Albright Syndrome Workup

  • Author: Noah S Scheinfeld, MD, JD, FAAD; Chief Editor: Dirk M Elston, MD   more...
 
Updated: Sep 21, 2011
 

Laboratory Studies

A highly sensitive polymerase chain reaction test can find activating mutations of the GNAS1 gene in peripheral blood cells of patients with McCune-Albright syndrome (MAS) or isolated fibrous dysplasia.[23]

Full endocrine studies should be performed. Testicular/ovarian hyperfunction is the most common abnormality. Testosterone or estradiol levels are elevated. Gonadotropin levels are usually reduced or normal. Hyperthyroidism is common (33%), with elevated thyroxine, but low or normal thyrotropin levels. Growth hormone (GH), prolactin, and, rarely, luteinizing hormone or follicle-stimulating hormone, levels may be elevated. The GH excess among patients with MAS has been noted to be as high as 21%. The basis of GH hypersecretion in MAS remains incompletely understood, but it appears to have a different basis from acromegaly/gigantism in non-MAS patients.[24] Elevated cortisol levels are not suppressed by dexamethasone. Hypophosphatemia with hyperphosphaturia is noted.

Arterial blood gas determination can be performed to evaluate for acidosis, if suspected.

A complete metabolic profile can be performed to screen for hyperbilirubinemia, elevated liver enzyme levels, and electrolyte abnormalities.

Amylase and lipase levels can be measured to evaluate for pancreatitis, if suspected.

To surmount the variations in mutations of GNAS1 analysis for MAS, sensitive and specific molecular methods are needed and must be performed on affected tissues and from easily accessible tissues. This was shown to be particularly true for atypical and monosymptomatic forms of MAS.[25]

Next

Imaging Studies

Plain radiography [26]

For PFD, lytic lesions are seen in the affected bones, with scalloped borders in the cortex and a central ground-glass pattern. The femur and pelvis are involved most commonly, as shown in the image below.

Lucency characteristic of polyostotic fibrous dyspLucency characteristic of polyostotic fibrous dysplasia in a patient with McCune-Albright syndrome.

Sclerosis of the basilar or temporal skull is seen, with possible involvement of the ossicles or impingement on the temporal nerve. Evidence of past or current pathologic fractures is seen. Findings of hypophosphatemic rickets may be present. Osteosarcoma is rare (2%) and is found most often in patients who have received radiation treatment to affected bone lesions.

CT scanning

The skull may show pituitary adenoma. The pathologic bone findings of MAS can be solitary (monostotic) or multiple (polyostotic). The bones most frequently affected in MAS are the femur, tibia, ribs, and facial skeleton. A specific change involving the fibula is pseudocystic areas, and ground glass–like areas occur in the femur. The specific change involving the fibula is referred to as the shepherd's crook deformation; it is due to the weight put on a less resistant bone, and the occurrence of many secondary cortical microfractures is not uncommon.

MRI and bone scintigraphy

MRI helps define bone pathology in persons with MAS. Bone scintigraphy with technetium Tc 99m is necessary to monitor disease progression.[26, 27]

Ultrasonography

The thyroid may show nodules. The ovaries may show cysts.

Previous
Next

Other Tests

Electrocardiogram can be performed to evaluate for arrhythmia, if suspected.

Previous
Next

Procedures

Endoscopy can be performed to evaluate for GI polyposis, if suspected.

Previous
Next

Histologic Findings

Skin biopsy of CALMs reveals hyperpigmentation of the epidermis, with a normal number of melanocytes. While some specimens show giant melanosomes, this is by no means diagnostic. Giant melanosomes can also be found in CALMs of patients with neurofibromatosis and in healthy patients.

