Graves' orbitopathy: a multidisciplinary approach.

Orbitopathy is the main extra thyroidal manifestation of Graves' disease. It is a very challenging condition, which requires a cooperation between many specialists (endocrinologists, ophthalmologists, radiologists, radiotherapeutic, orbital surgeons) for an optimal clinical management. An accurate diagnostic assessment is required, in order to plan an adequate treatment of Graves' orbitopathy. Medical therapy, radiotherapy or surgery may be necessary to control the disease. In this review, the authors analyze the various therapeutic strategies, as well the more recent therapies based on pharmacologic immunomodulation.

Is concomitant treatment with steroids and radiotherapy more favorable than sequential treatment in moderate-to-severe graves orbitopathy?

PURPOSE: Glucocorticoids (GCs) and external radiotherapy (RT) are used for treating moderate-to-severe Graves' orbitopathy (GO). We aimed to assess whether GCs and RT were more effective when administered concomitantly or sequentially. METHODS: We retrospectively analyzed clinical outcomes [assessed by Clinical Activity Score (CAS) and NOSPECS classification] in 73 patients treated with both i.v. GCs and RT. The patients were divided in two groups: In group A (53 patients), RT was delivered concomitantly with GCs, and in group B (20 patients) RT was administered subsequently to the end of methylprednisolone. RESULTS: At baseline, CAS (median 4.0) and the percentage of patients encompassing the various grades of the classes 2, 3 and 4 of the NOSPECS score were similar in both groups. Six months after RT, CAS decreased to 2 in both groups (p = 0.0003 vs baseline) as well as NOSPECS class 4 (p < 0.0001 vs baseline). NOSPECS class 2 improved more in group A than in group B (p = 0.016). The median cumulative dose of GCs was lower in group A than in group B (median 4.500 vs 6000 mg, p < 0.007); the overall length of therapy was shorter in group A than in group B (68 vs 106 days, p < 0,02). The most common acute adverse effect was transient conjunctivitis (five in group A and three in group B); seven patients (five in group A and two in group B, age between 60 and 66 years) developed cataract, requiring surgery in five cases. CONCLUSIONS: Concomitant administration of GC and RT showed a favorable effect in moderate-to-severe GO, thus suggesting that RT should be carried out early during steroid therapy, when clinical symptoms do not improve or deteriorate after the first i.v. administrations of GCs.

American Thyroid Association ultrasound system for the initial assessment of thyroid nodules: Use in stratifying the risk of malignancy of indeterminate lesions.

BACKGROUND: The ultrasound risk stratification system of the American Thyroid Association (ATA) is frequently adopted in clinical practice. Here, we evaluated its performance in a series of nodules with indeterminate fine-needle aspiration cytology (FNAC) report. METHODS: Indeterminate thyroid nodules diagnosed at 2 medical centers were retrospectively screened, ultrasound images were reevaluated, and lesions were classified according to the ATA. Single ultrasound parameters were also analyzed. RESULTS: One hundred seventy-three indeterminate lesions were included with 24.8% of malignancy. The high suspicion class showed a cancer rate (75%) significantly (P < .001) higher than that recorded in the other categories (16.8%). Between ultrasound parameters, halo and microcalcifications were the most sensitive and specific ones. The most accurate receiver operating characteristic (ROC)-derived cutoff of nodule's diameter was >4.1 cm. At multivariate analysis, only the ATA class of high suspicion and size >4.1 cm were significantly associated with cancer (odds ratios [ORs] 19.4 and 5.4, respectively). CONCLUSION: The ATA ultrasound system is reliable in the risk stratification of indeterminate thyroid lesions.

Diagnostic value of a cytomorphological subclassification of follicular patterned thyroid lesions: a study of 927 consecutive cases with histological correlation.

