Russell-Silver Syndrome With Growth Hormone Deficiency.

Russell-Silver syndrome (RSS) is a rare genetic disorder characterized by intrauterine growth restriction (IUGR), postnatal growth failure, and distinctive dysmorphic features. We present a case of a four-year-old male presenting with a slow growth velocity with a history of IUGR and surgical interventions, exhibiting classic RSS features. Laboratory investigations revealed low insulin-like growth factor 1 (IGF-1) and low growth hormone (GH) levels on stimulation tests. Clinical exome sequencing revealed a de novo mutation in the insulin-like growth factor 2 (IGF2) gene. Additionally, a variant of uncertain significance in the DHX37 gene was noted in the patient and the asymptomatic father. After genetic counseling, recombinant GH therapy was initiated. This case underscores the genetic complexity of RSS and highlights the importance of early diagnosis, genetic testing, and multidisciplinary management in optimizing outcomes for patients with RSS.

Transient Isolated, Idiopathic Growth Hormone Deficiency-A Self-Limiting Pediatric Disease with Male Predominance or a Diagnosis Based on Uncertain Criteria? Lesson from 20 Years' Real-World Experience with Retesting at One Center.

In the majority of children with growth hormone (GH) deficiency (GHD), normal GH secretion may occur before the attainment of final height. The aim of the study was to assess the incidence of persistent and transient GHD and the effectiveness of recombined human GH (rhGH) therapy in children with isolated, idiopathic GHD with respect to the moment of therapy withdrawal and according to different diagnostic criteria of GHD. The analysis included 260 patients (173 boys, 87 girls) with isolated, idiopathic GHD who had completed rhGH therapy and who had been reassessed for GH and IGF-1 secretion. The incidence of transient GHD with respect to different pre- and post-treatment criteria was compared together with the assessment of GH therapy effectiveness. The incidence of transient GHD, even with respect to pediatric criteria, was very high. Normal GH secretion occurred before the attainment of near-final height. Application of more restricted criteria decreased the number of children diagnosed with GHD but not the incidence of transient GHD among them. Poor response to GH therapy was observed mainly in the patients with normal IGF-1 before treatment, suggesting that their diagnosis of GHD may have been a false positive. Further efforts should be made to avoid the overdiagnosis GHD and the overtreatment of patients.

Evolving growth hormone deficiency: proof of concept.

Introduction: We present the evolution of GHD in adolescent males with persistent growth failure, in whom the diagnosis was established after a second GH stimulation test (GST). Methods: We performed a retrospective chart review of children who presented for short stature (height less < 2SD for mean/mid-parental height) and/or growth failure (sustained growth velocity < 0 SD) to pediatric endocrinology at Mount Sinai Kravis Children's Hospital, New York and who had 2 GSTs. Data collected from electronic medical records were analyzed using SPSS v28.0. Results: Of 53 patients included, 42 were males. Average GH peak on initial GST was 15.48 ± 4.92 ng/ml, at 10.07 ± 2.65 years, mean height -1.68 ± 0.56SD(28% had <2SD), IGF-1 -1.00 ± 0.88SD. After 2.23 ± 1.22 years, at 12.04 ± 2.41years, height SDs decreased to -1.82 ± 0.63SD and IGF-1 was -1.08 ± 0.84SD. At repeat GST, average GH peak was 7.59 ± 2.12 ng/dL, with 36% ≤7 ng/dl and 32% in puberty. 12 males reached adult height of 0.08 ± 0.69 SD with a mean height gain of 1.83 ± 0.56SD(p<0.005), IGF-1 of -1.15 ± 0.81SD after 4.64 ± 1.4 years of GH. Conclusion: We offer evidence for Evolving Growth Hormone Deficiency (EGHD) through repeat GST in children with persistent growth slowdown, even with pubertal progression; emphasizing the need for careful longitudinal follow-up to make accurate diagnosis.

