Adenohypophyseal function in dogs with primary hypothyroidism and nonthyroidal illness.

BACKGROUND: A recent study of dogs with induced primary hypothyroidism (PH) demonstrated that thyroid hormone deficiency leads to loss of thyrotropin (TSH) hypersecretion, hypersomatotropism, hypoprolactinemia, and pituitary enlargement with large vacuolated "thyroid deficiency" cells that double-stained for growth hormone (GH) and TSH, indicative of transdifferentiation of somatotropes to thyrosomatropes. HYPOTHESIS: Similar functional changes in adenohypophyseal function occur in dogs with spontaneous PH as do in dogs with induced PH, but not in dogs with nonthyroidal illness (NTI). ANIMALS: Fourteen dogs with spontaneous PH and 13 dogs with NTI. METHODS: Adenohypophyseal function was investigated by combined intravenous administration of 4 hypophysiotropic releasing hormones (4RH test), followed by measurement of plasma concentrations of ACTH, GH, luteinizing hormone (LH), prolactin (PRL), and TSH. In the PH dogs this test was repeated after 4 and 12 weeks of thyroxine treatment. RESULTS: In 6 PH dogs, the basal TSH concentration was within the reference range. In the PH dogs, the TSH concentrations did not increase with the 4RH test. However, TSH concentrations increased significantly in the NTI dogs. Basal and stimulated GH and PRL concentrations indicated reversible hypersomatotropism and hyperprolactinemia in the PH dogs, but not in the NTI dogs. Basal and stimulated LH and ACTH concentrations did not differ between groups. CONCLUSIONS AND CLINICAL IMPORTANCE: Dogs with spontaneous PH hypersecrete GH but have little or no TSH hypersecretion. Development of hyperprolactinemia (and possible galactorrhea) in dogs with PH seems to occur only in sexually intact bitches. In this group of dogs with NTI, basal and stimulated plasma adenohypophyseal hormone concentrations were not altered.

Functional and morphological changes in the adenohypophysis of dogs with induced primary hypothyroidism: loss of TSH hypersecretion, hypersomatotropism, hypoprolactinemia, and pituitary enlargement with transdifferentiation.

From case studies in humans it is known that primary hypothyroidism (PH) may be associated with morphological and functional changes of the pituitary. There is no insight into the time scale of these changes. In this study, seven beagle dogs were followed up for 3 years after the induction of primary hypothyroidism. Three of these dogs were followed up for another 1.5 years while receiving l-thyroxine. Adenohypophyseal function was investigated at 2-month intervals with the combined intravenous injection of CRH, GHRH, GnRH, and TRH, and measurement of the plasma concentrations of ACTH, GH, LH, PRL, and TSH. In addition, after 2 years of hypothyroidism a single TRH-stimulation test and a somatostatin test were performed, with measurements of the same pituitary hormones. Every 6 months the pituitary gland was visualized by computed tomography (CT). Induction of PH led to high plasma TSH concentrations for a few months, where after concentrations gradually declined to values no longer significantly different from pre-PH values. A blunted response to stimulation of TSH release preceded this decline. Basal plasma GH concentrations increased during PH and there was a paradoxical hyperresponsiveness to TRH stimulation. Basal GH concentrations remained elevated and returned only to low values during l-thyroxine treatment. Basal PRL concentrations decreased significantly during PH and normalized after several months of l-thyroxine treatment. The pituitary gland became enlarged in all dogs. Histomorphology and immunohistochemical studies in 4 dogs, after 3 years of PH, revealed thyrotroph hyperplasia, large vacuolated thyroid deficiency cells, and decreased numbers of mammotrophs. Several cells stained for both GH and TSH. In conclusion, with time PH led to a loss of the TSH response to low T4 concentrations, hypersecretion of GH, and hyposecretion of PRL. The enlarged pituitaries were characterized by thyrotroph hyperplasia, large vacuolated thyroid deficiency cells, and double-staining cells, which are indicative of transdifferentiation.

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

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 microg/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 microg/l. In addition, (99m)TcO(4)(-) 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 microg/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 microg/l, respectively). In the control dogs, the mean basal plasma GH concentration was 1.3+/-0.1 microg/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.

Assessment of thyroid function in dogs with low plasma thyroxine concentration.

