Pituitary-dependent Hyperadrenocorticism Research Articles

COMPUTED TOMOGRAPHIC ADRENAL GLAND QUANTIFICATION IN CANINE ADRENOCORTICOTROPH HORMONE‐DEPENDENT HYPERADRENOCORTICISM

We conducted a retrospective study to determine whether multidetector computed tomography (CT) could be of value for adrenal gland assessment in dogs with pituitary-dependent hyperadrenocorticism. Adrenal gland attenuation and volume values of 49 dogs with hyperadrenocorticism were recorded and age, body weight, and gender were examined to determine if a relationship existed between these variables and adrenal gland morphology. There was not a statistically significant difference in mean X-ray attenuation of the left vs. right adrenal gland in normal dogs (35.3 +/- 6.1 HU), or in dogs with hyperadrenocorticism. The mean adrenal X-ray attenuation (+/- standard deviation [SD]) in dogs with microadenoma was 33.1 +/- 6.8 vs. 31.8 +/- 12.7 HU for dogs with macroadenoma, and these values were not statistically different. The mean volume of the left adrenal gland in normal dogs (0.59 +/- 0.17 cm3) was greater than that of the right adrenal gland (0.54 +/- 0.19 cm3) (P < 0.05). The mean CT volume (+/- SD) of the adrenal glands in dogs with microadenoma vs. macroadenoma were 1.60 +/- 1.25 vs. 2.88 +/- 1.60 cm3, respectively. There was no effect of age or gender on adrenal gland morphology or X-ray attenuation. The weight effect was the most important source of variation for the volume measurement in dogs with hyperadrenocorticism.

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 using 99mTc-methylene diphosphonate (99mTc-MDP) in dogs with pituitary-dependent hyperadrenocorticism (PDH). Twenty-one dogs with PDH were prospectively evaluated using thoracic radiography, arterial blood gas analysis, and bone phase and pulmonary perfusion scintigraphy (using 99mTc-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 thoracic 99mTc-MDP images. Thoracic:vertebral ratios were calculated using 99mTc-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 (defined as an arterial partial pressure of oxygen [PaO2] < 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 using 99mTc-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.

Pituitary-dependent hyperadrenocorticism in a cockatoo

A 13-year-old female intact Moluccan cockatoo (Cacatua moluccensis) was evaluated because of coelomic distention, presumed to be secondary to an abdominal hernia. The patient also had a history of rapid weight gain and polyuria and polydipsia. Ultrasonography was used to confirm the existence of a pseudohernia that appeared to contain the small intestines, pancreas, and reproductive tract. Results of plasma biochemical analysis revealed hyperglycemia, hypophosphatemia, and high nonfasting bile acid concentrations and aspartate aminotransferase activity. A CBC revealed a relative heterophilia with a concomitant lymphopenia and mild monocytosis. Histologic evaluation of a liver biopsy specimen indicated chronic hepatic lipidosis. Despite a strong clinical suspicion of hyperadrenocorticism, ACTH stimulation test results were equivocal. The pseudohernia was strengthened with a prolene mesh. Despite ongoing medical and surgical care, the patient developed complications associated with the herniorrhaphy and was euthanatized. The clinical suspicion of hyperadrenocorticism was confirmed on the basis of histologic evaluation of the pituitary gland by use of special stains. To our knowledge, pituitary-dependent hyperadrenocorticism has not been previously confirmed in Psittaciformes. The condition should be considered in birds with clinical signs consistent with those observed in mammals. For the cockatoo of this report, ACTH stimulation test results were equivocal and additional diagnostic tests should be developed for avian patients.

Surgery for Cushing’s Syndrome: An Historical Review and Recent Ten‐year Experience

