A 29-year-old woman is evaluated for severe left hip pain after twisting her leg. She has bony deformities of the lower extremities, and her mobility is limited. The patient has a history of hyperthyroidism, which was managed with radioiodine therapy. Menarche was at age 7, and she has regular 30-day cycles. Physical examination shows large, hyperpigmented macules with irregular borders located on the left shoulder, left side of the neck, and left buttock. X-ray findings are shown in the image below. Which of the following is the most likely diagnosis?

Question

A 29-year-old woman is evaluated for severe left hip pain after twisting her leg.  She has bony deformities of the lower extremities, and her mobility is limited.  The patient has a history of hyperthyroidism, which was managed with radioiodine therapy.  Menarche was at age 7, and she has regular 30-day cycles.  Physical examination shows large, hyperpigmented macules with irregular borders located on the left shoulder, left side of the neck, and left buttock.  X-ray findings are shown in the image below.  Which of the following is the most likely diagnosis?

Quizplus · Accepted Answer

11ec160b_3a5b_d192_9249_bd13ed190a11_MD0001_00 This patient's triad of fibrous dysplasia (multiple osteolytic-appearing lesions of the hip and pelvis), endocrine abnormalities, and café-au-lait spots suggests a diagnosis of McCune-Albright syndrome (MAS). Her x-ray reveals a pathological fracture through the left hip in the region of fibrous dysplasia. MAS results from a mosaic somatic mutation during embryogenesis in the GNAS gene encoding the stimulatory α subunit of G protein. This mutation causes constitutive activation of the G protein/cAMP/adenylate cyclase signaling cascade, which leads to a gain of function of the affected cells. Persistent G-protein stimulatory activity in melanocytes results in prominent café-au-lait macules (CALMs). CALMs, usually the first manifestation of MAS, are often large and unilateral with an irregular, "coast of Maine" border. In addition, autonomous endocrine function most commonly results in precocious puberty (onset of secondary sexual development before age 8 in girls). The mutation also results in increased proliferation of fibroblast-like cells, increased secretion of IL-6, and activation of osteoclasts (fibrous dysplasia). The term polyostotic refers to the presence of lesions in many bones, although they are typically unilateral. (Choice A) Ewing sarcoma typically presents as a single lesion with months of pain and swelling in one of the long bones of the extremities or pelvis. Multiple layers of periosteal reaction result in a characteristic "onion peel" appearance on x-ray. (Choice B) Gaucher disease is an inherited lysosomal storage disease that is most common among Ashkenazi Jews and may also result in diffuse, painful lytic bone lesions. However, it leads to delayed puberty and growth. (Choice C) Legg-Calvé-Perthes disease is a disease of young children that results in isolated idiopathic osteonecrosis of the hip (red circle). (Choice E) Neurofibromatosis type 1 (NF1) is characterized by CALMs that are usually smaller, bilateral, and have a relatively smooth border ("coast of California"). These CALMs are usually accompanied by axillary/inguinal freckling and cutaneous neurofibromas. Bony abnormalities of NF1 include long-bone dysplasia (tibial bowing) and pseudoarthrosis that typically present in toddlers. Educational objective: McCune-Albright syndrome is characterized by the triad of fibrous dysplasia of the bone, endocrine abnormalities, and café-au-lait spots. The condition results from an activating mutation in the G protein/CAMP/adenylate cyclase signaling pathway. __________ References: McCune-Albright syndrome. (http://www.ncbi.nlm.nih.gov/pubmed/18489744) McCune-Albright syndrome and the extraskeletal manifestations of fibrous dysplasia. (http://www.ncbi.nlm.nih.gov/pubmed/22640971)

A 29-Year-Old Woman Is Evaluated for Severe Left Hip Pain