Investigations on the adrenocortical function of normal and obese dogs.
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17-Hydroxycorticosteroids↗
Biomedical subjects
A Rijnberk
Publications and source records attributed to A Rijnberk.
A nephrotic syndrome in the dog, treated with prednisone.
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Animals↗
Somatotroph and corticotroph pituitary adenoma (double adenoma) in a cat with diabetes mellitus and hyperadrenocorticism.
A 9-year-old castrated male European shorthair cat with insulin-resistant diabetes was referred with the preliminary diagnosis of pituitary-dependent hyperadrenocorticism, based on measurements of urinary corticoids. Further studies revealed not only resistance of plasma concentrations of cortisol, adrenocorticotropic hormone (ACTH) and alpha-melanocyte-stimulating hormone (alpha-MSH) to suppression by a low dose of dexamethasone, but also elevated plasma concentrations of growth hormone (GH) and insulin-like growth factor I (IGF-I). Pituitary imaging with dynamic contrast-enhanced computed tomography demonstrated an enlarged pituitary gland and an adenoma. The cat underwent trans-sphenoidal hypophysectomy after which the insulin resistance disappeared. On histopathological and immunocytochemical examination of the surgical specimen a double adenoma was found, consisting of a corticotroph adenoma and a somatotroph adenoma separated by unaffected pituitary tissue.
Adenoma↗
Congenital defect in iodothyronine synthesis. Clinical aspects of iodine metabolism in goats with congenital goitre and hypothyroidism.
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Animals↗
Transsphenoidal hypophysectomy for treatment of pituitary-dependent hyperadrenocorticism in 7 cats.
OBJECTIVE: Evaluation of microsurgical transsphenoidal hypophysectomy for the treatment of pituitary-dependent hyperadrenocorticism (PDH) in cats. STUDY DESIGN: Prospective clinical study. ANIMALS OR SAMPLE POPULATION: Seven cats with PDH. METHODS: Urinary cortisol/creatinine ratios, pituitary-adrenocortical function tests, and computed tomography (CT) were performed on 7 cats that presented with a provisional diagnosis of hyperadrenocorticism. All cats underwent microsurgical transsphenoidal hypophysectomy with histologic examination of the excised specimen. Follow-up consisted of clinical evaluation, repeat adrenocortical function testing, and CT. RESULTS: Four cats had concurrent diabetes mellitus. In all cats, the urinary cortisol/creatinine (C/C) ratios were elevated. The dexamethasone screening test showed that 2 cats did not meet the criterion for hyperadrenocorticism. The response of the cats' plasma concentrations of cortisol and adrenocorticotrophic hormone to a high dose of dexamethasone varied from very sensitive to completely dexamethasone resistant. Basal plasma alpha-melanocyte-stimulating hormone concentrations were elevated in 2 cats with a pars intermedia adenoma and in 3 cats with an adenoma that originated from the anterior lobe. Preoperative CT enabled accurate assessment of pituitary size (5 nonenlarged pituitaries with a height <4 mm and 2 enlarged pituitaries with a height >5 mm) and localization relative to intraoperative anatomic landmarks. Two cats died within 4 weeks after surgery of a nonrelated disease. In the remaining 5 cats, the hyperadrenocorticism went into both clinical and biochemical remission. Hyperadrenocorticism recurred in 1 cat after 19 months, but no other therapy was given and the cat died at home 28 months after surgery. CT evaluation of this cat had identified pituitary remnants 6 weeks after surgery. The main postoperative complications were oronasal fistula (1 cat), complete dehiscence of the soft palate (1 cat), and transient reduction of tear production (1 cat). One cat died at 6 months (undefined anemia), and another cat at 8 months (recurrent nose and middle ear infection secondary to soft palate dehiscence) after surgery. In the surviving 2 cats, the remission periods at the time of writing were 46 and 15 months. In the 2 cats with sufficient follow-up time, the concurrent diabetes mellitus disappeared, ie, insulin treatment could be discontinued at 4 weeks and 5 months after hypophysectomy. In all 7 cats, the histologic diagnosis was pituitary adenoma. CONCLUSIONS: Microsurgical transsphenoidal hypophysectomy is an effective method of treatment for feline PDH in specialized veterinary institutions having access to advanced pituitary imaging techniques. Concurrent diabetes mellitus is usually reversible after hypophysectomy. Thorough presurgical screening for coexisting diseases is imperative. CLINICAL RELEVANCE: PDH in cats can be effectively treated by hypophysectomy. The neurosurgeon performing hypophysectomy must master a learning curve and must be familiar with the most frequent complications of the operation to treat them immediately and effectively. Urinary C/C ratios are sensitive indicators for the assessment of remission and recurrence of hyperadrenocorticism.
