Scoliosis and Kyphosis Prevalence in Turner Syndrome: A Retrospective Review at a Pediatric Tertiary Care Medical Center.

BACKGROUND: The prevalence of major coronal and sagittal spinal curves (scoliosis and kyphosis) in Turner syndrome (TS) is not well established due to limited reporting. The relationship between growth hormone (GH) therapy and its effect on TS spinal curve incidence is also not well established. METHODS: A retrospective chart review of 306 TS patients from 2007 to 2021 evaluated major coronal and sagittal spinal curves, progression of the curve, and treatment with GH. Statistical significance (defined as P <0.05) between curvature rates and curve progression was compared between GH-treated patients and non-GH-treated patients using a χ 2 or Fisher exact test when appropriate. RESULTS: Thirty-seven of 306 (12%) TS patients had a radiographically relevant spinal deformity. Twenty-seven of 37 (73%) had mild; 4 of 37 (11%) had moderate, and 6 of 37 (16%) had severe curves. Of those with severe, 4 underwent spinal fusion, 1 was treated with bracing, and 1 was braced before a cardiovascular-related death. Regarding GH use among TS patients, 190 of 306 (62%) used GH versus 116 of 306 (38%) who did not. Of those with a spinal curve, 24 of 37 (65%) used GH compared with 13 of 37 (35%) who did not. On univariate analysis, GH therapy was not a risk factor for the diagnosis of a major spinal curve, a more severe degree of the curve at the time of diagnosis, or spinal curve progression ( P >0.05 for all). CONCLUSIONS: This is the largest single institution retrospective review of a TS cohort known to the authors assessing spinal curve prevalence and relation to GH treatment and demonstrates a TS spinal curve rate of 12% (37/306). Four of six (11%) TS patients with a severe curve underwent corrective spine fusion. There was no relationship between the use of GH and the presence of a spinal curve or curve progression. Further study is warranted to determine risk factors for curve progression. LEVEL OF EVIDENCE: Level III. CLINICAL RELEVANCE: This retrospective case series serves to review and address the prevalence of spinal deformity in TS patients and whether GH impacts worsening deformity.

Is Gadolinium Contrast Necessary for Pituitary MRI in the Evaluation of Pediatric Short Stature and Growth Hormone Deficiency?

INTRODUCTION: Short stature is a common concern that necessitates pediatric endocrinology evaluation. Growth hormone deficiency (GHD) is a commonly considered etiology. Brain and pituitary magnetic resonance imaging (MRI) with gadolinium-based contrast agents (GBCAs) is the most widely used imaging in assessing patients with GHD. Given the significant strides made in MRI technology, the need for contrast material should be reassessed. METHOD: We performed a retrospective review of healthy patients with short stature and/or GHD who underwent brain and pituitary MRI with and without contrast to assess the added value of contrast administration. RESULTS: 227/318 identified patients underwent growth hormone (GH) stimulation testing; 28 (12.3%) with normal GH response and 62 (27.3%) with severe GHD. We found a low incidence of sellar and suprasellar pathologies. When comparing noncontrast and contrast MRI, we found perfect agreement in detecting abnormal posterior pituitary bright spots (kappa:1.0) and substantial agreement in detecting pars intermedia cysts and posterior superior sellar cysts (kappa: 0.74 and 0.71, respectively). Initially, only moderate agreement was found in detecting infundibular abnormalities (kappa: 0.51), although a revised noncontrast MRI protocol with high-resolution 3D images enabled visualization of the infundibulum. CONCLUSION: The MRI evaluation of healthy patients with short stature and/or isolated GHD may be completed without the use of GBCAs. The slight overestimation of pituitary stalk interruption by noncontrast images can be overcome by adding newer high-resolution sequences.

Prevention of Growth Failure in Turner Syndrome: Long-Term Results of Early Growth Hormone Treatment in the "Toddler Turner" Cohort.

INTRODUCTION: In the randomized "Toddler Turner" study, girls who received growth hormone (GH) starting at ages 9 months to 4 years (early-treated [ET] group) had marked catch-up growth and were 1.6 ± 0.6 SD taller than untreated (early-untreated [EUT]) control girls after 2 years. However, whether the early catch-up growth would result in greater near-adult height (NAH) was unknown. Therefore, this extension study examined the long-term effects of toddler-age GH treatment on height, pubertal development, and safety parameters. METHODS: Toddler Turner study participants were invited to enroll in a 10-year observational extension study for annual assessments of growth, pubertal status, and safety during long-term GH treatment to NAH for both ET and EUT groups. RESULTS: The ET group was taller than the EUT group at all time points from preschool to maturity and was significantly taller at the onset of puberty (p = 0.016), however, the difference was not significant at NAH. For the full cohort (ET + EUT combined, n = 50) mean (± SD) NAH was 151.2 ± 7.1 cm at age 15.0 ± 1.3 years. NAH standard deviation score (SDS) was within the normal range (>-2.0) for 76% of ET and 60% of EUT subjects (68% overall) and correlated strongly with height SDS at GH start (r = 0.78; p < 0.01), which in turn had a modest inverse correlation with age at GH start (i.e., height SDS declined with increasing age in untreated girls [r = -0.30; p = 0.016]). No new safety concerns arose. CONCLUSION: Although the ET group was taller throughout, height SDS at NAH was not significantly different between groups due to catch-down growth of ET girls during lapses in GH treatment after the Toddler study and similar long-term GH exposure overall. Early initiation of GH by age 6 years, followed by uninterrupted treatment during childhood, can prevent ongoing growth failure and enable attainment of height within the normal range during childhood, adolescence, and adulthood.

