Growth hormone therapy does not impact the development of intracranial hypertension in children with Chiari malformation.

OBJECTIVES: Patients with Chiari malformation (CM) are prone to a variety of neurological sequelae, including benign intracranial hypertension (BIH). In these patients, BIH is attributed to impaired cerebrospinal fluid (CSF) flow due to anatomical abnormalities of the posterior fossa. Occasionally, patients with CM may require growth hormone therapy (GHT), which can increase the production of CSF. It is thought that patients with CM who undergo GHT are at high risk of BIH-associated symptoms (BIHAS). We describe the incidence of neurological symptoms in 34 patients with CM before and during GHT. METHODS: The database of a pediatric endocrinology center was queried for patients with CM who received GHT from 2010-22. Records were reviewed for adverse events. Demographic and radiological data were collected and analyzed. Patients with neoplastic disease, active inflammation, or acute trauma were excluded. CM diagnoses were independently assigned by a neuroradiology department. Patients were grouped based on the presence and nature of symptoms before and during GHT. Relationships between starting dose/BMI and occurrence of BIHAS/all GHT-associated symptoms were evaluated. RESULTS: GHT was not associated with new-onset or worsening of preexisting BIHAS in 33 out of 34 patients with CM. Five complex patients continued to have preexisting BIHAS, which did not worsen. Of the four patients who developed new-onset BIHAS during GHT, three patients' symptoms were attributed to other medical conditions. No patient permanently discontinued GHT due to BIHAS. CONCLUSIONS: Growth hormone therapy is likely a safe treatment in patients with Chiari malformation and is unlikely to cause BIHAS.

Exploring the sex difference in cardiovascular risk during growth hormone therapy in adults.

OBJECTIVE: Given the previously identified sex differences in cardiovascular (CV) morbidity and mortality in patients with growth hormone deficiency (GHD) receiving GH replacement therapy (GHRT), our aim is to investigate sex-specific differences in the efficacy of (long-term) GHRT on CV risk profile and disease in subjects with GHD. Our hypothesis is that women will experience less beneficial effects than men. DESIGN: Retrospective nationwide cohort study. METHODS: We compared all men (n = 1335) and women (n = 1251) with severe GHD registered in the Dutch National Registry of GH Treatment in Adults database with respect to CV risk profile and morbidity at baseline and during follow-up. RESULTS: Men had a more unfavourable CV risk profile at baseline. During the first years of GHRT, the reduction in waist circumference, waist-to-hip ratio, total cholesterol, and triglyceride levels was greater in men than in women (all P < .05). Between-sex differences in effects during later follow-up were less clear. No sex differences were found in the risk of developing non-fatal cardiovascular or cerebrovascular diseases during GHRT. CONCLUSIONS: Our results suggest that men with GHD did indeed experience more beneficial effects of GHRT on body composition and lipoprotein metabolism than women, at least in the early years of treatment. Also, the more unfavourable CV risk profile at baseline in men did not translate into a sex difference in the risk of developing CV and cerebrovascular morbidity during GHRT.

Post hoc subgroup analysis of Asian children with paediatric GHD from the global phase 3 efficacy and safety study of once-weekly somatrogon vs. once-daily somatropin.

OBJECTIVES: Somatrogon is a long-acting recombinant human growth hormone used to treat patients with paediatric growth hormone deficiency (pGHD). This global phase 3 study compared the efficacy and safety of once-weekly somatrogon with once-daily somatropin in children with GHD. METHODS: Prepubertal patients were randomized 1:1 to once-weekly somatrogon (0.66 mg/kg/week) or once-daily somatropin (0.24 mg/kg/week) for 12 months. The primary endpoint was height velocity (HV) at month 12; secondary endpoints included HV at month 6 and change in height standard deviation score (SDS) at months 6 and 12 and insulin-like growth factor 1 (IGF-1) SDS. RESULTS: This post hoc subgroup analysis focused specifically on Asian children (somatrogon: n=24 and mean age=7.76 years; somatropin: n=21 and mean age=8.10 years) across eight countries. Mean HV at month 12 was 10.95 cm/year (somatrogon) and 9.58 cm/year (somatropin); the treatment difference of 1.38 cm/year favoured somatrogon. The lower bound of the two-sided 95 % CI of the treatment difference (somatrogon-somatropin) was -0.20, similar to the overall study population (-0.24). Compared with the somatropin group, the somatrogon group had numerically higher HV at month 6 (8.31 vs. 11.23 cm/year); a similar trend was observed for height SDS and IGF-1 SDS at months 6 and 12. Safety and tolerability were similar between treatment groups; adverse events occurred in 83 % of somatrogon-treated children and 76 % of somatropin-treated children. CONCLUSIONS: This subgroup analysis demonstrated that somatrogon efficacy and safety in Asian children were consistent with the overall study population, where once-weekly somatrogon was non-inferior to once-daily somatropin. Clinicaltrials.gov: NCT02968004.

