Pituitary-dependent Hyperadrenocorticism Research Articles

Transsphenoidal hypophysectomy for treatment of pituitary-dependent hyperadrenocorticism in 7 cats.

Evaluation of microsurgical transsphenoidal hypophysectomy for the treatment of pituitary-dependent hyperadrenocorticism (PDH) in cats. Prospective clinical study. Seven cats with PDH. 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. 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. 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. 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.

Evaluation of Pituitary-Dependent Hyperadrenocorticism Response to Mitotane Treatment in Dogs. Length of Initial Phase of Treatment in Relation to the Initial Value of Urine Cortisol/Creatinine Ratio

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Ectopic ACTH syndrome: Molecular bases and clinical heterogeneity

There are roughly two types of ectopic ACTH syndrome (EAS). one associated with overt malignancies and one with occult neoplasms. The prototype of the first condition is Cushing's syndrome sustained by small-cell lung cancer (SCLC), while bronchial carcinoid tumors are the most common occult sources of ACTH. Patients with EAS and SCLC may have an atypical presentation with muscle wasting and weight loss that are more frequently observed than the classic cushingoid features. These patients have a poor prognosis because SCLC associated with the EAS is more resistant to chemotherapy and the severe hypercortisolism is responsible for a high rate of life-threatening complications during treatment. Conversely, the clinical and biochemical features of the EAS associated with carcinoid may overlap those seen in pituitary-dependent Cushing's syndrome. An extensive radiological and hormonal work-up is necessary to detect the extrapituitary source of ACTH. However, the differentiation between the pituitary, or eutopic, from the non-pituitary, or ectopic, source of ACTH secretion may be extremely difficult in some cases despite the wide diagnostic armamentarium available. Molecular biology studies have demonstrated that the carcinoid cells achieve a process of corticotroph differentiation being able to express the proopiomelanocortin (POMC) gene and to process POMC correctly to release large amounts of intact ACTH. Conversely, SCLC processes POMC in an aberrant way releasing high concentrations of ACTH precursors and less intact ACTH in the circulation.

コルチコトロピン放出ホルモン刺激試験により下垂体依存性副腎皮質機能亢進症と診断した犬の1例

コルチコトロピン放出ホルモン刺激試験により下垂体依存性副腎皮質機能亢進症と診断した犬の1例

Prevalence of pituitary tumors among diabetic cats with insulin resistance.

To determine prevalence of pituitary tumors, detectable by means of computed tomography or magnetic resonance imaging, in cats with insulin resistance suspected to have acromegaly or hyperadrenocorticism versus cats with well-controlled diabetes mellitus. Case series. 16 cats with insulin resistance that were also suspected to have acromegaly (n = 12) or pituitary-dependent hyperadrenocorticism (4) and 8 cats with well-controlled diabetes mellitus. Computed tomography was performed on all 16 cats with insulin resistance and 2 cats in which diabetes mellitus was well-controlled. The remaining 6 cats in which diabetes mellitus was well-controlled underwent magnetic resonance imaging. Images were obtained before and immediately after i.v. administration of contrast medium. Computed tomography revealed a mass in the region of the pituitary gland in all 16 cats with insulin resistance. Maximum width of the masses ranged from 4.4 to 12.7 mm; maximum height ranged from 3.1 to 12.6 mm. Results of computed tomography performed on 2 cats with well-controlled diabetes and magnetic resonance imaging performed on the remaining 6 cats were considered normal. Results suggest that cats with insulin resistance suspected to have acromegaly or pituitary-dependent hyperadrenocorticism are likely to have a pituitary mass detectable by means of computed tomography or magnetic resonance imaging.

Frequency of Pulmonary Mineralization and Hypoxemia in 21 Dogs with Pituitary‐Dependent Hyperadrenocorticism

