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Introduction: Craniopharyngiomas (CPG) have complex challenges in treatment due to their proximity to vital structures, surgical and radiotherapeutic complexities, and the tendency for recurrence. This study aims to identify the prevalence of endocrine and metabolic comorbidities observed during initial diagnosis and long-term follow-up in a nationwide cohort of pediatric CPG patients. The study also highlights the associated difficulties in their management. Methods: Sixteen centers entered 152 patients into the ÇEDD NET data system. We evaluated the clinical and laboratory characteristics at presentation, administered treatments, accompanying endocrine, metabolic, and other system involvements, and the patient's follow-up features. Results: Of the evaluated patients, 64 were female, and 88 were male. At presentation, the mean age was 9.1 ± 3.67 (min:1.46-max:16.92) years. The most common complaints at presentation were headache (68.4%), vision problems (42%), short stature (15%), nausea and vomiting (7%). The surgical procedure applied to the patients was gross total resection (GTR) in 97 cases (63.8%) and subtotal resection in 55 cases (36.2%). Radiotherapy was initiated in 11.8% of the patients. In the pathological examination, 92% of the cases were adamantinamatous type, 8% were papillary type. Postoperatively, hormone deficiencies consisted of thyroid-stimulating hormone (92.1%), adrenocorticotropic hormone (81%), antidiuretic hormone (79%), growth hormone (65.1%), and gonadotropin (43.4%) deficiencies. Recombinant growth hormone treatment (rhGH) was initiated on 27 patients. The study showed hesitancy among physicians regarding rhGH. The median survival without relapse was 2.2 years. Median time of relapse was 1.82 years (range: 0.13-10.35 years). Relapse was related to longer follow-ups and reduced GTR rates. The median follow-up time was 3.13 years. Among the last follow-up visits, the prevalence of obesity was 38%, but of these, 46.5% were already obese at diagnosis. However, 20% who were not obese at baseline became obese on follow-up. Permanent visual impairment was observed in 26 patients, neurological deficits in 13 patients, and diabetes mellitus in 5 patients. Conclusion: Recurrence was predominantly due to incomplete resection and the low rate of postoperative radiotherapy. It also emphasized challenges in multidisciplinary regular follow ups and suggested early interventions such as dietary restrictions and increased exercise to prevent obesity.
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Objective: Treatment adherence is crucial for the success of growth hormone (GH) therapy. Reported nonadherence rates in GH treatment have varied widely. Several factors may have an impact on adherence. Apart from these factors, the global impact of the COVID-19 pandemic, including problems with hospital admission and routine follow-up of patients using GH treatment, may have additionally affected the adherence rate. The primary objective of this study was to investigate adherence to treatment in patients receiving GH. In addition, potential problems with GH treatment during the pandemic were investigated. Materials and Methods: This was a multicenter survey study that was sent to pediatric endocrinologists in pandemic period (June 2021-December 2021). Patient data, diagnosis, history of pituitary surgery, current GH doses, duration of GH therapy, the person administering therapy (either parent/patient), duration of missed doses, reasons for missed doses, as well as problems associated with GH therapy, and missed dose data and the causes in the recent year (after the onset of the pandemic) were queried. Treatment adherence was categorized based on missed dose rates over the past month (0 to 5%, full adherence; 5.1 to 10% moderate adherence; >10% nonadherence). Results: The study cohort consisted of 427 cases (56.2% male) from thirteen centers. Median age of diagnosis was 8.13 (0.13-16) years. Treatment indications were isolated GH deficiency (61.4%), multiple pituitary hormone deficiency (14%), Turner syndrome (7.5%), idiopathic GH deficiency (7.5%), small for gestational age (2.8%), and "others" (6.8%). GH therapy was administered by parents in 70% and by patients in 30%. Mean daily dose was 32.3 mcg/kg, the annual growth rate was 1.15 SDS (min -2.74, max 9.3). Overall GH adherence rate was good in 70.3%, moderate in 14.7%, and poor in 15% of the patients. The reasons for nonadherence were mainly due to forgetfulness, being tired, inability to access medication, and/or pen problems. It was noteworthy that there was a negative effect on adherence during the COVID-19 pandemic reported by 22% of patients and the main reasons given were problems obtaining an appointment, taking the medication, and anxiety about going to hospital. There was no difference between genders in the adherence rate. Nonadherence to GH treatment decreased significantly when the patient: administered the treatment; was older; had longer duration of treatment; and during the pandemic. There was a non-significant decrease in annual growth rate as nonadherence rate increased. Conclusion: During the COVID-19 pandemic, the poor adherence rate was 15%, and duration of GH therapy and older age were important factors. There was a negative effect on adherence during the pandemic period.
