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Turner syndrome (TS) is associated with a high risk of fracture due to low bone mineral density (BMD). While hypogonadism is known to play a role in decreasing BMD, other factors have not been studied well. Focusing on diet, exercise, and bone metabolism markers, the present, multicentric, prospective, observational study aimed to identify factors contributing to decreased BMD in TS. In total, 48 patients with TS aged between 5 and 49 years comprising a pre-pubertal group (n = 9), a cyclical menstruation group (n = 6), and a hormone replacement therapy (HRT) group (n = 33) were enrolled. The cyclical menstruation group and the HRT group were referred to collectively as the post-pubertal group. The bone mineral apparent density (BMAD) Z-score was higher in the pre-pubertal group than in the post-pubertal group (–0.3 SD vs. –1.8 SD; p = 0.014). Within the post-pubertal group, the median BMAD Z-score was –0.2 SD in the cyclical menstruation group and –2.3 SD in the HRT group (p = 0.016). Spearman’s rank correlation revealed no correlation between the BMAD Z-score and bone metabolism markers. No significant relationship was observed between the BMAD Z-score and either the vitamin D sufficiency rate or the step sufficiency rate. A negative correlation was found between BMAD Z-score and serum sclerostin in the pre-pubertal group and serum FSH in the post-pubertal group. In conclusion, the present study found no relationship between the vertebral BMAD Z-score and diet or exercise habits in TS, indicating that estrogen deficiency is the chief reason for low BMD in TS.

X-linked hypophosphatemia (XLH) is a rare type of hereditary hypophosphatemic rickets. Patients with XLH have various symptoms that lower their QOL as defined by HAQ, RAPID3, SF36-PCS, and SF36-MCS in adult patients and SF-10 and PDCOI in pediatric patients. Early diagnosis and treatment are needed to reduce the burden, but the condition is often diagnosed late in childhood. The present review aims to summarize the symptoms, radiological and biological characteristics, and long-term prognosis of pediatric XLH. Typical symptoms of XLH are lower leg deformities (age six months or later), growth impairment (first year of life or later), and delayed gross motor development with progressive lower limb deformities (second year of life or later). Other symptoms include dental abscess, bone pain, hearing impairment, and Chiari type 1 malformation. Critical, radiological findings of rickets are metaphyseal widening, cupping, and fraying, which tend to occur in the load-bearing bones. The Rickets Severity Score, validated for XLH, is useful for assessing the severity of rickets. The biochemical features of XLH include elevated FGF23, hypophosphatemia, low 1,25(OH)2D, and elevated urine phosphate. Renal phosphate wasting can be assessed using the tubular maximum reabsorption of phosphate per glomerular filtration rate (TmP/GFR), which yields low values in patients with XLH. XLH should be diagnosed early because the multisystem symptoms often worsen over time. The present review aims to help physicians diagnose XLH at an early stage.

Background: Most patients with idiopathic growth hormone deficiency (iGHD) in childhood have normal GH stimulation test results in adulthood. The present study aimed to investigate the characteristics and possible etiology of transient iGHD. Methods: Patients with childhood-onset iGHD who completed their GH treatment between March 2010 and March 2021 were retrospectively studied. Patients with a clear history of child abuse or constitutional delay of growth and puberty were excluded. Ten patients with a diagnosis of iGHD based on a decreased growth rate and growth hormone stimulation test findings at the time of onset were included. Retesting demonstrated that these patients had a normal GH level. Results: Five patients had insufficient weight gain (BMI SD score < −1.0 at the start of treatment or a decrease in BMI SD score > 1.0 from one year before treatment to the start of treatment). The other five patients had no remarkable clinical features. One patient had decreased height velocity at the same time as their sibling. Conclusion: Insufficient pre-treatment weight gain or a familial cluster of cases may be related to low GH peaks of GHST, leading to a diagnosis of transient GHD.