[Safety considerations for the clinical application of recombinant human growth hormone]. / é‡ç»„äººç”Ÿé•¿æ¿€ç´ ä¸´åºŠåº”ç”¨çš„å®‰å ¨æ€§æ€è€ƒ.

Recombinant human growth hormone (rhGH) is an effective therapeutic drug for improving short stature. Currently, rhGH can be used for various causes of short stature, including growth hormone deficiency, and the expansion of its clinical application has raised concerns about its safety. Based on existing evidence, when rhGH is used in a standardized manner for physiological replacement therapy, its safety profile is favorable. In clinical practice, attention should be focused on short-term safety during rhGH treatment, with the combination of literature evidence and clinical experience. There is still no definitive conclusion on the long-term safety due to insufficient duration of rhGH treatment. This paper reviews the possible adverse events that may occur during rhGH treatment and their risk control measures, aiming to help clinical physicians understand the overall safety of rhGH treatment and improve its clinical standardization.

Safety and Effectiveness of a Biosimilar Recombinant Human Growth Hormone in Children Requiring Growth Hormone Treatment: Analysis of Final Data from PATRO Children, an International, Post-Marketing Surveillance Study.

Purpose: Omnitrope® (somatropin) was approved as a biosimilar recombinant human growth hormone (rhGH) in 2006. Here, we report final data from the PAtients TReated with Omnitrope® (PATRO) Children study, a post-marketing surveillance study designed to monitor the long-term safety and effectiveness of this treatment in pediatric patients. Methods: The study population included all pediatric patients treated with Omnitrope® (biosimilar rhGH), administered via daily injection, in routine clinical practice. The primary objective was to assess long-term safety, with effectiveness assessed as a secondary objective. Results: In total, 7359 patients were enrolled and treated in the PATRO Children study; 86.0% were treatment-naïve at baseline. Growth hormone deficiency was the most frequent indication (57.9%), followed by patients born small for gestational age (SGA; 26.6%). The mean (SD) duration of exposure to biosimilar rhGH was 3.66 years (2.39). A total of 16,628 adverse events (AEs) were reported in 3981 (54.1%) patients, most of which were mild/moderate. AEs suspected to be treatment related occurred in 8.3% of patients, most frequently headache (1.6%), injection-site pain (1.1%), or injection-site hematoma (1.1%). The incidence rate (IR) of type 2 diabetes mellitus was 0.11 per 1000 person-years (PY) across all patients, and 0.13 per 1000 PY in patients born SGA. The IR of newly diagnosed primary malignancies was 0.22 per 1000 PY across all patients. In the 6589 patients included in the effectiveness population, a sustained catch-up growth was observed across all indications. After 5 years of treatment, height SDS increased from baseline by a median (range) of +1.79 (-3.7 to 6.2) in treatment-naïve patients and +0.73 (-1.4 to 3.7) in pretreated patients. Conclusion: This final analysis of the PATRO Children study indicates that biosimilar rhGH is well tolerated and effective in real-world clinical practice. These data are consistent with the well-characterized safety profile of rhGH treatment in pediatric patients.

Growth hormone treatment in aged patients with comorbidities: A systematic review.

