Pheochromocytoma in Patients Suspected of Harboring Adrenal Meta stasis: Management and Clinical Predictors

ObjectiveTo study clinical management of patients with suspected adrenal metastasis and to assess whether there are clinical predictors of pheochromocytoma in this patient population.MethodsIn this retrospective cross-sectional study, we reviewed medical records of patients who had adrenalectomy for adrenal lesions or had adrenal biopsy performed between January 1997 and July 2007 in a large academic hospital. Patients who harbored adrenal masses that were suspected of being metastases were identified on clinical findings. Pathologic diagnosis, demographic data, clinical history, imaging studies, and laboratory test results were reviewed and compared among patients whose adrenal mass was determined to be metastasis, adenoma, or pheochromocytoma.ResultsOne-hundred sixty-three patients had adrenalectomy or had adrenal biopsy during the study period. Thirty patients (18%) had adrenal masses that were suspected of being metastases. Of the adrenal masses, 18 (60%) were metastases, 8 (27%) were benign adenomas, and 4 (13%) were pheochromocytomas. Eleven patients (37%) had biochemical testing for pheochromocytoma. Adrenal biopsy was performed without biochemical testing for pheochromocytoma in 9 patients (30%), including 2 subsequently found to have this tumor. Adrenalectomy was performed in 10 patients (33%) without biochemical testing for pheochromocytoma. Clinical parameters were similar among patients with metastasis, adenoma, or pheochromocytoma. There were no clinical predictors to suggest pheochromocytoma.ConclusionsPheochromocytoma occurs frequently in patients suspected of harboring adrenal metastasis, but this tumor is often not considered in clinical practice. The size and imaging characteristics of the adrenal mass and history of known metastasis may help clinicians in decision-making. Biochemical testing for pheochromocytoma should ideally be performed in all patients suspected of having adrenal metastasis. (Endocr Pract. 2008;14:967-972)     

Glucocorticoid- and Androgen-Secreting Black Adrenocortical Adenomas: Unique Cause of Corticotropin-Independent Cushing Syndrome

ObjectiveTo describe the unique association of corticotropin-independent Cushing syndrome caused by cortisoland androgen-secreting black adrenal cortical adenomas with myelolipomatous change.MethodsWe report the clinical, laboratory, radiologic, and pathologic findings from 2 patients who presented with androgen excess and typical signs and symptoms of Cushing syndrome.ResultsEndocrine investigations showed high serum cortisol concentrations that lacked diurnal rhythm, undetectable plasma corticotropin concentrations, and absence of serum cortisol suppression after overnight dexamethasone suppression tests. Serum levels of adrenal androgens were elevated. Computed tomography of the abdomen revealed unilateral adrenal masses (largest lesional diameters 4.0 and 3.1 cm). On the basis of the plurihormonal hypersecretion and the imaging characteristics, adrenocortical carcinoma was considered as a possible diagnosis. However, histopathologic analysis in both patients revealed black adrenal cortical adenomas with myelolipomatous change. After surgery, adrenal androgens normalized, and the signs and symptoms of Cushing syndrome and androgen excess resolved. There was no evidence of recurrent disease at last follow-up.ConclusionsA unique form of corticotropin-independent Cushing syndrome is described: cortisoland androgen-secreting black adrenal cortical adenomas with myelolipomatous change. Although most patients with corticotropin-independent Cushing syndrome associated with androgen excess prove to have adrenocortical carcinoma, the clinician should be aware of the possibility of benign, black adrenal adenomas in this clinical setting. (Endocr Pract. 2011;17:e73-e78)     

Adrenal Incidentalomas, 2003 to 2005: Experience After Publication of the National Institutes of Health Consensus Statement

