Excess Thyroid Hormone and Carbohydrate Metabolism

Matthew Potenza, MD; Michael A. Via, MD; Robert T. Yanagisawa, MD

Disclosures

Endocr Pract. 2009;15(3):254-262. 

In This Article

Leptin, Ghrelin, and Adiponectin Affecting Metabolism

Adipocyte-derived hormones adiponectin and leptin, as well as the orexigenic hormone ghrelin, affect insulin sensitivity and glucose homeostasis,[51] and these hormones are affected by the hyperthyroid state. Both adipocytokines and thyroid hormone may be affected by energy balance and body weight. A relationship between these 2 endocrine systems seems intuitive.

Ghrelin, secreted by G cells of the gastric fundus, increases in fasting states, decreases postprandially, and acts as a potent appetite stimulant. Ghrelin promotes positive energy balance by decreasing glucose and fat oxidation and increasing energy storage.[52] Levels of ghrelin are suppressed in states of hyperinsulinemia, such as in obesity and type 2 diabetes.[53,54,55] In hyperthyroid patients, ghrelin levels are also suppressed, corresponding to the degree of thyrotoxicosis and to glucose levels.[52] Thyroid hormone decreases ghrelin gene expression in mouse models.[56]

Ghrelin levels do not seem to correlate with hunger in the hyperthyroid state, as hyperthyroid patients consume more food than euthyroid patients even at low ghrelin levels.[57] Whether the hyperinsulinemic hyperglycemic state or excess of thyroid hormone itself is the cause of ghrelin suppression in hyperthyroidism, the resulting influence on carbohydrate metabolism is a shift away from energy storage and towards energy use and may have a role in the hypercatabolic state. Ghrelin levels increase back into the reference range when hyperthyroidism is treated.[58]

Leptin is secreted by adipocytes and has several actions that oppose ghrelin activity, including suppression of appetite and increased energy use. In contrast to ghrelin, leptin is elevated in obese persons. Findings from recent studies point toward the inflammatory properties of leptin as contributing factors to the increased cardiac risk associated with obesity.[59,60] In hyperthyroidism, leptin levels are decreased, creating a unique low-ghrelin, low-leptin state.[61,62] Older studies that fail to show the associated low leptin levels in hyperthyroid patients have been criticized for being small, for including partially treated hyperthyroid patients, and for not well characterizing euthyroid control participants.[63,64]

Interestingly, leptin increases peripheral type 2 deiodinase activity so that more T3 is available to peripheral tissues.[65,66] Euthyroid animal models demonstrate that leptin activity decreases type 2 deiodinase in the paraventricular nucleus, leading to enhanced thyrotropin-releasing hormone release, an effect that is lost in the hyperthyroid state.[66,67] In hyperthyroidism, the hypothalamic effects of leptin are likely overcome by the negative feedback of excess thyroid hormone itself. Nevertheless, the peripheral activity of leptin may have a role in raising T3 levels, thereby worsening hyperthyroidism, although this effect is obviated in the prolonged hyperthyroid state.[67] Thus, low leptin levels in hyperthyroidism may be compensatory. These complex interactions of leptin and tissue-specific deiodinases probably influence carbohydrate metabolism, but exact mechanisms and overall effects are not yet known.

Adiponectin is secreted by adipocytes and is also important in energy metabolism and insulin resistance. Low adiponectin levels are seen in obesity and are associated with increased risk for developing type 2 diabetes, independent of body mass index.[68] Some animal models have shown reversal of insulin resistance with adiponectin infusion.[51] Adiponectin levels appear unchanged in the hyperthyroid state compared with those observed in euthyroid counterparts.[61,69] In hyperthyroid patients, body mass index is the greatest predictor of adiponectin levels, which is not influenced by level of thyroid hormone excess.[61] Thus, while hyperthyroidism affects ghrelin and leptin, which may alter carbohydrate metabolism, it does not seem to affect adiponectin.

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