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Context: Typically, growth failure in Turner syndrome (TS) begins prenatally, and height sd score (SDS) declines progressively from birth., Objective: This study aimed to determine whether GH treatment initiated before 4 yr of age in girls with TS could prevent subsequent growth failure. Secondary objectives were to identify factors associated with treatment response, to determine whether outcome could be predicted by a regression model using these factors, and to assess the safety of GH treatment in this young cohort., Design: This study was a prospective, randomized, controlled, open-label, multicenter clinical trial (Toddler Turner Study, August 1999 to August 2003)., Setting: The study was conducted at 11 U.S. pediatric endocrine centers., Subjects: Eighty-eight girls with TS, aged 9 months to 4 yr, were enrolled., Interventions: Interventions comprised recombinant GH (50 mug/kg.d; n = 45) or no treatment (n = 43) for 2 yr., Main Outcome Measure: The main outcome measure was baseline-to-2-yr change in height SDS., Results: Short stature was evident at baseline (mean length/height SDS = -1.6 +/- 1.0 at mean age 24.0 +/- 12.1 months). Mean height SDS increased in the GH group from -1.4 +/- 1.0 to -0.3 +/- 1.1 (1.1 SDS gain), whereas it decreased in the control group from -1.8 +/- 1.1 to -2.2 +/- 1.2 (0.5 SDS decline), resulting in a 2-yr between-group difference of 1.6 +/- 0.6 SDS (P < 0.0001). The baseline variable that correlated most strongly with 2-yr height gain was the difference between mid-parental height SDS and subjects' height SDS (r = 0.32; P = 0.04). Although attained height SDS at 2 yr could be predicted with good accuracy using baseline variables alone (R(2) = 0.81; P < 0.0001), prediction of 2-yr change in height SDS required inclusion of initial treatment response data (4-month or 1-yr height velocity) in the model (R(2) = 0.54; P < 0.0001). No new or unexpected safety signals associated with GH treatment were detected., Conclusion: Early GH treatment can correct growth failure and normalize height in infants and toddlers with TS.

Context: Little information exists regarding FSH values in very young girls with Turner syndrome (TS)., Objectives: The objective of the study was to evaluate the pattern, natural progression, and karyotype-related differences in FSH secretion in young, prepubertal girls with TS., Study Design: FSH was measured at study entry and annually for 2 yr., Setting: The Toddler Turner study was conducted at 11 U.S. pediatric endocrine centers., Study Participants: Eighty-eight girls with karyotype-proven TS aged 9 months to 4 yr participated in the study., Main Outcome Measures: By-karyotype differences in FSH concentration and age-related changes in FSH were measured., Results: Mean (+/- SD) FSH was markedly elevated in the 45,X (n = 56: 68.3 +/- 36.0 IU/liter) and Other groups [n = 15 (excluding three subjects with Y-containing karyotypes): 52.7 +/- 50.8 IU/liter] but was minimally elevated in girls with 45,X/46,XX mosaicism (n = 14: 10.1 +/- 13.5 IU/liter, P < 0.005 both comparisons). Over the 2-yr period, FSH declined in the 45,X group (-13.4 IU/liter.yr, P < 0.0001). Nonetheless, only three of 159 FSH values fell within normal range for age at any time during the 2-yr study. FSH decline was similar in the Other group (-14.3 IU/liter.yr, P = 0.0032). In contrast, no significant decrease in FSH with age was observed in the 45,X/46,XX group., Conclusions: In contrast to the original report of FSH concentrations in individuals with TS, this study demonstrates distinct differences in patterns of FSH secretion between young girls with monosomy TS, who have persistent elevation of FSH to age 6 yr, and those with 45,X/46,XX mosaicism, whose FSH values suggest retained ovarian function in the majority. These findings have implications for patient management and family counseling.

Cushing syndrome is uncommon in childhood and rare in infancy. We report the case of a 3-yr-old child who presented with symptoms of Cushing syndrome beginning shortly after birth. Her hypercortisolemia was cyclical, causing relapsing and remitting symptoms, which eventually led to suspicions of possible Munchausen syndrome by proxy. Investigation at the National Institutes of Health excluded exogenous administration of glucocorticoids and indicated ACTH-independent Cushing syndrome. Paradoxical response to dexamethasone stimulation (Liddle's test) suggested a diagnosis of primary pigmented nodular adrenocortical disease (PPNAD). After bilateral adrenalectomy, both glands showed micronodular adrenocortical hyperplasia, but histology was not consistent with typical PPNAD. DNA analysis of the coding sequences of the PRKAR1A gene (associated with PPNAD and Carney complex) and the GNAS gene (associated with McCune-Albright syndrome) showed no mutations. We conclude that hypercortisolemia in infancy may be caused by micronodular adrenocortical hyperplasia, which can be cyclical and confused with exogenous Cushing syndrome. A paradoxical rise of glucocorticoid excretion during Liddle's test may delineate these patients. Infantile micronodular disease has some features of PPNAD and may represent its early form; however, at least in the case of the patient reported here, micronodular hyperplasia was not caused by coding mutations of the PRKAR1A or GNAS genes or associated with typical histology or any other features of Carney complex or McCune-Albright syndrome and may represent a distinct entity.