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Recombinant growth hormone (GH) is administered as daily subcutaneous injections. Daily treatment can be challenging for children/adolescents as well as for parents and/or caregivers (legal representatives, guardians of children in institutional care). Challenges associated with daily treatment may result in missing several doses and non-adherence with treatment leads to inadequate growth response. As an inadequate growth response does not meet criteria for continuing treatment, payers (commercial or public) may decide to end reimbursement. Novel long-acting GH formulations (LAGH) with extended half-life can be administered less frequently and target to improve patient convenience and consequently to improve adherence and responses to treatment. LAGH formulations can restore growth velocity and body composition as effectively as daily treatment, without unexpected adverse effects as reported in randomized clinical trials.
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INTRODUCTION: Pathogenic biallelic RNPC3 variants cause congenital hypopituitarism (CH) with congenital cataracts, neuropathy, developmental delay/intellectual disability, primary ovarian insufficiency, and pituitary hypoplasia. Here, we aimed to evaluate the clinical and molecular characteristics of 2 patients with CH and neuropathy. MATERIALS AND METHODS: Proband was evaluated by clinical, laboratory, and radiological exams, followed by exome sequencing (ES). Clinical investigation of an affected sibling and variant segregation in the family was performed by Sanger sequencing. A three-dimensional protein model study was conducted to predict the effect of the variant on the function of the RNPC3 peptide. RESULTS: Proband was a 16-month-old girl who was referred for the evaluation of failure to thrive. Her height, weight, and head circumference were 55.8 cm (-7.6 SDS), 6.5 kg (-3.6 SDS), and 41.8 cm (-3.82), respectively. She had a developmental delay and intellectual disability. Central hypothyroidism, growth hormone, and prolactin deficiencies were identified, and MRI revealed pituitary hypoplasia. Electroneuromyography performed for the gait abnormality revealed peripheral neuropathy. A homozygous novel variant c.484C>T/p.(Pro162Ser) in the RNPC3 was detected in the ES. Her brother had the same genotype, and he similarly had pituitary hormone deficiencies with polyneuropathy. CONCLUSION: Expanding our knowledge of the spectrum of RNPC3 variants, and apprehending clinical and molecular data of additional cases, is decisive for accurate diagnosis and genetic counseling.
Subject(s)
Hypopituitarism , Nuclear Proteins , Peripheral Nervous System Diseases , RNA-Binding Proteins , Female , Humans , Infant , Male , Genotype , Hypopituitarism/genetics , Intellectual Disability , Nuclear Proteins/genetics , Phenotype , RNA-Binding Proteins/geneticsABSTRACT
Objective: The rising global epidemic of childhood obesity is a major public health challenge. Despite the urgency, there is a lack of data on the awareness and implementation of preventative measures. The aim of this study was to identify areas for improvement in the prevention and management of childhood obesity worldwide. Methods: A cross-sectional electronic survey was distributed to 132 members of national pediatric societies of the International Pediatric Association. Results: Twenty-eight (21.2%) participants, each from a different country across six World Health Organization (WHO) regions completed the survey. Most participants reported that national prevalence data of childhood obesity is available (78.6%), and the number increased during the Coronavirus disease-2019 pandemic (60.7%). In most countries (78.6%), the amount of sugar and salt in children's products is provided but only 42.9% enacted regulations on children-targeted advertising. Childhood obesity prevention programs from the government (64.3%) and schools (53.6%) are available with existing support from private or non-profit organizations (71.4%). Participants were aware of WHO's guidance concerning childhood obesity (78.6%), while fewer were aware of The United Nations International Children's Emergency Fund's (UNICEF) guidance (50%). Participants reported that WHO/UNICEF guidance acted as a reference to develop policies, regulations and national programs. However, progress was hindered by poor compliance. Lastly, participants provided suggestions on tackling obesity, with responses ranging from developing and reinforcing policies, involvement of schools, and prevention across all life stages. Conclusion: There are different practices in implementing prevention measures to counter childhood obesity globally, particularly in statutory regulation on food advertising and national programs. While support and awareness was relatively high, implementation was hindered. This reflects the need for prompt, country-specific evaluation and interventions.