Cushing's syndrome (CS), due to multiple etiologies, is a disorder associated with the ravages of cortisol excess. The purpose of this review article is to provide a historical synopsis of surgery for CS, review a recent 10-year period of operative management at a tertiary care facility, and to outline a practical approach to diagnosis and management. From 1996 to 2005, 298 patients underwent 322 operative procedures for CS at Mayo Clinic, Rochester, Minnesota. A retrospective chart review was carried out. Data was gathered regarding demographics, preoperative assessment, procedures performed, and outcomes. Data are presented as counts and percentages. Five-year survival rates were calculated where applicable by the Kaplan-Meier method. Statistical analysis was carried out with SAS, version 9 (SAS Institute, Inc., Cary, NC). Two-hundred thirty-one patients (78%) had ACTH-dependent CS and 67 patients (22%) had ACTH-independent CS. One-hundred ninety-six patients (66%) had pituitary-dependent CS and 35 patients (12%) had ectopic ACTH syndrome. Fifty-four patients (18%) had cortisol-secreting adenomas, 10 patients (3%) had cortisol-producing adrenocortical carcinomas, and 1% had other causes. Cure rates for first time pituitary operations (transsphenoidal, sublabial, and endonasal) were 80% and 55% for reoperations. Most benign adrenal processes could be managed laparoscopically. Five-year survival rates (all causes) were 90%, 51%, and 23% for adrenocortical adenomas, ectopic ACTH syndrome, and adrenocortical carcinomas, respectively. Surgery for CS is highly successful for pituitary-dependent CS and most ACTH-independent adrenal causes. Bilateral total adrenalectomy can also provide effective palliation from the ravages of hypercortisolism in patients with ectopic ACTH syndrome and for those who have failed transsphenoidal surgery. Unfortunately, to date, adrenocortical carcinomas are rarely cured. Future successes with this disease will likely depend on a better understanding of tumor biology, more effective adjuvant therapies and earlier detection. Clearly, IPSS, advances in cross-sectional imaging, along with developments in transsphenoidal and laparoscopic surgery, have had the greatest impact on today's management of the complex patient with CS.

Cushing's Disease Complicated with Thrombosis in a Dog

Thrombosis is a potential complication of hyperadrenocorticism (HAC) in dogs. An 8-year-old male Beagle diagnosed with pituitary-dependent HAC had complicated with thrombosis in the caudal vena cava and abdominal aorta, which was treated by hypophysectomy and antithrombotic therapy. After hypophysectomy, hypercortisolemia disappeared and the general condition was also significantly improved. Ultrasonography after hypophysectomy revealed that the thrombus remained in the abdominal aorta, but the thrombus in the caudal vena cava had disappeared. However 692 days after the hypophysectomy, the dog had an acute onset of dyspnea and died. Postmortem examination revealed the presence of thrombi in the abdominal aorta and the pulmonary artery. Observations from this case show that HAC dogs must be attention to thrombosis.

Comparison of non-selective adrenocorticolysis with mitotane or trilostane for the treatment of dogs with pituitary-dependent hyperadrenocorticism

Forty-six dogs with pituitary-dependent hyperadrenocorticism were treated with mitotane by the non-selective adrenocorticolysis protocol and 40 were treated twice a day with trilostane. The treatment groups were compared by chi-squared...

Cushing's syndrome: aftermath of the cure

Cushing's syndrome (CS) is a chronic and systemic disease caused by endogenous or exogenous hypercortisolism, associated with an increase of mortality rate due to the clinical consequences of glucocorticoid excess, especially cardiovascular diseases. After cure, usually obtained by the surgical removal of the tumor responsible for the disease, the normalization of cortisol secretion is not constantly followed by the recovery of the clinical complications developed during the active disease, and it is often followed by the development of novel clinical manifestations induced by the fall of cortisol levels. These evidences were mostly documented in patients with pituitary-dependent CS, after surgical resection of the pituitary tumor. Indeed, despite an improvement of the mortality rate, metabolic syndrome and the consequent cardiovascular risk have been found to partially persist after disease remission, strictly correlated to the insulin resistance. Skeletal diseases, mainly osteoporosis, improve after normalization of cortisol levels but require a long period of time or the use of specific treatment, mainly bisphosphonates, to reach the normalization of bone mass. A relevant improvement or resolution of mental disturbances has been described in patients cured from CS, although in several cases, cognitive decline persisted and psychological or psychiatric improvement was erratic, delayed, or incomplete. On the other hand, development or exacerbation of autoimmune disorders, mainly thyroid autoimmune diseases, was documented in predisposed patients with CS after disease remission. The totality of these complications persisting or occurring after successful treatment contribute to the impairment of quality of life registered in patients with CS after disease cure.

