Increased Frequency of Goitre in Epileptic Patients on Long‐term Phenytoin or Carbamazepine Treatment

Abstract

Thyroid function, the clinical occurrence of goitre and ultrasonically determined thyroid gland volume were investigated in 23 patients with phenytoin- and 28 patients with carbamazepine-treated convulsive disorders and compared with matched healthy controls. In the phenytoin treated group median thyroid volume was 26 ml (range 14-57 ml) compared to 17 ml (range 8-41 ml) in the controls (P less than 0.01). Ten patients and four controls had a goitre (NS). Median serum T4 and FT4I levels were reduced, serum TSH level increased and serum T3, T3RU, FT3I and thyroglobulin levels unaltered compared with the controls. In the carbamazepine treated group median thyroid volume was 25 ml (range 13-66 ml) compared to 16 ml (range 9-44 ml) in the controls (P less than 0.01). Thirteen patients and three controls had a goitre (P less than 0.02). Median serum T4, FT4I and FT3I levels were reduced, serum thyroglobulin increased and serum T3, T3RU and TSH levels unaltered compared with the controls. The increase in thyroid size is probably a compensatory mechanism due to the low free thyroid hormones in serum caused by an increased hepatic degradation of thyroid hormones by phenytoin and carbamazepine.

Phenobarbital Confers its Diverse Effects by Activating the Orphan Nuclear Receptor Car

“…In humans, chronic treatment with PB-like inducer phenytoin is also reported to decrease levels of total serum T4, promoting thyroid hypertrophy (Hegedus et al, 1985, Curran and DeGroot, 1991. However, it is not known whether this decrease is caused by the augmentation of metabolism and/or excretion of TH or the attenuation of TH synthesis.…”

Thyroid Gland Volume in Adults with Epilepsy: Relationship to Thyroid hormonal function

“…The higher frequency of patients with thyroid enlargement were on combined therapy (CBZ + VPA) (45%) followed by those on VPA (30%). Previous studies reported thyroid enlargement with enzyme-inducing and non-enzyme inducing AEDs (5,29,40). Hegedüs et al (5) reported increased thyroid volume with CBZ (range: 13-66 ml, mean: 25 ml; versus range: 9-44 ml, mean: 16 ml for controls; p<0.010).…”

“…Some studies reported ultrsongraphic evidence of thyroid enlargement (goiter). Also, these studies reported significant correlation between thyroid volume and thyroid hormonal abnormalities (5,29).…”

CARs and Drugs: A Risky Combination

“…As mentioned, the chronic elevation in TSH secretion documented in both rodents and humans receiving such compounds causes thyroid malignancies in rodents, whereas only thyroid enlargement has been observed in humans (22)(23)(24)(25). In patients without the capacity for internal compensation, such as those with hypothyroidism, the xenobiotic-induced increase in the rate of hormone metabolism will increase the replacement dosage requirement that can be critically important to fetal development during pregnancy.…”

“…A increase in TSH would compensate for this by accelerating T 4 and T 3 secretion. The sustained TSH-driven increase in the rate of thyroid follicular cell division can lead to thyroid malignancies in rodents, although not in humans (22)(23)(24)(25). Despite this increased stress upon the thyroid, hypothyroidism should not occur as long as the hypothalamicpituitary thyroid axis is intact and iodine supplies are sufficient.…”