Acute Thyroid Hormone Withdrawal in Athyreotic Patients Results in a State of Insulin Resistance

Abstract

It is well known that thyroid hormones are important regulators of energy balance and intermediate metabolism. With regard to glucose homeostasis, hyperthyroidism is associated with a state of insulin resistance due to increased hepatic gluconeogenesis (1). In hypothyroidism however, despite the fact that hepatic gluconeogensis has been described as unchanged (2) or decreased (3,4), experiments in animal models have demonstrated a state of insulin resistance both in the adipocyte and in the skeletal muscle (5,6). In humans the literature referring to the connection between thyroid dysfunction and insulin resistance is not consistent; this is in part due to the complex and redundant mechanisms regulating glucose homeostasis, but also to the use of different methods and indexes to assess the insulin sensitivity (indexes derived by the fasting insulin and glucose levels, intravenous [IV] or oral glucose tolerance test, euglycemic hyperinsulinemic clamps, local infusion of insulin and glucose in isolated limbs, examination in vitro of adipocytes, etc.). Specifically, only few studies have evaluated the insulin sensitivity in hypothyroidism and the results are controversial, some (7-12), but not all (13-16) have found that thyroid hormone deficit leads to insulin resistance secondary to decreased glucose disposal. On the other hand, while overt hyperthyroidism has been clearly associated with insulin resistance (1), the data on insulin action in subclinical hyperthyroidism is limited and controversial (17,18).The use of thyroid hormone suppressive therapy for thyroid cancer and its withdrawal before diagnostic or therapeutic intervention offers a unique model to assess the effects of controlled manipulation of circulating thyroid hormones on target pathways, in this case glucose homeostasis.We hypothesized that the lack of thyroid hormones leads to an insulin-resistant state due to a decrease in glucose disposal in skeletal muscle and adipose tissue. Considering the critical impact of insulin resistance on cardiovascular risk (19), we have explored the changes in insulin sensitivity in relation to changes in thyroid hormone homeostasis both under the subclinical hyperthyroid and overt acute hypothyroid status in thyroid cancer patients undergoing thyroid hormone withdrawal.Six women (age 42 AE 11 years, body mass index [BMI] 24 AE 2 kg=m 2 ) that underwent total thyroidectomy for differentiated thyroid cancer were included in the study group. Eight healthy subjects (six women and two men, age 37 AE 2 years, BMI 23 AE 2 kg=m 2 ) served as controls. The characteristics of the thyroid cancer patients are reported in Table 1. All the volunteers had a normal response to a standard 75 g oral glucose tolerance test. No patient had clinical evidence of metastatic disease as assessed by suppressed thyroglobulin and neck ultrasound. The average dose of levothyroxine taken orally every morning for TSH suppression was 169 AE 34 mg=d. Four patients were studied under TSH suppression with levothyroxine (sub HYPER). Due to the fac...

T3Rapidly IncreasesSLC2A4Gene Expression and GLUT4 Trafficking to the Plasma Membrane in Skeletal Muscle of Rat and Improves Glucose Homeostasis

“…In fact, Figure 5 shows in Tx rats a reduced amount of GLUT4 on skeletal muscle and a decreased response to insulin stimulus, findings that have been reported in animal models (42,43) and hypothyroid patients (44,45). It also shows a reestablishment of the insulin response, in rats under 5-day T 3 treatment, a procedure that increased the GLUT4 content, as described (5,27).…”

The Relationship between Type 2 Diabetes Mellitus and Related Thyroid Diseases

“…Among the above-mentioned symptomatology, insulin resistance has been the most important facet connecting thyroid dysfunction and T2DM. Insulin resistance is a condition which occurs in both hypothyroidism and hyperthyroidism [27]. …”

“…Hyperthyroidism has been associated with insulin resistance which has been linked with elevated glucose turnover, increased intestinal glucose absorption, elevated hepatic glucose output, increased free fatty acid concentrations, increased fasting and or postprandial insulin an proinsulin levels, and increased peripheral glucose transport accompanied by glucose utilization [27, 34]. T2DM patients with thyroid dysfunction have been proven to be more susceptible to ketosis [35] and ketogenesis [36].…”

Insulinooporność a choroby tarczycy

“…This may be an alternative mechanism explaining the effect of hypothyreosis on decreasing glucose utilisation by peripheral cells [8]. Brenta et al observed that patients with hypothyroidism, compared to euthyreotic subjects, demonstrated a significantly lower glucose utilisation during a short intravenous insulin tolerance test [28].…”