Cushing’s disease in dogs: Cabergoline treatment

The treatment of pituitary-dependent hyperadrenocorticism (PDH) in dogs has for a long time been focused on inhibiting the adrenal gland using drugs such as o– p′-DDD, Ketoconazole and Trilostane, without attacking the primary cause: the corticotrophinoma. Corticotroph cells can express the D2 dopaminergic receptor; therefore cabergoline (Cbg) could be effective as a treatment. Follow-up over 4 years was carried out in 40 dogs with PDH that were treated with Cbg (0.07 mg/kg/week. Out of the 40 dogs, 17 responded to Cbg (42.5%). A year after the treatment, there was a significant decrease in ACTH ( p < 0.0001), α-MSH ( p < 0.01), urinary cortisol/creatinine ratio ( p < 0.001), and of the tumor size ( p < 0.0001) evaluated by nuclear magnetic resonance. Dogs responding to Cbg lived significantly longer ( p < 0.001) than those in the control group. To conclude, Cbg is useful in 42.5% of dogs with PDH, justifying its use as a treatment.

Diagnostic imaging findings and endocrine test results in dogs with pituitary-dependent hyperadrenocorticism that did or did not have neurologic abnormalities: 157 cases (1989–2005)

To compare imaging findings in dogs with pituitary-dependent hyperadrenocorticism (PDH) that did or did not have neurologic abnormalities. Design-Retrospective case series. 157 dogs with PDH that did (n = 73) or did not (84) have neurologic abnormalities. Medical records were reviewed for the presence and nature of clinical signs of CNS disease, and computed tomographic and magnetic resonance images were reviewed for evidence of a pituitary tumor. 60 of the 84 (71%) dogs without neurologic abnormalities and 48 of the 73 (66%) dogs with neurologic abnormalities had a detectable pituitary tumor. However, 17 of the 84 (20%) dogs without neurologic abnormalities had a pituitary macrotumor (ie, a tumor > or = 10 mm in height), and 41 of the 73 (56%) dogs with neurologic abnormalities did not have a detectable pituitary tumor or had a pituitary microtumor. Vague signs of CNS dysfunction (ie, lethargy, inappetence, and mental dullness) were more specific for detection of pituitary macrotumors than were CNS-specific signs (ie, seizure or blindness). Results suggested that there was no apparent relationship between a pituitary tumor and development of neurologic abnormalities in dogs with PDH. In addition, neurologic abnormalities in dogs with pituitary macrotumors were often vague (ie, lethargy, inappetence, and mental dullness).

Prognostic factors for outcome after transsphenoidal hypophysectomy in dogs with pituitary-dependent hyperadrenocorticism

Object The aim of this study was to determine prognostic factors for outcome after transsphenoidal hypophysectomy in dogs with pituitary-dependent hyperadrenocorticism (PDH). Methods One veterinary neurosurgeon performed transsphenoidal hypophysectomies in 181 dogs with PDH over a 12-year period. Survival analysis was performed with the Kaplan–Meier method. Prognostic factors were analyzed with the univariate Cox proportional hazard analysis followed by stepwise multivariate analysis. The log-rank test was used to assess disease-free fractions in three groups categorized according to early postoperative urinary corticoid/creatinine (C/C) ratios. Results Multivariate analysis revealed that old age, large pituitary size, and high preoperative concentrations of plasma adrenocorticotropic hormone were associated with an increased risk of PDH-related death. In addition, large pituitary size, thick sphenoid bone, high C/C ratio, and high concentration of plasma α-melanocyte–stimulating hormone (α-MSH) before surgery were associated with an increased risk of disease recurrence in the dogs that went into remission after hypophysectomy. Disease-free fractions were significantly higher in dogs with postoperative urinary C/C ratios in the lower normal range (< 5 × 10−6) than in dogs with postoperative C/C ratios in the upper normal range (5–10 × 10−6). Conclusions The results of this study indicate that pituitary size, sphenoid bone thickness, plasma α-MSH concentration, and preoperative level of urinary cortisol excretion are predictors of long-term remission after transsphenoidal hypophysectomy for PDH in dogs. Urinary C/C ratios measured 6 to 10 weeks after surgery can be used as a guide for predicting the risk of tumor recurrence.

