary carcinomas and locally invasive adenomas are indistinguishable from benign tumors and a new marker which would enable to differentiate those lesions is vital. The aim of the study was to evaluate Ki-67 and PTTG (pituitary tumour--transforming gene) expression in pituitary adenomas and their applicationas markers of tumour aggressiveness. MATERIAL AND METHODS: A retrospective analysis of 55 patients: 32 females(58%) and 23 males (42%), mean age 50 ± 16 years who underwent pituitary tumor surgery between 2003-2012. Ki-67 and PTTG indices were determined by immunohistochemical staining. Magnetic resonance imaging or computed tomography was performed beforehand and one year after surgery to figure a potential tumour progression, tumour size and correlation to adjacent tissues. RESULTS: The expression of Ki-67and PTTG was revealed in cell nucleiin 88% and 85% of adenomas, respectively. The median Ki-67 and PTTG indices were 1.4 and 1.0, respectively(p = 0.006). In the group with macroadenoma as compared with the group with microadenoma, median Ki-67 index was higher (1.4% vs. 1.03%; p = 0.02). We did not find correlation between both Ki-67 and PTTG indices and tumour progression. Tumours with positive immunostaining towards FSH revealed lower Ki-67 and PTTG indices than the rest with a negative one (0.6% vs.1.84%, p = 0.0004 and 0.67% vs 1.23%,p = 0.047; respectively). However, PTTG index was higher in the group with acromegaly as compared to the group with clinically non-functioning pituitary adenoma (NFPA) (1.28% vs.0.35%; p = 0.02). CONCLUSIONS: Positive nuclear expression of Ki-67 and PTTG was observed in the majority of pituitary adenomas. Only higher Ki-67 expression was related to the tumour invasiveness found on MRI/CT. Tumour progressionwas not related to both Ki-67 and PTTG expression.

Polish validation of the Transplant Effects Questionnaire.

Introduction: The Transplant Effects Questionnaire (TxEQ) assesses specific recipients' reactions to receiving a transplanted organ, including worry about the transplant, Guilt regarding the donor, disclosure of having undergone transplantation, adherence to medical treatment, and responsibility to the donor, family, or medical staff. Poland has no standardized tool for evaluating the emotional reaction to transplantation. The study aimed to assess the basic psychometric properties, such as the reliability and validity of the Polish translation of TxEQ-PL. Materials and methods: The study involved 84 patients after kidney transplantation. The average age of the subjects was 49.87 years (±15.27). The study used the diagnostic survey method, the Polish versions of the Revised Life Orientation Test (LOTR-R), the Mental Component Summary of the SF-36 (SF-36-MCS), and the Hospital Anxiety and Depression Scale (HADS). The Confirmatory Factor Analysis (CFA) was used to verify the factor structure of TxEQ -P.L. variables. Results: The TxEQ-PL version has satisfactory internal consistency for each subscale (Cronbach's alpha > 0.7). The analysis showed a significant negative relationship between optimism (LOT-R) and the TxEQ-PL subscales: worry about transplant and disclosure of having undergone transplantation and a positive relationship in the subscale of adherence to medical treatment. In addition, a significant negative relationship was found between the subscale: adherence to medical treatment and the severity of depression and intensity of anxiety (HADS); also, a positive relationship with the Mental Component Summary of the SF-36 (SF-36-MCS). The intensity of anxiety and severity of depression were positively related to the TxEQ-PL subscale of disclosure of having undergone transplantation and negatively associated with the Mental Component Summary of the SF-36 (SF-36-MCS). The Confirmatory Factor Analysis confirmed the five-factor structure of the TXEQ-PL questionnaire (RMSEA = 0.083). Not the best fit is indicated by the value of comparative fit indexCFI = 0.813 and SRMR = 0.10. The result of the chi-squared test (220) = 340 was statistically significant; p < 0.001. Conclusion: TxEQ-PL is useful for assessing emotional reactions to organ transplantation. The tool has a factor structure identical to the original English version and comparable psychometric properties.

Expression of cyclooxygenase-2 (COX-2) in pituitary tumours.

