Endocrine Involvement in Systemic Amyloidosis

ObjectiveTo present an overview of the published data on endocrine involvement and endocrine dysfunction in patients with systemic amyloidosis.MethodsWe conducted a review of the medical literature using MEDLINE data sources, including clinical trials, in vitro studies, and case reports on pituitary, thyroid, parathyroid, pancreatic, adrenal, and gonadal involvement in systemic amyloidosis.ResultsReports of endocrine involvement in systemic amyloidosis seem to consist primarily of small-samplesize clinical trials or case reports, probably because of the rarity of the disease itself. Systemic amyloidosis mainly involves and causes functional impairment in the thyroid and testes in the endocrine system. Evaluation of adrenal function necessitates special consideration because amyloid infiltration of the adrenal glands resulting in failure may be a life-threatening condition. Amyloid deposition commonly seen in the pituitary gland and the pancreas of patients with Alzheimer disease and type 2 diabetes mellitus, respectively, is generally classified as local amyloidosis and should not be confused with systemic involvement. Additionally, detection of amyloid deposition in the thyroid and testes may have a diagnostic role in patients with suspected systemic or renal amyloidosis.ConclusionPublished data suggest that systemic amyloidosis frequently involves the endocrine system, and endocrine dysfunction seems to be not as rare as previously thought. A rapidly growing goiter or symptoms and signs of adrenal or gonadal dysfunction should raise suspicion of amyloid infiltration. Involvement of pituitary, parathyroid, and pancreatic sites in systemic amyloidosis still remains to be clarified. Further studies with larger sample sizes are needed for complete characterization of the effect of systemic amyloidosis on the endocrine system. (Endocr Pract. 2010;16:1056-1063)     

Unusual Case of Metastatic Neuroendocrine Tumor

ObjectiveTo report a rare case of metastatic growth hormone (GH)-secreting pituitary carcinoma causing acromegaly.MethodsWe present a case report and review the available literature on this topic.ResultsA 68-year-old woman presented with persistent acromegaly after treatment for a GH-secreting pituitary adenoma. Evaluation of long-standing cervical adenopathy revealed findings consistent with a metastatic neuroendocrine tumor. Further work-up revealed additional thyroid, parathyroid, and cervical masses. After operative treatment including total thyroidectomy, subtotal parathyroidectomy, partial thymectomy, and right modified radical neck dissection, the patient’s symptoms diminished, and her GH levels approached the normal range. Surgical pathology findings were consistent with a GH-secreting pituitary carcinoma metastatic to the cervical lymph nodes, multinodular thyroid hyperplasia with a focus of papillary microcarcinoma, and parathyroid hyperplasia.ConclusionOverall, pituitary carcinomas are extremely rare. To date, about 100 cases have been reported in the world’s literature, and of these, only 19 cases originated from GH-secreting cells. Our examination of the symptoms, signs, diagnosis, and treatment of our patient, in comparison with the previously reported cases, should enhance awareness of this unusual disease process. (Endocr Pract. 2007;13:72-76)     

Histopathologic Findings of Autoimmunity in Thyroid,Pituitary, and Adrenal Diseases in Chronic Hepatitis C Postmortem Cases

ObjectiveTo assess the histologic prevalence of immune-mediated thyroid, pituitary, and adrenal diseases in postmortem cases with hepatitis C.MethodsWe reviewed 108 consecutive cases of chronic hepatitis C in patients in whom a complete postmortem examination was performed. All microscopic and histologic slides of the thyroid, pituitary, and adrenal reports were reviewed and assessed for evidence of autoimmune diseases. These were compared with a control group of 100 postmortem cases without hepatitis C.ResultsIn chronic hepatitis C infection, there is a heightened immune response resulting in many autoimmune diseases. The commonest endocrinopathy in association with this chronic infection is thyroid disease, a finding confirmed in our current study. Among the 108 postmortem cases of hepatitis C, there were 14 cases (13%) with evidence of thyroiditis. No cases of pituitary or adrenal disease were found. The mean age of the patients was 52 years (range, 29 to 68). This frequency compared with 7 cases of thyroid disease (7%) in the control group (no significant difference between the 2 groups).ConclusionOn the basis of our postmortem data, thyroid disease was the only major endocrinopathy associated with hepatitis C infection, with a prevalence of 13%. This was comparable with other serologic and nonhistologic antemortem findings. There was no evidence of pituitary or adrenal involvement. (Endocr Pract. 2010;16:566-569)     

