Active Crohn Disease and Hypercalcemia Treated With Infliximab: Case Report and Literature Review

ObjectiveTo report a case of 1,25-dihydroxyvitamin D–mediated hypercalcemia caused by active Crohn disease that improved with infliximab therapy.MethodsWe present the clinical and laboratory findings and describe the clinical course of a patient who had hypercalcemia during Crohn disease exacerbations. The literature is reviewed regarding 1,25-dihydroxyvitamin D production in Crohn disease, and the 3 cases of hypercalcemia in individuals with Crohn disease reported in the literature are described.ResultsA 50-year-old man with long-standing Crohn disease treated with multiple bowel resections presented for take-down ileostomy. He was hypercalcemic and had suppressed parathyroid hormone and parathyroid hormone–related peptide levels. Histopathology of the resected ileostomy site and adjacent small bowel indicated active Crohn disease. Hypercalcemia promptly resolved after a few days of treatment with intravenous glucocorticoids. One month later, hypercalcemia recurred in the presence of an inappropriately high 1,25-dihydroxyvitamin D level and increased urinary calcium and serum angiotensin-converting enzyme levels. The serum and urinary calcium levels became normal with infliximab therapy. Three previous reports of hypercalcemia caused by active Crohn disease describe effective treatment with glucocorticoids. This is the first report of successful response to infliximab in this setting.ConclusionHypercalcemia mediated by 1,25-dihydroxyvitamin D in the setting of Crohn disease may respond to glucocorticoid-sparing immunomodulators. (Endocr Pract. 2008;14:87-92)     

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)     

Splenic Sarcoidosis without Focal Nodularity: A Case of 1,25-Dihydroxyvitamin D-Mediated Hypercalcemia Localized with FDG PET/CT

ObjectiveTo report an uncommon cause of 1,25-dihydroxyvitamin D (1,25[OH]₂D)-mediated hypercalcemia associated with splenic sarcoidosis and illustrate the evaluation and potential role of fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT) in such patients.MethodsWe present detailed clinical features, laboratory results, imaging results, and pathology results for this rare entity, discuss evaluation and management options, and review previous literature.ResultsA 65-year-old male presented with symptomatic hypercalcemia, with a serum calcium level of 14.1 mg/dL 3 months after being initiated on ergocalciferol for vitamin D deficiency. He was found to have a suppressed parathyroid hormone level, normal 25-hydroxyvitamin D (25[OH]D) level, and elevated 1,25(OH)₂D level. Extensive evaluation did not yield a definitive diagnosis. Hiscalcium levels normalized and symptoms resolved on prednisone then recurred when prednisone was discontinued. FDG PET/CT showed intense uptake in the spleen. Splenectomy was performed, which resulted in resolution of hypercalcemia and yielded a diagnosis of splenic sarcoidosis.Conclusion:Splenic sarcoidosis causing hypercalcemia has been rarely reported. Our case is unique in that the spleen lacked typical focal nodularity on cross-sectional CT imaging, which is expected in sarcoid involvement of the spleen. Our case adds to an emerging literature documenting the potential value of FDG PET/CT in localizing otherwise occult 1,25(OH)₂D-mediated hypercalcemia. (Endocr Pract. 2014;20:e28-e33)     

Hypercalcemia of Malignancy with Simultaneous Elevation in Serum Parathyroid Hormone-Related Peptide and 1,25-Dihydroxyvitamin D in a Patient with Metastatic Renal Cell Carcinoma

