The risk of osteoporosis in patients with liver cirrhosis: a meta-analysis of literature studies.

OBJECTIVE: Data about the association between cirrhosis and osteoporosis are contrasting. Thus, we have performed a meta-analysis of literature studies on this topic. DESIGN: MEDLINE, Cochrane library, EMBASE, Scopus and Web of Science databases have been searched to retrieve all articles of interest. Data on prevalence of osteoporosis, bone mineral density (BMD) and bone turnover laboratory parameters were compared among cirrhotic patients and control subjects without cirrhosis. PATIENTS: Studies on patients with liver cirrhosis screened for the presence of osteoporosis were included. RESULTS: Six case-control studies (372 cirrhotic patients and 1579 controls) were included. The prevalence of osteoporosis was higher in cirrhotic patients than in controls (34·7% vs 12·8%, OR: 2·52, 95%CI: 1·11, 5·69; P = 0·03, I(2) = 81%; P = 0·005). Accordingly, a reduced lumbar spine BMD (MD: -0·13, 95%CI: -0·24, -0·02; P = 0·02, I(2) = 93%; P < 0·00001) and z-score (MD: -1·06, 95%CI: -1·79, -0·34; P = 0·004, I(2) = 95%; P < 0·00001) were found in cirrhotic patients as compared with controls. In contrast, no significant differences were reported in femoral neck BMD and z-score. Interestingly, bone turnover laboratory parameters widely confirmed these results showing higher levels of ALP and D-Pyr, accompanied by reduced levels of IGF-1, PTH and 25-OH-D in cirrhotic patients as compared with controls. CONCLUSIONS: Despite the high heterogeneity among studies, data showed an increased prevalence of osteoporosis in patients with cirrhosis. This information suggests the need of an accurate screening of bone mineral density in patients with liver cirrhosis to plan an adequate osteoporosis management.

An easy schedule for postsurgical radioiodine administration in newly diagnosed differentiated thyroid carcinoma patients.

OBJECTIVE: To validate the simplest approach to preparing patients with differentiated thyroid carcinoma (DTC) for (131) I-administration ((131) I-A), minimizing the impact of hypothyroidism. DESIGN: Panel study. PATIENTS: Ninety patients with DTC were enrolled in the study. Sixty (Group A) underwent total thyroidectomy (TT); L-T4 was not administered in preparation for (131) I-A planned for 3 weeks later. Thirty patients (Group B) with previous TT and (131) I-A stopped L-T4 in preparation for clinical evaluation, including whole-body scanning (WBS)/radioiodine therapy during thyrotrophin (TSH) stimulation planned for 3 weeks (or more) later. MEASUREMENTS: Thyrotrophin was measured the day before TT for group A, during L-T4 for group B (baseline-time 1) and then every week until it reached ≥ 30 mIU/l (time 2). Quality of life (QoL) was evaluated by Billewicz index. RESULTS: At week 3, 100% of patients in group A and 56.6% of group B exceeded TSH > 30 mIU/l. In group B, the cut-off was achieved in four patients at the fourth week (TSH 38.6 ± 8.7 mIU/l), in 3 at the fifth (53.2 ± 3) and in 6 at the sixth (42.3 ± 6.1). From time 1 to time 2, total QoL scores were less affected in group A (percentage decrease: 105%) than in group B (218%). At time 2, the total score was >+19 in group A in 46 patients and in 30 in group B. In group A, TSH levels in the higher tertile of QoL (61 ± 6 mIU/l) were not different from those in the lower tertile (62.3 ± 11.1)(P > 0.1); similar results were seen in group B (69.3 ± 13.3 vs 62.9 ± 13.1)(P > 0.1). There was a positive correlation between the time to obtain TSH ≥ 30 mIU/l and total QoL scores. CONCLUSIONS: Quality of life scores were not affected by thyrotrophin was measured the day before TT levels as absolute values. A longer time to obtain TSH ≥ 30 mIU/l was positively correlated with worse scores of QoL. We suggest 3 weeks without therapy can be used as an easy schedule in patients who undergo TT for DTC.

Teriparatide vs. alendronate as a treatment for osteoporosis: changes in biochemical markers of bone turnover, BMD and quality of life.

