Multiple Catecholamine-Secreting Paragangliomas: Diagnosis after Hemorrhagic Stroke in a Young Woman

ObjectiveTo describe a case of multiple catecholamine-secreting paragangliomas, with a hemorrhagicstroke as the main clinical manifestation.MethodsWe present a case report with clinical, laboratory, histologic, and genetic details.ResultsA 23-year-old woman with a history of hypertension treated with orally administered medications presented to our emergency department because of sudden onset of hemiplegia of the left side of the body. A computed tomographic scan of the brain showed a right frontoparietal hematoma, and her blood pressure was 185/115 mm Hg. She was admitted to the Department of Neurosurgery, and an external drain was inserted to evacuate the hematoma. She was then referred to the Department of Clinical Sciences, where a search for possible secondary causes of hypertension was undertaken. Substantially elevated urinary levels of vanillylmandelic acid and metanephrines were found, and a pheochromocytoma was suspected. Abdominal computed tomographic scans revealed a large retroperitoneal mass (3.6 by 4 cm) and similar smaller lesions in the right adrenal gland, between the aorta and the vena cava, and in the left paraaortic area. Iodine I 123 metaiodobenzylguanidine scintigraphy showed high uptake in those same areas, consistent with the diagnosis of multiple catecholamine-secreting paragangliomas. After adequate control of the patient’s hypertension was achieved with an a1-adrenergic receptor blocker, a Ca2 + antagonist, and a b-adrenergic blocking agent, the tumors were excised in the Department of Surgery. The histopathologic findings confirmed the diagnosis of multiple paragangliomas. The genetic analysis demonstrated an exon 4 mutation in codon 109 (CAA > TAA,Gln > Stop) of the SDHD gene.ConclusionAlthough cerebral hemorrhage is an unusual complication of pheochromocytomas or paragangliomas, early recognition of the characteristic symptoms of headache, palpitations, and diaphoresis in a patient with hypertension and prompt appropriate intervention can minimize the morbidity associated with such tumors and prevent a potentially fatal outcome. (Endocr Pract. 2008; 14:340-346)     

Familial Carotid Body Tumors In Patients With Sdhd Mutations: A Case Series

ObjectiveTo describe a family with hereditary paraganglioma due to a disease-causing mutation in the SDHD gene.MethodsWe present the clinical findings, diagnostic test results, treatment, and genetic test results in a family with hereditary paraganglioma.ResultsThree siblings with bilateral carotid body tumors presented at different time points and with varied clinical presentations. While the proband, a 20-year-old man, was not hypertensive and had normal urinary metanephrine and normetanephrine levels, his sister and brother had a more severe clinical picture, with hypertension in both and elevated normetanephrine levels in his brother (his brother had pheochromocytoma and 2 intra-abdominal paragangliomas). Mean age at presentation was 24 years. A 4-base pair frameshift mutation, c.337-340delGACT, was detected in exon 4 of the SDHD gene in all 3 patients.ConclusionThis is the first report of the c.337340delGACT mutation being associated with hereditary paraganglioma; this report emphasizes the need to screen all at-risk first-degree relatives for the disease-causing SDHD mutation once it has been identified in an affected family member. (Endocr Pract. 2012;18:e106-e110)     

Comparison of Pheochromocytomas and Abdominal and Pelvic Paragangliomas with Head and Neck Paragangliomas

