Guest Editor: Raffaella Origa THYROID DISORDERS IN HOMOZYGOUS β-THALASSEMIA: CURRENT KNOWLEDGE, EMERGING ISSUES AND OPEN PROBLEMS

Abstract

Abstract. Changes in thyroid function and thyroid function tests occur in patients with β-thalassemia major (TM). The frequency of hypothyroidism in TM patients ranges from 4% to 29 % in different reports. The wide variation has been attributed to several factors such as patients' genotype, age, ethnic variations, treatment protocols of transfusions and chelation, and varying compliance to treatment. Hypothyroidism is the result of primary gland failure or insufficient thy­roid gland stimulation by the hypothalamus or pituitary gland. The main laboratory parameters of thyroid function are the assessments of serum thyroid-stimulating hor­mone (TSH) and serum free thyroxine (FT4). It is of primary importance to interpret these measure­ments within the context of the laboratory-specific normative range for each test. An ele­vated serum TSH level with a normal range of serum FT4 level is consistent with subclinical hypothyroidism. A low serum FT4 level with a low, or inappropriately normal, serum TSH level is consistent with secondary hypothyroidism. Doctors caring for TM patients most commonly encounter subjects with subclinical primary hypothy­roidism in the second decade of life. Several aspects remain to be elucidated as the frequency of thyroid cancer and the possible existence of a relationship between thyroid dysfunction on one hand, cardiovascular diseases, components of metabolic syndrome (insulin resistance) and hypercoagulable state on the other hand. Further studies are needed to explain these emerging issues. Following a brief description of thyroid hormone regulation, production and actions, this article is conceptually divided into two parts; the first reports the spectrum of thyroid disease occurring in patients with TM, and the second part focuses on the emerging issues and the open problems in TM patients with thyroid disorders.

Iatrogenic Iron Overload in an End Stage Renal Disease Patient

“…Excessive iron infusions can lead to increased mortality and cardiovascular events in hemodialysis patients, these effects of iron supplementation can be attributed to the increased oxidative stress and induction of mononuclear cell adhesion to endothelial cells, which is an important step in the pathogenesis of atherosclerosis [8]. The risks of cerebrovascular and cardiovascular disease, infection, and hospitalization were significantly higher among patients who were treated with high weekly doses of intravenous iron compared with no intravenous iron [9].…”

Investigation and Management of Endocrinopathies in Thalassaemia Major

“…Hypothyroidism occurs either as a results of primary gland failure, or insufficient thyroid gland stimulation [74]. Hypothyroidism is thought to be a graded phenomenon and many types of hypothyroidism have been described: (1) sub-biochemical hypothyroidism: which consists of an exaggerated TSH response to TRH test in the presence of normal TSH and FT4; (2) sub-clinical hypothyroidism: elevated serum TSH with normal serum FT4 levels; (3) overt (clinical) hypothyroidism: High TSH with low FT4 level and (4) central Hypothyrodism: an inappropriately low or normal TSH with a low free T4 level [74]. The lack of autoimmune thyroiditis in thalassaemia patients continues to be supported by multiple studies [75,76].…”

“…The diagnosis of central hypothyroidism remains difficult from a clinical perspective, as its non-specific symptoms means that symptoms are usually attributed to another cause. From a biochemical perspective, central hypothyroidism is diagnosed based on a low to normal TSH level, in the presence of low levels of free T4 [74].…”

Does splenectomy influence the development of Hypothyroidism in Transfusion Dependent Thalassemia Patients? A retrospective study.

“…The toxicity of iron excess accumulated in thyroid tissues due to the high iron annual input is considered the key pathogenic factor. The prevalence of hypothyroidism in TDT patients varies widely from 5–29% 1,2. Higher incidences (>35%) were reported in cohorts comprised exclusively of adult TDT patients 3–5.…”

“…Higher incidences (>35%) were reported in cohorts comprised exclusively of adult TDT patients 3–5. This wide variation is due to extensive diversity of the cohorts and thyroid dysfunction related factors like genotype, age, clinical severity, frequency of transfusions, and compliance, and efficiency of chelation therapy 1. The occurrence of HT was recently evaluated in patients on long-term treatment with oral chelators.…”