A Case of Occult Ectopic Adrenocorticotropic Hormone-Secreting Tumor: Diagnostic and Management Dilemmas

ObjectiveTo report a case of ectopic adrenocorticotropic hormone (ACTH) syndrome in a patient whose tumor was not localized by radiographic or biochemical means and to discuss the difficulties inherent in this patient’s care, illustrative of the challenges encountered by clinicians faced with similar cases.MethodsWe describe the clinical presentation of our case and discuss its management.ResultsA 49-year-old woman presented with symptoms and physical findings strongly suggestive of Cushing syndrome. Findings on biochemical evaluation were consistent with ectopic ACTH syndrome. Radiographic imaging did not clearly identify a discrete tumor. Bilateral inferior petrosal sinus sampling and whole-body selected venous sampling were unsuccessful in localizing the source of ACTH secretion. Surgical exploration was undertaken with use of intraoperative ultrasonography. Both a primary tumor and metastatic disease were identified, and the patient underwent distal pancreatectomy and splenectomy, as well as sequential bilateral adrenalectomy. The primary lesion was a neuroendocrine tumor that did not stain positive for ACTH. Chemotherapeutic agents were used to control bulky hepatic metastatic lesions until the patient’s demise 2½ years after her initial presentation.ConclusionThis case illustrates the difficulties encountered in the assessment and management of a patient with ectopic ACTH syndrome when conventional methods of tumor localization fail to identify the source of hormone secretion. (Endocr Pract. 2008;14:588-591)     

Adrenal Cortical Carcinoma With Late Pulmonary Metastases Causing Clinicical Cushing’s Syndrome: Case Report With Immunohistochemical Analysis Of Steriodogenic Enzyme Production

ObjectiveTo present a case of pulmonary metastases from adrenocortical carcinomas (ACC) that were secreting fully-functional cortisol resulting in clinical Cushing’s syndrome and to compare the steroidogenic enzyme expression in the primary tumor and lung.MethodsWe analyzed and summarized the patient’s medical history, physical examination results, labora tory data, imaging studies, and histopathologic results. The original tumor and the pulmonary metastases were then immunohistochemically evaluated for steroidogenic enzymes.ResultsInitial endocrinological workup revealed hyperandrogenism and adrenocorticotropic hormone (ACTH) independent Cushing’s due to a 4 cm left adrenal mass. The patient was initially diagnosed with an adrenal adenoma. Four years later, the patient developed recurrent Cushing’s syndrome. Repeat magnetic resonance imaging (MRI) showed no adrenal masses; however, chest computed tomography (CT) showed multiple bilateral lung nodules and biopsy revealed metastases of adrenal origin. Upon immunohistochemical analysis, side chain cleavage, 17α hydroxylase, 3β hydroxysteroid dehydrogenase, and 21 hydroxylase immunoreactivity were detected in both the original and pulmonary metastatic lesions with patterns of disorganized steroidogenesis. Dehydroepiandrosterone sulfotransferase (DHEA-ST) immunoreactivity was detected in the original tumor but not in the lung metastases.ConclusionThis case demonstrates some inter esting features of ACC that pose challenges to its management, including the difficulties in establishing the pathologic diagnosis, the potential for fullyfunctional steroidogenesis even in late metastases, and the plasticity of steroidogenic potential in tumor cells. (Endocr Pract. 2012;18:e138-e143)     

Cushing's Syndrome Due to Ectopic Adrenocorticotrophic Hormone Production by Olfactory Neuroblastoma

