Central diabetes insipidus due to herpes simplex in a patient immunosuppressed by Cushing's syndrome.

OBJECTIVE: To describe a patient immunocompromised by Cushing's syndrome in whom central diabetes insipidus developed as a complication of herpes simplex involvement of the hypothalamus. METHODS: We present a case, including results of laboratory and histopathologic studies, in which herpes simplex was established as the causative agent for central diabetes insipidus. RESULTS: A woman with ectopic corticotropin-dependent Cushing's syndrome, diabetes mellitus, carcinoid tumor, and a history of thyroid cancer had the precipitous onset of seizure and fever, and hypotonic polyuria and progressive hypernatremia developed. Central diabetes insipidus was diagnosed and successfully treated with desmopressin. Nevertheless, the patient's condition deteriorated and she died. Autopsy revealed herpes simplex encephalitis involving the magnicellular neurons of the hypothalamus. CONCLUSION: Central diabetes insipidus caused by viral infections has been reported in immunosuppressed patients, such as those with acquired immunodeficiency syndrome (AIDS). To our knowledge, this is the first report of a herpes infection causing diabetes insipidus in a patient immunosuppressed by Cushing's syndrome. This case demonstrates that, in patients with Cushing's syndrome, diabetes insipidus may develop as a result of herpes simplex infection of the hypothalamus.

NPXY motif in the insulin-like growth factor-I receptor is required for efficient ligand-mediated receptor internalization and biological signaling.

The NPXY motif that was identified in the low density lipoprotein receptor serves as an internalization signal, and subsequent studies have indicated that the NPXY sequence is also an important recognition element for internalization of both insulin and transferrin receptors. The insulin-like growth factor (IGF-I) receptor contains an NPXY sequence (residues 947-950) in the immediate submembranous domain, and we sought to determine whether these residues play a role in facilitating ligand-mediated internalization of the IGF-I receptor. To study this, we have constructed stable cell lines expressing NPXY deletion mutant receptors (CHONPXY) or wild-type receptors (CHOWT). Ligand internalization studies showed that CHONPXY cells internalized [125I]IGF-I with a 40% defect (P < 0.005) compared to the CHOWT cells. Ligand-mediated receptor internalization and down-regulation were decreased by 90% in CHONPXY compared to CHOWT cells. The kinase activity of the mutant receptors was also defective as a result of removal of the NPXY motif. This is in contrast to the insulin receptor, in which deletion of the NPXY motif or deletions of even larger portions of amino acids in proximity to the NPXY motif do not affect the kinase activity of the receptor. Finally, the ability of the mutant receptors to mediate biological signaling is also defective, as measured by the thymidine incorporation assay.

Relative expression of insulin receptor isoforms does not differ in lean, obese, and noninsulin-dependent diabetes mellitus subjects.

The insulin receptor is expressed as two isoforms that differ by a 12-amino acid region at the carboxy-terminus of the alpha-subunit encoded by exon 11. These isoforms are produced by tissue-specific alternate splicing of the insulin receptor mRNA. To determine whether the relative expression of the isoforms is altered in skeletal muscle in two insulin-resistant states, NIDDM and obesity, relative mRNA levels were measured using a polymerase chain reaction technique. There were no differences in the relative amounts of skeletal muscle mRNA encoding the exon 11-containing form compared to the exon 11-lacking form of the insulin receptor among lean normal (30 +/- 2% Ex11-), obese nondiabetic (32 +/- 2%), and NIDDM (31 +/- 1%) subjects. We conclude that altered expression of insulin receptor isoform mRNAs does not account for skeletal muscle insulin resistance in NIDDM and obesity.