The bone histology of MAS has been reassessed in view of the pathological effect of the genetic lesions on mutated skeletal stem cells. MAS is a disease of excess abnormal and imperfect bone formation, a fact which helps elucidate its mechanisms.[28]

Previous
Proceed to Treatment & Management
 
 
Contributor Information and Disclosures
Author

Noah S Scheinfeld, MD, JD, FAAD  Assistant Clinical Professor, Department of Dermatology, Columbia University College of Physicians and Surgeons; Consulting Staff, Department of Dermatology, St Luke's Roosevelt Hospital Center, Beth Israel Medical Center, and New York Eye and Ear Infirmary; Private Practice

Noah S Scheinfeld, MD, JD, FAAD is a member of the following medical societies: American Academy of Dermatology

Disclosure: Optigenex Consulting fee Independent contractor

Specialty Editor Board

Eleanor E Sahn, MD  Director, Division of Pediatric Dermatology, Associate Professor, Departments of Dermatology and Pediatrics, Medical University of South Carolina

Eleanor E Sahn, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, and Southern Medical Association

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.

Van Perry, MD  Assistant Professor, Department of Medicine, Division of Dermatology, University of Texas School of Medicine at San Antonio

Van Perry, MD is a member of the following medical societies: American Academy of Dermatology and American Society for Laser Medicine and Surgery

Disclosure: Nothing to disclose.

Catherine M Quirk, MD  Clinical Assistant Professor, Department of Dermatology, University of Pennsylvania

Catherine M Quirk, MD is a member of the following medical societies: Alpha Omega Alpha and American Academy of Dermatology

Disclosure: Nothing to disclose.

Chief Editor

Dirk M Elston, MD  Director, Ackerman Academy of Dermatopathology, New York

Dirk M Elston, MD is a member of the following medical societies: American Academy of Dermatology

Disclosure: Nothing to disclose.

Additional Contributors

The authors and editors of eMedicine gratefully acknowledge the contributions of previous author, D. Stanton Whittaker Jr, MD, to the development and writing of this article.

References

  1. Weinstein LS, Liu J, Sakamoto A, Xie T, Chen M. Minireview: GNAS: normal and abnormal functions. Endocrinology. Dec 2004;145(12):5459-64. [Medline].

  2. Chanson P, Salenave S, Orcel P. McCune-Albright syndrome in adulthood. Pediatr Endocrinol Rev. Aug 2007;4 Suppl 4:453-62. [Medline].

  3. Robey PG, Kuznetsov S, Riminucci M, Bianco P. The role of stem cells in fibrous dysplasia of bone and the Mccune-Albright syndrome. Pediatr Endocrinol Rev. Aug 2007;4 Suppl 4:386-94. [Medline].

  4. Diaz A, Danon M, Crawford J. McCune-Albright syndrome and disorders due to activating mutations of GNAS1. J Pediatr Endocrinol Metab. Aug 2007;20(8):853-80. [Medline].

  5. Ozono K. GNAS1 gene abnormality in pseudohypoparathyroidism I a. Clin Calcium. Aug 2007;17(8):1214-9. [Medline].

  6. Wasniewska M, Matarazzo P, Weber G, Russo G, Zampolli M, Salzano G, et al. Clinical presentation of McCune-Albright syndrome in males. J Pediatr Endocrinol Metab. May 2006;19 Suppl 2:619-22. [Medline].

  7. Osada H, Sakamoto R, Seki K, Sekiya S. Accelerated bone turnover in pregnant women with McCune-Albright syndrome. Gynecol Obstet Invest. 2005;60(2):102-7. [Medline].

  8. Matarazzo P, Lala R, Andreo M, Einaudi S, Altare F, Viora E, et al. McCune-Albright syndrome: persistence of autonomous ovarian hyperfunction during adolescence and early adult age. J Pediatr Endocrinol Metab. May 2006;19 Suppl 2:607-17. [Medline].

  9. Volkl TM, Dorr HG. McCune-Albright syndrome: clinical picture and natural history in children and adolescents. J Pediatr Endocrinol Metab. May 2006;19 Suppl 2:551-9. [Medline].

  10. Kapoor S, Gogia S, Paul R, Banerjee S. Albright's hereditary osteodystrophy. Indian J Pediatr. Feb 2006;73(2):153-6. [Medline].

  11. Sargin H, Gozu H, Bircan R, Sargin M, Avsar M, Ekinci G, et al. A case of McCune-Albright syndrome associated with Gs alpha mutation in the bone tissue. Endocr J. Feb 2006;53(1):35-44. [Medline].