ObjectiveTo determine the cause of refractory hypercalcemia in a patient with metastatic renal cell carcinoma.MethodsWe describe the clinical, pathologic, and immunostain findings in a patient with metastatic renal cell carcinoma and hypercalcemia of malignancy refractory to intravenous bisphosphonates.ResultsA 57-year-old man with a remote history of clear cell renal cell carcinoma was referred to our clinic for evaluation of resistant hypercalcemia 12 years after nephrectomy. The patient had simultaneous elevation of serum 1,25-dihydroxyvitamin D and parathyroid hormone-related peptide. Computed tomographic scan of the chest and abdomen demonstrated numerous ring-enhancing lesions in the liver, and histologic examination of a biopsy specimen revealed liver tissue infiltrated by a malignant neoplasm composed of cells with clear and eosinophilic cytoplasm, arranged in tubules and nests. Findings were morphologically consistent with renal cell carcinoma of clear cell type, and positive immunostaining with the epithelial markers EMA and CAM 5.2 were supportive of the morphologic impression of renal cell carcinoma. The tumor showed expression of 25-hydroxyvitamin D 1a-hydroxylase by immunostaining. After failing to respond to intravenous bisphosphonates, the hypercalcemia improved with prednisone treatment.ConclusionsIn some patients with renal cell carcinoma, hypercalcemia of malignancy is associated with simultaneous elevation in serum 1,25-dihydroxyvitamin D and parathyroid hormone-related peptide. As our case exemplifies, it is imperative to identify such patients because hypercalcemia due to elevated 1,25-dihydroxyvitamin D levels may respond better to glucocorticoid treatment than to the conventional bisphosphonate therapy. (Endocr Pract. 2009;15:234-239)     

Suppressibility of Parathyroid Hormone in Primary Hyperparathyroidism

ObjectiveTo describe an unusual case of pathologically confirmed primary hyperparathyroidism in a patient presenting with severe hypercalcemia and an undetectable parathyroid hormone (PTH) level.MethodsWe present a detailed case report and outline the serial laboratory findings. In addition, the possible causes of low serum PTH levels in the setting of primary hyperparathyroidism are discussed.ResultsA 16-year-old female patient presented with severe epigastric pain, found to be attributable to acute pancreatitis. At hospital admission, her serum calcium concentration was high (14.0 mg/dL); the patient also had a normal serum phosphorus level of 3.6 mg/dL and an undetectable PTH level (< 0.2 pmol/L). An evaluation for non-PTH-mediated causes of hypercalcemia revealed a partially suppressed thyroid-stimulating hormone concentration and a below normal 1,25-dihydroxyvitamin D level, consistent with her suppressed PTH. One week after the patient was dismissed from the hospital, repeated laboratory studies showed a serum calcium value of 11.1 mg/dL, a serum phosphorus level of 2.8 mg/dL, and an elevated PTH concentration of 11.0 pmol/L, consistent with primary hyperparathyroidism. A repeated 1,25-dihy-droxyvitamin D measurement was elevated. A parathyroid scan showed a parathyroid adenoma in the left lower neck area, and she subsequently underwent successful surgical resection of a pathologically confirmed parathyroid adenoma.ConclusionThis case demonstrates that the serum PTH level can be suppressed in patients with primary hyperparathyroidism. Moreover, it emphasizes the need for careful evaluation of the clinical context in which the PTH measurement is determined. Consideration should be given to repeating measurement of PTH and serum calcium levels when the initial laboratory evaluation of hypercalcemia is unclear because dynamic changes in calcium metabolism may occur in the presence of secondary contributing factors. (Endocr Pract. 2007;13:785-789)     

Hypercalcemia and Local Production of Parathyroid Hormone-Related Protein by a Perisellar Rhabdomyosarcoma After Remote Pituitary Irradiation

ObjectiveTo describe a case of metastatic rhabdomyosarcoma originating from the sphenoid sinus in a patient previously treated with conventional irradiation for a prolactinoma, presenting as hypercalcemia in the setting of a normal level of serum parathyroid hormone-related protein (PTHrP).MethodsWe report the case of a patient who underwent remote pituitary irradiation for a prolactinoma and then presented decades later with hypercalcemia of unknown cause. His clinical course, the initial biochemical and radiologic investigations, and the results of examination of pathology specimens are reviewed.ResultsThe patient was found to have a mass in the sphenoid sinus. The pathologic features were consistent with alveolar rhabdomyosarcoma. Although he had a normal serum PTHrP level, staining of his tumor with an antibody against PTHrP revealed local production of PTHrP at the tumor margins. His bone marrow biopsy specimen showed 100% involvement with rhabdomyosarcoma.ConclusionPTHrP staining of pathology specimens might explain hypercalcemia of undetermined cause in patients with a known malignant lesion, in whom elevated serum PTHrP levels cannot be demonstrated. (Endocr Pract. 2005;11:184-189)     

An Interesting Case of Peripheral Vascular Disease,Vascular Reperfusion,and Subsequent Development of Pain Due to Paget's Disease of Bone