Growth Hormone Therapy: Comparison of Short- and Long-Term Outcomes between Children with Growth Hormone Deficiency and Small for Gestational Age.

INTRODUCTION: Direct comparisons of both short-term and long-term auxological outcomes of growth hormone therapy (GHT) between growth hormone deficiency (GHD) and small for gestational age (SGA) are scarce. METHODS: One hundred three patients with GHD and 53 patients with SGA treated at our tertiary center were investigated. Short-term and long-term outcomes were compared between these groups using multivariable linear regression models with adjustment for age, sex, and height at therapy start, also allowing for sex-specific group comparisons. RESULTS: Mean delta height standard deviation scores (SDS) after 1 year of treatment were significantly higher in GHD (0.90, CI: 0.82-0.99) compared to SGA (0.67, CI: 0.54-0.79) (p = 0.003) with no sex difference. As expected, the mean increase in height SDS at final height (FH) was significantly higher in GHD (2.21, CI: 2.00-2.42) compared to SGA (1.05, CI: 0.75-1.35) (p < 0.001), leading to a target height corrected FH of -0.39 SDS (CI: -0.62 to -0.15) in GHD and -1.22 SDS (CI: -1.57 to -0.87) in SGA (p < 0.001). Girls with GHD had a better long-term outcome, as did boys with SGA when compared to the respective opposite sex. The cut-off of delta height of 0.5 SDS during the first year had a low sensitivity to detect long-term non-responders. We found a relation between short-term and long-term outcomes in GHD but not in SGA (adjusted R2 = 0.66 vs. 0.01). CONCLUSION: In contrast to GHD, we observed practically no relationship between 1st-year and long-term outcomes in SGA patients treated with GH.

Clinical outcomes and medical management of achondroplasia in Japanese children: A retrospective medical record review of clinical data.

Achondroplasia (ACH) is a rare, autosomal dominant skeletal dysplasia characterized by short stature, characteristic facial configuration, and trident hands. Before vosoritide approval in Japan, patients with ACH could start growth hormone (GH) treatment at age 3 years. However, ACH and its treatment in young Japanese children have not been studied. This retrospective, longitudinal, medical records-based cohort study (before vosoritide approval) summarized symptoms, complications, monitoring, surgery/interventions, and height with/without GH in Japanese patients with ACH <5 years. Complications were observed in 89.2% of all 37 patients; 75.7% required surgery or intervention. All patients were monitored by magnetic resonance imaging; 73.0% had foramen magnum stenosis, while 54.1% had Achondroplasia Foramen Magnum Score 3 or 4. Of 28 GH-treated patients, 22 initiating at age 3 years were generally taller after 12 months versus 9 non-GH-treated patients. Mean annual growth velocity significantly increased from age 2 to 3 versus 3 to 4 years in GH-treated patients (4.37 vs. 7.23 cm/year; p = 0.0014), but not in non-GH-treated patients (4.94 vs. 4.20 cm/year). The mean height at age 4 years with/without GH was 83.6/79.8 cm. These results improve our understanding of young patients with ACH in Japan and confirm that early diagnosis of ACH and monitoring of complications help facilitate appropriate interventions.

Floating-Harbor Syndrome in a Korean Patient with Short Stature and Early Puberty: A Case Report.

Floating-Harbor syndrome (FHS) is a rare autosomal dominant genetic disorder characterized by proportionately short stature, lack of expressive language, and distinctive facial features, including a large nose, long eyelashes, deeply set eyes, and a triangular face. We present a case of an 11-year-old Korean girl who was initially suspected of having Noonan-like syndrome but was later diagnosed with Floating-Harbor syndrome. The patient exhibited short stature, developmental language delay, dysmorphic facial features, and early puberty. Targeted exome sequencing revealed a heterozygous mutation, c.7303C>T (p.Arg2435Ter), in the SRCAP gene, confirming a diagnosis of Floating-Harbor syndrome. She responded well to human recombinant growth hormone and gonadotropin-releasing hormone (GnRH) agonist, effectively suppressing bone maturation and improving her height SDS from -4.6 to -2.4.

