Recurrent Pleural Effusions and Elevated PTHrP: An Unusual Case of Sarcoidosis.

A 63-year-old male with a past medical history of stage 3 chronic kidney disease, type 2 diabetes mellitus, hypertension, and coronary artery disease presented with recurrent symptomatic pleural effusions, low back pain and unintentional weight loss. Labs revealed elevated serum calcium and parathyroid hormone-related peptide, but normal parathyroid hormone, vitamin D, and angiotensin-converting enzyme levels. Malignancy workup was revealing for salt-and-pepper appearance of the bone marrow on MRI of the lumbar spine consistent with multiple myeloma. CT of chest, abdomen, and pelvis was negative for neoplastic process but showed a pleural effusion and calcified granulomas in hilar lymph nodes. Bone marrow biopsy of the lumbar region was subsequently conducted and revealed granulomas confirming the diagnosis of sarcoidosis. Treatment of sarcoidosis resulted in complete resolution of his symptoms and pleural effusion. This case highlights the variable presentation of sarcoidosis and its ability to mimic malignancy. Prompt recognition and treatment is essential in avoiding unnecessary costs and harm to the patient.

Catecholamine-induced cardiomyopathy and multiple organ failure in pheochromocytoma.

A 55-year-old Caucasian woman with no significant past medical history presented with chest pain, palpitations, shortness of breath, and nausea. Physical examination was notable for a blood pressure of 182/87 mmHg, heart rate (HR) of 74 beats per minute (bpm), temperature of 98.3ºF, and oxygen saturation of 94% on 15 liters (L) of oxygen per minute. Her initial labs revealed troponin of 0.26 ng/mL (<0.01 ng/mL), blood glucose of 497 mg/dL (70-99 mg/dL), lactic acid of 6.9 mmol/L (0.4-1.9 mmol/L), and white blood cell (WBC) of 21.6 K/uL (4-11.0 K/uL). EKG showed ST elevation in leads V1 and V2. CT Pulmonary angiography with contrast ordered to rule out pulmonary embolism revealed a right adrenal mass measuring 3.5 cm x 4.1 cm. Patient was admitted to the intensive care unit for ST elevation myocardial infarction, hyperglycemia, and sepsis. She was started on heparin, broad-spectrum antibiotics, intravenous fluids, and insulin. Emergent echocardiogram revealed 40-45% ejection fraction with septal, lateral, anteroseptal, and posterolateral hypokinesis. Troponin elevation to 1.00 ng/mL (<0.01 ng/mL) warranted a cardiac angiography which revealed new-onset systolic heart failure with reduced ejection fraction with normal coronary vessels. A relatively rapid improvement in her clinical course suggested that a functioning tumor could be the underlying etiology. Diagnostic work-up for pheochromocytoma showed elevated metanephrine and normetanephrine. Subsequent surgical biopsy of the adrenal mass was consistent with pheochromocytoma. It was a rare case presentation of pheochromocytoma with catecholamine-induced cardiomyopathy and multiple organ failure.

Genome-wide association between Six4, MyoD, and the histone demethylase Utx during myogenesis.

Adult skeletal muscles can regenerate after injury, due to the presence of satellite cells, a quiescent population of myogenic progenitor cells. Once activated, satellite cells repair the muscle damage by undergoing myogenic differentiation. The myogenic regulatory factors (MRFs) coordinate the process of progenitor differentiation in cooperation with other families of transcription factors (TFs). The Six1 and Six4 homeodomain TFs are expressed in developing and adult muscle and Six1 is critical for embryonic and adult myogenesis. However, the lack of a muscle developmental phenotype in Six4-null mice, which has been attributed to compensation by other Six family members, has discouraged further assessment of the role of Six4 during adult muscle regeneration. By employing genome-wide approaches to address the function of Six4 during adult skeletal myogenesis, we have identified a core set of muscle genes coordinately regulated in adult muscle precursors by Six4 and the MRF MyoD. Throughout the genome of differentiating adult myoblasts, the cooperation between Six4 and MyoD is associated with chromatin repressive mark removal by Utx, a demethylase of histone H3 trimethylated at lysine 27. Among the genes coordinately regulated by Six4 and MyoD are several genes critical for proper in vivo muscle regeneration, implicating a role of Six4 in this process. Using in vivo RNA interference of Six4, we expose an uncompensated function of this TF during muscle regeneration. Together, our results reveal a role for Six4 during adult muscle regeneration and suggest a widespread mechanism of cooperation between Six4 and MyoD.