ObjectiveTo compare clinical, radiologic, and pathologic characteristics, as well as management and outcomes, in a series of pheochromocytomas, abdominal and pelvic paragangliomas, and pelvic paragangliomas with head and neck paragangliomas.MethodsIn this retrospective study, we reviewed charts of all patients seen at our institution between January 1995 and December 2006. We searched pathology and medical record databases under the terms pheochromocytoma, paraganglioma, head and neck tumors, carotid body tumors, glomus jugulare, and neuroendocrine tumors. We compared clinical, radiologic, and pathologic characteristics, as well as management and outcomes, between patients with pheochromocytoma, abdominal and pelvic paraganglioma, and head and neck paraganglioma.ResultsEighty-six patients were included (46 with head and neck paraganglioma, 23 with pheochromocytoma, and 17 with abdominal or pelvic paraganglioma). Compared with patients with head and neck paraganglioma, patients with pheochromocytoma or abdominal and pelvic paraganglioma were younger (35.7 ± 16 years vs 43 ± 17 years, P = .042) and were more likely to have the classic triad associated with catecholamine hypersecretion of palpitation, excessive sweating, and headache (40% vs 0%, P < .001); hypertension (70% vs 37%, P = .005); and benign tumors (65% vs 43%, P = .03). Patients with head and neck paraganglioma and patients with pheochromocytoma/abdominal and pelvic paraganglioma were not different in female to male ratios (27:19 vs 29:11, respectively, P = .18), tumor size (5.8 ± 2.7 cm vs 5.7 ± 3 cm, respectively; P = .85), or remission rate (43% vs 60%, respectively, P = .13).ConclusionsHead and neck paraganglioma are similar to pheochromocytoma and abdominal and pelvic paraganglioma in size and outcome, but occur at an older age, lack hyperadrenergic manifestations, and are more likely to have local pressure effects and result in persistent disease. (Endocr Pract. 2009;15:194-202)     

Large Adrenal Oncocytoma with Uncertain Malignant Potential: Case Report and Review of Literature

ObjectiveTo report a case of oncocytoma, a relatively rare adrenal tumor, which most commonly is detected as an adrenal incidentaloma.MethodsWe present a case report, including laboratory, imaging, and pathologic findings, of a 47-year-old obese woman who had hypertension and an incidentally found large, left adrenal mass.ResultsOn the basis of the hormonal evaluation, this mass was a nonsecreting adrenal tumor, which histologically proved to be an oncocytoma with borderline malignant characteristics. A collective analysis of the few cases of adrenal oncocytoma published in the medical literature showed that our case corresponded to the previously published cases in preponderant location (left side) as well as the general size (11.4 cm in the largest dimension) and weight (372 g).ConclusionAdrenal oncocytoma should be included in the differential diagnosis of adrenal incidentalomas, especially if large tumors are detected. In addition, a longterm follow-up is suggested because there are no certain clues about the true potential of this tumor. (Endocr Pract. 2010;16:641-645)     

Necessity for Long-Term Follow-Up of Patients With Head and Neck Paraganglioma and Mutation in the Succinate Dehydrogenase Genes: An Index Case Report and Literature Review

ObjectiveTo describe a patient with hereditary head and neck paraganglioma (HNPGL) and to review the literature on these rare tumors.MethodsWe review the English-language literature regarding SDH mutations, HNPGL, hereditary paraganglioma-pheochromocytoma syndrome, and the role of functional imaging in the follow-up of these tumors. We also describe the clinical findings, imaging results, and follow-up of a man who initially presented with HNPGL and subsequently developed metastatic pheochromocytoma 20 years later.ResultsA 66-year-old man presented with a history of hypertension, palpitations, sweating, and elevated urinary norepinephrine. Iodine-123-metaiodobenzylguanidine (¹²³I-MIBG) scan demonstrated a left suprarenal mass and multiple avid lesions in the abdomen, chest, and posterior cranial fossa. Histologic examination confirmed aSubmitted for publication February 25, 2012 Accepted for publication May 14, 2012To purchase reprints of this article, please visit: www.aace.com/reprints. Copyright © 2012 AACE.metastatic pheochromocytoma, and molecular genetic testing revealed a mutation in the SDHD gene. The patient had had surgery 20 years earlier for HNPGL. Although most HNPGLs arise sporadically, susceptibility genes have been identified in approximately one-third of cases. Optimal follow-up remains controversial. We reiterate a need for longterm follow-up of patients with a mutation in an SDH gene. ¹²³I-MIBG, highly specific for identifying ectopic neuroendocrine tissue, may have a role in long-term follow-up.ConclusionsAlthough HNPGLs rarely metastasize, their malignant potential is difficult to predict. Routine surveillance for at-risk patients is recommended. Patients with a mutation in an SDH gene should therefore undergo regular surveillance. (Endocr Pract. 2012;18:e130-e134)     

