Vitamin D status before and after hypophysectomy in dogs with pituitary-dependent hypercortisolism

Both spontaneous hypercortisolism and chronic glucocorticoid treatment are associated with osteoporosis and low circulating concentrations of 1,25-dihydroxy-vitamin D in humans. Pituitary-dependent hypercortisolism (PDH) is a common disorder in dogs, but little is known about the vitamin D status of affected dogs. Pituitary-dependent hypercortisolism in dogs can be treated effectively by hypophysectomy and subsequent hormone supplementation. Because hormone supplementation does not include GH, dogs that have undergone hypophysectomy have low circulating concentrations of GH and IGF-1, which may result in low plasma 1,25-dihydroxy-vitamin D concentrations and consequently increased parathyroid hormone secretion. The aim of this study was to determine whether dogs with PDH need vitamin D supplementation before and/or after hypophysectomy. To this end, we measured plasma concentrations of GH, IGF-1, parathyroid hormone, calcium, phosphate, and vitamin D metabolites in 12 dogs with PDH before and 8 wk after hypophysectomy and in 12 control dogs. Although plasma GH concentrations were lower in dogs with PDH than in control dogs both before and after hypophysectomy, the vitamin D status was similar. In conclusion, there is no need for vitamin D supplementation in dogs with PDH, either before or after hypophysectomy.     

Efficacy of transsphenoidal hypophysectomy in treatment of dogs with pituitary-dependent hyperadrenocorticism

The long-term survival, disease-free fractions, and the complications of hypophysectomy in 150 dogs with pituitary-dependent hyperadrenocorticism (PDH) were examined in a prospective study. Long-term survival and disease-free fractions in relation to pituitary size were analyzed by the Kaplan-Meijer estimate procedure. The 1-, 2-, 3-, and 4-year estimated survival rates were 84% (95% confidence interval [CI], 76-89%), 76% (67-83%), 72% (62-79%), and 68% (55-77%), respectively. Treatment failures included procedure-related mortalities (12 dogs) and incomplete hypophysectomies (9 dogs). The 1-, 2-, 3-, and 4-year estimated relapse-free fractions were 88% (CI: 80-93%), 75% (64-83%), 66% (54-76%), and 58% (45-70%), respectively. Postoperative reduction of tear production (58 eyes in 47 dogs) was often reversible but remained low until death in 11 eyes of 10 dogs. Central diabetes insipidus (CDI) occurred more frequently (62%) in dogs with enlarged pituitaries than in dogs with nonenlarged pituitaries (44%). Survival and disease-free fractions after hypophysectomy were markedly higher in dogs with nonenlarged pituitaries than in dogs with enlarged pituitaries. Transsphenoidal hypophysectomy is an effective treatment for PDH in dogs. The survival and disease-free fractions after hypophysectomy decrease and the incidence of CDI increases with increasing pituitary size. Therefore, early diagnosis of PDH is important and transsphenoidal hypophysectomy is expected to have the best outcome when used as primary treatment for dogs with nonenlarged or moderately enlarged pituitaries.     

Response of cats to familiar and unfamiliar human contact using continuous direct arterial blood pressure measurement

Continuous direct measurement of feline arterial blood pressure (ABP) was carried out via a modified method with percutaneous, ultrasound guided catheterization of the common carotid artery. In 21 healthy, conscious cats the ABP was measured during rest, alertness and activity. Furthermore, the ABP response to being petted by familiar and unfamiliar persons was assessed.Linear mixed modelling revealed that the mean blood pressure (MBP) in resting cats (114.6 mmHg) was lower (P < 0.001) than in alert cats (122.7 mmHg), which was lower (P < 0.001) than that of active cats (136.8 mmHg). The MBP during petting by a familiar person (144.7 mmHg) tended to be higher (P = 0.065) than that during petting by an unfamiliar person (139.4 mmHg). The MBP of active cats was lower (P = 0.003) than MBP of cats petted by a familiar person, but not different from MBP of cats petted by an unfamiliar person. The MBP returned to resting values between 16 and 20 min after the familiar person had left, whereas resting values were reached between 11 and 15 min after the unfamiliar person had left. The complications of the described method were limited considering the potential risks of continuous direct ABP measurement.In conclusion, the described technique enables accurate measurement of feline ABP, which is influenced by the cat’s activity level and the familiarity of persons.     