Prognostic factors for outcome after transsphenoidal hypophysectomy in dogs with pituitary-dependent hyperadrenocorticism

The aim of this study was to determine prognostic factors for outcome after transsphenoidal hypophysectomy in dogs with pituitary-dependent hyperadrenocorticism (PDH). One veterinary neurosurgeon performed transsphenoidal hypophysectomies in 181 dogs with PDH over a 12-year period. Survival analysis was performed with the Kaplan-Meier method. Prognostic factors were analyzed with the univariate Cox proportional hazard analysis followed by stepwise multivariate analysis. The log-rank test was used to assess disease-free fractions in three groups categorized according to early postoperative urinary corticoid/creatinine (C/C) ratios. Multivariate analysis revealed that old age, large pituitary size, and high preoperative concentrations of plasma adrenocorticotropic hormone were associated with an increased risk of PDH-related death. In addition, large pituitary size, thick sphenoid bone, high C/C ratio, and high concentration of plasma alpha-melanocyte-stimulating hormone (alpha-MSH) before surgery were associated with an increased risk of disease recurrence in the dogs that went into remission after hypophysectomy. Disease-free fractions were significantly higher in dogs with postoperative urinary C/C ratios in the lower normal range (< 5 x 10(-6)) than in dogs with postoperative C/C ratios in the upper normal range (5-10 x 10(-6)). The results of this study indicate that pituitary size, sphenoid bone thickness, plasma alpha-MSH concentration, and preoperative level of urinary cortisol excretion are predictors of long-term remission after transsphenoidal hypophysectomy for PDH in dogs. Urinary C/C ratios measured 6 to 10 weeks after surgery can be used as a guide for predicting the risk of tumor recurrence.

Bilateral laparoscopic adrenalectomy for corticotrophin–dependent Cushing's syndrome: a review of the Mayo Clinic experience

There has been a rapid shift from open to laparoscopic approaches in adrenal surgery, but the safety and efficacy of bilateral laparoscopic adrenalectomy (BLA) in patients with corticotrophin (ACTH)-dependent Cushing's syndrome continues to be defined. Review outcomes in the largest series of patients reported to date undergoing BLA for ACTH-dependent Cushing's syndrome. Retrospective review study. Between January of 1995 and October of 2006, BLA was attempted in 68 patients with ACTH-dependent Cushing's syndrome (26 ectopic ACTH syndrome; 42 persistent pituitary-dependent Cushing's syndrome following pituitary surgery). Review of peri-operative morbidity and mortality, biochemical parameters and patient-reported symptom response from chart review and mailed questionnaire. BLA was successfully completed in 59 of 68 patients (87%); nine (13%) required conversion to open adrenalectomy (OA). Intra-operative complications occurred in three patients (4.4%) (two BLA, one OA), and non-operative complications occurred in 11 (16%) patients (eight BLA, three OA). There were no peri-operative deaths. Median hospitalization was 5.5 days (range, 3-28) and 11.9 days (range, 4-29) for the BLA and OA groups, respectively. In patients with follow-up data available, all achieved biochemical resolution and at least partial clinical resolution of signs and symptoms associated with hypercortisolism. Resolution of hypertension, diabetes and obesity was achieved in 64%, 29% and 35% of patients carrying those diagnoses prior to surgery, respectively. This study further supports the role of BLA as an effective treatment option for patients with ACTH-dependent Cushing's syndrome.

Expression and mutation analysis of Tpit in the canine pituitary gland and corticotroph adenomas

Pituitary-dependent hyperadrenocorticism (PDH) in dogs is caused by a pituitary corticotroph adenoma. Although PDH is a common disorder in dogs, little is known about the underlying pathogenesis. In the pituitary glands of humans and mice, the pro-opiomelanocortin (POMC)-expressing cell lineages, the corticotrophs and melanotrophs, have a specific marker in common, the T-box transcription factor Tpit (Tbx19), which is obligate for POMC expression. Tpit also regulates the late differentiation of the corticotrophs and melanotrophs, and therefore may contribute to the pathogenesis of the corticotroph adenomas. The aim of this study was to perform an expression and mutation analysis of Tpit in the normal canine pituitary and in corticotroph adenomas. The distribution of the Tpit protein in the pituitary gland was studied with immunohistochemistry and the expression of the gene with RT-PCR. The coding region of Tpit cDNA from 14 dogs with PDH was screened for mutations. Tpit was expressed in corticotroph and melanotroph cells of the normal and adenomatous canine pituitary, and remained present in non-adenomatous corticotrophs of pituitaries from PDH dogs. No tumor-specific mutation in the Tpit cDNA from the corticotroph adenomas was found. However, a missense polymorphism in the highly conserved DNA-binding domain, the T-box, was discovered in one dog. It is concluded that Tpit can be used as a reliable marker for the corticotroph and melanotroph cells in the canine pituitary tissue and that mutations in the Tpit gene are unlikely to play a major role in the pathogenesis of canine corticotroph adenomas.