SALL4 Phenotype in Four Generations of One Family: An Interplay of the Upper Limb, Kidneys, and the Pituitary.

INTRODUCTION: The SALL4 gene encodes a transcription factor that is essential for early embryonic cellular differentiation of the epiblast and primitive endoderm. It is required for the development of neural tissue, kidney, heart, and limbs. Pathogenic SALL4 variants cause Duane-radial ray syndrome (Okihiro syndrome), acro-renal-ocular syndrome, and Holt-Oram syndrome. We report a family with vertical transmission of a SALL4 pathogenic variant leading to radial hypoplasia and kidney dystopia in several generations with additional growth hormone deficiency (GHD) in the proband. CASE PRESENTATION: Our male proband was born at the 39th week of gestation. He was born small for gestational age (SGA; birth weight 2,550 g, -2.2 SDS; length 47 cm, -2.0 SDS). He had bilateral asymmetrical radial ray malformation (consisting of radial hypoplasia, ulnar flexure, and bilateral aplasia of the thumb) and pelvic kidney dystopia, but no cardiac malformations, clubfoot, ocular coloboma, or Duane anomaly. He was examined for progressive short stature at the age of 3.9 years, where his IGF-1 was 68 µg/L (-1.0 SD), and growth hormone (GH) after stimulation 6.2 µg/L. Other pituitary hormones were normal. A brain CT revealed normal morphology of the cerebral midline and the pituitary. He had a dental anomaly - a central mandibular ectopic canine. MRI could not be done due to the presence of metal after multiple corrective plastic surgeries of his hands. His mother's and father's heights are 152.3 cm (-2.4 SD) and 177.8 cm (-0.4 SD), respectively. His father has a milder malformation of the forearm. The affected paternal grandfather (height 164 cm; -2.3 SD) has a radial ray defect with missing opposition of the thumb. The family reports a similar phenotype of radial dysplasia in the paternal grandfather's mother. The proband started GH therapy at age 6.5 years when his height was 109 cm (-2.8 SDS) and he experienced catch-up growth as expected in GHD. Puberty started spontaneously at the age of 12.5 years. At age 13, his height was 158.7 cm (-0.2 SDS). Whole-exome sequencing revealed a nonsense variant in the SALL4 gene c.1717C>T (p.Arg573Ter) in the proband, his father, and paternal grandfather. CONCLUSION: This is the first observation of a patient with a congenital upper limb defect due to a pathogenic SALL4 variant who has isolated GHD with no apparent cerebral or facial midline anomaly and has been successfully treated with growth hormone.

Effect of Growth Hormone Therapy on Pubertal Timing: Systematic Review and Meta-Analysis.

INTRODUCTION: Recombinant human growth hormone (rhGH) therapy effectively increases height in various disorders of childhood growth. However, whether rhGH affects pubertal timing is unclear. We aimed to review systematically published evidence on the effect of rhGH on pubertal timing. METHODS: Embase, MEDLINE, and Cochrane Library databases were searched until December 2021 on randomized and non-randomized controlled studies of rhGH in children. RESULTS: Twenty-five articles (n = 1,433 children) were identified, describing 12 randomized and 13 non-randomized controlled studies in children with idiopathic short stature (ISS; 15 studies), small for gestational age (n = 6 studies), chronic renal failure (n = 3), Noonan syndrome (n = 1), and growth hormone deficiency (n = 1). Significant differences in the effects of rhGH on pubertal timing were found by clinical indication. Only among children with ISS, rhGH promoted earlier age at pubertal timing (mean difference = -0.46 years; 95% CI, -0.90 to -0.03; 9 studies; n total = 397) or higher relative risk for pubertal onset during study follow-up (1.26; 95% CI, 1.03 to 1.54; 6 studies; n total = 284). CONCLUSIONS: Treatment with rhGH appears to promote earlier pubertal timing among children with ISS. Evidence was lacking in children with growth hormone deficiency due to the absence of studies with untreated controls.