ObjectiveTo present a case of Paget’s disease of bone that was unmasked after vascular reperfusion.MethodsIn this case study, we review the presentation, evaluation, diagnosis, and management of a patient with Paget’s disease and peripheral vascular disease.ResultsA 79-year-old-woman with a history of coronary artery heart disease and recent finding of a T5 compression fracture was hospitalized for evaluation of right lower extremity claudication. Angiography demonstrated a focal complete occlusion of the distal right femoral and popliteal arteries. A self-expanding stent was placed in the distal femoral and popliteal arteries. Approximately 48 hours after the procedure, the patient developed severe, right lower leg pain. On endocrine evaluation, the patient was found to have clinical signs suggesting Paget’s disease of bone, which was subsequently confirmed by imaging.ConclusionThis patient’s development of severe pain following reperfusion of distal femoral and popliteal arteries is in keeping with the known and aforementioned hypervascularity of pagetic bone. The finding of increased warmth over an area of skeletal deformation should always raise the possibility of Paget’s disease of bone.(Endocr Pract. 2013;19:e61-e63)     

Diagnostic Confusion Attributable to Spurious Elevation of Both Total Thyroid Hormone and Thyroid Hormone Uptake Measurements in the Setting of Autoantibodies: Case Report and Review of Related Literature

ObjectiveTo review the effect of thyroid autoantibodies on thyroid function assays and to present a case in which thyroid autoantibodies resulted in spurious assay readings for both total thyroid hormone levels and thyroid hormone uptake measurements.MethodsWe present a detailed case, including serial laboratory data, and review the relevant literature.ResultsA 61-year-old man with a history of autoimmune disease presented for evaluation of abnormal results of thyroid function tests. The patient had been treated for hypothyroidism with levothyroxine and was noted to have an elevated total thyroxine (T₄) level in the setting of a low total triiodothyronine (T₃) value and a mildly elevated thyrotropin concentration. He had been referred for evaluation of a presumed deiodinase deficiency that impaired conversion of T₄ to T₃. During treatment with levothyroxine, these test results were confirmed, and the patient was also found to have an elevated T₄ uptake. These findings were initially thought to be due to an excess of transthyretin; however, more extensive testing revealed that the patient had an autoantibody to T₄ that interfered with the assays for both T₄ and T₄ uptake.ConclusionAutoantibodies to both T₃ and T₄ have been described. Such antibodies are not uncommon in patients with thyroid disease. On rare occasions, these antibodies may cause spurious assay readings and obscure the diagnosis. To our knowledge, this is the first report in which both the total T₄ level and the T₄ uptake were elevated because of the presence of autoantibodies. Thyroid hormone autoantibodies must be considered when clinicians encounter patients with unexplained abnormal results of thyroid function tests. (Endocr Pract. 2008; 14:738-742)     

Parathyroid Hormone- Related Protein:An Unusual Mechanism for Hypercalcemia in Sarcoidosis

ObjectiveTo describe parathyroid hormonerelated protein (PTHrP) as a mediator of hypercalcemia in sarcoidosis.MethodsWe present a detailed case report including history, physical, laboratory testing, pathology findings, and followup data over 2 years. We also propose a possible mechanism for PTHrPmediated hypercalcemia in sarcoidosis.ResultsA 56yearold man presented with abdominal pain, fatigue, and excess thirst. Routine laboratory testing demonstrated severe hypercalcemia. The patient was admitted for treatment and workup. Inpatient workup was significant for suppressed parathyroid hormone, low 25- hydroxyvitamin D, normal 1, 25- dihydroxyvitamin D, and elevated PTHrP. The patient was treated for hypercalcemia and discharged for followup. Malignancy screening included computed tomography of the chest, which revealed parenchymal nodules and diffuse lymphadenopathy. Biopsy revealed nonnecrotizing granulomatous sinflammation with positive PTHrP staining by immunohistochemistry. After treatment with intravenous hydration and glucocorticoids, the hypercalcemia resolved and on subsequent followup, PTHrP levels had normalized to 0.5 pmol/L.ConclusionPTHrP may be a possible mediator of hypercalcemia in sarcoidosis. The differential diagnosis of PTHrP- induced hypercalcemia should include sarcoidosis, and further research is needed to establish the incidence and source of PTHrP in sarcoidosis. (Endocr Pract. 2011;17:e84- e86)     

