A critical review of food-associated factors proposed in the etiology of feline hyperthyroidism

Abstract

Since the first description of feline hyperthyroidism (HT) in 1979, several studies have been undertaken to define the etiology of the disease. Epidemiologic studies, after investigating non-food- and food-associated factors, suggest a multifactorial etiology. However, in the absence of prospective cohort studies that can confirm a cause-and-effect relationship between HT and associated risk factors, no causative factor for HT has been identified to date. Feline HT resembles toxic nodular goiter in humans, with autonomously functioning upregulated iodide uptake systems. Contribution of the diet to HT development remains controversial. The purpose of this paper is to review critically the reported food-associated risk factors for HT.

Figure 1

Hypothalamic–pituitary–thyroid axis and key steps in thyroid hormone formation. The thyroid is part of the hypothalamus–pituitary–thyroid axis. The hypothalamus releases thyrotropin-releasing hormone (TRH), which stimulates the pituitary to release thyroid-stimulating hormone (TSH). TSH, consisting of α and β subunits, binds to and activates the TSH receptor (TSHR) coupled to G proteins. Stimulation of the adenosine 3′,5′- cyclic monophosphate pathway results in enhanced iodide uptake, growth, differentiation and hormone synthesis. Iodide is actively transported into thyroid follicular cells by the sodium–iodide symporter (NIS) at the basolateral membrane. Thyroid peroxidase (TPO) oxidizes iodide and subsequently iodinates tyrosil residues of thyroglobulin (Tg) in the presence of hydrogen peroxide. The iodotyrosines, mono- and diiodothyrosil, are coupled to T4 and T3; this reaction is also catalyzed by TPO (coupling), and Tg is recycled in the follicular cell, and the thyronines T3 and T4 are released into the bloodstream. T3 and T4 have peripheric actions, but also act with a negative feedback on the release on TRH and TSH. Solid lines: effect. Dashed lines: inhibition

Figure 2

Causes and effects of preferential proliferation of thyrocytes. Several factors can cause increased thyroid-stimulating hormone (TSH)-dependent stimulatory pathways. These pathways or other factors like toxins, goitrogens or nutritional factors from the diet can cause preferential proliferation of certain thyrocytes or thyroid hyperplasia. Hyperplastic nodules of autonomous growing and functioning thyrocytes form, and clinical signs of hyperthyroidism develop. Solid lines: effect. Dashed lines: inhibition^–