X-linked hypophosphatemic rickets/osteomalacia is an inherited disease caused by the loss of function in PHEX. Elevated plasma FGF23 in patients with XLH leads to hypophosphatemia. The conventional treatment for XLH, consisting of oral phosphate and active vitamin D, is often poorly adhered to for various reasons, such as the requirement to take multiple daily doses of phosphate. Burosumab, an anti-FGF23 antibody, is a new drug that directly targets the mechanism underlying XLH. We report herein three adult patients with poor adherence to the conventional treatment. In Patient 1, adherence was poor throughout childhood and adolescence. The treatment of Patients 2 and 3 became insufficient after adolescence. All of the patients suffered from gait disturbance caused by pain, fractures, and lower extremity deformities early in life. We prescribed burosumab for the latter two patients, and their symptoms, which were unaffected by resuming conventional treatment, dramatically improved with burosumab. Maintaining adherence to the conventional treatment is crucial but challenging for patients with XLH. Starting burosumab therapy from childhood or adolescence in pediatric patients with poor adherence may help prevent the early onset of complications.

Background and objectivesWe herein reported ten, female neonates with transient clitoral preputial edema, which was mistaken for clitoromegaly. Although it is well known that the clitoris is prominent in premature, female neonates, there are as of yet no reports of clitoral preputial edema in full-term neonates. The present study was conducted to clarify the clinical course of clitoral preputial edema.MethodsSeventeen, Japanese patients aged < 6 months with suspected clitoromegaly were enrolled, and their clinical course was analyzed retrospectively. Clitoral preputial edema was defined by 1) a normal clitoral glans despite edema; and 2) the absence of established differences of sexual development, such as 21-hydroxylase deficiency.ResultsTen of the 17 patients with suspected clitoromegaly had clitoral preputial edema; eight of the ten patients were full-term, and the remaining two were preterm neonates. The median age at the first visit was 8 days. Edema of the labia minora and labia majora, rugosity of the labia majora, and hymenal polyps often accompanied the clitoral preputial edema. Seven patients were examined at our division during the neonatal period, and three patients were examined in the post-neonatal period. Age at reduction of the clitoral width to < 7 mm ranged from 8 to 74 days in four of the seven neonatal patients. In the three post-neonatal patients, age to reduction in the clitoral width ranged from 107 to 243 days.ConclusionsTransient clitoral preputial edema is often mistaken for clitoromegaly. The key to diagnosing clitoral preputial edema lies in its characteristic appearance and improvement course.

Rickets and osteomalacia are associated with impaired mineralization in growth plate cartilage and the bone osteoid [...]

Turner syndrome (TS) is a chromosomal disorder characterized by a short stature and gonadal dysgenesis, the latter of which requires estrogen replacement therapy (ERT) to induce and maintain secondary sexual characteristics. Insufficient ERT is associated with compromised skeletal health, including bone fragility, in adults with TS. In particular, estrogen insufficiency during adolescence is critical because the acquisition of a defective bone mass during this period results in impaired bone strength later in the life. In addition to bone mass, bone geometry is also a crucial factor influencing bone strength; therefore, a more detailed understanding of the skeletal characteristics of both bone mass and geometry during childhood and adolescence and their relationships with the estrogen status is needed to prevent compromised skeletal health during adulthood in TS. Although a delay in the initiation of ERT is associated with a lower bone mineral density during adulthood, limited information is currently available on the effects of ERT during adolescence on bone geometry. Herein, we summarize the current knowledge on skeletal characteristics in children and adolescents with TS and their relationships with estrogen sufficiency, and discuss the potential limitations of the current protocol for ERT during adolescence in order to achieve better skeletal health in adulthood.