OBJECTIVE: Hormonal substitution with growth hormone in aged patients remains a debated research topic and is rarely initiated in clinical practice. This reluctance may originate from concerns about adverse effects and the uncritical use as an anti-aging agent. Nevertheless, beneficial effects for selected patients suffering from certain acute and chronic illnesses could justify its use at an advanced age. This systematic review analyzes randomized controlled studies of GH interventions in older patients with different comorbidities to assess both, beneficial and harmful effects. DESIGN: A systematic search strategy was implemented to identify relevant studies from PubMed, MEDLINE, and The Cochrane Library. INCLUSION CRITERIA: participants aged over 65 years, randomized controlled trials involving human growth hormone (GH) and presence of at least one additional comorbidity independent of a flawed somatotropic axis. RESULTS: The eight eligible studies encompassed various comorbidities including osteoporosis, frailty, chronic heart failure, hip fracture, amyotrophic lateral sclerosis and hemodialysis. Outcomes varied, including changes in body composition, physical performance, strength, bone mineral density, cardiovascular parameters, quality of life and housing situation. Study protocols differed greatly in GH application frequency (daily, 2nd day or 3×/week), doses (0.41 mg-2.6 mg; mean 1.3 mg per 60 kg patient) and duration (1-12 months; mean 7 months). Mild dose-related side effects were reported, alongside noticeable positive impacts particularly on body composition, functionality, and quality of life. CONCLUSION: Despite limited evidence, GH treatment might offer diverse benefits with few adverse effects. Further research with IGF-I dependent indication and clear outcomes, incorporating IGF-I dependent GH titration in older adults is warranted.

[Growth hormone - 30 years of clinical practice: past, present, future].

The recombinant technologies era, which began in the second half of the XX century, made it possible to produce recombinant growth hormone (rGH) necessary for the treatment of stunting of various genesis. The time of practically unlimited possibilities of rGH production has come, which served as a stimulus for studying the efficacy and safety of rGH application, searching for optimal ways of its use and dosing regimes. Many years of experience in the use of somatropin in clinical practice allowed us to obtain data on its effectiveness primarily in somatotropic insufficiency in children, to study its effect on the functional state of various organs and systems, and to expand the indications for the use of RGR.

Cerebrovascular Abnormalities in Adults Born SGA at 12 Years After Growth Hormone Cessation Compared to Controls.

CONTEXT: Increased cerebrovascular morbidity was reported in adults born small for gestational age (SGA) who were treated with growth hormone (GH) during childhood compared to the general population. However, previous studies did not have an appropriate control group, which is a major limitation. OBJECTIVE: To study cerebrovascular abnormalities (aneurysms, previous intracerebral hemorrhages and microbleeds) using magnetic resonance imaging (MRI) in adults born SGA at 12 years after cessation of childhood GH treatment (SGA-GH) compared to appropriate controls. METHODS: In this single-center, prospective study, brain MRIs were performed between May 2016 and December 2020 on a 3T MRI system. MRI images were scored by 2 neuroradiologists who were blinded to patient groupings. Participants included adults born SGA previously treated with GH and 3 untreated control groups: adults born SGA with persistent short stature (SGA-S), adults born SGA with spontaneous catch-up growth to a normal height (SGA-CU) and adults born appropriate for gestational age with a normal height (AGA). The intervention was long-term GH treatment during childhood and the main outcome measure was cerebrovascular abnormalities. RESULTS: A total of 301 adults were investigated. Aneurysms were found in 6 adults: 3 (3.6%) SGA-GH, 1 (2.9%) SGA-S and 2 (2.2%) AGA adults, without differences between SGA-GH adults and the controls. Previous intracerebral hemorrhages were only found in 2 SGA-S adults (4.8%). Microbleeds were found in 17 adults: 4 (4.3%) SGA-GH, 4 (9.5%) SGA-S, 3 (4.3%) SGA-CU and 6 (6.3%) AGA adults, without differences between SGA-GH adults and the controls. CONCLUSION: Our findings suggest that SGA-GH adults at 12 years after GH cessation have no increased prevalence of cerebrovascular abnormalities compared to appropriate controls. Further research is needed to confirm our findings.

Impact of long-acting growth hormone replacement therapy in adult growth hormone deficiency: Comparison between adolescent, adult, and elderly patients.