Subject(s)
Pediatric Obesity , Child , Humans , Pediatric Obesity/epidemiology , Pediatric Obesity/prevention & control , Cross-Sectional Studies , Schools , World Health OrganizationABSTRACT
INTRODUCTION: Genetic forms of growth hormone deficiency (GHD) may occur as isolated GHD (IGHD) or as a component of multiple pituitary hormone deficiency (MPHD). This study aimed to present the clinical and molecular characteristics of patients with IGHD/MPHD due to the GH1 gene variants. METHODS: A gene panel accommodating 25 genes associated with MPHD and short stature was used to search for small sequence variants. Multiplex ligation-dependent probe amplification was performed in patients with normal panel results to investigate gross deletion/duplications. Segregation in the family was performed by Sanger sequencing. RESULTS: The GH1 gene variants were detected in 5 patients from four unrelated families. One patient had IGHD IA due to homozygous whole GH1 gene deletion and one had IGHD IB due to novel homozygous c.162C>G/p.(Tyr54*) variant. Two patients from a family had previously reported heterozygous c.291+1G>A/p.(?) variant in which clinical and genetic characteristics were compatible with IGHD II accompanying MPHD. One patient had clinical and laboratory characteristics of IGHD II with MPHD but the heterozygous c.468 C>T/p.(R160W) variant had conflicting results about the relationship with the phenotype. CONCLUSION: Expanding our knowledge of the spectrum of GH1 gene variants by apprehending clinical and molecular data of more cases, helps to identify the genotype-phenotype correlation of IGHD/MPHD and the GH1 gene variants. These patients must be regularly followed up for the occurrence of additional pituitary hormone deficiencies.
Subject(s)
Dwarfism, Pituitary , Human Growth Hormone , Hypopituitarism , Humans , Dwarfism, Pituitary/genetics , Dwarfism, Pituitary/epidemiology , Human Growth Hormone/genetics , Hypopituitarism/genetics , Homozygote , Phenotype , Genetic Association Studies , Growth Hormone/geneticsABSTRACT
Background: Complications are frequently reported after hypospadias repair and there is a need to understand the factors that influence their occurrence. Methods: Data from boys with hypospadias born between 2000 and 2020 were obtained from the International Disorders of Sex Development (I-DSD) Registry. Logistic regressions, fisher's exact tests and spearman's correlation tests were performed on the data to assess associations between clinical factors and complication rates. Results: Of the 551 eligible boys, data were available on 160 (29%). Within the cohort, the median (range) External Masculinization Score (EMS) was 6 (2, 9). All presented with one or more additional genital malformation and 61 (38%) presented with additional extragenital malformations. Disorders of androgen action, androgen synthesis and gonadal development were diagnosed in 28 (18%), 22 (14%) and 9 (6%) boys, respectively. The remaining 101 (62%) patients were diagnosed as having non-specific 46,XY Disorders of Sex Development. Eighty (50%) boys had evidence of abnormal biochemistry, and gene variants were identified in 42 (26%). Median age at first hypospadias surgery was 2 years (0, 9), and median length of follow-up was 5 years (0, 17). Postsurgical complications were noted in 102 (64%) boys. There were no significant associations with postsurgical complications. Conclusions: Boys with proximal hypospadias in the I-DSD Registry have high rates of additional comorbidities and a high risk of postoperative complications. No clinical factors were significantly associated with complication rates. High complication rates with no observable cause suggest the involvement of other factors which need investigation.
