Neurological Complications of Endocrine Disease.

The endocrine system is a complex group of organs and glands that relates to multiple other organs and systems in the body with the ultimate goal of maintaining homeostasis. This complex network functions through hormones excreted by several glands and released in the blood, targeting different body tissues and modulating their function. Any primary disorders affecting the endocrine glands and altering the amount of hormones synthesized and released will lead to disruption in the functions of multiple organs. The central nervous system of a developing child is particularly sensitive to endocrine disorders. A variety of neurological manifestations have been described as features of several endocrine diseases in childhood. Their knowledge may contribute to an early diagnosis of a particular endocrine condition, especially when more typical features are not present yet. In this article, we discuss specific neurological manifestations found in various endocrine disorders in children.

Vitamin D supplementation, the metabolic syndrome and oxidative stress in obese children.

BACKGROUND: Previous studies suggest that vitamin D may play a role in cardiovascular and metabolic health. Oxidative stress has also been implicated in the development of cardiovascular disease. Evidence suggests that vitamin D deficiency may contribute to the occurrence of oxidative stress. This study aimed to determine whether treatment and correction of vitamin D deficiency in obese children led to changes in their metabolic profile, independent of changes in adiposity. In addition, we aimed to determine whether vitamin D deficiency and oxidative stress are causally related in obese children. METHODS: In the retrospective arm, chart review identified 32 obese children who experienced normalization of vitamin D deficiency or insufficiency with vitamin D supplementation. We then correlated laboratory and anthropometric data with vitamin D levels. In the prospective arm of the study, urinary 8-isoprostane and hydrogen peroxide were measured before and after correction of vitamin D deficiency/insufficiency and correlated to vitamin D levels in seven patients. RESULTS: In our predominantly Hispanic population of obese children in an urban setting, we demonstrated a cause-effect relationship between vitamin D deficiency and oxidative stress. In contrast, we found no association between vitamin D status, adiposity, and markers of insulin sensitivity, nor any effect of vitamin D treatment on the same parameters. CONCLUSIONS: These discordant findings suggest a differential effect of vitamin D on cardiovascular risk factors such as oxidative stress and insulin resistance. To confirm these findings, further prospective studies with larger sample size and longer follow-up are warranted.

Role of Fibroblast Growth Factor 21 (FGF21) in the Regulation of Statural Growth.

In this review, we discuss the evidence supporting the causative role of increased FGF21 expression in reduced GH action and impaired longitudinal bone growth. Fibroblast Growth Factor (FGF) 21 (FGF21) is a member of a subfamily of FGFs which lack the FGF heparin-binding domain. Thus, these FGFs can function as endocrine as well as paracrine factors. During fasting, increased expression of FGF21 induces gluconeogenesis, fatty acid oxidation, and ketogenesis: as a result, FGF21 is considered a key regulator of the metabolic adaptation to fasting. In addition, recent evidence indicates that FGF21 may regulate longitudinal bone growth. It has been shown that transgenic mice overexpressing FGF21 exhibit reduced bone growth and hepatic Growth Hormone (GH) insensitivity. FGF21 knock-out mice exposed to chronic food restriction experience greater body and tibial growth than their food-restricted wild-type littermates, suggesting that the increased FGF21 expression in wild-type mice during undernutrition leads to reduced skeletal growth. The FGF21-mediated attenuation of bone growth appears to be secondary to reduced GH sensitivity, both systemically and locally in the long bones' growth plate. The effects of FGF21 on GH action are direct, and may result from the reduced translocation of GH receptors from the cytoplasm to the cell membrane. Lastly, we discuss recent studies which have shown that FGF21 in infancy is inversely correlated with linear growth rate. In conclusion, all the evidence discussed in this review indicates that FGF21 may be an important negative regulator of mammalian growth.

Increased expression of fibroblast growth factor 21 (FGF21) during chronic undernutrition causes growth hormone insensitivity in chondrocytes by inducing leptin receptor overlapping transcript (LEPROT) and leptin receptor overlapping transcript-like 1 (LEPROTL1) expression.

During calorie restriction in mice, increased expression of FGF21 causes growth attenuation and growth hormone (GH) insensitivity. Previous evidence also indicates that fasting-associated increased expression of leptin receptor overlapping transcript (LEPROT) and LEPROT-like 1 (LEPROTL1) (two proteins that regulate intracellular protein trafficking) reduces GH receptor cell-surface expression in the liver. Thus, we hypothesized that FGF21 causes GH insensitivity through regulation of LEPROT and/or LEPROTL1 expression. After 4 weeks of food restriction, LEPROT and LEPROTL1 mRNA expression in the liver and in the tibial growth plate of wild-type (WT) mice was increased compared with WT mice fed ad libitum. In Fgf21 knock-out (KO) mice, LEPROT and LEPROTL1 mRNA expression in food-restricted and fed ad libitum was similar, with the exception of a subgroup of food-restricted Fgf21 KO mice treated with recombinant human (rh) FGF21 that experienced increased LEPROT and LEPROTL1 mRNA expression compared with untreated food-restricted Fgf21 KO mice. In cultured growth plate chondrocytes, FGF21 stimulated LEPROT and LEPROTL1 mRNA expression, with such effect being prevented in chondrocytes transfected with FGFR1 siRNA or ERK1 siRNA. In cells transfected with control siRNA, GH increased [(3)H]thymidine incorporation, collagen X, and IGF-1 mRNA expression, with all effects being prevented by rhFGF21. In addition, rhFGF21 decreased (125)I-GH binding. In LEPROT siRNA- and/or LEPROTL1 siRNA-transfected cells, rhFGF21 did not prevent the GH stimulatory effects on thymidine incorporation, collagen X, and IGF-1 expression; furthermore, rhFGF21 did not prevent (125)I-GH binding. Consistent with the effects of rhFGF21, LEPROT overexpression in chondrocytes resulted in the inhibition of GH action. Our findings indicate that the increased expression of FGF21 during chronic undernutrition inhibits GH action on chondrocytes by activating LEPROT and LEPROTL1.

A description of two surgical and anesthetic management techniques used for a patient with fibrodysplasia ossificans progressiva.

Fibrodysplasia ossificans progressiva (FOP) is a rare and debilitating genetic disorder of skeletal malformations and progressive heterotopic ossification. Flare-ups are episodic, with bone formation in skeletal muscle and connective tissue leading to ankylosis of major joints of the axial and appendicular skeleton. This report outlines the management of a patient with FOP who had ankylosis of the temporomandibular joint and progressive ossification of the neck structures. The patient underwent two different surgical and anesthetic procedures within a 10-year period to manage his oral pain. The authors compare the surgical techniques, osteotomy versus the more conservative buccal approach, anesthesia techniques, and conventional intubation versus sedated fiberoptic intubation. This report emphasizes the importance of a less invasive surgical technique and an appropriate anesthetic management that reduces the risks, cost, and morbidity associated with routine surgical management of patients with FOP.