Baquedano M.S.,Endocrine Service
The Journal of clinical endocrinology and metabolism | Year: 2013
Steroid acute regulatory (StAR) protein is a mitochondria-targeted protein that is part of the transduceosome complex crucial for transport of cholesterol to mitochondria. Recessive mutations cause classic and nonclassic congenital lipoid adrenal hyperplasia. The aim of this study was to report the clinical, hormonal, genetic, and functional data of a novel heterozygous mutation in the StAR gene found in a 46,XY patient with ambiguous genitalia and neonatal severe steroidogenic deficiency. Undetectable serum steroids with high ACTH and plasma renin activity but normal acute GnRH response were found in infancy. After gonadectomy (at 3 yr of age), serum LH and testosterone were undetectable, whereas FSH was normal but increased slowly afterward. Estrogen replacement therapy, started at 10.2 yr of age, suppressed gonadotropins (for 2 yr). However, after 1 month off estrogens, the patient showed castrated levels. At 11.9 yr old, after fludrocortisone withdrawal because of hypertension, plasma renin activity and aldosterone remained normal, suggesting mineralocorticoid recovery by a StAR-independent mechanism. We found a de novo heterozygous IVS-2A>G StAR mutation and the reported heterozygous p.G146A SF1 polymorphism with normal CYP11A1, FDXR, FDX1, VDAC1, and TSPO genes. The mutant StAR transcript lacked exon 2, resulting in the in-frame loss of amino acids 22 to 59 in the N-terminal mitochondrial targeting signal. In vitro, the mutant protein exhibited reduced StAR activity in a dominant-negative manner and almost no mitochondria localization. A misfolded p.G22_L59del StAR might interfere with wild-type StAR activity by blocking the transduceosome complex, causing an autosomal dominant form of StAR deficiency, explaining the clinical phenotype. We speculated that estrogen might have modulated mineralocorticoid function and pubertal maturation in a human natural model lacking endogenous steroid production.
Chow C.,Neurology Service |
Fortier M.V.,KK Womens and Childrens Hospital |
Das L.,Rheumatology and Immunology Service |
Menon A.P.,Childrens Intensive Care Unit |
And 8 more authors.
Pediatric Neurology | Year: 2015
Background Anatomical localization of the rapid-onset obesity with hypothalamic dysfunction, hypoventilation, and autonomic dysregulation (ROHHAD) syndrome has proved elusive. Most patients had neuroimaging after cardiorespiratory collapse, revealing a range of ischemic lesions. Patient Description A 15-year-old obese boy with an acute febrile encephalopathy had hypoventilation, autonomic dysfunction, visual hallucinations, hyperekplexia, and disordered body temperature, and saltwater regulation. These features describe the ROHHAD syndrome. Cerebrospinal fluid analysis showed pleocytosis, elevated neopterins, and oligoclonal bands, and serology for systemic and antineuronal antibodies was negative. He improved after receiving intravenous steroids, immunoglobulins, and long-term mycophenolate. Screening for neural crest tumors was negative. Conclusion Magnetic resonance imaging of the brain early in his illness showed focal inflammation in the periaqueductal gray matter and hypothalamus. This unique localization explains almost all symptoms of this rare autoimmune encephalitis. © 2015 Elsevier Inc.
Pinto M.E.,Endocrine Service |
Pinto M.E.,University of Lima |
Escalaya G.R.,University of Lima |
Escalaya M.E.,University of Lima |
And 2 more authors.
Endocrine Practice | Year: 2010
Objective: To report a case of a young normolipidemic woman with mucocutaneous xanthomas who developed neurogenic diabetes insipidus and hyperprolactinemia because of an inflammatory pituitary stalk lesion. Methods: The clinical features, laboratory results, magnetic resonance imaging, and pathology findings are presented. In addition, the pertinent literature is reviewed. Results: A 23-year-old woman presented with a 9-month history of polydipsia, polyuria, galactorrhea, secondary amenorrhea, and weight gain. Her previous medical history included chronic anemia and widespread mucocutaneous xanthomas. Laboratory tests showed hyperprolactinemia, normal electrolytes, and a normal lipid profile. The results of a water deprivation test were compatible with neurogenic diabetes insipidus, and cerebral magnetic resonance imaging showed pituitary stalk thickening. Histologic findings on a skin biopsy specimen supported the diagnosis of non-Langerhans histiocytosis. Treatment was initiated with cabergoline, nasally administered desmopressin, radio-frequency ablation of facial skin lesions, and surgical excision of other accessible lesions. Conclusion: Xanthoma disseminatum is a rare, benign proliferative disorder characterized by extensive cutaneous and mucous membrane xanthomas in normolipidemic patients. Central nervous system involvement is rare and usually occurs in the systemic variety. Pituitary stalk disease commonly causes hyperprolactinemia, diabetes insipidus, and various degrees of hypopituitarism. The natural history of xanthoma disseminatum usually is benign, but lesions in critical anatomic sites may result in morbidity and mortality. Copyright © 2010 AACE.
Andreopoulou P.,Endocrine Service |
Bockman R.S.,Endocrine Service |
Bockman R.S.,New York Medical College
Annual Review of Medicine | Year: 2015
A hallmark of menopause, which follows the decline in the ovarian production of estrogen, is the aggressive and persistent loss of bone mineral and structural elements leading to loss of bone strength and increased fracture risk. This review focuses on newer methods of diagnosing osteoporosis and assessing fracture risk, as well as on novel management strategies for prevention and treatment. Fracture-risk prediction has been significantly enhanced by the development of methods such as the trabecular bone score, which helps assess bone microarchitecture and adds value to standard bone densitometry, and the Fracture Risk Assessment Tool (FRAX) algorithm techniques. The treatment of osteoporosis, which has the goals of fracture prevention and risk reduction, is moving beyond traditional monotherapies with antiresorptives and anabolic agents into new combination regimens. © 2015 by Annual Reviews.
Iyer N.G.,Sloan Kettering Cancer Center |
Tuttle R.M.,Endocrine Service
Annals of Surgery | Year: 2011
Objective: The objective of this study was to determine the incidence and significance of Delphian node (DN) metastasis in papillary thyroid cancer. Summary of Background Data: Despite the historic association, the prognostic implications of thyroid cancer metastasis to the DN remain unclear. Methods: Retrospective analysis of 101 patients who underwent thyroid surgery from 2007 to 2009 for papillary thyroid cancer, and had their DN harvested ab initio. Of these, 25 had metastatic disease to the DN. DN status was correlated with clinical and pathologic factors including age, gender, tumor size, histologic variant, extra-thyroidal extension (ETE), and central and lateral nodal metastasis. Results: DN positivity was seen consequent to higher rates of ETE of the primary tumor (52% vs. 28%; P = 0.025) and is associated with further nodal metastases to the central (72% vs. 22%; P < 0.0001) and lateral (28% vs. 4%; P < 0.0001) neck compartments. DN positivity was also associated with heavier nodal burden, in terms of number of metastatic nodes (median 5 vs. 2 nodes; P = 0.005) and nodal size (median 1 cm vs. 0.5 cm; P = 0.03). Conclusions: Metastatic involvement of the DN is often associated with ETE and increased incidence of metastatic disease to the central and lateral neck compartments. If the DN is positive on intraoperative frozen section, careful evaluation of the central and lateral nodal compartments is essential. © 2011 Lippincott Williams & Wilkins.