BACKGROUND: We studied the use of teriparatide in postmenopausal women with severe osteoporosis. MATERIAL/METHODS: Two groups (A and B) of patients affected by severe osteoporosis (T-score ≤-2.5 at bone mineral density were analyzed and 2 vertebral fractures on radiograph). Group A was treated for 18 months with 20 µg/day of teriparatide. Group B was treated with bisphosphonates 70 mg/week. Every woman assumed 1 g of calcium and 800 IU of vitamin D3 daily. We evaluated the effects of therapy after 18 months (T18) from the beginning with bone turnover markers (alkaline phosphatase, procollagen type 1 N-terminal propeptide, and N-telopeptide cross-links) and dual-energy X-ray absorptiometry. RESULTS: Group A, at T18 procollagen type 1 N-terminal propeptide levels, increased 127%; bone alkaline phosphatase levels increased to 65%; N-telopeptide cross-links levels increased to 110%. Group B, at T18 procollagen type 1 N-terminal propeptide levels, decreased to 74%; bone alkaline phosphatase levels decreased to 41%; N-telopeptide cross-links levels decreased to 72%. After 18 months, lumbar bone mineral density increased to 12.4% and femoral bone mineral density increased to 5.2% in group A. Group B lumbar bone mineral density increased to 3.85% and femoral bone mineral density increased to 1.99%. Only a new vertebral fracture occurred in group A (2.4%), whereas 6 fractures occurred in group B (15.7%). The quality of life questionnaire of the European Foundation for Osteoporosis (QUALEFFO) revealed a significant improvement in daily living, performed domestic jobs, and locomotor function in groups A and B. CONCLUSIONS: The use of rhPTH in patients with severe osteoporosis offers more protection against fractures and improves the QoL more than bisphosphonates.

Impaired endothelial- and nonendothelial-mediated vasodilation in patients with acute or chronic hypothyroidism.

OBJECTIVE: Vascular dysfunction and accelerated atherosclerosis are prominent features of hypothyroidism. The relative roles of thyroid hormone (TH) deficiency and the associated vascular risk conditions are still unclear. We studied the impact of acute and chronic hypothyroidism on vascular reactivity. PATIENTS: We studied 12 patients with chronic primary hypothyroidism (cHY; TSH: 52 +/- 14 mU/l), seven patients with acute hypothyroidism secondary to total thyroidectomy (aHY; TSH: 97 +/- 24) and 13 healthy subjects (TSH: 1.2 +/- 0.5). MEASUREMENTS: We measured forearm blood flow (FBF) using plethysmography during intra-brachial infusion of: acetylcholine (ACh), sodium nitroprusside (NP) and norepinephrine (NE). We also measured serum C-reactive protein (CRP), TNF-alpha, asymmetric dimethylarginine (ADMA) and the forearm balance of nitric oxide (NO) during ACh infusion. RESULTS: As compared with the controls, the vasodilatory response to ACh was reduced in cHY (P = 0.001) and aHY (P = 0.04), as was the forearm release of NO (P < 0.05). During NP infusion, FBF rose to 24 +/- 2 ml/dl/min in the controls and to significantly lower values in cHY (12 +/- 1; P = 0.001) and aHY (15 +/- 2; P = 0.004). NE-induced vasoconstriction was similar in the controls and aHY, but blunted in cHY. Serum CRP, TNF-alpha and ADMA were not different in the three groups. CONCLUSIONS: (i) Hypothyroidism associates with endothelial and nonendothelial mediated vascular dysfunction; (ii) these defects are evident even after short-term hypothyroidism, indicating that TH deficiency per se is sufficient to alter vascular homeostasis; and (iii) chronic, but not acute, hypothyroidism impairs the vasoconstrictory effect of NE in the resistance vessels.

Stricter criteria increase the validity of a quick intraoperative parathyroid hormone assay in primary hyperparathyroidism.

BACKGROUND: A "quick" intraoperative parathyroid hormone (PTH) (QPTH) assay evaluates parathyroid hypersecretion during parathyroidectomy. We investigated the likelihood of increasing surgical success rates by introducing stricter parameters in intraoperative PTH monitoring. MATERIAL/METHODS: One hundred one patients with sporadic primary hyperparathyroidism were studied. Intraoperative plasma intact PTH (iPTH) levels were measured with a modified 2-site antibody immunochemiluminometric assay. iPTH values were determined before the manipulation of parathyroid tissue (t-10') and then 3 (t+3') and 10 (t+10') minutes after resection of the suspected pathologic parathyroid gland(s). RESULTS: The median (interquartile range) baseline iPTH level was 259.6 (536) ng/L at t-10' and 64.1 (139.5) ng/L at t+10'. At t+3' and t+10', the median percentage decrease of iPTH from baseline was 56.1% and 77.3%, respectively. In 7 patients, the iPTH level decreased very slowly, and in patients with a double adenoma, an initial increase in the iPTH level occurred because of considerable manipulation during surgery. Despite a decrease of about 50% in iPTH level, persistent hyperparathyroidism was identified after a few months in 2 patients with a multiglandular pathologic condition in which a relatively larger parathyroid "masked" the hyperactivity of other parathyroid glands. CONCLUSIONS: A QPTH is useful during parathyroidectomy. A decrease in the iPTH level of > or =70% from baseline indicates a successful operation and reduces the likelihood of false-positive results. The evaluation of more than 1 PTH level is required if multiglandular disease is suspected or excessive intraoperative manipulation occurs.