ObjectiveTo determine the clinical outcomes and follow-up imaging characteristics for incidentally discovered adrenal nodules at a large metropolitan health care center, as well as compliance with National Institutes of Health guidelines for the evaluation of these lesions.MethodsBetween October 2003 and June 2005, computed tomographic (CT) scanning performed at Harvard Vanguard Medical Associates detected 165 adrenal nodules (incidentalomas) in 129 patients without extra-adrenal malignant lesions or evidence of adrenal hyperfunction. Nodule characteristics, including size at baseline, change in size at follow-up, CT attenuation values, biochemical data, and clinical outcomes, were analyzed.ResultsOf the 165 adrenal incidentalomas, 96% were smaller than 4 cm. When attenuation values were determined, 65% were low (< 10 Housfield units). Ninetyeight patients (76%) with 142 nodules (86% of all incidentalomas) had at least 1 follow-up CT scan. Of these 142 lesions, 20 (14%) changed significantly in size (grew or became smaller by 0.5 cm or more). Growth was detected within 12 months in 5 of the 7 lesions (71%) that grew. For 95% of patients, the adrenal nodule did not necessitate intervention, including change in medication or surgical treatment. Biochemical studies for adrenal hyperfunction were done in 39 of the overall 129 patients (30%), but in only 20 of 109 patients (18%) not seen by endocrinologists.ConclusionMost adrenal incidentalomas are benign, nonfunctional tumors. Growth typically occurs within 12 months after detection. Despite the 2002 National Institutes of Health guidelines, 82% of patients at our medical center with adrenal nodules who were not seen by endocrinologists did not have hormonal testing. More physician education about the evaluation of incidentalomas should be provided, and prospective studies to establish the appropriate duration of follow-up should be conducted. (Endocr Pract. 2008;14:279-284)     

Clinical Outcomes in Adrenal Incidentaloma: Experience From one Center

Objective: To investigate the outcome in patients with adrenal incidentaloma (AI).Methods: A retrospective evaluation of 637 patients with AI referred to a tertiary center over 8 years. Radiologic and hormonal evaluations were performed at baseline. Follow-up imaging was carried out if necessary, and hormonal evaluation was performed at 24 months according to national guidelines.Results: The mean age was 62.7 ± 11.6 years, and the mean AI size was 25.3 ± 17.0 mm at presentation. Hormonal evaluation revealed that 85.4% of all tumors were nonfunctioning adenomas, 4.1% subclinical Cushing syndrome (SCS), 1.4% pheochromocytoma, 1.4% primary hyperaldosteronism, 0.8% Cushing syndrome, 0.6% adrenocortical carcinoma, 0.3% congenital adrenal hyperplasia, 2.2% metastasis to adrenals, and 3.8% other lesions of benign origin. Bilateral tumors were found in 11%, and compared to unilateral tumors, SCS was more prevalent. Only 2 cases were reclassified during follow-up, both as SCS, but neither had had a dexamethasone suppression test performed at initial work-up. In patients diagnosed with an adrenal metastasis, 92.9% were deceased within 2 years. Excluding those with malignant tumors, 12.9% of patients died during the study period of up to 11 years due to other causes than adrenal.Conclusion: Most AIs were benign, but a small fraction of tumors were functional and malignant. The prognosis of patients with adrenal metastasis was extremely poor, but otherwise, the mortality rate was similar to that for the general population. Follow-up of AIs <4 cm with an initial nonfunctional profile and benign radiologic appearance appears unwarranted, but screening for congenital adrenal hyperplasia should be considered.Abbreviations: 17OHP = 17-hydroxyprogesterone ACC = adrenal cortical carcinoma ACTH = adrenocorticotropic hormone AI = adrenal incidentaloma CAH = congenital adrenal hyperplasia CT = computed tomography CS = Cushing syndrome DST = dexamethasone suppression test HPA = hypothalamic-pituitary-adrenal axis MRI = magnetic resonance imaging SCS = subclinical Cushing syndrome T2DM = type 2 diabetes mellitus UFC = urinary free cortisol     

Safety and Feasibility of Laparoscopic Resection for Large (≥ 6 CM) Pheochromocytomas Without Suspected Malignancy

