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Gigantism and Acromegaly Differential Diagnoses

  • Author: Alicia Diaz-Thomas, MD, MPH; Chief Editor: Stephen Kemp, MD, PhD  more...
 
Updated: Jan 06, 2015
 
 

Diagnostic Considerations

Differentials in gigantism include the following:

  • Familial tall stature
  • Exogenous obesity
  • Cerebral gigantism (Sotos syndrome): From NSD1 gene mutation or other causes
  • Weaver syndrome
  • Estrogen receptor mutation

Carney complex

Carney complex is a familial multiple neoplasia and lentiginosis syndrome. Growth hormone (GH) ̶ producing pituitary tumors have been described in individuals with the disorder.

Carney complex can exist in the following forms:

  • Carney complex (NAME syndrome [nevi, atrial myxoma, myxoid neurofibroma, ephelides])
  • Carney complex (LAMB syndrome [lentigines, atrial myxoma, mucocutaneous myxomas, blue nevi])

Manifestations and primary findings in Carney complex include cardiocutaneous syndrome, which is characterized by the following:

  • Pigmented skin lesions and atrial myxomas
  • Lentigines (mucocutaneous)
  • Atrial myxomas (may be fatal)
  • Mucocutaneous myxomas
  • Blue nevi
  • Congenital melanocytic nevi
  • Schwannomas

Endocrine abnormalities of Carney complex include the following:

  • Acromegaly
  • Endocrine overactivity
  • Cushing syndrome
  • Sexual precocity in boys
  • Thyroid hyperplasia
  • Primary pigmented nodular adrenocortical disease
  • Testicular tumors
  • Uterine myxomas

McCune-Albright syndrome

McCune-Albright syndrome is manifested clinically by the presence of the following:

  • Polyostotic fibrous dysplasia of bone
  • Hyperpigmented skin macules
  • Precocious sexual development in children
  • Goiter
  • Hyperthyroidism
  • Acromegaly
  • Cushing syndrome
  • Hyperprolactinemia
  • Sexual precocity
  • Hyperparathyroidism,
  • Hypophosphatemic hyperphosphaturic rickets

Other

Pseudoacromegaly is defined as the presence of acromegaloid features in the absence of elevated levels of GH or insulinlike growth factor I (IGF-I) in patients with severe insulin resistance.

Pachydermoperiostosis syndrome is manifested clinically by finger clubbing, extremity enlargement, hypertrophic skin changes, and periosteal bone formation.

Differential Diagnoses

 
 
Contributor Information and Disclosures
Author

Alicia Diaz-Thomas, MD, MPH Assistant Professor of Pediatrics, University of Tennessee Health Science Center

Alicia Diaz-Thomas, MD, MPH is a member of the following medical societies: American Association of Clinical Endocrinologists, Endocrine Society, Pediatric Endocrine Society, Tennessee Medical Association

Disclosure: Nothing to disclose.

Coauthor(s)

Robert A Schwartz, MD, MPH Professor and Head of Dermatology, Professor of Pathology, Pediatrics, Medicine, and Preventive Medicine and Community Health, Rutgers New Jersey Medical School; Visiting Professor, Rutgers University School of Public Affairs and Administration

Robert A Schwartz, MD, MPH is a member of the following medical societies: Alpha Omega Alpha, New York Academy of Medicine, American Academy of Dermatology, American College of Physicians, Sigma Xi

Disclosure: Nothing to disclose.

Melanie Shim, MD 

Melanie Shim, MD is a member of the following medical societies: American Diabetes Association, Endocrine Society

Disclosure: Nothing to disclose.

Chief Editor

Stephen Kemp, MD, PhD Former Professor, Department of Pediatrics, Section of Pediatric Endocrinology, University of Arkansas for Medical Sciences College of Medicine, Arkansas Children's Hospital

Stephen Kemp, MD, PhD is a member of the following medical societies: American Academy of Pediatrics, American Association of Clinical Endocrinologists, American Pediatric Society, Endocrine Society, Phi Beta Kappa, Southern Medical Association, Southern Society for Pediatric Research

Disclosure: Nothing to disclose.

Acknowledgements

Barry B Bercu, MD Professor, Departments of Pediatrics, Molecular Pharmacology and Physiology, University of South Florida College of Medicine, All Children's Hospital

Barry B Bercu, MD is a member of the following medical societies: American Academy of Pediatrics, American Association of Clinical Endocrinologists, American Federation for Clinical Research, American Medical Association, American Pediatric Society, Association of Clinical Scientists, Endocrine Society, Florida Medical Association, Pediatric Endocrine Society, Pituitary Society, Society for Pediatric Research, Society forthe Study of Reproduction, and Southern Society for Pediatric Research

Disclosure: Nothing to disclose.

