American Association of Clinical Endocrinology Disease State Clinical Review on the Evaluation and Management of Adrenocortical Carcinoma in an Adult: a Practical Approach

Objective: The aim of this Disease State Clinical Review is to provide a practical approach to patients with newly diagnosed adrenocortical carcinoma, as well as to follow-up and management of patients with persistent or recurrent disease.Methods: This is a case-based clinical review. The provided recommendations are based on evidence available from randomized prospective clinical studies, cohort studies, cross-sectional and case-based studies, and expert opinions.Results: Adrenocortical carcinoma is a rare malignancy, often with poor outcomes. For any patient with an adrenal mass suspicious for adrenocortical carcinoma, the approach should include prompt evaluation with detailed history and physical exam, imaging, and biochemical adrenal hormone assessment. In addition to adrenal-focused imaging, patients should be evaluated with chest-abdomen-pelvis cross-sectional imaging to define the initial therapy plan. Patients with potentially resectable disease limited to the adrenal gland should undergo en bloc open surgery by an expert surgeon. For patients presenting with advanced or recurrent disease, a multidisciplinary approach considering curative repeat surgery, local control with surgery, radiation therapy or radiofrequency ablation, or systemic therapy with mitotane and/or cytotoxic chemotherapy is recommended.Conclusion: As most health care providers will rarely encounter a patient with adrenocortical carcinoma, we recommend that patients with suspected adrenocortical carcinoma be evaluated by an expert multidisciplinary team which includes clinicians with expertise in adrenal tumors, including endocrinologists, oncologists, surgeons, radiation oncologists, pathologists, geneticists, and radiologists. We recommend that patients in remote locations be followed by the local health care provider in collaboration with a multidisciplinary team at an expert adrenal tumor program.Abbreviations: ACC = adrenocortical carcinoma; ACTH = adrenocorticotropic hormone; BRACC = borderline resectable adrenocortical carcinoma; CT = computed tomography; DHEAS = dehydroepiandrosterone sulfate; EDP = etoposide, doxorubicin, cisplatin; FDG = ¹⁸F-fluorodeoxyglucose; FNA = fine-needle aspiration; HU = Hounsfield units; IVC = inferior vena cava; LFS = Li-Fraumeni syndrome; MEN1 = multiple endocrine neoplasia type 1; MRI = magnetic resonance imaging; OAC = oncocytic adrenocortical carcinoma; PC = palliative care; PET = positron emission tomography     

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)     

Efficacy and tolerability of Sorafenib plus metronomic chemotherapy S-1 for advanced hepatocellular carcinoma in preclinical and clinical assessments

ObjectiveAlthough sorafenib, a molecular targeted agent, has survival benefits for advanced hepatocellular carcinoma (HCC) patients, its disease control rate remains limited. To explore the potential for augmenting its antitumor effect, we assessed the preclinical and clinical efficacy and tolerability of S-1 metronomic chemotherapy (MC) plus sorafenib.MethodsAntitumor effects and toxicity of this combination were tested with HAK-1B xenograft and spontaneous HCC mouse models, and a prospective pilot study was performed to compare therapeutic effects and safety between sorafenib plus MC S-1 for 12 advanced HCC cases and the historical control of 363 sorafenib-treated advanced HCC patients at our hospital from July 2011 to June 2015.ResultsIn mice, the combination chemotherapy enhanced anti-angiogenic effects, resulting in a stronger tumor hypoxic environment and increased tumor cell apoptosis. Clinically, the objective response rate of the combination chemotherapy was higher than that of sorafenib mono therapy (16.7%; 2/12 vs 5.2%; 19/363, p < 0.05); however, there were no significant differences in overall survival and time to progression. Adverse events including alopecia, thrombocytopenia, and pancreatic enzymes elevation in the combination chemotherapy were higher than those of sorafenib. No patient treated with the combination chemotherapy discontinued treatment due to severe adverse events.ConclusionsSorafenib plus MC S-1 seems to be effective and tolerable for patients with advanced HCC and could be considered a treatment option for these patients.     

