Subclinical hypothyroidism is associated with migraine: A case-control study.

BACKGROUND: Recent studies suggested a potential association between both overt and subclinical hypothyroidism and migraine. Aims of this study were to estimate the comorbidity of migraine in patients with subclinical hypothyroidism and to evaluate associated clinical characteristics. METHODS: Using a case-control strategy, 151 consecutive subclinical hypothyroidism patients (mean age 48.36 ± 15.86 years) and 150 controls (mean age 50.86 ± 9.19 years) were recruited. In all subjects, migraine characteristics were collected through a direct interview. Clinical and biochemical parameters (thyroid-stimulating hormone, free triiodothyronine, free thyroxine, and anti-thyroid antibodies) were compared between subclinical hypothyroidism patients in comorbidity with migraine and subclinical hypothyroidism patients without migraine. RESULTS: The prevalence of lifetime migraine was significantly higher in subclinical hypothyroidism patients in comparison with controls (46% vs. 13%, p < 0.001; OR 5.80; 95% CI = 3.35-10.34). Both migraine without and with aura were significantly higher in subclinical hypothyroidism patients than controls ( p < 0.001 and p = 0.010, respectively). Thyroid hormones and concentrations of antibodies did not differ between subclinical hypothyroidism patients with and without migraine. Interestingly, a comorbidity for autoimmune diseases was observed in subclinical hypothyroidism patients with migraine in respect to those without migraine ( p = 0.005). CONCLUSIONS: Our data suggest that migraine is more frequent in patients with subclinical hypothyroidism in respect to controls. Further studies are needed in order to confirm this association.

Continuous subcutaneous rhPTH infusion for managing difficult chronic hypoparathyroidism. A systematic review.

PURPOSE: Standard treatment for chronic hypoparathyroidism is represented by long-life per os supplementation of calcium and vitamin D. Since 90s, exogenous PTH is also available, but a not negligible number of patients experience a poor control. Starting from the experience with pumps in diabetes, it has been hypothesized that the infusion of PTH through pump might result in a better disease control. The aim of this systematic review is to summarize the published data about continuous subcutaneous PTH infusion in chronic hypoPTH patients and achieve conclusions for clinical practice. METHODS: A comprehensive computer literature search of the PubMed/MEDLINE, Embase, and Scopus databases was conducted by two authors independently (last search on November 30, 2022). All findings were summarized and critically discussed. RESULTS: We included 14 of the 103 retrieved articles, 2 RCTs, 8 case reports, and 4 case series, published between 2008 and 2022. Of the total 40 patients, 17 were adults, and 23 pediatric. The etiology was postsurgical in 50% of cases and genetic in the other 50%. All had a failure of standard care and a rapid improvement of clinical and biochemical parameters on PTH pump therapy, without severe adverse events. CONCLUSIONS: Based on literature, pump PTH infusion may represent an effective, safe, and feasible option for patients with chronic hypoparathyroidism refractory to standard therapy. From a clinical perspective, careful patient selection, a skilled healthcare team, the assessment of the local setting and the collaboration with pump suppliers are essential.

US-guided percutaneous radiofrequency thermal ablation for the treatment of solid benign hyperfunctioning or compressive thyroid nodules.

