McCune-Albright Syndrome

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McCune-Albright Syndrome

• JEROME ELUSIYAN
• Paed. Endocrinology Fellowship
• Nairobi, Kenya

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Introduction

• syndrome of endocrine dysfunction associated
  with
• patchy cutaneous pigmentation
• fibrous dysplasia of the skeletal system
• sexual precocity
• and associated pituitary, thyroid, and adrenal
  aberrations

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Genetic

• characterized by autonomous hyperfunction of many
  glands
• the mutation is somatic rather than genomic,
  (occurring early in the embryo)
• it is expressed differently in different glands
  or tissues, hence the variability of clinical
  expression.
• No reported case in parent and children of
  affected women are normal

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.

• and is caused by a missense mutation in the gene
  encoding the a-subunit of GS, (the G protein that
  stimulates cyclic adenosine monophosphate (cAMP)
  formation),
• resulting in the formation of the putative gsp
  oncoprotein
• Activation of receptors (corticotropin ACTH,
  TSH, FSH, and LH receptors) that operate via a
  cAMP-dependent mechanism, as well as cell
  proliferation, ensue

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Clinical Features

• Precocious puberty- average age at onset in
  affected girls is about 3 yr, (vaginal bleeding
  has occurred as early as 4 mo of age and
  secondary sex characteristics have occurred as
  early as 6 mo)
• Hyperthyroidism and goiters (multinodular).
  Clinical hyperthyroidism is uncommon in children
• Cushing syndrome
• Café-au-lait spots

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.

• gigantism or acromegaly or by increased rates of
  growth even in the absence of precocious puberty
• deformities, repeated fractures, pain, and
  occasional cranial nerve compression may result
  from the bony lesions-polyostotic fibrous
  dysplasia
• phosphaturia, leading to rickets or osteomalacia
  
• Cardiovascular and hepatic involvement is rare
  but may be life-threatening (severe neonatal
  cholestasis).

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Diagnosis

• LH FSH are low and no response to GnRH
  stimulation
• Oestradiol is elevated( up to gt900pg/mL)
• Ovarian cyst (up to 50cc)
• Multinodular thyroid goitre
• Low TSH, N to High T3 T4
• Bilateral nodular adrenal hyperplasia
• Low ACTH, very high cortisol

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.

• High level of growth hormone and increase during
  sleep
• Fewer than half have demonstrable pituitary tumor
• High level of prolactin
• Increase urinary phosphate
• Xray shows polyostotic fibrous dysplasia or by
  radioisotope scan

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Treatment

• Precocious puberty- aromatase inhibitors eg
  testolactone or letrozole (1.25-2.5 mg/day p.o)
  or anastrozole 1mg/day or antiestrogens (e.g
  tamoxifen). In boys add antiandrogens eg
  spironolactone
• True gonadotropin-dependent PP may ensure
• Ovarian cysts usually regress spontaneously

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.

• In hyperthyroidism give PTU or Methimazol
• Surgery is rarely indicated
• Adrenal function is not suppreseed by large doses
  of Dexamethazone, the treatment for the cushings
  syndrome is bilateral adrenalectomy
• Hypersomatotropism is treated with octreotide a
  long acting somatostatin analog

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.

• If pituitary tumour is identified, then surgery
  is indicated
• In hypophosphateamia or ricket give oral
  phosphate and Vitamin D
• No known medical or hormonal treatment for the
  PFD of the bone, surgical procedures like
  grafting, pinning and casting are employed to
  correct fracture and deformities

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