BACKGROUND: Fine-needle aspiration cytology (FNAC) has proved to be an effective diagnostic tool in patients with thyroid nodules. Several reporting schemes have been suggested to define the risk of malignancy and consequent clinical management. To date, however, among lesions showing a follicular pattern, FNAC is still unable to differentiate between benign and malignant ones. The aim of our study was to evaluate whether a subclassification of follicular cytologic specimens, based on cytoarchitectural patterns, could differentiate categories with a different risk of malignancy, thus improving the clinical management of patients harboring follicular nodules. METHODS: We report a cohort of 927 consecutive cases who underwent thyroid surgery in our hospital between 2000 and 2008. Each patient underwent FNAC before surgery. All the cytologic specimens were divided into five categories (Thy 1: inadequate material, Thy 2: benign, Thy 3: indeterminate, Thy 4: suspicious for malignancy, Thy 5: malignant). Thy3 specimens were further divided into three subcategories (Thy 3a, or "follicular lesions of indeterminate significance": scant colloid, microfollicular pattern, or small clusters of thyrocytes with round nuclei usually without, but sometimes with, minimal cellular pleomorphism; Thy 3b, or "follicular neoplasm": absence of colloid, small clusters, or microfollicles of medium-large sized cell populations arranged in cohesive groups with nuclear overlapping, crowding, and pleomorphisms; and Thy 3c or "Hurthle-cell neoplasm": scant colloid, sheets or clusters of oxyphilic cells). RESULTS: Thy 1 specimens (51 cases on the whole) proved to be malignant in 5.88% (3 cases), Thy 2 specimens (319) in 3.45% (11 cases), Thy 4 specimens (91) in 84.62% (77 cases), and Thy 5 specimens (172) in 98.84% (170 cases). Thy 3 specimens (294 cases) proved to be malignant in 17.35% as a whole, but when divided into the three subcategories, the percentage of malignant cases was significantly different between the Thy 3a group (4.95%) and the Thy 3b and Thy 3c groups (25.0% and 22.77% respectively). CONCLUSIONS: This study supports the National Cancer Institute consensus showing a different risk of malignancy for "follicular lesions of undetermined significance" compared with "follicular neoplasms" and "Hurthle cells neoplasms," which are more suspect for malignancy. This subclassification could improve clinical management of thyroid nodules, helping to better select patients for surgery or follow up.

Thyroid nodules and related symptoms are stably controlled two years after radiofrequency thermal ablation.

BACKGROUND: Percutaneous radiofrequency thermal ablation (RTA) is a promising new therapeutic approach to manage thyroid nodules (TNs). The aim of this study was to investigate the long-term effectiveness of RTA in inducing shrinkage of TNs as well as in controlling compressive symptoms and thyroid hyperfunction in a large series of elderly subjects with solid or mainly solid benign TNs. METHODS: Ninety-four elderly patients with cytologically benign compressive TNs were prospectively enrolled in the study; 66 of them had nontoxic goiter and 28 had toxic or pretoxic goiter. RTA was performed by using a RITA StarBurst Talon hook-umbrella needle inserted in every single TN under ultrasonographic real-time guidance. TN volume, TN-related compressive symptoms and thyroid function were evaluated at baseline and 12 to 24 months after RTA. RESULTS: All TNs significantly decreased in size after RTA. The mean decrease in TN volume 12 months after RTA was from 24.5 +/- 2.1 to 7.5 +/- 1.2 mL (p < 0.001), with a mean percent decrease of 78.6 +/- 2.0%. Two years after RTA, a 79.4 +/- 2.5% decrease of TNs size was observed. Compressive symptoms improved in all patients and completely disappeared in 83 of 94 (88%) patients. Hyperthyroidism resolved in most patients allowing methimazole therapy to be completely withdrawn in 79% of patients with pretoxic and toxic TNs (100% with pretoxic TNs and 53% with toxic TNs). The treatment was well tolerated by all patients. No patient needed hospitalization after RTA and no major complications were observed. CONCLUSIONS: RTA is an effective and simple procedure for obtaining lasting shrinkage of TNs, controlling compressive symptoms, and treating thyroid hyperfunction. When performed in experienced medical centers, RTA may be a valid alternative to conventional treatments for nontoxic and pretoxic TNs. It is particularly attractive for elderly people for whom surgery and radioiodine therapy are often contraindicated or ineffective.