Evolving Approaches in Managing Radioactive Iodine-Refractory Differentiated Thyroid Cancer

ObjectiveTo discuss the approach to care of patients with advanced differentiated thyroid cancer (DTC), in particular those with radioactive iodine (RAI)-refractory disease, and the transition to systemic treatment.MethodsA PubMed search was conducted using the search terms “radioactive iodine-refractory, differentiated thyroid cancer and treatment” restricted to a 2000-2012 timeframe, English language, and humans. Relevant articles were identified from the bibliographies of selected references. Four patient cases are presented to illustrate the clinical course of RAI-refractory DTC.ResultsThe current standard of care for early stage DTC could include surgery, RAI in some cases, and thyroid hormone suppression. For advanced RAI-refractory DTC, clinical practice guidelines established by the National Comprehensive Cancer Network and the American Thyroid Association recommend, as one option, the use of systemic therapy, including kinase inhibitors. Numerous trials are underway to evaluate the clinical benefit of these targeted therapies.ConclusionPreliminary results are encouraging with respect to the clinical benefit of targeted systemic therapies. However, at present there is no consensus on the criteria that define RAI-refractory disease and the optimal timing for transition to systemic therapy. There remains a need to establish common criteria to enhance patient care and enable better comparison across clinical studies. (Endocr Pract. 2014;20:263-275)     

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)     

Clinical Characteristics and Pituitary Dysfunction in Patients with Metastatic Cancer to the sella

ObjectiveMetastatic disease to the sella is uncommon and there are limited available data regarding the clinical aspects of this disease. We therefore sought to characterize the clinical demographics of sellar metastases.MethodsRetrospective chart review of adults treated at Stanford University Medical Center from 1980 to 2011 with metastatic disease to the sella.ResultsA total of 13 subjects were identified (9 females). The mean age at diagnosis was 55 years (range, 25 to 73 years). A total of 6 patients (46%) had breast car-cinoma, 3 (23%) had renal cell carcinoma, 2 (15%) had squamous cell carcinoma of the head and neck, 1 had bronchoalveolar carcinoma of the lung, and 1 had nodular sclerosing Hodgkin’s lymphoma. The most common presenting signs and symptoms were headache (58%), followed by fatigue (50%), polyuria (50%), visual field defects (42%), and ophthalmoplegia (42%). Seventy-five percent of patients presented with at least one pituitary hormone insufficiency, which included 6 patients (50%) with diabetes insipidus (DI). Eight (67%) subjects had secondary hypothyroidism and 5 (45%) had secondary adrenal insufficiency. Of the patients with stalk involvement, 86% had DI. All patients had a prior diagnosis of malignancy, with a mean duration of 95 months.ConclusionThe most common neoplastic sources to the sella were breast and renal cell carcinomas. Secondary hypothyroidism was the most common endocrine abnormality, followed by DI and adrenal insufficiency. Newonset central hypothyroidism and DI along with known malignancy in a patient with a sellar lesion should raise the suspicion of a metastatic source. (Endocr Pract. 2013; 19:914-919)     

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)     

Bronchogenic Cyst Masquerading As an Adrenal Tumor: A Case of Mistaken Identity

ObjectiveTo describe a patient with a bronchogenic cyst that was erroneously diagnosed as an adrenal tumor and the surgical management strategy to address the operative challenges.MethodsWe summarize the clinical presentation, diagnostic workup, surgical management, and pathologic features of the study patient and review the pertinent literature.ResultsIn this report, we present the case of a 23-year-old woman who underwent retroperitoneoscopic exploration after imaging identified an enlarging left adrenal lesion. Preoperative biochemical testing confirmed that the mass was nonfunctional. No lesion was found after a thorough retroperitoneoscopic exploration under standard high insufflation pressure. Serendipitously, low-pressure inspection for hemostasis after failed exploration enabled discovery of an intradiaphragmatic mass that proved to be a bronchogenic cyst rather than an adrenal tumor. Not only was this a difficult operative dilemma, but it was also an unusual presentation for this tumor.ConclusionsDiscovery of a retroperitoneal or intradiaphragmatic bronchogenic cyst is a rare occurrence. The unusual location and tumor characteristics contributed to near surgical failure. The fortuitous surgical strategy of lowpressure inspection allowed visualization of the tumor for definitive resection. (Endocr Pract. 2012;18:e102-e105)     

Papillary Carcinoma of the Thyroid with Fibromatosislike Stroma: Case Report and Review of Literature

ObjectiveTo describe a case of papillary carcinoma of the thyroid with fibromatosislike stroma, emphasize the need for a diligent search for papillary thyroid cancer in the presence of a fibroproliferative lesion, highlight the peculiar hormonal response of the stromal component, and review the pertinent literature.MethodsWe present the clinical, laboratory, radiologic, and pathologic findings in a patient with papillary carcinoma of the thyroid with fibromatosislike stroma and review the related published material.ResultsA 29-year-old woman presented to our surgical department because of a large mediastinal mass. She underwent surgical removal of the mass by means of a median sternotomy and neck extension. Pathology examination revealed macroscopically tan scarlike tissue, which by histologic study consisted of a dominant fibroproliferative lesion overshadowing a minor component of papillary carcinoma of the thyroid. Further neck exploration with total thyroidectomy revealed multifocal papillary carcinoma of the thyroid. Postoperatively, the patient received radioiodine treatment. A local and aggressive recurrent tumor was observed during a subsequent pregnancy; the lesion was not amenable to complete resection but fascinatingly responded to antiestrogen therapy (orally administered tamoxifen).ConclusionThe presence of a fibroproliferative lesion could be misleading. A diligent search should be made for a papillary thyroid carcinoma component within fibromatosislike stroma. The mode of manifestation of the tumor and its response to hormonal manipulation are distinctive features of this case. (Endocr Pract. 2010;16:650-655)     