BACKGROUND: Microvessel density in angiogenesis is regarded as a prognostic factor of tumour invasiveness, independent of cell proliferation. In recent studies of pituitary tumours, correlation between the expression of cyclooxygenase-2 (COX-2) and micro-vascularization density and microvessel surface density has been established. We studied the expression of COX-2 in different types of pituitary adenomas to determine the usefulness of COX-2 expression as a prognostic factor of tumour progression or recurrence in patients with hypophyseal tumours. MATERIAL/METHODS: We retrospectively studied a group of 60 patients of mean age 46.7±17.6 (range, 18 to 85) years who underwent pituitary tumour surgery. Expression of COX-2, as determined by immunohistochemistry, was analyzed in relation to histopathology features of tumour, clinical symptoms, MR imaging and post-operative recurrence/progression of disease. RESULTS: COX-2 was expressed in adenomas of 87% of patients, with a median index value of 57.5% [IQR=60.5]. Highest COX-2 expression was observed in hormonally inactive adenomas and gonadotropinomas and lowest in prolactinomas. We found no differences in COX-2 expression with respect to patient age, gender, tumour size, degree of tumour invasiveness, or whether tumours were immunopositive or immunonegative for pituitary hormones, nor have we found any relation between COX-2 expression and recurrence or progression of tumour size. CONCLUSIONS: COX-2 does not appear to be a predictive factor for recurrence or progression of tumour size. Nevertheless, due to the observed relatively high expression of COX-2 in pituitary adenomas, further studies with COX-2 inhibitors are justified in these tumours.

Dietary patterns as risk factors of differentiated thyroid carcinoma.

UNLABELLED: Nutritional factors are known to be important in the development of different metabolic diseases. The history of nodular or diffuse goiter is closely related to risk of thyroid carcinoma. On account of the function of the thyroid gland, many studies focus on iodine intake. The aim of the study was to assess whether dietary patterns could be risk factors of differentiated thyroid carcinoma. MATERIAL/METHODS: The case-control study was based on a questionnaire, which included information about dietary patterns and was carried out on 284 patients comprising 30 males (mean age 58.4±13.7 years), and 254 females (mean age 52.1±13.8 years), as well as 345 randomly selected controls: 58 males (mean age 60.2±12 years) and 287 females (mean age 53.4±14.3 years) randomly selected from the Population Register and adjusted by age and gender to the group of TC. The main groups of nutritional products, i.e. starchy foods, meat, dairy products, vegetables, fruits, and beverages, were analyzed. RESULTS: Consumption of vegetables, fruits, saltwater fish and cottage cheese was significantly lower in patients with differentiated thyroid carcinoma than in controls, quite the contrary to starchy foods, especially white bread. CONCLUSIONS: Dietary patterns appear to modify the risk of thyroid carcinoma. A diet rich in vegetables and fruit, as well as saltwater fish (a source of iodine) and low-fat meat, could be an important protective factor.

Efficacy and complications of neurosurgical treatment of acromegaly.

The aim of the study was to evaluate the frequency of occurrence of pituitary failure following neurosurgery and the efficacy of transsphenoidal tumour resection in acromegalic patients. We retrospectively evaluated 85 patients (60 female and 25 male), of mean age 43.9 ± 13.2 years, treated by transsphenoidal neurosurgery. Macroadenoma and microadenoma of pituitary were found in 66 (77.6%) and 19 (22.4%) of these patients, respectively. Criteria of cure following neurosurgery were: basal GH<2.5 µg/l, GH at 120 min in OGTT<1.0 µg/l and serum concentration of IGF-1 within normal ranges for age and sex. After surgery 32 patients (37.6%) were cured and 53 patients (62.4%) required somatostatin analogue treatment. In patients cured by surgery, lower levels of basal GH (P<0.05), IGF-1 (P<0.001), GH at 120 min in OGTT and smaller size of pituitary tumour (P<0.05) were found at diagnosis, as compared to patients in whom surgery was unsuccessful. Significant correlation between basal serum level of GH at diagnosis and size of pituitary tumour was found (P<0.001). Invasive tumours were found in 45 of 53 (84.9%) patients not cured and in only 8 of 32 (25.0%) patients cured (P<0.001). Impaired function of pituitary anterior lobe after surgery was observed in 30% and 4% of patients with macro- and microadenoma, respectively (P<0.05). The efficacy of neurosurgery is affected by concentration of basal serum GH and IGF-1, GH at 120 min in OGTT, tumour size and invasiveness. Hypopituitarism after surgery is more frequent in patients with macroadenoma. Pituitary insufficiency, as a consequence of surgery, was found in 21% of patients with normal pituitary function prior to operation.

