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The Physician's Guide to Laboratory Test Selection and Interpretation

Acromegaly

Diagnosis

Indications for Testing · Chronic headaches or musculoskeletal growth in an adult Laboratory Testing · Fasting or random GH and IGF-1 levels · GH secretion is pulsatile and may or may not be elevated · IGF-1 usually elevated · GH <0.25 ng/mL and normal IGF-1 excludes acromegaly · Consensus criteria ­ nadir GH >1 ng/mL with high IGF-1 levels is diagnostic · If either test does not meet the criteria above, perform oral glucose tolerance test (OGTT) and measure GH · Administer 75g glucose and perform GH measurements over 120 minutes · Failure to suppress GH is diagnostic · GH <0.25 ng/mL excludes acromegaly · Usefulness limited in high catabolic states, patients on estrogen replacement, tall adolescents Histology · Immunohistochemistry staining for growth hormone; may need to stain for other anterior pituitary hormones Imaging Studies · MRI ­ preferred modality to evaluate adenoma · Can detect tumors as small as 2 mm Differential Diagnosis · Headache, visual field cuts ­ other pituitary tumors · Glucose intolerance ­ Cushing syndrome, diabetes mellitus type 2 · Malignancy with ectopic GH secretion

Monitoring

· Monitor GH and IGF-1 levels for effectiveness of therapy · Active disease · Random GH >1 ng/mL and nadir GH after OGTT 0.4 ng/mL · IGF-1 elevated · Also consider periodic MRI for active disease · Controlled disease · GH <1 ng/mL or nadir GH after OGTT <0.4 ng/mL · IGF-1 normal

Clinical Background

Acromegaly is a rare chronic endocrine disorder caused by hypersecretion of growth hormone (GH). Epidemiology · Incidence ­ 3-5/1,000,000 · Age ­ mean onset is 40 years · Sex ­ M:F, equal

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The Physician's Guide to Laboratory Test Selection and Interpretation

Etiology · Most cases are secondary to pituitary adenomas · Rare causes ­ growth hormone secretion from tumors (carcinoid or small cell lung cancer) · Genetic diseases associated with acromegaly ­ MEN1, McCune-Albright syndrome, Carney complex Pathophysiology · GH is synthesized and has pulsatile secretion from the somatotroph cells of the anterior lobe of the pituitary gland · GH secretion is regulated by the hypothalamus · Stimulation by GH releasing hormone (GHRH) · Inhibition by somatostatin · Circulating GH stimulates synthesis and secretion of insulin-like growth factor 1 (IGF-1) from the liver · IGF-1 inhibits GH secretion at the pituitary and hypothalamus level, creating a negative feedback loop · Pituitary tumors mimic stimulation of adenylyl cyclase by GHRH receptor activation, causing autonomous GH secretion · Symptoms are related to both excess GH and IGF-1 secretion and to the expanding pituitary mass Clinical Presentation · Indolent course · Pituitary mass expansion symptoms · Headaches · Visual field defects · Cranial nerve palsies · GH excess symptoms · Musculoskeletal · Hypertrophic arthropathy ­ both axial and peripheral skeleton · Carpal tunnel syndrome · Coarse facial features, macrognathia · Spade-shaped hands · Enlarged feet · Growth of mandible ­ prognathism · If epiphyses are open ­ linear bone growth causes gigantism · Cardiovascular · Hypertension ­ about 30% of patients · Cardiomyopathy · Arrhythmias · Endocrine · May cause deficiency of other pituitary hormones from mass effect · Dermatologic · Acanthosis nigricans · Metabolic · Diabetes mellitus · Dyslipidemia · Neoplastic · Development of premalignant colon polyps increases risk of colon cancer · Carney complex ­ rare syndrome associated with acromegaly

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The Physician's Guide to Laboratory Test Selection and Interpretation

· Pigmented skin, myxoma, cardiac myxoma, thyroid nodules or carcinoma, primary pigmented nodular adrenocortical disease Treatment · Three goals of treatment · Control hypersecretion of GH · Decrease morbidity/mortality related to hypersecretion · Reduce mass effects of tumor · Surgical removal of tumor ­ usually initial therapy · Radiotherapy · Medical therapy · Dopamine agonists · Somatostatin analogues · GH receptor antagonists

Lab Tests

Indications for Laboratory Testing Tests generally appear in the order most useful for common clinical situations. For test-specific information, refer to the test number in the ARUP Laboratory Test Directory on the ARUP Web site at www.aruplab.com. Test Name and Number Growth Hormone 0070080 Method: Quantitative Chemiluminescent Immunoassay IGF-1 (Insulin-Like Growth Factor 1) 0070125 Method: Quantitative Chemiluminescent Immunoassay Growth Hormone by Immunohistochemistry 2003929 Method: Immunohistochemistry Additional Tests Available Test Name and Number Growth Hormone, 60 Minutes 0070083 Method: Quantitative Chemiluminescent Immunoassay Comments Measure after glucose administration Recommended Use Use as initial test in the evaluation of suspected growth hormone excess Use in conjunction with IGF-1 testing Limitations Follow Up