Parathyroid Carcinoma in Multiple Endocrine Neoplasia Type 1 with a Classic Germline Mutation

ObjectiveTo report the case of a patient with multiple endocrine neoplasia type 1 (MEN 1) syndrome with concomitant parathyroid carcinoma and a classic MEN1 germline mutation.MethodsWe present the clinical findings, laboratory results, imaging studies, and surgical histopathologic features in a woman with MEN 1 syndrome and concomitant parathyroid carcinoma. We also review the literature regarding patients with similar clinical entities and the use of adjuvant radiotherapy for parathyroid carcinoma.ResultsA 53-year-old woman presented with nausea and severe primary hyperparathyroidism. Computed tomography revealed parathyroid masses, shown later to be bilateral parathyroid carcinomas and adenomas. Magnetic resonance imaging demonstrated a pituitary macroadenoma, and gastrinomas were confirmed by computed tomography and a secretin stimulation test. She was successfully treated with total thyroidectomy, subtotal parathyroidectomy, and adjuvant radiotherapy. Genetic analysis revealed a classic MEN1 germline mutation.ConclusionThis report describes a patient with parathyroid carcinoma occurring in conjunction with MEN 1, further characterizing this rare condition. In contrast to previously described patients, our patient is the first with a classic MEN1 germline mutation, confirming that parathyroid cancer can occur in association with classic MEN 1 genetics. (Endocr Pract. 2009;15:567-572)     

Management Of Catecholamine-Secreting Tumors In Pregnancy: A Review

Objective: Catecholamine-secreting tumors (pheochromocytomas and paragangliomas) presenting during pregnancy are extremely rare, but they can be fatal to both mother and fetus. Recent discoveries in the genetic background of these tumors are expected to address an increasing number of at-risk women to prenatal diagnosis.Methods: The literature was reviewed in order to provide clinicians with a practical and updated guide on how to manage this life-threatening condition.Results: The clinical presentation of catecholamine-secreting tumors can be deceptive and mimic common disorders of pregnancy. Silent catecholamine-secreting tumors can become evident during pregnancy, and hypertension cannot be considered a hallmark for this condition: some women may be normotensive or develop orthostatic hypotension. Biochemical screening includes measurement of plasma free metanephrines or urinary fractioned metanephrines. Measurement of catecholamines, dopamine, and methoxytyramine can provide further information on tumor biology, location, and prognosis. Diagnostic imaging is limited, and medical treatment requires a cautious balance between hemodynamic control and effects on the fetoplacental unit. Several genes have been associated with syndromes including catecholamine-secreting tumors, and positive genetic testing can correlate with tumor behavior. Timing and modalities for tumor removal and delivery, including anesthetic management, depend on gestational age, maternal and fetal wellbeing, control of catecholamine excess, suspicion of multiple or malignant disease, and surgical accessibility to the tumor.Conclusion: A timely diagnosis and a multidisciplinary approach are the keys to improve pregnancy outcomes in patients with a catecholamine-secreting tumor; each case should be managed in a tertiary referral center.Abbreviations:CCB = calcium channel blockerCST = catecholamine-secreting tumorMRI = magnetic resonance imagingPG = paragangliomaPHEO = pheochromocytoma     