A Case of “Late-Onset” Idiopathic Infantile Hypercalcemia Secondary to Mutations in the CYP24A1 Gene

ObjectiveMutations in the 24-hydroxylase gene, CYP24A1, have recently been reported to cause idiopathic infantile hypercalcemia (IIH), a rare disease presenting in the first year of life that is characterized by increased sensitivity to vitamin D, leading to severe symptomatic hypercalcemia.MethodsWe present a case report and review the relevant literature.ResultsA 24-year-old Caucasian man presented with repetitive signs of nephrolithiasis since the age of 18 years, hypercalciuria (17.1 mmol/24 h), slightly elevated serum calcium concentration (2.64 mmol/L), and inappropriately high levels of 1,25-dihydroxyvitamin D (101 pg/mL) in combination with suppressed levels of circulating parathormone (7.9 pg/mL). Exogenous vitamin D intoxication as well as granulomatous disease or malignancy were excluded. Genetic analysis revealed a loss-of-function mutation in CYP24A1. Of note, our patient denied any prior clinical signs of impaired calcium homeostasis during childhood.ConclusionHere, we describe the exceptional case of a patient with hypercalciuria and recurrent nephrolithiasis secondary to mutations in CYP24A1, without any signs of IIH in childhood, indicating that the phenotypic spectrum includes mild “late-onset” disease that becomes symptomatic in adolescence. Therefore, reduced CYP24A1 activity should be considered as a possible reason for recurrent nephrolithiasis in adults. (Endocr Pract. 2014;20: e91-e95)     

Spontaneous Hemorrhage of a Parathyroid Adenoma Into the Mediastinum

ObjectiveTo describe the case of a previously healthy 56-year-old woman, who presented with acute, nontraumatic pain in the left side of the neck and mild dysphagia.MethodsWe report the results of the physical examination, imaging studies, and clinical laboratory studies. In addition, we describe the patient’s hospital course after surgical intervention.ResultsA patient who sought medical attention because of acute, nontraumatic neck pain and dysphagia was subsequently found to have acute extracapsular hemorrhage of a parathyroid adenoma. Computed tomography and magnetic resonance imaging studies revealed a mass effect beginning in the neck and extending into the mediastinum. Surgical exploration of the neck and histopathologic evaluation confirmed the diagnosis of spontaneous rupture of a parathyroid adenoma with associated hemorrhage.ConclusionExtracapsular hemorrhage of a parathyroid adenoma is rare and necessitates a high index of clinical suspicion for diagnosis. This diagnosis should be considered in a patient who presents with acute anemia, hypercalcemia, and a neck mass. (Endocr Pract. 2012;18: e57-e60)     

1,25-Dihydroxyvitamin D-Mediated Hypercalcemia in Oleogranulomatous Mastitis (Paraffinoma), Ameliorated by Glucocorticoid Administration

ObjectiveTo report a case of oleogranulomatous mastitis (paraffinoma) in which both the hypercalcemia and the inappropriately elevated 1,25-dihydroxyvitamin D [1,25(OH)2D] levels were successfully reduced by administration of prednisone.MethodsWe describe the clinical, imaging, and laboratory findings in the study patient. Furthermore, we review the relevant literature regarding hypercalcemia in oleogranulomatous mastitis.ResultsA 58-year-old man with oleogranulomatous mastitis (paraffinoma)-related hypercalcemia, renal failure, and inappropriately elevated levels of 1,25(OH)2D presented to our institution. Treatment with prednisone—0.5 mg/kg of body weight or 30 mg daily—for 10 days resulted in a reduction of his serum calcium and 1,25(OH)2D levels to near-normal or normal values and a substantial improvement of his renal function. Nevertheless, the patient ultimately died 11 months later of multiple paraffinomarelated complications.ConclusionIn selected cases, treatment with glucocorticoids may offer a temporary relief from paraffinomarelated hypercalcemia until definitive treatment options are feasible. (Endocr Pract. 2010;16:102-106)     

Nonischemic Cardiomyopathy Associated with Autoimmune Polyglandular Syndrome Type II