Use as initial test in the evaluation of Increased in pubertal suspected growth hormone excess and in pregnant patients Use in conjunction with growth hormone testing Monitor adequacy of growth hormone therapy Aid in histologic diagnosis of acromegaly Stained and returned to client pathologist; consultation available if needed

ARUP LABORATORIES | 500 Chipeta Way | Salt Lake City, Utah 84108-1221 | (800) 522-2787 | www.arupconsult.com | www.aruplab.com

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The Physician's Guide to Laboratory Test Selection and Interpretation

Growth Hormone, 120 Minutes 0070164 Method: Quantitative Chemiluminescent Immunoassay IGF Binding Protein-3 0070060 Method: Quantitative Chemiluminescent Immunoassay Insulin, 30 Minutes 0070064 Method: Quantitative Chemiluminescent Immunoassay Insulin, 60 Minutes 0070066 Method: Quantitative Chemiluminescent Immunoassay Insulin, 120 Minutes 0070068 Method: Quantitative Chemiluminescent Immunoassay Parathyroid Hormone (PTH) by Immunohistochemistry 2004118 Method: Immunohistochemistry ACTH by Immunohistochemistry 2003427 Method: Immunohistochemistry Guidelines Bonadonna S, Doga M, Gola M, Mazziotti G, Giustina A. Diagnosis and treatment of acromegaly and its complications: consensus guidelines.J Endocrinol Invest. 2005; 28 (11 Suppl International) :43-47. Chanson P, Bertherat J, Beckers A, Bihan H, Brue T, Caron P, Chabre O, Cogne M, Cortet-Rudelli C, Delemer B, Dufour H, Gaillard R, Gueydan M, Morange I, Souberbielle JC, Tabarin A. French consensus on the management of acromegaly.Ann Endocrinol (Paris). 2009; 70 (2) :92-106. Giustina A, Barkan A, Chanson P, Grossman A, Hoffman A, Ghigo E, Casanueva F, Colao A, Lamberts S, Sheppard M, Melmed S. Guidelines for the treatment of growth hormone excess and growth hormone deficiency in adults.J Endocrinol Invest. 2008; 31 (9) :820-838. Giustina A, Chanson P, Bronstein MD, Klibanski A, Lamberts S, Casanueva FF, Trainer P, Ghigo E, Ho K, Melmed S. A consensus on criteria for cure of acromegaly.J Clin Endocrinol Metab. 2010; 95 (7) :3141-3148. Melmed S, Colao A, Barkan A, Molitch M, Grossman AB, Kleinberg D, Clemmons D, Chanson P, Laws E, Schlechte J, Vance ML, Ho K, Giustina A. Guidelines for acromegaly management: an update.J Clin Endocrinol Metab. 2009; 94 (5) :1509-1517.

Evaluate short stature in children and for acromegaly Use in conjunction with GH and IGF-1 testing

ARUP LABORATORIES | 500 Chipeta Way | Salt Lake City, Utah 84108-1221 | (800) 522-2787 | www.arupconsult.com | www.aruplab.com

© 2006­2013 ARUP Laboratories. All Rights Reserved. Acromegaly - p. 4 of 5

The Physician's Guide to Laboratory Test Selection and Interpretation

General References Ayuk J, Sheppard MC. Growth hormone and its disorders.Postgrad Med J. 2006; 82 (963) :24-30. Bidlingmaier M, Strasburger CJ. Growth hormone assays: current methodologies and their limitations.Pituitary. 2007; 10 (2) :115-119. Chanson P, Salenave S, Kamenicky P, Cazabat L, Young J. Pituitary tumours: acromegaly.Best Pract Res Clin Endocrinol Metab. 2009; 23 (5) :555-574. Chanson P, Salenave S. Acromegaly.Orphanet J Rare Dis. 2008; 3 :17-. Cordero RA, Barkan AL. Current diagnosis of acromegaly.Rev Endocr Metab Disord. 2008; 9 (1) :13-19. Ferone D, Resmini E, Bocca L, Giusti M, Barreca A, Minuto F. Current diagnostic guidelines for biochemical diagnosis of acromegaly.Minerva Endocrinol. 2004; 29 (4) :207-223. Katznelson L. Diagnosis and treatment of acromegaly.Growth Horm IGF Res. 2005; 15 Suppl A :S31-S35. Tzanela M. Dynamic tests and basal values for defining active acromegaly.Neuroendocrinology. 2006; 83 (3-4) :200-204. Reviewed by Meikle, A. Wayne, MD. Medical Director, Endocrinology and Automated Endocrinology at ARUP Laboratories; Professor of Medicine, Endocrinology, and Pathology, University of Utah Diagnostic Algorithm(s) PDF algorithm(s) available at www.arupconsult.com. Acromegaly Testing Algorithm Related Content Adrenal Hyperfunction - Cushing Syndrome Cardiovascular Disease (Traditional Risk Markers) - Risk Markers - CVD (Traditional) Colorectal Cancer Diabetes Mellitus Multiple Endocrine Neoplasias - MEN Thyroid Disease

Last Update: December 2012

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