A Case of Adrenal Cavernous Hemangioma Presenting with Progressive Enlargement and Apparent Hormonal Hypersecretion

ObjectiveTo report the case of a man with an adrenal cavernous hemangioma presenting as a progressively enlarging adrenal mass with apparent hormonal hyper-secretion.MethodsWe report the clinical, laboratory, imaging findings, and clinical course of this patient, and we highlight the important atypical features of this case. The literature is reviewed for the typical presentations of adrenal cavernous hemangiomas.ResultsA 59-year-old man presented with an adrenal incidentaloma that had an imaging phenotype suggestive of a pheochromocytoma or an adrenal carcinoma. The hormonal profile also suggested a state of aldosterone and catecholamine hypersecretion. Surgery, however, proved the diagnosis to be an adrenal cavernous hemangioma.ConclusionAlthough adrenal cavernous hemangioma is a rare entity, it should be considered in the differential diagnosis of an adrenal incidentaloma. Its radiologic features are not specific, and the presence of hormonal hypersecretion does not exclude the diagnosis. (Endocr Pract. 2008;14:104-108)     

Metformin-Responsive Classic Salt-Losing Congenita L Adrenal Hyperplasia Due to 21-Hydroxylase Deficiency: a Case Report

ObjectiveTo study the effect of adding metformin to standard steroid replacement therapy in a patient with classic salt-losing congenital adrenal hyperplasia due to 21- hydroxylase deficiency with suboptimal biochemical and clinical control.MethodsWe present the clinical and laboratory findings before and after the addition of metformin to the therapeutic regimen of the study patient.ResultsA 17-year-old girl had been diagnosed as a neonate with classic salt-losing congenital adrenal hyperplasia caused by 21-hydroxylase deficiency (CYP21A2 deficiency). She was treated with hydrocortisone, 20 mg in the morning and 10 mg at bedtime, and fludrocortisone, 50 mcg daily. While on steroid replacement, she maintained normal serum electrolytes, glucose, blood pressure, and external genitalia, but she continued to express clinical features of obesity, hirsutism, amenorrhea, and acanthosis nigricans. Elevated laboratory measurements included the following: fasting 17-hydroxyprogesterone, 3410 ng/dL; total testosterone, 326 ng/dL; and androstenedione, 390 ng/dL. She was initiated on metformin, 500 mg twice daily after meals. After 3 months, the patient lost 2 kg, amenorrhea resolved, 17-hydroxyprogesterone decreased to 1539 ng/dL, total testosterone decreased to 163 ng/dL, and androstenedione levels remained unchanged.ConclusionsMetformin, an agent known to reduce insulin resistance, further suppressed the 17-hydroxyprogesterone concentration in a patient with classic congenital adrenal hyperplasia on steroid replacement therapy. Metformin may improve clinical and biochemical outcomes in classic congenital adrenal hyperplasia without the risk of iatrogenic Cushing syndrome. (Endocr Pract. 2008;14:889-891)     

Diagnostic Challenge of Pheochromocytoma in a Patient Receiving Levodopa for Parkinson's Disease

ObjectiveThe diagnosis of pheochromocytoma in patients receiving levodopa is challenging because the standard diagnostic biochemical tests may be confounded by dopaminergic therapy. We aim to showcase our experience with the diagnosis of pheochromocytoma in a patient with a known case of Parkinson’s disease who was receiving levodopa.MethodsWe present the case of an elderly male who was diagnosed as having pheochromocytoma while receiving dopaminergic therapy for Parkinson’s disease.ResultsA 75-year-old man presented with vague abdominal symptoms. Computed tomography revealed a 3.5 × 3.2 cm right adrenal mass with a well-defined margin. As revealed by magnetic resonance imaging, the mass was hypointense on T1-weighted and hyperintense on T2-weighted images. Biochemical tests revealed elevated levels of urinary dopamine, which was considered to be caused by levodopa therapy. However, concurrent elevation in urinary adrenaline and his metanephrine and vanillylmandelic acid levels suggested an underlying case of pheochromocytoma. An ¹²³I-metaiodobenzylguanidine (¹²³I-MIBG) scintigraphy scan performed under levodopa therapy showed positive tracer uptake in the right adrenal gland. Histopathology of the adrenalectomy specimen confirmed the diagnosis of pheochromocytoma.ConclusionOur experience with the present case indicates that although the standard diagnostic biochemical tests for pheochromocytoma may be confounded by dopaminergic therapy, ¹²³I-MIBG scintigraphy has diagnostic value for confirming pheochromocytoma even in patients receiving dopaminergic therapy. (Endocr Pract. 2014;20:e112-e115)     