ObjectiveTo report a case of nonischemic cardiomyopathy associated with autoimmune polyglandular syndrome type II (APS-II).MethodsWe describe our patient’s clinical features, evaluation, and outcome. In addition, a literature review of cardiomyopathy associated with polyendocrinopathy syndromes is presented.ResultsThe component disorders of APS-II are Addison’s disease in combination with either autoimmune thyroid disease or type 1 (insulin-dependent) diabetes. Although numerous other autoimmune conditions have been reported in conjunction with APS-II, cardiomyopathy has not been previously described as part of this syndrome. The current patient was a 32-year-old man who, during a 5-year period, was diagnosed as having type 1 diabetes mellitus, Crohn’s disease, and Addison’s disease. In 2001, he presented with severe heart failure that progressed rapidly and eventually necessitated cardiac transplantation.ConclusionAlthough autoimmune cardiomyopathy has been associated with other autoimmune disorders, to our knowledge this is the first reported case of cardiomyopathy in association with an autoimmune polyglandular syndrome. Patients with this syndrome should undergo clinical evaluation for heart failure. (Endocr Pract. 2007;13:59-62)     

Parathyroid carcinoma arising from four-gland hyperplasia

ObjectiveTo report the use of immunohistochemical staining for parafibromin, APC, and galectin-3 to evaluate the malignant potential of a resected parathyroid specimen in a patient initially presenting with primary hyperparathyroidism attributable to 4-gland hyperplasia, who subsequently developed metastatic parathyroid carcinoma.MethodsWe describe a patient with primary hyperparathyroidism who underwent a 3-gland resection of hypercellular parathyroid glands, with postoperative normalization of her serum calcium and parathyroid hormone levels. She returned 4 years later with recurrent hypercalcemia and underwent partial resection of her remaining hypercellular parathyroid gland, without improvement of her hypercalcemia. Selective venous sampling localized the source as draining into her azygos vein, and metastatic parathyroid carcinoma was ultimately diagnosed.ResultsImmunohistochemical staining for parafibromin, APC, and galectin-3 suggested the malignant potential of the atypical adenoma removed during the patient’s original operation, which is believed to be the source of her metastatic disease. Access to this information by the treating surgeon may have prompted a more extensive en bloc resection or more vigilant follow-up that could have altered the patient’s clinical course.ConclusionImmunohistochemical staining for parafibromin, APC, and galectin-3 can be used to help distinguish the source of metastatic disease in patients with parathyroid carcinoma. Selective venous sampling may help localize metastatic parathyroid carcinoma when the source is otherwise not apparent. (Endocr Pract. 2011;17:e37-e42)     

Primary hyperparathyroidism and familial hypocalciuric hypercalcemia: relationships and clinical implications

ObjectiveTo discuss the unusual occurrence of both familial hypocalciuric hypercalcemia (FHH) and primary hyperparathyroidism in the same patient and to explore potential mechanisms of association and issues related to clinical management.MethodsWe discuss the diagnosis, compare the clinical presentations of FHH and primary hyperparathyroidism, review the literature regarding patients who have presented with both disorders, and discuss management considerations. We also describe 2 patients who have both FHH (confirmed by genetic testing for a mutation in the gene encoding the calcium-sensing receptor [CASR]) and primary hyperparathyroidism.ResultsThe occurrence of both FHH and primary hyperparathyroidism in the same patient has been reported in a few cases, including 2 patients described here, one of whom was documented to have a novel CASR mutation. Inthose with clinical sequelae of hyperparathyroidism, parathyroidectomy has led to reduction, but not normalization, of serum calcium levels.ConclusionsThe coexistence of FHH and primary hyperparathyroidism should be considered in patients with hypercalcemia, hypophosphatemia, frankly elevated parathyroid hormone levels, and low urinary calcium excretion. Genetic testing for inactivating CASR gene mutations can confirm the diagnosis of FHH. Although surgical intervention does not resolve hypercalcemia, it may be beneficial by reducing the degree of hypercalcemia, alleviating the symptoms, and preventing potential complications of hyperparathyroidism. (Endocr Pract. 2012;18:412-417)     

Neuroendocrine Thymic Carcinoma Metastatic to the Parathyroid Gland that was Reimplanted into the Forearm in Patient with Multiple Endocrine Neoplasia Type 1 Syndrome: A Challenging Management Dilemma

