Fetal-placental inflammation, but not adrenal activation, is associated with extreme preterm delivery.

OBJECTIVE: Spontaneous labor at term involves the activation of placental corticotropin-releasing hormone and the fetal adrenal axis, but the basis for extreme preterm labor is unknown. Our objective was to determine whether placental corticotropin-releasing hormone is activated in extreme preterm labor. STUDY DESIGN: One thousand five hundred six mothers delivering at less than 28 weeks' gestation were enrolled. Each mother/infant pair was assigned to the category that described the primary reason for hospitalization. Observers who had no knowledge of patient categorization assessed placenta microbiology, histology, and corticotropin-releasing hormone expression. These were correlated with the primary reason for hospitalization. RESULTS: Among infants delivered at less than 28 weeks' gestation, spontaneous (vs induced) delivery was associated with less placental corticotropin-releasing hormone expression and more frequent signs of placental inflammation and infection. CONCLUSION: Inflammation and infection, rather than premature activation of the fetal adrenal axis, should be the major focus of research to prevent extremely preterm human birth.

Lipoprotein lipase links dietary fat to solid tumor cell proliferation.

Many types of cancer cells require a supply of fatty acids (FA) for growth and survival, and interrupting de novo FA synthesis in model systems causes potent anticancer effects. We hypothesized that, in addition to synthesis, cancer cells may obtain preformed, diet-derived FA by uptake from the bloodstream. This would require hydrolytic release of FA from triglyceride in circulating lipoprotein particles by the secreted enzyme lipoprotein lipase (LPL), and the expression of CD36, the channel for cellular FA uptake. We find that selected breast cancer and sarcoma cells express and secrete active LPL, and all express CD36. We further show that LPL, in the presence of triglyceride-rich lipoproteins, accelerates the growth of these cells. Providing LPL to prostate cancer cells, which express low levels of the enzyme, did not augment growth, but did prevent the cytotoxic effect of FA synthesis inhibition. Moreover, LPL knockdown inhibited HeLa cell growth. In contrast to the cell lines, immunohistochemical analysis confirmed the presence of LPL and CD36 in the majority of breast, liposarcoma, and prostate tumor tissues examined (n = 181). These findings suggest that, in addition to de novo lipogenesis, cancer cells can use LPL and CD36 to acquire FA from the circulation by lipolysis, and this can fuel their growth. Interfering with dietary fat intake, lipolysis, and/or FA uptake will be necessary to target the requirement of cancer cells for FA.

Unusual manifestation of parathyroid carcinoma in the setting of papillary thyroid cancer.

OBJECTIVE: To describe a rare manifestation of parathyroid carcinoma in association with papillary thyroid carcinoma. METHODS: We 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. RESULTS: A 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. CONCLUSION: Synchronous 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.

Unusual recurrence of hypercalcemia due to concurrent parathyroid adenoma and parathyroid sarcoidosis with lymph node involvement.

OBJECTIVE: To describe a patient presenting with the rare findings of synchronous parathyroid adenoma and parathyroid sarcoidosis. METHODS: We describe the clinical history, physical examination findings, laboratory values, imaging findings, and pathologic data of a man who developed recurrent severe hypercalcemia after successful parathyroidectomy. RESULTS: A 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 (reference range, 10-69 pg/mL); creatinine, 1.9 mg/dL; 25-hydroxyvitamin 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 patient 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 adenoma, and subsequent review disclosed the presence of noncaseating granulomas within the adenoma. CONCLUSIONS: Sarcoidosis with parathyroid involvement causing severe hypercalcemia is unique to this case. Recurrent hypercalcemia after successful resection of a parathyroid adenoma may require consideration of potential causes other than the initial diagnosis.