Multiple ovarian cysts in a young girl with severe hypothyroidism.

Case study of a young female patient with severe hypothyroidism due to autoimmune thyroiditis and multiple ovarian cysts is reported. A 14-year 7-month-old girl presented with pelvic and abdominal pain and severe asthenia. Her last menstrual period was 10 months before presentation. Physical examination showed obesity; apathetic and flat expression; periorbital puffiness; pale, cold, dry skin and slow sustained reflexes; swelling in the hands and feet; no galactorrhea; a hardly palpable thyroid gland; and ovaries with a palpable irregular surface. Her heart rate was 90 bpm with a blood pressure within the normal range (110/70 mmHg). Laboratory findings showed severe hypothyroidism (thyroid-stimulating hormone [TSH]: 960 mIU/L), gravis macrocytic anemia, hyperfibrinogenemia, and hyperprolactinemia. Imaging examinations revealed a normal-size thyroid with irregular echogenicity, strongly hypoechogenous area at the neck ultrasonography, bilateral multilocular ovarian masses with cystic components at pelvic ultrasound and computed tomography, and both anterior and posterior pericardial effusion at echocardiography. As soon as thyroid replacement therapy was initiated, all symptoms progressively disappeared and biochemical and hormonal values normalized, while the right ovary did not decrease in size during the follow-up period. For this reason, our patient underwent right ovarian wedge resection 14 months after the initiation of medication replacement. Ovarian histological examination showed a benign ovarian cyst with extensive hemorrhage and myxedematous infiltration. It is concluded that it is important to recognize early in young girls the association between large multiple ovarian cysts and high elevated levels of TSH in order to resolve this disorder with substitutive therapy.

Quality of life in overweight (obese) and normal-weight women with polycystic ovary syndrome.

OBJECTIVE: Polycystic ovary syndrome (PCOS) is characterized by phenotypic heterogeneity and has a wide variety of consequences. Approximately half of women with PCOS are overweight or obese, and their obesity may be a contributing factor to PCOS pathogenesis through different mechanisms. The aim of this study was to evaluate if PCOS alone affects the patients' quality of life and to what extent obesity contributes to worsen this disease. DESIGN: To evaluate the impact of PCOS on health-related quality-of-life (HRQoL), 100 Mediterranean women with PCOS (group A), 50 with a body mass index (BMI) >25 kg/m2 (group A1) and 50 with BMI <25 kg/m2 (group A2), were recruited. They were evaluated with a specific combination of standardized psychometric questionnaires: the Symptom Checklist-90 Revised, the 36-Item Short-Form Health Survey, and the Polycystic Ovary Syndrome Questionnaire. The patients were compared with a normal-weight healthy control group of 40 subjects (group B). Another control group of 40 obese healthy women (group C) was used to make a comparison with PCOS obese patients (A1). RESULTS: Our results showed a considerable worsening of HRQoL in PCOS patients (A) compared with controls (B). In addition, patients with PCOS and BMI >25 (A1) showed a significant and more marked reduction in scores, suggesting a lower quality of life, compared with controls (B) and with normal-weight PCOS patients (A2). CONCLUSION: PCOS is a complex disease that alone determines a deterioration of HRQoL. The innovative use of these psychometric questionnaires in this study, in particular the PCOS questionnaire, has highlighted that obesity has a negative effect on HRQoL. It follows that a weight decrease is associated to phenotypic spectrum improvement and relative decrement in psychological distress.

Improvement of Bone Physiology and Life Quality Due to Association of Risedronate and Anastrozole.