The purpose of this study was to determine the frequency of hypoxemia and pulmonary mineralization using99mTc‐methylene diphosphonate (99mTc‐MDP) in dogs with pituitary‐dependent hyperadrenocorticism (PDH). Twenty‐one dogs with PDH were pro‐spectively evaluated using thoracic radiography, arterial blood gas analysis, and bone phase and pulmonary perfusion scintigraphy (using99mTc‐macro‐aggregated albumin [99mTc‐MAA]). The radiographs and bone and perfusion studies were evaluated subjectively. An averaged quantitative count density ratio was calculated between the thorax and cranial thoraco‐lumbar vertebrae from lateral thoracic99mTc‐MDP images. Thoracic: vertebral ratios were calculated using99mTc‐MDP studies from 21 control dogs. The thoracic: vertebral ratios were compared between the 2 groups (PDH and control). The mean age (±SD) of the 21 PDH dogs was 10.2 (±3) years, whereas the mean age of the control group was 9.8 (±3) years. Seven of the 21 dogs with PDH were hypoxemic (denned as an arterial partial pressure of oxygen [PaO2] &lt;80 mm Hg) with an average PaO2(±SD) of 62 (±15) mm Hg. Of the 7 hypoxemic dogs, 2 were found to have pulmonary mineralization based on bone scintigraphic images. Pulmonary perfusion abnormalities were not identified using99mTc‐MAA in any of the 21 PDH dogs. Six PDH dogs had an abnormal interstitial pulmonary pattern and 5 of these dogs were hypoxemic. The average quantitative thoracic: vertebral ratio was not significantly different between the PDH and control dogs (0.5 ± 0.4 versus 0.4 ± 0.1,P= .16). Causes of hypoxemia other than pulmonary thromboembolism should be considered in dogs with PDH. Pulmonary mineralization may contribute to hypoxemia in dogs with PDH.

Assessment of cortisol and ACTH responses to the desmopressin test in patients with Cushing's syndrome and simple obesity.

The desmopressin test has recently been introduced in clinical practice as an adjunctive tool in the differential diagnosis of ACTH-dependent Cushing's syndrome (CS). It has been reported that the majority of patients with pituitary-dependent CS (Cushing's disease, CD) respond to desmopressin, while no such response is usually observed in other forms of this syndrome. In the present study, the responsiveness of the HPA axis to desmopressin was studied in a group of obese subjects. In addition, the ability of desmopressin administration to differentiate between patients with obesity and the various forms of Cushing's syndrome was investigated. Cortisol and ACTH responses to the administration of desmopressin (10 microg bolus i.v.) were examined in 20 consecutive patients with obesity (14 women and six men; BMI range: 34.5-66.7 kg/m2). Obese subjects had no clinical stigmata of CS. In all obese patients, either an overnight (dex 1 mg at 2300 h) (n = 8) or a formal low-dose (dex 0.5 mg 6-hourly for 2 days) (n = 12) dexamethasone suppression test was performed for the exclusion of Cushing's syndrome. Three of eight subjects showed failure of cortisol suppression (i.e. F > 28 nmol/l) to the overnight dexamethasone suppression test, but they had undetectable cortisol levels (< 28 nmol/l) on further testing with the formal 2-day test. All but two of the remaining subjects had undetectable cortisol levels (< 28 nmol/l) following the formal 2-day, low-dose, dexamethasone suppression test. For comparison, desmopressin responses were also tested in 33 patients with CS of varied aetiologies (25 patients with pituitary-dependent CS, three patients with occult ectopic ACTH secretion and five patients with primary adrenal CS). A positive response was considered to be an increment greater than 20% and 50% from baseline levels of cortisol and ACTH, respectively. Mean cortisol (F) and ACTH levels did not differ from the baseline at any time point following desmopressin administration in the obese group (basal F: 417 +/- 41, peak F: 389 +/- 32 nmol/l, P > 0.05; basal ACTH: 33.5 +/- 4.3, peak ACTH: 50.6 +/- 16.6 ng/l, P > 0.05), or in patients with occult ectopic or primary adrenal CS. In contrast, in the group of patients with CD, there was a significant rise in the mean ACTH and F levels from baseline (basal F: 725 +/- 50, peak F: 1010 +/- 64 nmol/l, P < 0.01; basal ACTH: 88.6 +/- 11.8, peak ACTH: 351 +/- 64 ng/l, P < 0.01). Cortisol responses greater than 20% from baseline were observed in 21/25 (84%) patients with CD, but in only 3/20 (15%) of the obese patients. With regard to ACTH, increments greater than 50% over baseline were observed in 23/25 (92%) of patients with CD, and in only 3/20 (15%) of the obese patients. As previously reported, none of the patients with occult ectopic ACTH secretion or primary adrenal CS had a positive response. The prevalence of subjects who met the criteria adopted to define positive cortisol and ACTH responses to the desmopressin test was significantly higher in the group of patients with Cushing's disease than in the group of patients with obesity. It is therefore suggested that this test may be occasionally useful in the differentiation between simple obesity and the pituitary-dependent form (but not other forms) of Cushing's syndrome.