The predominant features of the adult growth hormone deficiency (GHD) syndrome may vary between patients of different age and age of onset of GHD. Evidence from clinical trials and long-term observational studies has informed our ability to understand the unique considerations regarding risks and benefits of daily growth hormone replacement therapy (GHRT) and specific dosing and monitoring strategies for these patient subgroups. High rates of nonadherence with daily GHRT presents a challenge to achieving optimal treatment outcomes and long-acting growth hormone (LAGH) formulations have been developed with the promise of improving treatment adherence resulting in improved therapeutic outcomes. While existing data from short-term studies have demonstrated noninferiority of efficacy and safety of LAGH compared to daily GHRT, long-term studies are needed to assess the full spectrum of outcomes of interest and long-term safety considerations specific to patients in adolescence, adulthood and the elderly GHD population. Since each LAGH formulation has a unique pharmacodynamic and pharmacokinetic profile optimal dosing and monitoring strategies will need to be developed to allow for the provision of individualized patient treatment.

Growth hormone therapy for children with Duchenne muscular dystrophy and glucocorticoid induced short stature.

OBJECTIVE: To evaluate the outcome of recombinant human Growth Hormone (rhGH) therapy in patients with Duchene Muscular Dystrophy (DMD) and glucocorticoid treatment with compromised growth. DESIGN: Four DMD patients on Deflzacort 0.6-0.85 mg/kg/day or prednisolone 0.625 mg/kg/day recieved rhGH (0.24 mg/kg/week) for 6-18 months. Primary outcomes were Growth velocity and Height for age Z-scores (Height SD). RESULTS: Growth velocity increased from 0 to 3.25 cm/year prior to GH therapy to 3.3-7.8 cm/year over a period of 6-18 months. The typical Height SD decline in DMD was reversed in two patients and blunted in one. No adverse events or deterioration in cardiac or respiratory parameters were associated with the rhGH treatment. CONCLUSIONS: rhGH appears to be safe and efficient in promoting growth of patients with glucocorticoid induced growth failure in DMD.

Efficacy and Safety of Pegvisomant in the Treatment of Acromegaly.

Pegvisomant, the first and currently only clinically available growth hormone receptor antagonist, is an effective therapeutic option for the medical treatment of acromegaly, a rare disorder characterized by excessive growth hormone secretion. With now over 20 years of real world experience, its safety and efficacy is well-established. However, several aspects of its clinical use are still controversially discussed. The high cost of pegvisomant has limited its use in several countries, and recent studies have reported a lower efficacy than the initial clinical trials. A reported increase in tumor volume under therapy varies between studies and has been attributed to either actual growth or re-expansion after cessation of somatostatin receptor ligand therapy. Furthermore, different combinations of pegvisomant and other therapeutic agents aiming at reduction of acromegaly disease activity have been proposed to increase or retain effectiveness while lowering side effects and cost. This review aims to assess current clinical data on the safety and efficacy of pegvisomant while also addressing controversies surrounding its use.

Safety of long-term use of daily and long-acting growth hormone in growth hormone-deficient adults on cancer risk.

Daily injections of recombinant human growth hormone (rhGH) have been used in clinical practice for almost four decades as a replacement therapy in adult patients with GH deficiency (GHD). Long-term adherence to daily injections of rhGH is a clinical concern that may result in reduced therapeutic efficacy, and long-acting GH (LAGH) formulations have been developed in an attempt of overcoming this problem. Long-term safety issues of rhGH are the other side of the coin that has been carefully monitored over the years, particularly related to the proliferative actions of GH that could increase the risk of tumor recurrence or induce the development of new benign and malignant tumors. In this review, we present what is currently known about the cancer risk in GHD adults treated with daily rhGH injections and we discuss the major concerns and responses needed from future surveillance studies regarding the safety of LAGH preparations.

Effective GH Replacement With Somapacitan in Children With GHD: REAL4 2-year Results and After Switch From Daily GH.