Pulmonary Atypical Carcinoid Tumor with Metastatic Involvement of the Pituitary Gland Causing Functional Hypopituitarism

ObjectiveTo report a unique case of a peripherally located pulmonary atypical carcinoid tumor with metastatic involvement of the pituitary, manifesting with evidence of functional hypopituitarism and compressive symptoms of dysarthria, bitemporal loss of vision, and ataxia.MethodsWe present a case report, including detailed laboratory, radiologic, and pathologic findings in a 50-year-old woman with a peripherally located pulmonary atypical carcinoid tumor and a lesion metastatic to the pituitary gland. The pertinent literature is also reviewed.ResultsA 50-year-old woman with a medical history of metastatic pulmonary atypical carcinoid tumor presented with symptoms of bitemporal hemianopia, ataxia, and dysarthria. Laboratory evaluation revealed functional hypopituitarism, and magnetic resonance imaging of the brain with use of gadolinium contrast demonstrated a pituitary lesion measuring 3.5 by 2.5 by 2.5 cm. Visual field testing revealed bitemporal superior quadrantanopia, consistent with a pituitary lesion of the chiasm. Computed tomographic angiography excluded the presence of an aneurysm of the internal carotid artery. Subsequently, the patient underwent subtotal transsphenoidal hypophysectomy. Findings on pathology examination were consistent with a lesion metastatic from the primary pulmonary atypical carcinoid tumor. The patient subsequently received monthly octreotide injections as well as chemotherapeutic regimens of capecitobine and temozolomide. At 18-month follow-up, disease had not recurred.ConclusionThis case of metastatic involvement of the pituitary gland from a peripherally located pulmonary atypical carcinoid tumor manifesting with evidence of functional hypopituitarism is highly uncommon. To our knowledge, such a case has not been previously reported. The presentation of an advanced pituitary metastatic lesion can be particularly dramatic, and the course can be potentially complicated. Therefore, heightened awareness of the possibility of a pituitary lesion metastatic from a pulmonary atypical carcinoid tumor is important. (Endocr Pract. 2007;13:291-295)     

Pituitary Macroadenoma in a Patient with Poems Syndrome in Conjunction with Castleman Disease: First Report of a Case and Review of Related Literature

ObjectiveTo describe the first reported case of a patient with POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes) in conjunction with the endocrinologic manifestation of panhypopituitarism due to a large clinically nonfunctioning pituitary adenoma.MethodsWe present the clinical, laboratory, and radiologic details of the case and review the relevant updated literature.ResultsA 48-year-old man with hypopituitarism and progressive polyneuropathy presented to an outside hospital with confusion and diaphoresis. He also had diffuse lymphadenopathy, monoclonal gammopathy, and skin lesions consistent with a diagnosis of POEMS syndrome. Cytopathologic study of a lymph node showed findings consistent with Castleman disease. A large suprasellar mass was found to be the cause of the hypopituitarism.ConclusionPOEMS syndrome is a rare paraneoplastic condition, commonly associated with Castleman disease, that manifests with progressive distal polyneuropathy and a monoclonal plasma cell disorder, often accompanied by endocrinopathy, organomegaly, skin changes, sclerotic bone lesions, ascites, erythrocytosis, and thrombocytosis. Our current patient had all 5 classic features of POEMS syndrome along with some diagnostic elements of Castleman disease, sclerotic bone lesions, and thrombocytosis. To our knowledge, this is the first known reported case of a patient whose endocrinologic manifestation of POEMS syndrome was panhypopituitarism attributable to a large clinically nonfunctioning pituitary adenoma. (Endocr Pract. 2010;16:97-101)     

