Consistent evidence associates IGF-1 deficiency and metabolic syndrome. In this review, we will focus on the metabolic effects of IGF-1, the concept of metabolic syndrome and its clinical manifestations (impaired lipid profile, insulin resistance, increased glucose levels, obesity, and cardiovascular disease), discussing whether IGF-1 replacement therapy could be a beneficial strategy for these patients. The search plan was made in Medline for Pubmed with the following mesh terms: IGF-1 and “metabolism, carbohydrate, lipids, proteins, amino acids, metabolic syndrome, cardiovascular disease, diabetes” between the years 1963–2015. The search includes animal and human protocols. In this review we discuss the relevant actions of IGF-1 on metabolism and the implication of IGF-1 deficiency in the establishment of metabolic syndrome. Multiple studies (in vitro and in vivo) demonstrate the association between IGF-1 deficit and deregulated lipid metabolism, cardiovascular disease, diabetes, and an altered metabolic profile of diabetic patients. Based on the available data we propose IGF-1 as a key hormone in the pathophysiology of metabolic syndrome; due to its implications in the metabolism of carbohydrates and lipids. Previous data demonstrates how IGF-1 can be an effective option in the treatment of this worldwide increasing condition. It has to distinguished that the replacement therapy should be only undertaken to restore the physiological levels, never to exceed physiological ranges.

/pdf/insulin-like-growth-factor-1-deficiency-and-metabolic-zkbub0r2j0.pdf

Insulin-like growth factor-1 deficiency and metabolic syndrome

Objective To provide outcome data concerning pregnancies exposed to the Interleukin-1 (IL-1) inhibitors prior to conception in both men and women, during pregnancy and breast feeding. Methods Retrospective data were collected from members of the International Society for Systemic Autoinflammatory diseases and collated in a single centre. A uniform data collection sheet was used to obtain standardized data including maternal age and diagnosis, type, duration of and response to IL-1 blockade, pregnancy duration, delivery, mode of feeding and neonatal development. Results There were 31 maternal-exposed pregnancies from seven countries and we report the first data on paternal exposure: six to anakinra and five to canakinumab, with no negative outcomes. We also report the first data on canakinumab-exposed pregnancies: eight pregnancies that resulted in the delivery of seven healthy infants of normal gestational age and birthweight. There were 23 anakinra-exposed pregnancies resulting in the birth of 21 healthy infants, and one baby with unilateral renal agenesis and ectopic neurohypophysis. There were two first trimester miscarriages affecting a mother with active disease. There were no serious neonatal infections. Fourteen infants were breast fed with no complications. There were no reports of developmental delay, with follow-up of up to 10 years (median 18 months). Conclusion This series substantially increases the published experience of IL-1 blockade and reproduction including the first data on canakinumab and on paternal exposure to these agents. Data are generally reassuring, although the case of renal agenesis is the second reported in an anakinra-exposed pregnancy.

/pdf/international-multi-centre-study-of-pregnancy-outcomes-with-32lv58w1xt.pdf

International multi-centre study of pregnancy outcomes with interleukin-1 inhibitors

:The clinical and pathological features of 63 steroid cell tumors, not otherwise specified, were reviewed. The patients ranged in age from 2'A to 80 years. The most common initial manifestation was virilization (41%); four patients had estrogenic manifestations, and four had hypercortisolemi

Ovarian Steroid Cell Tumors (Not Otherwise Specified): A Clinicopathological Analysis of 63 Cases

Autoimmune forms of hypoglycemia are a rare cause of low blood sugar levels among Caucasians, and often go misdiagnosed, exposing patients to lengthy series of pointless, potentially harmful and expensive tests. There are two types of autoimmune hypoglycemia. One is insulin autoimmune syndrome (IAS), which is characterized by hyperinsulinemic hypoglycemia, elevated insulin autoantibody (IAA) titers, no prior exposure to exogenous insulin, and no of pathological abnormalities of the pancreatic islets. This condition is also known as “Hirata’s disease”. The other is type B insulin resistance syndrome (TBIRS), a rare autoimmune disorder resulting in a broad array of abnormalities in glucose homeostasis—from hypoglycemia to extremely insulin-resistant hyperglycemia—caused by the presence of insulin receptor autoantibodies (IRAbs). This review focuses on these two syndromes, describing their epidemiology, possible genetic background, clinical presentation, pathophysiology, diagnosis and treatment.