The conventional treatment for X-linked hypophosphatemia (XLH), consisting of phosphorus supplementation and a biologically active form of vitamin D (alfacalcidol or calcitriol), is used to treat rickets and leg deformities and promote growth. However, patients’ adult height often remains less than −2 SD. Moreover, adverse events, such as renal calcification and hyperparathyroidism, may occur. The main pathology in XLH is caused by excessive production of fibroblast growth factor 23 (FGF23). Several studies have demonstrated that treatment with burosumab, a blocking neutralizing antibody against FGF23, is better than conventional therapy for severe XLH and has no serious, short-term side effects. Thus, treatment with burosumab may be an option for severe XLH. The present article reviews the conventional and burosumab therapies. In addition to the fact that the long-term efficacy of antibody-based treatment has not been demonstrated, there are other, unresolved issues concerning the burosumab treatment of XLH.

Delayed and absent puberty and infertility in Turner syndrome (TS) are caused by primary hypogonadism. A majority of patients with TS who are followed at hospitals during childhood will not experience regular menstruation. In fact, almost all patients with TS need estrogen replacement therapy (ERT) before they are young adults. ERT in TS is administered empirically. However, some practical issues concerning puberty induction in TS require clarification, such as how early to start ERT. The present monograph aims to review current pubertal induction therapies for TS without endogenous estrogen production and suggests a new therapeutic approach using a transdermal estradiol patch that mimics incremental increases in circulating, physiological estradiol. Although evidence supporting this approach is still scarce, pubertal induction with earlier, lower-dose estrogen therapy more closely approximates endogenous estradiol secretion.

21-hydroxylase deficiency (21-OHD) is the most common form of congenital adrenal hyperplasia. In most developed countries, newborn screening enables diagnosis of 21-OHD in asymptomatic patients during the neonatal period. In addition, recent advances in genetic testing have facilitated diagnosing 21-OHD, particularly in patients with equivocal clinical information. On the other hand, many challenges related to treatment remain. The goals of glucocorticoid therapy for childhood 21-OHD are to maintain growth and maturation as in healthy children by compensating for cortisol deficiency and suppressing excess adrenal androgen production. It is not easy to calibrate the glucocorticoid dosage accurately for patients with 21-OHD. Auxological data, such as height, body weight, and bone age, are considered the gold standard for monitoring of 21-OHD, particularly in prepuberty. However, these data require months to a year to evaluate. Theoretically, biochemical monitoring using steroid metabolites allows a much shorter monitoring period (hours to days). However, there are many unsolved problems in the clinical setting. For example, many steroid metabolites are affected by the circadian rhythm and timing of medication. There is still a paucity of evidence for the utility of biochemical monitoring. In the present review, we have attempted to clarify the knowns and unknowns about treatment parameters in 21-OHD during childhood.

Introduction11-ketotestosterone (11KT), which is derived by the bioconversion of testosterone via 11β-hydroxytestosterone (11OHT), is a potent agonist of the human androgen receptor. The adrenal gland is considered an important organ in 11KT production because CYP11B1, which catalyzes testosterone to 11OHT, is expressed in the adrenal glands. The present study aimed to demonstrate adrenal gland involvement in 11KT production in prepubertal children, a topic which has not yet been addressed by any previous studies.MethodsThree, retrospective, observational studies were performed. Study 1 enrolled patients aged 8 months to 7 years with severe Kawasaki disease (KD) who were treated with mPSL pulse. Studies 2 and 3 included patients who had received a corticotropin-releasing hormone (CRH) stimulation test and adrenocorticotropic hormone (ACTH) stimulation test, respectively. Samples were collected before and after treatment or drug administration, and serum 11KT, 11OHT, and other 11-oxygenated androgens were measured by LC-MS/MS. Steroid hormone values before and after medication were analyzed using the Wilcoxon signed rank test.ResultsStudies 1, 2, and 3 included twenty patients with severe KD, eight patients with a CRH stimulation test, and eight patients with an ACTH stimulation test, respectively. Study 1 demonstrated that the median (IQR) 11KT level was significantly higher before, than after, mPSL pulse (0.39 (0.28-0.47) nmol/L versus 0.064 (0.012-0.075) nmol/L; P < 0.001). Studies 2 and 3 indicated no significant difference in the median 11KT value before and after the CRH or ACTH stimulation test while the 11OHT value was significantly higher after the test.ConclusionIn conclusion, the mediation of 11KT production by ACTH demonstrated the importance of the adrenal glands in the synthesis of this androgen in prepubertal children.