The aim of the study was to define the effectiveness and safety of ultrasound-guided percutaneous radiofrequency (RF) thermal ablation in the treatment of compressive solid benign thyroid nodules. Thirty-one patients not eligible for surgery or radioiodine (131I) treatment underwent RF ablation for benign nodules; a total of 33 nodules were treated (2 patients had 2 nodules treated in the same session): 10 cold nodules and 23 hyperfunctioning. Fourteen patients complained of compressive symptoms. Nodule volume, thyroid function and compressive symptoms were evaluated before treatment and at 1, 3 and 6 mo. Ultrasound-guided RF ablation was performed using a Starbust RITA needle, with nine expandable prongs; total exposure time was 6 to 10 min at 95 degrees C in one area or more of the nodule. Baseline volume (measured at the time of RF ablation) was 27.7 +/- 21.5 mL (mean +/- SD), but significantly decreased during follow-up: 19.2 +/- 16.2 at 1 mo (-32.7%; p < 0.001), 15.9 +/- 14.1 mL at 3 mo (-46.4 %; p < 0.001) and 14.6 +/- 12.6 mL at 6 mo (-50.7%; p < 0.001). After treatment, all patients with cold nodules remained euthyroid: five patients with hot nodules normalized thyroid function, and the remaining sixteen showed a partial remission of hyperthyroidism. Besides a sensation of heat and mild swelling of the neck, no major complications were observed. Improvement in compressive symptoms was reported by 13 patients, with a reduction on severity scale from 6.1 +/- 1.4 to 2.2 +/- 1.9 (p < 0.0001). Radiofrequency was effective and safe in reducing volume by about 50% and compressive symptoms in large benign nodules. Hyperfunction was fully controlled in 24% of patients and partially reduced in the others.

Efficacy and Safety of Radiofrequency Ablation Versus Observation for Nonfunctioning Benign Thyroid Nodules: A Randomized Controlled International Collaborative Trial.

BACKGROUND: Percutaneous radiofrequency thermal ablation (RFA) has been reported as an effective tool for the management of benign thyroid nodules (BTN). However, large, randomized controlled trials (RCTs) are lacking. OBJECTIVE: The aims of this study were to assess the volume reduction of BTN after a single RFA performed using the moving-shot technique and to compare the volume reduction obtained in patients treated in two centers with different experience of the moving-shot technique. METHOD: This study was an international prospective RCT. It was carried out at the Mauriziano Hospital (Turin, Italy) and the Asan Medical Center (Seoul, Korea). Eighty patients harboring solid, compressive, nonfunctioning BTN (volume 10-20 mL) were enrolled. Twenty patients in each country were treated by RFA using a 18-Gauge internally cooled electrode (group A); 20 nontreated patients in each country were followed as controls (group B). RESULTS: At six months, BTN volume significantly decreased in group A (15.1±3.1 mL vs. 4.2±2.7 mL; p<0.0001), whereas it remained unchanged in group B (14.4±3.3 mL vs. 15.2±3.5 mL). The baseline volume was larger in the Italian series (16.4±2.5 mL vs. 13.9±3.3 mL, p=0.009). However, at six months, there was no significant difference between the Korean group and the Italian group (3.7±2.9 mL vs. 5.5±2.2 mL). Both cosmetic and compressive symptoms significantly improved (3.6±0.5 vs. 1.7±0.4 and 3.6±1.9 vs. 0.4±0.7, respectively; p<0.001). No side effects occurred. CONCLUSIONS: RFA was effective in reducing the volume of BTN. The outcome was similar in centers with different experience in the moving-shot technique.

Diagnostic performance of elastography in cytologically indeterminate thyroid nodules.