Daily blood pressure profile in Cushing's syndrome before and after surgery.

No significant difference has been demonstrated in the altered circadian blood pressure pattern between the pituitary-dependent and adrenal forms of Cushing's syndrome before surgery. The effect of therapy, however, proved to be different. The mesor was normalized in the pituitary-dependent Cushing's syndrome more conspicuously for systolic than for diastolic blood pressure. In Cushing's syndrome due to adrenal adenoma, systolic and diastolic blood pressure mesors have been even significantly "overnormalized" after treatment, being 11 to 27 and 2 to 13 mmHg (95% confidence) lower than corresponding mesors in controls. There was no difference between forms in the effect of treatment on blood pressure amplitudes, which remained significantly lower than in controls. Finally, acrophase patterns were partly normalized after treatment of the pituitary-dependent form only for diastolic blood pressure, while both systolic and diastolic blood pressure acrophases were normalized in the treated adrenal form. In conclusion, complete normalization of the pattern of daily blood pressure profile has not been achieved in either form of the syndrome. This may be one of the reasons for the reduced long-term survival after surgical cure of hypercortisolism, than expected.

Increased pressor response to noradrenaline in pituitary dependent Cushing's syndrome.

The mechanism of hypertension in Cushing's syndrome remains undetermined. Some studies have demonstrated an increased sensitivity to pressor agents but it is not clear if patients with Cushing's syndrome of different aetiologies demonstrate this finding. We have examined pressor sensitivity in a group of patients with Cushing's disease (pituitary dependent hypercortisolism) by measuring blood pressure during incrementally increasing infusions of noradrenaline. Eight subjects (7 female, 1 male), aged 42.2 +/- 4.5 years (mean +/- SEM) with Cushing's disease were studied. Eight age- and sex-matched control subjects were also studied. Four of the eight controls and five patients with Cushing's disease had elevated blood pressure. All medication for this had been stopped at least seven days prior to the study. After subjects ate a light breakfast, ECG leads and a sphygmomanometer were attached, an intravenous cannula was inserted and all subjects then rested quietly for 60 minutes. Noradrenaline was then infused intravenously for 10-minute periods at concentrations of 0.01, 0.03, 0.07, 0.11 and 0.18 microg/kg/minute. On the day of the study the baseline blood pressures and pulse rates in the patients with Cushing's disease (blood pressure; 138/87 +/- 6/3 mmHg, pulse 76.5 +/- 4.8 beats/minute) and controls (blood pressure; 126/86 +/- 6/6 mmHg, pulse 71.2 +/- 3.7 beats/minute) were not significantly different. The mean change in diastolic blood pressure from baseline at the time of the peak increase or when the test was stopped was 21. 5 +/- 4.7 mmHg in Cushing's disease compared to 7.0 +/- 2.5 mmHg in controls (P = 0.03). The mean change in mean arterial pressure from baseline at the time of the peak increase or when the test was stopped was 22.0 +/- 4.0 mmHg in Cushing's disease compared to 13.0 +/- 2.4 mmHg in controls (P = 0.03). No significant difference in mean change of systolic pressure (26.0 +/- 4.6 vs. 25 +/- 4.0 mmHg) or pulse rates (- 11.1 +/- 1.8 vs. - 4.7 +/- 2.6) was seen in the group with Cushing's disease as compared to the control group. We conclude that patients with pituitary-dependent Cushing's syndrome have enhanced pressor diastolic and mean arterial responses to noradrenaline and this may be an important underlying mechanism for the hypertension seen in this particular group of Cushing's syndrome patients.

