Pituitary function and morphology in dogs with primary hypothyroidism

Thyroid hormones have effect on almost every organ system in the body. This explains the wide range of clinical manifestations of primary hypothyroidism in dogs. The signs and symptoms are often nonspecific and the disease onset is insidious. It may therefore take a long time before hypothyroidism is diagnosed. On the other hand, canine hypothyroidism is frequently diagnosed erroneously because many non-thyroidal factors (e.g. drug therapy, concurrent disease) may result in a low plasma total thyroxine (TT4) concentration. The introduction of homologous immunoassays for measuring canine plasma thyroid-stimulating hormone (TSH) concentrations in the 1990s enabled the assessment of the canine pituitary-thyroid axis by measuring the hormone pair T4 and TSH, with the diagnosis of primary hypothyroidism being established on the basis of a low plasma TT4 concentration and a high plasma TSH concentration. However, in studies using the TSH-stimulation test as gold standard, it appeared that plasma TSH concentrations were not elevated in as many as a third of dogs with primary hypothyroidism. The main aim of the studies described in this thesis was to test the hypothesis that primary hypothyroidism leads to adenohypophyseal alterations that may explain the occurrence of low plasma TSH concentrations. It was hoped that these studies would also bring about better ways to diagnose primary hypothyroidism in dogs. From the studies described in this thesis the following main conclusions can be drawn: • In dogs with suspected hypothyroidism, in which measurement of plasma concentrations of thyroxine (TT4 and/or fT4) and thyroid-stimulating hormone (TSH) provides inconclusive results, measurement of thyroid 99mTcO4- uptake can discriminate between primary hypothyroidism and non-thyroidal illness. • In healthy dogs, TSH is secreted in a pulsatile manner with only small fluctuations. In dogs with primary hypothyroidism, the TSH pulses are more pronounced and may occasionally result in plasma TSH concentrations within the reference range for euthyroid dogs. • Primary hypothyroidism in dogs is associated with elevated plasma concentrations of growth hormone (GH) and of the growth factor IGF-I. This explains some of the physical changes of canine hypothyroidism, mimicking the syndrome of GH excess (acromegaly). • In contrast to healthy dogs, dogs with primary hypothyroidism respond to the administration of thyrotropin-releasing hormone (TRH) with an increase in plasma GH concentrations. • The pituitary function of dogs with primary hypothyroidism is characterized by: - Initially high plasma TSH concentrations that decrease with time to levels that may fall within the reference range for healthy dogs. A gradual loss of TSH response to suprapituitary stimulation precedes this lowering of basal plasma TSH concentrations. - Development of GH hypersecretion, persisting with time. - Hyposecretion of prolactin (PRL) in neutered bitches and PRL hypersecretion in sexually intact bitches during the luteal phase of the estrus cycle. • Pituitary enlargement with time, associated with thyrotrope hyperplasia, large vacuolated “thyroid deficiency cells”, and cells double-staining for TSH and GH