Cytological examination of material from fine-needle aspiration biopsy is the mainstay of diagnosis of thyroid nodules, thanks to its remarkable accuracy and scarcity of complications. However, follicular lesions (also called indeterminate lesions or Thy3 in the current classification), a heterogeneous group of lesions in which cytology is unable to give a definitive diagnosis to, represent its main limit. Elastography has been proposed as a potential diagnostic tool to define the risk of malignancy in the aforementioned nodules, but at present there is no conclusive data due to the small number of specifically addressed studies and the lack of concordance among them. The objective of our study was to evaluate the role of real-time elastography (RTE) for refining diagnosis of Thy3 nodules, by integrating diagnostic information provided by traditional ultrasound (US). The study included 108 patients with Thy3 nodules awaiting for surgery, which were evaluated by US (considering hypoecogenicity, irregular margins, microcalcifications, halo sign, and intranodular vascularization) and RTE. Nodules were classified at RTE using a four-class color scale. At histologic examination, 75 nodules were benign and 33 malignant. As expected, none of the ultrasound parameters alone was adequate in predicting malignancy or benignity of the nodules; in the presence of at least two US risk factors, we obtained 61 % sensitivity, 83 % specificity, and 77 % accuracy with 6.8 OR (95 % CI 2.4-20.4). RTE scores 3 and 4 showed 76 % sensitivity, 88 % specificity, 74 % PPV, and 89 % NPV with diagnostic accuracy of 84 %; the data are statistically significant (p < 0.0001) with a OR of 21.9 (95 % CI 7.1-76). By combining RTE with US parameters, the presence of at least 2 characters of suspicion had 88 % sensitivity and 94 % NPV with 23.8 OR (95 % CI 7-106.3). The use of combined RTE and US leads to the identification of two patients subpopulations which have a significantly different malignancy risk (6 vs. 63 %); further studies are needed to verify if it is possible to send only the first group to thyroidectomy and the other to follow-up.

GHRH and GH secretagogues: clinical perspectives and safety.

The diagnosis and treatment of growth hormone deficiency (GHD), as well as the possibility of counteracting somatopause and age-related changes in body composition, structural functions, and metabolism, prompted interest in potential clinical uses of GH-releasing hormone (GHRH) and GH secretagogues (GHS). GHD often reflects hypothalamic GHRH deficiency and it has been clearly demonstrated that the age-related decline in the function of the GH/IGF-I axis reflects a reduction in hypothalamic function as evidenced by the preservation of the releasable pool of pituitary GH in aged subjects. The effectiveness of recombinant human GH (rhGH) is well established, but it is also recognized that GH replacement does not mimic physiological GH secretion which theoretically would be restored by GHRH and/or GHS. At present, it has been clearly demonstrated that GHRH and/or GHS represent reliable tools for the diagnosis of GHD. On the other hand, neither GHRH nor GHS has been shown to provide effective alternatives to rhGH for the treatment of GHD. Although GHRH and/or GHS represent the most logical approaches for the restoration of the GH/IGF-I axis to a youthful level of activity and for counteracting the somatopause, this hypothesis has never been proven definitively. Conceptually, GHRH replacement would be the most physiological approach and its safety is guaranteed, provided an appropriate dose is used, in order to avoid hyperactivity of the GH/IGF-I axis. However, a long-acting preparation is needed. On the other hand, GHS, e.g., ghrelin analogues, could be considered as a function of their selectivity of action. However, ghrelin has a wide spectrum of endocrine and non-endocrine actions at both central and peripheral levels. Thus, non-selective GHS, although available in orally active forms, could elicit unforeseen side effects. Previous studies with GHRH and/or GHS in aging patients provided encouraging results. However, it still remains to be definitively demonstrated that aged subjects would benefit from chronic treatment with these molecules.

High diagnostic accuracy and interobserver reliability of real-time elastography in the evaluation of thyroid nodules.

Elastography is a new diagnostic tool in the evaluation of thyroid nodules. Aim of the study was to evaluate the accuracy and reliability of elastography in discriminating thyroid lesions and the interobserver variability. One hundred thirty-two nodules in 115 patients selected for thyroid surgery underwent conventional ultrasound and elastographic evaluation. Elastography score was divided in four categories (totally elastic nodule, mainly elastic, mainly rigid and totally rigid) according to signal distribution. Three independent operators conducted the study. Final histology showed 92 benign nodules and 40 malignant. On elastography, 77/92 benign nodules were classified as score 1 or 2 and 34/40 malignant nodules as score 3 or 4 (sensitivity 85%, specificity 83.7%, positive predictive value [PPV] 69.3%, negative predictive value [NPV] 92.7%). Rate of concordance between operators was good (K test: 0.64, p < 0.0001). Simple to use, with good interobserver agreement, elastography has all the requisites to become an important complement of conventional US examination in the near future.

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.