Santiago A Centurion, MD Staff Physician, Department of Dermatology, New Jersey Medical School, University of Medicine and Dentistry of New Jersey

Santiago A Centurion, MD is a member of the following medical societies: American Academy of Dermatology, American Medical Association, and Sigma Xi

Disclosure: Nothing to disclose.

Arthur B Chausmer, MD, PhD, FACP, FACE, FACN, CNS Professor of Medicine (Endocrinology, Adj), Johns Hopkins School of Medicine; Affiliate Research Professor, Bioinformatics and Computational Biology Program, School of Computational Sciences, George Mason University; Principal, C/A Informatics, LLC

Arthur B Chausmer, MD, PhD, FACP, FACE, FACN, CNS is a member of the following medical societies: American Association of Clinical Endocrinologists, American College of Endocrinology, American College of Nutrition, American College of Physicians, American College of Physicians-American Society of Internal Medicine, American Medical Informatics Association, American Society for Bone and Mineral Research, International Society for Clinical Densitometry, and The Endocrine Society

Disclosure: Nothing to disclose.

Robert J Ferry Jr, MD Le Bonheur Chair of Excellence in Endocrinology, Professor and Chief, Division of Pediatric Endocrinology and Metabolism, Department of Pediatrics, University of Tennessee Health Science Center

Robert J Ferry Jr, MD is a member of the following medical societies: American Academy of Pediatrics, American Diabetes Association, American Medical Association, Endocrine Society, Pediatric Endocrine Society, Society for Pediatric Research, and Texas Pediatric Society

Disclosure: Eli Lilly & Co Grant/research funds Investigator; MacroGenics, Inc Grant/research funds Investigator; Ipsen, SA (formerly Tercica, Inc) Grant/research funds Investigator; NovoNordisk SA Grant/research funds Investigator; Diamyd Grant/research funds Investigator; Bristol-Myers-Squibb Grant/research funds Other; Amylin Other; Pfizer Grant/research funds Other; Takeda Grant/research funds Other

Barry J Goldstein, MD, PhD Director, Division of Endocrinology, Diabetes and Metabolic Diseases, Professor, Department of Internal Medicine, Thomas Jefferson University

Barry J Goldstein, MD, PhD is a member of the following medical societies: Alpha Omega Alpha, American College of Clinical Endocrinologists, American College of Physicians-American Society of Internal Medicine, American Diabetes Association, and The Endocrine Society

Disclosure: Nothing to disclose.

George T Griffing, MD Professor of Medicine, St Louis University School of Medicine

George T Griffing, MD is a member of the following medical societies: American Association for the Advancement of Science, American College of Medical Practice Executives, American College of Physician Executives, American College of Physicians, American Diabetes Association, American Federation for Medical Research, American Heart Association, Central Society for Clinical Research, International Society for Clinical Densitometry, Southern Society for Clinical Investigation, and The Endocrine Society

Disclosure: Nothing to disclose.

William D James, MD Paul R Gross Professor of Dermatology, Vice-Chairman, Residency Program Director, Department of Dermatology, University of Pennsylvania School of Medicine

William D James, MD is a member of the following medical societies: American Academy of Dermatology and Society for Investigative Dermatology

Disclosure: Nothing to disclose.

Hasnain M Khandwala, MD, FRCPC Endocrinologist, LMC Endocrinology Centers, Canada

Hasnain M Khandwala, MD, FRCPC is a member of the following medical societies: American Association of Clinical Endocrinologists, American Diabetes Association, Canadian Medical Association, and The Endocrine Society

Disclosure: Nothing to disclose.

Jeffrey J Miller, MD Associate Professor of Dermatology, Pennsylvania State University College of Medicine; Staff Dermatologist, Pennsylvania State Milton S Hershey Medical Center

Jeffrey J Miller, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, Association of Professors of Dermatology, North American Hair Research Society, and Society for Investigative Dermatology

Disclosure: Nothing to disclose.

Robert A Schwartz, MD, MPH Professor and Head, Dermatology, Professor of Pathology, Pediatrics, Medicine, and Preventive Medicine and Community Health, Rutgers New Jersey Medical School

Robert A Schwartz, MD, MPH is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American College of Physicians, New York Academy of Medicine, and Sigma Xi

Disclosure: Nothing to disclose.

