Comparison between transient and permanent congenital hypothyroidism on a thyroid function test after re-evaluation.

PURPOSE: Congenital hypothyroidism (CH) is diagnosed with neonatal screening and is treated early in the neonatal period. Among these patients, transient CH (TCH) is included and requires re-evaluation. The purpose of this study was to find the best way to discontinue levothyroxine and to find trends in thyroid function tests (TFTs) after re-evaluation. METHODS: We retrospectively reviewed 388 patients diagnosed with CH. They were classified as permanent CH (PCH) and TCH. The total number of the PCH and TCH groups was 83 (51 boys and 32 girls). We compared clinical parameters to predict TCH and to identify the trends of TFT. RESULTS: The first thyroid-stimulating hormone (TSH) value after discontinuation and the average TSH value for 1, 2, and 3 years were all significantly higher in the PCH group (P<0.01). The first fT4 value after discontinuation and the average fT4 value for 1, 2, and 3 years were all significantly higher in the TCH group (P<0.01). The optimal cutoff value on the receiver operating characteristic curve for PCH prediction with an average of 3 years of TSH was greater than 9.05 µIU/mL, which was predicted with a sensitivity of 100% and a specificity of 100%. CONCLUSION: When the TSH value ranges from 10 µIU/mL to 20 µIU/mL, clinicians can discontinue levothyroxine if the next result is around 10 µIU/mL or shows a decreasing trend.

Classic and backdoor pathways of androgen biosynthesis in human sexual development.

Both genes and hormones regulate human sexual development. Although ovarian hormones are not essential for female external genitalia development, male sexual development requires the action of testicular testosterone and dihydrotestosterone (DHT). DHT is the most active endogenous androgen formed by the conversion of testosterone in genital skin. This synthesis route from cholesterol to DHT is called the conventional classic pathway. Recent investigations have reported an alternative ("backdoor") route for DHT formation that bypasses fetal testicular testosterone. This alternative route plays a crucial role in human hyperandrogenic disorders like congenital adrenal hyperplasia caused by P450c21 deficiency, polycystic ovary syndrome, and P450 oxidoreductase deficiency. In addition, mutations in AKR1C2 and AKR1C4, genes encoding 3α-reductases, have been implicated in disorders of sexual development, indicating that both the classic and backdoor routes are required for normal human male sexual development. More recently, androsterone was found to be the primary androgen of the human backdoor route. Androsterone and steroidal substrates specific to the backdoor route are predominantly found in the placenta, liver, and adrenal glands rather than in the testes. These findings are essential to understanding human sexual development.

Severe hypernatremia in soft drink ketoacidosis and hyperglycemic hyperosmolar state at the onset of type 2 diabetes mellitus: a case series of three adolescents.

Diabetic ketoacidosis (DKA) and hyperglycemic hyperosmolar state (HHS) are diabetic emergencies. Some patients with a hyperglycemic crisis can present with an overlap of DKA and HHS. The coexistence of DKA and HHS is associated with higher mortality than in isolated DKA and HHS. In addition, electrolyte derangements caused by global electrolyte imbalance are associated with potentially life-threatening complications. Here, we describe three cases of mixed DKA and HHS with severe hypernatremia at the onset of type 2 diabetes mellitus. All patients had extreme hyperglycemia and hyperosmolarity with acidosis at the onset of diabetes mellitus. They consumed 2 to 3 L/d of high-carbohydrate drinks prior to admission to relieve thirst. They showed severe hypernatremia with renal impairment. Two patients recovered completely without any complications, while one died. Severe hypernatremia with mixed DKA and HHS is rare. However, it may be associated with excess carbohydrate beverage consumption. Reduced physical activity during the COVID19 pandemic and unhealthy eating behaviors worsened the initial presentation of diabetes mellitus. We highlight the impact of lifestyle factors on mixed DKA and HHS.

Efficacy and adverse events related to the initial dose of methimazole in children and adolescents with Graves' disease.

PURPOSE: The first-line antithyroid drug for children and adolescents with Graves' disease (GD) is methimazole (MMI). This study evaluated the relationship between the initial MMI dose and the clinical course of GD after treatment. METHODS: We studied the efficacy of the initial MMI dose and the relationship between the initial MMI dose and adverse events (AEs). We retrospectively enrolled 22 males and 77 females and divided those subjects into 3 groups according to the initial dose of MMI: <0.4 mg/kg/day (group A; n=32); 0.4-0.7 mg/kg/day (group B; n=39); and >0.7 mg/kg/day (group C; n=28). RESULTS: The mean time to the normalization of free thyroxine (fT4) levels upon initial treatment was 5.64, 8.61, and 7.98 weeks in groups A, B, and C, respectively (P=0.116). The incidence of liver dysfunction, neutropenia, and skin rash was 12.5%, 20.5%, and 42.9% in groups A, B, and C, respectively (P=0.018). Neutropenia, as a severe AE, was absent in group A, but its prevalence was 7.7% in group B and 21.4% in group C (P=0.015). When comparing only groups B and C, the incidences of liver dysfunction and neutropenia were higher in group C (P=0.04 and P=0.021, respectively). CONCLUSION: The mean time to the normalization of fT4 levels did not differ among the 3 groups, but the incidence of AEs was higher in the groups that received high MMI doses. High doses of MMI (>0.7 mg/kg/day) should be reconsidered as an initial treatment for children and adolescents with GD.