Turner Syndrome Systematic Review: Spontaneous Thelarche and Menarche Stratified by Karyotype.

BACKGROUND: Girls with Turner syndrome (TS) have a high incidence of primary ovarian insufficiency. Recent data show rates of spontaneous thelarche (ST) of 38% and spontaneous menarche (SM) of 15-16%, with higher rates in those with mosaicism. SUMMARY: We systematically reviewed the literature for evidence regarding rates of ST and SM in TS and evaluated rates based on the type of chromosomal mosaicism. We searched MEDLINE via PubMed, Embase, and the Cochrane Database of Controlled Trials. Reference lists were screened. Studies reporting outcomes of ST and SM in girls with TS, diagnosed by genetic analysis, were included. Data was collected regarding study design, cohort type, cohort age, the number of participants with ST and SM, the individual age at diagnosis of ST and SM, the mean age of patients with ST and SM, sample size, the number of participants with secondary amenorrhea, and karyotype. Key Messages: In total 2,699 patients were assessed for ST and 2,890 for SM from 43 articles. Overall the rates of ST were 32% (95% CI 26.4-38.9) and SM 20.8% (95% CI 19.3-22.4). Girls with X monosomy had the lowest rates of ST (i.e., 13%; 95% CI 8.7-19.7) and SM (i.e., 9.1%; 95% CI 7.3-11.3). Girls with 45,X/47,XXX had the highest rates of ST (i.e., 88.1%; 95% CI 62-97.1) and SM (i.e., 66.2%; 95% CI 49.3-79.6). CONCLUSIONS: Rates of ST and SM differ by karyotype in TS. When counseling patients, the karyotype should strongly influence discussions regarding pubertal development and the future reproductive potential.

Refractory hypoglycemia in a pediatric patient with desmoplastic small round cell tumor.

Background Tumor-induced hypoglycemia is a rare and serious complication that is usually a consequence of either excessive insulin secretion (insulinoma) or because of non-islet cell tumor hypoglycemia (NICTH). NICTH is a rare phenomenon seen most often in adult patients. It is associated with different tumor types. Here, we report the first case to the best of our knowledge in the literature of a pediatric patient with NICTH associated with desmoplastic small round cell tumor (DSRT). Case presentation This is a 15-year-old girl who presented with symptomatic hypoglycemia and abdominal mass. She required an intravenous glucose infusion rate as high as 9 mg/kg/min in addition to glucose containing oral supplements in order to maintain her blood glucose above 60 mg/dL. Computed tomography (CT) scan of the chest, abdomen and pelvis showed multiple hepatic lesions with an intraperitoneal soft tissue mass which subsequently was diagnosed as DSRT. When the blood glucose was 45 mg/dL, the insulin, growth hormone (GH) and insulin-like growth factor-1 (IGF-1) levels were suppressed with an appropriate elevation of cortisol. Subsequently, an insulin-like growth factor-2 (IGF-2) level was sent and the IGF-2:IGF-1 ratio was found to be elevated >10 consistent with NICTH. After the first dose of chemotherapy, hypoglycemia improved, and she was weaned off glucose containing fluids. Conclusions NICTH should be considered in all cancer patients regardless of their age with refractory hypoglycemia.

Growth Hormone Excess in Children with Optic Pathway Tumors Is a Transient Phenomenon.

BACKGROUND/AIMS: Growth hormone (GH) excess in children with chiasmal optic pathway tumors (OPT), often associated with neurofibromatosis type 1 (NF1), is likely underrecognized. These children have elevated insulin-like growth factor 1 (IGF-1) levels, evidence of rapid growth despite treatment of precocious puberty, and failure to suppress GH levels following oral glucose challenge. The aim of this report is to describe the treatment course and natural history of this rare clinical condition in 7 patients. METHODS: This is a descriptive case series of 5 children previously described and 2 additional children more recently diagnosed at our institution. All 7 children had clinical and biochemical evidence of GH excess and received treatment with the somatostatin analog octreotide. RESULTS: Length of treatment varied among the patients. Five of the 7 patients have had resolution of GH excess and currently have normal IGF-1 levels without treatment. CONCLUSIONS: Unrestrained GH secretion occurs in a subset of children with OPT with potential adverse outcomes. Since GH excess appears to resolve over time, the benefit of treatment to alter outcomes or prevent tumor progression is unclear.