Cushing syndrome in the McCune-Albright syndrome: This paper represents >20 years of NIH in treating patients with MAS, and details the prevalence, diagnosis, natural history, treatment, and long term morbidity associated with Cushing syndrome in MAS. It serves as a useful guide for clinicians who care for these patients, and suggests several areas for potential future research. Specifically, we found the prevalence of CS among NIH patients was 7.1%. The median age at diagnosis was 3 months. Clinical features included Cushingoid facies (66.7%), failure to thrive (60.0%), low birth weight (50.0%), liver disease (36.7%), and heart disease (26.7%). Six patients (20.0%) died, four after adrenalectomy. Death was more likely in patients with comorbid heart disease (odds ratio, 13.3;P<0.05). Of 23 survivors, 13 underwent adrenalectomy, and 10 exhibited spontaneous resolution. Two patients with spontaneous resolution who were tested later in life (3 and 15 yr after resolution) continued to have low-level, autonomous adrenal function with biochemical adrenal insufficiency. Compared to MAS patients without CS, patients with CS were more likely to have a cognitive/developmental disorder (44.4 vs. 4.8%;P<0.001;odds ratio, 8.8). We concluded that comorbid heart and liver disease were indicators of a poor prognosis and may indicate the need for prompt adrenalectomy. The high incidence of cognitive disorders indicates a need for close developmental follow-up and parental counseling. Patients with spontaneous resolution of CS may develop adrenal insufficiency, and they require long-term monitoring. Reoperation for parathyroid adenoma: a contemporary experience: We reviewed reoperations for persistent or recurrent sporadic parathyroid adenoma at NIH from 1996-2008 to evaluate and compare our current results and outcomes to our previous experience. Patients were re-explored with the assistance of non-invasive and sometimes invasive imaging. A missed adenoma was suspected pre-operatively in 163 patients. Reoperation resulted in long-term resolution of hypercalcemia in 92%. Adenomas were in entopic locations in 32%;the most frequent ectopic location was the thymus (20%). Sestamibi scanning and ultrasonography were the most successful non-invasive imaging studies (96% positive predictive value (PPV) and 84% PPV respectively). Forty-four percent of patients had a reoperation based solely on non-invasive imaging. Of the invasive procedures performed, arteriography resulted in the best localization (92% PPV). Permanent recurrent laryngeal nerve injury occurred in 1.8%. In conclusion, compared to our prior experience (1982-1995), outcomes remained similar (92% resolution of hypercalcemia and 1.8% recurrent nerve injury currently versus 96% and 1.3% previously). Fewer patients received invasive studies for pre-operative localization (56% vs 73%, respectively). The decreased use of invasive imaging is due to technical improvements and greater confidence in the combination of ultrasonography and sestamibi scanning. En bloc spondylectomy for treatment of tumor-induced osteomalacia: En bloc spondylectomy represents a radical resection of a spinal segment most often reserved for patients presenting with a primary extradural spine tumor or a solitary metastasis in the setting of an indolent, well-controlled systemic malignancy. We report a case in which en bloc spondylectomy was conducted to control a metabolically active spine tumor. A 56-year-old woman, who suffered from severe tumor-induced osteomalacia, was found to have a fibroblast growth factor-23-secreting phosphaturic mesenchymal tumor in the T-8 vertebral body. En bloc resection was conducted, leading to resolution of her tumor-induced osteomalacia. This case suggests that radical spondylectomy may be beneficial in the management of metabolically or endocrinologically active tumors of the spine. Alternate protein kinase A activity identifies a unique population of stromal cells in adult bone: A population of stromal cells that retains osteogenic capacity in adult bone (adult bone stromal cells or aBSCs) exists and is under intense investigation. Mice heterozygous for a null allele of prkar1a (Prkar1a(+/-)), the primary receptor for cyclic adenosine monophosphate (cAMP) and regulator of protein kinase A (PKA) activity, developed bone lesions that were derived from cAMP-responsive osteogenic cells and resembled fibrous dysplasia (FD). Prkar1a(+/-) mice were crossed with mice that were heterozygous for catalytic subunit Calpha (Prkaca(+/-)), the main PKA activity-mediating molecule, to generate a mouse model with double heterozygosity for prkar1a and prkaca (Prkar1a(+/-)Prkaca(+/-)). Unexpectedly, Prkar1a(+/-)Prkaca(+/-) mice developed a greater number of osseous lesions starting at 3 months of age that varied from the rare chondromas in the long bones and the ubiquitous osteochondrodysplasia of vertebral bodies to the occasional sarcoma in older animals. Cells from these lesions originated from an area proximal to the growth plate, expressed osteogenic cell markers, and showed higher PKA activity that was mostly type II (PKA-II) mediated by an alternate pattern of catalytic subunit expression. Gene expression profiling confirmed a preosteoblastic nature for these cells but also showed a signature that was indicative of mesenchymal-to-epithelial transition and increased Wnt signaling. These studies show that a specific subpopulation of aBSCs can be stimulated in adult bone by alternate PKA and catalytic subunit activity;abnormal proliferation of these cells leads to skeletal lesions that have similarities to human FD and bone tumors. Percent effort: 1) studies in McCune-Albright syndrome/fibrous dysplasia: 50% 2) studies in disorders of mineral metabolism (FGF23): 40% 3) stidies in """"""""other"""""""" disorders of bone and mineral metabolism: 10%
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