[Assessement of the usefulness of whole body scintigraphy after administration of 6 MBq of 131I in the diagnostic of breast cancer]. / Ocena mozliwosci zastosowania scyntygrafii calego ciala po podaniu 6 MBq 131I w diagnostyce raka sutka.

INTRODUCTION: Sodium-iodine symporter (NIS) belongs to a large family of natrium dependent ion transporters found in normal thyroid cells located on the basilar membrane of tyreocytes. Under physiologic conditions, the NIS is also present in other tissues: salivary glands, gastric mucosa, mammary glands during lactation, and vascular plexus of the fourth ventricle. NIS expression has also been found in many tumors, including breast cancer. AIM: The aim of this study was to evaluate the usefulness of whole body scintigraphy after administration of relatively low activity of 131I (6 MBq)in the diagnostics of breast cancer. MATERIAL AND METHODS: The study included nine women with breast cancer, aged 38-73 years (mean 55.6 +/- 11.7 years) and a control group of 14 women aged 29-84 years (mean 48.8 +/- 16.7 years). The uptake of radioiodine in whole body scintigraphy 24 hours after administration of 131I radioiodine (6 MBq) was compared between the control group and breast cancer patients. No pharmaceuticals reducing thyroid iodine uptake or increasing NIS expression were used. RESULTS: Whole body scans using 6 MBq 131I activity revealed no focal radioiodine uptake outside the thyroid tissue in patients with breast cancer as well as volunteers from the control group. CONCLUSIONS: Whole body scintigraphy using 131I, dosed at 6 MBq, with no additional treatment increasing extrathyroidal uptake of radioiodine, appears to be ineffective in the imaging of breast cancer.

Five-year follow-up of a randomized clinical trial of unilateral thyroid lobectomy with or without postoperative levothyroxine treatment.

BACKGROUND: The aim of this study was to compare the prevalence of recurrent nodular goiter in the contralateral thyroid lobe among patients after unilateral thyroid lobectomy for unilateral multinodular goiter (MNG) receiving versus not receiving postoperative prophylactic levothyroxine (LT4) treatment. METHODS: From January 2000 through December 2003, 150 consenting patients underwent a unilateral thyroid lobectomy for unilateral MNG at our institution. They were randomized to two groups with 75 patients in each group. Patients in group A received prophylactic LT4 treatment postoperatively (dose range 75-125 microg/day to maintain thyroid-stimulating hormone values below 1.0 mU/L), whereas patients in group B received no postoperative LT4 treatment. All the patients underwent ultrasonographic, cytologic, and biochemical follow-up for at least 60 months postoperatively. The primary outcome was the prevalence of recurrent goiter in the contralateral thyroid lobe. The secondary outcome was the reoperation rate for recurrent goiter. The outcomes were stratified according to individual iodine metabolism status assessed by urinary iodine excretion. RESULTS: During the 5-year follow-up, among patients receiving vs. not receiving LT4, recurrent goiter within the contralateral thyroid lobe was found in 1.4% vs. 16.7% of patients, respectively (p = 0.001). Moreover, 1.4% vs. 8.3%, respectively, of patients receiving vs. not receiving LT4 required contralateral thyroid lobe surgery (p = 0.05). LT4 decreased the recurrence rate among iodine-deficient patients (3.4% vs. 36%, respectively; p = 0.002) but not among iodine-sufficient patients (0% vs. 6.4%, respectively; p = 0.09). CONCLUSIONS: Prophylactic LT4 treatment significantly decreased the recurrence rate of nodular goiter in the contralateral thyroid lobe and the need for completion thyroidectomy, mostly among patients with iodine deficiency.

Five-year follow-up of a randomized clinical trial of total thyroidectomy versus Dunhill operation versus bilateral subtotal thyroidectomy for multinodular nontoxic goiter.

