A rare iatrogenic association of syndrome of inappropriate secretion of antidiuretic hormone, neuroleptic malignant syndrome and rhabdomyolysis.

Syndrome of inappropriate antidiuretic hormone secretion (SIADH) is considered the prevalent cause of hyponatremia in hospitalized patients. Neuroleptic malign syndrome (NMS) is an idiosyncratic drug reaction showing fever, dysautonomia and rigidity with increased levels of Creatinine-phosphokinase (CPK) dependent on leakage of muscle contents into the circulation and defined as rhabdomyolysis. Although different diagnostic criteria for NMS have been established, it should be recognized that atypical presentations occur, particularly during treatment with atypical antipsychotics. We here present a case report of a psychiatric patient affected by a SIADH complicated with NMS/rhabdomyolysis, induced by second-generation (atypical) antipsychotic drugs in combination with carbamazepine and promazine.

Localized herpes zoster infection: a rare cause of syndrome of inappropriate secretion of antidiuretic hormone.

Hyponatremia is the most common electrolyte abnormality observed in clinical practice and syndrome of inappropriate secretion of antidiuretic hormone (SIADH) is diagnosed in nearly 40% of the hospitalized hyponatremic patients. We present a case report of herpes zoster infection causing a severe hyponatremia/hypokalemia. This rare association between SIADH and varicella-zoster virus infection is described in only few case in the literature. In our case report, the associated hypokalemia was not related to the use of diuretics but, probably, dependent on the frank serum hyposmolality able to induce an aldosterone release.

Prevalence of Y microdeletions in azoospermic and severe oligozoospermic men in Southern Italy: application of a rapid capillary electrophoresis method.

Male infertility is correlated with several genetic and non-genetic conditions. Microdeletions of Y chromosome are one of the most frequent genetic defects associated with male infertility. Evaluating this in infertile patients is important to assess an etiological diagnosis and possible prognosis of infertility, as well as to address clinical decision during treatment of infertility by intracytoplasmatic sperm injection, where the probability of success depends on the type and the number of deleted regions (azoospermia factor regions). To improve genetic counseling, it is useful to characterize Yq regions by a rapid and accurate method. In the current study, we evaluated the diagnostic efficiency and the time required of an in-house automated capillary electrophoresis method for Y microdeletions screening and applied it to estimate the prevalence of Y microdeletions in 100 infertile males affected by azoospermia or severe oligozoospermia (sperm count <5x10(6)/ml) and in 100 fertile male controls. In south Italian infertile men, the overall frequency of Y microdeletions was 9% (12.7% in azoospermic and 4.5% in severe oligozoospermic men). In conclusion, we think that the abovementioned procedure is suitable for the routine characterization of Y microdeletions.

RAS and MTHFR gene polymorphisms in a healthy exercise-trained population: association with the MTHFR (TT) genotype and a lower hemoglobin level.

The aim of this study was to determine the frequencies of ACE (I/D), AGT (M235T), AT1R (A1166C) and MTHFR (C677T) polymorphisms in a well-defined (in regards to health and nutritional status and lifestyle) population of young, healthy, exercise-trained subjects (no. 100) from the Campania region of Southern Italy. We also investigated whether there was any correlation between these polymorphisms and biochemical, hematological and hemostatic parameters in this "low-risk" population. Gene polymorphisms were analyzed with the polymerase chain reaction and restriction enzyme analysis. Allele frequencies of the genotypes examined were in Hardy-Weinberg equilibrium and agree with those reported in the Italian population. No associations were found between ACE, AGT, AT1R gene polymorphisms and anthropometric, clinical and laboratory parameters. However, the MTHFR (C677T) polymorphism was significantly associated with lower hemoglobin plasma levels in TT vs. CC + CT females (p < 0.016). This report is the first to describe the frequencies of RAS and MTHFR gene polymorphisms in young, exercise-trained volunteers from Campania and to identify an association between the MTHFR gene polymorphisms and lower hemoglobin plasma levels in young healthy females.

Loss of heterozygosity at the RET protooncogene locus in a case of multiple endocrine neoplasia type 2A.

We describe a patient affected by multiple endocrine neoplasia type 2A (MEN 2A) bearing a heterozygous germline mutation (Cys(634)Arg) in exon 11 and an additional somatic mutation of the RET protooncogene. A large intragenic deletion, spanning exon 4 to exon 16, affected the normal allele and was detected by quantitative PCR, Southern blot analysis, and screening of several polymorphic markers. This deletion causes RET loss of heterozygosity exclusively in the metastasis, thus suggesting a role for this second mutational event in tumor progression. No additional mutations were found in the other exons analyzed. We provide the first evidence that RET, a dominant oncogene, is affected by a germline mutation and by an additional somatic deletion of the wild-type allele. This unusual genetic profile may be related to the clinical course and very poor outcome.

Germline and somatic mutations of the RET proto-oncogene in apparently sporadic medullary thyroid carcinomas.