Adenocarcinoma↗
Results of transsphenoidal hypophysectomy in 52 dogs with pituitary-dependent hyperadrenocorticism.
OBJECTIVE: To evaluate microsurgical transsphenoidal hypophysectomy in dogs with pituitary-dependent hyperadrenocorticism (PDH). STUDY DESIGN: Prospective study to evaluate the results (survival and disease-free interval, remission, recurrence) and complications of microsurgical transsphenoidal hypophysectomy by clinical follow-up, computed tomography (CT), and urinary corticoid-to-creatinine (C/C) ratios in dogs with PDH. The effect of surgical experience was investigated by comparing results of hypophysectomy cases 1 through 26 and 27 through 52. ANIMALS OR SAMPLE POPULATION: 52 dogs with PDH. RESULTS: Preoperative CT enabled accurate assessment of pituitary size (24 nonenlarged and 28 enlarged) and localization relative to intraoperative anatomic landmarks. Treatment failures included procedure-related mortalities (five dogs) and incomplete hypophysectomies (four dogs). The 1-year estimated survival rate was 84% (95% confidence interval [CI], 71% to 92%). The 2-year estimated survival rate was 80% (95% CI, 65% to 90%). In 43 dogs, the hyperadrenocorticism went into remission. Hyperadrenocorticism recurred in five dogs. The 1-year estimated relapse-free fraction was 92% (95% CI, 76% to 97%). The main complications were transient, mild, postoperative hypernatremia; transient reduction or cessation of tear production (25 eyes in 18 dogs); permanent (five dogs) or prolonged (nine dogs) diabetes insipidus; and secondary hypothyroidism. Normal tear production had resumed in all but one case after a median period of 10 weeks. In the second case series (27 through 52), the hospitalization period was shorter, the number of dry eyes fewer, the survival fraction greater, and the postoperative mortality lower than in the first series. In 15 dogs in which remission was obtained, postoperative CT images suggested the presence of small pituitary remnants; in 1 of these, hyperadrenocorticism recurred. In 46 dogs, the histological diagnosis was pituitary adenoma. CONCLUSIONS: Microsurgical transsphenoidal hypophysectomy in dogs with PDH is an effective method of treatment in specialized veterinary institutions having access to advanced pituitary imaging techniques. Postoperative CT findings do not correlate well with remission or subsequent recurrence of hyperadrenocorticism. CLINICAL RELEVANCE: The neurosurgeon performing hypophysectomies must master a learning curve and must be familiar with the most frequent complications of the operation to recognize them as early as possible and to treat them immediately and effectively. Urinary C/C ratios are sensitive indicators for the assessment of remission and recurrence of hyperadrenocorticism.
Adrenocortical Hyperfunction↗
Quantitative aspects of thyroid scintigraphy with pertechnetate (99mTcO4-) in cats.