Growth Hormone Treatment to Final Height in Turner Syndrome: Systematic Review.

PURPOSE: Turner syndrome (TS) is the most common sex chromosomal abnormality found in female subjects. It is a result of a partial or complete loss of one of the X chromosomes. Short stature is a hallmark of TS. Attainment of adult height (AH) within the normal range for height within the general female population represents the usual long-term goal of growth hormone (GH) treatment. The aim of this systematic review was to understand the efficacy of GH therapy on AH of patients with TS. METHODS: The literature review yielded for analysis 9 articles published from 2010 to 2021. Using the data from this literature search, the goal was to answer 5 questions: (1) What is the efficacy of GH on AH of girls with TS?; (2) Is AH influenced by the age at initiation of GH treatment?; (3) What is the optimal dose of GH to improve AH?; (4) Can the timing of either spontaneous or induced puberty influence AH?; and (5) Can the karyotype influence AH in patients with TS? FINDINGS: GH therapy and adequate dose could enable patients with TS to achieve appropriate AH compared with the possible final height without therapy. The greatest increase in height during GH therapy occurs in the prepubertal years, and if therapy is continued to AH, there is no further increase. Furthermore, karyotype did not show a predictive value on height prognosis and did not affect the outcome of GH administration or the height gain in girls with TS. IMPLICATIONS: Even if GH therapy is safe, close monitoring is indicated and recommended. Further evidence is needed to understand what other parameters may influence AH in patients undergoing GH therapy.

Development of hepatocellular adenomas in a patient with glycogen storage disease Ia treated with growth hormone therapy.

Glycogen storage disease Ia (GSD Ia), also known as von Gierke disease, is caused by pathogenic variants in the G6PC1 gene (OMIM 232200) which encodes glucose-6-phosphatase. Deficiency of glucose-6-phosphatase impairs the processes of gluconeogenesis and glycogenolysis by preventing conversion of glucose-6-phosphate to glucose. Clinical features include fasting hypoglycemia, lactic acidosis, hypertriglyceridemia, hyperuricemia, hepatomegaly, and development of hepatocellular adenomas (HCAs) with potential for malignant transformation. Additionally, patients with GSD Ia often exhibit short stature, in some instances due to growth hormone (GH) deficiency. Patients with short stature caused by GH deficiency typically receive GH injections. Here, we review the literature and describe a female with GSD Ia who had short stature, failure of growth progression, and suspected GH deficiency. This patient received GH injections from ages 11 to 14 years under careful monitoring of an endocrinologist and developed HCAs during that time. To date, there is no reported long-term follow up data on patients with GSD Ia who have received GH therapy, and therefore the clinical outcomes post-GH therapy are unclear.

Advantages and limitations of estrogen replacement therapy on hypogonadal survivors of childhood cancer.

BACKGROUND: Hypogonadism is a significant late complication in childhood cancer survivors (CCS). The aim of this study was to elucidate the advantages and limitations of estrogen replacement therapy (ERT) for CCS with hypogonadism. METHODS: Seventeen CCS were divided into two groups: gonadal hypogonadism (GH) group (n = 8) and central hypogonadism (CH) group (n = 9). Pearson correlation coefficients were used to investigate the impact of cancer management on final height, bone density, and uterine development. RESULTS: Seven of GH group had hematologic malignancies, and all of them underwent total body irradiation before bone marrow transplantation. The GH group showed significant positive correlations between the onset age of disease treatment and final height (p < 0.05, R = 0.712) and uterine size following ERT (p < 0.05, R = 0.775). All CCS in the CH group had brain tumors, and seven of them received chemotherapy. There were trends towards positive and negative correlations between the onset age of disease treatment and final height (p = 0.09, R = 0.598) or uterine size (p = 0.07, R = - 0.669), respectively. A negative correlation trend was observed between the age at ERT initiation and final height (p = 0.07, R = - 0.769) or bone density (p = 0.18, R = - 0.626) in six CH patients who received growth hormone therapy. Five CCS in both groups experienced osteoporosis, despite receiving ERT. CONCLUSION: Individualized management strategies beyond ERT are essential to reduce long-term complications in CCS with hypogonadism, considering the type and timing of cancer treatment.