CONTEXT: Somapacitan is a long-acting GH derivative for treatment of GH deficiency (GHD). OBJECTIVE: Evaluate the efficacy and tolerability of somapacitan in children with GHD after 2 years of treatment and after the switch from daily GH. DESIGN: A randomized, multinational, open-labelled, controlled parallel group phase 3 trial, comprising a 52-week main phase and 3-year safety extension (NCT03811535). SETTING: Eighty-five sites across 20 countries. PATIENTS: A total of 200 treatment-naïve prepubertal patients were randomized and exposed; 194 completed the 2-year period. INTERVENTIONS: Patients were randomized 2:1 to somapacitan (0.16 mg/kg/wk) or daily GH (0.034 mg/kg/d) during the first year, after which all patients received somapacitan 0.16 mg/kg/wk. MAIN OUTCOME MEASURES: Height velocity (HV; cm/year) at week 104. Additional assessments included HV SD score (SDS), height SDS, IGF-I SDS, and observer-reported outcomes. RESULTS: HV was sustained in both groups between 52 and 104 weeks. At week 104, mean (SD) for HV between weeks 52 and 104 was 8.4 (1.5) cm/year after continuous somapacitan treatment and 8.7 (1.8) cm/year after 1 year of somapacitan treatment following switch from daily GH. Secondary height-related endpoints also supported sustained growth. Mean IGF-I SDS during year 2 was similar between groups and within normal range (-2 to +2). Somapacitan was well tolerated, with no safety or tolerability issues identified. GH patient preference questionnaire results show that most patients and their caregivers (90%) who switched treatment at year 2 preferred once-weekly somapacitan over daily GH treatment. CONCLUSIONS: Somapacitan in children with GHD showed sustained efficacy and tolerability for 2 years, and after switching from daily GH. Patients/caregivers switching from daily GH expressed a preference for somapacitan. CLINICAL TRIAL REGISTRATION: NCT03811535.

Comparing treatment with daily and long-acting growth hormone formulations in adults with growth hormone deficiency: Challenging issues, benefits, and risks.

Daily administration of growth hormone (GH) treatment has been in clinical use for treatment for GH deficiency (GHD) in adults for more than 30 years. Numerous studies have demonstrated evidence that GH treatment improves body composition, cardiovascular risk factors and quality of life with few side effects. Less frequent GH injections are hypothesized to improve adherence and several long-acting GH (LAGH) formulations have been developed and a few have been approved and marketed. Different pharmacological modifications have been applied and the pharmacokinetics and pharmacodynamics of LAGH are different to each other and to those of daily injections and require different dosing and monitoring specific for each LAGH. Studies have shown improved adherence with LAGH, and short-term efficacy and side effects are comparable between daily GH injections and LAGHs. Long-term treatment with daily GH injections is effective and safe, while long-term studies for LAGHs are awaited. In this review challenges, benefits, and risks of treatment with daily and long-acting GH preparations will be compared.

Growth hormone replacement in adults with cured acromegaly: Efficacy and safety.

Between 2% and 60% of patients with cured acromegaly may eventually develop growth hormone deficiency. In adults, growth hormone deficiency is associated with abnormal body composition, decreased exercise capacity and quality of life, dyslipidemia, insulin resistance and increased cardiovascular risk. Similar to patients with other sellar lesions, the diagnosis of growth hormone deficiency in adults with cured acromegaly generally requires stimulation testing, with the exception of patients with very low serum insulin-like growth factor I levels and multiple additional pituitary hormone deficiencies. In adults with cured acromegaly, growth hormone replacement may have beneficial effects on body adiposity, muscle endurance, serum lipids and quality of life. Growth hormone replacement is generally well-tolerated. Arthralgias, edema, carpal tunnel syndrome and hyperglycemia may occur in patients with cured acromegaly, as is true of patients with growth hormone deficiency of other etiologies. However, there is evidence of increased cardiovascular risk in some studies of growth hormone replacement in adults with cured acromegaly. More studies are needed to fully establish the beneficial effects and elucidate the risks of growth hormone replacement in adults with cured acromegaly. Until then, growth hormone replacement can be considered in these patients on a case-by-case basis.

Efficacy, safety, quality of life, adherence and cost-effectiveness of long-acting growth hormone replacement therapy compared to daily growth hormone in children with growth hormone deficiency: A systematic review and meta-analysis.