Phyllis W Speiser, MD Chief, Division of Pediatric Endocrinology, Steven and Alexandra Cohen Children's Medical Center of New York; Professor of Pediatrics, Hofstra-North Shore LIJ School of Medicine at Hofstra University

Phyllis W Speiser, MD is a member of the following medical societies: American Association of Clinical Endocrinologists, Endocrine Society, Pediatric Endocrine Society, and Society for Pediatric Research

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

Shyam Verma, MBBS, DVD, FAAD Clinical Associate Professor, Department of Dermatology, University of Virginia; Adjunct Associate Professor, Department of Dermatology, State University of New York at Stonybrook, Adjunct Associate Professor, Department of Dermatology, University of Pennsylvania

Shyam Verma, MBBS, DVD, FAAD is a member of the following medical societies: American Academy of Dermatology

Disclosure: Nothing to disclose.

Richard P Vinson, MD Assistant Clinical Professor, Department of Dermatology, Texas Tech University Health Sciences Center, Paul L Foster School of Medicine; Consulting Staff, Mountain View Dermatology, PA

Richard P Vinson, MD is a member of the following medical societies: American Academy of Dermatology, Association of Military Dermatologists, Texas Dermatological Society, and Texas Medical Association

Disclosure: Nothing to disclose.

Mary L Windle, PharmD Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

References
  1. Berg C, Petersenn S, Lahner H, Herrmann BL, Buchfelder M, Droste M, et al. Cardiovascular risk factors in patients with uncontrolled and long-term acromegaly: comparison with matched data from the general population and the effect of disease control. J Clin Endocrinol Metab. 2010 Aug. 95(8):3648-56. [Medline].

  2. Nainggolan L. Gene Discovery in Giants Could Shed Light on Human Growth. Medscape Medical News. Available at http://www.medscape.com/viewarticle/836216.. Accessed: December 12, 2014.

  3. Trivellin G, Daly AF, Faucz FR, Yuan B, Rostomyan L, Larco DO, et al. Gigantism and acromegaly due to Xq26 microduplications and GPR101 mutation. N Engl J Med. 2014 Dec 18. 371(25):2363-74. [Medline].

  4. Al-Bedaia M, Al-Khenaizan AS. Acromegaly presenting as cutis verticis gyrata. Int J Dermatol. 2008 Feb. 47(2):164. [Medline].

  5. Bush ZM, Vance ML. Management of acromegaly: is there a role for primary medical therapy?. Rev Endocr Metab Disord. 2008 Mar. 9(1):83-94. [Medline].

  6. Colao A, Pivonello R, Auriemma RS, Briganti F, Galdiero M, Tortora F, et al. Predictors of tumor shrinkage after primary therapy with somatostatin analogs in acromegaly: a prospective study in 99 patients. J Clin Endocrinol Metab. 2006 Jun. 91(6):2112-8. [Medline].

  7. Giustina A, Chanson P, Bronstein MD, Klibanski A, Lamberts S, Casanueva FF, et al. A consensus on criteria for cure of acromegaly. J Clin Endocrinol Metab. 2010 Jul. 95(7):3141-8. [Medline].

  8. Colak Ozbey N, Kapran Y, Bozbora A, Erbil Y, Tascioglu C, Asa SL. Ectopic growth hormone-releasing hormone secretion by a neuroendocrine tumor causing acromegaly: long-term follow-up results. Endocr Pathol. 2009 Summer. 20(2):127-32. [Medline].

  9. Khandelwal D, Khadgawat R, Mukund A, Suri A. Acromegaly with no pituitary adenoma and no evidence of ectopic source. Indian J Endocrinol Metab. 2011 Sep. 15 Suppl 3:S250-2. [Medline]. [Full Text].

  10. Uchoa HB, Lima GA, Corrêa LL, Vidal AP, Cavallieri SA, Vaisman M, et al. Prevalence of thyroid diseases in patients with acromegaly: experience of a Brazilian center. Arq Bras Endocrinol Metabol. 2013 Dec. 57(9):685-90. [Medline].

  11. Soares BS, Eguchi K, Frohman LA. Tumor deletion mapping on chromosome 11q13 in eight families with isolated familial somatotropinoma and in 15 sporadic somatotropinomas. J Clin Endocrinol Metab. 2005 Dec. 90(12):6580-7. [Medline].

