Background and Objectives Patients with β-thalassemia, like those with genetic hemochromatosis, develop iron overload due to increased iron absorption, and their iron burden is further exacerbated by transfusion therapy. Hepcidin, a hepatic hormone, regulates systemic iron homeostasis by inhibiting the absorption of iron from the diet and the recycling of iron by macrophages. In turn, hepcidin release is increased by iron loading and inhibited by erythropoietic activity. Hepcidin deficiency is the cause of iron overload in most forms of hereditary hemochromatosis. We sought to determine hepcidin’s role in the pathogenesis of iron overload in β-thalassemia. Design and Methods We assessed the degree of iron overload in thalassemia intermedia and major patients by measuring hepatic iron concentration in liver biopsy samples and serum ferritin, estimated erythropoietic drive by assaying soluble transferrin receptor and serum erythropoietin levels and correlated these with urinary hepcidin measurements. Results Urinary hepcidin levels in β-thalassemia demonstrate severe hepcidin deficiency in thalassemia intermedia. There was a strong inverse relationship between urinary hepcidin levels and both erythropoietin and soluble transferrin receptor, markers of erythropoietic activity. In contrast, hepcidin levels were elevated in thalassemia major, presumably due to transfusions that reduce erythropoietic drive and deliver a large iron load. Despite similar liver iron concentrations in the two conditions, serum ferritin was much lower in thalassemia intermedia. Interpretation and Conclusions In thalassemia intermedia, high erythropoietic drive causes severe hepcidin deficiency. The lack of hepcidin results in hyperabsorption of dietary iron, but also in iron depletion of macrophages, lowering their secretion of ferritin and, consequently, serum ferritin levels. In contrast, in thalassemia major, transfusions decrease erythropoietic drive and increase the iron load, resulting in relatively higher hepcidin levels. In the presence of higher hepcidin levels, dietary iron absorption is moderated and macrophages retain iron, contributing to higher serum ferritin. In the future, hepcidin measurements may allow a more accurate assessment of the degree of iron overload and the maldistribution of iron in thalassemia.

Serum thyroglobulin (Tg) is the marker of differentiated thyroid carcinoma (DTC) after total thyroidectomy, but its value is limited by the interference of anti-Tg antibodies (TgAb). Detection of Tg in fine-needle aspiration biopsy (Tg-FNAB) washout fluid is used to identify neck DTC recurrences/metastases, but the interference of serum TgAb in this procedure is unknown. Seventy-three patients (41 after surgery for thyroid cancer and 32 with thyroid nodules) evaluated for suspicious cervical lymph nodes were retrospectively reviewed. Tg was assayed by immunoradiometric assay or chemiluminescent assay in ultrasound-guided FNAB used for cytology. Serum TgAb were detected by passive agglutination or chemiluminescent assay. On the basis of preliminary data obtained in lymphadenitis, Tg-FNAB more than 36 ng/ml and more than 1.7 ng/ml (in the presence or absence of thyroid gland, respectively) was considered as indicative of metastasis. In 51 TgAb-negative patients, Tg-FNAB was positive in 15 (12 with malignant and three with nondiagnostic cytology), all with histologically confirmed DTC metastases. Of the remaining 36 patients with negative Tg-FNAB, 30 had nonsuspicious and six had suspicious cytology. Histology of the latter showed four undifferentiated thyroid cancer metastases and two lymphadenitis. In 22 TgAb-positive patients, Tg-FNAB was positive in 14 (12 with malignant and two with nondiagnostic cytology), all with histologically confirmed DTC metastases. Clinical performance of Tg-FNAB appears to be not substantially affected by TgAb, and this procedure remains superior to cytology in the identification of DTC neck metastases. However, cytology should always be performed because, irrespective of TgAb, Tg is undetectable in FNAB from undifferentiated metastases.

The aim of this review is to attempt to answer extremely important questions related to aluminium-related diseases. Starting from an overview on the main sources of aluminium exposure in everyday life, the principal aspects of aluminium metabolism in humans have been taken into consideration in an attempt to enlighten the main metabolic pathways utilised by trivalent metal ions in different organs. The second part of this review is focused on the available evidence concerning the pathogenetic consequences of aluminium overload in human health, with particular attention to its putative role in bone and neurodegenerative human diseases.