Pheochromocytoma: A Genetic And Diagnostic Update

Objective: Pheochromocytomas and paragangliomas (PPGLs) are neuroendocrine tumors derived from adrenal or extra-adrenal locations, respectively. Upon suspicion of PPGL, specific metabolomic, molecular, biochemical, imaging, and histopathologic studies are performed to prove, localize, treat, and monitor disease progression. Improved diagnostic tools allow physicians to accurately diagnose PPGL, even in patients presenting with small (<1 cm) or biochemically silent tumors, which previously delayed proper detection and treatment.Methods: This review outlines the most updated approach to PPGL patients and presents a new diagnostic protocol for physicians to increase earlier tumor identification and accurately assess metastatic behavior.Conclusion: We present the most recent advances in genetics, epigenetics, metabolomics, biochemical, and imaging diagnoses of this rare tumor to properly assess disease, decide treatment options, and manage follow-up. We also elaborate on new therapeutic perspectives in these very rare neoplastic entities.Abbreviations: ATRX = ATRX chromatin remodeler; ccRCC = clear cell renal cell carcinoma; c-MYC = MYC proto oncognene; CT = computed tomography; DOTATATE = DOTA-octreotate; EGLN1/2 = egl-9 family hypoxia inducible factor 1/2; EGLN2/PHD1 = egl-9 family hypoxia inducible factor 2; EPAS1/HIF2A = endothelial PAS domain protein 2/hypoxia-inducible factor 2α; ERK = extracellular signal-regulated kinase; HIFs = hypoxia-inducible factors; HIF-α = hypoxia-inducible factor alpha; HNPGLs = head and neck paragangliomas; ¹⁷⁷Lu-DOTATATE = lutetium octreotate; MAX = myc-associated factor X; MDH2 = malate dehydrogenase; MIBG = metaiodobenzylguanidine; MN = metanephrine; MRI = magnetic resonance imaging; mTOR = mammalian target of rapamycin; NETs = neuroendocrine tumors; NF1 = neurofibromin 1; NMN = normetanephrine; PHD = prolyl hydroxylase domain protein; PI3K = phosphoinositide 3-kinase; PPGLs = pheochromocytoma and paragangliomas; PRRT = peptide receptor radionuclide therapy; Pvhl = von Hippel-Lindau protein; RAS = rat sarcoma oncogene; RET = rearranged during transfection proto-oncogene; SDH = succinate dehydrogenase; SDHA, -B, -C, -D = succinate dehydrogenase subunits A, B, C, D; SDHAF2 = succinate dehydrogenase complex assembly factor 2; SDHB, C, D = succinate dehydrogenase subunits B, C, D; SDHx = succinate dehydrogenase subunits; SSTRs = somatostatin receptors; VHL = von Hippel-Lindau     

Primary Hyperparathyroidism and Jaw Tumor Syndrome: A Novel Mutation of the HRPT2 Gene

ObjectiveTo discuss a case of hyperparathyroidismjaw tumor syndrome (HPT-JT) and its clinical course, as well as describe a new mutation within HRPT2, the gene associated with HPT-JT.MethodsWe describe the clinical course, laboratory data, and diagnostic imaging of a patient with HPT-JT, including the mutation analysis of the HRPT2 gene. A review of the related literature is also presented.ResultsA 22-year-old man presented with progressive bone pain and weakness, and investigation revealed a serum calcium level of 17.6 mg/dL, a phosphorus concentration of 1.8 mg/dL, and an intact parathyroid hormone value of 2,808 pg/mL. X-ray examinations showed a fracture of the left hip and compression fractures of the lumbar spine. Computed tomography disclosed a mass in his mandible, clinically suggesting HPT-JT. Genetic analysis of the HRPT2 gene demonstrated a frameshift mutation resulting in a premature stop codon. The patient underwent parathyroidectomy, and 1 year later his fractures had healed and dual-energy x-ray absorptiometry showed substantial improvement in bone mineral density.ConclusionPrevious reports have cited mutations of the gene HRPT2 leading to HPT-JT and its associated phenotypes. We report one such mutation, not reported previously, in a patient with HPT-JT. This case adds to the growing evidence that different mutations in the HRPT2 gene can lead to HPT-JT, although it remains unclear whether specific mutations are more strongly associated with a particular phenotype. (Endocr Pract. 2008;14: 743-747)     