Osteogenic Sarcoma of the Sella After Radiation Treatment of a Pituitary Adenoma

ObjectiveTo report an uncommon case of osteogenic sarcoma of the sella turcica after radiation treatment of a pituitary adenoma.MethodsWe present the clinical history, physical findings, laboratory data, imaging studies, and pathologic findings in a patient found to have osteogenic sarcoma of the sella after radiation therapy for a nonfunctioning pituitary adenoma.ResultsSix years after transsphenoidal resection and postoperative fractionated radiation therapy for a nonfunctioning pituitary adenoma that extended to the cavernous sinus, a 45-year-old man presented with a sinus infection, diplopia, and ophthalmoplegia of the right eye. A computed tomographic scan of the head showed a mass in the sella with involvement of the optic chiasm and right cavernous sinus. Transsphenoidal resection and debulking of the tumor revealed an osteogenic sarcoma. The patient was discharged from the hospital with residual diplopia and ophthalmoplegia. He was treated with levothyroxine, testosterone, and hydrocortisone. Six weeks later, the patient was readmitted after he was found unresponsive, and computed tomographic scans disclosed a massive cerebrovascular accident. He died a few days later.ConclusionOsteogenic sarcoma is a rare, late complication of radiation treatment of pituitary adenoma. Although radiotherapy remains an effective adjunctive treatment in patients with pituitary adenomas, particularly those with residual or recurrent tumor, potential complications must be acknowledged. (Endocr Pract. 2004;10: 335-338)     

Xanthoma Disseminatum: Case Report and Literature Review

ObjectiveTo report a case of a young normolipidemic woman with mucocutaneous xanthomas who developed neurogenic diabetes insipidus and hyperprolactinemia because of an inflammatory pituitary stalk lesion.MethodsThe clinical features, laboratory results, magnetic resonance imaging, and pathology findings are presented. In addition, the pertinent literature is reviewed.ResultsA 23-year-old woman presented with a 9-month history of polydipsia, polyuria, galactorrhea, secondary amenorrhea, and weight gain. Her previous medical history included chronic anemia and widespread mucocutaneous xanthomas. Laboratory tests showed hyperprolactinemia, normal electrolytes, and a normal lipid profile. The results of a water deprivation test were compatible with neurogenic diabetes insipidus, and cerebral magnetic resonance imaging showed pituitary stalk thickening. Histologic findings on a skin biopsy specimen supported the diagnosis of non-Langerhans histiocytosis. Treatment was initiated with cabergoline, nasally administered desmopressin, radio-frequency ablation of facial skin lesions, and surgical excision of other accessible lesions.ConclusionXanthoma disseminatum is a rare, benign proliferative disorder characterized by extensive cutaneous and mucous membrane xanthomas in normolipidemic patients. Central nervous system involvement is rare and usually occurs in the systemic variety. Pituitary stalk disease commonly causes hyperprolactinemia, diabetes insipidus, and various degrees of hypopituitarism. The natural history of xanthoma disseminatum usually is benign, but lesions in critical anatomic sites may result in morbidity and mortality. (Endocr Pract. 2010;16:1003-1006)     

Gonadotropin-Releasing Hormone Agonist-Induced Pituitary Apoplexy in Treatment of Prostate Cancer: Case Report and Review of Literature

ObjectiveTo describe a case and review the literature on the rare complication of pituitary apoplexy after administration of a gonadotropin-releasing hormone agonist (GnRHa) for treatment of patients with prostate cancer.MethodsWe present a detailed case report of a patient with immediate signs of pituitary apoplexy after receiving a GnRHa and review the 6 previously reported cases in the literature.ResultsA 60-year-old man presented to a local hospital with severe headache, nausea, vomiting, and diplopia. Prostate cancer had recently been diagnosed, and he had received his first dose of a GnRHa 4 hours before this presentation. On physical examination, he was confused and had ptosis of the left eye. A head computed tomographic scan without contrast enhancement showed soft tissue filling the sella, without intracranial hemorrhage or mass effect. He was discharged with the diagnosis of viral meningitis. Three weeks later, he presented again with severe headache and diplopia. He had confusion, lethargy, disorientation, a blood pressure of 88/64 mm Hg, and left cranial nerve III, IV, and VI paralysis. Magnetic resonance imaging of the brain revealed an enhancing pituitary mass with hemorrhage extending to the optic chiasm, consistent with pituitary apoplexy. Laboratory results were consistent with panhypopituitarism. Surgical excision revealed a necrotic pituitary macroadenoma with hemorrhage. Tumor immunohistochemical staining was positive only for luteinizing hormone.ConclusionWe describe a rare adverse effect of GnRHa therapy, which unmasked a gonadotropin-secreting pituitary macroadenoma. This case adds to the 6 previously reported cases of GnRHa administration inducing pituitary apoplexy in men with prostate cancer. (Endocr Pract. 2007;13:642-646)     