Acute Kidney Injury in Pediatric Diabetic Ketoacidosis.

OBJECTIVE: To assess the incidence and clinical characteristics of acute kidney injury (AKI) and identify the associated risk factors for AKI in children with type 1 diabetes mellitus (T1DM) and diabetic ketoacidosis (DKA). METHODS: This was a retrospective study performed over 15 y in a single Korean center. Children aged ≤18-y-old with T1DM and DKA were enrolled and divided into 2 groups according to the presence of AKI. RESULTS: This study included 90 episodes of DKA in 58 children with T1DM. AKI occurred in a total of 70 hospitalizations (77.8%) of 44 children: 18 (20.0%) with stage 1 AKI, 39 (43.3%) with stage 2 AKI, and 13 (14.4%) with stage 3 AKI. The number of AKI decreased to 28 (47.4%) and 13 (28.3%) after 12 h and 24 h of admission, respectively. The white blood cell count (P = 0.001) and anion gap levels (P = 0.025) were significantly higher and serum bicarbonate level (P = 0.004) was lower in the AKI group. Logistic regression analysis revealed that a longer duration of TIDM and high anion gap were independent predictors of developing severe AKI in pediatric DKA with T1DM (odds ratio, 1.225, P = 0.013; odds ratio, 1.130, P = 0.038). CONCLUSIONS: AKI frequently occurred in TIDM children with DKA. Longer duration of TIDM and elevated anion gap are associated with occurrence of severe AKI.

Biphenotypic acute leukemia or acute leukemia of ambiguous lineage in childhood: clinical characteristics and outcome.

BACKGROUND: Acute leukemia (AL), not clearly assigned to myeloid, B-lymphoid, or T-lymphoid lineage, is classified as either biphenotypic acute leukemia (BAL) based on the European Group for Immunological Classification of Leukemias (EGIL) or acute leukemia of ambiguous lineage (ALAL) encompassing acute undifferentiated leukemia (AUL) and mixed-phenotype acute leukemia (MPAL) based on the World Health Organization (WHO) criteria. METHODS: Medical records of children newly diagnosed with BAL or ALAL, based on the EGIL or the 2008/2016 WHO criteria, respectively, admitted at Chonnam National University Hospital in 2001-2017 were retrospectively reviewed. RESULTS: Twelve (3.2%) of 377 AL patients satisfied the BAL or ALAL definitions based on the EGIL or the WHO criteria, respectively. Among 12 patients including 11 with BAL and another with undefined case based on the EGIL criteria, 7 (1.9%) had ALAL based on more stringent 2016 WHO criteria (AUL, 2; MPAL, 5). One patient had MPAL with t(9;22)(q34;q11.2), BCR-ABL+, and two had MLL gene abnormality. ALL-directed regimen was associated with better complete remission rate compared with AML-directed regimen (100.0% vs. 16.7%; P=0.015). The 5-year overall survival (OS) and event-free survival (EFS) were 51.1±15.8% and 51.9±15.7%, respectively. AUL was associated with poor OS and EFS compared with MPAL (0.0% vs. 75.0±21.7%; P=0.008). CONCLUSION: Due to the rarity of the cases, future multicenter, prospective studies incorporating large number of cases are urgently warranted to identify the clinical, biologic, and molecular markers for the prediction of prognosis and determine the best tailored therapy for each patient.

Site-Specific and Coherent Manipulation of Individual Qubits in a 1D Optical Lattice with a 532-nm Site Separation.

We demonstrate gate operations on a single qubit at a specific site without perturbing the coherence of an adjacent qubit in a 1D optical lattice when the site separation is only 532 nm. Three types of spin rotations are performed on the target qubit with fidelities between 0.88±0.05 and 0.99±0.01, whereas the superposition state of the adjacent one is preserved with fidelities between 0.93±0.04 and 0.97±0.04. The qubit is realized by a pair of Zeeman-sensitive ground hyperfine states of a ^{7}Li atom, and each site is identified by its resonance frequency in a magnetic field gradient of 1.6 G/cm. We achieve the site-specific resolving power in the frequency domain by using magic polarization for the lattice beam that allows a Fourier-limited transition linewidth as well as by highly stabilizing the lattice parameters and the ambient conditions. We also discuss a two-atom entanglement scheme using a blockade by cold collisional shifts in a 1D superlattice, for which a coherent manipulation of individual qubits is a prerequisite.