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McCune-Albright syndrome

McCune-Albright syndrome, described in 1937 by McCune and Albright, is a disease where two of the three following features are present:

  • (autonomous) endocrine hyperfunction
  • Fibrous dysplasia
  • CafĂ©-au-lait spots


The endocrine aspect of the disease can manifest itself as extremely premature puberty.

Genetically, there is a post-zygotic mutation of a gene involved in G-protein signalling, preventing downregulation of cAMP signalling.

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Cut-off age for precocious puberty is too young - Tips from Other Journals
From American Family Physician, 5/1/03 by Caroline Wellbery

A 1997 study published by the Pediatric Research in Office Settings (PROS) led a joint committee of the Lawson Wilkins Pediatric Endocrine Society to state that pubertal findings in black girls six years and older and in white girls seven years and older were normal. The age revision defining precocious puberty resulted from observations that girls in the United States were reaching puberty at a younger age than was previously considered normal. Midyett and colleagues hypothesize that the new guidelines, if followed, will lead to a significant underdiagnosis of endocrine conditions.

The authors performed a retrospective medical record review to determine the extent to which girls six to eight years of age who were referred to the pediatric endocrinology clinic had endocrine pathology, and whether they had true precocious puberty (characterized by two signs of puberty) or merely isolated premature thelarche or adrenarche. They also investigated whether the girls without pathology were more likely to be obese.

The authors reviewed 1,570 outpatient visits to their pediatric endocrinology clinic by white girls seven to eight years of age and black girls six to eight years of age. Of the 663 patients making these visits, 223 had been referred solely to be evaluated for precocious puberty. Statistical analysis was performed to compare differences in height, weight, and bone age between girls with two signs of puberty versus one, and to compare pathology between lean and obese girls.

Of the 223 study patients, 105 (47 percent) had two signs of puberty, 83 (37 percent) had pubic hair alone, and 24 (11 percent) had breast development alone. The remaining 11 girls (5 percent) had no actual pubertal findings. Of the 212 patients found to have signs of puberty, 95 (45 percent) were obese. Although the majority of girls were diagnosed with idiopathic pubertal development, 26 girls had additional endocrine diagnoses, among them neurofibromatosis, growth hormone deficiency, McCune-Albright syndrome, hypothyroidism, congenital adrenal hyperplasia, pituitary microadenoma, and hyperinsulinism.

Patients with two signs of pubertal development had significantly greater weight z scores, greater height z scores, higher body mass index, and more advanced bone age than girls with only one sign of puberty. Although 45 percent of the total patients were obese, 81 percent of the girls with a diagnosis of additional endocrine conditions were obese.

Pathologic endocrine conditions were present in a subset of referred patients who would have been defined as normal by the PROS study. Overall, 12.3 percent of the patients six to eight years of age manifested pathologic explanations for their sexual precocity. In addition, a sizable proportion of patients presented with advanced bone age, which signified loss of adult height potential. Adding to possible concerns, the authors cite studies suggesting that premature adrenarche may be a marker for hyperinsulinism. They also question whether the current onset of puberty is that much earlier than it has been in the past. They did not find any statistically significant differences in the incidence of true precocious puberty between black and white girls. Moreover, obesity was not associated with a decreased rate of pathologic findings.

The authors conclude that all girls younger than eight years with two signs of puberty should be referred for endocrine evaluation. Girls younger than eight years with one sign of puberty should, at a minimum, have a bone age evaluation.

CAROLINE WELLBERY, M.D.

Midyett LK, et al. Are pubertal changes in girls before age 8 benign? Pediatrics January 2003;111:47-51.

COPYRIGHT 2003 American Academy of Family Physicians
COPYRIGHT 2003 Gale Group

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