The Boy:Girl Ratio of Children Diagnosed with Growth Hormone Deficiency-Induced Short Stature Is Associated with the Boy:Girl Ratio of Children Visiting Short Stature Clinics.

BACKGROUND: About twice as many boys as girls undergo growth hormone (GH) therapy in GH deficiency (GHD). However, this sex difference may not correctly reflect a real incidence. OBJECTIVES: We analyzed the evidence of a selection bias whereby more boys seek treatment at short stature clinics. SUBJECTS AND METHODS: The present study included 3,902 children who visited 17 short stature clinics with a height SD score of -2 SD or less. The percentage of children who underwent the GH stimulation test was compared between boys and girls, as was the percentage of children ultimately diagnosed with GHD. RESULTS: The children comprised 2,390 boys (61.3%) and 1,512 girls (38.7%), with a boy:girl ratio of 1.58:1. The percentage of children who underwent the GH stimulation test did not differ between boys (45.7%) and girls (49.8%). Among the children who underwent the GH stimulation test, the percentage diagnosed with GHD did not differ significantly between boys (22.0%) and girls (20.1%). The boy:girl ratio of children diagnosed with GHD was 1.59:1. CONCLUSIONS: The boy:girl ratio of children with short stature (1.58:1) did not differ significantly from that of children diagnosed with GHD (1.59:1). These results indicate that the predominance of boys in GHD does not reflect a real incidence, but rather a selection bias whereby a higher proportion of boys with short stature seek treatment at clinics. This difference arises because parents are more concerned about boys' height, and because boys reach adult height at an older age.

Clinical features at diagnosis and responses to antithyroid drugs in younger children with Graves' disease compared with adolescent patients.

OBJECTIVE: The aim of this study was to evaluate clinical manifestations, laboratory findings, and effects of antithyroid drugs in younger children with Graves' disease (GD). DESIGN: A retrospective and collaborative study. SETTING: Nine facilities in Chiba prefecture, Japan. PATIENTS: We analyzed 132 children and adolescents with GD. The subjects were divided according to the median age into a group of young children (group I, 4.1-12.4 years, n=66) and an adolescent group (group II, 12.5-15.9 years, n=66). MAIN OUTCOME MEASURES: Clinical manifestations, laboratory findings, incidence of adverse effects, and remission rates 5 years after initial therapy were assessed. RESULTS: The mean height SD score of group I (1.0) was higher than that of group II (0.3, p<0.001). The mean BMI SD score of group I (-0.7) was lower than that of group II (-0.3, p<0.05). The most common presentations were goiter, sweating, and hyperactivity in group I, whereas the most common presentations were goiter, sweating, and easy fatigability in group II. Hyperactivity was more frequent in group I (56.7%) than in group II (37.9%, p<0.05). Liver dysfunction appeared more often in group I (14.3%) than in group II (1.9%, p<0.05). There was no difference in the appearance of adverse effects between the two groups. The remission rate was slightly lower in group I (23.1%) than in group II (31.3%), but was not significant. CONCLUSIONS: Thyrotoxicosis had more influence on the growth and liver function in younger children.

Higher dose of methimazole causes frequent adverse effects in the management of Graves' disease in children and adolescents.

OBJECTIVE: Methimazole (MMI) is used as a first-line antithyroid drug in children and adolescents with Graves' disease (GD). The aim of this study was to evaluate the correlation between the initial dose of MMI and the clinical course of GD after treatment. DESIGN: Retrospective and collaborative study. SETTING: Nine facilities in Chiba prefecture, Japan. PATIENTS: Sixty-four children and adolescents with GD were analyzed. The subjects were divided into three groups by the initial daily dose of MMI: group A, 0.4±0.1 mg/kg (mean±SD, n=11); group B, 0.7±0.2 (n=37); group C, 0.9±0.2 (n=16). MAIN OUTCOME MEASURES: The duration of time required for normalization of serum free T4 on initial treatment and the incidence of adverse effects for 1 year after the start of MMI were compared. Outcomes were compared among patients who were followed more than 3 years (group A, n=7; group B, n=24; group C, n=12). RESULTS: Mean duration of times for normalization of T4 was 1.9±1.5 months in group A, 1.6±0.9 in group B and 1.9±1.5 in group C (NS). No major adverse reactions were observed. Minor adverse effects occurred in 9.1% of cases in group A, 13.5% in group B and 62.0% in group C (p<0.01). Remission rates did not differ among the three groups. CONCLUSIONS: Higher doses of MMI are harmful for initial use in children and adolescents with GD.

Comparison of methimazole and propylthiouracil in the management of children and adolescents with Graves' disease: efficacy and adverse reactions during initial treatment and long-term outcome.