ObjectiveTo review a case of olfactory neuroblastoma (ON) with Cushing’s syndrome (CS) due to ectopic production of adrenocorticotrophic hormone (ACTH) and compare the histopathologic diagnosis, treatment modality, and prognostic factors with the literature.MethodsWe report the clinical presentation, biochemistry, imaging, histopathology, treatment, and outcome of a patient with ON. We conducted an English language literature review of CS due to ectopic ACTH production and ON.ResultsCS due to ectopic ACTH production is uncommon, and CS due to ON is extremely rare. A 19-year-old Hispanic man presented with right nasal obstruction, involuntary weight gain, and intensely pruritic skin rash. Examination revealed large, wide purple striae on both arms and the abdomen. Head magnetic resonance imaging (MRI) revealed a right ethmoid sinus enhancing mass extending into the orbit, nasal cavity, and maxillary and sphenoid sinuses. Laboratory results showed a pm cortisol level of 26 mcg/dL, a 24-hour urinary free cortisol level of 7,507 mcg, an ACTH level of 83 pg/mL, and nonsuppression of cortisol with an overnight dexamethasone suppression test (1 and 8 mg). A biopsy revealed ON, and immunohistochemistry (IHC) was positive for ACTH. He underwent chemotherapy followed by surgical debulking and adjuvant radiation therapy, with no disease recurrence through the last follow-up in February 2012. Plasma and urinary cortisol levels normalized following surgery.ConclusionThis is the first case reported of a Hispanic male with an uncommon tumor (ON) and an even more uncommon presentation, ectopic ACTH production causing CS. The extremely high ACTH levels and plasma and urine cortisol levels dramatically dropped following multimodality management. So far, he has had 2.5 years of disease-free survival. (Endocr Pract. 2014;20:e47-e52)     

Adrenocorticotropic Hormone Independent Macronodular Adrenal Hyperplasia due to Aberrant Receptor Expression: Is Medical Treatment Always an Option?

ObjectiveTo investigate the efficacy of medical treatment as an alternative option to bilateral adrenalectomy in patients with cortisol excess due to adrenocorticotropic hormone (ACTH) independent macronodular adrenal hyperplasia (AIMAH).MethodsWe focused on the efficacy of somatostatin analogues in a patient with food-dependent AIMAH and of leuprolide acetate in a patient with AIMAH due to aberrant LH/hCG receptor expression.ResultsTwo female patients with bilateral macronodular adrenal hyperplasia and cortisol excess were evaluated for the presence of aberrant cortisol responses. One patient demonstrated an aberrant response to mixed meal and the other, a menopausal female, to luteinizing hormonereleasing hormone (LHRH) and human chorionic gonadotropin (hCG) administration. In the first patient, subcutaneous octreotide was administered prior to mixed meal and completely abolished food-induced cortisol secretion. Thus, the patient was treated with the long-acting somatostatin analogue octreotide long-acting release (LAR) for 3 months. There was no control of cortisol excess upon reevaluation and acute subcutaneous octreotide administration prior to meal was no longer effective in blocking food-induced cortisol secretion. The second patient successfully responded to leuprolide acetate and, for 40 months, her cortisol excess remains in long-term control.ConclusionA luteinizing hormone/human chorionic gonadotropin (LH/hCG) responsive patient with AIMAH sustained long-term control of cortisol excess on leuprolide acetate. In contrast, in a meal-responsive patient with apparent gastric inhibitory polypeptide (GIP) dependent AIMAH, did not achieve remission under somatostatin analogues. (Endocr Pract. 2013;19:e77-e82)     

Genetic Basis of Bilateral Macronodular Hyperplasia

Objective: To review the genetic basis of bilateral macronodular hyperplasia (BMAH).Methods: Case presentation, review of literature, table, and bullet point conclusions.Results: BMAH, also known as adrenocorticotropic hormone (ACTH)-independent macronodular hyperplasia (AIMH), can cause Cushing syndrome or mild hypercortisolism. Recent studies have demonstrated that hyperplastic tissue reproduces ectopic ACTH, implying that BMAH is the more proper term, as the syndrome is not ACTH-independent. BMAH was thought to be sporadic, but recent data have shown that there is likely a genetic component in the majority of cases. Mutations in ARMC5, a putative suppressor gene, have been found in many familial cases of BMAH and are thought to be responsible for the disorder. As these nodules inefficiently produce cortisol, large nodules are required to produce a clinical syndrome. ARMC5 likely requires a second somatic mutation to become clinically apparent. Clinical manifestations are not generally noted until the fifth to sixth decades of life.Conclusion: BMAH is an underrecognized genetic condition that can lead to Cushing syndrome and should be screened for in patients and susceptible family members.Abbreviations: ACTH = adrenocorticotropic hormone AIMAH = ACTH-independent macronodular adrenal hyperplasia ARMC5 = armadillo-repeat containing 5 BMAH = bilateral macronodular adrenal hyperplasia CAH = congenital adrenal hyperplasia CT = computed tomography MEN1 = multiple endocrine neoplasia 1 UFC = urinary free cortisol     

