Is there any association between psoriasis, psoriatic arthritis and thyroid autoimmunity?

BACKGROUND: Autoimmune diseases share a significant part of their genetic background and tend to coexist in the same patient. Some studies have investigated the possible association between autoimmune thyroiditis and psoriasis or psoriatic arthritis (PsA), with conflicting results. This study aimed to investigate the prevalence of autoimmune thyroiditis in psoriatic patients with (PsA) or without (PsC) joint involvement. METHODS: 208 patients with psoriasis and/or PsA were recruited. These patients were divided into two groups: psoriasis patients (without PsA) (PsC group: 100 patients; mean age of 50.1 ± 11.7 years) and subjects with psoriasis and psoriatic arthritis (PsA group: 108 subjects: mean age of 39.8 ± 10.8 years). Assessment of psoriasis severity was conducted using the Psoriasis Area and Severity Index (PASI) score. The diagnosis of psoriatic arthritis was made according to CASPAR criteria. All patients had thyroid evaluation through evaluation of thyroid function, thyroperoxidase antibodies and thyroid ultrasound examination. RESULTS: A statistically significant difference was found between the prevalence of autoimmune thyroiditis in the PsA group than the PsC group (25.9 vs 9.0 %; P = 0.018) with higher trends to hypothyroidism in the PsA group compared to the PsC group (13.9% vs 2.0%, P = 0.0018). CONCLUSIONS: The higher prevalence of autoimmune thyroiditis in the PsA group may be due to an immune dysfunction pathway in patients with psoriatic arthritis with a higher risk to develop other autoimmune diseases. This evidence confirms that psoriatic arthritis is an autoimmune disease with an overactive immune system that can involve multiple organs. Thyroid function evaluation should be part of the clinical and laboratory examination of patients with psoriatic arthritis.

Coeliac disease is a risk factor for the development of seronegative arthritis in patients with autoimmune thyroid disease.

OBJECTIVE: Hashimoto's thyroiditis is known to cluster with other systemic autoimmune disorders. Rheumatic manifestations, such as a seronegative non-erosive polyarthritis have been described. The aim of this study was to evaluate the characteristics and the prevalence of rheumatic features in thyroiditis patients, and to ascertain whether the association with systemic autoimmune disorders improved the arthritis manifestations. METHODS: In total, 180 thyroiditis patients were enrolled. Major clinical and demographic characteristics have been recorded. Patients underwent a rheumatological clinical assessment and extra-articular manifestations allowing for a differential diagnosis with systemic autoimmune diseases and spondyloarthropathy. Presence of systemic autoimmune diseases was recorded. RESULTS: A total of 8.33% of thyroiditis patients shown a peripheral inflammatory arthritis (P = 0.002). Female gender (P = 0.042) and thyroid peroxidase (TPOAbs) positivity (P = 0.001) were more frequent. In total, 37 patients had systemic autoimmune diseases (P = 0.0003). A significant high prevalence of coeliac disease and Addison disease was found (P = 0.034 and P = 0.049, respectively). In patients with coeliac disease, the articular manifestations were more frequent (21.21%) (P = 0.001) and the risk to develop joint involvement was 2.96. CONCLUSION: Although we found an articular involvement in about one-third of thyroiditis patients, the prevalence of inflammatory arthropathy was only 8.33%. The prevalence of other coexisting autoimmune disorders was 34.26% with a significant prevalence of coeliac disease (7.41%). Thyroiditis patients with coeliac disease have an articular involvement more frequently than those without. In these patients, we have found a high risk of developing arthritis than patients with only thyroiditis, suggesting cumulative autoimmune effects in the developing articular involvement.

Falsely elevated thyroglobulin and calcitonin due to rheumatoid factor in non-relapsing thyroid carcinoma: A case report.