ObjectiveTo describe a unique case of a metastatic thymic carcinoma to the hyperplastic parathyroid gland and to present a challenging management dilemma.MethodsOur patient is 60-year-old, intellectually disabled man with history of the multiple endocrine neoplasia type 1 (MEN1) syndrome, a surgery in 1985 for hypercalcemia with removal of one parathyroid gland, surgery in 2007 with findings of extensively necrotic well differentiated neuroendocrine carcinoma (carcinoid tumor) of the thymus. In 2012, he presented with persistent hypercalcemia (calcium level 11.7 mg/dL [range, 8.6-10.2]), and a parathyroid hormone (PTH) level of 225 pg/mL (range, 15-65 pg/mL). He underwent a repeat neck exploration with removal of 2 small inferior and a large left superior 4.5 × 2.5 × 1.5cm parathyroid glands, all of which showed hyperplasia on intraoperative frozen section. A small portion of the superior gland was reimplanted into the patient’s forearm. Final pathology showed the presence of a focus of neuroendocrine tumor within the left superior parathyroid gland with immunostain identical to the thymic carcinoma. His postoperative PTH level was 14 pg/mL and calcium 8.5 mg/dL. A positron emission tomography – computed tomography (PET-CT) and octreotide scans revealed an extensive metastatic disease within the lung, mediastinum, and bones.ResultsWe decided to leave a portion of the reimplanted parathyroid gland with possible metastatic thymic carcinoid in his forearm because of the presence a widespread metastatic disease and his intellectual disability that would result in noncompliance with calcium replacement in case of permanent hypocalcemia.ConclusionMetastatic thymic carcinoma to the parathyroid gland has never been reported in the literature. We have described the first case and presented a challenging management dilemma. (Endocr Pract. 2013;19:e163-e167)     

Unusual Clinical Course of Graves’ Thyrotoxicosis and Concomitant Sarcoidosis: Case Report and Review of Literature

ObjectiveTo report a case of Graves’ disease with concomitant sarcoidosis involving the thyroid gland.MethodsWe present the clinical, laboratory, imaging, and pathologic findings and describe the clinical course of a patient with Graves’ disease and sarcoidosis, who was unresponsive to propylthiouracil and radioiodine treatment.ResultsA 23-year-old woman presented with thyrotoxicosis and a large goiter. Laboratory studies and findings on thyroid uptake and scan were consistent with Graves’ disease. She was also found to have hilar lymph-adenopathy and hepatosplenomegaly. Despite treatment with antithyroid drugs and radioiodine therapy, her hyperthyroidism persisted. Surgical resection of the thyroid gland and 2 lymph nodes disclosed noncaseating granulomas, consistent with sarcoid.ConclusionAutoimmune endocrinopathies and, less commonly, thyroid autoimmune disease have been reported in patients with sarcoidosis. Similarities exist in the pathogenesis of these two conditions. Concomitant sarcoidosis in the thyroid gland in patients with Graves’ disease may contribute to the resistance to antithyroid drugs and radioiodine therapy. (Endocr Pract. 2007;13:159-163)     

Congenital Craniopharyngioma and Hypercalcemia Induced by Parathyroid Hormone-Related Protein

ObjectiveTo report a case of congenital craniopharyngioma and parathyroid hormone-related protein (PTHrP)-associated humoral hypercalcemia.MethodsDetails of this unusual case are reviewed, from detection of fetal hydrocephalus and a brain tumor, through cesarean delivery at 36 weeks of gestation, to subsequent laboratory studies, management, and confirmation of the diagnosis.ResultsAlthough PTHrP has been well documented as a cause of humoral hypercalcemia of malignancy (HHM) in adult patients with cancer, HHM is uncommon in children. In addition, HHM has rarely been ascribed to nonmalignant tumors. To the best of our knowledge, we report the first case of a neonate with congenital craniopharyngioma and refractory hypercalcemia (peak ionized calcium level of 1.92 mmol/L; normal, 1.05 to 1.3) attributed to an elevated PTHrP value of 8.6 pmol/L (normal, less than 4.7). Intact parathyroid hormone was appropriately undetectable (less than 10 pg/mL; normal, 15 to 65). Despite calcitonin treatment, the hypercalcemia persisted. Although pamidronate infusion stabilized the serum calcium level, the baby did not survive.ConclusionThe diagnosis of craniopharyngioma was confirmed at autopsy, and immunohistochemical studies substantiated that the craniopharyngioma produced PTHrP. (Endocr Pract. 2007;13:67-71)     