BACKGROUND: The extent of thyroid resection in multinodular nontoxic goiter (MNG) is controversial. The aim of the present study was to evaluate results of various thyroid resection modes, with special emphasis put on the recurrence rate and morbidity rate, in a 5-year follow-up. MATERIALS AND METHODS: From 01/2000 through 12/2003, 600 consenting patients with MNG qualified for thyroidectomy at our institution were randomized to three groups equal in size, n = 200 in each. Patients in group A underwent total thyroidectomy (TT); patients in group B underwent Dunhill operation (DO), whereas patients in group C underwent bilateral subtotal thyroidectomy (BST). All patients were subjected to ultrasonographic, cytological, and biochemical follow-up at least for 60 months postoperatively. The primary outcome measure was prevalence of recurrent goiter and need for redo surgery. The secondary outcome measure was the postoperative morbidity rate (hypoparathyroidism and recurrent laryngeal nerve injury). RESULTS: Recurrent goiter was found in 0.52% TT versus 4.71% DO versus 11.58% BST (p = 0.01 for TT versus DO, p = 0.02 for DO versus BST, p < 0.001 for TT versus BST), and completion thyroidectomy was necessary in 0.52% TT versus 1.57% DO versus 3.68% BST (p = 0.03 for TT versus BST). Transient postoperative hypoparathyroidism was present in 10.99% versus 4.23% versus 2.1% (p = 0.007 for TT versus DO, p < 0.001 for TT versus BST), whereas the recurrent laryngeal nerve injury rate was 5.49% and 1.05% TT versus 4.23% and 0.79% DO versus 2.1% and 0.53% BST (transient and permanent, respectively; p = 0.007 for transient events TT versus BST). CONCLUSIONS: Total thyroidectomy can be regarded as the procedure of choice for patients with MNG. It is associated with a significantly lower incidence of goiter recurrence and less frequent need for completion thyroidectomy than other more limited thyroid resections. However, TT involves a significantly higher risk of postoperative transient but not permanent hypoparathyroidism and recurrent laryngeal nerve paresis.

[Gastrointestinal tract polyps in acromegaly patients]. / Polipy przewodu pokarmowego u chorych z akromegalia.

Acromegaly is a rare, chronic disease due to hypersecretion of growth hormone (GH) by pituitary adenoma arising from somatotrophs. The course of the disease is related to long-term organ and systemic complications and malignancies. Colon polyps seem to constitute the most frequent tumours in acromegaly apart from thyroid nodules. The aim of this study was to evaluate the prevalence of colon polyps in patients with acromegaly. Thirty one acromegaly patients, 22 females and 9 males (mean age 46.3 +/- 11.9 yrs), were enrolled to the study. Colonoscopy with histopathological assessment of specimens taken during examination was carried out in all patients. Colon polyps were found in 13 patients (41.9%) i.e. 8 females and 5 males. In two patients multiple polyps were discovered (2 and 3 respectively). Polyps were histopatologically verified as tubular adenoma with low-grade dysplasia (10 patients, 76.9%) and hyperplastic polyps (3 patients, 23.1%). The prevalence of colon polyps was significantly related to the duration of uncontrolled acromegaly (p < 0.01). Median duration of uncontrolled acromegaly in patients with and without colon polyps were 10.0 (IQR = 2.0) yrs and 6.5 (IQR = 5.0) yrs, respectively. IGF-1, GH basic and in 120 min of OGTT serum concentrations on diagnosis were not significantly related to the prevalence of colon polyps. Our study indicates that duration of uncontrolled acromegaly, contrary to IGF-1, GH basic and in OGTT serum concentrations at diagnosis are essential for the colon polyps development. Colonoscopy is considered to be routine in patients with acromegaly.

The prevalence of benign and malignant neoplasms in acromegalic patients.