  12. Melmed S, Casanueva FF, Klibanski A, Bronstein MD, Chanson P, Lamberts SW, et al. A consensus on the diagnosis and treatment of acromegaly complications. Pituitary. 2013 Sep. 16(3):294-302. [Medline]. [Full Text].

  13. Oshino S, Nishino A, Suzuki T, et al. Prevalence of cerebral aneurysm in patients with acromegaly. Pituitary. 2013 Jun. 16(2):195-201. [Medline].

  14. Stelmachowska-Banas M, Zdunowski P, Zgliczynski W. Abnormalities in glucose homeostasis in acromegaly. Does the prevalence of glucose intolerance depend on the level of activity of the disease and the duration of the symptoms?. Endokrynol Pol. 2009 Jan-Feb. 60(1):20-4. [Medline].

  15. Dworakowska D, Gueorguiev M, Kelly P, Monson JP, Besser GM, Chew SL, et al. Repeated colonoscopic screening of patients with acromegaly: 15-year experience identifies those at risk of new colonic neoplasia and allows for effective screening guidelines. Eur J Endocrinol. 2010 Jul. 163(1):21-8. [Medline].

  16. Loeper S, Ezzat S. Acromegaly: re-thinking the cancer risk. Rev Endocr Metab Disord. 2008 Mar. 9(1):41-58. [Medline].

  17. Kurimoto M, Fukuda I, Hizuka N, Takano K. The prevalence of benign and malignant tumors in patients with acromegaly at a single institute. Endocr J. 2008 Mar. 55(1):67-71. [Medline].

  18. Izzard AS, Emerson M, Prehar S, Neyses L, Trainer P, List EO, et al. The cardiovascular phenotype of a mouse model of acromegaly. Growth Horm IGF Res. 2009 Oct. 19(5):413-9. [Medline].

  19. [Guideline] Katznelson L, Atkinson JL, Cook DM, Ezzat SZ, Hamrahian AH, Miller KK. American Association of Clinical Endocrinologists Medical Guidelines for Clinical Practice for the Diagnosis and Treatment of Acromegaly--2011 update: executive summary. Endocr Pract. 2011 Jul-Aug. 17(4):636-46. [Medline].

  20. Wang M, Mou C, Jiang M, Han L, Fan S, Huan C, et al. The characteristics of acromegalic patients with hyperprolactinemia and the differences in patients with merely GH-secreting adenomas: clinical analysis of 279 cases. Eur J Endocrinol. 2012 May. 166(5):797-802. [Medline].

  21. Almalki MH, Chesover AD, Johnson MD, Wilkins GE, Maguire JA, Ur E. Characterization of management and outcomes of patients with acromegaly in Vancouver over 30 years. Clin Invest Med. 2012 Feb 1. 35(1):E27-33. [Medline].

  22. Sata A, Ho KK. Growth hormone measurements in the diagnosis and monitoring of acromegaly. Pituitary. 2007. 10(2):165-72. [Medline].

  23. Daroszewski J, Bolanowski M, Kaluzny M, Siewinski M. The imbalance of cathepsin B-like activity in acromegalic patients--preliminary report. Neuro Endocrinol Lett. 2010. 31(2):256-60. [Medline].

  24. Roelfsema F, Biermasz NR, Romijn JA, Pereira AM. Treatment strategies for acromegaly. Expert Opin Emerg Drugs. 2005 Nov. 10(4):875-90. [Medline].

  25. [Guideline] Katznelson L, Laws ER Jr, Melmed S, et al. Acromegaly: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2014 Nov. 99(11):3933-51. [Medline].

  26. [Guideline] Nainggolan L. New Guidelines for Acromegaly Include Advice on Pregnancy. Medscape Medical News. Nov 10 2014. [Full Text].

  27. Azkur D, Yoldas T, Toyran M, Kocabas CN. A pediatric case of anaphylaxis due to octreotide. Asian Pac J Allergy Immunol. 2011 Dec. 29(4):361-3. [Medline].

  28. Shimatsu A, Teramoto A, Hizuka N, Kitai K, Ramis J, Chihara K. Efficacy, safety, and pharmacokinetics of sustained-release lanreotide (lanreotide Autogel) in Japanese patients with acromegaly or pituitary gigantism. Endocr J. 2013. 60(5):651-63. [Medline].

  29. Sheppard M, Bronstein MD, Freda P, Serri O, De Marinis L, Naves L, et al. Pasireotide LAR maintains inhibition of GH and IGF-1 in patients with acromegaly for up to 25 months: results from the blinded extension phase of a randomized, double-blind, multicenter, Phase III study. Pituitary. 2014 Aug 8. [Medline].