  12. Leet AI, Wientroub S, Kushner H, Brillante B, Kelly MH, Robey PG, et al. The correlation of specific orthopaedic features of polyostotic fibrous dysplasia with functional outcome scores in children. J Bone Joint Surg Am. Apr 2006;88(4):818-23. [Medline].

  13. Hamadani M, Chaudhary AL. McCune-Albright syndrome. Med J Aust. Dec 4-18 2006;185(11-12):597. [Medline].

  14. Ozcan-Kara P, Mahmoudian B, Erbas B, Erbas T. McCune-Albright syndrome associated with acromegaly and bipolar affective disorder. Eur J Intern Med. Dec 2007;18(8):600-2. [Medline].

  15. Narayan RL, Maldjian PD. Restrictive lung disease and cor pulmonale secondary to polyostotic fibrous dysplasia. Int J Cardiol. Aug 22 2007;[Medline].

  16. Bhat MH, Bhadada S, Dutta P, Bhansali A, Mittal BR. Hyperthyroidism with fibrous dysplasia: an unusual presentation of McCune-Albright syndrome. Exp Clin Endocrinol Diabetes. May 2007;115(5):331-3. [Medline].

  17. Román R, López P, Johnson MC, Boric MA, Gallo M, Ponce C, et al. Sudden infant death syndrome and activating gnas1 gene mutations. Fetal Pediatr Pathol. Jul-Aug 2007;26(4):199-205. [Medline].

  18. Bajpai A, Greenway A, Zacharin M. Platelet dysfunction and increased bleeding tendency in McCune-Albright syndrome. J Pediatr. 2008;153:287-9. [Medline].

  19. Xavier SP, Ribeiro MC, Sicchieri LG, Brentegani LG, Lacerda SA. Clinical, microscopic and imaging findings associated to McCune-Albright syndrome: report of two cases. Braz Dent J. 2008;19:165-70. [Medline].

  20. Ohata Y, Yamamoto T, Mori I, Kikuchi T, Michigami T, Imanishi Y, et al. Severe arterial hypertension: a possible complication of McCune-Albright syndrome. Eur J Pediatr. 2009;168:871-6. [Medline].

  21. Arrigo T, Pirazzoli P, De Sanctis L, Leone O, Wasniewska M, Messina MF, et al. McCune-Albright syndrome in a boy may present with a monolateral macroorchidism as an early and isolated clinical manifestation. Horm Res. 2006;65(3):114-9. [Medline].

  22. Medow JE, Agrawal BM, Resnick D. Polyostotic fibrous dysplasia of the cervical spine: case report and review of the literature. Spine J. Nov-Dec 2007;7(6):712-5. [Medline].

  23. Lietman SA, Ding C, Levine MA. A highly sensitive polymerase chain reaction method detects activating mutations of the GNAS gene in peripheral blood cells in McCune-Albright syndrome or isolated fibrous dysplasia. J Bone Joint Surg Am. Nov 2005;87(11):2489-94. [Medline].

  24. Christoforidis A, Maniadaki I, Stanhope R. McCune-Albright syndrome: growth hormone and prolactin hypersecretion. J Pediatr Endocrinol Metab. May 2006;19 Suppl 2:623-5. [Medline].

  25. de Sanctis L, Delmastro L, Russo MC, Matarazzo P, Lala R, de Sanctis C. Genetics of McCune-Albright syndrome. J Pediatr Endocrinol Metab. May 2006;19 Suppl 2:577-82. [Medline].

  26. Esmaili J, Chavoshi M, Noorani MH, Eftekhari M, Assadi M. Late diagnosed polyostotic fibrous dysplasia. Bone scan, radiography and magnetic resonance imaging findings. Hell J Nucl Med. Jan-Apr 2010;13(1):65-6. [Medline].

  27. Defilippi C, Chiappetta D, Marzari D, Mussa A, Lala R. Image diagnosis in McCune-Albright syndrome. J Pediatr Endocrinol Metab. May 2006;19 Suppl 2:561-70. [Medline].