Subject(s)
Endocrinology , Gender Dysphoria , Humans , Child , Adolescent , Gender Dysphoria/diagnosis , Gender Dysphoria/therapy , Turkey/epidemiology , Gender Identity , PubertyABSTRACT
BACKGROUND: Polycystic ovary syndrome (PCOS) is the most prevalent, chronic endocrine-metabolic disorder of adolescents and young women (AYAs), affecting 5-10% of AYAs worldwide. There is no approved pharmacological therapy for PCOS. Standard off-label treatment with oral contraceptives (OCs) reverts neither the underlying pathophysiology nor the associated co-morbidities. Pilot studies have generated new insights into the pathogenesis of PCOS, leading to the development of a new treatment consisting of a fixed, low-dose combination of two so-called insulin sensitisers [pioglitazone (PIO), metformin (MET)] and one mixed anti-androgen and anti-mineralocorticoid also acting as an activator of brown adipose tissue [spironolactone (SPI)], within a single tablet (SPIOMET). The present trial will evaluate the efficacy, tolerability and safety of SPIOMET, on top of lifestyle measures, for the treatment of PCOS in AYAs. METHODS: In this multicentre, randomised, double-blind, placebo-controlled, four-arm, parallel-group, phase II clinical trial, AYAs with PCOS will be recruited from 7 clinical centres across Europe. Intention is to randomise a total of 364 eligible patients into four arms (1:1:1:1): Placebo, PIO, SPI + PIO (SPIO) and SPI + PIO + MET (SPIOMET). Active treatment over 12 months will consist of lifestyle guidance plus the ingestion of one tablet daily (at dinner time); post-treatment follow-up will span 6 months. Primary endpoint is on- and post-treatment ovulation rate. Secondary endpoints are clinical features (hirsutism, menstrual regularity); endocrine-metabolic variables (androgens, lipids, insulin, inflammatory markers); epigenetic markers; imaging data (carotid intima-media thickness, body composition, abdominal fat partitioning, hepatic fat); safety profile; adherence, tolerability and acceptability of the medication; and quality of life in the study participants. Superiority (in this order) of SPIOMET, SPIO and PIO will be tested over placebo, and if present, subsequently the superiority of SPIOMET versus PIO, and if still present, finally versus SPIO. DISCUSSION: The present study will be the first to evaluate-in a randomised, double-blind, placebo-controlled way-the efficacy, tolerability and safety of SPIOMET treatment for early PCOS, on top of a lifestyle intervention. TRIAL REGISTRATION: EudraCT 2021-003177-58. Registered on 22 December 2021. https://www.clinicaltrialsregister.eu/ctr-search/search?query=%092021-003177-58 .
Subject(s)
Metformin , Polycystic Ovary Syndrome , Adolescent , Female , Humans , Carotid Intima-Media Thickness , Clinical Trials, Phase II as Topic , Insulin , Life Style , Metformin/adverse effects , Multicenter Studies as Topic , Pioglitazone/adverse effects , Polycystic Ovary Syndrome/diagnosis , Polycystic Ovary Syndrome/drug therapy , Quality of Life , Randomized Controlled Trials as Topic , Spironolactone , Young AdultABSTRACT
Objective: Recent reports have indicated the role of the prokineticin receptor 2 gene (PROKR2) in the etiology of pituitary hormone deficiencies, suggesting a potential role for the PROK2 pathway in pituitary development, in addition to its role in gonadotropin releasing hormone-expressing neuron development. Here, we present the clinical and molecular findings of four patients with PROKR2 mutations. Methods: Next-generation targeted sequencing was used to screen 25 genes in 59 unrelated patients with multiple pituitary hormone deficiency (MPHD), isolated growth hormone (GH) deficiency, or idiopathic short stature. Results: Two different, very rare PROKR2 missense alterations classified as pathogenic (NM_144773.4:c.518T>G; NP_658986.1:p. (Leu173Arg)) and likely pathogenic (NM_144773.4:c.254G>A; NP_658986.1:p.(Arg85His)) were identified in four patients in heterozygous form. Patient 1 and Patient 2 presented with short stature and were diagnosed as GH deficiency. Patient 3 and Patient 4 presented with central hypothyroidism and cryptorchidism and were diagnosed as MPHD. No other pathogenic alterations were detected in the remaining 24 genes related to short stature, MPHD, and hypogonadotropic hypogonadism. Segregation analysis revealed asymptomatic or mildly affected carriers in the families. Conclusion: PROKR2 dominance should be kept in mind as a very rare cause of GH deficiency and MPHD. Expressional variation or lack of penetrance may imply oligogenic inheritance or other environmental modifiers in individuals who are heterozygous carriers.