Plasma aldosterone concentrations and plasma renin activity in healthy dogs and dogs with hyperadrenocorticism

The mean (se) basal plasma aldosterone concentrations were significantly lower in 31 dogs with pituitary-dependent hyperadrenocorticism (PDH) (75 [9] pmol/litre) than in 12 healthy dogs (118 [14] pmol/litre), whereas in five dogs with hyperadrenocorticism due to an adrenocortical tumour they were significantly higher (205 [109] pmol/litre). The mean basal renin activity was not significantly different between the dogs with PDH (303 [48] fmol/litre/second), the dogs with an adrenocortical tumour (141 [63] fmol/litre/second), and the control dogs (201 [25] fmol/litre/second). At three and four hours after the intravenous administration of 0.1 mg/kg dexamethasone, the concentrations of aldosterone decreased significantly to about 60 per cent of their initial values in the control dogs but did not change in the dogs with PDH or an adrenocortical tumour. In the dogs with PDH the renin activity increased significantly after the administration of dexamethasone.     

Pulsatile secretion pattern of vasopressin under basal conditions, after water deprivation, and during osmotic stimulation in dogs

Measurement of plasma osmolality (Posm) and plasma vasopressin (VP) concentration in response to hypertonicity is regarded as the gold standard for the assessment of VP release in polyuric conditions. Yet the interpretation of the VP curve as a function of Posm may be hampered by the occurrence of VP pulses. To determine whether VP is secreted in a pulsatile fashion in the dog and whether stimulation of VP release changes the secretion pattern of VP, we measured VP at 2-min intervals for 2 h under basal conditions, after 12 h of water deprivation, and during osmotic stimulation with hypertonic saline (20%) in eight healthy dogs. Vasopressin was secreted in a pulsatile fashion with a wide variation in number of VP pulses, VP pulse duration, and VP pulse amplitude and height. After water deprivation, total and basal VP secretion, the number of significant VP pulses, as well as the pulse characteristics did not differ from the basal situation. During osmotic stimulation, there was a large increase in both basal and pulsatile VP secretion, and the number of VP pulses and VP pulse height and amplitude were significantly increased. The VP pulse amplitude correlated significantly with the basal plasma VP concentration during osmotic stimulation. It is concluded that VP is secreted in a pulsatile manner in healthy dogs. The basal and pulsatile VP secretion increases during osmoreceptor-mediated stimulation. The VP pulses may occur to the magnitude that they may be interpreted as erratic bursts, when occurring in the hypertonic saline infusion test.     

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.     

Hyperadrenocorticism in a dog due to ectopic secretion of adrenocorticotropic hormone

Spontaneous hyperadrenocorticism in dogs is known to be the result of excessive secretion of adrenocorticotropic hormone (ACTH) by the pituitary gland or excessive autonomous glucocorticoid secretion by an adrenocortical tumor. Here, we report on an 8-year-old German shepherd dog in which ACTH-dependent hyperadrenocorticism was a result of ectopic ACTH secretion and could be related to an abdominal neuroendocrine tumor. Hyperadrenocorticism was diagnosed on the basis of the history, clinical signs, and elevated urinary corticoid/creatinine ratios (UCCRs; 236 and 350 x 10(-6); reference range < 10 x 10(-6)). The UCCR remained elevated (226 x 10(-6)) after three oral doses of dexamethasone (0.1 mg/kg body weight) at 8-h intervals. Ultrasonography revealed two equivalently enlarged adrenal glands, consistent with adrenocortical hyperplasia. Plasma ACTH concentration was clearly elevated (159 and 188 ng/l; reference range 5-85 ng/l). Computed tomography (CT) revealed that the pituitary was not enlarged. These findings were interpreted as indicating dexamethasone-resistant pituitary-dependent hyperadrenocorticism. Transsphenoidal hypophysectomy was performed but within 2 weeks after surgery, there was exacerbation of the clinical signs of hyperadrenocorticism. Plasma ACTH concentration (281 ng/l) and UCCRs (1518 and 2176 x 10(-6)) were even higher than before surgery. Histological examination of the pituitary gland revealed no neoplasia. Stimulation of the pituitary with corticotropin-releasing hormone did not affect plasma ACTH and cortisol concentrations. Treatment with trilostane was started and restored normocorticism. CT of the pituitary fossa, 10 months after hypophysectomy, revealed an empty sella. Hence, it was presumed that there was ectopic secretion of ACTH. CT of the abdomen revealed a mass in the region of the pancreas and a few nodules in the liver. Partial pancreatectomy with adjacent lymph node extirpation was performed and the liver nodules were biopsied. Histological examination revealed a metastasized neuroendocrine tumor. Abdominal surgery was not curative and medical treatment with trilostane was continued. At 18 months after the abdominal surgery, the dog is still in good condition. In conclusion, the combination of (1) severe dexamethasone-resistant hyperadrenocorticism with elevated circulating ACTH levels, (2) definitive demonstration of the absence of pituitary neoplasia, and (3) an abdominal neuroendocrine tumor allowed the diagnosis of ectopic ACTH secretion.     