Adrenocorticotropic Hormone-Independent Cushing Syndrome Manifesting During Pregnancy

ObjectiveTo report a case of adrenocorticotropic hormone-independent Cushing syndrome(CS) diagnosed and treated surgically during the third trimester of pregnancy and resulting in delivery of a healthy baby boy.MethodsWe present a detailed case report, and we review and evaluate the English-language literature on CS during pregnancy.ResultsDuring pregnancy, the occurrence of CS is a rare event. The diagnosis of CS during pregnancy is difficult to establish because of the normal physiologic hypercortisolemia of pregnancy. In our patient, laboratory testing revealed a random serum cortisol level of 56.5 μg/dL, a suppressed plasma adrenocorticotropic hormone level (< 5 pg/mL), and a substantially elevated 24-hour urinary cortisol (1,708 μg). Noncontrast magnetic resonance imaging of the abdomen disclosed a 3.5-cm left adrenal mass. Laparoscopic left adrenalectomy was successfully performed during the early third trimester, and a healthy baby was born at 36 weeks of gestation by means of a cesarean delivery.ConclusionThe occurrence of CS during pregnancy is rare; however, when it does occur, adrenal tumors are more common than pituitary tumors. Caution should be used during interpretation of laboratory tests to evaluate for CS during pregnancy because of the normal increase in hypothalamic-pituitary-adrenal axis function during pregnancy. The current case demonstrates the safety and utility of noncontrast magnetic resonance imaging for localization of a tumor during pregnancy, as well as the safe use of laparoscopic surgical treatment of CS during the early third trimester. (Endocr Pract. 2010;16:260-263)     

Corticotropin-Independent Macronodular Adrenal Hyperplasia Associated With Insulinoma

ObjectiveTo report a case of corticotropin-independent macronodular adrenal hyperplasia (AIMAH) associated with an insulinoma.MethodsWe describe the clinical, radiographic, laboratory, and histopathologic findings of the study patient; review the current protocols for management of AIMAH; and discuss the disease etiology.ResultsA 64-year-old woman with multiple intradermal facial nevi experienced intermittent light-headedness, tremor, and confusion and was found to have a venous plasma glucose concentration of 52 mg/dL. Hypoglycemia and hyperinsulinemia after 18 hours of fasting suggested the presence of an insulinoma. Hepatic venous sampling for insulin after selective arterial calcium injection localized the insulinoma to the pancreatic head. The insulinoma was excised, and there was no recurrence over the 5 years the patient was in our care. During the workup for insulinoma, bilateral adrenal masses were incidentally discovered on computed tomography. Twenty-hour urinary free cortisol excretion was elevated and serum corticotropin was suppressed. Overt signs of Cushing syndrome were not present, and subsequent urinary cortisol measurements were within the reference range for several years. After 4 years, Cushing syndrome developed and bilateral adrenalectomy was performed. AIMAH was diagnosed on the basis of histopathologic findings.ConclusionsThis appears to be the first reported case of AIMAH associated with an insulinoma. In the absence of other stigmata of multiple endocrine neoplasm type 1 and in the presence of multiple nevi, it may represent a novel endocrine syndrome. (Endocr Pract. 2011;17:e43-e47)     

