LAKE BUENA VISTA, FLA. – Patients with low thyroid function may experience a “double whammy” of hypothyroidism and metabolic syndrome.
Even subclinical hypothyroidism affects many metabolic pathways that can contribute to deranged glucose and lipid metabolism, raising the risk of metabolic syndrome, according to Dr. Gabriela Brenta of the department of endocrinology at the Dr. Cesar Milstein Hospital in Buenos Aires. Though some mechanisms are incompletely understood, the association is clear enough to warrant screening all metabolic syndrome patients for hypothyroidism, she said.
Dr. Brenta described the recent work she and others have completed in the field. Basic science work revealed some early clues. For example, those who studied the effects of acute thyroid hormone withdrawal on patients with no thyroid gland found that these patients saw a rapid rise in insulin resistance. It’s known that even subclinical insulin resistance can lead to impaired glucose metabolism, making it logical to follow both normal and deranged metabolic pathways to help sort out the relationship between thyroid dysfunction and impaired glucose metabolism, she reported at the International Thyroid Congress.
Hypothyroidism can affect glucose homeostasis through multiple mechanisms, said Dr. Brenta. Firstly, hypothyroidism can lead to decreased hepatic gluconeogenesis and glycogenolysis. Hypothyroidism also can lead to reduced baseline plasma insulin levels and increased postglucose insulin secretion. In the peripheral tissues, hypothyroidism can interfere with glucose metabolism and disposal. All of these mechanisms can decrease hepatic glucose metabolism and lead to a postabsorptive hyperglycemia state, said Dr. Brenta, noting: “Insulin resistance is in some way the backbone of metabolic syndrome.”
Lipid metabolism is also affected by subclinical hypothyroidism, which can decrease expression of mRNA for LDL-C receptors, leading to LDL-C receptor down-regulation. With fewer receptors available, serum levels of LDL-C increase, with resultant increased susceptibility to oxidative effects and increased foam cell generation.
Dr. Brenta cited her earlier work showing that “triglyceride enrichment of LDL particles correlates with lower hepatic lipase activity” for individuals with subclinical hypothyroidism, with significantly lower hepatic lipase activity and a higher LDL-C to triglyceride ratio for those patients than for controls (Thyroid. 2007 May;17[5]:453-60). Overall, in hypothyroidism, “LDL particles are exposed to more substances that make them more atherogenic with decreased degradation and increased half-life,” said Dr. Brenta.
The increased risk for hypertension in both subclinical and overt hypothyroidism may be related, in part, to the fact that triiodothyronine deficiency can contribute to endothelial dysfunction. The relationship between subclinical hypothyroidism and hypertension was confirmed in a 2011 meta-analysis, said Dr. Brenta (Hypertens Res. 2011 Oct;34[10]:1098-105).
Though many factors contribute to obesity and thyroid function alone does not regulate body weight, a large population-based Danish study found that “even mild elevations of TSH are important for body weight,” said Dr. Brenta. The relationship is complex and bidirectional – a classic “chicken and egg” story – since obesity also may modulate TSH, she said; “however, we must not forget the ample literature on low levels of thyroid hormones reducing resting energy expenditure” (J Clin Endocrinol Metab. 2005 Jul;90[7]:4019-24).
Even though TSH tends to rise naturally through the lifespan, the association between elevated TSH and increased risk of metabolic syndrome held true even for older patients in one study, with “each one unit increase in TSH predicting a 3% increase in the odds of metabolic syndrome,” even after adjustment for age, BMI, and HOMA-IR status, among other variables, said Dr. Brenta (Clin Endocrinol [Oxf]. 2012 Jun;76[6]:911-8).
Advocating for universal screening for hypothyroidism among patients with metabolic syndrome, Dr. Brenta said that “hypothyroid disturbances are associated with an adverse metabolic profile, and even low normal TSH levels are associated with the metabolic traits of metabolic syndrome.”
The meeting was held by the American Thyroid Association, Asia-Oceania Thyroid Association, European Thyroid Association, and Latin American Thyroid Society. Dr. Brenta did not identify any conflicts of interest.