eMedicine Specialties > Dermatology > Pediatric Diseases

Albright Syndrome: Differential Diagnoses & Workup

Author: Noah S Scheinfeld, MD, JD, FAAD, Assistant Clinical Professor, Department of Dermatology, Columbia University; Consulting Staff, Department of Dermatology, St Luke's Roosevelt Hospital Center, Beth Israel Medical Center, New York Eye and Ear Infirmary; Private Practice
Coauthor(s): D Stanton Whittaker Jr, MD, Consulting Staff, Boone Dermatology Clinic
Contributor Information and Disclosures

Updated: Mar 13, 2008

Differential Diagnoses

Other Problems to Be Considered

Café au lait macules

Neurofibromatosis type I or II
Tuberous sclerosis
Bloom syndrome
Ataxia-telangiectasia
Russell-Silver syndrome
Fanconi anemia

Precocious puberty

Ovarian/testicular tumors
Adrenal tumors
Congenital adrenal hyperplasia
Exogenous estrogens/androgens
Organic brain disease/tumors

Workup

Laboratory Studies

  • A highly sensitive polymerase chain reaction test can find activating mutations of the GNAS1 gene in peripheral blood cells of patients with MAS or isolated fibrous dysplasia.20
  • 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.21
    • 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.22

Imaging Studies

  • Plain radiography
    • 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 (see Media File 2).
    • 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.23
  • Ultrasound
    • The thyroid may show nodules.
    • The ovaries may show cysts.

Other Tests

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

Procedures

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

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.24

More on Albright Syndrome

Overview: Albright Syndrome
Differential Diagnoses & Workup: Albright Syndrome
Treatment & Medication: Albright Syndrome
Follow-up: Albright Syndrome
Multimedia: Albright Syndrome
References
[ CLOSE WINDOW ]

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. 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].

  19. 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].

  20. 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].

  21. 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].

  22. 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].

  23. 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].

  24. 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].

  25. 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].

  26. 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].

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

  28. 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].

  29. 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].

  30. 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].

  31. 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].

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

  33. Cavanah SF, Dons RF. McCune-Albright syndrome: how many endocrinopathies can one patient have?. South Med J. Mar 1993;86(3):364-7. [Medline].

  34. Danon M, Robboy SJ, Kim S, Scully R, Crawford JD. Cushing syndrome, sexual precocity, and polyostotic fibrous dysplasia (Albright syndrome) in infancy. J Pediatr. Dec 1975;87(6 Pt 1):917-21. [Medline].

  35. Hamadani M, Awab A, Rashid A, Ali T, Brown B. Fibrous dysplasia protuberans in a patient with McCune-Albright syndrome. J Coll Physicians Surg Pak. May 2006;16(5):376-7. [Medline].

  36. Lee PA, Van Dop C, Migeon CJ. McCune-Albright syndrome. Long-term follow-up. JAMA. Dec 5 1986;256(21):2980-4. [Medline].

  37. Levine MA. The McCune-Albright syndrome. The whys and wherefores of abnormal signal transduction. N Engl J Med. Dec 12 1991;325(24):1738-40. [Medline].

  38. Papadopoulou M, Doula S, Kitsios K, Kaltsas T, Kosta K. A boy with McCune-Albright syndrome associated with GH secreting pituitary microadenoma. Clinical findings and response to treatment. Hormones (Athens). Jul-Sep 2006;5(3):205-9. [Medline].

  39. Riminucci M, Fisher LW, Shenker A, Spiegel AM, Bianco P, Gehron Robey P. Fibrous dysplasia of bone in the McCune-Albright syndrome: abnormalities in bone formation. Am J Pathol. Dec 1997;151(6):1587-600. [Medline].

  40. Ringel MD, Schwindinger WF, Levine MA. Clinical implications of genetic defects in G proteins. The molecular basis of McCune-Albright syndrome and Albright hereditary osteodystrophy. Medicine (Baltimore). Jul 1996;75(4):171-84. [Medline].

  41. Shenker A, Weinstein LS, Moran A, Pescovitz OH, Charest NJ, Boney CM, et al. Severe endocrine and nonendocrine manifestations of the McCune-Albright syndrome associated with activating mutations of stimulatory G protein GS. J Pediatr. Oct 1993;123(4):509-18. [Medline].

  42. Spiegel AM. The molecular basis of disorders caused by defects in G proteins. Horm Res. 1997;47(3):89-96. [Medline].

  43. Weinstein LS, Shenker A, Gejman PV, Merino MJ, Friedman E, Spiegel AM. Activating mutations of the stimulatory G protein in the McCune-Albright syndrome. N Engl J Med. Dec 12 1991;325(24):1688-95. [Medline].

[ CLOSE WINDOW ]

Further Reading

[ CLOSE WINDOW ]

Keywords

McCune-Albright syndrome, Albright's syndrome, café au lait macules, CALMs, cafe au lait macules, cafe-au-lait macules, polyostotic fibrous dysplasia, PFD, endocrine dysfunction, precocious puberty, MAS, PPP

[ CLOSE WINDOW ]

Contributor Information and Disclosures

Author

Noah S Scheinfeld, MD, JD, FAAD, Assistant Clinical Professor, Department of Dermatology, Columbia University; Consulting Staff, Department of Dermatology, St Luke's Roosevelt Hospital Center, Beth Israel Medical Center, 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

Coauthor(s)

D Stanton Whittaker Jr, MD, Consulting Staff, Boone Dermatology Clinic
D Stanton Whittaker Jr, MD is a member of the following medical societies: Phi Beta Kappa
Disclosure: Nothing to disclose.

Medical Editor

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.

Pharmacy Editor

Richard P Vinson, MD, Assistant Clinical Professor, Department of Dermatology, Texas Tech University 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.

Managing Editor

Van Perry, MD, Assistant Professor, Department of Medicine, Division of Dermatology, University of Texas Health Science Center
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.

CME Editor

Catherine Quirk, MD, Clinical Assistant Professor, Department of Dermatology, Brown University
Catherine 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, Department of Dermatology, Geisinger Medical Center
Dirk M Elston, MD is a member of the following medical societies: American Academy of Dermatology
Disclosure: Nothing to disclose.

 
 
HONcode

We subscribe to the
HONcode principles of the
Health On the Net Foundation

All material on this website is protected by copyright, Copyright© 1994- by Medscape.
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.