Effects of Early Initiation of Growth Hormone Therapy on Different Auxological Parameters in Growth Hormone Deficient Children: Experience from an Indian Tertiary Care Center.

OBJECTIVES: The aim of the study was to evaluate the efficacy of early initiation versus late growth hormone in improving the predicted adult height in growth hormone deficiency (GHD) children. METHODS: A retrospective study of 550 GHD children with short stature, who had taken rGH for duration of minimum 12 months were included. They were divided into groups of less than 8 years and more than 8 years of age based on the initiation of growth hormone therapy. Their pretreatment and post-treatment auxological parameters were evaluated. RESULTS: There were 148 children in less than 8 years group and 402 children in more than 8 years old group. In 8 years or younger age group, the pre-treatment mean height of -2.015 SDS improved to -0.7753 SDS after one year of treatment. There was an improvement in the mean height from -2.0447 SDS to -1.2658 SDS post-treatment in more than 8 years group. The pre- and post-treatment difference between the Z score of height, weight, and BMI were statistically significant (<0.001). CONCLUSION: A significant height improvement occurred in both the groups' children after 1 year of GH treatment but the gain in final adult height was better when initiated less than 8 years of age. No significant side effects were noted during this period.

Heterozygous Insulin Receptor (INSR) Mutation Associated with Neonatal Hyperinsulinemic Hypoglycaemia and Familial Diabetes Mellitus: Case Series

Mutations in the insulin receptor (INSR) gene are associated with insulin resistance and hyperglycaemia. Various autosomal dominant heterozygous INSR mutations leading to hyperinsulinemic hypoglycaemia (HH) have been described in adults and children (more than 3 years of age) but not in the neonatal period. Family 1: A small for gestational age (SGA) child born to a mother with gestational diabetes presented with persistent hypoglycaemia, was diagnosed with HH and responded well to diazoxide treatment. Diazoxide was gradually weaned and discontinued by 8 months of age. Later, the younger sibling had a similar course of illness. On genetic analysis a heterozygous INSR missense variant p.(Met1180Lys) was found in the siblings, mother and grandfather but not in the father. Family 2: A twin preterm and SGA baby presented with persistent hypoglycaemia, which was confirmed as HH. He responded to diazoxide, which was subsequently discontinued by 10 weeks of life. Genetic analysis revealed a novel heterozygous INSR missense variant p.(Arg1119Gln) in the affected twin and the mother. Family 3: An SGA child presented with diazoxide responsive HH. Diazoxide was gradually weaned and discontinued by 9 weeks of age. Genetic analysis revealed a novel heterozygous INSR p.(Arg1191Gln) variant in the proband and her father. We report, for the first time, an association of INSR mutation with neonatal HH responsive to diazoxide therapy that resolved subsequently. Our case series emphasizes the need for genetic analysis and long-term follow up of these patients.

Obesity is common at diagnosis of childhood pituitary adenoma and may persist following successful treatment.

OBJECTIVE: There is a paucity of data describing long-term outcomes of paediatric patients with pituitary adenoma. In this report, we describe clinical features, treatment and outcomes of a paediatric cohort. DESIGN: Retrospective cohort study. PATIENTS: Twenty-four white Caucasian patients aged <16 years from a single tertiary care centre in the United Kingdom at diagnosis followed for (median, range) 3.3, 0.7-8.4 years. MEASUREMENTS: Clinical and radiological data at diagnosis and follow-up. RESULTS: Thirteen patients had prolactinomas (54.1%, age: 15.2 years, 13.2-15.8 years; all females), including ten macroadenomas (11.0-35.0 mm). Patients presented with menstrual disorders (91%), headache (46%), galactorrhoea (46%) and obesity (body mass index [BMI] SDS > 2): (38%). Ten patients with prolactinoma were treated with dopamine agonist alone, 3 also required surgery and 2 patients, cabergoline, surgery plus radiotherapy. Five patients had Cushing's disease (20.8%, age: 14.0, 4.0-15.7 years; 2 female), including one macroadenoma (24 mm). Patients presented with obesity (100%), short stature (60%) and headache (40%). Transsphenoidal resection resulted in biochemical cure (09.00 cortisol < 50 nmol/L). Two patients relapsed 3- and 6 years following surgery, requiring radiotherapy. One patient also required bilateral adrenalectomy. Six patients had nonfunctioning pituitary adenoma (25.0%, age: 15.8, 12.5-16.0 years; 2 female), including two macroadenomas (20.0-53.0 mm). Patients presented with obesity (67%), visual field defects (50%) and headache (50%). Four required surgical resections; two recurred following surgery and required radiotherapy. On latest follow-up; 13 (54.1%) patients were obese (BMI 3.09 SDS; range: 2.05-3.73 SDS). CONCLUSION: Obesity is common at diagnosis of pituitary adenoma in childhood and may persist despite successful treatment. Adenomas were larger, more resistant to treatment, and more likely to recur than in adult populations.

