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)     

Sarcoidosis: an update for the primary care physician

Sarcoidosis is a systemic inflammatory disorder of unknown etiology, characterized by the formation of noncaseating granulomas, multisystem involvement, intrathoracic (pulmonary and lymph node) involvement in more than 90% of cases, and activation of T cells and macrophages at sites of granulomatous inflammation with the release of various chemokines and cytokines including tumor necrosis factor (TNF)-alpha. Despite the fact that sarcoidosis is seen all over the world, the study of its epidemiology has been a challenge for several reasons, including the lack of consistency in case definition, variability in disease presentation, the lack of sensitive and specific diagnostic tests, underrecognition and misdiagnosis of the disease, and a dearth of systematic epidemiologic studies. The ACCESS (A Case Control Etiologic Study of Sarcoidosis) study, a multicenter study done at 10 centers in the United States, is an attempt to better characterize the disease. A study of a subset of patients in the ACCESS study showed there was a delay in making the diagnosis of sarcoidosis, even when patients presented with pulmonary symptoms. The role of the primary care physician includes the establishment of a supportive physician-patient relationship. The morbidity and psychosocial problems associated with this condition necessitate educating patients about the disease because of the overwhelming concerns about its etiology, prognosis, and potential adverse effects of medication. This supportive role enhances patients' roles in the process of shared decision making during testing and treatment decisions.     

An Unusual Case of Recurrent Hyperparathyroidism and Papillary Thyroid Cancer

ObjectiveTo report an unusual occurrence of recurrent hyperparathyroidism due to papillary thyroid carcinoma.MethodsWe describe the clinical history, physical examination findings, laboratory values, imaging findings, and pathologic findings of a woman who developed recurrent hyperparathyroidism 13 years after successful parathyroidectomy.ResultsA 59-year-old woman presented to our clinic with recurrent primary hyperparathyroidism. In 1994, she presented with nephrolithiasis and underwent resection of a right superior parathyroid adenoma that resulted in clinical and biochemical cure. Her clinical course had been followed at periodic intervals, and she had been symptom-free and normocalcemic. In 2007, she again developed nephrolithiasis and was documented to have recurrent hyperparathyroidism. Imaging studies suggested a parathyroid adenoma near the right inferior pole of the thyroid. The patient had reoperative neck exploration. No obvious parathyroid adenoma was found and a right thyroid lobectomy was performed, which resulted in normalization of intraoperative intact parathyroid hormone levels, and the incision was closed. Final pathology demonstrated no parathyroid adenoma, but instead, a 1-cm papillary thyroid carcinoma that stained positive for parathyroid hormone. More than 6 months after surgery, she remains clinically and biochemically cured.ConclusionsRecurrent hyperparathyroidism occurs secondary to multiple causes. This case demonstrates the challenge a surgeon faces in managing recurrent disease and highlights a rare phenomenon of papillary thyroid cancer causing recurrent hyperparathyroidism. (Endocr Pract. 2009;15:349-352)     

S-Methylmethionine Conversion to Dimethylsulfoniopropionate: Evidence for an Unusual Transamination Reaction

Leaves of Wollastonia biflora (L.) DC. synthesize the osmoprotectant 3-dimethylsulfoniopropionate (DMSP) from methionine via S-methylmethionine (SMM) and 3-dimethylsulfoniopropionaldehyde (DMSP-ald); no other intermediates have been detected. To test whether the amino group of SMM is lost by transamination or deamination, [methyl-2H3,15N]SMM was supplied to leaf discs, and 15N-labeling of amino acids was monitored, along with synthesis of [2H3]DMSP. After short incubations more 15N was incorporated into glutamate than into other amino acids, and the 15N abundance in glutamate exceeded that in the amide group of glutamine (Gln). This is more consistent with transamination than deamination, because deamination would be predicted to give greater labeling of Gln amide N due to reassimilation, via Gln synthetase, of the 15NH4+ released. This prediction was borne out by control experiments with 15NH4Cl. The transamination product of SMM, 4-dimethylsulfonio-2-oxobutyrate (DMSOB), is expected to be extremely unstable. This was confirmed by attempting to synthesize it enzymatically from SMM using L-amino acid oxidase or Gln transaminase K and from 4-methylthio-2-oxobutyrate using methionine S-methyltransferase. In each case, the reaction product decomposed rapidly, releasing dimethylsulfide. The conversion of SMM to DMSP-ald is therefore unlikely to involve a simple transamination that generates free DMSOB. Plausible alternatives are that DMSOB is channeled within a specialized transaminase-decarboxylase complex or that it exists only as the bound intermediate of a single enzyme catalyzing an unusual transamination-decarboxylation reaction.     

Unusual Manifestation of Parathyroid Carcinoma in the Setting of Papillary Thyroid Cancer

ObjectiveTo describe a rare manifestation of parathyroid carcinoma in association with papillary thyroid carcinoma.MethodsWe describe the clinical history, findings on physical examination, results of laboratory studies, imaging findings, and histopathologic features of a woman with 2 previously palpable thyroid nodules and mild hypercalcemia.ResultsA 79-year-old woman presented to our endocrinology clinic for reevaluation of 2 thyroid nodules and long-standing hyperparathyroidism. She initially had undergone assessment 6 years previously, at which time an intact parathyroid hormone level was 89 pg/mL (reference range, 10 to 69) and the serum calcium concentration was 10.4 mg/dL (reference range, 8.2 to 10.2) in conjunction with normal alkaline phosphatase, creatinine, and 25-hydroxyvitamin D levels. Subsequently, she was found to have multifocal papillary thyroid cancer in the right thyroid lobe and a 5-cm parathyroid carcinoma in the left side.ConclusionSynchronous parathyroid and thyroid carcinomas are extremely rare. To our knowledge, our current case is the first documented patient with parathyroid carcinoma who had a clinical presentation consistent with longstanding mild adenoma in addition to synchronous papillary thyroid carcinoma. (Endocr Pract. 2010;16:664-668)     