We evaluated the efficacy, safety, adherence, quality of life (QoL) and cost-effectiveness of long-acting growth hormone (LAGH) vs daily growth hormone (GH) preparations in the treatment of growth hormone deficiency (GHD) in children. Systematic searches were performed in PubMed, Embase and Web of Science up to July 2022 on randomized and non-randomized studies involving children with GHD receiving LAGH as compared to daily GH. Meta-analyses for efficacy and safety were performed comparing different LAGH/daily GH formulations. From the initial 1393 records, we included 16 studies for efficacy and safety, 8 studies for adherence and 2 studies for QoL. No studies reporting cost-effectiveness were found. Pooled mean differences of mean annualized height velocity (cm/year) showed no difference between LAGH and daily GH: Eutropin Plus® vs Eutropin® [- 0.14 (-0.43, 0.15)], Eutropin Plus® vs Genotropin® [- 0.74 (-1.83, 0.34)], Jintrolong® vs Jintropin AQ® [0.05 (-0.54, 0.65)], Somatrogon vs Genotropin® [- 1.40 (-2.91, 0.10)], TransCon vs Genotropin® [0.93 (0.26, 1.61)]. Also, other efficacy and safety outcomes, QoL and adherence were comparable for LAGH and daily GH. Our results showed that, although most of the included studies had some concerns for risk of bias, regarding efficacy and safety all the LAGH formulations were similar to daily GH. Future high quality studies are needed to confirm these data. Adherence and QoL should be addressed from real-world data studies for both the mid and long term and in a larger population. Cost-effectiveness studies are needed to measure the economic impact of LAGH from the healthcare payer's perspective.

Safety of Growth Hormone Replacement Therapy in Childhood-Onset Craniopharyngioma: A Systematic Review and Cohort Study.

INTRODUCTION: Survival of childhood-onset craniopharyngioma (cCP) is excellent; however, many survivors suffer from hypothalamic-pituitary dysfunction. Growth hormone replacement therapy (GHRT) is of high importance for linear growth and metabolic outcome. Optimal timing for initiation of GHRT in cCP is on debate because of concerns regarding tumor progression or recurrence. METHODS: A systematic review and cohort studys were performed for the effect and timing of GHRT on overall mortality, tumor progression/recurrence, and secondary tumors in cCP. Within the cohort, cCP receiving GHRT ≤1 year after diagnosis were compared to those receiving GHRT >1 year after diagnosis. RESULTS: Evidence of 18 included studies, reporting on 6,603 cCP with GHRT, suggests that GHRT does not increase the risk for overall mortality, progression, or recurrent disease. One study evaluated timing of GHRT and progression/recurrence-free survival and found no increased risk with earlier initiation. One study reported a higher than expected prevalence of secondary intracranial tumors compared to a healthy population, possibly confounded by radiotherapy. In our cohort, 75 of 87 cCP (86.2%) received GHRT for median of 4.9 years [0.0-17.1]. No effect of timing of GHRT was found on mortality, progression/recurrence-free survival, or secondary tumors. CONCLUSION: Although the quality of the evidence is low, the available evidence suggests no effect of GHRT or its timing on mortality, tumor progression/recurrence, or secondary neoplasms in cCP. These results support early initiation of GHRT in cCP aiming to optimize linear growth and metabolic outcome. Prospective studies are needed to increase the level of evidence upon the optimal timing to start GHRT in cCP patients.

Efficacy and safety of growth hormone therapy in children with Noonan syndrome.

Patients with Noonan syndrome typically have a target height <2 standard deviations compared to the general population, and half of the affected adults remain permanently below the 3rd centile for height, though their short stature might result from a multifactorial etiology, not-yet fully understood. The secretion of growth hormone (GH) following the classic GH stimulation tests is often normal, with baseline insulin-like growth factor-1 (IGF-1) levels at the lower normal limits, but patients with Noonan syndrome have also a possible moderate response to GH therapy, leading to a final increased height and substantial improvement in growth rate. Aim of this review was to evaluate both safety and efficacy of GH therapy in children and adolescents with Noonan syndrome, also evaluating as a secondary aim the possible correlations between the underlying genetic mutations and GH responses.

