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Pancreatic dysfunction is common among patients with iron overload, leading over time to diabetes mellitus [27, 28]. Even with chelation therapy, diabetes mellitus is observed in approximately 5% of adults with ß-thalassemia. Insulin resistance, due to iron deposition in the liver or muscle tissue, may contribute to the progression of diabetes [29, 30].
In the pituitary gland, iron deposition can produce a wide variety of systemic endocrine disturbances [31]. When present in childhood and adolescence, reduced gonadotropin production, coupled with reductions in gonadal synthesis of growth hormone or insulin-like growth factor, can result in delayed sexual maturation, and growth failure [32]. Diminished libido and infertility may result later in life [33].
Excess iron in patients with ß-thalassemia can also damage the thyroid, parathyroid, and adrenal glands. Iron overload can produce functional hypoparathyroidism [34], leading to hypocalcemia and potential skeletomuscular complications.
Arthropathy of large joints, such as the hips is common in hereditary hemochromatosis, but does not occur in transfusional iron overload [35]. This is possibly because such damage develops gradually over decades of iron deposition in articular cartilage. Osteoporosis is common among patients with thalassemia [36].
Other musculoskeletal problems include severe muscle cramps and disabling myalgia. Muscle biopsy often reveals iron deposits in myocytes [37].
Patients with iron overload appear to have increased susceptibility to infections, often with unusual microorganisms [38–40]. This apparent immune compromise may result from the abnormally high transferrin saturations seen in patients with iron overload.
Cutaneous iron deposition induces melanin production, causing a characteristic bronze pigmentation in fair-skinned people. Exposure to ultraviolet light acts synergistically with this process, and as a result many people with iron overload tan very easily, although these effects are variable. Fair-skinned people seldom develop hyperpigmentation even with a large iron burden, while people of moderate baseline pigmentation often develop a striking almond-colored hue.
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