Hyperthyroidism due to an intrathoracic tumour in a dog with test results suggesting hyperadrenocorticism

The elevated urinary corticoid/creatinine ratios of an 11-year-old Jack Russell terrier with polyuria were suppressible in a high-dose dexamethasone suppression test, which was suggestive of pituitary-dependent hyperadrenocorticism. The absence of physical and routine-laboratory changes compatible with hyperadrenocorticism and the relatively high plasma thyroxine concentration were the impetus for additional studies of thyroid and adrenocortical functions. A high plasma thyroxine concentration (62 nmol/l; 5.0 microg/100 ml) suggested the presence of hyperthyroidism. Radiography, (99m)TcO(4) (-) scintigraphy, ultrasonography, computed tomography and cytology revealed a hyperfunctioning intrathoracic thyroid tumour. In the low-dose dexamethasone suppression test, the plasma cortisol concentration exceeded the reference value of 40 nmol/l (1.4 microg/100 ml) at eight hours after dexamethasone administration (0.01 mg/kg intravenously), a test result compatible with hyperadrenocorticism. In conclusion, this report represents the first case of a dog with an autonomously hyperfunctioning thyroid tumour in the thorax. The elevated urinary corticoid excretion and the positive low-dose dexamethasone suppression test may be explained by alterations in cortisol metabolism, the stress of the hyperthyroid state or both.

Increased Osteoprotegerin Levels in Cushing’s Syndrome Are Associated with an Adverse Cardiovascular Risk Profile

Patients with Cushing's syndrome (CS) have a mortality rate four times higher than age- and sex-matched subjects, mainly due to cardiovascular events. Serum osteoprotegerin (OPG) levels are increased in patients with cardiovascular disease and/or excess bone resorption. The aim of the study was to assess serum OPG and soluble receptor activator of nuclear factor-kappaB ligand (sRANKL) levels in CS and their possible relationship with coronary risk profile. We conducted a cross-sectional study at a tertiary referral center. We studied 48 adult patients with CS and 48 age- and sex-matched controls. Twenty-six patients had pituitary-dependent CS; five patients had CS caused by ectopic ACTH secretion; and 17 patients had adrenal-dependent CS, accounted for by cortisol-secreting adenoma (n = 9), ACTH-independent macronodular bilateral adrenal hyperplasia (n = 4), or World Health Organization stage II cortisol-secreting carcinoma (n = 4). Patients underwent assessment of the absolute coronary risk and measurement of bone mineral density by dual-energy x-ray absorptiometry. Serum OPG and total sRANKL were measured by ELISA. Serum OPG (but not sRANKL) levels were significantly higher in CS patients than in controls (P < 0.01). In patients, serum OPG showed a positive correlation with age (r = 0.36; P = 0.01). OPG levels were higher in patients with the metabolic syndrome [median, 1262 (range, 199-2306) pg/ml vs. 867 (412-2479) pg/ml; P = 0.03], and showed a positive correlation with the absolute coronary risk (r = 0.36; P = 0.01). Serum OPG levels were higher in patients with pituitary-dependent CS in comparison with adrenal-dependent CS. In patients with CS, serum OPG levels are increased and appear to be associated with coronary risk.

Histological evaluation of the adrenal glands of seven dogs with hyperadrenocorticism treated with trilostane

The lesions in the adrenal glands of seven dogs with hyperadrenocorticism that had been treated with trilostane were studied histologically. The glands of the six dogs with pituitary-dependent hyperadrenocorticism had...

Medical Management of Pituitary-Dependent Hyperadrenocorticism: Mitotane versus Trilostane

Pituitary-dependent hyperadrenocorticism is a common endocrine disorder in dogs in the United States. Once a diagnosis is established, a decision must be made whether or not to pursue treatment, and if so, which medication to use. Historically, mitotane (Lysodren, o,p'-DDD, Bristol-Myers Squibb, New York) has been the most commonly used treatment for medical management. Its use is complicated and comes with many potential side effects, making many practitioners wary of its use. Recently, trilostane has been proven to be an effective treatment of pituitary-dependent hyperadrenocorticism and is approved for use in other countries. Treatment with trilostane is somewhat simpler and the incidence of side effects seems to be less when compared with mitotane therapy. Either treatment can be a safe and effective method of treatment for pituitary-dependent hyperadrenocorticism when the practitioner and client are well educated regarding their use and an appropriate monitoring protocol is used.