The endocrine therapy is the new frontiers of many breast cancers hormone sensitive. Hormone therapy for treating women with hormone receptor-positive cancer suppresses breast cancer growth either by reducing estrogen synthesis or by interfering with the action of estrogen within tumor cells. In this prospective randomized observational study we investigate the effect of adjuvant anastrozole in monotherapy or associated with risedronate on bone physiology and quality of life in postmenopausal, hormone-sensitive early breast cancer women at mild to moderate risk of fragility fractures. Methods : 84 women were randomly assigned to receive anastrozole alone (group A) or anastrozole plus oral risedronate (group A+R). At baseline and after 24 months lumbar spine (LS) and femoral neck (FN) BMD were evaluated with dual-energy x-ray absorptiometry and health-related quality of life (HRQoL) was examined using the short-form healthy survey. Results : After 24 months, the group A+R has showed a significant increase in T-score for LS (p < 0.05) and for FN (p < 0.05) whereas women of group A had a statistically significant rate of bone loss both in LS T-score (p < 0.05) and in FN (p < 0.05). A significant change in T-score BMD was seen for group A+R compared with group A at the LS (p = 0.04) and at FN (p = 0.04). Finally, group A+R showed an overall significant improvement of health profile (SF-36) in group A (p = 0.03). Conclusion : Postmenopausal breast cancer women with osteopenia during treatment with anastrozole have considerable risk of developing osteoporosis during the first 2 years; preventive measures such as healthy lifestyle and daily supplements of calcium and vitamin D alone seem to be insufficient in holding their bones healthy. Our findings suggest the usefulness of addition of risedronate in order to prevent aromatase inhibitors-related bone loss, not only in case of high-risk of fractures, but also for women at mild-moderate risk. This determines a significant improvement in bone health and a positive impact on HRQoL.

Primary and Secondary Hemostasis in Patients With Subclinical Hypothyroidism: Effect of Levothyroxine Treatment.

CONTEXT: Subclinical hypothyroidism (SH) is associated with some abnormalities in primary and secondary hemostasis. OBJECTIVE: The objective of the study was to evaluate changes in primary and secondary hemostasis induced by levothyroxine (L-T4) treatment in SH patients. DESIGN: This was a prospective cohort study with a 6-month follow-up. STUDY SETTING: Outpatients were referred to "Federico II" University of Naples. PATIENTS: Subjects with a SH without previous/ongoing L-T4 therapy participated in the study. MAIN OUTCOME MEASURE: Changes in major hemostatic/fibrinolytic variables and platelet reactivity [mean platelet volume (MPV), arachidonic acid (AA), or ADP concentrations inducing a ≥ 50% irreversible aggregation (AC-50%)] in SH patients before and after a 6-month L-T4 treatment. RESULTS: At baseline, 41 SH patients showed higher levels of factor VII activity (123.9 ± 20.4 vs 107.7 ± 12.2, P < .001), plasminogen activator inhibitor-1 (33.6 ± 13.9 vs 22.5 ± 5.74, P < .001) and tissue plasminogen activator (5.56 ± 2.22 vs 4.75 ± 1.61, P = .010), with lower levels of D-dimer (220.3 ± 67.1 vs 252.1 ± 72.4, P = .017) compared with healthy controls. SH patients also showed a higher MPV (9.92 ± 1.15 vs 8.9 ± 0.9, P < .001) and AC-50% to AA (0.18 ± 0.12 vs 0.36 ± 0.10, P < .001) and to ADP (1.5 ± 0.6 vs 1.9 ± 1.3, P = .024). After a 6-month L-T4 therapy, a reduction of factor VII activity (from 123.9 ± 20.4 to 102.6 ± 14.3, P < .001), plasminogen activator inhibitor-1 (33.6 ± 13.9 to 19.4 ± 7.6, P < .001), and tissue plasminogen activator (5.56 ± 2.22 to 1.91 ± 4:43, P = .002) was found in SH subjects, with a marginal increase in D-dimer (from 220.3 ± 67.1 to 245.2 ± 103.1, P = .053). AC-50% to AA (from 0.18 ± 0.12 to 0.54 ± 0.3, P < .001) and to ADP (from 1.5 ± 0.6 to 1.86 ± 0.3, P = .042) were reduced, paralleled by a significant reduction of MPV (from 9.92 ± 1.15 to 9.10 ± 1.23, P = .016). CONCLUSIONS: SH patients exhibit a prothrombotic status, which is reverted by a 6-month L-T4 treatment.

Left ventricular myocardial impairment in subclinical hypothyroidism assessed by a new ultrasound tool: pulsed tissue Doppler.