RATIONALE: Thyroglobulin (Tg) is an accurate indicator of clinical outcome after total thyroidectomy in patients with differentiated thyroid carcinoma. Usually, Tg levels agree with whole body scan. However, in some patient, discordant results were found, often because of Tg immunoassay interference. Several reports indicated that 2-site immunoassay interference with heterophile antibodies (HAb) can lead to misinterpretation of the laboratory test result. PATIENT CONCERNS: We report a case of a 46-year-old woman referred to our endocrine clinic for markedly increased calcitonin (CT) without the associated clinical picture. The measurement was repeated with the same patient sample on a different analytical platform and the result was an undetectable CT level. The measurement of Tg was repeated on 3 different analytical platforms using chemiluminescence and electrochemiluminescence immunoassays and the results were different on each platform. HAb blocking tubes resulted in a different level of both CT and Tg, suggesting the presence of a heterophile substance in the serum sample. Further characterization showed reactivity to several animal species antibodies and an elevated level of the rheumatoid factor (RF). DIAGNOSES: She was diagnosed as papillary thyroid carcinoma. INTERVENTIONS: She had undergone thyroidectomy with lymph node dissection and radioactive therapy. OUTCOMES: She was found not to have recurrence despite a high serum Tg level. LESSONS: Our report illustrates a rare case of falsely elevated tumor markers levels due to assay interference caused by RF. This finding pointed out the importance of close communication between the clinician and laboratory staff in order to bring to light discordance between laboratory test results and clinical picture and avoid unnecessary diagnostic procedures and overtreatment.

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.

Markers of atherosclerosis in patients with Cushing's syndrome: a meta-analysis of literature studies.

BACKGROUND: Several studies reported an increased cardiovascular (CV) risk in Cushing's syndrome (CS). We performed a meta-analysis on the impact of CS on major markers of atherosclerosis. METHODS: Studies on intima-media thickness (IMT), carotid plaques prevalence, and flow-mediated dilation (FMD) in CS patients and controls were searched in the PubMed, Web of Science, Scopus, and EMBASE. Differences between cases and controls were expressed as mean difference (MD) with 95% confidence intervals (95%CI) for continuous variables, and as Odds Ratio (OR) with 95%CI for dichotomous variables. RESULTS: Fourteen studies (332 CS, 462 controls) were included. Compared with controls, CS patients showed higher IMT (MD: 0.20 mm; 95% CI: 0.12, 0.28; p < .001), increased prevalence of carotid plaques (OR: 8.85, 95%CI: 4.09, 19.14; p < .001), and lower FMD (MD: -2.65%; 95% CI: -3.65, -1.65; p < .001). Difference in IMT and in the prevalence of carotid plaques was confirmed also in patients with CS remission (MD: 0.24 mm; 95% CI: 0.07, 0.40; p = .005 and OR: 9.88, 95%CI: 2.69, 36.3; p < 0.001, respectively). Regression models showed that age, diabetes, obesity, ACTH-dependent CS, serum and urinary cortisol levels impacted on the observed difference in IMT. CONCLUSIONS: CS is significantly associated with markers of subclinical atherosclerosis and CV risk. These findings could help establish more specific CV prevention strategies in this clinical setting. Key messages A series of studies reported an increased cardiovascular risk in patients with Cushing's syndrome (CS). In the present meta-analysis we demonstrated that CS is associated with an increased intima-media thickness, higher prevalence of carotid plaques, and lower flow-mediated dilation as compared with controls. These data consistently suggest the need for a strict monitoring of early signs of subclinical atherosclerosis in CS patients.

Cardiovascular risk markers in patients with primary aldosteronism: A systematic review and meta-analysis of literature studies.

BACKGROUND/OBJECTIVES: Several studies reported an increased cardiovascular (CV) morbidity and mortality in patients with primary aldosteronism (PA). We performed a meta-analysis on the impact of PA on major markers of CV risk. METHODS: Studies on the relationship between PA and common carotid artery intima-media thickness (CCA-IMT), prevalence of carotid plaques, flow-mediated dilation (FMD), nitrate-mediated dilation (NMD), pulse-wave velocity (PWV), augmentation index (AIx), and ankle-brachial index (ABI) were systematically searched in the PubMed, Web of Science, Scopus and EMBASE databases. RESULTS: 12 case-control studies (445 cases, 472 controls) were included. Compared to subjects with essential hypertension (EH), PA patients showed a higher CCA-IMT (MD: 0.12 mm; 95% CI: 0.09, 0.16; P<0.00001), and a higher aortic-PWV (272 cases and 240 controls, MD: 1.39 m/s; 95% CI: 0.90, 1.87; P<0.00001). In contrast, non-significant differences were found in AIx and AIx normalized to a heart rate of 75 beats per minute (AIx@75). When compared to normotensive subjects, PA patients showed significantly higher CCA-IMT (MD: 0.16 mm; 95% CI: 0.05, 0.27; P=0.004), aortic-PWV (MD: 3.74 m/s; 95% CI: 3.43, 4.05; P<0.00001), AIx@75 (MD: 8.59%; 95% CI: 0.69, 16.50; P=0.03), and a significantly lower FMD (MD: -2.52%; 95% CI: -3.64, -1.40; P<0.0001). Sensitivity and subgroup analyses substantially confirmed our results. Metaregression models showed that male gender, diabetes, and smoking habit impact on the observed results. CONCLUSIONS: PA appears significantly associated with markers of subclinical atherosclerosis and CV risk. These findings could help establish more specific CV prevention strategies in this clinical setting.