Transformation of a Pituitary Macroadenoma into to a Corticotropin-Secreting Carcinoma Over 16 Years

ObjectiveTo describe a case of a pituitary macroadenoma that differentiated into a corticotropin (ACTH)-secreting carcinoma with metastasis to the thigh.MethodsWe present a case report with a 16-year follow-up that includes anatomic and endocrine documentation of the history of an ACTH-secreting carcinoma.ResultsA 32-year-old woman presented for evaluation in 1989 because of visual feld defects. Magnetic resonance imaging revealed a locally invasive 3-cm macroadenoma. She had no clinical signs of cortisol excess. The patient underwent surgical debulking followed by a course of radiation directed to the pituitary. Results from retrospective immunohistochemical staining with antibodies against ACTH, prolactin, and MIB-1 were negative. Postoperatively, she could not be weaned from exogenous steroids without developing symptoms of adrenal insuffciency. In 1995, she developed left facial palsy and diplopia caused by tumor growth. In 1997, the patient developed progressive symptoms of cortisol excess, which continued after exogenous steroid replacement was discontinued. The patient’s clinical status continued to deteriorate because of local mass effect from tumor growth and uncontrolled hypercortisolism. She underwent bilateral adrenalectomy in 2003. The patient remained debilitated in a long-term care facility for 2 years when she was found to have a mass on her left hip. Biopsy results of the obturator muscle revealed metastatic tumor of neuroendocrine origin with strong reactivity to ACTH antibodies and MIB-1 labeling in 8% of tumor cell nuclei.ConclusionA pituitary tumor can transform into an ACTH-secreting carcinoma in an indolent manner. Patients with invasive pituitary adenomas require long-term surveillance to monitor for differentiation into pituitary carcinoma. (Endocr Pract. 2007;13:463-471)     

Multiple Unilateral adrenal Adenomas in a Patient with Primary Hyperaldosteronism

ObjectiveTo report a rare case of multiple unilateral adrenal adenomas in which immunohistochemistry results confirmed primary hyperaldosteronism in each of 3 adenomas.MethodsWe present the clinical, laboratory, radiographic, and pathologic findings of a case of multiple unilateral adrenal adenomas.ResultsAlthough multiple nodules in both adrenal glands are fairly common in patients with bilateral hyperplasia, multiple unilateral nodules are extremely rare. A 45-year-old woman with a long-standing history of severe hypertension was found to have biochemical parameters consistent with primary hyperaldosteronism, multiple unilateral adrenal adenomas, and immunohistochemical test results confirming primary hyperaldosteronism arising from each of 3 adrenal nodules (measuring 2.2 × 2.2 cm, 1.7 × 0.7 cm, and 0.5 × 0.5 cm).ConclusionThis case illustrates the rare presentation of primary hyperaldosteronism as multiple unilateral adrenal adenomas in which immunohistochemistry results can confirm the suspected preoperative diagnosis as suggested by biochemical and radiographic evidence. (Endocr Pract. 2008;14:76-79)     

Autoimmune Hyperthyroidism due to Secondary Adrenal Insufficiency: Resolution with Glucocorticoids

ObjectiveTo describe the course of autoimmune hyperthyroid disease in a patient with corticotropin (ACTH) deficiency treated with glucocorticoids.MethodsWe report the clinical presentation, laboratory data, imaging studies, and management of a patient with weight loss, fatigue, apathy, hallucinations, and arthritis.ResultsAutoimmune hyperthyroidism (positive thyroperoxidase and thyroglobulin antibodies and borderline positive thyrotropin receptor antibody) was diagnosed in a 71-year-old woman. New psychotic symptoms prompted brain magnetic resonance imaging, which revealed a partially empty sella. Undetectable morning cortisol, undetectable ACTH, and failure to stimulate cortisol with synthetic ACTH (cosyntropin 250 mcg) secured the diagnosis of long-standing secondary adrenal insufficiency. Hydrocortisone replacement improved the patient’s symptoms, resolved the thyroid disease, and decreased thyroid antibody titers. In retrospect, the patient recalled severe postpartum hemorrhage requiring blood transfusion at age 38 years. A Sheehan event probably occurred 33 years before the patient presented with corticotropin deficiency. Hyperthyroidism accelerated cortisol metabolism and provoked symptoms of adrenal insufficiency.ConclusionsThe hypocortisolemic state may precipitate hyperimmunity and autoimmune thyroid disease. Rapid resolution of hyperthyroidism and decreased thyroid antibody titers with glucocorticoid treatment support this hypothesis. (Endocr Pract. 2011;17:85-90)     