Recurrent Hyperparathyroidism and a Novel Nonsense Mutation in a Patient with Hyperparathyriodism-Jaw Tumor Syndrome

ObjectiveTo present the case of a hyperparathyroidism-jaw tumor (HPT-JT) patient with a novel nonsense mutation of the CDC73 gene.MethodsWe present the case of a patient with a history of three prior maxillectomies and two prior parathyroidectomies who presented with recurrent primary hyperparathyroidism (PHPT). We also briefly review the literature pertaining to HPT-JT.ResultsGenetic analysis revealed a novel nonsense mutation (c.85G>T; pGlu29) in exon 1 of CDC73. The patient’s son underwent genetic testing for a CDC73 mutation and was found to be negative.ConclusionHPT-JT is a rare condition characterized by PHPT and benign tumors of the mandible and maxilla. Up to 15% of HPT-JT patients with PHPT have parathyroid carcinoma. HPT-JT is associated with an inactivating mutation of CDC73, a gene that codes for the tumor suppressor protein parafibromin. This report expands our understanding of the genetics underlying this rare disorder and emphasizes the importance of early detection in order to prevent hypercalcemic complications such as parathyroid carcinoma. (Endocr. Pract. 2013;19:e134-e137)     

Apparent Mineralocorticoid Excess Caused by a Novel Mutation in 11-β Hydroxysteroid Dehydrogenase type 2 Enzyme: its Genetics and Response to Therapy

ObjectiveTo present a case of apparent mineralocorticoid excess (AME) due to a novel mutation in the HSD11B2 gene and describe the patient’s response to therapy.MethodsThe clinical, biochemical, and genetic features of the proband and his family are presented. For the genetic study, DNA was extracted from peripheral leucocytes. The exons and exon-intron boundaries were polymerase chain reaction (PCR)-amplified and directly sequenced.ResultsA 10-year-old male presented with hypertension (HTN) and weakness and was found to have hypokalemia of 2.6 mmol/L. Plasma renin was undetectable, and plasma and urinary aldosterone were low. Serum cortisol and deoxycorticosterone were normal. Daily urinary excretion of cortisol was normal, but urinary and serum cortisone levels were undetectable. The patient was treated with spiranolactone with inadequate response. A small dose of dexamethasone was added and led to excellent control of HTN and hypokalemia. Genetic studies showed a novel missense biallelic mutation changing guanine to adenine in exon 3 (c.G526A) of the HSD11B2. This mutation changes the amino acid aspartic acid to asparagine at codon 176 (p.D176N). A monoallelic form of the same mutation was found in the parents and 3 of his 4 healthy siblings but not in a healthy sister or 100 normal subjects.ConclusionsA case of AME due to a novel mutation in HSD11B2 showed the usual features of AME but exhibited an inadequate response to spironolactone. A small dose of dexamethasone resulted in an excellent response. (Endocr Pract. 2014;20:e151-e156)     

Hyperandrogenism Due to a Testosterone-Secreting Sertoli-Leydig Cell Tumor Associated With a Dehydroepiandrosterone Sulfate-Secreting Adrenal Adenoma in a Postmenopausal Woman: Case Presentation and Review of Literature