Intrathyroidal Parathyroid Carcinoma as Cause of Hypercalcemia and Pitfall of Localization Techniques: Clinical and Biologic Features

ObjectiveTo describe an unusual case of intrathyroidal parathyroid carcinoma (PC), which was retrospectively diagnosed in a woman who underwent surgical treatment of a recurrent nodular goiter.MethodsWe report the clinical and biologic features of an intrathyroidal PC, discuss the challenges with distinguishing PC from parathyroid adenoma, and review the related literature.ResultsA 67-year-old woman sought medical attention for dysphagia attributable to the recurrence of a normal functioning multinodular goiter. Thyroid ultra-sonography disclosed a 3-cm solid inferior nodule. Because she refused surgical treatment and a trial of levothyroxine was unsuccessful, periodic follow-up examinations were scheduled. At 1-year follow-up, hypercalcemia (12.1 to 12.6 mg/dL) and low phosphorus levels (2.0 to 2.3 mg/dL) were found, and parathyroid hormone (PTH) levels were profoundly increased (481 to 721 pg/mL). Neck ultrasonography showed a large hypoechogenic solid nodule, not clearly cleaved from the right thyroid lobe, which was possibly compatible with an enlarged parathyroid gland; however, a sestamibi scan was negative. During total thyroidectomy, intraoperative frozen sections of the intrathyroid nodule were compatible with nodular goiter with cellular pleomorphism. Final histologic examination showed cellular nests with nuclear pleomorphism and invasive behavior into the thyroid tissue and likely into the vessels, in conjunction with immuno-histochemical negativity for thyroglobulin and strong positivity for PTH. These findings were highly suggestive of and supported the diagnosis of PC. Postoperatively, calcium levels normalized, and PTH values declined considerably but remained slightly increased. Vitamin D supplementation helped normalize the PTH levels. The patient has undergone follow-up for 5 years and has shown no morphologic or biochemical signs of tumor recurrence.ConclusionPC is a rare entity but should be suspected in patients with hypercalcemia, substantially increased PTH levels, and a neck mass. In such patients, techniques such as sestamibi scanning may fail to localize the neoplasm. Surgical treatment remains the preferred technique for an optimal outcome of the disease. Nevertheless, lifelong follow-up is necessary. (Endocr Pract. 2007;13:176-181)     

Vitamin D–Mediated Hypercalcemia and Cushing Syndrome as Manifestations of Malignant Pleural Mesothelioma

ObjectiveTo report a case of coincident hypercalcemia and Cushing syndrome arising from mesothelioma.MethodsWe describe the clinical, laboratory, imaging, and pathologic findings of a patient with malignant pleural mesothelioma and elucidate the underlying biologic mechanisms resulting in concurrent overexpression of steroid and polypeptide hormones.ResultsA 62-year-old woman presented with chest discomfort and cough. Radiologic imaging revealed a diffuse pleural-based mass encasing the right lung. There was no invasion into the chest wall, diaphragm, or mediastinum, and there was no distant disease. Laboratory analyses documented hypercalcemia and Cushing syndrome, which were due to ectopic overproduction of 1,25-dihydroxyvitamin D (1,25[OH]₂D) and corticotropin. Surgical resection resulted in normocalcemia with normalization of serum 1,25(OH)₂D and reduction in hypercortisolemia. The extrapleural pneumonectomy specimen revealed overexpression of the 1,25(OH)₂D synthetic enzyme 25- hydroxyvitamin-D-1α-hydroxylase (1α-hydroxylase) and underexpression of the 1,25(OH)₂D catabolic enzyme 24- hydroxylase. Immunohistochemistry and electron microscopy demonstrated corticotropin and secretory granules in the tumor tissue.ConclusionThese findings support the evidence for a paracrine role of vitamin D in the resistance of the human host to antigen. (Endocr Pract. 2008;14:1011-1016)