Intravascular Lymphoma: an Unusual Diagnostic Outcome of an Incidentally Detected Adrenal Mass

ObjectiveTo describe a rare diagnosis of intravascular lymphoma in a patient presenting with an incidentally discovered adrenal mass.MethodsWe describe the patient’s clinical history and the findings from biochemical evaluation, radiologic studies, and surgical pathology and review the relevant literature.ResultsA 43-year-old woman developed sudden onset of flank pain associated with a flushing sensation and presented to the emergency department where computed tomography showed a 5-cm left adrenal mass. She had normal electrolytes, and serum and urinary test results were negative for pheochromocytoma. A 24-hour urinary cortisol level was minimally elevated, and the midnight salivary cortisol value was within the reference range. Magnetic resonance imaging revealed a 6.5 × 5.8-cm left adrenal lesion that demonstrated moderate T2-weighted signal and gradual delayed enhancement with no drop in signal on out-of-phase images. Since the lesion lacked high intensity and the biochemical testing results did not suggest a pheochromocytoma, it was deemed likely that the mass was a malignant lesion of the left adrenal gland. A laparoscopic left adrenalectomy was performed. Morphologic and immunohistochemical findings were consistent with a large B-cell lymphoma, which by virtue of its near exclusive distribution in vascular spaces, was consistent with the diagnosis of intravascular large B-cell lymphoma.ConclusionIntravascular large B-cell lymphoma should be included in the differential diagnosis of an incidentally detected adrenal mass even though the diagnosis is rare. (Endocr Pract. 2008;14:884-888)     

Unusual Cause of Ectopic Secretion of Adrenocorticotropic Hormone: Cushing Syndrome Attributable to Small Cell Prostate Cancer

ObjectiveTo report a rare cause of ectopic adrenocorticotropic hormone (ACTH) secretion leading to severe Cushing syndrome.MethodsWe describe the clinical presentation and management of a case of Cushing syndrome attributable to ectopic ACTH secretion from small cell cancer of the prostate.ResultsIn a 70-year-old man with hypertension and diabetes, congestive heart failure developed. He was found to have severe hypokalemia (serum potassium, 1.7 mEq/L) and a huge pelvic mass on a computed tomographic scan performed because of a complaint of urinary retention. Transurethral biopsy of the prostate showed features of small cell prostate cancer. Hormonal evaluation revealed a high urine free cortisol excretion of 6,214.5 μg/d (reference range, 36 to 137), confirming the diagnosis of Cushing syndrome. A serum ACTH level was elevated at 316 ng/dL (reference range, 10 to 52). An overnight highdose (8 mg orally) dexamethasone suppression test was positive (serum cortisol levels were 43.2 and 41 μg/dL before and after suppression, respectively), and magnetic resonance imaging of the pituitary gland disclosed no abnormalities. A prostate biopsy specimen showed small cell prostate cancer with positive staining for ACTH. The tumor was found to be unresectable, and the poor condition of the patient did not allow for bilateral adrenalectomy. He was treated with ketoconazole and metyrapone, which yielded good temporary control of his Cushing syndrome (24-hour urine free cortisol decreased to 55.2 μg/d). He received 1 cycle of chemotherapy (etoposide and cisplatin), but he died 6 months later as a result of sepsis.ConclusionSmall cell prostate cancer is a rare subtype that can be associated with ectopic secretion of ACTH and severe Cushing syndrome. With this subtype of prostate cancer, Cushing syndrome should be considered and appropriately managed. (Endocr Pract. 2010;16:249-254)     