ObjectiveTo report a case of hyperandrogenism attributable to the presence of an adrenal adenoma secreting dehydroepiandrosterone sulfate (DHEA-S) and an ovarian Sertoli-Leydig cell tumor secreting testosterone in a postmenopausal woman.MethodsThe laboratory, radiologic, and pathologic findings in our case are described. In addition, the pertinent literature is reviewed.ResultsA 56-year-old woman presented with a history of gradual increase in facial and body hair, scalp hair loss, male pattern baldness, and deepening of her voice, beginning a few years after spontaneous menopause at age 49 years. She had hypertension, obesity, and type 2 diabetes mellitus. Laboratory tests showed elevated levels of total testosterone (348 ng/dL) and DHEA-S (2,058 μg/dL), and a left adrenal tumor (3 by 4 cm) was detected on abdominal computed tomographic scan. Laparoscopic left adrenalectomy was performed, and the pathologic diagnosis was adrenal adenoma. The DHEA-S returned to normal levels, but the serum testosterone concentration remained elevated. Transvaginal ultrasonography disclosed an ovarian tumor. Bilateral oophorectomy was performed, and an ovarian Sertoli-Leydig cell tumor was diagnosed. The hormonal and clinical picture normalized after this surgical intervention.ConclusionAfter extensive review of the literature, we believe that this is the first reported case of a coincidental DHEA-S-secreting adrenal adenoma and a testosterone-secreting ovarian Leydig cell tumor causing signs of virilization. (Endocr Pract. 2009;15:149-152)     

Pheochromocytoma and Paraganglioma

Objective: Pheochromocytomas (PHEOs) and paragangliomas (PGLs) are neural crest cell tumors associated with catecholamine production and assessed by a metanephrine/methoxytyramine measurement. This review summarizes the genetics of these tumors.Methods: Case presentation, review of the relevant literature, and bullet point conclusions.Results: Genetic research over the past 10 years has led to a better understanding of the pathogenesis of these tumors, currently associated with 20 susceptibility genes (both somatic and germ-line mutations). Although most of these genes can be divided into two clusters (clusters 1 and 2), recent data suggest that all mutations converge on the hypoxia-inducible factor signaling pathway. Most of the susceptibility genes are well characterized and associated with specific clinical presentations, including biochemical phenotype, tumor location and behavior, as well as neoplasms or similar characteristics. Correct and early detection of hereditary PHEO/PGL is paramount, as early diagnosis leads to improved and focused treatment, along with better outcomes. However, missed or delayed diagnosis of hereditary PHEO/PGL forestalls proper treatment and results in multiple, recurrent, or metastatic tumors and avoidable complications in some patients.Conclusion: Early diagnosis allows prompt screening for potentially lethal cancers associated with specific gene mutations and makes genetic testing more readily available to first-degree and other relatives of an index patient. Thus, understanding the genetics of these tumors is an essential part of endocrinology.Abbreviations: HIF2A = hypoxia-inducible factor 2α MAX = Myc-associated factor X MEN2 = multiple endocrine neoplasia type 2 NF1 = neurofibromatosis type 1 PGL = paraganglioma PHEO = pheochromocytoma SDHAF2 = succinate dehydrogenase complex assemble factor 2 TMEM127 = transmembrane protein 127 VHL = von Hippel-Lindau     

P450C17 (CYP17) Deficiency in Native Mexican Patient with a Novel CYP17A1 Mutation

ObjectiveTo report a case of congenital adrenal hyperplasia due to CYP17 deficiency caused by a novel CYP17A1 mutation.MethodsWe describe the clinical, biochemical, genetic, and radiologic findings of a sporadic case of congenital adrenal hyperplasia due to CYP17 deficiency in a young patient.ResultsAn 18-year-old woman presented with hypogonadism and progressive muscle weakness and had not yet undergone thelarche, adrenarche, and menarche. Blood pressure was 155/90 mm Hg, she had no axillary or pubic hair, breasts were Tanner stage 1, and female genitalia were Tanner stage 1. Further laboratory studies showed hypokalemia with metabolic alkalosis, hypergonadotropic hypogonadism, a 46,XY karyotype, a low 17-hydroxyprogesterone level, and a high deoxycorticosterone level. Sequencing of the CYP17A1 gene demonstrated homozygous transversion of cytosine to adenine (TCAàTAA) in exon 5, which causes a premature stop codon at position 288 (Ser288X). Imaging studies showed large adrenal glands, cystic picture in the inguinal canal (suggestive of intra-abdominal testes), and absent Müllerian structures. Exploratory laparotomy was performed to remove the remaining gonads, and the final histologic examination showed atrophic testes.ConclusionsCongenital adrenal hyperplasia due to CYP17 deficiency should be suspected in patients with hypertension, hypokalemic alkalosis, and hypogonadism. In such cases, it is mandatory to assess the karyotype and perform hormonal and molecular genetic studies. (Endocr Pract. 2011;17:99-103)     