ObjectiveTo determine whether laparoscopic adrenalectomy in patients without radiologic evidence of cancer compromises the perioperative and long-term outcomes in patients with large (≥ 6 cm) pheochromocytomas.MethodsWe analyzed a prospective adrenal database of consecutive patients who underwent adrenalectomy at our institution between September 2000 and September 2010. Patients with diagnosed pheochromocytoma who underwent laparoscopic adrenalectomy were included. Patients with tumors smaller than 6 cm were compared with those presenting with tumors 6 cm or larger.ResultsOne hundred fifty-seven patients underwent adrenalectomy, and there were 32 catecholamine-secreting tumors. Of the 33, 7 were excluded from the study because of open surgery. Thus, 25 patients presented with 26 pheochromocytomas and underwent laparoscopic adrenalectomy. Thirteen of the 25 patients (52%) were women. Mean age (± standard error of the mean) was 53 ± 3 years. Mean tumor size was 5.2 ± 0.5 cm, and 11 pheochromocytomas (42%) were 6 cm or larger. Tumor size was significantly different between the large pheochromocytoma and the small pheochromocytoma groups (7.6 ± 0.4 vs 3.6 ± 0.4 cm, P <.001), but there was no significant difference in intraoperative complications, estimated blood loss, cancer diagnosis, or recurrence. The length of stay was comparable between the 2 cohorts, and there were no incidents of capsular invasion or adverse cardiovascular events.ConclusionLaparoscopic adrenalectomy of pheochromocytomas larger than 6 cm is feasible and safe with comparable results to those achieved with laparoscopic adrenalectomy in patients with smaller pheochromocytomas. (Endocr Pract. 2012;18:720-726)     

Disordered expression of adrenal steroidogenic P450 mRNAs in incidentally discovered nonfunctioning adrenal adenoma.

In order to elucidate the steroidogenesis of clinically nonfunctioning adrenocortical adenoma, we studied the aldosterone, cortisol (F) and dehydroepiandrosterone (DHEA) content and the expression of mRNA of cytochrome P450 for side chain cleavage (P450scc), 17 alpha-hydroxylase (P450c17). 21-hydroxylase (P450c21) and 11 beta-hydroxylase (P450c11) in four clinically nonfunctioning adrenocortical adenomas discovered incidentally in asymptomatic patients (Cases 1, 2, 3 and 4). The results were compared with those in normal adrenal glands. In the adenomas from cases 1 and 2, the abundance of steroidogenic P450s mRNA were similar to those in normal adrenal glands, except P450c11 mRNA expression in the adenoma from case 1 which was slightly higher than normal. The steroid content was normal level, except for higher F in the adenoma from case 1 and lower aldosterone in case 2 adenoma than normal. The adenoma from case 3 contained much less P450scc, P450c17 and P450c21 mRNA, while the amount of P450c11 mRNA was slightly greater than in normal adrenals. The adenoma showed normal aldosterone, high F and low DHEA content compared with normal adrenal glands. In the adenoma from case 4, the accumulation of all four P450 mRNAs decreased, whereas aldosterone, F and DHEA content in the adenoma was similar to that of normal adrenal glands. These data indicated that nonfunctioning adrenocortical adenoma showed similar or decreased expression of steroidogenic P450 mRNAs that the normal adrenal gland. This decreased expression of steroidogenic P450 mRNAs may be at least partly concerned with the absence of clinical symptoms in patients with nonfunctioning adenoma.     

ACTH sensitivity of isolated human pathological adrenocortical cells: variability of responses in aldosterone, corticosterone, deoxycorticosterone and cortisol production

In vitro aldosterone, deoxycorticosterone, corticosterone and cortisol production of human adrenocortical cells derived from adenomas (Conn's syndrome, Cushing's syndrome), from hyperplastic adrenals (Cushing's syndrome) and from adrenals surrounding aldosteronoma are described. Cells from adenomas causing either Cushing's syndrome or Conn's syndrome harboured the highest basal and ACTH-stimulated corticosteroid production. Adrenocortical cells derived from micronodular hyperplasia causing Cushing's syndrome and cells from cortisol producing adenoma displayed predominantly cortisol and corticosterone secretion both under basal conditions and following stimulation with ACTH. Aldosteronoma cells showed highly variable aldosterone, deoxycorticosterone, corticosterone and cortisol response to ACTH. However, in aldosteronoma cell suspensions, the basal and ACTH-stimulated ratios of aldosterone to cortisol were increased when compared to ratios of steroids produced by cells from other adrenal tissues. Chronic treatment with spironolactone of patients with Conn's syndrome before surgery was associated with a decreased ratio of aldosterone to corticosterone, revealing that 18-hydroxylase in aldosteronoma cells may be inhibited during long-term therapy. Non-tumorous cells isolated from adrenals surrounding aldosteronoma displayed less aldosterone prior to and after stimulation with ACTH than aldosteronoma cells.     

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.     