The Efficacy of L‐Deprenyl in Dogs with Pituitary‐Dependent Hyperadrenocorticism

Ten dogs with pituitary‐dependent hyperadrenocorticism (PDH) received 2 mg/kg of L‐Deprenyl once daily for 6 months. Monthly patient assessment consisted of evaluation of the owner's daily observation protocol, a standardized owner questionnaire, physical examination, CBC, biochemical profile, determination of the urine cortisol/creatinine ratio (UC/C), low‐dose dexamethasone suppression (LDDS) test, corticotropin releasing hormone (CRH) test, and adrenal ultrasonography. At the beginning and the end of the study, an adrenocorticotropic hormone (ACTH) stimulation test and computed tomography also were performed. Two dogs developed neurologic signs and 2 dogs developed acute pancreatitis. An increase in activity, decrease in polyphagia, and decrease in panting were reported by 6, 4, and 2 owners, respectively. Seven owners believed that water intake decreased, but this was confirmed in only 3 dogs. Water intake increased in 2 dogs and remained unchanged in 5 dogs. The condition of the hair coat and skin improved in 2 dogs, worsened in 3, and remained unchanged in 5. Urine specific gravity, urine osmolality, ACTH test results, UC/C, and adrenal gland size did not change significantly throughout the study. In 4 of 8 dogs, LDDS was abnormal at the start of the study but normal at the end of the study, and in 2 dogs, the opposite occurred. Marked individual variation was noted in the CRH test, with a tendency for smaller increases in ACTH toward the end of the study. A marked increase in hypophyseal tumor size occured in 4 dogs. Treatment with L‐Deprenyl resulted in improvement, deterioration, and stagnation of clinical signs in 2, 4, and 4 dogs, respectively. The results of this study indicate that L‐Deprenyl cannot be recommended as the sole treatment for canine PDH.

Dynamic adrenal function testing in eight dogs with hyperadrenocorticism associated with adrenocortical neoplasia

The results of adrenocorticotropin (ACTH) stimulation and low-dose dexamethasone suppression tests (LDDST) were evaluated retrospectively in eight dogs with clinical signs of hyperadrenocorticism arising from functional adrenocortical tumours, and compared...

Results of non-selective adrenocorticolysis by O,p'-DDD in 129 dogs with pituitary-dependent hyperadrenocorticism

One hundred and twenty-nine dogs with pituitary-dependent hyperadrenocorticism were treated according to a protocol aimed at the complete destruction of the adrenal cortices by the administration of O,p'-DDD (mitotane) at...

The modulation of glucocorticoid receptor content by 3-O-methyl-D-glucose transport in human mononuclear leukocyte in obesity.

Glucocorticoid receptors (GR) and 3-O-methyl-D glucose (3-O-MG) transport were determined in mononuclear leukocytes (MNL) from 11 abdominal obese subjects, 10 pituitary-dependent Cushing's syndrome (Cushing's disease) and 10 healthy controls. Using a whole-cell competitive binding assay and 3H-dexamethasone as tracer, MNL of abdominal obese subjects were found to have 4855 +/- 1389 sites/cell which was significantly lower (p < 0.05) than controls (6234 +/- 1568 sites/cell), although no significant difference was found in the mean serum cortisol level. Their mean Kd (affinity) was also significantly lower than that found in the healthy controls (obese Kd:2.92 +/- 0.84 nmol/l, control Kd: 4.55 +/- 0.67 nM, p < 0.05). On the other hand, the receptor characteristics in Cushing's disease patients were within the normal range. At the same time, 3-O-MG transport was determined in the same subjects. In Cushing's disease, 3-O-MG transport was within the normal range, whereas in abdominal obesity this value was significantly lower than the healthy controls (abdominal obese: 31.90 +/- 8.20; control: 46.26 +/- 12.91 fmol/10(6) cell, min, p < 0.05). We also found a positive correlation between 3-O-MG transport and GR binding capacity in abdominal subjects (r = 0.89, p < 0.001), however we did not find such a correlation in Cushing's disease (r = 0.60, p > 0.05). These results indicated that, in abdominal obesity, the GR binding capacity in MNL is influenced by the changes in glucose transport.

Pharmacokinetics of exogenous corticotropin in normal dogs, hospitalized dogs with non adrenal illness and adrenopathic dogs.