Medullary Thyroid Carcinoma Manifesting as an Ovarian Mass: Case Report and Review of Literature

ObjectiveTo report the uncommon case of a woman with abdominal pain and a complex adnexal mass, who was subsequently found to have medullary thyroid carcinoma (MTC) metastatic to the ovary.MethodsWe present the clinical history, physical findings, laboratory and imaging studies, and pathologic findings in a woman with metastatic MTC and locally aggressive disease. The genetic associations, variable clinical course, and histopathologic findings in MTC are reviewed.ResultsA 38-year-old woman with abdominal and pelvic pain underwent a computed tomographic scan of the abdomen, which showed a complex left adnexal mass. After laparoscopic left oophorectomy, histopathologic analysis of the resected ovary suggested the presence of a metastatic neuroendocrine tumor. The patient recovered but was referred to the surgery clinic 3 months later because of hoarseness, a left neck mass, and left-sided vocal cord paralysis. Further work-up was suggestive of MTC, which prompted RET testing for multiple endocrine neoplasia. The patient underwent left thyroid lobectomy and selective lymph node dissection but later required tracheostomy because of tumoral invasion of the trachea, laser debulking of the tumor, and external beam radiation therapy. One year postoperatively, development of a metastatic lesion in her right ovary necessitated a second oophorectomy.ConclusionMTC usually manifests as a solitary thyroid nodule but should be considered in patients with metastatic lesions characterized by neuroendocrine features. This unusual case highlights the biologic and clinical variability of this often aggressive thyroid cancer, which necessitates an attentive work-up, a rigorous operative strategy, and a periodic postoperative surveillance program. (Endocr Pract. 2008;14:351-357)     

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)     

Cushing Syndrome Secondary to A Thymic Carcinoid Tumor Due to Multiple Endocrine Neoplasia Type 1

ObjectiveTo present an Iranian patient with a nonclassic form of multiple endocrine neoplasia type 1 (MEN 1) who presented with ectopic Cushing syndrome (CS) secondary to a corticotropin (ACTH)-producing thymic neuroendocrine tumor (NET), recurrent renal stones, and a giant cell granuloma of the jaw due to primary hyperparathyroidism (PHPT) without involvement of the pituitary or pancreas.MethodsRelevant imaging and hormonal evaluations were performed. The patient was operated on 2 occasions for a thymic NET and on 3 occasions for PHPT. DNA from a peripheral blood sample was extracted for sequencing of the MEN1 gene.ResultHistopathologic evaluation of the thymic tumor removed during the first surgery showed an atypical carcinoid tumor with a Ki-67 labeling index of 5%. Evaluation after the second surgery revealed an invasive carcinoid tumor with a Ki-67 labeling index of 30%.Parathyroid pathology was suggestive of glandular hyperplasia. Menin gene sequencing revealed a novel frameshift mutation c.1642_1648dup in exon 10.ConclusionThis case of MEN 1 is unusual because most thymic NETs in MEN 1 are nonfunctional, and secretion of ACTH or other ectopic hormones rarely occurs. In patients presenting with thymic NETs, the possibility of MEN 1 should be considered, especially in the presence of hyperparathyroidism. This case also demonstrates that the behavior of thymic NETs can change over time from slow-growing tumors to highly invasive neoplasia, and that ectopic ACTH can be produced by these tumors in the context of MEN 1. (Endocr Pract. 2011;17:e92-e96)     

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)