Pituitary Adenoma: A Clinician’S Perspective

ObjectiveTo review the underlying causes of pituitary lesions, a rational approach to their diagnosis, and therapeutic options.MethodsThe types of pituitary lesions and their clinical manifestations are reviewed, and treatment strategies and long-term follow-up are discussed.ResultsA pituitary adenoma is quite common and poses a challenge to the clinician to determine the clinical significance, the appropriate diagnosis, the need for treatment, and the appropriate therapy or therapies. The treatment of a pituitary adenoma depends on the type of tumor; a prolactinoma is treated medically with a dopamine agonist drug, and other lesions are usually treated by transsphenoidal surgical removal. Replacement of a deficient hormone or hormones is necessary for optimal functioning. Some patients require more than one treatment, including surgical intervention, replacement of a hormone or hormones, medications to lower hormone hypersecretion to normal (for prolactinoma, acromegaly, or Cushing disease), pituitary radiation therapy (optimally with focused irradiation such as the Gamma Knife or LINEAC), and, in the situation of persistent Cushing disease, bilateral adrenalectomy as a last resort. Lifelong monitoring is necessary for all these patients.ConclusionThe goal is to decrease the mass effect of the adenoma, to restore normal pituitary function, and to suppress hormone hypersecretion. Achievement of this goal necessitates the cooperation and interdisciplinary efforts of several medical specialties. (Endocr Pract. 2008;14:757-763)     

Mixed Corticomedullary Carcinoma of the Adrenal Gland: A Case Report

ObjectiveTo report the case of a 78-year-old woman with mixed corticomedullary carcinoma of the adrenal gland, and to review other reported lesions that exhibit clinical and/or histopathologic features of both adrenal cortical and medullary differentiation.MethodsWe describe the patient’s clinical findings and laboratory test results, as well as the gross and histopathologic features of her tumor. We also review the literature pertaining to mixed corticomedullary adenomas and cortical tumors with clinical features of pheochromocytoma, and vice versa.ResultsA 78-year-old woman with a 10-cm left adrenal mass was hospitalized for management of hypertensiveurgency. Laboratory workup revealed elevated urinary metanephrine excretion and elevated serum dehydroepiandrosterone sulfate levels. She underwent left adrenalectomy. Pathologic examination of the lesion showed mixed cortical and medullary histologic characteristics, as well as gross and microscopic evidence of malignancy. Including the present case, we identified 17 cases of neoplasms that exhibit features of mixed corticomedullary differentiation.ConclusionsThis report represents the first documented case of mixed corticomedullary carcinoma. Several benign lesions combine clinical, biochemical, and/or histopathologic evidence of both adrenal cortical and medullary differentiation, including mixed corticomedullary adenomas and corticotropin-secreting pheochromocytomas. The differential diagnosis of a lesion with mixed cortical and medullary features should also include a malignant neoplasm. (Endocr Pract. 2012;18:e37-e42)     

Serum Matrix Metalloproteinase-9 Levels in the Diagnosis of Functioning Adrena Tumors

ObjectiveTo investigate whether serum matrix metalloproteinase-9 (MMP-9) levels can be used as a diagnostic tool in determining the functioning status of benign adrenal tumors.MethodsIn this case-control study, medical records of patients with adrenal tumors who consecutively presented to an endocrinology clinic between August 2005 and October 2008 were evaluated. Operation was recommended when the incidentaloma was larger than 4 cm or when a hypersecreting tumor was suspected. A control group of healthy persons matched for age, body mass index, and sex was also enrolled. Patients underwent routine endocrinologic examinations. MMP-9 levels were compared preoperatively and postoperatively. Findings were compared among patients with functioning adrenal tumors, patients with nonfunctioning adrenal tumors, and control participants.ResultsOf 370 patients with adrenal tumors, 50 with adrenal incidentaloma met the inclusion criteria. Twenty- five healthy individuals were enrolled as controls. Group 1 included 20 patients with functioning adrenal tumors (14 with Cushing syndrome and 6 with pheochromocytoma), and Group 2 included 30 patients with nonfunctioning adrenal tumors. MMP-9 levels were higher in patients with nonfunctioning adrenal tumors and functioning adrenal tumors than in control participants (P < .001). MMP-9 levels in patients with functioning adrenal tumors were significantly higher than those in patients with nonfunctioning adrenal tumors (P = .002). After operation, levels decreased significantly in patients with Cushing syndrome and in those with pheochromocytoma; however, patients with Cushing syndrome and pheochromocytoma had similar MMP-9 levels preoperatively and postoperatively. No significant linear correlation existed between tumor volume and MMP-9 levels. A significant positive correlation was determined between preoperative MMP-9 concentrations and 24-hour urinary fractionated metanephrine and epinephrine (r = 0.938, P = .006; r = 0.965, P = .002, respectively), between MMP-9 levels and baseline cortisol levels (r = 0.402, P = .003), and between MMP-9 levels and cortisol levels obtained after dexamethasone suppression testing (r = 0.357, P = .006).ConclusionOur data suggest that serum MMP-9 levels may be useful in differentiating benign subclinical functioning adrenal tumors from benign nonfunctioning adrenal tumors. (Endocr Pract. 2010;16:419-427)     