Corticotropin (ACTH) pharmacokinetics was assessed in 10 normal dogs receiving exogenous ACTH (0.5 U/kg, i.v.). A two-compartment open model was most appropriate for description of exogenous ACTH pharmacokinetics. The apparent distribution and elimination rate constants (alpha and beta) were 7.4 +/- 2.7 x 10(-2) min(-1) and 5.5 +/- 3.8 x 10(-3) min(-1), respectively. Area under the concentration-time curve (AUC) was 2.91 +/- 0.78 x 10(4) pg x min/mL, mean residence time (MRT) was 45.0 +/- 12.2 min, the distribution half-life (t1/2alpha) was 9.4 min (harmonic mean), and the elimination half-life (t1/2beta) was 128 min (harmonic mean). The total body clearance of ACTH (ClB) was 1.83 +/- 0.46 x 10(4) mL x min/kg and volume of distribution (Vd(area)) was 30 +/- 15 L/kg. Corticotropin pharmacokinetics was also assessed in 12 client owned dogs, six dogs with non adrenal illness (NAI) and six dogs with hyperadrenocorticism (HAC), receiving exogenous ACTH (0.5 U/kg, i.v.). For these patients, data was best fitted to a one-compartment open model. In dogs with NAI, the AUC was 6.23 +/- 0.62 x 10(5) pg x min/mL, MRT was 38.7 +/- 12 min, the apparent elimination rate constant (k(el)) was 0.26 +/- 0.0017 min(-1) elimination half-life was 26.7 min, ClB was 0.84 +/- 0.1 x 10(4) mL/min/kg, and Vd(area) was 31.9 +/- 5.7 L/kg. In dogs with HAC, AUC was 4.74 +/- 0.23 x 10(5) pg x min/mL, MRT was 20.4 min, k(el) was 0.034 +/- 0.009 min(-1), half-life was 20.4 min, CIB was 1.06 +/- 6.0 x 10(4) mL/min/kg and Vd(area) was 29.7 +/- 6.7 L/kg. Dogs with pituitary-dependent hyperadrenocorticism showed more rapid elimination and clearance of exogenous corticotropin than dogs with NAI.

Correction: Evaluation of urine protein content in dogs with pituitary-dependent hyperadrenocorticism

Correction: Evaluation of urine protein content in dogs with pituitary-dependent hyperadrenocorticism

Megavoltage irradiation of pituitary macrotumors in dogs with neurologic signs

Objective To assess the efficacy and determine prognostic factors of megavoltage irradiation for pituitary macrotumors in dogs with neurologic signs. Design Prospective clinical trial. Animals 24 dogs with pituitary macrotumor syndrome; 19 ACTH-secreting and 5 clinically endocrine-inactive tumors. Procedure Dogs were treated with 48 Gy of radiation during 4 weeks on an alternate-day schedule of 4 Gy/fraction. Three (12.5%) dogs did not complete the planned treatment because of progression of neurologic signs. Results A significant correlation was found between relative tumor size (ie, size of tumor relative to calvarium size) and severity of neurologic signs and between relative tumor size and remission of neurologic signs after irradiation. In dogs with pituitary dependent hyperadrenocorticism, a significant correlation was found between relative tumor size and plasma endogenous ACTH concentrations. Prognostic factors that independently affected duration of remission of neurologic signs were relative tumor size and endocrine activity. The prognostic factor that independently affected overall survival time was severity of neurologic signs. Prognostic factors of duration of eucortisolism were not found. Use of a large field of irradiation was associated with substantial damage to brain tissue. Clinical Implications Because radiation therapy was effective for treatment of tumors of small relative size in dogs, early treatment of pituitary tumors should improve prognosis. Further improvements may be obtained, using protocols in which higher total radiation doses and smaller radiation dose fractions are given. Irradiation was effective for long-term control of functional pituitary macrotumors and resulted in acceptably low complication rates when small fields of radiation were used. (J Am Vet Med Assoc 1998;213:225-231)

Results of transsphenoidal hypophysectomy in 52 dogs with pituitary-dependent hyperadrenocorticism.

To evaluate microsurgical transsphenoidal hypophysectomy in dogs with pituitary-dependent hyperadrenocorticism (PDH). 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. 52 dogs with PDH. 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. 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. 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.

Use of the urine cortisol-to-creatinine ratio for monitoring dogs with pituitary-dependent hyperadrenocorticism during induction treatment with mitotane (o, p'-DDD)