Turner syndrome (TS), the most common type of X chromosomal disorder, has various, clinical manifestations. Among these, primary hypogonadism, which may lead to osteoporosis, is a life-long health issue. A high prevalence of fractures associated with osteoporosis is a major problem in patients with TS, where it may be 1.4-2.2 times higher than in healthy individuals and increases with age.Among the risk factors associated with fractures in TS, hypogonadism is arguably the most important. Estrogen deficiency due to hypogonadism leads to low bone mineral density (BMD), resulting in a high prevalence of bone fractures. Estrogen replacement therapy (ERT) in patients with TS reportedly improved their BMD. However, other causes of low BMD may exist, given that this condition begins in the prepubertal period in patients with TS.Most previous studies have reported low BMD in patients with TS using dual-energy X-ray absorptiometry (DXA), but this method has some limitations. Areal BMD values assessed by DXA were influenced by bone size and short stature, resulting in an underestimation of BMD. Currently, volumetric BMD values may be accurately obtained using peripheral quantitative computed tomography (pQCT). pQCT, high-resolution pQCT, and the trabecular bone score can also be used to evaluate bone quality, including bone geometry and microarchitecture, in TS.The present review discusses the high fracture risk, role of estrogen deficiency in low BMD, advantages and disadvantages of various bone assessment methods, and characteristics of bone quality in TS.

Abstract Background A cisplatin plus irinotecan (CPT‐11) regimen is used for patients with extensive disease small cell lung cancer (ED‐SCLC). Amrubicin (AMR) is primarily used for relapsed SCLC. The HOT1401/NJLCG1401 trial, an open‐label randomized phase II trial, was designed to assess the benefit of maintenance therapy in patients with ED‐SCLC who responded to induction therapy. Methods Patients with histologically‐ or cytologically‐confirmed ED‐SCLC were included and were treated with an induction therapy of four cycles of cisplatin (60 mg/m2 on day 1) plus CPT‐11 (60 mg/m2 on days 1, 8, and 15) every four weeks. After induction therapy, patients who had nonprogressive disease were randomized to receive either maintenance CPT‐11 (60 mg/m2 on days 1 and 8) every three weeks, or AMR (35 mg/m2 on days 1–3) every three weeks. Results A total of 34 patients were enrolled; 20 patients had progressive disease or received incomplete induction chemotherapy. Finally, 14 patients were randomly assigned to receive CPT‐11 (n = 7) or AMR (n = 7). This study was terminated prematurely because of low patient accrual. The overall objective response rate was 73%, the median PFS was 5.7 months (95% confidence interval [CI]: 3.6–11.8), and the median overall survival was 20.1 months (95% CI: 13.7–not reached). No statistically significant difference in progression‐free survival (PFS) were noted between patients treated with CPT‐11 and those treated with AMR. There were no treatment‐related deaths in this study. Conclusions Maintenance therapy with CPT‐11 or AMR after induction therapy might be effective in some patients.

Bone age (BA) is a clinical marker of bone maturation which indicates the developmental stage of endochondral ossification at the epiphysis and the growth plate. Hormones that promote the endochondral ossification process include growth hormone, insulin-like growth factor-1, thyroid hormone, estrogens, and androgens. In particular, estrogens are essential for growth plate fusion and closure in both sexes. Bone maturation in female children is more advanced than in male children of all ages. The promotion of bone maturation seen in females before the onset of puberty is thought to be an effect of estrogen because estrogen levels are higher in females than in males before puberty. Sex hormones are essential for bone maturation during puberty. Since females have their pubertal onset about two years earlier than males, bone maturation in females is more advanced than in males during puberty. In the present study, we aimed to review the factors affecting prepubertal and pubertal BA progression, BA progression in children with hypogonadism, and bone maturation and deformities in children with Turner syndrome.