Early Clinical Response after 2 Weeks of Sorafenib Therapy Predicts Outcomes and Anti-Tumor Response in Patients with Advanced Hepatocellular Carcinoma

Background & Aims

We evaluated the relationship between the early clinical response after 2 weeks of sorafenib therapy and the outcomes and anti-tumor response in patients with advanced hepatocellular carcinoma.

Methods

Fifty-seven patients who had intrahepatic hypervascular hepatocellular carcinoma and Child-Pugh (CP) class A disease at baseline were enrolled in this prospective, multicenter, observational, non-interventional study. As an early clinical response after 2 weeks of sorafenib therapy, changes in intra-tumor blood flow on contrast-enhanced computed tomography (CE-CT), alpha-fetoprotein (AFP) levels, and remnant liver function were investigated.

Results

After 2 weeks of sorafenib therapy, there were 26 patients (45.6%) without disappearance of arterial tumor enhancement on CE-CT, 15 patients (26.3%) with an AFP ratio of >1.2, and seven patients (12.3%) with two or more increments in the CP score. Multivariate analysis showed that the absence of disappearance of arterial tumor enhancement on CE-CT, AFP ratio of >1.2, and two or more increments in the CP score after 2 weeks of sorafenib therapy were significant and independent predictors of worse survival. Upon scoring these three variables as "poor prognostic factors", patients with poor prognostic score 4, 3 or 2 (n = 17) had significantly worse outcomes and a significantly higher progressive disease (PD) rate based on modified Response Evaluation Criteria in Solid Tumors at 6 weeks after sorafenib therapy than those with poor prognostic score 1 or 0 (n = 40) (median overall survival: 194 days vs. 378 days; p = 0.0010, PD rate: 70.6% vs. 20.0%; p = 0.0003, respectively).

Conclusions

Changes in intra-tumor blood flow on CE-CT, AFP levels, and remnant liver function after 2 weeks of sorafenib therapy may be useful for predicting the outcomes and anti-tumor response to sorafenib in patients with advanced hepatocellular carcinoma.     

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)     

Acute Myocardial Infarction Attributable to Adrenergic Crises in a Patient with Pheochromocytoma and Neurofibromatosis 1

ObjectiveTo describe a rare case of acute myocardial infarction in a patient with neurofibromatosis 1 and pheochromocytoma and to review the literature on the coexistence of these 2 diseases, the causes of myocardial injury in patients with pheochromocytoma, and the utility of genetic testing and pheochromocytoma screening for those patients and their families.MethodsWe present a case report, including the detailed clinical, laboratory, and radiographic data, results of adrenal mass pathology, and results of coronary angiography. We also survey other relevant reports available in the literature.ResultsA 43-year-old woman with a history of longstanding hypertension, neurofibromatosis 1, headaches, sweating, and palpitations presented to the hospital with chest pain and shortness of breath. She was found to have an acute myocardial infarction and pulmonary edema, as well as a right adrenal mass. A pheochromocytoma was suspected, and phenoxybenzamine was added to her treatment regimen. Cardiac catheterization showed nonobstructive coronary disease. The levels of plasma catecholamine metabolites were extremely high. The patient underwent uncomplicated laparoscopic right adrenalectomy 2 weeks after this admission. Surgical pathology confirmed the diagnosis of pheochromocytoma.ConclusionAdrenergic crisis attributable to pheochromocytoma can result in acute myocardial infarction even in the absence of obstructive coronary disease. Inclusion of pheochromocytoma in the differential diagnosis of hypertension in patients with neurofibromatosis is very important and helps avoid mistakes in the management of such patients. (Endocr Pract. 2007;13:269-273)     

Ganglioneuroma Manifesting as an Incidental Adrenal Mass in an Adult With Turner’s Syndrome