Thyroidal 99mTcO4- (pertechnetate) uptake percentages were determined in unanesthetized euthyroid (n = 13) and hyperthyroid (n = 18) cats. Maximal uptakes were observed 60 minutes after IV injection of the radionuclide and ranged from 0.3 to 3.9% of the dose in euthyroid cats (median 2.23%) and from 5.2% to 23.9% of the dose in hyperthyroid cats (median 14.8%) (P < .05). There were no overlaps in pertechnetate uptake percentages during any of the intervals evaluated. It is concluded that the optimal time for visualization of the thyroid by 99mTcO4(-)-scanning is 60 minutes after IV injection of the radionuclide. Calculation of the percentage uptake is of additional diagnostic value.
Animals↗
Central diabetes insipidus in a dog with a pro-opiomelanocortin-producing pituitary tumor not causing hyperadrenocorticism.
Central diabetes insipidus was diagnosed by vasopressin measurements during hypertonic stimulation in a 9-year-old male giant Schnauzer with polyuria and polydipsia. The impaired release of vasopressin was believed to be caused by a large pituitary tumor, which was visualized by computed tomography. Studies of the function of the anterior lobe and the pars intermedia of the pituitary gland were conducted, and high concentrations of ACTH and alpha-melanotrophic hormone (alpha-MSH) were found without concomitant hyperadrenocorticism. Studies of the molecular size of the immunoreactive ACTH in plasma by gel filtration revealed that most of the circulating immunoreactivity was not ACTH but its precursor pro-opiomelanocortin (POMC) and low-molecular-weight POMC-derived peptides. The pituitary tumor of this dog probably originated from melanotrophic cells of the pars intermedia. The sensitivity of the pituitary-adrenocortical system for the suppressive effect of dexamethasone was unaffected.
Adrenocortical Hyperfunction↗
Intra- and interindividual variation in urine osmolality and urine specific gravity in healthy pet dogs of various ages.
Urine specific gravity (Usg) and urine osmolality (Uosm) are used routinely to assess renal concentrating ability, but limited data on these variables are available for healthy dogs. Consequently, we studied the intra- and interindividual variations in Usg and Uosm in healthy dogs as well as the influence of age and gender on these variables. Dogs were selected for health and anestrus in female dogs through the use of a detailed questionnaire. Eighty-nine owners collected morning and evening urine samples from their dogs on 2 consecutive days. In 8 dogs in which the Uosm of different samples varied more than 50%, owners collected urine for 24 hours at 2-hour intervals during the day and at 4-hour intervals at night. The possible effect of changes in adrenocortical function with age was assessed by measurements of urinary corticoid/creatinine (C/C) ratios. Among all samples, Uosm ranged from 161 to 2,830 mOsm/kg and Usg from 1.006 to > 1.050. In the morning, Uosm (1,541 +/- 527 mOsm/kg, range 273-2,620 mOsm/kg) and Usg (1.035 +/- 0.010, range 1.009-->1.050) were higher than in the evening (Uosm 1,400 +/- 586 mOsm/kg, range 161-2,830 mOsm/kg; Usg 1.031 +/- 0.012, range 1.006-->1.050). The interindividual coefficient of variation in Uosm was 34.2% for morning urine samples and 41.9% for evening samples. In 8 dogs with large differences in urine concentration, there were 2- to 3-fold increases or decreases in Uosm during the day, and the intraindividual coefficient of variation was 33.0%. There was no relation between gender and urine concentration. Urine concentration in both the morning and evening samples decreased with age. Urinary corticoid/ creatinine ratios did not change with age. It can be concluded that Uosm and Usg vary widely among healthy dogs. Urine concentration is generally lower in the evening than in the morning and is not related to gender. Urine concentration decreases with age, and this cannot be ascribed to an associated increase in endogenous corticoids. In some dogs, Uosm varies widely during the day, with an intraindividual coefficient of variation approaching the interindividual coefficient of variation. This may be regarded as a biologic variation but also could represent an early undiagnosed clinical abnormality.
Adrenal Cortex Hormones↗
Influence of veterinary care on the urinary corticoid:creatinine ratio in dogs.
