J. Blake Tyrrell

Cushing's syndrome: Problems in diagnosis

Cushings syndrome, an unusual group of disorders characterized by hypercortisolism, must be considered in the differential diagnosis of such common clinical problems as hirsutism, menstrual irregularity, hypertension, diabetes mellitus, and obesity. Its distinct forms--pituitary-dependent Cushings syndrome (Cushings disease), adrenal tumor and ectopic ACTH syndrome--must be identified correctly so that specific therapy can be administered. In the majority of cases, use of a relatively simple diagnostic sequence will provide accurate and rapid diagnosis. However, in our experience with more than 60 patients, diagnostic difficulties may arise from a variety of conditions (e.g., drug interference, alcohol ingestion, and depression). In addition, unusual circumstances, such as unexpected responses to dexamethasone, may complicate the diagnosis. Our approach to these problems is illustrated through a report of seven cases, and we emphasize that the proper management of Cushings syndrome mandates a thorough marshalling of all the available data.

Pituitary ACTH dependency of nodular adrenal hyperplasia in Cushing's syndrome: Report of two cases and review of the literature

Cushings syndrome due to nodular adrenal hyperplasia comprises a clinically and biochemically heterogeneous group of disorders whose pathogenesis is unclear. We describe two patients with atypical steroid dynamics and large unilateral adrenal nodules who had pituitary ACTH-dependent disease. In the differential diagnosis of Cushings syndrome, we recommend repeated ACTH measurement and selective venous sampling-particularly in those patients with impaired dexamethasone suppressibility and abnormal findings on computerized tomography.

Delayed onset of hyponatremia after transsphenoidal surgery for pituitary adenomas.

Hyponatremia is rarely reported as a delayed complication of transsphenoidal resection of pituitary adenoma. Usually attributed to the syndrome of inappropriate secretion of antidiuretic hormone (SIADH), hyponatremia causes nonspecific symptoms, often after hospital discharge. To clarify the frequency, presentation, and outcome of this poorly understood complication, we reviewed our database of 2297 patients who underwent transsphenoidal pituitary surgery between February 1971 and June 1993. Of 53 patients (2.3%) treated for symptomatic hyponatremia, 11 were excluded (2 received arginine vasopressin within 24 hours, 1 had untreated hypothyroidism, 4 had untreated adrenal insufficiency, and 4 had incomplete records). The remaining 42 patients (1.8%), 11 men and 31 women aged 21 to 79 years, presented 4 to 13 days (mean, 8 d) postoperatively with nausea and vomiting (20 patients), headache (18 patients), malaise (12 patients), dizziness (4 patients), anorexia (2 patients), and seizures (1 patient). Hyponatremia was unrelated to sex, age, adenoma type, tumor size, or glucocorticoid tapering. Although the clinical picture in our patients is consistent with SIADH, this was not supported by the antidiuretic hormone levels, which were normal or low-normal in the two patients in whom they were measured, suggesting the possibility that low serum sodium may not reflect SIADH. In all patients, hyponatremia resolved within 6 days (mean, 2 d); treatment consisted of salt replacement and mild fluid restriction in 37 patients and fluid restriction only in 4 (treatment unknown in 1). Delayed hyponatremia after transsphenoidal resection of pituitary adenoma is not as rare as previously thought, nor is it necessarily associated with SIADH or with hypoadrenalism during glucocorticoid tapering.(ABSTRACT TRUNCATED AT 250 WORDS)

Waiting for change: symptom resolution after adrenalectomy for Cushing's syndrome.

BACKGROUND The debilitating symptoms and physical changes from Cushings syndrome may resolve after treatment, but the time course to resolution is not well established. METHODS Between February 1995 and May 2007, 60 patients underwent adrenalectomy for Cushings syndrome. Pre-operative and operative variables were collected from a prospective database. Long-term follow-up was obtained via patient survey. RESULTS Unilateral adrenalectomy was performed in 53% and a bilateral adrenalectomy in 47% of patients. Median time to diagnosis was 24 months (range, 1-384). Three percent had intra-operative complications, and 28% developed post-operative complications. Steroids were required post-operatively for a median of 30 months after unilateral adrenalectomy (range, 0-96). At a median follow-up of 3.7 years (range, 0-13.3), 85% of patients are still alive. The majority of the physical changes resolved after adrenalectomy. The time to symptom resolution varied from a few weeks to up to 4 years. Most of the physical changes resolved by a mean of 7-9 months after surgery. Quality of life improved in 78% of patients, with 68% improving dramatically (P < .001). CONCLUSION Adrenalectomy can provide excellent palliation of the symptoms of cortisol excess and can dramatically improve patient quality of life, but both patients and physicians must know that these changes may take years.