Unusual Recurrence of Hypercalcemia Due to Concurrent Parathyroid Adenoma and Parathyroid Sarcoidosis with Lymph Node Involvement

ObjectiveTo describe a patient presenting with the rare findings of synchronous parathyroid adenoma and parathyroid sarcoidosis.MethodsWe describe the clinical history, physical examination findings, laboratory values, imaging findings, and pathologic data of a man who developed recurrent se- vere hypercalcemia after successful parathyroidectomy.ResultsA 67-year-old man had the following initial blood test results: calcium, 11.1 mg/dL (reference range, 8.5-10.6 mg/dL); albumin 4.0 g/dL (reference range, 3.2-5.2 g/dL); intact parathyroid hormone, 166 pg/mL (refer- ence range, 10-69 pg/mL); creatinine, 1.9 mg/dL; 25-hy- droxyvitamin D, 15 ng/mL (reference range, 30-80 ng/ mL); and 1, 25-dihydroxyvitamin D, 44 pg/mL (reference range, 16-72 pg/mL). Chest x-ray was normal, and delayed images from a technetium Tc 99m sestamibi scan showed increased activity in the right lower pole of the thyroid. Two months after successful parathyroidectomy, the pa- tient was admitted to the hospital with a serum calcium concentration of 17 mg/dL. Pathologic examination of the resected gland confirmed the diagnosis of parathyroid ad- enoma, and subsequent review disclosed the presence of noncaseating granulomas within the adenoma.ConclusionsSarcoidosis with parathyroid involve- ment causing severe hypercalcemia is unique to this case.Recurrent hypercalcemia after successful resection of a parathyroid adenoma may require consideration of poten- tial causes other than the initial diagnosis. (Endocr Pract. 2010;16:463-467)     

Autoimmune Thyroid Disease: A Risk Factor for Thyroid Cancer

ObjectiveTo examine the relationship between clinical markers of autoimmune thyroid disease and the risk of thyroid cancer in patients with thyroid nodules.MethodsA retrospective cohort analysis was performed in a single clinical practice. In 2, 500 consecutive patients, fine-needle aspiration biopsy (FNAB) was performed on all 3, 658 ultrasonography-positive thyroid nodules that were ≥ 1.0 cm in diameter or ≥ 0.5 cm in diameter with ultrasound features suspicious for thyroid cancer. Serum concentrations of thyroglobulin antibodies (TgAb), thyroid peroxidase antibodies, and thyroid-stimulating hormone were measured before FNAB. Diagnosis of thyroid cancer was based on pathologic analysis of thyroidectomy tissue. Associations of thyroid cancer with the independent variables were determined by multivariate logistic regression analysis and reported as the adjusted odds ratio (OR) with the 95% confidence interval (CI).ResultsThere were 202 patients with malignant thyroid nodules, 51 patients with microscopic unsuspected thyroid cancer distal to the nodule under investigation (found at thyroidectomy), and 2, 247 patients with benign thyroid nodules. To evaluate the association of clinical markers for autoimmune thyroid disease with thyroid cancer, we included all 253 patients with thyroid cancer in the malignant cohort. Thyroid cancer was associated with elevated levels of TgAb (OR = 1.57; CI = 1.11 to 2.23) and age < 55 years (OR = 2.01; CI = 1.45 to 2.78), and a strong trend was demonstrated for association with male sex (OR = 1.45; CI = 0.99 to 2.12). Thyroid cancer was not associated with elevated levels of thyroid peroxidase antibodies.ConclusionIn patients who have thyroid nodules with indications for FNAB, elevated levels of TgAb are associated with thyroid cancer. (Endocr Pract. 2011;17: 201-209)     

Genitourinary Sarcoidosis

Genitourinary involvement of sarcoidosis can mimic many common urologic conditions. Although sarcoidosis is a benign inflammatory condition, it can present much like malignant or infectious conditions; thus, failed diagnosis can lead to unnecessary medications or surgical procedures. In addition, management choices for patients with scrotal findings have important implications for future fertility. Thus, this uncommon condition should be on the differential diagnosis for any urologic patient. The authors report on a patient with a scrotal mass as his presenting symptom of sarcoidosis and review the diagnosis, implications, and management of sarcoidosis involving all potential sites in the urinary tract.Key words: Sarcoidosis, Genitourinary, Scrotal mass, UrologyScrotal masses comprise a wide differential diagnosis. Although the vast majority of isolated epididymal masses are benign, solid testicular masses in adults are generally considered malignant until proven otherwise. Benign sarcoid lesions can occur in the testis, epididymis, or any other scrotal structure. In fact, sarcoidosis can involve many organs of the genitourinary (GU) system, commonly masquerading as other, more common conditions, including malignancy and infection.We present a patient with a scrotal mass as his presenting manifestation of sarcoidosis. This is followed by a concise review of the diagnosis and management of sarcoidosis, and a review of the limited literature available specifically pertaining to sarcoidosis of the GU tract. Finally, we provide initial management recommendations for each GU site of disease.