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.

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.

Effects of treatment with metformin on TSH levels: a meta-analysis of literature studies.

CONTEXT: Some data suggest that metformin affects the thyroid profile in patients with type 2 diabetes, but contrasting results are reported in different settings. OBJECTIVE: The aim of this meta-analysis was to assess the effect of metformin treatment on TSH in subjects with or without thyroid dysfunction. DATA SOURCES: We performed a systematic search of articles evaluating changes in TSH levels in patients receiving metformin. STUDY SELECTION: Studies evaluating TSH levels before and after metformin treatment were included. DATA EXTRACTION: Clinical data, demographic variables, and TSH levels before and after treatment with metformin were extracted. Data were analyzed according to the underlying thyroid disease. DATA SYNTHESIS: A total of 7 datasets (206 patients) were included in the final analysis. After metformin treatment, a slight but significant reduction in TSH levels was found in 4 datasets on 119 patients with overt hypothyroidism receiving l-T4 replacement (mean difference, 1.08; 95% confidence interval [CI], 0.50, 1.65; P=.0003). Similarly, in 2 datasets reporting on a total of 33 patients with subclinical hypothyroidism not receiving treatment with l-T4, a significant reduction in TSH levels was reported (mean difference, 1.59; 95% CI, 1.32, 1.87; P<.00001) after treatment with metformin. In 1 dataset, including 54 euthyroid patients not receiving l-T4, no changes in TSH levels were reported after treatment with metformin (mean difference, 0.18; 95% CI, -0.20, 0.56; P=.35). CONCLUSIONS: Metformin induces a reduction in TSH levels both in overt and in subclinical hypothyroidism. In contrast, no change in TSH levels is found in euthyroid patients.

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.

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.

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.

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).

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.

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.

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.

Overexpression of the phosphoprotein enriched in diabetes gene product (Ped/pea-15) in women with polycystic ovary syndrome.

OBJECTIVE: To evaluate Ped/pea-15 (phosphoprotein enriched in diabetes) expression in polycystic ovary syndrome (PCOS) women. DESIGN AND PATIENTS: Thirty PCOS women were studied and compared with other 30 age- and body mass index (BMI)-matched women, considered as the control group. Both patients and controls were divided according to BMI. All subjects underwent endocrine and metabolic investigation and Ped/pea-15 expression was evaluated by western blot analysis. Insulin resistance was assessed by HOMA model and insulin sensitivity index (ISI) composite. RESULTS: Insulin resistance, evaluated by HOMA-R and ISI composite, was significantly higher in PCOS women and in obese controls than in normal weight controls. Ped/pea-15 expression (%) was higher in PCOS women than in controls (440.4 +/- 220.7 vs. 163.0 +/- 45.5; P < 0.001; range 145.5-987% and 97-281%, respectively), and was positively correlated with insulin, BMI, total testosterone, HOMA index, and family history (P < 0.001). In patients with PCOS univariate analysis of variance showed no effect of BMI variation (P = 0.13) on Ped/pea-15 expression levels. On multiple linear regression analysis, the major determinants of Ped/pea-15 overexpression were family history, insulin, and PCOS status independent of BMI. CONCLUSION: These preliminary data (1) highlight the overexpression of Ped/pea-15 in PCOS compared to normal controls, independent of obesity; (2) suggest that Ped/pea-15 overexpression might be an early component of the metabolic syndrome in PCOS; and (3) support the hypothesis that Ped/pea-15 represents a possible useful tool to assess the presence of a genetic condition associated with insulin resistance in PCOS.

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.

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.

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.