Response to growth hormone therapy in ring chromosome 15: Review and evidence from a new case on possible beneficial effect in neurodevelopment.

Type 1 Insulin-like Growth Factor Receptor(IGF1R) plays a fundamental role in normal growth and development. Its disruption is usually characterized by severe intrauterine and postnatal growth retardation, microcephaly and neurodevelopmental delay.The efficacy of recombinant human growth hormone treatment remains a challenge for children with IGF1 resistance and pathogenic mutations of IGF1R, with limited data in patients carrying the most severe form of IGF1R defect, the ring chromosome 15. SUBJECT AND METHOD: We tested a high dose of rhGH in a new patient with ring chromosome 15, as confirmed by karyotype and CGH array. We performed a systematic review, and all published r(15) syndrome cases treated by growth hormone(GH) up to April 2023 were searched, and their response to GH therapy was recorded and summarized. RESULTS: Twelve patients with ring chromosome 15 received GH therapy according to a literature review. We expand the spectrum by the 13th case treated by GH, and we report an impressive improvement in intellectual performance and progressive catch-up growth after 5 and 20 months of follow-up. By introducing our new case in the analysis, the sex ratio was 3:10, and GH therapy was started at the age of 5.5 (3/9.4) (years) for an age of diagnosis of 4.75 (1.3/9.5) (years). The height before GH therapy was -5.1(-5.9/-4.1) SDS. The median duration of treatment was 1.7(0.9/2) (years), with a median height gain of 1(0.3/1.8) SDS and an improvement in growth velocity of 4.1(2.8/5.3) (cm/year). CONCLUSION: GH seems to be effective for r(15) syndrome patients with short stature.

Components of the metabolic syndrome in girls with Turner syndrome treated with growth hormone in a long term prospective study.

Background: Components of the metabolic syndrome are more common in patients with Turner syndrome (TS) than in the general population. Long-term growth hormone (GH) treatment also affects the parameters of carbohydrate metabolism. Therefore, all these factors should be monitored in girls with TS. Objective: To assess the occurrence of metabolic syndrome components in TS girls before GH treatment and to monitor changes in metabolic parameters throughout GH therapy. Patients and method: 89 TS patients were enrolled in the study. Clinical and laboratory data after the 1st (V1), 3rd (V3), 5th (V5) and 10th (V10) year of GH therapy was available respectively in 60, 76, 50 and 22 patients. The patients' biochemical phenotypes were determined by glucose 0', 120', insulin 0', 120', HOMA-IR, Ins/Glu ratio, HDL-cholesterol and triglycerides (TG) concentration. Results: Obesity was found during V0 in 7.9% of patients,V1 - 5%, V3 - 3.9%, V5 - 2%, V10 - 0%. No patient met diagnostic criteria for diabetes. A significant increase in the basal plasma glucose 0' was found in the first five years of therapy (pV0-V1 < 0.001; pV0-V3 = 0.006; pV0-V5 < 0.001). V10 glucose 120' values were significantly lower than at the onset of GH treatment (pV0-V10 = 0.046). The serum insulin 0' and 120' concentrations as well as insulin resistance increased during treatment. No statistically significant differences in serum TG and HDL-cholesterol levels during GH therapy were found. Conclusion: The development of insulin resistance and carbohydrate metabolism impairment have the greatest manifestations during GH therapy in girls with TS. Monitoring the basic parameters of carbohydrate-lipid metabolism in girls with TS seems particularly important.