Pulsed tissue Doppler (TD) is a new ultrasound tool that allows quantification of myocardial regional wall motion. To investigate the cardiac effects of subclinical hypothyroidism (SH), the present study assessed left ventricular (LV) myocardial regional function in SH by pulsed TD. Twenty women with SH and 20 healthy women underwent standard Doppler echocardiograms and pulsed TD, placing a sample volume at the level of posterior septum and LV mitral annulus. Myocardial systolic and diastolic velocities and time intervals were determined for both levels. Doppler-echocardiographic and TD measurements were adjusted for body surface area and heart rate. Standard Doppler showed an increases in LV preejection period, preejection period/LV ejection time ratio, and isovolumic relaxation time (IVRT) in SH. By TD analysis, myocardial precontraction time (PCT(m)), PCT(m)/myocardial contraction time ratio, and myocardial relaxation time (RT(m)) were prolonged at the level of both posterior septum and mitral annulus in SH. In the whole population, IVRT, PCT(m), and RT(m) were negatively related to FT(4), whereas IVRT, PCT(m)/myocardial contraction time ratio, and RT(m) were positively correlated to TSH. In conclusion, this study underscores the usefulness of TD to detect cardiac functional abnormalities due to stable SH, mainly by changes in myocardial time intervals in several LV segments.

Influence of body surface area on serum peak thyrotropin (TSH) levels after recombinant human TSH administration.

Recombinant human TSH (rhTSH) has been proposed as an alternative method to the withdrawal of thyroid hormones in the follow-up of differentiated thyroid cancer. The aim of the present study was to evaluate the influence of several demographic and anthropometric parameters [age, body weight, height, body mass index, and body surface area (BSA)] on serum peak TSH levels after rhTSH administration. rhTSH was administered to 112 patients with differentiated thyroid carcinoma according to the conventional two-dose schedule (0.9 mg/d). Serum TSH levels were measured 24 h before and after the first administration of rhTSH, and then 24, 48, and 72 h after the second administration of rhTSH. In one severely obese patient, serum peak TSH values did not reach a valid stimulation range. Serum peak TSH levels were negatively related to body weight (r = -0.69; P < 0.0001), body mass index (r = -0.51; P < 0.0001), and BSA (r = -0.72; P < 0.0001). In a multivariate regression analysis including demographic and anthropometric variables, only BSA was independently associated to serum peak TSH concentrations (standardized beta coefficient = -0.721; P < 0.0001). In conclusion, body size seems to influence serum peak TSH levels after rhTSH administration. Future studies should evaluate the possibility of using personalized rhTSH doses, adjusted in relation to BSA.

Reduced bone mass detected by bone quantitative ultrasonometry and DEXA in pre- and postmenopausal women with endogenous subclinical hyperthyroidism.

BACKGROUND: Although overt hyperthyroidism is a well known cause of bone loss, systemic effects of subclinical hyperthyroidism (SH) are still a matter of debate. OBJECTIVE: The aim of this cross-sectional study was to evaluate the effect of endogenous SH on bone in relation to the menopausal status. METHODS: Bone mass and turnover were assessed in a group of 60 patients with endogenous SH due to multinodular goitre; 30 of them were premenopausal and 30 early postmenopausal (mean age, 40.9 +/- 7.3 and 57.7 +/- 6.75, respectively). Sixty healthy women matched for age-, BMI- and menopausal status served as controls. Three different skeletal sites were evaluated using two different techniques: lumbar spine and femoral neck were assessed by DEXA whereas the proximal phalanges were evaluated by quantitative ultrasonometry (QUS), measuring the amplitude-dependent speed of sound (Ad-SoS). Serum osteocalcin and urinary deoxypyridinoline (DPD) were also determined as markers of bone turnover. RESULTS: A significant decrease was found in femoral BMD (P < 0.05) and phalangeal Ad-SoS (P < 0.001) in pre- and postmenopausal patients compared to controls, being greater in those postmenopausal. Lumbar BMD was decreased only in postmenopausal patients (P < 0.05). Bone turnover markers were higher in patients than in controls and in post- than in the premenopausal ones. A significant negative correlation was found between femoral BMD, Ad-SoS and serum free T3 levels, the latter considered a marker of disease activity. CONCLUSIONS: A significant increase in bone turnover markers and a decrease in bone mass was found in women affected by endogenous SH, being greater in early postmenopausal patients. Cortical rich bone was mainly affected. Both QUS and the conventional DEXA technique were equally able to determine bone density decrease related to mild thyroid hormone excess and sexual hormone decrease.