A 30-Year,Single-Center Experience of Unilateral Adrenalectomy for Primary Bilateral Macronodular Adrenal Hyperplasia

ObjectiveThe aim was to assess the short- and long-term outcomes of unilateral adrenalectomy (UA) in patients with primary bilateral macronodular adrenal hyperplasia (PBMAH).MethodsWe conducted a retrospective study of 124 patients with PBMAH who underwent UA.ResultsOne hundred sixteen patients were available for follow-up (median, 28.5 months). Cushingoid features remitted in 43 of 65 patients (70.8%) with overt Cushing syndrome (CS). Hypertension and diabetes mellitus improved in 79 of 96 (82.3%) and 29 of 42 patients (69.0%), respectively. Glucocorticoid insufficiency developed in 7 of 116 patients (6.0%) after the surgery, and it resolved in all the patients during follow-up. The mean 24-hour urinary free cortisol level decreased gradually from 456.02 ± 422.33 mg/24 h at baseline to 84.47 ± 70.06 mg/24 h within 3 months and then increased progressively in some patients. Sixty-four of the 116 patients (55.2%) had biochemical recurrence and 43 patients (67.2%) underwent contralateral adrenalectomy. The median time interval between the second operation and the first UA was 24 months. Patients with overt CS had a larger surgical-side or contralateral adrenal volume than patients without overt CS. Patients with a contralateral adrenal volume of >33.54 mL or with a preoperative urinary free cortisol level of >216.08 mg/24 h were more likely to have recurrence.ConclusionThe efficiency of UA is transient for the majority of patients, and the indications should be strictly limited to those with subclinical or milder CS. Patients who undergo successful UA still require close life-time follow-up for the recurrence of hypercortisolism.     

Diagnostic Challenges in Adrenocortical Carcinoma: Recommendations for Surveillance after Surgical Resection of Selected Adrenal Nodules

ObjectiveTo discuss challenges in the diagnosis of adrenocortical carcinoma and to suggest surveillance measures after removal of selected adrenal nodules.MethodsWe present the case of a 65-year-old man with worsening hypertension and new-onset hypokalemia attributed to primary hyperaldosteronism due to a 3-cm right adrenal nodule.ResultsA laparoscopic right adrenalectomy was performed, and the histologic diagnosis was a benign adenoma. The patient’s hypertension and hypokalemia improved postoperatively but recurred 8 months later, and florid Cushing’s syndrome developed. Magnetic resonance imaging showed an 8-cm mass in the right adrenal bed and multiple hepatic metastatic lesions. Fine-needle biopsy confirmed the presence of adrenocortical carcinoma.ConclusionDespite a comprehensive biochemical, radiologic, and histologic assessment, the diagnosis of adrenocortical carcinoma can be missed. Particularly, we caution against undue reliance on the initial tumor size. We recommend that abdominal imaging be performed every 3 months for the first year and every 6 months for the second year after surgical removal of selected adrenal nodules. (Endocr Pract. 2007;13:636-641)     

The Low-Dose Acth Stimulation Test: is 30 Minutes Long Enough?