INTRODUCTION: In acromegalic patients, the prevalence of certain benign and malignant neoplasms is higher than that in the healthy population. We retrospectively evaluated the prevalence of tumours in acromegalic patients treated at our department: the regional centre for acromegalic patients for the Malopolskie voivodeship in Poland. MATERIAL AND METHODS: During the years 1983-2008, a hundred and one acromegalic patients (30 males and 71 women), of mean age 51.8 +/- 15.4 years, were diagnosed and treated. Pituitary macroadenoma and microadenoma were stated in 63.4% and 25.7% of these patients, respectively. In 10.9% of these patients no data on tumour diameter were available. The mean observation period was 9.4 +/- 6.5 years. The median levels of hGH and IGF-1 prior to neurosurgery were 20.2 (IQR = 34.9) ng/ml and 764.5 (IQR = 569.6) ng/ml, respectively. RESULTS: In the studied group of patients, we found the following prevalence of various tumours: nodular goitre - 64/101 patients (63.0%), polyps of the colon - 13/101 patients (13.0%); uterine polyps - 4/101 patients (4.0%); and prostate adenoma - 2/101 patients (2.0%). Among malignant tumours, thyroid cancer, endometrium and cervix cancer were the most frequent, each of these occurring in 3 patients (3.0%). Colon cancer prevalence was 2.0% (in 2 patients). CONCLUSIONS: From our retrospective study, we suggest an overall increase of tumour incidence in acromegalic patients. Prospective multicentre studies are required to resolve the significance of this observation. In our study group, the number of malignant neoplasms was significantly higher in patients with long-lasting uncontrolled disease (over 5 years), compared to patients with controlled disease. (Pol J Endocrinol 2010; 61 (1): 29-34).

Radioiodine ablation of thyroid remnants in patients with differentiated thyroid carcinoma (DTC) following administration of rhTSH - a comparison with L-thyroxine withdrawal.

INTRODUCTION: A group of differentiated thyroid carcinoma (DTC) patients receiving post thyroidectomy rhTSH-aided radioiodine treatment (group I) was compared with patients treated with ¹³¹I following endogenous stimulation of TSH (group II) after L-thyroxine withdrawal. MATERIAL AND METHODS: Group I consisted of 66 patients of mean age 51.7 ± 16.2 years (58 females and 8 males). Group II included 76 patients of mean age 54.8 ± 14.7 years (67 females and 9 males). All patients underwent total thyroidectomy and central lymph node dissection and additionally lateral lymph node excision, if required. Prior to radioiodine treatment thyroid volume (VT) and 24-hour ¹³¹I uptake were evaluated. TSH and Tg concentrations were measured prior to and after endogenous and exogenous stimulation of TSH. Whole-body post-therapeutic scintigraphy was evaluated. Basic statistics, W Shapiro-Wilk, Wilcoxon, and U Mann-Whitney tests were applied. RESULTS: Median values of VT and of 24-hr ¹³¹I uptake in groups I and II were not significantly different. The differences between median values of serum TSH concentration after stimulation in groups I and II were statistically significant (p < 0.05), respective medians being 100.0 µU/mL (IQR = 107.3) and 78.8 µU/mL (IQR = 47.7). Median values of serum Tg concentrations in groups I and II following TSH stimulation prior to radioiodine treatment were 2.6 ng/ml (IQR = 8.4) and 4.9 ng/mL (IQR = 12.6), respectively, the difference not being statistically significant. Following rhTSH treatment no adverse effects were observed compared to LT4 withdrawal. CONCLUSIONS: rhTSH may be safely used for ¹³¹I thyroid remnant ablation in low-risk DTC patients.

A case of acromegaly and disseminated follicular thyroid carcinoma.

INTRODUCTION: A particularly challenging case of concurrent acromegaly and follicular thyroid carcinoma in a patient of the Clinic of Endocrinology, UJCM in Krakow is discussed. CASE DESCRIPTION: A 59-year-old male with post total thyroidectomy performed in 2005 and histopathologically confirmed metastases of the follicular thyroid carcinoma to the lungs was admitted to the Clinic in April 2006 for complementary ¹³¹I treatment. Acromegaly was treated in 1996 by trans-sphenoidal surgery. In December 2005 a relapse of pituitary adenoma was shown by MRI, which correlated with increased levels of hGH and IGF-1. Biochemical control of acromegaly was achieved with Sandostatin LAR. Pre-therapeutic whole-body scintigraphy (WBS) revealed numerous conjoined hot spots of ¹³¹I accumulation in both lungs and in thyroid remnants. In May and November 2006 the patient received ¹³¹I treatment. Post-therapeutic WBS in November 2006 revealed complete ablation of the thyroid remnants. Laboratory tests confirmed lowering of thyroglobulin concentration. In the years 2007, 2008, and 2009 the patient was qualified for therapy with ¹³¹I aided by rhTSH, achieving further reduction of Tg levels. Post-therapeutic WBS performed in 2009 revealed weak bilateral tracer uptake in the lung parenchyma. In 2010, chest CT revealed fibrosis in left lung segments, no infiltrative changes, and no lymph node enlargement. Patient follow-up continues at our Department. CONCLUSIONS: Disseminated thyroid cancer in a patient with pituitary insufficiency may be successfully treated by rhTSH-supported ¹³¹I treatment.