Usefulness of pulsed tissue Doppler for the assessment of left ventricular myocardial function in overt hypothyroidism.

BACKGROUND: The aim of this study was to assess the role of tissue Doppler (TD) in the identification of left ventricular (LV) myocardial regionl abnormalities in overt hypothyroidism. METHODS: Fourteen women with newly diagnosed, never treated overt hypothyroidism and 14 healthy women, matched for age, underwent standard echocardiography and pulsed TD, by placing the sample volume at the basal posterior septum and lateral mitral annulus, in the apical 4-chamber view. The myocardial systolic (SM) and diastolic velocities (Em, Am and their ratio) and time intervals (relaxation time [RTm], pre-contraction time [PCTm], contraction time) were measured. RESULTS: The two groups were comparable for body surface area, blood pressure and heart rate. At standard echocardiography, patients with overt hypothyroidism had a significantly greater septal thickness and LV mass index, a longer LV pre-ejection period (PEP), deceleration time and isovolumic relaxation time (IVRT) and a lower E peak velocity and E/A ratio. TD showed a significantly longer PCTm and RTm and a lower Em and Em/Am ratio of both the septum and mitral annulus in overt hypothyroidism. The ratio of the standard Doppler E to Em of the mitral annulus was 5.5 +/- 1.2 in controls and 5.3 +/- 1.7 in overt hypothyroidism (p = NS). In the overall population, PEP, IVRT, PCTm and RTm were correlated negatively with FT3 and FT4, and positively with thyroid-stimulating hormone. After adjusting for age, body surface area and heart rate in separate multivariate analyses, the associations of TD PCTm with the thyroid hormones and thyroid-stimulating hormone were greater than the homologous associations of standard Doppler PEP. CONCLUSIONS: Standard echocardiography confirms itself as a satisfactory diagnostic technique for the identification of LV global dysfunction in overt hypothyroidism. Pulsed TD may be useful to determine the severity of LV myocardial dysfunction in relation to the degree of hormonal impairment.

Clinical outcome in differentiated thyroid carcinoma and microcarcinoma.

INTRODUCTION: Due to the frequent use of neck ultrasonography, the incidence of differentiated thyroid microcarcinoma (DTMC), defined as a lesion with greatest dimension ≤1 cm, is increasing worldwide. Although DTMC generally has a lower aggressivity and a better prognosis than differentiated thyroid carcinoma (DTC), some cases of clinically aggressive DTMC were found. The aim of this study is to compare the rate of recurrence in DTMC and DTC, during a 3-year follow-up. METHODS: Patients with differentiated thyroid carcinoma, who underwent total thyroidectomy and postoperative (131)I-RAI ablation, were stratified according to lesion diameter (DTC for diameter > 1 cm or DTMC ≤ 1 cm). After surgery, patients underwent a 3-year follow-up. Recurrent disease was defined on the basis of positive biochemical (Tg > 2 ng/ml under TSH-suppression or after rhTSH-stimulation) and/or imaging (US, WBS, CT, PET/CT) findings. RESULTS: 449 patients have been included in the final analysis. Linfoadenectomy rate and RAI ablative dose were significantly higher in DTC than in DTMC (32.7% vs. 22.4%, p = 0.018 and 112.3 ± 21 vs. 68.3 ± 24.1 mCi, p < 0.001). During the follow-up, 50 carcinoma recurrences occurred, more frequent in DTC than in DTMC (15.6% vs. 7.6%, p = 0.010). After adjustment for gender, age, rate of lymph node dissection and 131I dose of RAI treatment, the difference in the risk of recurrence was no longer significant among DTC and DTMC patients (HR: 1.585, 95% CI 0874-2877, p = 0.130). CONCLUSIONS: The prediction of disease severity cannot be based exclusively on lesion diameter. A more careful therapeutic approach and follow-up should be recommended in DTMC patients.

Interleukin-2 and lanreotide in the treatment of medullary thyroid cancer: in vitro and in vivo studies.