ObjectiveTo report a case of ganglioneuroma masquerading as an incidental adrenal mass in an adult patient with Turner’s syndrome.MethodsWe present the clinical, laboratory, radiologic, and pathologic findings in this patient.ResultsA 31-year-old woman with Turner’s syndrome who had previously been treated with growth hormone replacement had an incidentally discovered mass, apparently arising from the left adrenal gland. The mass was “silent” clinically and biochemically, but imaging characteristics were not reassuring for a benign cortical adenoma. Because of uncertainty regarding the nature of the mass, it was removed laparoscopically; during this procedure, it was noted to be intimately associated with, but anatomically distinct from, the left adrenal gland. The pathology report confirmed the presence of a benign ganglioneuroma.Conclusion: Although ganglioneuroma has previously been noted to be associated with Turner’s syndrome (especially in pediatric patients), to the best of our knowledge this is the first report of a ganglioneuroma manifesting as an incidental adrenal mass in an adult patient with Turner’s syndrome. (Endocr Pract. 2005;11:382-384)     

Association of ipilimumab therapy for advanced melanoma with secondary adrenal insufficiency: a case series

ObjectiveTo present a case series of ipilimumabrelated secondary adrenal insufficiency.MethodsIn this cases series, we review the presentation, evaluation, diagnosis, and management of patients with advanced melanoma who received ipilimumab and were referred to our endocrinology clinic for evaluation of hormonal abnormalities.ResultsSeven patients presented with symptoms, signs, or biochemical evidence of adrenal insufficiency 6 to 12 weeks after starting ipilimumab therapy. Ipilimumab is a cytotoxic T-lymphocyte antigen 4 (CTLA-4) monoclonal antibody that is approved for the treatment of metastatic melanoma and has widespread use for this disease. All 7 patients had biochemical evidence of profound secondary adrenal insufficiency. Thyroid function abnormalities, central hypogonadism, and low insulinlike growth factor 1 levels were seen in a subset of patients. Only 2 patients had abnormal findings on pituitary magnetic resonance imaging. Posterior pituitary function remained normal.ConclusionsOur findings suggest that the enhanced immune response associated with ipilimumab therapy may have a predilection for corticotroph and possibly thyrotroph cells. We recommend periodic hypothalamic-pituitary-adrenal axis monitoring for patients on this therapy.(Endocr Pract. 2012;18:351-355)     

Bilateral Ovary Adrenal Rest Tumor in a Congenital Adrenal Hyperplasia Following Adrenalectomy

Objective:In contrast to the high incidence of testicular adrenal rest tumors in adult male patients with congenital adrenal hyperplasia (CAH), ovarian adrenal rest tumors (OARTs) in female CAH patients are rare. In this case report, we describe a case of bilateral OART in a female patient with CAH due to 21-hydroxylase deficiency.Methods:We present a detailed case report with the clinical, imaging, and laboratory findings of the patient. The pertinent literature is also reviewed.Results:A 17-year-old patient was known to have CAH due to 21-hydroxylase deficiency. Since the second month of her gestational age, her mother was treated with cortisone-replacement therapy. The patient was treated with hydrocortisone and fludrocortisone since the neonatal period. Her pertinent history included a bilateral adrenalectomy at the age of 13 years in 2006, and for 3 years she led a normal puberty life with no complaint with hormonal replacement therapy. Nevertheless, in 2009, she developed a virilizing syndrome. Subsequently, she underwent surgery in December 2009 for right adnexectomy. However, the regression of the masculinizing mass was not complete and worsened several months after the surgery. A new pelvic magnetic resonance image showed the activation of a contralateral ovarian mass, necessitating a left adnexectomy in August 2010.Conclusion:This case demonstrates some interesting features of OART that pose challenges to its management. If an OART is detected early enough and glucocorticoid therapy is received, it is possible that the OART will decrease in size following suppression of adrenocorticotropic hormone levels. (Endocr Pract. 2014;20:e69-e74)     

Reversible decrease of portal venous flow in cirrhotic patients: a positive side effect of sorafenib

Portal hypertension, the most important complication with cirrhosis of the liver, is a serious disease. Sorafenib, a tyrosine kinase inhibitor is validated in advanced hepatocellular carcinoma. Because angiogenesis is a pathological hallmark of portal hypertension, the goal of our study was to determine the effect of sorafenib on portal venous flow and portosystemic collateral circulation in patients receiving sorafenib therapy for advanced hepatocellular carcinoma. Porto-collateral circulations were evaluated using a magnetic resonance technique prior sorafenib therapy, and at day 30. All patients under sorafenib therapy had a decrease in portal venous flow of at least 36%. In contrast, no specific change was observed in the azygos vein or the abdominal aorta. No portal venous flow modification was observed in the control group. Sorafenib is the first anti-angiogenic therapy to demonstrate a beneficial and reversible decrease of portal venous flow among cirrhotic patients.