OBJECTIVE: The aim of this study was to compare the efficacy and adverse reactions during initial treatment and long-term outcome between children and adolescents with Graves' disease (GD) treated with propylthiouracil (PTU) and those treated with methimazole (MMI). DESIGN, SETTING AND PARTICIPANTS: Retrospective and collaborative study. Children and adolescents with GD were divided into group M (MMI: n=64) and group P (PTU: n=69) and into four subgroups by initial dose: group M1 (<0.75 mg/kg of MMI, n=34), group M2 (> or = 0.75 mg/kg, n=30), group P1 (<7.5 mg/kg of PTU, n=24) and group P2 (> or = 7.5 mg/kg, n=45). MAIN OUTCOME MEASURES: The duration for normalization of serum T4 on initial treatment, the incidence of adverse effects for one year and outcomes at 10 years after were compared. RESULTS: Mean durations for normalization of T4 (+/- SD) were 1.7 +/- 1.0 months in group M and 2.3 +/- 2.4 in group P [not significant (NS)], while the mean duration in group P1 (3.1 +/- 3.3) was significantly longer than those in the other subgroups (M1: 1.9 +/- 1.2; M2: 1.4 +/- 0.7; P2; 1.7 +/- 1.3). No major adverse reaction was observed. Minor adverse effects occurred in 25.0% of cases in group M and 31.9% in group P (NS). The incidence in group P2 (44.4%) was significantly higher than those in group M1 (20.6%) and group P1 (8.3%). Remission rates did not differ between the MMI-treated group (35.0%, n=20) and PTU-treated group (50.0%, n=40). CONCLUSIONS: PTU may not be suitable for initial use in children and adolescents with GD, even with the risk of major adverse reactions such as liver failure excluded.

Intravascular large B cell lymphoma: proposed of the strategy for early diagnosis and treatment of patients with rapid deteriorating condition.

We summarize our experience and propose methods for early diagnosis and treatment of intravascular large B cell lymphoma (IVL). A total of 16 patients with IVL between 1994 and 2007 were included and analyzed in this study. Predicted survival durations were short until September 2003. However, there have been marked improvement since the introduction of rituximab, and all patients responded to treatment and survived for more than 1 year following diagnosis of IVL. We propose an early clinical diagnostic strategy for starting treatment for IVL patients with quite poor performance status (PS) and in whom time is a limiting factor: (1) age >40 years, (2) fever above 38 degrees C with poor PS (ECOG 2-4), (3) lactate dehydrogenase (LDH) more than twice the upper limit of the normal level and/or sIL2R >5,000 IU/ml in serum, (4) worsening PS and/or elevation of serum LDH on a daily basis, and (5) confirmation of pathological lymphoid cells in peripheral blood or bone marrow smear and/or flow cytometry. Although accurate pathological diagnosis is quite important, time is a limiting factor for most of IVL patients. In such cases, we can start chemotherapy based on early clinical diagnostic strategy with high sensitivity and obtain good clinical outcome.

Phase III study of ranimustine, cyclophosphamide, vincristine, melphalan, and prednisolone (MCNU-COP/MP) versus modified COP/MP in multiple myeloma: a Japan clinical oncology group study, JCOG 9301.

To investigate whether combination chemotherapy with vincristine, cyclophosphamide, prednisolone, and melphalan (COP/ MP) with the addition of ranimustine (MCNU) (MCNU-COP/MP) is superior to the slightly modified COP/MP (mCOP/MP) regimen in multiple myeloma (MM), a multicenter randomized study was performed. Two hundred ten patients with newly diagnosed, overt MM not treated with chemotherapy were enrolled from 32 institutions of the Lymphoma Study Group of the Japan Clinical Oncology Group and were randomized to receive either MCNU-COP/MP or mCOP/MP. The response rate (RR) to mCOP/MP was 43.7% (95% confidence interval [CI], 33.9%-53.8%] and to MCNU-COP/MP was 56.1% (95% CI, 46.1%-65.7%) (P = .097). The progression-free survival (PFS) was significantly longer for patients treated with MCNU-COP/MP than for patients treated with mCOP/MP (median, 23.0 months [95% CI, 18.9-25.8] versus 15.8 months [95% CI, 14.1-19.4]) (P = .014). However, no significant difference in overall survival rate (OS) was observed between the groups (median, 49.9 months [95% CI, 40.4-59.1] versus 44.0 months [95%, CI, 32.8-59.8]) (P = .75). Grades 3 and 4 hematological toxicities were more frequently observed with MCNU-COP/MP than with mCOP/MP, but the incidence of grades 3 and 4 nonhematological toxicities was low in both groups. In conclusion, MCNU-COP/MP in comparison with mCOP/MP improved RR and PFS in overt MM; however, this outcome did not contribute to prolonging OS, indicating that addition of MCNU to mCOP/MP has no benefit on survival.