/pdf/insulin-autoimmune-syndrome-from-diagnosis-to-clinical-23jq7biacz.pdf

Insulin autoimmune syndrome: from diagnosis to clinical management.

Lessons from 50 years of study of laron syndrome

There are different opinions concerning changes in glucose metabolism in patients with Laron syndrome. In this paper we discuss the treatment results of our patient with Laron syndrome who developed diabetes during late adolescence. A 19-year-old boy with Laron syndrome was referred to our clinic for follow-up. He had been diagnosed with Laron syndrome (LS) at 4 years old and rIGF-1 therapy was initiated. After 4 months the treatment was discontinued. At the age of 17, rIGF-1 therapy was restarted. A height gain of 8.8 cm. was observed during the 2-year treatment period. He was admitted to our hospital at the age of 19 years following discontinuation of the therapy. At that time, his height was 142 cm, and weight for height was 136%. His blood glucose was 85 mg/dL (4.72 mmol/L), insulin was 26.39 pmol/L, and HbA1c was 5.4%. At the age of 20, when he has not been receiving IGF-1 therapy for 1 year, his weight for height was 143 cm. Laboratory evaluation revealed that fasting blood glucose was 176 mg/dL (9.77 mmol/L), fasting insulin was 29.86 pmol/L, and HbA1c was 7.5%. Primary insulin therapy was then initiated. His parents both had a diagnosis of type 2 diabetes. Insulin therapy was switched to oral antidiabetic (OAD) therapy at the end of the second year because of a normal C-peptide level of 0.8 nmol/L under insulin therapy. After 6 months of OAD, HbA1c was 5.7%. The treatment was then switched to IGF-1 therapy, but his blood glucose profile was impaired and OAD therapy was restarted. In conclusion, we observed that genetic susceptibility and abdominal obesity caused type 2 diabetes in this patient. We believe that oral antidiabetic agents and life-style changes may be the appropriate approach when diabetes is developed in LS patients.

Diabetes mellitus with Laron syndrome: case report

Objective: Hyperinsulinemic hypoglycemia (HIH) is a genetically heterogeneous disorder with both familial and sporadic variants. Patients with HIH may present during the neonatal period, infancy, or childhood and may show transient, prolonged, and persistent features. In this study, we aimed to discuss our experience with HIH patients, based on a series of 17 patients.

Methods: We retrospectively analyzed the clinical and laboratory characteristics at the time of diagnosis and during treatment and evaluated the neurodevelopmental outcomes during follow-up in 17 HIH patients, who presented or were referred to the Pediatric Endocrinology Clinic of Dr. Sami Ulus Training and Research Children’s Hospital between 1998 and 2011. The patients (7 male, 10 female) were aged between the first day of life and 7 years - 10 were in their first week of life, 6 in their infancy, and 1 in childhood.

Results: None of the mothers had gestational diabetes. Hypoglycemic seizure (76.5%) was the most common presenting symptom. Medical treatment failed in two patients, and was stopped in eight patients. Of two diazoxide-unresponsive patients, one underwent near-total pancreatectomy, but hypoglycaemic episodes continued after surgery. The parents of other patient refused surgery, the medical treatment was continued, nevertheless, severe motor and mental retardation developed. At follow-up, 23.5% of the patients were found to have mild or moderate psychomotor retardation, and 23.5% developed epilepsy. There was no marked difference in neurological results between cases with onset in the neonatal period or in infancy.

Conclusions: Clinical course and treatment response in HIH cases are very heterogeneous. Long-term careful monitoring is needed to detect and treat the complications. 

Conflict of interest:None declared.

/pdf/hyperinsulinemic-hypoglycemia-experience-in-a-series-of-17-5xup8drv64.pdf

Hyperinsulinemic hypoglycemia: experience in a series of 17 cases.

