Type 4B hereditary hemochromatosis due to heterozygous p.D157A mutation in SLC40A1 complicated with hypopituitarism.

Hemochromatosis is a clinical syndrome characterized by iron overload in various organs. We present here a case of type 4 hereditary hemochromatosis due to heterozygous mutation in SLC40A1 gene (p.D157A). SLC40A1 encodes ferroportin, a macromolecule only known as iron exporter from mammalian cells. He first presented symptoms correlated with hypopituitarism. Furthermore, marked hyperferritinemia and high transferrin saturation were revealed in combination with the findings of iron overload in the liver, spleen and pituitary gland by computed tomography and magnetic resonance imaging. Liver biopsy revealed iron deposition in both hepatocytes and Kupffer cells. SLC40A1 mutations are considered to cause wide heterogeneity by various ferroportin mutations. Thus, clinicopathological examinations seem to be very important for diagnosing phenotype of type 4 hemochromatosis in addition to the gene analysis. We diagnosed him as type 4B hereditary hemochromatosis (ferroportin-associated hemochromatosis) by the findings of high transferrin saturation and iron deposition in hepatocytes, and then started iron chelating treatment. We should suspect the possibility of hereditary hemochromatosis even in Japanese with severe iron overload. Although the same mutation in SLC40A1 gene (p.D157A) had been reported to cause "loss of function" phenotype, we considered that the mutation of our case caused "gain of function" phenotype.

Two Cases of Painful Thyroiditis With Subsequent Hypothyroidism Following Cord Blood Transplant.

We report two rare cases of painful thyroiditis approximately 100 days after unrelated cord blood transplantation (CBT), which progressed to hypothyroidism. Patient one, a 45-year-old woman, developed goiter, tenderness, and thyrotoxicity on day 100 after CBT for relapsed acute lymphocytic leukemia. Scintigraphy suggested destructive thyroiditis; symptoms improved with one-month beta-blocker and prednisolone treatment. Two months later, hypothyroidism developed which required supplementation-based treatment. Patient two, a 49-year-old man, developed goiter, tenderness, and thyrotoxicosis on day 96 after CBT for acute myelogenous leukemia. Hypothyroidism developed after nonsteroidal anti-inflammatory drug treatment. Thyroiditis and hypothyroidism should be considered in patients who develop neck pain after CBT.

Hyperparathyroidism Which Developed after Resection of a Fibroblast Growth Factor 23-producing Tumor.

A 53-year-old woman presented with bone pain and was diagnosed with osteomalacia because of hypophosphatemia, hyperphosphatasemia, bone pain, and radiographic findings. Because her intact-fibroblast growth factor 23 (FGF23) levels were high and contrast-enhanced computed tomography revealed a mass in the anterior ethmoid sinus, FGF23-related osteomalacia was diagnosed. The tumor was resected, but she developed hypercalcemia and elevated blood parathyroid hormone (PTH) levels. Primary hyperparathyroidism (PHPT) was diagnosed, and surgical resection was performed. To our knowledge, this is the first case of a FGF23-producing tumor complicated by PHPT. Because PHPT manifested after resecting the FGF23-producing tumor, FGF23 is thus considered to suppress PTH secretion in humans.

Hyperparathyroidism-jaw Tumor Syndrome Confirmed by Preoperative Genetic Testing.

We herein report the case of a young woman who was diagnosed with primary hyperparathyroidism and in whom genetic testing confirmed a diagnosis of hyperparathyroidism-jaw tumor syndrome. Familial hyperparathyroidism was suspected based on the patient's young age at the onset of the disease. Thus, genetic testing was performed. It showed a germline mutation in the HRPT2/CDC73 gene and confirmed the diagnosis of hyperparathyroidism-jaw tumor syndrome. Total parathyroidectomy was performed to prevent recurrence. In patients with early-onset hyperparathyroidism, genetic testing should be considered to facilitate the selection of a proper surgical procedure based on the consideration of future life expectancy.

Early effects of sodium-glucose co-transporter 2 inhibitors in type 2 diabetes: study based on continuous glucose monitoring.

BACKGROUND: Inhibitors of sodium-glucose co-transporter 2 (SGLT2) have immediate glucose-lowering effects by promoting urinary glucose excretion, without altering insulin level. Only a few studies have evaluated blood glucose dynamics in the early period after administration. The present retrospective study was designed to determine the immediate effects of SGLT2 inhibitors on blood glucose dynamics. METHODS: The study subjects were 24 patients with type 2 diabetes whose blood glucose dynamics were evaluated with continuous glucose monitoring for 1 week before and after initiation of SGLT2 inhibitor therapy. Blood glucose dynamics were examined on days -1, 0 (treatment commencement day), 3, and 7 by evaluating different continuous glucose monitoring parameters and blood glucose before each meal. Furthermore, blood glucose levels at 1 and 2 h after each meal and daily urinary glucose levels were determined. RESULTS: A significant reduction in blood glucose levels 2 h after breakfast was observed between the day before treatment (249.8 mg/dL) and the day treatment started (218.9 mg/dL). The mean daily blood glucose level improved significantly from 201.4 to 142.3 mg/dL from the day the treatment started. Blood glucose variation also improved significantly by week 1, as demonstrated by changes in standard deviation and mean amplitude of glycemic excursions (from 39.6 to 31.7 and 106.9 to 87.4 mg/dL, respectively). The percent time at blood glucose <70 mg/dL remained unchanged while urinary glucose on day 7 correlated with minimum blood glucose level (r = 0.474, p = 0.022). CONCLUSIONS: The results showed that the SGLT2 inhibitors lower blood glucose from 2 h after the first dose and improve blood glucose variation by week 1 after start of the treatment. Furthermore, SGLT2 inhibitors did not alter the incidence of hypoglycemic episodes at week 1, suggesting that SGLT2 protects against severe hypoglycemia by inhibiting urinary glucose excretion.