Feasibility of bisphosphonate therapy in an Indian pediatric patient of fibrodysplasia ossificans progressiva.

Fibrodysplasia ossificans progressiva, also known as myositis ossificans progressiva, is a rare autosomal dominant disorder (1 in 2 million). It produces a catastrophic and crippling illness in young people for which there is no effective treatment. This case report presents a case of 7-year-old child misdiagnosed as osteogenesis imperfecta admitted with severe disability and pain. He was diagnosed by clinical and radiological methods, treated with bisphosphonates for pain relief along with calcium and Vitamin D, and followed till 4 years.

A Novel Variant c.847T>C in CTSK Gene Leading to Pycnodysostosis: A Case Report.

Pycnodysostosis is a rare genetic disorder with a prevalence of 1.7 per million births; it usually presents with short stature, osteosclerosis, increased bone fragility, and acro-osteolysis of distal phalanges. There are less than 200 cases reported worldwide and very few from South-East Asia. We present a case of pycnodysostosis who presented with short stature, acro-osteolysis of distal phalanges, and on genetic testing revealing a variant c.847T>C, p.Y283H, in exon 7 of the CTSK in homozygous state: not reported till date to the best of our knowledge.

A variable course of Cushing's disease in a 7 year old: diagnostic dilemma.

Background Cushing's syndrome (CS) or hypercortisolism results from disruption of the hypothalamus-pituitary-adrenal (HPA) axis with the resultant increase in the circulating serum and urinary cortisol levels and lack of cortisol circadian rhythm. The resultant effects cause the physical manifestation of hypercortisolism. The appearance of Cushing's disease in children is insidious, the most common features being growth failure, obesity, early puberty and facial appearance. Case presentation We report a case of a 7-year-old male with a very unusual course of the disease, which could have led to diagnostic delays.

Real-world efficacy and safety of insulin degludec with mealtime rapid-acting insulin in type 1 diabetes in Indian pediatric population.

BACKGROUND: Insulin Degludec (IDeg) is a new ultra-long-acting basal insulin that has not been yet evaluated in Indian pediatric population. We aim to evaluate the efficacy and safety of IDeg as basal-bolus therapy in Indian pediatric patients affected by type 1 diabetes mellitus (T1DM). METHODS: A total of 30 pediatric and adolescent patients (17 boys, 13 girls; 22 were pre-pubertal) with T1DM who were on IDeg once daily participated in the study. All the patients received IDeg for at least 26 weeks along with rapid-acting mealtime insulin and their pre- and post-baseline characteristics (anthropometric data (BMI), age, duration of diabetes), metabolic (HbA1C), insulin requirement (unit/kg body weight per day) and number of hypoglycemia episodes were recorded along with the daily self-monitoring of blood glucose. RESULTS: There was a significant decline in HbA1c, FPG and bolus insulin dose from baseline to 26 weeks in the overall population (HbA1c: 9.65 ± 1.998% to 8.60 ± 1.631%, P = 0.0014; FPG: 156.93 ± 42.373 mg/dL to 109.37 ± 28.531 mg/dL, P = 0.000004; bolus insulin dose: 0.49 ± 0.208 U/kg/day to 0.35 ± 0.155 U/kg/day, P = 0.00032). The basal insulin dose was significantly higher at 26 weeks compared to baseline dose (0.42 ± 0.134 U/kg/day to 0.46 ± 0.139 U/kg/day, P = 0.04219). There was no significant change in BMI at 26 weeks.None of the patients experienced any DKA episode for 26 weeks. 16.7% patients had experienced at least one symptomatic hypoglycemia episode. On CGMS among the patients who were shifted from Glargine to degludec hypoglycemia were reduced significantly (overall hypoglycemia: 1.92 ± 1.26 to 0.35 ± 0.49 episodes over 3 days, P = 0.0026 while nocturnal hypoglycemia: 0.92 ± 0.47 to 0.21 ± 0.42 episodes, P = 0.0021). None of the patients had severe hypoglycemia episode. CONCLUSION: In our study IDeg is found to be safe and effective long-acting basal insulin that can be used in Indian pediatric population with T1DM. However further long term prospective studies are required to evaluate the long term effects.

Metformin in Adolescent PCOS: The Way Forward.

Polycystic ovarian syndrome (PCOS) is one of the most common endocrine disorders in adolescent girls and often over or under-diagnosed due to common features with normal puberty. Metformin an insulin sensitizer has been widely used in adult PCOS with benefits but the studies in adolescents are few. This use in adults has been translated to use in adolescents and we have done a review of these studies of metformin in adolescent PCOS and reported its use in weight reduction and hyperandrogenism.