Introduction: Recent research has shown that spinal sagittal alignment plays a critical role in health-related quality of life. However, most of these studies were cross-sectional in nature, and longitudinal studies of lumbar lordosis (LL) in healthy subjects were few. This study aims to evaluate the change in lumbar sagittal parameters during a 10-year period. Methods: The study population included 45 individuals (mean age, 65.7 years; male, n=20; female, n=25) who underwent sagittal lumbar radiography and a basic health checkup during a 10-year period. The radiologic parameters were LL, disc angle, sacral slope angle (SS), and pelvic incidence (PI). The change of LL during the 10-year period was defined as ΔLL. The subjects were divided into the LL maintenance group (n=33) and the LL non-maintenance group (n=12) based on their LL values. Results: The radiologic baseline/final parameters were as follows: LL, 45/34 degrees (P

The Thyroid Storm (TS) is the severest form of thyrotoxicosis and is associated with a high mortality rate. TS presents with fever, tachycardia, gastrointestinal symptoms, and central nervous system dysfunction and may be overlooked if patients do not present thyrotoxic symptoms or have precipitating factors. We reported a pediatric case of TS with mild proptosis but no obvious precipitating factors in a previously healthy child. A 9-year-old, female patient with a history of attention-deficit hyperactivity disorder presented with the complaint of frequent vomiting. She was alert but lethargic with fever and tachycardia. Physical examination was unremarkable except for coolness in the extremities and a delayed capillary refill time of two seconds. Fluid resuscitation was ineffective in alleviating the tachycardia. Additional history-taking revealed a one-month history of mild proptosis but no other thyrotoxic findings or precipitating factors were found. Markedly elevated thyroxine and triiodothyronine and suppressed thyroid-stimulating hormone on thyroid function tests led to a diagnosis of TS. Methimazole, potassium iodine, bisoprolol, and hydrocortisone were administered. Her vital signs and thyroid functions gradually improved, and she was discharged 18 days after admission without any serious complications. She is currently euthyroid and clinically stable on 5 mg of methimazole at three months after admission. When tachycardia that is resistant to usual resuscitation is found, careful history-taking and physical examination targeting thyroid disorders should be performed to assess for TS.

BackgroundBiochemically monitoring 21-hydroxylase deficiency (21-OHD) is challenging. Serum/blood 17-hydroxyprogesterone (17OHP) measurements are normally used for this purpose. Urinary pregnanetriol (PT), a urinary metabolite of 17OHP, may also be used. Based on auxological data, we previously reported that the optimal first morning PT value fell in the range of 2.2–3.3 mg/gCr (95% confidence interval of the mean) and 0.59-6.0 mg/gCr (10th – 90th percentile) for monitoring 21-OHD treatment. No report thus far has directly compared the first morning urinary PT value with the 17OHP value at various times during the day.ObjectiveTo explore the correlation between the first morning urinary PT value before glucocorticoid administration and the serum/blood 17OHP value at three time points, namely, before and two and four hours after glucocorticoid administration.DesignThis was a prospective study done at two children’s hospitals.MethodsIn total, 25 patients with 21-OHD aged 3-25 years were recruited. Their urinary PT levels and 17OHP levels were measured for three days within a total period of one week. The first morning PT value was collected on all three days. Dried blood spots and serum were used to measure 17OHP.ResultsThe range for the first morning PT value for all the samples (n=69) was 0.10-56.1 mg/gCr. A significant, positive correlation was found between the first morning PT and 17OHP values before medication (r=0.87, p