Objective: Controversy persists regarding the use of the low-dose adrenocorticotropic hormone (ACTH) stimulation test (LDST) for the diagnosis of adrenal insufficiency (AI) and optimal test result interpretation. However, many centers are now using the LDST to assess cortisol secretion adequacy, and some only use a 30-minute cortisol level to determine adrenal sufficiency or AI. This study examined both 30- and 60-minute cortisol levels to assess whether the interpretation of the test was affected when both cortisol levels were taken into consideration.Methods: Data were obtained by retrospective chart review from a single pediatric endocrinology unit over a 7-year period. We identified 82 patients who completed the LDST. Their mean age was 11.7 years, and 37% were female. Cortisol levels were evaluated at baseline and 30 and 60 minutes after cosyntropin administration. A cutoff value ≥18 μg/dL was used to define adrenal sufficiency.Results: We found that 54% of patients reached peak cortisol levels at 60 minutes, and 11 patients who did not pass the test at 30 minutes did so at 60 minutes. The only predictive characteristic was weight status; overweight and obese individuals tended to peak at 30 minutes, and normal and underweight individuals tended to peak at 60 minutes.Conclusion: Although further studies are necessary to confirm our findings, it appears that measuring cortisol both 30 and 60 minutes following synthetic ACTH administration may be necessary to avoid overdiagnosing AI.Abbreviations: ACTH = adrenocorticotropic hormone AI = adrenal insufficiency BMI = body mass index LDST = low-dose ACTH stimulation test MRI = magnetic resonance imaging     

Desmopressin test in the diagnosis and follow-up of cyclical Cushing's disease

ObjectiveTo assess the utility of the desmopressin (DDAVP) test in the diagnosis and follow-up of a cyclical Cushing's disease (CCS) case.Material and methodsLaboratory tests included morning and midnight serum cortisol levels, 24 h urine free cortisol excretion, midnight salivary cortisol levels, serum cortisol levels after low (1 mg) and high (8 mg) dexamethasone, plasma ACTH and serum cortisol levels after DDAVP. Magnetic resonance imaging (MRI) was used to assess the presence of a pituitary adenoma. The resected tumor specimen was studied by histological, immunohistochemical and cell biology techniques.ResultsA patient was referred to our unit with a diagnosis of Cushing's syndrome (CS) for further evaluation and treatment. However, no biochemical evidence of hypercortisolism was observed in the follow-up evaluations. Furthermore, the typical features of CS fluctuated throughout this period. A consistent positive response to the DDAVP stimulation test was observed during the diagnostic work-up, even when overt clinical features of CS were not apparent, raising suspicion for CCS. After two years of follow-up a definitive diagnosis of hypercortisolism was established. An MRI scan revealed a pituitary adenoma, as the source of ACTH production. After transphenoidal surgery, clinical signs of CS resolved and the response to DDAVP became negative. DDAVP induced a significant increase in ACTH levels in cultured pituitary adenoma cells, consistent with the in vivo DDAVP test results.ConclusionsOur case illustrates the utility of the DDAVP test in the evaluation of patients with suspected CCS. The DDAVP test could facilitate the management of CCS by shortening the time of diagnosis.     

Adenoma adrenal como etiología de síndrome de Cushing: veinte años de experiencia en un centro mexicano de tercer nivel

IntroductionCushing's syndrome (CS) includes a wide range of clinical and laboratory abnormalities and is the final outcome of chronic glucocorticoid exposure. Adrenal adenomas are an uncommon cause of adult CS.ObjectiveTo describe the characteristics and outcome of patients with CS caused by adrenal adenomas in a referral center.MethodsWe performed a retrospective cross-sectional observational study of patients with a diagnosis of CS caused by adrenal adenomas managed in our center over a 20-year period. Our clinical experience in the diagnosis and treatment of this entity was analyzed.ResultsThere were a total of 20 patients, 19 women and one man. The mean age was 25.9 years (14 to 52). The most frequently recorded clinical data were hirsutism and moon face. The mean morning cortisol level was 26.9±10.7 mcg/dl, the mean afternoon level was 24.4±8.5 mcg/dl and the mean corticotropin (ACTH) concentration was 24±19.4 pg/ml. Only four patients (20%) had ACTH levels below 5 pg/ml. The results of dynamic testing with dexamethasone suggested adrenal adenoma in 100% of the patients. Seventy percent of adenomas were found in the left gland. The mean size of the lesion was 2.8±0.47 cm.ConclusionsIn dynamic testing, the criteria of non-suppression with high doses of dexamethasone were evident in almost all patients. ACTH measurement in our center was not reliable in identifying adrenal adenoma as a cause of CS.     