Physical and emotional stresses are known to increase the production and secretion of glucocorticoids by the adrenal cortex in both humans and experimental animals. The urinary corticoid: creatinine (C:C) ratio is increasingly used as a measure of adrenocortical function. In this study we investigated whether a visit to a veterinary practice for vaccination, a visit to a referral clinic for orthopedic examination, or hospitalization in a referral clinic for 1.5 days resulted in increases of the urinary C:C ratio in pet dogs. In experiment 1, owners collected voided urine samples from 19 healthy pet dogs at specified times before and after taking the dogs to a veterinary practice for yearly vaccination. In experiment 2, 12 pet dogs were evaluated in a similar way before and after an orthopedic examination at a referral clinic. In experiment 3, 9 healthy pet dogs were hospitalized for 1.5 days and urine samples were collected before, during, and after this stay. Basal urinary C:C ratios in all experiments ranged from 0.8 to 8.3 x 10(-6). In experiment 1, the urinary C:C ratio after the visit to the veterinary practice ranged from 0.9 to 22.0 x 10(-6). Six dogs had a significantly increased urinary C:C ratio (responders), but in 5 of these dogs the ratio was < or = 10 x 10(-6). In experiment 2, 8 of 12 dogs responded significantly with urinary C:C ratios ranging from 3.1 to 27.0 x 10(-6). In experiment 3, 8 of 9 dogs had significantly increased urinary C:C ratios, ranging from 2.4 to 24.0 x 10(-6), in some or all urine samples collected during hospitalization. In 4 dogs urinary C:C ratios 12 hours after hospitalization were still significantly higher than the initial values. Thus, a visit to a veterinary practice, an orthopedic examination in a referral clinic, and hospitalization can be considered stressful conditions for dogs. A large variation occurs in response, and in individual dogs the increases in urinary C:C ratios can exceed the cutoff level for the diagnosis of hyperadrenocorticism. Therefore, urine samples for measurement of the C:C ratio in the diagnosis of hyperadrenocorticism should be collected in the dog's home environment, to avoid the influence of stress on glucocorticoid secretion.
Age Factors↗
Disturbed vasopressin release in 4 dogs with so-called primary polydipsia.
Primary polydipsia is characterized by a marked increase in water intake and secondary polyuria, and in dogs often is described as a behavioral problem or a psychological disorder. We describe 4 dogs with primary polydipsia, diagnosed on the basis of a modified water deprivation test, in which further examination included serial measurements of urine osmolality (UOsm) and plasma vasopressin (VP) measurements during water deprivation and hypertonic saline infusion. The dogs, ranging in age from 4 months to 4 years, all were presented for evaluation of polyuria and polydipsia. Physical examination, routine blood chemistry, and urinalysis disclosed no specific cause for the polyuria and polydipsia. During serial measurements UOsm spontaneously reached high concentrations in 2 dogs, whereas in the other 2 dogs UOsm also fluctuated but on no occasion exceeded 1,000 mosm/kg. Primary polydipsia was diagnosed when UOsm exceeded 1,000 mosm/kg at the end of the modified water deprivation test and plasma osmolality did not exceed the upper limit of the reference range during testing. During water deprivation, plasma VP concentrations remained relatively low. The VP response to hypertonic saline infusion was abnormal, with an increased threshold value in 3 dogs, an increased sensitivity in 2 dogs, and an exaggerated response in 1 dog. It is concluded that some dogs fulfilling current criteria for primary polydipsia produce concentrated urine spontaneously throughout the day in a pattern similar to what has been observed in healthy pet dogs. This finding can be regarded as diagnostic and precludes the need for a water deprivation test. During water deprivation testing, all 4 dogs produced highly concentrated urine in the face of low basal plasma VP concentrations. The observed abnormal VP release in response to hypertonic stimulation may be interpreted as a primary disturbance in the regulation of VP secretion, although it might also be the result of overhydration caused by a primary abnormality in drinking behavior.
Animals↗
Anterior pituitary function in female dogs with spontaneous mammary tumors: I. Growth hormone.