Background: The INPULSIS trials revealed that nintedanib reduced the decline in lung function in patients with idiopathic pulmonary fibrosis. We aimed to evaluate the efficacy and safety of nintedanib in Japanese idiopathic pulmonary fibrosis patients in real-world settings. Method: Medical records of idiopathic pulmonary fibrosis patients, who received treatment with nintedanib in five institutions between July 2015 and June 2017, were reviewed. Patients with % forced vital capacity ⩾50% and % predicted diffusing capacity of the lung carbon monoxide ⩾30% were classified as the moderate group and those with more impaired lung functions as the severe group. Result: Among 158 patients analyzed, 132 (84.6%) were classified as the moderate group and 26 (15.4%) as the severe group. In the moderate group, changes in forced vital capacity in 12 months were significantly different between before and after nintedanib administration (−253 ± 163 vs −125 ± 235 mL; p = 0.0027). In contrast, changes in forced vital capacity in 12 months were not significantly changed by nintedanib treatment in the severe group (−353 ± 250 vs −112 ± 341 mL; p = 0.2374). Incidence of acute exacerbation was higher in the severe group than in the moderate group (30.8% vs 18.9%). The overall survival of the moderate and the severe groups was 17.2 and 10.1 months. Conclusion: In real-world practice, nintedanib showed comparable efficacy to those observed in previous trials. In the severe group, the efficacy of nintedanib might be limited.

Abstract Background Paraneoplastic neurological syndromes (PNS) are rare disorders associated with cancer and are believed to be immune mediated. Patients with autonomic PNS suffer from variable combinations of parasympathetic and sympathetic failure. Autonomic PNS are usually associated with other PNS, such as encephalomyelitis and sensory neuropathy; however, autonomic symptoms may rarely manifest as PNS symptoms. Autonomic symptoms, therefore, may be overlooked in patients with cancer. Case presentation We described a 65-year-old Japanese man who was diagnosed with autonomic PNS due to small-cell lung carcinoma (SCLC) with Eastern Cooperative Oncology Group (ECOG) performance status 3, who suffered from orthostatic hypotension, and urinary retention needing a urethral balloon. Laboratory studies showed decreased levels of noradrenaline, and were positive for anti-ganglionic acetylcholine receptor antibody, type 1 antineuronal nuclear antibody, and sry-like high mobility group box 1 antibody. Nerve conduction evaluations and 123I-metaiodobenzylguanidine myocardial scintigraphy showed no abnormalities. Abdominal contrast-enhanced computed tomography revealed marked colonic distention. The patient’s autonomic symptoms resolved following integrated treatment (symptomatic treatment, immunotherapy, and additional chemotherapy) enabling the patient to walk, remove the urethral balloon, and endure further chemotherapy. ECOG performance status remained at 1, 10 months after admission. Conclusions Integrated treatment for autonomic PNS may improve autonomic symptoms and ECOG performance status of patients with cancer.

Ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1) was originally reported as a responsible gene for generalized arterial calcification in infancy (GACI). Though the prognosis of GACI patients is poor because of myocardial infarction and heart failure in relation to medial calcification of the coronary arteries, some patients rescued by bisphosphonate treatment have been reported. Recently, ENPP1 is also reported as responsible for autosomal recessive hypophosphatemic rickets type 2. We show here a boy with homozygous ENPP1 mutations diagnosed as having GACI in early infancy. After the diagnosis, he was treated with etidronate disodium (EHDP) in combination with antihypertensive drugs. The calcification of major arteries was diminished and disappeared by the age of eight months. He also showed mild hypophosphatemia (2.6–3.7 mg/dl) from the age of one year. After the treatment with EHDP for five years, he showed genu valgum with hypophosphatemia (2.6 mg/dl). He was diagnosed as having hypophosphatemic rickets at the age of seven years. The findings that hyper-mineralization of the arteries and hypo-mineralization of the bone observed in the same patient are noteworthy. ENPP1 could be regarded as a controller of the calcification of the whole body at least in part.

