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 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.

Prevalence of antisperm antibodies by SpermMARtest in subjects undergoing a routine sperm analysis for infertility.

To evaluate the prevalence of antisperm antibodies (ASA) attached to the sperm plasma membrane in male partners of infertile couples, the binding of latex particles to spermatozoa was investigated using SpermMARtest, included routinely in semen analysis. A total of 860 men were examined, who were referred consecutively for semen analysis. Of these, 750 men were referred because of infertility (0.6-10 years in duration) whereas 110 were volunteers with a history of previous fertility. Samples were assessed by the SpermMARtest kit using latex particles sensitized with human IgG. Sperm-latex binding was read after 3 min and samples scored as negative, positive or highly positive when < 10, > 10-40, or > 40% binding occurred, respectively. Of the samples 132 (17.3%) were excluded because of azoo- or severe oligo-asthenozoospermia. IgG attached to spermatozoa were detected in nearly 13% of semen samples from the infertile population and in one of 110 fertile men (0.9%). From the infertile group, 6.2% of samples showed > 40% binding, and 6.7% intermediate binding, with an overall ASA prevalence of 12.9% in subjects undergoing semen analysis for infertility.

Late gonadal function and autoimmunization in familial testicular torsion.

Testicular torsion, one of the most common pediatric urological emergencies, is rarely familial. This study deals with the sixth recorded family with familial testicular torsion and the effects on the spermatogenesis and the appearance of testicular autoantibodies in three affected subjects (two brothers, aged 18 and 15 years, and their father, aged 48 years). The father and one of the brothers, who had peripubertal unilateral testicular torsion, presented normal fertility and oligozoospermia, respectively. The other brother, who had a history of bilateral testicular torsion, did not present pubertal development until he was 18 years old and he needed substitutive testosterone therapy. Sperm autoantibody titer increased only in the two cases with unilateral torsion and remained unmodified at a 5-year follow-up. The results indicate that testicular torsion can cause variable degrees of spermatogenesis impairment and induce development of autoantibodies against spermatozoa and gonadal antigens. The persistence of fertility in the father and the progressive spermatogenesis recovery in one of the affected sons suggest that the damaging effects of these autoantibodies deserve further investigation.