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)     

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)     

Burden of Illness,Annual Healthcare Utilization,and Costs Associated with Commercially Insured Patients with Cushing Disease in The United States

ObjectiveTo describe the burden of illness, healthcare utilization, and costs associated with Cushing disease (CD), a rare disorder resulting from adrenocorticotropic hormone-secreting pituitary tumors, in commercially insured patients in the U.S.MethodsPatients with CD were identified in 2010 in the IMS Health PharMetrics and Truven Health Analytics MarketScan claims databases. Because there is no diagnosis code for CD, patients were identified with a claim for Cushing syndrome and either benign pituitary adenoma or hypophysectomy. We estimated total sand CD-related utilization and costs using pharmacy and medical claims.ResultsWe identified 685 CD patients (81% female; mean age, 41.7 years; mean Charlson comorbidity index, 1.6; mean number of chronic conditions, 4.2); 30.5% of the patients had diabetes, 22.5% had psychiatric disturbances, 21% had infections, 8.6% had osteoporosis, 8% had cardiovascular disease/stroke, 5.5% had kidney stones, and 0.7% had compression fracture of a vertebra. Patients had a mean of 19.8 office visits per year; 38.4% had inpatient hospitalizations and 34.2% visited the emergency department (ED). Patients had a mean of 3.2 CD-related office visits per year; 26.9% had CD-related hospitalizations, 0.9% had CD-related ED visits, and 36.8% had CD treatments. Mean annual total costs were $34,992 (pharmacy, $3,597; medical costs, $31,395). CD-related costs accounted for $14,310 of total costs (CD treatment costs, $9,353; other CD-related costs, $4,957).ConclusionCD patients have a high burden of illness. Among CD patients in this study, 30.5% had diabetes, 22.5% had psychiatric disturbances, 21% had infections, 8.6% had osteoporosis, 8% had cardiovascular disease/ stroke, and 5.5% had kidney stones. Patients had 19.8 office visits per year, and > 34% of patients were hospitalized. Mean total cost of care was approximately $35,000 per year. (Endocr Pract. 2015;21:77-86)     

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)     

Hypercalcemia and Acromegaly-Clarifying the Connections: A Case Report and Review of the Literature

ObjectiveHypercalcemia in patients with acromegaly is rare and usually due to co-existent primary hyperparathyroidism. The etiology of hypercalcemia directly related to acromegaly is debated.MethodsWe present a case report of 1,25(OH)2D3-mediated hypercalcemia in a patient with acromegaly and discuss potential pathophysiological mechanisms contributing to the development of hypercalcemia late in the course of the disease.ResultsA 67-year-old female presented with classical features of acromegaly. A review of her previous photographs suggested a disease duration of approximately 10 years, and her serum calcium (Ca) was normal during this period. A biochemical work up confirmed a combined growth hormone (GH-) and prolactin (PRL-) cosecreting tumor with a GH level of 92.03 ng/mL (normal 0-3.61), an insulin-like growth factor-1 (IGF-1) level of 1,498 ng/ mL (59-225), and a PRL level of 223.3 ng/mL (2-17.4). Magnetic resonance imaging (MRI) of the pituitary showed a 1.9-cm macroadenoma. Her preoperative work up revealed new onset hypercalcemia with a corrected serum Ca level of 10.7 mg/dL (8.5-10.5), an ionized Ca level of 1.37 mmol/L (1.08-1.30), a parathyroid hormone (PTH) level of 13.0 pg/mL (10-60), and a high 1,25(OH)2D3 level of 72.6 pg/mL (15-60). She underwent resection of the pituitary adenoma with normalization of GH and PRL levels, and her IGF-1 level decreased to 304 ng/mL. Her serum Ca (9.3 mg/dL), ionized Ca(1.22) and 1,25(OH)2D3 levels (38.6 pg/mL) normalized after surgery.ConclusionWhile overt hypercalcemia in acromegaly is rare, it tends to occur late in the disease course. The hypercalcemia is mediated by elevated 1,25(OH)2D3 levels rather than PTH. (Endocr Pract. 2014;20:e86-e90)     

Development of Thyroid Storm After Surgical Resection of A Thyrotropin-Secreting Pituitary Adenoma