[Evaluation of the efficacy of Octreotide LAR in the treatment of acromegaly--a yearly observation]. / Ocena skutecznosci leczenia Oktreotydem LAR u chorych z akromegalia--obserwacja roczna.

Since acromegaly is associated with high rates of comorbidities and increased mortality risk compared to the general population, over the last few years somatostatin analogues have been used to treat acromegaly patients who, following surgery, have not fulfilled cure criteria (basal hGH < 2.5 ng/ml, IGF-1 below normal ranges for age and sex and hGH < 1.0 ng/ml in the 120th min of the OGTT test). We assessed the efficacy of Octreotide LAR (OCT-LAR) in managing such patients. 72 patients underwent diagnostic tests to qualify them for Octreotide LAR treatment. Treatment efficacy evaluation was based on measuring the concentration of hGH and IGF-1 prior to and 3 and 12 months and performing control MRI 6 and 12 months after the beginning of OCT-LAR treatment. The dose of O ctreotide LAR was 20 mg/month, increased to 30 mg/month if unsatisfactory response was observed. We evaluated the efficacy of Octreotide LAR in 48 acromegaly patients (66.7% of 72 evaluated), in whom criteria of postsurgery cure were not fulfilled. 24 patients (33.3%) did not require further treatment. After 3 months of OCT-LAR treatment, hGH < 2.5 ng/ml was stated in 37.0% of patients, median value--3.4 ng/ml (IQR = 5.3), as compared to median value of 5.5 ng/ml (IQR = 5.6) before treatment (p < 0.05). After 3 months of treatment IGF-1 below normal ranges for age and sex was stated in 55.5% of patients, median value--336.8 ng/ml (IQR = 290.0), as compared to median value of 520.0 ng/ml (IQR = 351.0) prior to OCT-LAR treatment (p < 0.05). After 12 months hGH < 2.5 ng/l ml and IGF-1 below normal ranges for age and sex were found in 63.0% and 54.5% of patients, respectively. In control MRI recurrence, correlated with enhanced concentration of IGF-1, was stated in 7 patients (14.6%). Thus, we conclude that satisfactory acromegaly control, in terms of hGH and IGF-1 levels, was obtained in above 50% of patients treated with Octreotide LAR. Since in the studied group hGH secretion had achieved cure criteria after 3 months in 37.5% as compared to 63.0% after 12-months, assessment of OCT-LAR treatment should be extended over periods exceeding 3 months.

[Evaluation of radioiodine 131I treatment in Graves' disease patients with mild orbitopathy]. / Ocena wyników leczenia radiojodem 131I pacjentów z choroba Gravesa-Basedowa i lagodna orbitopatia.