It has been hypothesized that growth hormone (GH) plays a major role in the pathogenesis of canine mammary tumor disease. In order to test this hypothesis, plasma GH levels were measured at rest and during dynamic function tests in dogs with benign or malignant proliferative mammary lesions and in control dogs. Both in control dogs and in dogs with benign disease, basal GH levels were found to be elevated during both metestrus and progestin treatment, as compared to anestrus. Dogs with benign or malignant disease did not have higher basal GH levels than control dogs matched for the effect of endogenous or exogenous progestin exposure. The GH response to glucose or thyrotropin releasing hormone (TRH) did not vary significantly with progestin exposure, nor between the 3 groups of animals. The stimulatory effect of clonidine upon GH secretion was reduced in dogs with benign or malignant disease as compared to controls matched for the effect of progestin exposure. These findings indicate that mammary tumor disease in the dog is associated with a disturbance in the regulation of GH release.
Animals↗
Diurnal rhythms of plasma corticosterone concentrations in racing pigeons (Columba livia domestica) exposed to different light regimens, and the influence of frequent blood sampling.
The effects of two different light regimens and the frequency of blood sampling on the diurnal plasma corticosterone concentrations in racing pigeons (Columba livia domestica) were investigated. The daily light regimens tested were a period of light during the day (DL; lights on 0515-2215) and shifting of the light period by 12 hours (SL; lights on 1715-1015). In the first experiment, the influence of the frequency of blood sampling was investigated by comparing plasma corticosterone concentrations at 28-hr intervals for several days and at 4-hr intervals during one day. Sampling at 4-hr intervals resulted in significantly higher corticosterone concentrations in plasma than sampling at 28-hr intervals. Within both groups, the plasma corticosterone concentrations at the first and last sampling times did not differ significantly. Concentrations of plasma corticosterone were always highest during the dark period, and the corticosterone rhythm in the SL experiment was strictly in phase with the altered light/dark schedule.
Animals↗
Sensitivity of the hypothalamic-pituitary-adrenal system of pigeons (Columba livia domestica) to suppression by dexamethasone, cortisol, and prednisolone.
The sensitivity of the hypothalamic-pituitary-adrenal system in pigeons (Columba livia domestica) to glucocorticoid feedback was studied after single intravenous administration of dexamethasone (500, 100, 50, 10, 5, 1, 0.5, and 0.1 micrograms/kg), cortisol (15,000, 3000, 1500, 300, 150, 30, 15, and 3 micrograms/kg), and prednisolone (3500, 700, 350, 70, 35, 7, 3.5, 0.7, and 0.35 micrograms/kg). Dose responses, the threshold doses, and the onset of maximum suppression were determined by measuring plasma corticosterone concentrations around the expected peak of plasma corticosterone in pigeons kept on a shifted-light regimen. At 52 hr following the highest dose of dexamethasone, and at 48 hr following the highest doses of cortisol and prednisolone, plasma corticosterone concentrations were similar to the initial values and to the control values. Following the minimum doses that resulted in suppression of the normal diurnal variation in plasma corticosterone concentration (0.5 microgram dexamethasone/kg, 15 micrograms cortisol/kg, and 0.7 microgram prednisolone/kg), plasma corticosterone concentrations were similar to values of the control group and to initial values within 24 hr. The onset of suppression of plasma corticosterone concentrations was between 30 and 60 min following 1 microgram dexamethasone/kg, 7 micrograms prednisolone/kg, or 30 micrograms cortisol/kg. Suppression was greatest at 60 min following prednisolone and cortisol administration, and at 90 min following dexamethasone administration. It is concluded that the hypothalamic-pituitary-adrenal system of pigeons reacts to exogenous glucocorticoids by early delayed feedback, is more sensitive to suppression by glucocorticoids than that of mammals, and is suppressed for the longest time by dexamethasone. These observations indicate that some of the side effects of glucocorticoid therapy are likely to be at least as frequent and as severe in birds as in mammals.
Animals↗