{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T05:04:56Z","timestamp":1790485496767,"version":"4.1.0"},"reference-count":10,"publisher":"The Endocrine Society","issue":"1","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2017,1,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Context:<\/jats:title>\n                  <jats:p>Dopamine \u03b2-hydroxylase (DBH) deficiency is a rare genetic disorder characterized by failure to convert dopamine to norepinephrine. DBH-deficient patients lack sympathetic adrenergic function and are therefore predisposed to orthostatic hypotension. DBH-deficient mice exhibit hyperinsulinemia, lower plasma glucose levels, and insulin resistance due to loss of tonic sympathetic inhibition of insulin secretion. The impact of DBH deficiency on glucose homeostasis in humans is unknown.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Case Description:<\/jats:title>\n                  <jats:p>We describe the metabolic profile of an adolescent female DBH-deficient patient. The patient underwent genetic testing, cardiovascular autonomic function testing, and evaluation of insulin secretion and sensitivity with hyperglycemic clamp under treatment-naive conditions. All procedures were repeated after 1 year of treatment with the norepinephrine prodrug droxidopa (300 mg, 3 times a day). Genetic testing showed a homozygous mutation in the DBH gene (rs74853476). Under treatment-naive conditions, she had undetectable plasma epinephrine and norepinephrine levels, resulting in sympathetic noradrenergic failure and orthostatic hypotension (\u221232 mm Hg supine to seated). She had high adiposity (41%) and fasting plasma insulin levels (25 \u03bcU\/mL), with normal glucose (91 mg\/dL). Hyperglycemic clamp revealed increased glucose-stimulated insulin secretion and insulin resistance. Droxidopa restored plasma norepinephrine and improved orthostatic tolerance, with modest effects on glucose homeostasis.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions:<\/jats:title>\n                  <jats:p>We provide evidence for impairment in cardiovascular autonomic regulation, hyperinsulinemia, enhanced glucose-stimulated insulin secretion, and insulin resistance in a DBH-deficient patient. These metabolic derangements were not corrected by chronic droxidopa treatment. These findings provide insight into the pathophysiology and treatment of DBH deficiency and into the importance of catecholaminergic mechanisms to resting metabolism.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1210\/jc.2016-3274","type":"journal-article","created":{"date-parts":[[2016,10,25]],"date-time":"2016-10-25T11:29:41Z","timestamp":1477394981000},"page":"10-14","source":"Crossref","is-referenced-by-count":18,"title":["Hyperinsulinemia and Insulin Resistance in Dopamine \u03b2-Hydroxylase Deficiency"],"prefix":"10.1210","volume":"102","author":[{"given":"Amy C.","family":"Arnold","sequence":"first","affiliation":[{"name":"Department of Neural and Behavioral Sciences, Pennsylvania State University College of Medicine, Hershey, Pennsylvania 17033;"},{"name":"Division of Clinical Pharmacology and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emily M.","family":"Garland","sequence":"additional","affiliation":[{"name":"Division of Clinical Pharmacology and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jorge E.","family":"Celedonio","sequence":"additional","affiliation":[{"name":"Division of Clinical Pharmacology and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Satish R.","family":"Raj","sequence":"additional","affiliation":[{"name":"Division of Clinical Pharmacology and"},{"name":"Department of Cardiac Sciences, Libin Cardiovascular Institute of Alberta, University of Calgary, Calgary, Alberta T2N 2T9, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naji N.","family":"Abumrad","sequence":"additional","affiliation":[{"name":"Department of Surgery, Vanderbilt University Medical Center, Nashville, Tennessee 37232; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Italo","family":"Biaggioni","sequence":"additional","affiliation":[{"name":"Division of Clinical Pharmacology and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Robertson","sequence":"additional","affiliation":[{"name":"Division of Clinical Pharmacology and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James M.","family":"Luther","sequence":"additional","affiliation":[{"name":"Division of Clinical Pharmacology and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cyndya A.","family":"Shibao","sequence":"additional","affiliation":[{"name":"Division of Clinical Pharmacology and"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"80","published-online":{"date-parts":[[2016,10,25]]},"reference":[{"key":"2020071615370205300_B1","article-title":"Dopamine beta-hydroxylase deficiency","volume-title":"GeneReviews","author":"Robertson","year":"1993"},{"issue":"11","key":"2020071615370205300_B2","doi-asserted-by":"crossref","first-page":"542","DOI":"10.1007\/s11886-014-0542-z","article-title":"New developments in the management of neurogenic orthostatic hypotension","volume":"16","author":"Biaggioni","year":"2014","journal-title":"Curr Cardiol Rep"},{"issue":"10","key":"2020071615370205300_B3","doi-asserted-by":"crossref","first-page":"4427","DOI":"10.1210\/en.2003-0561","article-title":"Norepinephrine and epinephrine-deficient mice are hyperinsulinemic and have lower blood glucose","volume":"144","author":"Ste Marie","year":"2003","journal-title":"Endocrinology"},{"issue":"4","key":"2020071615370205300_B4","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1055\/s-2004-817725","article-title":"Testing the autonomic nervous system","volume":"23","author":"Low","year":"2003","journal-title":"Semin Neurol"},{"issue":"1","key":"2020071615370205300_B5","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1172\/JCI113298","article-title":"Plasma dihydroxyphenylglycol and the intraneuronal disposition of norepinephrine in humans","volume":"81","author":"Goldstein","year":"1988","journal-title":"J Clin Invest"},{"issue":"10","key":"2020071615370205300_B6","doi-asserted-by":"crossref","first-page":"E1895","DOI":"10.1210\/jc.2014-2122","article-title":"Dietary sodium restriction decreases insulin secretion without affecting insulin sensitivity in humans","volume":"99","author":"Luther","year":"2014","journal-title":"J Clin Endocrinol Metab"},{"issue":"4","key":"2020071615370205300_B7","doi-asserted-by":"crossref","first-page":"e38","DOI":"10.1136\/jmg.2003.009282","article-title":"DBH gene variants that cause low plasma dopamine beta hydroxylase with or without a severe orthostatic syndrome","volume":"41","author":"Deinum","year":"2004","journal-title":"J Med Genet"},{"key":"2020071615370205300_B8","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1186\/1472-6823-13-47","article-title":"Insulin resistance (HOMA-IR) cut-off values and the metabolic syndrome in a general adult population: effect of gender and age: EPIRCE cross-sectional study","volume":"13","author":"Gayoso-Diz","year":"2013","journal-title":"BMC Endocr Disord"},{"issue":"8","key":"2020071615370205300_B9","doi-asserted-by":"crossref","first-page":"1198","DOI":"10.1210\/me.2013-1083","article-title":"Minireview: dopaminergic regulation of insulin secretion from the pancreatic islet","volume":"27","author":"Ustione","year":"2013","journal-title":"Mol Endocrinol"},{"issue":"1","key":"2020071615370205300_B10","doi-asserted-by":"crossref","first-page":"25","DOI":"10.2174\/157339913804143225","article-title":"Regulation of insulin synthesis and secretion and pancreatic beta-cell dysfunction in diabetes","volume":"9","author":"Fu","year":"2013","journal-title":"Curr Diabetes Rev"}],"container-title":["The Journal of Clinical Endocrinology &amp; 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