Long Term Growth Hormone Therapy in a Patient with IGF1R Deletion Accompanied by Delayed Puberty and Central Hypothyroidism.

Insulin-like growth factor-1 (IGF-1) is the main driver of growth during prenatal life and acts through insulin-like growth factor 1 receptor (IGF1R). Patients with IGF1R defects exhibit variable phenotypic features. A 10.9-year-old boy presented with severe short stature, microcephaly, minor dysmorphic features and mild mental retardation. Genetic analysis for IGF1R revealed heterozygous deletion of the complete IGF1R. At the age of 12.3 years, daily subcutaneous rhGH was started and continued for a total of 5.7 years in two courses with improvement of height velocity as well as final height. Puberty was delayed and eventually he could not develop full puberty suggesting partial hypogonadotropic hypogonadism. Hypothyroidism initially developed during rhGH therapy. However, low T4 levels sustained after cessation of rhGH therapy thus central hypothyroidism is a likely diagnosis. rhGH has partial effect for induction of growth in cases with IGF1R defects. However, long-term treatment with an early onset may have more beneficial effects. In addition, patients with IGF1R defects should be followed for delayed puberty-hypogonadism, and hypothyroidism.

Long-Acting Growth Hormone Preparations and Their Use in Children with Growth Hormone Deficiency.

BACKGROUND: Daily recombinant human growth hormone (rhGH) is approved and marketed worldwide to treat children and adults with GH deficiency and other conditions. Efficacy of rhGH therapy is influenced by several variables. Drop of treatment adherence over time has been recognized as a cause of reduced rhGH efficacy and has driven considerable efforts from pharmaceutical companies and scientists to develop long-acting rhGH (LAGH) formulations in order to relieve patients and their families from the burden of daily injections. SUMMARY: Different technologies to manipulate drug release have been produced allowing weekly, biweekly, or monthly rhGH administration. The LAGH formulations developed at present have demonstrated a comparable or even higher efficacy as compared with daily rhGH in most of the cases and no major safety issues in phase 3 studies. A greater incidence of injection-site reactions has been reported but mainly of mild and transient nature. KEY MESSAGES: Despite LAGH analogs appearing promising, potential drawbacks still need to be addressed. Long-term consequences of nonphysiological GH profile and its consequences on metabolism and risk of cancer, optimal therapeutic monitoring, immunogenicity of LAGH molecules, and potential novel side effects related to the technologies used to develop these molecules are among the major concerns that require answers from long-term surveillance. Finally, increased acceptance of LAGH formulations from patients and their caregivers is yet to be demonstrated and cost-effectiveness evaluated consequently.

Early corticosteroid withdrawal is associated with improved adult height in pediatric kidney transplant recipients.

BACKGROUND: Catch-up growth after pediatric kidney transplantation (kTx) is usually insufficient to reach normal adult height. We aimed to analyze the effect of pre-transplant recombinant human growth hormone (rhGH) and corticosteroid withdrawal on linear growth in the first year after kidney transplantation and identify factors associated with final height (FH). METHODS: Patients who underwent kTx between 1996 and 2018 at below 18 years old in five Belgian and Dutch centers were included. We analyzed the differences between height Z-scores at kTx and 1 year post-transplant (Δ height Z-score) in children with and without corticosteroids at 1 year (CS + /CS -) and with and without rhGH treatment before kTx (rhGH + /rhGH -). Univariable and multivariable linear regression analysis was applied to identify factors associated with height Z-score at 1 year post-kTx, Δ height Z-score, and FH Z-score. RESULTS: A total of 177 patients were included, with median age 9.3 years at kTx. Median height Z-scores pre-kTx and 1 year later in the CS - /rhGH - , CS + /rhGH - , CS - /rhGH + , and CS + /rhGH + groups were - 1.42/ - 0.80, - 0.90/ - 0.62, - 1.35/ - 1.20, and - 1.30/ - 1.60 (p = 0.001). CS use 1 year post-kTx was the only factor associated with Δ height (p = 0.003) on multivariable analysis. CS use at 1 year was the only variable associated with FH (p = 0.014) in children with pre-transplant height Z-score below - 1 (n = 52). CONCLUSIONS: Increase in height Z-score in the first year post-kTx was highest in the CS - /rhGH - group and lowest in the CS + /rhGH + group. The use of corticosteroids at 1 year post-kTx is associated with catch-up growth and in children with pre-transplant height Z-score below - 1 also with final height. A higher resolution version of the Graphical abstract is available as Supplementary information.