BACKGROUND: Differentiation between hypothyroidism and nonthyroidal illness in dogs poses specific problems, because plasma total thyroxine (TT4) concentrations are often low in nonthyroidal illness, and plasma thyroid stimulating hormone (TSH) concentrations are frequently not high in primary hypothyroidism. HYPOTHESIS: The serum concentrations of the common basal biochemical variables (TT4, freeT4 [fT4], and TSH) overlap between dogs with hypothyroidism and dogs with nonthyroidal illness, but, with stimulation tests and quantitative measurement of thyroidal 99mTcO4(-) uptake, differentiation will be possible. ANIMALS: In 30 dogs with low plasma TT4 concentration, the final diagnosis was based upon histopathologic examination of thyroid tissue obtained by biopsy. Fourteen dogs had primary hypothyroidism, and 13 dogs had nonthyroidal illness. Two dogs had secondary hypothyroidism, and 1 dog had metastatic thyroid cancer. METHODS: The diagnostic value was assessed for (1) plasma concentrations of TT4, fT4, and TSH; (2) TSH-stimulation test; (3) plasma TSH concentration after stimulation with TSH-releasing hormone (TRH); (4) occurrence of thyroglobulin antibodies (TgAbs); and (5) thyroidal 99mTcO4(-) uptake. RESULTS: Plasma concentrations of TT4, fT4, TSH, and the hormone pairs TT4/TSH and fT4/TSH overlapped in the 2 groups, whereas, with TgAbs, there was 1 false-negative result. Results of the TSH- and TRH-stimulation tests did not meet earlier established diagnostic criteria, overlapped, or both. With a quantitative measurement of thyroidal 99mTcO4(-) uptake, there was no overlap between dogs with primary hypothyroidism and dogs with nonthyroidal illness. CONCLUSIONS AND CLINICAL IMPORTANCE: The results of this study confirm earlier observations that, in dogs, accurate biochemical diagnosis of primary hypothyroidism poses specific problems. Previous studies, in which the TSH-stimulation test was used as the "gold standard" for the diagnosis of hypothyroidism may have suffered from misclassification. Quantitative measurement of thyroidal 99mTcO- uptake has the highest discriminatory power with regard to the differentiation between primary hypothyroidism and nonthyroidal illness.

Thrombosis of the portal vein in a miniature schnauzer.

A miniature schnauzer with a history of apathy, anorexia and jaundice was presented to the Utrecht University Clinic for Companion Animals. Abnormal laboratory findings included highly increased levels of total bile acids and alkaline phosphatase, and hyponatraemia. Abdominal ultrasonography revealed that the right side of the liver was enlarged and the left side was small, together with a thrombus in the portal vein. Biopsies from the right side of the liver demonstrated subacute to chronic active hepatitis, for which the dog was treated with prednisolone (1 mg/kg/day for four weeks). No improvement was observed and the owner requested euthanasia. At necropsy the left lobes of the liver were found to be small and firm, while the right lobes were large and soft. There were two thrombi in the portal vein. Microscopic examination revealed chronic active hepatitis and cirrhosis.

Idiopathic detrusor-urethral dyssynergia in dogs: a retrospective analysis of 22 cases.

Results of a retrospective study of 22 dogs with signs of dysuria and/or stranguria in which a diagnosis of idiopathic detrusor-urethral dyssynergia was made are presented. The diagnosis was based on the exclusion of detectable pathological conditions which could also cause urine outflow obstruction. The affected cases were 22 middle-aged male dogs (mean age 4.9 years) of large and giant breeds (mean bodyweight 36.7 kg). Nine dogs had had periodic clinical signs for longer than one year, one for seven months and eight for two to five weeks, while in four dogs signs had begun four to five days before referral. All dogs received the alpha-sympatholytic agent prazosin as an initial treatment and in 11 it remained the only therapy. There was a good effect in seven and a moderate response in the other four dogs. In one dog, prazosin was ineffective and was replaced by diazepam, which markedly reduced the signs. Three other dogs required frequent catheterisation and antibiotics were administered. These dogs responded favourably. Another three dogs with evidence of impaired bladder contractility were also treated with the parasympathomimetic agent carbachol. One did not improve and was euthanased. Four dogs developed bladder paralysis and severe infectious cystitis. Only one of these could be managed satisfactorily by long-term administration of prazosin, carbachol and antibiotics, and the others had to be euthanased.

A case of autochthonous canine leishmaniasis in The Netherlands.

The transmission of visceral leishmaniasis (VL) in the absence of its natural vector, the sandfly, is considered exceptional. This report describes VL in a 12-month-old dog which had never been in an area in which VL is endemic but was born in the Netherlands from a bitch that had been infected in Spain. Although the mode of transmission, via the placenta or otherwise, is unknown, it can be concluded that bitches with VL can be a source of infection for their pups, even in a sandfly-free non-endemic area. The dog was successfully treated with allopurinol.