  30. Gadelha MR, Bronstein MD, Brue T, Coculescu M, Fleseriu M, Guitelman M, et al. Pasireotide versus continued treatment with octreotide or lanreotide in patients with inadequately controlled acromegaly (PAOLA): a randomised, phase 3 trial. Lancet Diabetes Endocrinol. 2014 Nov. 2(11):875-84. [Medline].

  31. Sandret L, Maison P, Chanson P. Place of cabergoline in acromegaly: a meta-analysis. J Clin Endocrinol Metab. 2011 May. 96(5):1327-35. [Medline].

  32. van der Lely AJ, Biller BM, Brue T, Buchfelder M, Ghigo E, Gomez R, et al. Long-term safety of pegvisomant in patients with acromegaly: comprehensive review of 1288 subjects in ACROSTUDY. J Clin Endocrinol Metab. 2012 May. 97(5):1589-97. [Medline].

  33. Higham CE, Atkinson AB, Aylwin S, Bidlingmaier M, Drake WM, Lewis A, et al. Effective combination treatment with cabergoline and low-dose pegvisomant in active acromegaly: a prospective clinical trial. J Clin Endocrinol Metab. 2012 Apr. 97(4):1187-93. [Medline].

  34. Rix M, Laurberg P, Hoejberg AS, Brock-Jacobsen B. Pegvisomant therapy in pituitary gigantism: successful treatment in a 12-year-old girl. Eur J Endocrinol. 2005 Aug. 153(2):195-201. [Medline].

  35. Castinetti F, Morange I, Dufour H, Regis J, Brue T. Radiotherapy and radiosurgery in acromegaly. Pituitary. 2009. 12(1):3-10. [Medline].

  36. Weber DC, Momjian S, Pralong FP, Meyer P, Villemure JG, Pica A. Adjuvant or radical fractionated stereotactic radiotherapy for patients with pituitary functional and nonfunctional macroadenoma. Radiat Oncol. 2011 Dec 8. 6:169. [Medline]. [Full Text].

  37. Jagannathan J, Yen CP, Pouratian N, Laws ER, Sheehan JP. Stereotactic radiosurgery for pituitary adenomas: a comprehensive review of indications, techniques and long-term results using the Gamma Knife. J Neurooncol. 2009 May. 92(3):345-56. [Medline].

  38. Espinosa-de-Los-Monteros AL, Sosa E, Cheng S, Ochoa R, Sandoval C, Guinto G, et al. Biochemical evaluation of disease activity after pituitary surgery in acromegaly: a critical analysis of patients who spontaneously change disease status. Clin Endocrinol (Oxf). 2006 Mar. 64(3):245-9. [Medline].

  39. Abe T, Tara LA, Lüdecke DK. Growth hormone-secreting pituitary adenomas in childhood and adolescence: features and results of transnasal surgery. Neurosurgery. 1999 Jul. 45(1):1-10. [Medline].

  40. Ronchi CL, Giavoli C, Ferrante E, Verrua E, Bergamaschi S, Ferrari DI, et al. Prevalence of GH deficiency in cured acromegalic patients: impact of different previous treatments. Eur J Endocrinol. 2009 Jul. 161(1):37-42. [Medline].

  41. van der Klaauw AA, Bax JJ, Roelfsema F, Bleeker GB, Holman ER, Corssmit EP, et al. Uncontrolled acromegaly is associated with progressive mitral valvular regurgitation. Growth Horm IGF Res. 2006 Apr. 16(2):101-7. [Medline].

  42. Thanabalasingham G, Grossman AB. Acromegaly: Beyond surgery. Indian J Endocrinol Metab. 2013 Jul. 17(4):563-7. [Medline]. [Full Text].

  43. Chahal HS, Stals K, Unterländer M, Balding DJ, Thomas MG, Kumar AV, et al. AIP mutation in pituitary adenomas in the 18th century and today. N Engl J Med. 2011 Jan 6. 364(1):43-50. [Medline].

  44. Kannan S, Kennedy L. Diagnosis of acromegaly: state of the art. Expert Opin Med Diagn. 2013 Sep. 7(5):443-53. [Medline].

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Image shows a coauthor of this article with a statue of Robert Wadlow, who was called the Alton giant. The tallest person on record, he was 8 feet 11 inches tall at the time of his death.
A 12-year-old boy with McCune-Albright syndrome. His growth-hormone excess manifested as tall stature, coarse facial features, and macrocephaly.
 
 
 
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