Growth hormone excess and the effect of octreotide in cats with diabetes mellitus

In this prospective study 16 cats with diabetes mellitus were examined for concurrent acromegaly by measuring plasma growth hormone (GH) and insulin-like growth factor-I concentrations, and magnetic resonance imaging (MRI) of the pituitary fossa. Additionally, the effects of octreotide administration on the plasma concentrations of glucose, GH, α-melanocyte-stimulating hormone (α-MSH), adrenocorticotrophic hormone (ACTH), and cortisol were measured.Five cats were diagnosed with hypersomatotropism. The pituitary was enlarged in these 5 cats and in 2 other cats. Six cats that required a maximum lente insulin dosage ≥1.5 IU/kg body weight per injection had pituitary enlargement and 5 of these cats had acromegaly. Plasma concentrations of GH, ACTH, and cortisol decreased significantly after single intravenous administration of the somatostatin analogue octreotide in the acromegalic cats. The effect on GH concentrations was more pronounced in some of the acromegalic cats than in others. In the non-acromegalic cats only ACTH concentrations decreased significantly. In both groups plasma glucose concentrations increased slightly but significantly, whereas α-MSH concentrations were not significantly affected.In conclusion, the incidence of hypersomatotropism with concomitant pituitary enlargement appears to be high among diabetic cats with severe insulin resistance. Some of these cats responded to octreotide administration with a pronounced decrease in the plasma GH concentration, which suggests that octreotide administration could be used as a pre-entry test for treatment with somatostatin analogues.     

Acromegaly due to a somatroph adenoma in a dog

A 10-year-old uncastrated male Dalmatian dog was referred for gait abnormalities consisting of chronic progressive stiffness and rigidity. Other symptoms were polyphagia associated with weight gain, polyuria and polydipsia, excessive panting, and an inspiratory stridor. The owner had noticed progressive thickening of the skin and enlargement of the tongue over the last 3 years. Physical examination revealed thickening of the skin, redundant skin folds, and enlargement of the tongue. The only remarkable abnormalities found on routine laboratory examination were mild anaemia and an increased serum fructosamine concentration. Circulating concentrations of total thyroxine, free thyroxine, and cTSH, and the results of an ACTH stimulation test were all within reference ranges. The basal serum growth hormone (GH) concentration was markedly elevated (23microg/l) and did not decrease during a glucose tolerance test or after somatostatin administration. The serum insulin-like growth factor-1 concentration was also markedly elevated (1254microg/l). Basal serum insulin concentration was high (95mU/l) and insulin concentrations increased considerably after glucose loading, consistent with insulin resistance. Abdominal ultrasonography showed no abnormalities. Survey radiographs of the vertebral column showed severe spondylosis deformans extending from the cervical to the lumbosacral spine. CT scanning of the skull showed an enlarged pituitary gland with normal enhancement pattern. On post-mortem examination, the entire vertebral column appeared as a single and inflexible structure due to the presence of multiple fused osteophytes. The pituitary gland contained an acidophilic adenoma that immunostained positively for GH (and negatively for ACTH and alpha-MSH). In conclusion, this Dalmatian dog with acromegaly and insulin resistance represents the first case of GH hypersecretion proven to be due to a somatotroph adenoma.     

Aldosterone-to-renin and cortisol-to-adrenocorticotropic hormone ratios in healthy dogs and dogs with primary hypoadrenocorticism

In dogs with primary hypoadrenocorticism, hypocortisolism and hypoaldosteronism usually are present, but these deficiencies also may occur in isolated forms. The diagnosis is commonly made by measuring plasma cortisol concentration before and after stimulation with ACTH, thereby ignoring aldosterone. In search of an alternative approach that would include assessment of glucocorticoid and mineralocorticoid production, 2 pairs of endocrine variables were measured: (1) plasma concentration of cortisol and ACTH, and (2) plasma aldosterone concentration and plasma renin activity. In addition, the cortisol-to-ACTH ratio (CAR) and the aldosterone-to-renin ratio (ARR) were calculated. Reference intervals were established in a population of 60 healthy dogs. In these dogs, CAR ranged from 1.1 to 26.1 and ARR ranged from 0.1 to 1.5. The variables were compared with those of 22 dogs with spontaneous primary hypoadrenocorticism. Plasma concentration of cortisol and ACTH in both groups of dogs overlapped, whereas CAR did not. Similarly, plasma aldosterone concentration and plasma renin activity overlapped, whereas ARR did not. These observations indicate that measurement of these endogenous variables (in one blood sample) allows the specific diagnoses of primary hypocortisolism and primary hypoaldosteronism.