UNLABELLED: Radioiodine (131I) treatment of patients with Graves-Basedow disease may cause or aggravate the course of orbitopathy (GO) in some 15% of patients; while only 3% of patients treated with methimazole develop GO. The aim of this study was to evaluate the frequency of GO progression in patients with mild GO treated with 131I, compared to a control group. MATERIALS AND METHODS: The studied group consisted of 21 hyperthyroid patients (mean age 49 +/- 12.8 years) with mild orbitopathy (CAS < 3 pts, NOSPECS < 4 pts). The control group included 18 hyperthyroid patients with Graves-Basedow disease (mean age 50 +/- 9.9 years) with no GO symptoms (CAS = 0 pts, NOSPECS < 1 pts). All patients were treated with 131I. Patients with GO underwent treatment with oral methyloprednisolone (MP) over 30 days in decreasing doses, commencing with a dose of 16 mg/day. TSH, FT4 and hTRAb serum concentrations were measured prior to, and 14, 30, 60 days and 12 months after administration of 131I, always accompanied by an ophthalmic evaluation. RESULTS: In the studied group, mean TSH and FT4 concentrations prior to treatment were 0.05 +/- 0.08 microU/ml and 23.7 +/- 10.7 pmol/l, respectively. Mean 131I activity applied in this group was 605.0 +/- 89.0 MBq. No significant differences were stated between values of respective parameters in the studied and control groups. Prior to treatment, median hTRAb concentrations in the studied and control groups were 6.8 U/l (max 53.8, min 0.1) and 8.9 U/l (max 57.1, min 4.2), respectively, and did not differ significantly. After 14 days post commencing MP treatment the median hTRAb concentration in the studied group decreased (4.5 U/l, max 51.1, min 0.1) with respect to the control group (7.5 U/l, max 50.0, min 2.9). After 60 days and 12 months, median hTRAb concentrations in the studied group were 8.3 U/l (max 16.9, min 0.7) and 8.5 U/l (max 9.8, min 3.0) respectively, being higher than those in the control group and also higher than the initial value in studied group. Cured were 16/21 patients in the studied group and 16/18 patients in the control group. Within 12 months observation, progression of GO symptoms in 2 patients (9%) of the studied group was noted and exophthalmos observed in 3 patients (17%) of the control group. CONCLUSIONS: In patients with mild GO treated with methyloprednisolone 131I administration is effective and does not lead to aggravation of GO symptoms, compared with the control group. Long-term elevation of hTRAb concentration in studied and control group of patients with Graves' disease treated with 131I1 was found.

[A case of Graves-Basedow disease with orbitopathy and papillary thyroid cancer]. / Przypadek pacjenta z choroba Gravesa-Basedowa, orbitopatia i rakiem brodawkowatym tarczycy.

Coexistence of Graves-Basedow disease with orbitopathy and thyroid cancer is believed to be a rare event. A 39-year-old man with clinical features of hyperthyroidism associated with exophthalmos and goitre presented to out patient clinic. Thyroid function tests showed hyperthyroidism with elevated thyroid-stimulating antibodies. Graves-Basedow disease was diagnosed. Ultrasound revealed diffuse thyroid enlargement with hypoechoic pattern and hypoechoic lesions with regular edges of 1.0 cm diameter at the left and right lobe. Fine needle aspiration biopsy was negative. Due to the patient's nodular goitre and mild orbitopathy, after some further 3 months of anti-thyroid medication, near total thyroidectomy was performed. Histologically, papillary microcarcinoma was found. Following surgery, the patient was referred to our Department of Endocrinology, L-thyroxine suppression treatment was commenced. Approximately 8 weeks post surgery, the patient reported with eye discomfort, soft tissue oedema and double vision. On CT thickening of the left superior rectus muscle was found. Methylprednisolone pulse therapy was applied (4 weeks, 2 grams per week). Glucocorticoid therapy resulted in significant improvement of soft tissue inflammation and of diplopia. The patient was qualified for 131I radioiodine complementary therapy (3657 MBq) and orbital irradiation. While some authors suggest that radioiodine therapy may be associated with worsening of pre-existing orbitopathy, so far we have not observed it in our patient, perhaps due to thyroid removal as a source of autoreactive T lymphocytes and the protective effect of applied glucocorticoids.

Markers of proliferation and invasiveness in somatotropinomas.

Introduction In the search for markers of invasiveness of pituitary adenomas, we studied the expression of Ki-67 antigen, TOPO 2A (topoisomerase 2 alpha), AIP (Aryl Hydrocarbon Receptor-Interacting Protein) and VEGF (Vascular Endothelial Growth Factor) in somatotropinomas. Material and Methods We retrospectively studied a group of 31 patients who underwent pituitary tumour surgery. Expression of Ki-67, TOPO 2A, AIP and VEGF in surgical specimens was determined by immunohistochemistry. Relations between quantitatively determined markers and clinical symptoms, tumour features, and MR imaging, were analysed. Acromegaly was confirmed by hormonal tests in all patients studied. Local invasiveness (cavernous sinus penetration, optic chiasm compression or suprasellar extension) was observed in 18/31 patients (58,1%). Results Ki-67 was expressed in 77.4%, TOPO 2A in 87.1%, AIP in 83.8%, and VEGF in 87.1% of 31 cases of somatropinoma. Median values of Ki-67, TOPO 2A, AIP and cytoplasmic VEGF indices were 1.2% [IQR=2.2], 1.5% [IQR=1.6], 21.26% [IQR=20.1] and 20.4% [IQR=15.4], respectively. Ki-67, TOPO 2A, AIP and VEGF expression was not correlated with age nor with patient gender (p > 0.05). Only Ki-67 and TOPO 2A correlated with tumour size (for Ki-67: r=0.42, p=0.025; for TOPO 2A: r=0.53, p=0.003). Ki-67 and TOPO 2A levels were significantly higher in invasive compared to noninvasive somatropinomas (Ki67 mean values: 1.85±1.33% vs. 0.95±1.07%, p=0.024; TOPO 2A mean values: 2.19±1.63% vs. 1.45±1.23%, , p=0.011). Conclusions Ki-67, TOPO 2A, AIP and VEGF were expressed in over 70% of all somatotropinomas. Only Ki-67 and TOPO 2A expression correlated with tumour size and tumour invasiveness.