Subject(s)
Dwarfism, Pituitary , Growth Hormone , Pituitary Hormones , Receptors, G-Protein-Coupled , Growth Hormone/genetics , Pituitary Hormones/genetics , Dwarfism, Pituitary/genetics , Humans , Pedigree , Male , Female , Infant , Child , Receptors, G-Protein-Coupled/genetics , ConsanguinityABSTRACT
OBJECTIVE: Brain tumors in childhood carry a high risk for endocrine disorders due to the direct effects of the tumor and/or surgery and radiotherapy. Somatotropes are vulnerable to pressure and radiotherapy; therefore, growth hormone deficiency is one of the most frequent abnormalities. This study aimed to evaluate endocrine disorders and recombinant growth hormone treatment outcomes in brain tumor survivors. MATERIALS AND METHODS: In this study, 65 (27 female) patients were classified into 3 groups as craniopharyngioma (n = 29), medulloblastoma (n = 17), and others (n = 19). "Others" group included astrocytoma, ependymoma, germinoma, pineoblastoma, and meningioma patients. Anthropometric data and endocrine parameters of patients and their growth outcome with/without recombinant growth hormone therapy were collected from medical records, retrospectively. RESULTS: Mean age at the first endocrinological evaluation was 8.7 ± 3.6 years (range: 1.0- 17.1 years). Height, weight, and body mass index standard deviation score, mean ± standard deviation (median) values were -1.7 ± 1.7 (-1.5), -0.8 ± 1.9 (-0.8), and 0.2 ± 1.5 (0.4), respectively. Hypothyroidism (central 86.9%, primary 13.1%) was detected during follow-up in 81.5% of patients. Primary hypothyroidism in medulloblastoma (29.4%) was significantly higher compared to other groups (P = .002). The frequency of hypogonadotropic hypogonadism, central adrenal insufficiency, and diabetes insipidus was significantly high in the craniopharyngioma cases. CONCLUSION: In our study, endocrine disorders other than growth hormone deficiency were also frequently observed. In craniopharyngioma cases, the response to recombinant growth hormone therapy was satisfactory. However, there was no improvement in height prognosis during recombinant growth hormone therapy in medulloblastoma patients. A multidisciplinary approach to the care of these patients, referral for endocrine complications, and guidelines on when recombinant growth hormone therapy is required.
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INTRODUCTION: Although it was common in the 1970s-1990s to assign female gender of rearing to 46,XY infants with limited virilization of varying etiologies, including those with partial androgen insensitivity syndrome (PAIS), long-term data on outcomes for these individuals are sparse. Therefore, our goal was to use the power of an international registry to evaluate clinical features, surgical management, and pubertal data in patients with a molecularly confirmed diagnosis of PAIS who were born before 2008 and were raised as girls. METHODS: The current study interrogated the International Disorders of Sex Development Registry for available data on management and pubertal outcomes in individuals with genetically confirmed PAIS who were raised as girls. RESULTS: Among the 11 individuals who fulfilled the key criteria for inclusion, the external masculinization score (EMS) at presentation ranged from 2 to 6 (median 5); 7 girls underwent gonadectomy before the age of 9 years, whereas 4 underwent gonadectomy in the teenage years (≥ age 13). Clitoral enlargement at puberty was reported for 3 girls (27%) who presented initially at the time of puberty with intact gonads. In the 9 individuals (82%) for whom gonadal pathology data were provided, there was no evidence of germ cell tumor at median age of 8.1 years. All girls received estrogen replacement, and 8/11 had attained Tanner stage 4-5 breast development at the last assessment. CONCLUSION: In general, although it appears that female assignment in PAIS is becoming uncommon, our data provide no evidence to support the practice of prophylactic prepubertal gonadectomy with respect to the risk of a germ cell tumor.