Concomitant Secretion of Glucocorticoid,Androgens, and Mineralocorticoid by an Adrenocortical Carcinoma: Case Report and Review of Literature

ObjectiveTo present a case of concomitant secretion of cortisol, androgens, and 11-deoxycorticosterone (DOC) by an adrenocortical carcinoma and review the literature in an attempt to identify similar cases.MethodsThe patient’s medical history, physical examination, laboratory data, computed tomographic scan, and histopathologic results were analyzed and summarized in a case report, and an extensive review of the literature was performed.ResultsEndocrinologic data showed excess cortisol production, substantially elevated testosterone and androstenedione levels, and profoundly increased DOC in the setting of suppressed aldosterone. An abdominal computed tomographic scan showed a left adrenal tumor. A left adrenalectomy was performed, and the histopathologic diagnosis was stage II adrenocortical carcinoma. The review of the pertinent literature revealed the absence of any identical cases in the past.ConclusionOur patient presented with a rare case of cosecretion of cortisol, testosterone, androstenedione, and DOC by an adrenocortical carcinoma, resulting in a clinical picture consistent with Cushing’s syndrome, hyperandrogenism, and primary hypermineralocorticoidism. We recommend the routine performance of a DOC assay in the setting of mineralocorticoid excess in association with low plasma aldosterone levels. (Endocr Pract. 2007;13: 408-412)     

Utility of a Single Late-Night Plasma Cortisol and Acth for the Diagnosis of Cushing Syndrome

Objective: To evaluate the diagnostic efficacy of various screening tests for the diagnosis of Cushing syndrome (CS).Methods: Thirty-five patients with CS and 16 patients of pseudo-CS were enrolled. Assessment of 24-h urinary free cortisol (UFC), late-night salivary cortisol (LNSC), overnight dexamethasone suppression test (ONDST), late-night plasma cortisol (LNPC), and adrenocorticotropic hormone (ACTH) on outpatient basis, and during sleep as well as in awake state after 48 hours of hospital admission.Results: We found that 24-h UFC performed the best among the screening tests with sensitivity, specificity and areas under the curve (AUCs) of 96.0%, 99%, and 0.988, respectively, at a cut-off of 144.6 μg/24 h. A cut-off of 10.5 nmol/L for LNSC had sensitivity 85.7%, specificity 88.2%, and an AUC of 0.897. A cut-off of 412.4 nmol/L for LNPC on outpatient basis had sensitivity 88.2%, specificity 91.2%, and an AUC of 0.957. Cut-offs of 215 and 243.3 nmol/L for LNPC during sleep and awake states after acclimatization had sensitivity, specificity, and an AUC of 94.1%, 88.2%, and 0.958, respectively. An ONDST cut-off of 94.6 nmol/L provided sensitivity, specificity, and an AUC of 96.0%, 99.03% and 0.995, respectively. A cut-off of 30.3 pg/mL for late-night ACTH on outpatient basis had sensitivity 67.6%, specificity 99.9%, and an AUC 0.796.A cut-off of 22.6 pg/mL for ACTH during sleep state after acclimatization had sensitivity, specificity, and an AUC of 73.5%, 99.2%, and 0.827, respectively.Conclusion: UFC is the best screening test for CS. Furthermore, single measurements of LNPC and ACTH help to establish the diagnosis and ACTH dependency of CS in the majority of patients with CS.Abbreviations:ACTH = adrenocorticotropic hormoneAUC = area under the curveCRH = corticotropin-releasing hormoneCS = Cushing syndromeECLIA = electrochemiluminescence immuno-assayLDDST = low-dose dexamethasone suppression testLNPC = late-night plasma cortisolLNSC = late-night salivary cortisolONDST = overnight dexamethasone suppression testRIA = radio-immuno assayUFC = urinary free cortisol