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        Low-dose mitotane-induced neurological and endocrinological complication in a 5-year-old girl with adrenocortical carcinoma

        Heo You Joung,Yoo Jae Ho,Choe Yun Soo,Park Sang Hee,Lee Seung Bok,Kim Hyun A,Choi Jung Yoon,Lee Young Ah,Lim Byung Chan,Chueh Hee Won 대한소아내분비학회 2022 Annals of Pediatirc Endocrinology & Metabolism Vol.27 No.3

        Mitotane is an adrenolytic drug that exhibits therapeutic effects within a narrow target range (14–20 μg/dL). Various complications develop if the upper limit is exceeded. We present the case of a 5-year-old girl with breast development, acne, and pubic hair who was diagnosed with an adrenal mass that was subsequently excised. The pathological finding was adrenocortical carcinoma with a high risk of malignancy, and adjuvant therapy (combined mitotane and radiation therapy) was recommended. Mitotane was initiated at a low dose to allow monitoring of the therapeutic drug level, and high-dose hydrocortisone was also administered. However, the patient exhibited elevated adrenocorticotropic hormone levels and vague symptoms such as general weakness and difficulty concentrating. It was important to determine if these symptoms were signs of the neurological complications that develop when mitotane level is elevated. Encephalopathy progression and pubertal signs appeared 6 months after diagnosis, induced by high mitotane level. The mitotane decreased to subtherapeutic level several months after its discontinuation, at which time endocrinopathy (central hypothyroidism, hypercholesterolemia, and secondary central precocious puberty) developed. The case shows that low-dose mitotane can trigger neurological and endocrinological complications in a pediatric patient, indicating that the drug dose should be individualized with frequent monitoring of the therapeutic level.

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        Ambient air pollution and endocrinologic disorders in childhood

        Heo You Joung,Kim Hae Soon 대한소아내분비학회 2021 Annals of Pediatirc Endocrinology & Metabolism Vol.26 No.3

        Ambient air pollution has been proposed as an important environmental risk factor that increases global mortality and morbidity. Over the past decade, several human and animal studies have reported an association between exposure to air pollution and altered metabolic and endocrine systems in children. However, the results for these studies were mixed and inconclusive and did not demonstrate causality because different outcomes were observed due to different study designs, exposure periods, and methodologies for exposure measurements. Current proposed mechanisms include altered immune response, oxidative stress, neuroinflammation, inadequate placental development, and epigenetic modulation. In this review, we summarized the results of previous pediatric studies that reported effects of prenatal and postnatal air pollution exposure on childhood type 1 diabetes mellitus, obesity, insulin resistance, thyroid dysfunction, and timing of pubertal onset, along with underlying related mechanisms.

      • Quality assessment by using Rhod-2 staining in porcine matured and fertilized oocytes

        Ho-Guen Jega,Hyo-Jin Park,Jin-Woo Kim,Seul-Gi Yang,Min-Ji Kim,In-Su Kim,Sang-Min Lee,Bo-You Heo,Joung Jun Park,Deog-Bon Koo 한국수정란이식학회 2018 한국수정란이식학회 학술대회 Vol.2018 No.11

        Mitochondrion is an organelle for regulating calcium (Ca2+) homeostasis. Mitochondrial Ca2+ plays important roles on oocyte maturation, fertilization and embryonic development for ATP production. Low quality oocytes have mitochondrial dysfunction, which lead to overloaded Ca2+ in mitochondria. Recently, Rhod-2 is well known as a mitochondrial derived Ca2+ indicator. However, the changes of Rhod-2 in matured or fertilized porcine oocytes have not been reported. Therefore, the aim of study was to identify the effects of mitochondrial Ca2+ using Rhod-2 on quality assessment of matured oocyte and zygotes in pigs. Thus, we classified two groups (group 1: G1, compact COCs and group 2: G2, uncompact COCs) according to differences of cumulus cells amount and cytoplasm morphology in germinal vesicle (GV) stage of porcine COCs. Therefore, we investigated number of Rhod-2 spots in matured and fertilized oocytes from G1 and G2 groups. The Rhod-2 spot numbers were separated into four parts; n<10, 10≤ n < 20, 20 ≤ n < 30, and 30 < n. The Rhod-2 spots number of G2 group had greater than G1 group in part of 20 ≤ n. Additionally, we investigate mean number of Rhod-2 spots from G1 and G2 groups in matured and fertilized oocytes. As a result, we confirmed that average number of Rhod-2 spots in G2 group increased than that of G2 group. Finally, we also measured the Rhod-2 intensity in matured and fertilized oocytes of G1 and G2 groups. Interestingly, the Rhod-2 intensity in G2 group was higher than that of G1 group. (oocyte: p < 0.001 and fertilized oocyte: p < 0.05). These results demonstrated that changes in Rhod-2 spots and intensity were increased in low quality of matured and fertilized oocytes. Therefore, our results suggest that the differences in mitochondrial calcium level are associated with morphological quality of porcine COCs.

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