Abstract Objective To determine whether the urine cortisol-to-creatinine ratio (UCCR) could replace the ACTH stimulation test in monitoring effectiveness of mitotane induction treatment in dogs with pituitary-dependent hyperadrenocorticism (PDH). Animals 15 dogs with PDH. Procedure All 15 dogs were given an induction dose of mitotane (o, p'-DDD: 35 to 50 mg/kg of body weight/d) for 3 to 14 days. During the induction period, free-catch morning urine samples were collected for determination of UCCR, followed by ACTH stimulation testing, every other day. Treatment response was divided into 3 categories: well-controlled PDH (post-ACTH serum cortisol concentration ≥ 28 nmol/L but ≤ 138 nmol/L), deficient cortisol secretion (post-ACTH serum cortisol concentration &lt; 28 nmol/L), and excess cortisol secretion (post-ACTH serum cortisol concentration &gt; 138 nmol/L). Results The linear relation between UCCR and post-ACTH serum cortisol concentration was significant (P &lt; 0.001); however, the prediction intervals surrounding the line were too broad to be clinically useful. The UCCR overlapped among the 3 categories of treatment response. Nevertheless, dogs with PDH receiving mitotane induction treatment and with UCCR &gt; 79 × 10−6 were always classified as having excess cortisol secretion. Conclusion and Clinical Relevance The UCCR failed to predict post-ACTH cortisol concentration during mitotane induction treatment sufficiently close to be a clinically reliable indicator of treatment control. Seemingly, however, UCCR &gt; 79 × 10−6 obtained from a dog with PDH during mitotane induction would indicate inadequate adrenal cortex destruction and the need for continued mitotane induction; UCCR ≤ 79 × 10−6 would be inconclusive. (Am J Vet Res 1998;59:258–261)

Efficacy of cobalt 60 radiotherapy in dogs with pituitary-dependent hyperadrenocorticism

ObjectiveTo determine efficacy of cobalt 60 radiotherapy in dogs with pituitary-dependent hyperadreno-corticism (PDH) that have detectable tumors but no neurologic abnormalities. Design Case series. Animals 6 dogs with PDH that had a detectable pituitary mass on magnetic resonance images. Procedure Radiation was delivered in 11 fractions during a 3.5-week period for a total dose of 44 Gy. Clinical signs were evaluated, a urinalysis and ACTH stimulation test were performed, and urine cortisol-to-creatinine ratio and plasma endogenous ACTH concentration were measured before, immediately after, and 1, 3, 6, 9, and 12 months after radiotherapy. Magnetic resonance imaging was repeated 1 year after radiotherapy. Results Clinical signs of hyperadrenocorticism resolved in 3 dogs but recurred in 2 of the 3. Clinical condition of 2 dogs improved but did not return to normal. One dog did not improve. Results of ACTH stimulation tests and urine cortisol-to-creatinine ratios correlated with clinical signs. Plasma endogenous ACTH concentration transiently decreased in all 6 dogs. One year after radiotherapy, size of tumors was decreased by 25% in 2 dogs; in the other 4 dogs, tumors could no longer be detected. None of the dogs developed neurologic abnormalities. Adverse effects of radiotherapy were mild. Clinical Implications Radiotherapy did not result in adequate control of clinical signs of hyperadrenocorticism in 5 of 6 dogs, but size of pituitary tumors was dramatically reduced. Thus, it may be reasonable to recommend radiotherapy in dogs with PDH that have pituitary tumors for which greatest vertical height is 8 mm or more. (J Am Vet Med Assoc 1998; 212:374-376)

Laparoscopic bilateral adrenalectomy for persistent Cushing's disease after transsphenoidal surgery

Background: We performed bilateral laparoscopic adrenalectomies on four patients (three women and one man) with Cushing's disease (pituitary-dependent Cushing's syndrome) showing persistent hypercortisolism after transsphenoidal surgery. Methods: The technique for bilateral transperitoneal laparoscopic adrenalectomy was derived from the one previously adopted by our group for unilateral adrenalectomy and previously described. Eight trocars were used, of which two were used for both left and right adrenalectomy. Results: Bilateral laparoscopic adrenalectomy was performed in a one-stage procedure in the three women and, because of the abundant abdominal fat of the patient, in a two-stage procedure (after a 1-week interval) in the man. Operating times for the three women were 255 minutes, 230 minutes, and 220 minutes , and for the man 170 minutes for right adrenalectomy and 140 minutes for left adrenalectomy. No surgical or anesthesiologic complications were encountered. All patients were discharged from the hospital within 5 days after operation. At present, after follow-up periods of 23, 8, 6, and 18 months, all patients show remission of Cushing's disease and undetectable cortisol levels. Conclusions: Our experience suggests that bilateral laparoscopic adrenalectomy is a safe and effective procedure and a valid therapeutic option in patients with Cushing's disease showing persistent hypercortisolism after transsphenoidal surgery. However, the decision to remove both adrenal glands in such patients needs to be weighed against the risk of their having Nelson's syndrome or other long-term complications. (Surgery 1998;123:144-50.)