Arginine vAsopressin (Avp) is an antidiuretic hormone which is synthesized in the supraoptic and paraventricular nuclei in the hypothalamus, and released into the systemic circulation from the posterior pituitary [1,2]. Secretion of AVP is precisely controlled by plasma osmolality so that even as little as 1% increases in plasma osmolality or serum sodium levels significantly increase plasma AVP levels [1,2]. Increases in plasma osmolality are sensed via the osmoreceptors in the hypothalamus, and induce not Abstract. Central diabetes insipidus (CDI) is caused by deficiency of arginine vasopressin, an antidiuretic hormone. Patients with CDI manifest polyuria which is usually compensated for by increases in water intake. However, some patients are not able to sense thirst due to the destruction of osmoreceptors in the hypothalamus. These adipsic CDI patients are easily dehydrated and the consequent dehydration could be life-threatening. The objective of this study was to investigate the prognosis of adipsic CDI patients. We have reviewed 149 patients with CDI in three hospitals using databases of the electronic medical recording systems, and examined whether adipsia could affect the morbidity and mortality in CDI patients with multivariable analyses. Twenty-three patients with CDI were adipsic while the remaining 126 patients were non-adipsic. The multivariate analyses showed that the incidence of serious infections which required hospitalization was significantly higher in the adipsic CDI patients compared to that in non-adipsic CDI patients (p <0.001). A total of 6 patients with CDI died during the follow-up (median duration; 60 months, range 1 to 132 months). Four of them were adipsic, three of whom died of infection. The statistical analyses revealed that the risk of death in adipsic CDI patients was significantly higher than in non-adipsic patients (p =0.007). It is thus suggested that adipsic CDI patients were susceptible to serious infections which could be the causes of death.

Complete T4-binding globulin deficiency (TBG-CD) is inherited in an X-linked fashion. A nucleotide substitution has been shown to cause this hereditary condition in caucasians of French Canadian origin. Heterogeneity in molecular mechanisms for TBG-CD has also been reported. Genomic DNA from a Japanese male exhibiting TBG-CD was subjected to polymerase chain reaction, and the generated DNA fragments were sequenced. A single nucleotide deletion was found in the first base of the codon for amino acid 352 of the common-type TBG molecule. This mutation causes a frameshift in translation and premature termination. Compared with common-type TBG, the mutated polypeptide results in 1) 22 different amino acids on its carboxy-terminus, 2) a 22-amino acid truncation, and 3) the absence of a potential N-linked glycosylation site. These alterations may lead to profound changes in the secondary and tertiary structures of the molecule. To ascertain the presence of this nucleotide deletion in the genomic DNA of affected subjects, a mutated primer was designed which together with the nucleotide deletion produced a new endonuclease restriction site in the polymerase chain reaction fragment. Results revealed the presence of the mutation in genomic DNA of the subject, and his mother was shown to have both mutant and normal alleles. The same mutation was also detected in five other unrelated families carrying TBG-CD. This mutation may be frequent in Japanese subjects with TBG-CD.

A 55-year-old woman with Ph-negative acute lymphoblastic leukemia in primary induction failure received allogeneic peripheral blood stem cell transplantation from her HLA-compatible sister. Pseudohyponatremia developed due to extreme hypercholesterolemia of 4091 mg/dL accompanied by lipoprotein X and lipoprotein Y. The hypercholesterolemia was caused by cholestasis due to chronic GVHD and ischemic cholangiopathy. In addition, we found that hepatic triglyceride lipase (HTGL) activity was severely decreased, which could be another novel factor causing extreme hypercholesterolemia after allogeneic transplantation. The total cholesterol has been gradually decreasing followed by the improvement of cholestasis with bezafibrate, ursodeoxycholic acid and prednisone treatments, and by a slight increase in HTGL-protein. To our knowledge, this is the first report to describe the association of decreased HTGL with extreme hypercholesterolemia after allogeneic transplantation.

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Two acute leukemia cases who presented autoimmune thyroid diseases after bone marrow transplantation (BMT) are described with reference to the pathogenesis of their autoimmune clones. A 37-year old Japanese woman developed Graves' hyperthyroidism 39 months after allogeneic BMT for acute myeloid leukemia (AML) donated from her sister. Although both donor and recipient were euthyroid and negative for thyroid autoimmunity before BMT, the donor was positive for anti-nuclear and anti-single strand DNA autoantibodies. Studies on polymorphism for variable number of tandem repeat region of T-cell receptor gene suggested that the lymphocytes responsible for the hyperthyroidism were of donor origin. The second case was a 12-year-old Japanese schoolboy who presented nongoitrous hypothyroidism 2 years after autologous BMT for acute lymphoblastic leukemia (ALL). He had been clinically euthyroid before transplantation. Family history revealed that his mother and sister had a history of Graves' disease. His serum was positive for thyroid-stimulation blocking antibody. It is highly likely that the autoimmune process was activated after transient immune suppression during peri-BMT period in this patient. Pathogenesis, incidence, and observed time lag between BMT and development of autoimmune thyroid diseases were discussed.