Early Growth Hormone Initiation Leads to Favorable Long-Term Growth Outcomes in Children Born Small for Gestational Age.

CONTEXT: Early initiation of growth hormone (GH) therapy is recommended for short children born small for gestational age (SGA); however, real-world data indicate that treatment is often delayed. OBJECTIVE: We aimed to assess the impact of patient age at GH therapy initiation on long-term growth outcomes and safety in short children born SGA. METHODS: Analysis of pooled data from NordiNet® International Outcome Study (NCT00960128; 469 European clinics) and the ANSWER Program (NCT01009905; 207 US clinics), two large, complementary observational studies. Patients received GH as prescribed by their treating physician. Enrolled patients born SGA were categorized into three groups based on their age at GH treatment initiation: 2 to <4 years, 4 to <6 years, and ≥6 years. Patient characteristics at birth and GH initiation, auxology, and safety data were evaluated. RESULTS: The effectiveness analysis (treatment-naïve and prepubertal patients at GH initiation) included 3318 patients: 10.7% aged 2 to <4 years at therapy initiation, 31.6% aged 4 to <6 years, and 57.7% aged ≥6 years. Following 8 years of therapy, the mean improvement in height standard deviation score from baseline was significantly greater in the 2 to <4 years group vs the 4 to <6 years (+2.5 vs +2.2; P = 0.0054) and ≥6 years groups (+2.5 vs +1.7; P < 0.0001). No unexpected safety events were reported. CONCLUSION: Early initiation of GH therapy in short children born SGA may be an important contributor to height optimization. The data are reassuring regarding the long-term safety of GH therapy in this population.

The evolution of pituitary cysts in growth hormone-treated children.

OBJECTIVES: We have previously shown that pituitary cysts may affect growth hormone secretion. This study sought to determine cyst evolution during growth hormone treatment in children. METHODS: Forty-nine patients with short stature, a pituitary cyst, and at least two brain MRI scans were included. The percent of the pituitary gland occupied by the cyst (POGO) was calculated, and a cyst with a POGO of ≤15% was considered small, while a POGO >15% was considered large. RESULTS: Thirty-five cysts were small, and 14 were large. Five of the 35 small cysts grew into large cysts, while 6 of the 14 large cysts shrunk into small cysts. Of 4 cysts that fluctuated between large and small, 3 presented as large and 1 as small. Small cysts experienced greater change in cyst volume (CV) (mean=61.5%) than large cysts (mean=-0.4%). However, large cysts had a greater net change in CV (mean=44.2 mm3) than small cysts (mean=21.0 mm3). Older patients had significantly larger mean pituitary volume than younger patients (435.4 mm3 vs. 317.9 mm3) and significantly larger mean CV than younger patients (77.4 mm3 vs. 45.2 mm3), but there was no significant difference in POGO between groups. CONCLUSIONS: Pituitary cyst size can vary greatly over time. Determination of POGO over time is a useful marker for determining the possibility of a pathologic effect on pituitary function since it factors both cyst and gland volume. Large cysts should be monitored closely, given their extreme, erratic behavior.