Mutations in transcription factors genes, which are well regulated spatially and temporally in the pituitary gland, result in congenital hypopituitarism (CH) in humans. The prevalence of CH attributable to transcription factor mutations appears to be rare and varies among populations.This study aimed to define the prevalence of CH in terms of nine CH-associated genes among Japanese patients. We enrolled 91 Japanese CH patients for DNA sequencing of POU1F1, PROP1, HESX1, LHX3, LHX4, SOX2, SOX3, OTX2, and GLI2. Additionally, gene copy numbers for POU1F1, PROP1, HESX1, LHX3, and LHX4 were examined by multiplex ligation-dependent probe amplification. The gene regulatory properties of mutant LHX4 proteins were characterized in vitro. We identified two novel heterozygous LHX4 mutations, namely c.249-1G>A, p.V75I, and one common POU1F1 mutation, p.R271W. The patient harboring the c.249-1G>A mutation exhibited isolated growth hormone deficiency at diagnosis and a gradual loss of ACTH, whereas the patient with the p.V75I mutation exhibited multiple pituitary hormone deficiency. In vitro experiments showed that both LHX4 mutations were associated with an impairment of the transactivation capacities of POU1F1 andαGSU, without any dominant-negative effects. The total mutation prevalence in Japanese CH patients was 3.3%. This study is the first to describe, a gradual loss of ACTH in a patient carrying an LHX4 mutation. Careful monitoring of hypothalamic-pituitary -adrenal function is recommended for CH patients with LHX4 mutations.

Patients with diffuse congenital hyperinsulinism (CHI) refractory to drug therapy require subtotal or near-total pancreatectomy. Although almost all patients develop diabetes postoperatively, the clinical course and timing of insulin therapy remain unclear. A 7-yr-old girl presented with recurrent hypoglycemia shortly after birth and a relatively elevated insulin level, which confirmed the diagnosis of CHI. Genetic analysis revealed compound heterozygous ATP-binding cassette, Subfamily C, Member 8 pathogenic variants and diffuse CHI was suspected. Because her condition was refractory to diazoxide and octreotide, she underwent a subtotal pancreatectomy at the age of 4 mo. The drug therapy was discontinued. Although an oral glucose tolerance test at the age of 2 yr showed hyperglycemia after loading, continuous glucose monitoring (CGM) revealed that her daily glucose trends were almost within the 70-180 mg/dL range, and mild hypoglycemia appeared during the daytime. After the age of 6 yr, CGM showed an elevation in glucose trends from midnight to early morning, suggesting that insulin secretion was attenuated and hepatic glucose production was insufficiently suppressed. Insulin therapy was initiated at the age of 7 yr. These results indicate that CGM can be useful for making treatment decisions. [ABSTRACT FROM AUTHOR]

In Japan, most neonates undergo screening for congenital hypothyroidism (CH). A TRH stimulation test (TRH-T) may be performed after initial treatment as a useful method for reevaluating the patient’s thyroid status. However, no studies have compared basal and peak TSH values in TRH-T in patients with long-term follow-up. This was a retrospective and observational study. The inclusion criteria were as follows: (1) CH diagnosis based on positive newborn screening, (2) follow-up > 15 yr, and (3) TRH-T after LT4 discontinuation. The participants were divided into a no-treatment group (No-T group) and a treatment group (T group). The No-T and T groups included 14 and nine patients, respectively. The age at TRH-T was 5.38 yr for the No-T group and 4.25 yr for the T group, with no significant difference. The basal and peak TSH levels were significantly lower in the No-T group. The areas under the Receiver operating characteristic curve for basal and peak TSH values were 0.984 and 0.905, respectively. When the basal TSH level was under 4.594 IU/mL, the No-T group had a sensitivity of 1.00 and a specificity of 0.93. Basal TSH levels alone may be sufficient for predicting the long-term therapeutic prognosis of patients with CH. [ABSTRACT FROM AUTHOR]