Combined pituitary hormone deficiency harboring CHD7 gene missense mutation without CHARGE syndrome: a case report.

BACKGROUND: Heterozygous loss-of-function mutations in the chromodomain helicase DNA-binding protein 7 (CHD7) gene cause CHARGE syndrome characterized by various congenital anomalies. A majority of patients with CHARGE syndrome present with congenital hypogonadotropic hypogonadism (HH), and combined pituitary hormone deficiency (CPHD) can also be present. Whereas CHD7 mutations have been identified in some patients with isolated HH without a diagnosis of CHARGE syndrome, it remains unclear whether CHD7 mutations can be identified in patients with CPHD who do not fulfill the criteria for CHARGE syndrome. CASE PRESENTATION: A 33-year-old woman was admitted to our hospital. She had primary amenorrhea and was at Tanner stage 2 for both pubic hair and breast development. She was diagnosed with CPHD (HH, growth hormone deficiency, and central hypothyroidism), and a heterozygous rare missense mutation (c.6745G > A, p.Asp2249Asn) in the CHD7 gene was identified. Our conservation analysis and numerous in silico analyses suggested that this mutation had pathogenic potential. She had mild intellectual disability, a minor feature of CHARGE syndrome, but did not fulfill the criteria for CHARGE syndrome. CONCLUSIONS: We report a rare case of CPHD harboring CHD7 mutation without CHARGE syndrome. This case provides valuable insights into phenotypes caused by CHD7 mutations. CHD7 mutations can have a continuous phenotypic spectrum depending on the severity of hypopituitarism and CHARGE features. Therefore, we would like to propose a novel concept of CHD7-associated syndrome.

Exogenous insulin antibody syndrome in a patient with diabetes secondary to total pancreatectomy.

Exogenous insulin can induce insulin antibodies that have a low affinity/high binding capacity. Similar to what is observed in insulin autoimmune syndrome, these insulin antibodies can cause fasting hypoglycemia and postprandial hyperglycemia, a phenomenon known as "exogenous insulin antibody syndrome" (EIAS). Cases of EIAS in patients with type 1 and type 2 diabetes have been sporadically reported, mainly in Asia. However, there has been no report on EIAS in patients with diabetes secondary to total pancreatectomy treated with insulin analogs. A 74-year-old man with diabetes after total pancreatectomy had been treated with continuous subcutaneous insulin infusion using an insulin analog, lispro, and developed recurrent early morning hypoglycemia even after discontinuation of nocturnal basal insulin. His fasting serum lispro level was high even approximately 9 h after the last lispro dose. He had a high titer (72.7%) of insulin antibodies, and a Scatchard analysis revealed low affinity/high binding capacity. These findings suggested that the patient's recurrent early morning hypoglycemia was associated with insulin antibodies against lispro, and we, therefore, switched from lispro to another insulin analog, glulisine. His hypoglycemia improved, accompanied by a dramatic decrease in his insulin antibodies and serum glulisine levels. Early morning hypoglycemia in patients with diabetes secondary to total pancreatectomy may often be explained by high glycemic variability, malnutrition, and/or glucagon deficiency. However, in cases of recurrent early morning hypoglycemia, EIAS should be considered as a potential differential diagnosis.

Endocrinological Features of Hartsfield Syndrome in an Adult Patient With a Novel Mutation of FGFR1.

Hartsfield syndrome (HS: OMIM 615465) is a rare congenital disease associated with a mutation of the fibroblast growth factor receptor 1 gene (FGFR1) with the main features of holoprosencephaly and ectrodactyly. Patients with HS also present with endocrinological deficits, such as isolated hypogonadotropic hypogonadism and central diabetes insipidus. Although there are several studies on infancy/childhood history, there is no study of infant/childhood/adolescent/young adult HS natural history and endocrinological findings. Here, we report a male patient with HS associated with a novel de novo FGFR1 mutation (c. 1868A > C). The endocrinological profile was evaluated at ages 1 and 31 years. This long-term follow-up study highlights functional changes in the posterior pituitary gland and features of bone metabolism disorder. We also describe the anterior pituitary function. To our knowledge this is the first description of the natural history of an HS patient through birth to young adult age. Although the HS infants reported in the literature develop central diabetes insipidus, little is known about the serial changes in pituitary gland function during growth in HS patients. In this study we describe an adult patient with HS who showed improvement of hypernatremia during early adulthood. In addition, we emphasize the importance of prevention and treatment of osteoporosis in HS.

Effects of alogliptin on the ratio of glycated albumin to HbA1c in patients with type 2 diabetes mellitus.

The ratio of glycated albumin (GA) to HbA1c (the GA/HbA1c ratio) has been used as a glycemic control indicator that reflects postprandial plasma glucose levels or glycemic variability. In this study, we investigated the effects of alogliptin, a DPP-4 inhibitor, on the GA/HbA1c ratio in patients with type 2 diabetes mellitus. Thirty-eight patients with type 2 diabetes mellitus whose glycemic control was stable were enrolled, and alogliptin (12.5 or 25 mg/day) was then administered to them for 24 weeks. HbA1c and GA levels both significantly decreased after 24 weeks (P < 0.0001), whereas the GA/HbA1c ratio did not (P = 0.129). No correlation was observed between the change in the GA/HbA1c ratio (the ΔGA/HbA1c ratio) and HbA1c or GA level before the administration of alogliptin; however, a negative correlation was found between the ΔGA/HbA1c ratio and the GA/HbA1c ratio before the administration of alogliptin (R = -0.322, P = 0.049). Although the GA/HbA1c ratio in the low-value group (<2.80) was not significantly affected by the administration of alogliptin, that in the high-value group (≥2.80) significantly decreased (P = 0.008). The administration of alogliptin significantly decreased the GA/HbA1c ratio in the high-value group after 24 weeks. Alogliptin may be more useful for patients with high postprandial plasma glucose levels than in those with low postplandial plasma glucose levels.