Weekly Growth Hormone (Lonapegsomatropin) Causes Severe Transient Hyperglycemia in a Child with Obesity.

INTRODUCTION: A 12-year-and-9-month-old non-Hispanic black male with a history of growth hormone deficiency, pituitary hypoplasia, prediabetes, obesity, hypertension, and hyperlipidemia was initiated on weekly growth hormone (lonapegsomatropin-tcgd) and then transiently developed symptomatic hyperglycemia to 500 mg/dL. We aimed to describe this medication's effect. CASE PRESENTATION: He was born full term and appropriate for gestational age. He was referred to endocrinology at 3.5 years of age for short stature with a height SDS of -2.48. IGF-1 51.1 ng/mL and IGFBP-3 1.2 ng/mL were low. GH stimulation test noted baseline and peak GH of 0.1 ng/mL. MRI brain showed hypoplastic adenohypophysis, aplastic pituitary stalk, and ectopic neurohypophysis. There had been difficulty with adherence to daily GH over the following 9 years. BMI trajectory rose above 180% of the 95th percentile. By age 12, A1c was 6.6%. Metformin was started and increased to 1,000 mg twice daily. Subsequent A1c was 6.0%. Due to poor compliance with daily GH, at 12 years and 9 months, he was initiated on 22 mg (0.25 mg/kg/week) of weekly lonapegsomatropin-tcgd to improve compliance. The day after his first injection, he developed non-bloody, non-bilious emesis. He denied headaches and endorsed polyuria. Due to concern for increased intracranial pressure, he was sent to the emergency department; however, ophthalmologic exam was negative. Initial serum glucose was 500 mg/dL, then 336 mg/dL after 1-L normal saline. Hemoglobin A1c was 5.7%, urine glucose 3+ mg/dL, and urine ketones 2+ mg/dL. Venous pH of 7.379 and bicarbonate of 20.6 mmol/L ruled out diabetic ketoacidosis. Metformin was held during the hospitalization. Hyperglycemia rapidly improved with transient insulin administration. He received one dose of glargine 20 units. He was initiated on lispro carb ratio of 1:8 and correction factor 1:15 for target glucose 150 mg/dL. By day four, glucoses were below 100 mg/dL; lispro was discontinued, and he was discharged home. Weekly GH was discontinued with plans to resume daily GH therapy in several months. CONCLUSION: Lonapegsomatropin-tcgd offers the convenience of weekly rather than daily GH treatment; however, this patient developed a rapid increase in insulin resistance and hyperglycemia requiring insulin. The discrepancy between the glucose of 500 mg/dL and A1c of 5.7%, along with the rapid resolution of hyperglycemia, is further consistent with a medication side effect. Close glucose monitoring of patients initiated on weekly growth hormone is crucial, particularly in those with a history of prediabetes.

Long-term safety of growth hormone replacement therapy in survivors of cancer and tumors of the pituitary region.

Growth hormone deficiency (GHD) is a common complication in survivors of cancer and patients with tumors of the pituitary region. Growth hormone replacement therapy (GHT) has proven beneficial effects, including increased growth velocity, positive effects on body composition and skeletal integrity, and increased quality of life. However, due to known pro-proliferative, angiogenic, and anti-apoptotic properties of growth hormone, there are still some concerns about the safety of GHT in survivors. This narrative review aims to provide an overview of the long-term sequelae, and subsequently long-term safety, of GHT in survivors of (childhood) cancer and patients with tumors of the pituitary region. We identified predominantly reassuring results regarding the safety of survivors with GHT, although we must take into account the shortcomings of some studies and limited information on adult cancer survivors. Besides the already increased risk for second neoplasms, recurrences, or mortality in survivors due to host-, disease-, and treatment-related factors, we could not identify an increased risk due to GHT in particular. Therefore, we support the consensus that GHT can be considered in survivors after careful individual risk/benefit analysis and in open discussion with the patients and their families, taking into account the known morbidity of untreated GHD in cancer survivors and the positive effects of GHT.