Subject(s)
Androgen-Insensitivity Syndrome , Neoplasms, Germ Cell and Embryonal , Male , Infant , Adolescent , Humans , Female , Child , Androgen-Insensitivity Syndrome/pathology , Gonads/pathology , Castration , Sexual Development , Neoplasms, Germ Cell and Embryonal/pathologyABSTRACT
Objective: A significant rise in the number of trans adolescents seeking medical interventions has been reported in recent years. The aim of this study was to report the clinical features, treatment, and follow-up of adolescents with gender dysphoria (GD) with our increased experience. Methods: Twenty-six male-to-female (MTF) and twenty-seven female-to-male (FTM) adolescents who were referred to the GD-outpatient clinic between 2016 and 2022 were reviewed. The clinical and laboratory findings of thirty transgender adolescents (15 FTM /15 MTF) who received medical intervention were evaluated retrospectively. Results: Most individuals (60.4%) were admitted between 2020 and 2022, and the remaining (39.6%) were admitted between 2016 and 2019. At the time of referral, median age was 16.3 years [interquartile range (IQR) 1.53; range 13.2-19.4] in 26 MTF, and 16.4 years (IQR 1.74; range 11.7-21.6) in 27 FTM adolescents. The median age at pubertal blockage with gonadotropin-releasing hormone analog and androgen receptor blocker was 16.4 years (IQR 1.4; range 11.7-17.8) in 22 adolescents (9 MTF, 13 FTM), and 17.4 years (IQR 1.4; range 15.5-19.4) in 6 MTF individuals, respectively. Cross-sex hormone therapy was commenced in 21 adolescents (12 MTF, 9 FTM) at the median age of 17.7 years (IQR 0.61; range 16-19.5). Fifteen individuals (8 MTF, 7 FTM) have been transferred to the adult endocrinology department in transition clinics. Conclusion: All treatments were generally well tolerated and effective, including bicalutamide, and no significant side effects were observed. Transition clinics played an important role in the better management of gender reassignment processes.
Subject(s)
Gender Dysphoria , Transgender Persons , Transsexualism , Adult , Humans , Male , Child , Female , Adolescent , Infant , Retrospective Studies , Gender Dysphoria/therapy , Turkey/epidemiology , Transsexualism/drug therapySubject(s)
Growth Hormone , Human Growth Hormone , Child , Humans , Human Growth Hormone/adverse effects , Child DevelopmentABSTRACT
Transaldolase deficiency is a rare inborn autosomal recessive disorder caused by biallelic mutations in the TALDO1 gene. It is characterized by intrauterine growth restriction, dysmorphism, abnormal skin, cytopenia, hepatosplenomegaly, liver cirrhosis, endocrine problems, renal and cardiac abnormalities. We present two siblings of Turkish origin with early-onset form of transaldolase deficiency and hypergonadotropic hypogonadism in both sexes. The girl (index) was followed-up with cryptogenic cirrhosis, leukopenia and thrombocytopenia, skin abnormalities, congenital heart defects, hypercalciuria, nephrolithiasis, proteinuria, chronic kidney disease throughout childhood. She developed hypergonadotropic hypogonadism in adolescence period. Whole exome sequencing due to the multisystemic involvement revealed a previously described homozygous inframe deletion in TALDO1 gene. Her brother was born as a small for gestational age baby and was also followed-up with cryptogenic cirrhosis since his infancy, together with cytopenia, congenital heart defects, bilateral cryptorchidism, short stature, hypercalciuria, proteinuria and chronic kidney disease in childhood. He presented with testicular microlithiasis and hypergonadotropic hypogonadism in adolescence. Sanger sequencing of TALDO1 gene confirmed the presence of the same homozygous deletion with his sister. The mother was found to be a heterozygous carrier for this deletion. We describe two patients with multisystemic involvement since neonatal period who presented with an additional hypergonadotropic hypogonadism in adolescence. The diagnosis of transaldolase deficiency should be kept in mind for these patients, and they must be evaluated for gonadal functions especially during puberty.