Pheochromocytoma crisis is not a surgical emergency.

CONTEXT Pheochromocytoma crisis is a feared and potentially lethal complication of pheochromocytoma. OBJECTIVE We sought to determine the best treatment strategy for pheochromocytoma crisis patients and hypothesized that emergency resection is not indicated. DESIGN Retrospective cohort study (1993-2011); literature review (1944-2011). SETTING Tertiary referral center. PATIENTS There were 137 pheochromocytoma patients from our center and 97 pheochromocytoma crisis patients who underwent adrenalectomy from the literature. INTERVENTION Medical management of pheochromocytoma crisis; adrenalectomy. MAIN OUTCOME MEASURE(S) Perioperative complications, conversion, and mortality. RESULTS In our database, 25 patients (18%) presented with crisis. After medical stabilization and α-blockade, 15 patients were discharged and readmitted for elective surgery and 10 patients were operated on urgently during the same hospitalization. None underwent emergency surgery. Postoperatively, patients who underwent elective surgery had shorter hospital stays (1.7 vs 5.7 d, P = 0.001) and fewer postoperative complications (1 of 15 [7%] vs 5 of 10 [50%], P = 0.045) and were less often admitted to the intensive care unit (1 of 15 [7%] vs 5 of 10 [50%], P = 0.045) in comparison with urgently operated patients. There was no mortality. Review of the literature (n = 97) showed that crisis patients who underwent elective or urgent surgery vs emergency surgery had less intraoperative (13 of 31 [42%] vs 20 of 25 [80%], P < 0.001) and postoperative complications (15 of 45 [33%] vs 15 of 21 [71%], P = 0.047) and a lower mortality (0 of 64 vs 6 of 33 [18%], P = 0.002). CONCLUSIONS Management of patients presenting with pheochromocytoma crisis should include initial stabilization of the acute crisis followed by sufficient α-blockade before surgery. Emergency resection of pheochromocytoma is associated with high surgical morbidity and mortality.

Cavernous and inferior petrosal sinus sampling in the evaluation of ACTH-dependent Cushing's syndrome

objective  Central venous sampling (CVS) is used frequently in the evaluation of ACTH‐dependent Cushings syndrome. However, several controversies exist including the diagnostic accuracy, the sampling site of choice (cavernous sinus vs. inferior petrosal sinus) and the use of lateralization data in tumour localization. We have analysed our experience with CVS to address these controversies.

Cushing's disease revisited.

Harvey Cushing [I] presented and subsequently published his extraordinary study of basophilic pituitary adenomas in 1932. Validation of these observations followed long after his death through the fortunate coincidence of two developments: first, conclusive biochemical definition of pituitary-based hypercortisolism, for the first time differentiating this distinct clinical entity from other causes of hypercortisolism [2,3], and second, the evolution of transsphenoidal microsurgery not only providing an effective means of treating the disease but also permitting unequivocal documentation of ACTH-secreting microadenomas as a distinct entity [4]. Because it is now possible, in one simultaneous maneuver, to detect and remove minute adenomas situated in a pituitary gland of normal dimensions, the management of Cushing’s disease has undergone a revolutionary change. Until a superior form of treatment evolves, microsurgical removal of these remarkably occult adenomas offers the highest probability of restoring normal pituitary function to patients affected with the disease. The endocrinologic data from our initial series of patients were reported earlier [5]. When presented with a patient with Cushing’s disease, the surgeon can assume that the pituitary gland contains an ACTH-secreting adenoma. In a series of 44 intrasellar explorations in patients with Cushing’s disease, an adenoma was removed in every case. Three tumors, the smallest in the series, were missed at exploration and identified subsequently in serial sections of the excised glands. Microadenomas (diameter less than 10 mm) constituted the majority of adenomas.