Parathyroid transplantation in thyroid surgery.

Permanent hypoparathyroidism following thyroid surgery is rare. Its prevalence is reported to be below 1-2% if surgery is performed by experienced thyroid surgeons. Parathyroid identification and preservation in situ with good vascular supply is the mainstay of safe thyroid surgery. However, if the parathyroid glands are damaged, autotransplantation should be undertaken to preserve their function. Parathyroid transplantation can be considered in three distinct modes of application: (I) fresh parathyroid tissue autotransplantation during thyroidectomy in order to reduce the risk of permanent hypoparathyroidism; (II) cryopreserved parathyroid tissue autotransplantation in patients with permanent hypoparathyroidism; (III) parathyroid allotransplantation in patients with permanent hypoparathyroidism when cryopreserved parathyroid tissue is not available for grafting. Nowadays, allotransplantation of cultured parathyroid cells without immunosuppression should be taken into consideration in selected patients as an alternative to calcium and vitamin D3 supplementation in management of permanent hypoparathyroidism. This paper is aimed to provide a review of current status of various parathyroid transplantation techniques in thyroid surgery.

[Evaluation of the efficacy of long-acting somatostatin analog as adjunctive therapy in patients with active acromegaly]. / Ocena skutecznosci dlugodzialajacego analogu somatostatyny w leczeniu uzupelniajacym chorych z czynna akromegalia.

UNLABELLED: Transsphenoidal surgery is the first-line therapy for patients with acromegaly, but can achieve biochemical control with normalization of somatomedin C in 40-80% of cases. All patients with continued growth hormone hypersecretion after neurosurgery require adjunctive therapy to prevent morbidity and premature mortality. The aim of our study was to evaluate the efficacy of long-acting somatostatin analog--octreotide LAR (OCT-LAR) as adjunctive therapy for patients with persistent disease. 14 adult subjects (age 45 +/- 15 years) were included into the study. All patients were diagnosed as having growth hormone secreting pituitary tumor and underwent transsphenoidal surgery (TSS). Radiotherapy (RT) was used as adjunctive therapy in 7 of investigated persons. In all subjects elevated level of somatomedin C was found, 9 have increased level of growth hormone (hGH) as well. After 6 months therapy with OCT-LAR we noticed drop in somatomedin C and hGH levels in all patients. Mean drop in somatomedin C level was 42.3% (p=0.001), in GH level was 52.3% (p=0.001). We found entire normalization of GH in 12 (85.7%) patients, nearly normalization of somatomedin C (level lower than 110% of normal upper limit) in 8 (57%) patients. We found no significant correlation between decrease in somatomedin C and its level prior to the treatment (p=0.8), but high positive correlation between decrease in hGh level and its initial value (R=0.75, p=0.002). Decreases in both somatomedin C (p=0.7) and hGH (p=0.6) levels were not correlated with patients' age. The therapeutic outcome defined as decrease in somatomedin C level was not significantly different between patients with or without adjunctive radiotherapy in the past (p=0.08) and between patients with intensive or weak isotope collection in the pituitary in 99mTc-octreotide scintiscan (p=0.2). CONCLUSIONS: Octreotide-LAR efficiently reduces somatomedin C and GH levels in patients with active acromegaly. Initial values of somatomedin C as well as age and isotopic imaging findings are not valuable predictor factors for therapeutic outcome.