Unexpected Clinical Course During Treatment of a TSH-Secreting Pituitary Adenoma

ObjectiveTo report the rare occurrence of a patient with thyrotropinoma that transitioned into a secretory thyro-somatotroph adenoma during medical treatment with somatostatin analogue.MethodsWe report the case of a patient with a thyrotroph pituitary adenoma who developed de novo evidence of growth hormone cosecretion following one year of successful medical treatment.ResultsA 78-year-old woman was diagnosed with a thyroid stimulating hormone (TSH) secreting pituitary macroadenoma (TSHoma) based on classical clinical and biochemical features. There was no clinical or biochemical evidence of growth hormone (GH) cosecretion. She declined surgical resection and was treated with primary medical therapy, octreotide long acting repeatable (LAR), to which she had an antitumor and antisecretory response; however, following 12 months of successful medical treatment she developed de novo hypersecretion of growth hormone despite involution of the tumor mass. TSH-secreting pituitary adenomas may rarely become plurihormonal during apparently successful medical treatment. This may represent an unusual form of secondary resistance to somatostatin analogue or the rarer phenomenon of tumor transformation into a secretory thyro-somatotroph adenoma.ConclusionThe unexpected clinical course of this case highlights the need for careful long-term surveillance in patients with TSH secreting pituitary adenomas. (Endocr. Pract. 2013;19:e88-e91)     

Composite Pheochromocytoma-Ganglioneuroma:A Rare Experiment of Nature

ObjectiveTo present a rare case of composite pheochromocytoma-ganglioneuroma (Pheo-GN) of the adrenal medulla, review the related literature, and discuss the clinical features, pathologic findings, behavior, and management of such tumors.MethodsA case report of a patient with composite Pheo-GN of the adrenal gland is presented. Using the online database PUBMED, we searched and analyzed all cases of composite pheochromocytoma reported in the English-language literature during the past 70 years.ResultsOn computed tomography, a 61-year-old man was incidentally found to have a 3.8-cm nonadenomatous right adrenal lesion. Adrenalectomy revealed a 5-cm mass consistent with composite Pheo-GN. To date, 45 cases of composite pheochromocytomas have been reported during the past 70 years, 71% of which coexisted with ganglioneuromas. These tumors occurred with approximately equal frequency in male and female patients, the majority of whom were from 40 to 60 years old. Only 14 cases have been reported in the United States. Bilateral tumors were found in 3 cases. The mean size was 4 to 6 cm. Preoperatively, functional evidence was found in 76.3% of all composite pheochromocytomas (and in 67% of Pheo-GN). Only one Pheo-GN was found to have liver metastatic lesions at the time of autopsy; the rest were not aggressive.ConclusionTo our knowledge, this is the first literature review describing the characteristics and behavior of all reported cases of composite pheochromocytomas, with an emphasis on those with ganglioneuromas. Composite pheochromocytoma is a rare variant of a relatively uncommon disease diagnosed by pathologists only. Fortunately, the treatment of such an entity remains the same as for any pheochromocytoma. (Endocr Pract. 2010;16:291-299)     

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)     

Differential expression of the human somatostatin receptor subtypes sst1 to sst5 in various adrenal tumors and normal adrenal gland.