CONTEXT: To date no efficacious treatments are available for advanced medullary thyroid carcinoma (MTC). OBJECTIVE: We investigated in vitro and in vivo a new strategy for the therapy of MTC, combining human recombinant IL-2 with lanreotide (LAN), a somatostatin analog. METHODS: The in vitro effects of LAN on the sensitivity of TT cells, a MTC cell line, to IL-2-stimulated human peripheral blood mononuclear cells were determined by a lactate dehydrogenase release assay. In addition, we evaluated the toxicity, the effects on quality of life, and the antitumor activity of sc low-dose IL-2 in combination with LAN (90 mg every 28 days) in a series of 6 patients with symptomatic and advanced MTC. RESULTS: The cytotoxicity of IL-2-activated peripheral blood mononuclear cells was significantly increased in TT cells treated with LAN or LAN plus IL-2 compared with that in TT cells without treatment. The therapy was well tolerated, and a statistically significant improvement of quality of life was observed in patients treated with the combination of LAN and IL-2. After 6 months of therapy, partial response and stable disease have been recorded in 2 and 3 patients, respectively, with a significant decrease in calcitonin levels in 3 patients. CONCLUSIONS: Both in vitro and in vivo evidence suggests that the combination of LAN and IL-2 may have a role in the management of advanced and symptomatic MTC. However, these preliminary data require further validation in larger randomized trials.

Prevalence of thyroid autoimmunity in patients with spondyloarthropathies.

OBJECTIVE: To evaluate the prevalence of chronic autoimmune thyroiditis or Hashimoto's thyroiditis (HT) in a group of patients with spondyloarthritis (SpA). METHODS: We evaluated serum levels of thyroid-stimulating hormone, free triiodothyronine, and free thyroxine, and titers of antithyroglobulin and antithyroid peroxidase (anti-TPO) antibodies in 357 consecutive patients with SpA. We also recruited 318 healthy age-matched controls. Ultrasonography of the thyroid gland was performed in all subjects and rheumatic activity was evaluated. RESULTS: Indices of thyroid autoimmunity were significantly more frequent in patients with SpA than in controls (24.09% vs 10.69%, respectively; p < 0.05). In the SpA group, a higher prevalence of HT was found in patients with an active disease than in those with low-moderate disease levels. Also in the SpA group, patients with a disease duration > 2 years had a higher prevalence of HT and anti-TPO antibodies positivity than patients with a disease duration ≤ 2 years. Ultrasonography detected a significantly higher frequency of thyroid nodules and hypoechoic pattern in patients with SpA than in controls. Among patients with SpA, HT and anti-TPO antibodies positivity were significantly more frequent in patients with peripheral involvement (68.6%) than in patients with axial involvement (31.4%; p < 0.05). CONCLUSION: Our study shows a significantly higher prevalence of thyroid autoimmunity in patients with SpA as compared to controls. Thyroiditis occurs more frequently in patients with longer disease duration and active rheumatic disease. We suggest that thyroid function tests be part of the clinical evaluation in patients with SpA.

Osteoporosis and thyrotropin-suppressive therapy: reduced effectiveness of alendronate.

BACKGROUND: Many reports of the effect of exogenous thyroxine therapy on bone mineral density (BMD) show a relationship between excess thyroid hormone administration and osteoporosis. The aim of this study was to evaluate the effect of antibone resorptive agents, in particular alendronate (ALN) on BMD in postmenopausal osteoporotic women with thyroid carcinoma who were receiving long-term thyrotropin (TSH)-suppressive therapy with thyroxine. METHODS: Seventy-four postmenopausal women with low BMD (T-score < or =-2.5) and differentiated thyroid carcinoma on long-term TSH-suppressive therapy (TSH > or =0.05 and < or =0.1 microU/mL) for about 3-9 years were selected for the study. The patients were divided into three groups according to the length of levothyroxine (LT(4)) treatment prior to the beginning of the study: group A (TSH-suppressive therapy for about 3 years), group B (for about 6 years), and group C (for about 9 years). These patients were compared with 74 matched women not taking LT(4). All patients and controls were treated with bisphosphonates, calcium, and vitamin D for 2 years and evaluated. RESULTS: After 24 months of treatment group A showed a 7.8% increase in lumbar BMD; group B, a 4.6% increase; and group C, a 0.86% increase. In the control group BMD increased 8.2%. A significant difference was found in both lumbar and femoral BMD increase among the three groups: group C had a lower BMD increase than group A (p < 0.001) and B (p < 0.001). CONCLUSIONS: In postmenopausal women who were receiving adequate amounts of calcium and vitamin D in their diet ALN was less effective for those who were also receiving TSH-suppressive doses of LT(4) for either 6 or 9 years. The positive effect of ALN on BMD was less for longer periods of LT(4) treatment. It seems likely that other bisphosphonates would also be less effective in increasing BMD in postmenopausal women receiving TSH-suppressing doses of LT(4).

Recombinant human thyrotropin enhances endothelial-mediated vasodilation of conduit arteries.