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Objective: Reports on the association between growth hormone (GH) therapy and cardiovascular risk factors in children are limited. This study aimed to evaluate carotid intima-media thickness (cIMT) in children treated with recombinant human GH (rhGH) and assess the effects of rhGH therapy and changes in serum carbohydrate metabolism, lipid profile and adipocytokines on cIMT. Methods: Seventy-one isolated idiopathic GH deficiency (GHD) children and 44 age- and sex-matched healthy controls were enrolled in this study. The study group was divided into two subgroups according to insulin resistance (IR) on oral glucose tolerance tests. Insulin secretion [homeostatic model assessment (HOMA) B, total insulin] and sensitivity (HOMA-IR, QUICKI, Matsuda) indices were calculated. cIMT was measured and the standard deviation scores (SDS) were calculated. Associations between cIMT-SDS and insulin secretion and sensitivity indices, serum lipid levels, adipocytokines (leptin, resistin, ghrelin), and other rhGH treatment-related factors were evaluated. Results: cIMT-SDS was increased in GHD children treated with rhGH compared to the controls [0.02 (2.27) vs. -1.01 (1.63), p=0.003]. cIMT-SDS did not differ between those children on rhGH treatment with or without IR. High cIMT-SDS was significantly associated with higher serum ghrelin levels and lower serum high density lipoprotein (HDL) levels (ß=0.491, p=0.001 and ß=-0.027, p=0.017), but not with BMI-SDS, blood pressure, insulin secretion and sensitivity indices, or the dose and duration of rhGH therapy. Conclusion: Our findings showed that GHD children treated with rhGH have increased cIMT. Alterations in carbohydrate metabolism were not associated with cIMT in children treated with rhGH. GH therapy per se appears to be associated with this increased cIMT but causality should be elucidated in further studies. cIMT also appears to be associated with higher ghrelin and lower HDL levels.
Subject(s)
Human Growth Hormone , Insulin Resistance , Humans , Child , Growth Hormone , Ghrelin , Carotid Intima-Media Thickness , Adipokines , Recombinant Proteins/adverse effects , LipidsABSTRACT
IGSF1 deficiency is a rare X-linked condition characterized by central hypothyroidism and a wide variety of other clinical features with variable prevalence, including a delayed pubertal testosterone rise and growth spurt in the context of normal or accelerated testicular growth, and adult macroorchidism with relatively low serum testosterone concentrations. Other features include increased waist circumference, attention deficit, prolactin deficiency and transient partial growth hormone (GH) deficiency in childhood, contrasting with an increased GH secretion in adulthood. Patients with this disorder are not detected shortly after birth if neonatal screening programs are based on thyroid-stimulating hormone (TSH) concentrations. A 13.2-year-old male patient was referred to pediatric endocrinology for evaluation of short stature. He was born large for gestational age into a nonconsanguineous family. During work-up for short stature, deficiencies of TSH, prolactin and GH were detected, leading to treatment with levothyroxine and GH. At 16.9 years, GH treatment was stopped and during transition to adult care, his insulin-like growth factor 1 level was above the normal range. This prompted an analysis of IGSF1, in which a novel hemizygous variant causing a stop codon at c.3559C>T (p.Q1187*) was found, confirming the diagnosis of IGSF1 deficiency syndrome. In this report, we describe his clinical and hormonal characteristics at presentation and during long-term follow-up.
Subject(s)
Dwarfism, Pituitary , Hypothyroidism , Transition to Adult Care , Adolescent , Humans , Male , Hypothyroidism/drug therapy , Immunoglobulins , Insulin-Like Growth Factor I , Membrane Proteins , Prolactin , Testosterone , ThyrotropinABSTRACT
CONTEXT: The Kabi/Pfizer International Growth Database (KIGS) is a large, international database (1987-2012) of children treated with recombinant human growth hormone (rhGH) in real-world settings. OBJECTIVE: This work aimed to evaluate the safety and efficacy of rhGH from the full KIGS cohort. METHODS: Data were collected by investigators from children with growth disorders treated with rhGH (Genotropin [somatropin]; Pfizer). Safety was evaluated in all treated patients, and efficacy in those treated for 1 year or more. A subgroup included patients treated for 5 years or more (≥â 2 years prepubertal) who had reached near-adult height (NAH). Main outcomes included adverse events (AEs), serious AEs (SAEs), and height growth. RESULTS: The full KIGS cohort (N = 83 803 [58% male]) was treated for idiopathic GH deficiency (IGHD; 46.9%), organic GHD (10.0%), small for gestational age (SGA; 9.5%), Turner syndrome (TS; 9.2%), idiopathic short stature (ISS; 8.2%), and others (16.2%). Median rhGH treatment duration was 2.7 years and observation 3.1 years. SAEs occurred in 3.7% of patients and death in 0.4%. The most common SAEs were recurrence of craniopharyngioma (n = 151), neoplasm (n = 99), and cancer (n = 91); and scoliosis (n = 91). Median first-year delta height-SD score (SDS) (Prader) in prepubertal patients was 0.66 (IGHD), 0.55 (ISS), 0.58 (TS), and 0.71 (SGA). Median gains in NAH-SDS were 1.79 (IGHD), 1.37 (ISS), and 1.34 (SGA) for boys, and 2.07 (IGHD), 1.62 (ISS), 1.07 (TS), and 1.57 (SGA) for girls. CONCLUSION: Data from KIGS, the largest and longest running international database of rhGH-treated children, show that rhGH is safe and increases short-term height gain and adult height across GHD and non-GHD conditions.