ObjectiveTo describe a patient with a thyrotropinsecreting pituitary adenoma in whom postoperative thyroid storm developed.MethodsWe present a case report with details of the initial presentation, laboratory evaluation, surgical and pathologic findings, and subsequent course in a patient with a thyrotropin (thyroid-stimulating hormone or TSH)- secreting adenoma and postoperative thyroid storm.ResultsAn 18-year-old male patient presented with severe headaches and was found to have a large suprasellar tumor and a mildly elevated level of TSH. Thyroid storm developed immediately after surgical resection of the pituitary mass. Results of laboratory evaluation undertaken preoperatively became available after the patient had undergone the surgical procedure and revealed thyroid hormone levels 2 to 3 times the upper limit of normal. Propylthiouracil and β-adrenergic blocking agents controlled the postoperative thyrotoxicosis and were subsequently discontinued as his TSH and thyroid hormone levels normalized.ConclusionThis case demonstrates the rare case of a TSH-secreting adenoma in a young patient, which was complicated by the development of postoperative thyroid storm. In addition, this case emphasizes the importance of preoperative pituitary hormonal evaluation and treatment of hormonal abnormalities in all patients presenting with sellar or suprasellar tumors. (Endocr Pract. 2008;14:732- 737)     

Cushing Disease Revealed by Bilateral Atypical Central Serous Chorioretinopathy: Case Report

ObjectiveWe report the case of a patient with Cushing disease revealed by bilateral central serous chorioretinopathy (CSCR).MethodsWe present the clinical history, physical findings, laboratory results, and imaging studies of a 53-year- old Chinese woman with a Cushing disease revealed by bilateral CSCR. The association with CSCR and the pertinent literature are reviewed.MethodsWe present the clinical history, physical findings, laboratory results, and imaging studies of a 53-year- old Chinese woman with a Cushing disease revealed by bilateral CSCR. The association with CSCR and the pertinent literature are reviewed.ResultsA 53-year-old patient initially presented to the Department of Ophthalmology with a 4-week history of decreased vision in the left eye. Standard ophthalmologic examination and fluorescein angiography established the diagnosis of bilateral CSCR. Systemic clinical signs and biochemical analysis indicated hypercortisolism. Magnetic resonance imaging (MRI) of the pituitary gland showed a left-side lesion compatible with a microadenoma. The diagnosis of Adrenocorticotropic hormone (ACTH)-dependent Cushing syndrome secondary to a pituitary microadenoma was selected. Endoscopic endonasal transsphenoidal surgery was performed and the pituitary adenoma was successfully removed. The histology confirmed the presence of ACTH-immunopositive pituitary adenoma. Early postoperative morning cortisol levels indicated early remission. At 6 weeks postoperatively, the patient’s morning cortisol remains undetectable, and serous retinal detachments had regressed.ConclusionCSCR is an uncommon manifestation of endogenous Cushing syndrome. It can be the first presentation of hypercortisolism caused by Cushing disease. CSCR should be considered when assessing patients with Cushing syndrome complaining of visual disorders. On the other hand, it is useful in patients with an atypical form of CSCR to exclude Cushing’s syndrome. (Endoer. Praet. 2013;19:el29-el33)     

Effective Long-Term Treatment of Cushing’s Disease with Pasireotide: A Case Report

ObjectiveCushing’s disease is a rare, devastating condition associated with high morbidity and increased mortality. Primary treatment for Cushing’s disease is transsphenoidal surgery to remove the pituitary adenoma; however, recurrence can occur in up to 25% of patients. Second-line medical therapies do not directly target the pituitary tumor. Thus, normalization of adrenocorticotropic hormone (ACTH) and inhibition of tumor growth is not usually achieved.MethodsIn this case report, we present a de novo patient with a pituitary macroadenoma who was randomized to receive treatment with subcutaneous twice-daily injections of pasireotide 900 μg as part of the double-blind, Phase III CSOM230B2305 clinical trial.ResultsAround one month after treatment initiation, the patient’s urinary free cortisol (UFC) level showed a dramatic reduction (from 151.1 to 7.4 μg/24h) necessitating a dose reduction to 600 μg to relieve the symptoms of corticosteroid withdrawal. One month after dose reduction, the patient’s UFC levels remained stable and were associated with improvements in clinical signs and symptoms. These improvements continued into the 12-month extension phase following a dose increase to 900 μg and were accompanied by a significant reduction in tumor volume (from 0.797 cm³ at baseline to 0.359 and 0.365 cm³ at months 18 and 24, respectively). UFC remained normalized throughout the extension period. During the study, the patient developed hyperglycemia, which was effectively controlled with diet and then medication.ConclusionIn this case study, long-term pasireotide treatment as first-line therapy led to normalization of UFC, reduction of tumor volume and significant improvement in the clinical signs and symptoms of Cushing’s disease. (Endocr. Pract. 2013;19:e92-e96)     