CONTEXT: Endothelial cells possess receptors to TSH. Their role is largely unknown. OBJECTIVES: The objective of the study was to determine whether elevated serum TSH levels, as occur in hypothyroidism, affect endothelial function of large arteries and vascular risk biomarkers. SUBJECTS AND METHODS: Thirty-four consecutively recruited patients, who had undergone thyroidectomy for thyroid carcinoma, were studied in connection with one of the monitoring procedures based on recombinant human (rh) TSH administration. Flow-mediated dilation (FMD) of the brachial artery and serum vascular risk markers were measured at baseline and for 5 d after the administration of rhTSH (0.9 mg im on d 1 and 2). Holter electrocardiogram and echocardiography were performed on d 2. RESULTS: rhTSH caused a rapid increase in flow-mediated dilation from the basal value of 10.2 to 15.6% at 6 h (P < 0.0000001), to 16.1% on d 2 (P < 0.0000001), and to 14.9% on d 6 (P = 0.0015). The results were identical when the analysis was made in a subgroup of 19 patients free of vascular risk conditions. Vascular cell adhesion molecule-1, TNFalpha, IL-6, and high sensitive C-reactive protein were unaffected by rhTSH, whereas homocysteine was decreased. Arterial blood pressure, mean 24-h heart rate, and left ventricular function were unaffected by rhTSH. CONCLUSIONS: rhTSH causes marked and persistent activation of the endothelial mediated vasodilation, independent of systemic hemodynamic changes.

Current management of differentiated thyroid carcinoma.

Papillary and follicular thyroid cancers, together termed differentiated thyroid cancers (DTC), comprise the majority of thyroid carcinomas and have an optimal prognosis. Most DTCs appear as asymptomatic thyroid nodules. Fine-needle aspiration (FNA) cytology is the first diagnostic test for a thyroid nodule in a euthyroid patient. Surgery is the primary treatment for thyroid cancers. Most clinicians recommend near-total or total thyroidectomy, and then 131I ablation therapy, since its consequences are minimal and follow-up is facilitated. A total body scan (TBS) is performed 4 to 7 days after 131I treatment. At a later stage, all patients should be treated with L-tiroxine so as to suppress TSH, and must undergo a periodic evaluation of TSH and thyroglobulin (Tg), the most sensitive and specific marker of DTC. After 6-12 months, TBS with 131I is performed, a technique complementary to serum Tg evaluation. For this technique, it is also necessary to have a high serum TSH concentration, obtained by withdrawing thyroxine therapy for 4 to 6 weeks. This standard method induces hypothyroidism. An alternative method to the withdrawal of thyroid hormones in the follow-up of DTC patients is to administer recombinant human TSH (rh-TSH). After the dose of rhTSH, 131I is administered, and then TBS can be performed 48-72 hours later. Currently, several authors have explored the possibility that rh-TSH-stimulated Tg levels may represent the only necessary test to differentiate patients with persistent disease from disease-free patients, without performing a diagnostic TBS.

Comparison of two provocative tests for calcitonin in medullary thyroid carcinoma: omeprazole vs pentagastrin.

BACKGROUND: Provocative tests for calcitonin (CT) are fundamental in the diagnosis and follow-up of C-cell disease and in the detection of hereditary medullary thyroid carcinoma (MTC) carriers with unknown RET mutations. A recent report has proposed omeprazole, which can increase endogenous gastrin (GT), as a new provocative test for MTC. METHODS: We compared the omeprazole test (20 mg twice a day for 4 days) to the pentagastrin test (0.5 microg/kg of body weight) for the diagnosis and management of MTC. Twenty healthy individuals and 20 MTC patients with mildly or moderately increased basal CT serum concentrations underwent the pentagastrin and omeprazole tests. RESULTS: In MTC patients, the pentagastrin test produced a significantly higher increase in serum CT than did omeprazole. After the pentagastrin injection, several patients reported unpleasant side effects, including substantial tightness in 38 of 40 participants. No adverse effects were observed during the omeprazole test. A significant direct correlation was recorded between CT% (ratio of CT peak to basal value x 100) and GT% (ratio of GT peak to basal value x 100) during the omeprazole test in MTC patients (r = 0.73; P <0.001). CONCLUSIONS: In spite of several adverse effects, pentagastrin remains the best provocative test for the diagnosis of MTC. Omeprazole may be useful when pentagastrin is contraindicated or refused because of the unpleasant side effects, but further validation is needed.