  28. Riminucci M, Robey PG, Bianco P. The pathology of fibrous dysplasia and the McCune-Albright syndrome. Pediatr Endocrinol Rev. Aug 2007;4 Suppl 4:401-11. [Medline].

  29. Lala R, Matarazzo P, Andreo M, Marzari D, Bellone J, Corrias A, et al. Bisphosphonate treatment of bone fibrous dysplasia in McCune-Albright syndrome. J Pediatr Endocrinol Metab. May 2006;19 Suppl 2:583-93. [Medline].

  30. Mansoori LS, Catel CP, Rothman MS. Bisphosphonate Treatment in Polyostotic Fibrous Dysplasia of the Cranium: Case Report and Literature Review. Endocr Pract. Jun 21 2010;1-14. [Medline].

  31. Chan B, Zacharin M. Maternal and infant outcome after pamidronate treatment of polyostotic fibrous dysplasia and osteogenesis imperfecta before conception: a report of four cases. J Clin Endocrinol Metab. Jun 2006;91(6):2017-20. [Medline].

  32. Dunkel L. Use of aromatase inhibitors to increase final height. Mol Cell Endocrinol. Jul 25 2006;254-255:207-16. [Medline].

  33. Feuillan P, Calis K, Hill S, Shawker T, Robey PG, Collins MT. Letrozole treatment of precocious puberty in girls with the McCune-Albright syndrome; a pilot study. J Clin Endocrinol Metab. Apr 3 2007;[Medline].

  34. Messina MF, Arrigo T, Wasniewska M, Lombardo F, Crisafulli G, Salzano G, et al. Combined treatment with ketoconazole and cyproterone acetate in a boy with McCune-Albright syndrome and peripheral precocious puberty. J Endocrinol Invest. 2008;31:839-40. [Medline].

  35. Gesmundo R, Guanà R, Valfrè L, De Sanctis L, Matarazzo P, Marzari D, et al. Laparoscopic management of ovarian cysts in peripheral precocious puberty of McCune-Albright syndrome. J Pediatr Endocrinol Metab. May 2006;19 Suppl 2:571-5. [Medline].

  36. Verma RR, Paul A. Fibrous dysplasia of the fourth metacarpal: en-bloc resection and free metatarsal transfer. Orthopedics. Apr 2006;29(4):371-2. [Medline].

  37. Feuillan P, Calis K, Hill S, Shawker T, Robey PG, Collins MT. Letrozole treatment of precocious puberty in girls with the McCune-Albright syndrome: a pilot study. J Clin Endocrinol Metab. Jun 2007;92(6):2100-6. [Medline].

  38. DiMeglio LA. Bisphosphonate therapy for fibrous dysplasia. Pediatr Endocrinol Rev. Aug 2007;4 Suppl 4:440-5. [Medline].

  39. Jayaraman M, Karikumar K, Verma A, Modi KD. Alendronate therapy in polyostotic fibrous dysplasia presenting with pathologic fracture. Am J Orthop (Belle Mead NJ). Mar 2011;3:E48-51. [Medline].

  40. Rastogi A, Bhadada SK, Bhansali A. Recurrent Femur Neck Fracture and Response to Bisphosphonates in Polyostotic Fibrous Dysplasia. Indian J Pediatr. Jul 2011;[Medline].

 
Previous
Next
 
Large café au lait patches around the shoulder in a child with McCune-Albright syndrome.
Lucency characteristic of polyostotic fibrous dysplasia in a patient with McCune-Albright syndrome.
 
 
 
All material on this website is protected by copyright, Copyright © 1994-2012 by WebMD LLC.
This website also contains material copyrighted by 3rd parties.

DISCLAIMER: The content of this Website is not influenced by sponsors. The site is designed primarily for use by qualified physicians and other medical professionals. The information contained herein should NOT be used as a substitute for the advice of an appropriately qualified and licensed physician or other health care provider. The information provided here is for educational and informational purposes only. In no way should it be considered as offering medical advice. Please check with a physician if you suspect you are ill.