Thyrotropin-releasing hormone-induced growth hormone secretion in dogs with primary hypothyroidism

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Abstract

Primary hypothyroidism in dogs is associated with increased release of growth hormone (GH). In search for an explanation we investigated the effect of intravenous administration of thyrotropin-releasing hormone (TRH, 10 μg/kg body weight) on GH release in 10 dogs with primary hypothyroidism and 6 healthy control dogs. The hypothyroid dogs had a medical history and physical changes compatible with hypothyroidism and were included in the study on the basis of the following criteria: plasma thyroxine concentration <2 nmol/l and plasma thyrotropin (TSH) concentration >1 μg/l. In addition, 99mTcO4 uptake during thyroid scintigraphy was low or absent.

TRH administration caused plasma TSH concentrations to rise significantly in the control dogs, but not in the hypothyroid dogs. In the dogs with primary hypothyroidism, the mean basal plasma GH concentration was relatively high (2.3 ± 0.5 μg/l) and increased significantly (P = 0.001) 10 and 20 min after injection of TRH (to 11.9 ± 3.5 and 9.8 ± 2.7 μg/l, respectively). In the control dogs, the mean basal plasma GH concentration was 1.3 ± 0.1 μg/l and did not increase significantly after TRH administration.

We conclude that, in contrast to healthy control dogs, primary hypothyroid dogs respond to TRH administration with a significant increase in the plasma GH concentration, possibly as a result of transdifferentiation of somatotropic pituitary cells to thyrosomatotropes.

Introduction

Insufficient levels of thyroid hormones affect almost all organ systems, including other endocrine glands such as the pituitary gland [1]. The effect of hypothyroidism on the release of pituitary hormones varies per species and this is particularly true for growth hormone (GH). In some mammals, such as sheep and steers (experimentally induced) primary hypothyroidism does not affect GH secretion [2], [3], whereas in rats and pigs hypothyroidism leads to low plasma GH concentrations [4], [5], [6], [7], [8], [9]. In contrast, in dogs primary hypothyroidism is associated with elevated basal GH secretion [10]. Although the pulsatile character of GH release is maintained, less GH is released per pulse. However, integral GH release calculated as area under the curve for GH above zero level is significantly elevated in hypothyroid dogs. This elevated GH secretion has endocrine effects as reflected by elevated plasma IGF-I concentrations and physical changes mimicking acromegaly [10].

In the search for an explanation for this unique situation in dogs, it has been suggested that the low plasma thyroid hormone concentration affects the regulation of GH release at the hypothalamic level. In healthy humans administration of thyrotropin-releasing hormone (TRH) does not result in appreciable changes in plasma GH levels [11], [12], [13], whereas in humans with primary hypothyroidism TRH administration results in a significant increase in the plasma GH concentration [4], [11], [12], [13]. This paradoxical response of GH to TRH in primary hypothyroidism may in part be caused by the relative deficiency in somatostatin [6], [7], [10]. Infusion of somatostatin inhibits the GH response to TRH in humans with primary hypothyroidism [14].

So far, there is no information on the effect of TRH on GH secretion in dogs with primary hypothyroidism. Here we report on the effect of TRH administration on the plasma GH concentration in healthy control dogs and in dogs with primary hypothyroidism.

Section snippets

Dogs

Ten clinical cases, presented with a medical history and physical changes compatible with hypothyroidism, were included in the study on the basis of the following criteria: plasma thyroxine (T4) concentration <2 nmol/l and plasma thyrotropin (TSH) concentration >1 μg/l (Table 1). In addition, 99mTcO4 uptake during thyroid scintigraphy was low or absent [15]. There were six male dogs (four castrated) and four female dogs (two spayed) of a wide variety of breeds; the median age was 6 years (range

Results

In the TRH-stimulation test the basal plasma TSH concentrations of the healthy dogs were within the reference range (<0.6 μg/l). Administration of TRH caused the plasma TSH concentrations to rise significantly (Fig. 1) from 0.35 ± 0.05 to 1.8 ± 0.4 μg/l (P = 0.025). Similar to the initial values on admission, in the hypothyroid dogs the basal plasma TSH concentrations of the TRH-stimulation test (3.1 ± 0.6 μg/l) exceeded the upper limit of the reference range and were significantly higher (P = 0.005) than

Discussion

It can be difficult to establish the diagnosis of primary hypothyroidism in dogs because of the common occurrence of low plasma T4 concentrations in non-thyroidal illness and the frequent absence of an elevated plasma TSH concentration in primary hypothyroidism [17]. In order to prevent inclusion of misdiagnosed cases, we entered only dogs in which the presence of primary hypothyroidism was beyond any doubt. All dogs had a relatively long history of physical changes compatible with

Acknowledgements

The technical assistance of Mrs. Y.W.E.A. Pollak, Mr. H.G.H. van Engelen, Ms. J. Wolfswinkel, and Ms. M.E. van Wolferen is highly appreciated.

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    Preliminary results have been presented at the 15th congress of the European College of Veterinary Internal Medicine—Companion Animals, Glasgow, Scotland, 1–3 September 2005.

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