Thyroid nodule prevalence is about 1.8% in healthy children; however, malignancy frequency is higher than in adults. Approximately 26.4% of thyroid nodules generate thyroid cancer in childhood. Coexisting thyroid disease, history of irradiation of the neck, post-pubertal age, female sex, and thyroid malignancy in the family are risk factors for developing nodules. After evaluation of the medical history and detailed physical examination, the second step is assessment of thyroid function and measurement of calcitonin level. Thyroid stimulating hormone (TSH) value in the upper range seems to be correlated with cancer. Calcitonin levels must be evaluated, especially if medullary cancer is suspected. Ultrasonography (USG) is the first-line imaging tool in the diagnosis of thyroid nodules. It gives information about the nodule size, echogenicity and location. Hypoechogenicity, microcalcifications, undefined margins, high internodular vascular flow, and subcapsular localization are clues of malignant lesions. Scintigraphy is only recommended in a solid nodule with the presence of suppressed TSH. Fine-needle aspiration biopsy (FNAB) has 90% accuracy and is very useful in the selection of patients for surgery. It must be applied to all nodules ≥1 cm and nodules ≤1 cm suspicious for malignancy. The other diagnostic tools are elastography, immunocytochemical markers and genetic evaluation. In the management of thyroid nodules, surgery is advised, especially if there is difficulty in distinguishing benign lesions from carcinoma.

Approach to thyroid nodules in children and adolescents.

Objective To determine the demographic and biochemical features of childhood and juvenile thyrotoxicosis and treatment outcome. Methods We reviewed the records of children from 22 centers in Turkey who were diagnosed with thyrotoxicosis between 2007 to 2017. Results A total of 503 children had been diagnosed with thyrotoxicosis at the centers during the study period. Of these, 375 (74.6%) had been diagnosed with Graves’ disease (GD), 75 (14.9%) with hashitoxicosis and 53 (10.5%) with other less common causes of thyrotoxicosis. The most common presenting features in children with GD or hashitoxicosis were tachycardia and/or palpitations, weight loss and excessive sweating. The cumulative remission rate was 17.6% in 370 patients with GD who had received anti-thyroid drugs (ATDs) for initial treatment. The median (range) treatment period was 22.8 (0.3-127) months. No variables predictive of achieving remission were identified. Twenty-seven received second-line treatment because of poor disease control and/or adverse events associated with ATDs. Total thyroidectomy was performed in 17 patients with no recurrence of thyrotoxicosis and all became hypothyroid. Ten patients received radioiodine and six became hypothyroid, one remained hyperthyroid and restarted ATDs and one patient achieved remission. Two patients were lost to follow up. Conclusion This study has demonstrated that using ATDs is the generally accepted first-line approach and there seems to be low remission rate with ATDs in pediatric GD patients in Turkey.

Management of Thyrotoxicosis in Children and Adolescents: A Turkish Multi-center Experience

Objective. GnRH analogues (GnRHa) are used in the treatment of central precocious puberty (CPP). The purpose of this study was to evaluate the efficacy of treatment with a GnRHa (leuprolide acetate) in patients with CPP. Subjects and Methods. A total of 62 female child patients who had been diagnosed with CPP, rapidly progressive precocious puberty (RP-PP), or advanced puberty (AP) and started on GnRHa treatment (leuprolide acetate, Lucrin depot, 3.75 mg once every 28 days) were included in the study. The efficacy of treatment was evaluated with anthropometric data obtained, progression of pubertal symptoms observed, as well as GnRHa tests, and, when necessary, intravenous GnRH tests carried out in physical examinations that were performed once every 3 months. Results. In the current study, treatment of early/advanced puberty at a dose of 3.75 mg once every 28 days resulted in the suppression of the HHG axis in 85.5% of the patients. Conclusion. The findings of this study revealed that a high starting dose of leuprolide acetate may not be necessary in every patient for the treatment of CPP. Starting at a dose of 3.75 mg once every 28 days and increasing it with regard to findings in follow-ups would be a better approach.

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Aşan Önder

Papers

Diabetes mellitus with Laron syndrome: case report

Hyperinsulinemic hypoglycemia: experience in a series of 17 cases.

Approach to thyroid nodules in children and adolescents.

Management of Thyrotoxicosis in Children and Adolescents: A Turkish Multi-center Experience

Evaluating the Efficacy of Treatment with a GnRH Analogue in Patients with Central Precocious Puberty.