Somatostatin (SRIF) is a widely distributed peptide with growth-inhibiting effects in various tumors. So far, five distinct human SRIF receptor subtypes (sst1-sst5) have been identified. We investigated expression of the five ssts in various adrenal tumors and in normal adrenal gland. Tissue was obtained from ten pheochromocytomas (PHEOs), nine cortisol-secreting adenomas (CPAs), eleven aldosterone secreting adenomas (APAs) and eight non-functional adenomas (NFAs) after retroperitoneoscopic surgery, and used for RNA extraction. Adrenal tissue surrounding the tumor was available for analysis in twenty-seven cases. Receptor expression was studied by RT-PCR using sst-specific primers and subsequently confirmed by Southern blotting. Expression of all five receptor subtypes was observed in RNA obtained from normal adrenal gland. Furthermore, each receptor subtype was expressed in more than 50 % of all tumors analyzed. No sst5 expression was found in PHEOs, while sst1 was present in nearly all of these tumors. Only a few of the CPAs expressed subtypes sst1 and sst4. Expression of all five subtypes was distributed equally in APAs. No sst4 was found in any of the NFAs. Differential expression of ssts in various adrenal tumors may point to new aspects in the pathogenesis of these adenomas. Furthermore, the presence of specific ssts could expand the diagnostic and therapeutic strategies during management. New subtype specific analogues of SRIF may be used in the future depending on the type of adrenal tumor and receptor subtype expressed.     

The Role of Temozolomide in the Treatment of a Patient With a Pure Silent Pituitary Somatotroph Carcinoma

ObjectiveTo describe a case of a pure silent somatotroph pituitary carcinoma.MethodsWe describe a 54-year-old female with a clinically nonfunctioning pituitary macroadenoma diagnosed 15 years earlier.ResultsThe patient underwent transsphenoidal surgery and no visible tumor remnant was observed for 6 years. A magnetic resonance imaging (MRI) detected the recurrence of a 1.2 × 1.5 cm macroadenoma. The patient was submitted to conventional radiotherapy (4500 cGy), and the tumor volume remained stable for 7 years. Then, an MRI revealed a slight increase in tumor size, and 2 years later, a subsequent MRI detected a very large, invasive pituitary mass. The patient was resubmitted to transsphenoidal surgery, and the histopathological examination showed diffuse positivity for growth hormone (GH). The nadir GH level during an oral glucose tolerance test was 0.06 ng/mL, and the pre- and postoperative insulin like growth factor type I (IGF-I) levels were within the normal range. Abdominal, chest, brain, and spine MRI showed multiple small and hypervascular liver and bone lesions suggestive of metastases. Liver biopsy confirmed metastasis of GH-producing pituitary carcinoma. The patient has been treated with temozolomide and zoledronic acid for 7 months and with octreotide long-acting release (LAR) for 4 months. The primary tumor and metastases are stable.ConclusionDespite being an extremely rare event, pituitary carcinoma may develop several years after the successful treatment of even a silent GH-producing pituitary adenoma, which suggests that close long-term follow-up is necessary. (Endocr. Pract. 2013;19:e145-e149)     

Clinical and Radiological Features of Pheochromocytoma/Ganglioneuroma Composite Tumors: A Case Series with Comparative Analysis

ObjectiveTo describe and compare the clinical, biochemical, radiologic, and pathologic features of adrenal pheochromocytoma-ganglioneuroma (PC-GN) composites with the features of isolated pheochromocytomas (PCs) and adrenal ganglioneuromas (AGNs).MethodsWe reviewed data for PC-GN composite cases seen at a single tertiary center between 1993 and 2012 and compared them with cases of isolated AGN and relatively similar median-size PCs.ResultsNine PC-GN composites were included. The median age at diagnosis was 52 years (range, 28 to 83 years) for PC-GN compared with 55 years (range, 24 to 78 years) for PC patients and 40 years (range, 18 to 64 years) for AGN patients. Similar to PCs, all PC-GN composites were associated with catecholamine overproduction, whereas AGNs were nonfunctioning. On pathology, the median tumor sizes were 7 cm (range, 2.5 to 13 cm) for PC-GN tumors, 6.5 cm (range, 3.5 to 7 cm) for PCs, and 8 cm (range, 3.2 to 20 cm) for AGNs. On computed tomography (CT) imaging, PC-GN composites and PCs were heterogeneous, with both having significantly higher postcontrast density values than AGNs, which typically looked homogeneous and had a progressive enhancement pattern without contrast washout in most cases.ConclusionThe presence of a PC component significantly increases tumor heterogeneity and postcontrast density values. CT imaging could be very helpful in distinguishing AGNs from both PC-GN and PC tumors, but only pathologic examination can yield the diagnosis. Clinically and radiologically, PC-GN composites are indistinguishable from PCs and need to be managed similarly. (Endocr Pract. 2014;20:864-869)