Medullary thyroid carcinomas (MTC) occur sporadically or as part of inherited multiple endocrine neoplasia (MEN) type 2 syndromes. To recognize misdiagnosed familial cases and to establish the frequency of somatic mutations, a series of 50 patients, clinically diagnosed with sporadic MTC, were analyzed for mutations in the RET proto-oncogene. The clinical management of the patient and of the family is different in the two cases. Germline mutations were detected in three independent cases, demonstrating that they were associated to familial MTC. The mutations affected exon 11 in two cases and exon 14 in one case. Somatic mutations were detected in eight patients (30%) and they were indicative of sporadic MTC. In seven cases the mutation affected codon 918 of exon 16 and in one case codon 634 in exon 11. No RET mutations were detected in the remaining patients. A different genetic and clinical management is proposed for individuals with a diagnosis of familial or sporadic MTC.

Seventeen-year-long follow-up of a family affected by type 2A multiple endocrine neoplasia (MEN 2A).

This paper reports the results of a 17-year-long follow-up covering 17 members of a family affected by multiple endocrine neoplasia (MEN) type 2A, first diagnosed in 1980. This family is enrolled in our screening program. The thyroid, parathyroid and adrenal glands of the family members were investigated using the most sophisticated and sensitive techniques which have become available during this period, and their DNA was genetically tested for detecting RET mutations. Thanks to the combination of these two approaches it was possible to confirm the diagnosis in the members concerned from the genetic point of view, and to achieve an early diagnosis in the young members of the last generation before the clinical onset of the disease. The detection of a RET mutation also prompted a prophylactic thyroidectomy in a four year-old boy, in a pre-tumoral stage of the disease. Lastly, evidence is provided that genetic analysis of the DNA of the chorionic villi can be carried out as a prenatal test during routine amniocentesis.

A novel point mutation in the intracellular domain of the ret protooncogene in a family with medullary thyroid carcinoma.

Specific mutations in the ret protooncogene have been found associated with multiple endocrine neoplasia type 2A (MEN 2A) and type 2B (MEN 2B) and familial medullary thyroid carcinoma (FMTC). Mutations in one of five cysteine residues in the extracellular domain have been found in over 95% of families with MEN 2A and 88% of families with FMTC. In MEN 2B patients, a specific mutation at codon 918, substituting a threonine for a methionine, has been found in 95% of cases. In FMTC, in addition to the mutations of the extracellular cysteines, three intracellular base pair changes have been reported at codons 768 and 804. Here we describe a novel intracellular mutation in exon 15 of the ret gene that leads to the substitution of an alanine for a serine at codon 891 in a family with medullary thyroid carcinoma. This amino acid change may be important in determining substrate specificity or, alternatively, may play a role in ATP binding.

A primary, lateral-cervical medullary thyroid carcinoma: a case report.

Medullary thyroid carcinoma (MTC) arises from the parafollicular cells of the thyroid and occurs in a sporadic or in an inherited form. We present a case of an aberrant MTC in a patient with a functioning thyroid gland. At surgical dissection, the thyroid was present in its anatomical site with a nodule in the upper one third of the right lobe. A mass was also found in a lateral-cervical position distinct from the thyroid gland. Histological examination showed the mass to be the primary MTC, whereas the thyroid nodule was a follicular adenoma. Analysis of DNA extracted from the MTC, from the adenoma, and from peripheral blood revealed a mutation within exon 16 of the RET proto-oncogene only in the DNA from the tumor. The reported case represents a sporadic MTC in an aberrant localization, probably originating from a developmental abnormality of the primordial C cells. This event might have occurred during the migration and/or differentiation of the C cells and might be related to, or caused by, the mutated RET proto-oncogene.

A mutation in the RET proto-oncogene in Hirschsprung's disease affects the tyrosine kinase activity associated with multiple endocrine neoplasia type 2A and 2B.

We demonstrate that a Hirschsprung (HSCR) mutation in the tyrosine kinase domain of the RET proto-oncogene abolishes in cis the tyrosine-phosphorylation associated with the activating mutation in multiple endocrine neoplasia type 2A (MEN2A) in transiently transfected Cos cells. Yet the double mutant RET2AHS retains the ability to form stable dimers, thus dissociating the dimerization from the phosphorylation potential. Co-transfection experiments with single and double mutants carrying plasmids RET2A and RET2AHS in different ratios drastically reduced the phosphorylation levels of the RET2A protein, suggesting a dominant-negative effect of the HSCR mutation. Also, the phosphorylation associated with the multiple endocrine neoplasia type 2B (MEN2B) allele was affected in experiments with single and double mutants carrying plasmids co-transfected under the same conditions. Finally, analysis of the enzymic activity of MEN2A and MEN2B tumours confirmed the relative levels of tyrosine phosphorylation observed in Cos cells, indicating that this condition, in vivo, may account for the RET transforming potential.