Endocrine Disturbances in Empty Sella Syndrome: Case Reports and Review of Literature

ObjectiveTo report 5 cases of empty sella syndrome (ESS) manifesting with various degrees of pituitary dysfunction.MethodsWe describe the initial manifestations in 5 patients with primary ESS and in previous cases of ESS reported in the English language literature.ResultsReview of our recent medical records identified 5 patients referred for evaluation of pituitary deficiencies in whom ESS was diagnosed. Glucocorticoid replacement was required in 3 patients, 2 of whom presented initially with symptoms of severe glucocorticoid deficiency. In each case, magnetic resonance imaging of the brain demonstrated an empty sella.ConclusionOur cases suggest that endocrine abnormalities are not rare as the initial manifestation of ESS and that, contrary to many studies in the literature, the endocrine abnormalities may be quite severe. (Endocr Pract. 2005;11:120-124)     

Medical Management of Extrathyroidai-Man I Festation of Graves Disease

ObjectiveTo review preventive measures and the current medical management of extrathyroidal manifestation of Graves disease and to provide an overview of potential immune therapies.MethodsA literature review of investigative trials of treatments for Graves disease and its extrathyroidal manifestations.ResultsGiven new knowledge of the stages of the autoimmune cascade responsible for the development of these extrathyroidal manifestations, the possibility has been raised of performing randomized trials of agents shown to provide benefits in other immune conditions. Two randomized trials on the efficacy of rituximab in moderate-to-severe Graves ophthalmopathy have reported conflicting results.ConclusionAdditional studies of rituximab and other agents are needed before they become routinely used in treating Graves disease. Meanwhile, the standard medical therapy for moderate-to-severe ophthalmopathy is intravenous (IV) or oral corticosteroids and, for dermopathy, local corticosteroid application with occlusive dressing. Because major adverse effects such as life-threatening hepatic failure can occur with very high doses of IV prednisolone, the cumulative total dose should not exceed 8 g. (Endocr Pract. 2014;20:1333-1344)     

Health Care Resource Use and Costs Among Patients with Cushing Disease

ObjectiveTo assess health care costs associated with Cushing disease and to determine changes in overall and comorbidity-related costs after surgical treatment.MethodsIn this retrospective cohort study, patients with Cushing disease were identified from insurance claims databases by International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9-CM) codes for Cushing syndrome (255.0) and either benign pituitary adenomas (227.3) or hypophysectomy (07.6x) between 2004 and 2008. Each patient with Cushing disease was age- and sex-matched with 4 patients with nonfunctioning pituitary adenomas and 10 population control subjects. Comorbid conditions and annual direct health care costs were assessed within each calendar year. Postoperative changes in health care costs and comorbidity-related costs were compared between patients presumed to be in remission and those with presumed persistent disease.ResultsOf 877 identified patients with Cushing disease, 79% were female and the average age was 43.4 years. Hypertension, diabetes mellitus, and hyperlipidemia were more common among patients with Cushing disease than in patients with nonfunctioning pituitary adenomas or in control patients (P < .01). For every calendar year studied, patients with Cushing disease had significantly higher total health care costs (2008: $26440 [Cushing disease] vs $13 708 [nonfunctioning pituitary adenomas] vs $5954 [population control], P < .01). Annual outpatient costs decreased significantly for patients in remission after surgery, and there was a trend towards improvement in overall disease-related costs with remission. A significant increase in postoperative health care costs was observed in those patients not in remission.ConclusionsPatients with Cushing disease had more comorbidities than patients with nonfunctioning pituitary adenomas or control patients and incurred significantly higher annual health care costs; these costs decreased after successful surgery and increased after unsuccessful surgery. (Endocr Pract. 2011;17:681-690)     

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)