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Signs, Symptoms, and Consequences of Iron Overload

The classic symptom of iron overload is skin hyperpigmentation (to a bronze or grey color), due to deposits of iron and melanin complexes in the skin. The liver, as a primary source of iron storage, is particularly susceptible to iron overload and related damage, which may range from enlargement (hepatomegaly) and elevated serum liver enzymes, to fibrosis or cirrhosis (Siddique 2012).

Long-term iron overload can result in liver cancer (Kew 2009). High serum iron (measured as greater than 60% transferrin saturation) increases the 10-year absolute risk of liver cancer almost six-fold and risk of any cancer over three-fold (Ellervik 2012).

Iron accumulation in endocrine organs has been associated with diabetes, hypogonadism (decreased production of sex hormones), and less commonly hyper- or hypothyroidism; some of these may be reversed by bringing iron levels back into a healthy range (Siddique 2012; NIH MedlinePlus 2010).

Osteoporosis is possible with severe iron overload, and may be due to hypogonadism (Valenti 2009; Siddique 2012).

Arthropathy (joint disease with or without inflammation) is common with iron overload, causing pain with minimal inflammation in the joints of the hands, wrists, elbows, shoulders, and hips (Siddique 2012).

Iron deposition in the heart can cause cardiomyopathy, arrhythmia, heart failure, and sudden cardiac death (Kremastinos 2011; Klintschar 2004). It can also increase vascular damage and atherosclerosis risk (Dongiovanni 2011).

The brain is another potential site of excess iron accumulation, as it requires iron for several neuron-specific reactions, e.g. the synthesis of myelin, which sheaths neuronal axons, and the production of neurotransmitters (Williams 2012). Excess iron can form complexes with melanin in the substantia nigra of the brain in much the same way it does in skin; this has been observed in the brains of Parkinson’s disease patients, and may be related to progression of the disease (Nandar 2011; Shima 1997; Jellinger 1992). Iron deposits in the amyloid plaques of Alzheimer’s disease patients may contribute to neurodegeneration through free-radical toxicity (Crichton 2011). Abnormal brain iron deposition has also been observed in Multiple Sclerosis as well as other neurodegenerative movement disorders (Williams 2012; Gregory 2011).

Bacteria require iron for many of the same reactions as humans; excess iron in the blood or tissues can stimulate the growth of invading pathogens (Pietrangelo 2010).

Iron Overload and Endocrine Dysfunction

Hormonal imbalance is a significant problem among individuals with primary or secondary iron overload (Noetzli 2011; McDermott 2005; Van deursen 2003).

Excess iron accumulates in the pituitary gland and disrupts synthesis of gonadotropin-releasing hormone (GnRH), which is responsible for stimulating the production of sex hormones from the gonads (i.e., testes and ovaries). The consequence of this disruption is abnormally low levels of important sex hormones like testosterone and estrogen (Van deursen 2003; McDermott 2005).

However, pituitary dysfunction alone does not account for all the hormonal perturbations observed in all iron overload cases (Walsh 1976). This can be partly explained by another phenomenon observed among some iron overload patients - elevated sex hormone binding globulin (SHBG) levels; although the mechanism for this elevation is not entirely clear (Gautier 2011).

SHBG is a transport protein that carriers sex hormones through circulation. The problem, however, is that when hormones are bound to SHBG, their ability to bind and activate their receptors is greatly hindered. So, when SHBG levels are elevated due to iron accumulation in the liver, hormonal signaling may be disrupted (Selby 1990).

Thus, iron accumulation in the brain and the liver among those with iron overload may precipitate considerable hormonal irregularities, which can lead to a barrage of complications ranging from diabetes to cardiovascular problems and loss of libido to osteoporosis (Rochira 2006; Corona 2011; Dandona 2011; Dandona 2010).

An unfortunate reality is that many conventional physicians may not appreciate the role of iron overload in hormone-related complications (Cundy 1989; McCarthy 2002). Therefore, it is likely that many patients whose hormone-related ailments may be attributable to excess iron levels are not properly diagnosed and treated.

Life Extension suggests that individuals with known or suspected hormonal imbalances consider blood tests for iron overload. Likewise, individuals with iron overload should consider blood tests for hormone imbalances. Identification and treatment of these commonly concurrent conditions may improve quality of life for many people.