Tertiary hypothyroidism in a dog

A nine-year-old male entire Labrador was diagnosed with pituitary dependent hyperadrenocorticism. Following seven months of successful mitotane therapy, the dog presented with marked weight gain, seborrhoea and alopecia. Routine clinicopathological analyses revealed marked hypercholesterolaemia. Serum total and free thyroxine (T4) concentrations were below their respective reference ranges. Serum thyroid stimulating hormone (cTSH) concentration was within reference range. TSH and thyrotropin releasing hormone (TRH) response tests revealed adequate stimulation of total T4 in both, and cTSH in the latter test. Magnetic resonance imaging revealed a mass arising from the pituitary fossa, with suprasellar extension. A diagnosis of tertiary hypothyroidism was made. Following four weeks of levothyroxine therapy, circulating cholesterol concentration had declined, weight loss had ensued and dermatological abnormalities had improved. Euthanasia was performed four months later due to the development of neurological signs. A highly infiltrative pituitary adenoma, with effacement of the overlying hypothalamus was identified on post mortem examination. Tertiary hypothyroidism has not been previously reported in dogs.

Gallbladder Mucocele in Two Dogs with Pituitary-Dependent Hyperadrenocorticism: A Case Report

Melián, C., Morales, M., Perez-Alenza, M.D., Corbera, J.A. and Bru, N.D. 2006. Gallbladder mucocele in two dogs with pituitary-dependent hyperadrenocorticism: a case report. J. Appl. Anim. Res., 30: 117–120. Gallbadder mucocele in two clinical cases of dogs with hyperadrenocorticism has been described. Decreased gallbladder motility, biliary stasis and altered absortion of water from the gallbladder lumen are predisposing factors to the formation of biliary sludge and it is possible that biliary sludge is a precipitating factor in the formation of gallbladder mucoceles. Dogs with hyperadrenocorticism commonly present biliary sludge and hepatomegaly and might be predisposed to gallbladder mucocele. Hyperadrenocorticism is associated with thrombosis and a hypercoagulability state, which can contribute to gallbladder ischemia and necrosis. Further studies are needed to fully understand the effect on hyperadrenocorticism on gallbladder function.

Plasma profiles of adrenocorticotropic hormone, cortisol, α-melanocyte-stimulating hormone, and growth hormone in dogs with pituitary-dependent hyperadrenocorticism before and after hypophysectomy

The 6-h plasma profiles of adrenocorticotropic hormone (ACTH), cortisol, alpha-melanocyte-stimulating hormone (alpha-MSH), and GH were studied in 17 dogs with pituitary-dependent hyperadrenocorticism (PDH) before and after hypophysectomy. The aim of the study was to investigate the relation between the hormone profile characteristics and recurrence of PDH after surgery. The hormones were secreted in a pulsatile fashion. The basal plasma cortisol concentration and area under the curve (AUC) for cortisol were significantly higher in the PDH cases than in eight controls. The characteristics of the plasma profiles of ACTH and alpha-MSH were not significantly different between the PDH cases and the controls. In the PDH cases, less GH was secreted in pulses than in the controls, but the difference was not significant. The basal plasma cortisol concentration, the AUC for ACTH and cortisol, and the pulse frequency of ACTH and cortisol decreased significantly after hypophysectomy for the group of PDH cases. The basal plasma concentrations of ACTH and alpha-MSH, the AUC for alpha-MSH, and the characteristics of the plasma GH profiles of the PDH cases remained unchanged after hypophysectomy. No pulses of alpha-MSH were observed after hypophysectomy. The co-occurrence between the ACTH and cortisol pulses decreased significantly with hypophysectomy. The postoperative pulse frequency of ACTH was the only characteristic with predictive value for the recurrence of PDH after hypophysectomy. The results of this study demonstrate that ACTH, cortisol, alpha-MSH, and GH are secreted in a pulsatile fashion in dogs with PDH. Hypophysectomy effectively reduces the secretion of ACTH and cortisol. The presence of ACTH pulses after hypophysectomy is a risk factor for the recurrence of hyperadrenocorticism.