Subject(s)
Dwarfism, Pituitary , Human Growth Hormone , Adult , Female , Child , Humans , Male , Human Growth Hormone/adverse effects , Growth Hormone , Growth Disorders/drug therapy , Body Height , Recombinant Proteins/adverse effectsABSTRACT
Objective: The aim of this study was to assess the prevalence of ovarian and paraovarian adrenal rest tumors (ARTs) in gonadectomy materials of a subgroup of congenital adrenal hyperplasia (CAH) patients. Methods: A total of 20 historical cases with clinical/molecular diagnosis of classical CAH were included in the study. All patients had 46,XX karyotype and underwent gonadectomy because of being raised as male. Results: Median age at diagnosis of CAH was 5.7 years and was markedly delayed. All patients revealed severe virilization. Bone age was significantly advanced, and bone age/chronological age ratio was increased with a median ratio of 1.8. Median age at the time of gonadectomy was 9.2 years. Ovarian and paraovarian ARTs were detected during the pathological evaluation of gonadectomy materials in four patients (20%) (two with simple virilizing 21-hydroxylase and two with 11-beta-hydroxylase deficiency) with previously normal pelvic imaging. In three cases with ARTs, paraovarian area was composed of medium-sized polygonal cells, with round or oval monomorphic nuclei and abundant granular eosinophilic cytoplasm which is characteristic of adrenocortical tissue. The fourth case had bilateral ovarian 'steroid cell tumors, not otherwise specified', and the tumor was accepted as benign. Except for the ARTs, heterotopic prostate and bilateral paratubal epididymis tissue were detected in a patient. Conclusions: Ovarian and paraovarian ARTs might be more common than previously described, especially among patients with excessive and prolonged adrenocorticotropic hormone exposure. These tumors could be detected histopathologically even if not detected by classical imaging methods.
Subject(s)
Adrenal Hyperplasia, Congenital , Adrenal Rest Tumor , Ovarian Neoplasms , Adrenal Hyperplasia, Congenital/diagnosis , Adrenal Rest Tumor/epidemiology , Adrenal Rest Tumor/surgery , Castration , Female , Humans , Male , Ovarian Neoplasms/surgery , Steroid 21-HydroxylaseABSTRACT
Osteoporosis-pseudoglioma syndrome (OPPG; MIM #259770) is a rare autosomal recessively inherited disease, characterized by early-onset osteoporosis and congenital blindness, caused by loss-of-function mutations in the LRP5 gene. Beneficial effects of bisphosphonate treatment in patients with OPPG are well known, while follow-up data on growth and pubertal parameters are limited. This article provides clinical follow-up data and long-term bisphosphonate treatment results in four OPPG patients from three unrelated families, ranging between 2.5 and 7 years of age at presentation. Clinical diagnosis was molecularly confirmed in all patients, with four different germline biallelic LRP5 mutations including a novel nonsense variant c.3517C>T (p.(Gln1173*)) in two siblings with marked phenotypic variability. Anthropometric and pubertal data and bone mineral density (BMD) measurements were evaluated retrospectively. Early puberty was observed in two patients. The bisphosphonate treatment duration of patients varied around 4-7 years and improvement in BMD z-scores with bisphosphonate treatment was demonstrated in all patients (z-score changes were +5.6, +4.0, +1.0, and +1.3). Although further research is needed to identify the possible association between early puberty and OPPG, all OPPG patients should be followed up with detailed endocrinological evaluation regarding pubertal status.