Late diagnosis of congenital adrenal hyperplasia due to 21-hydroxylase deficiency.

Congenital adrenal hyperplasia results from 21-hydroxylase deficiency in more than ninety percent of cases. The classical form of 21-hydroxylase deficiency presents in the neonatal period with virilization or adrenal insufficiency, with or without concurrent salt wasting. We report on a rare case of classic 21-hydroxylase deficiency diagnosed in late adulthood. A 39-year-old male patient presented for workup of infertility. Urologic investigation revealed small testes, bilateral testicular masses, and asthenozoospermia. The patient's steroid metabolism showed markedly increased levels of adrenal androgens, in particular of 17-hydroxyprogesterone amd 21-deoxycortisol. The gas chromatographic-mass spectrometric (GC-MS) urinary steroid profile was dominated by metabolites of 17-hydroxyprogesterone, while the endogenous glucocorticoid production was subnormally low. ACTH levels in plasma were elevated. These hormonal findings were consistent with 21-hydroxylase deficiency. Therapy with dexamethasone was initiated. The CTP21A2 gene analysis revealed the mutation I172N (ATC --> AAC) in exon 4 of allele 1 and a large gene deletion in allele 2. Cases of 21-hydroxylase deficiency diagnosed in late adulthood are rare; however, clinicians should be alert of this possibility.     

Phylogenetic analysis of the hexon loop 1 region of an adenovirus from psittacine birds supports the existence of a new psittacine adenovirus (PsAdV)

Summary. Adenovirus infections in psittacine birds have been well known. Most of these infections were caused by fowl adenoviruses (FAdV). In this study, liver samples showing typical histological signs of an adenovirus infection were collected from Poicephalus spp. with acute disease. A PCR amplifying the variable loop 1 region of the hexon gene was developed using primers located in two conserved pedestal regions. A PCR product of approximately 590 bp in size was amplified and sequenced. The sequence obtained grouped outside of the FAdV reference strains of the 12 serotypes as well as egg drop syndrome virus and turkey adenovirus 3 indicating that a new avian adenovirus was detected. In comparison to the FAdV reference strains, the percentage of identical nucleotides ranged between 60.3 and 67.0 and that of identical amino acids (aa) between 51.3 and 61.0. Furthermore, 37 unique aa exchanges were observed; out of these, 27 are located in the 4 hypervariable regions of loop 1, which encode the serotype-specific epitops. The g/c content, the isoelectric point and the charge of the amplified fragment, however, are in the range as those of group I avian adenoviruses. It was proposed, therefore, to designate this new adenovirus as psittacine adenovirus (PsAdV).     

Presymptomatic genetic screening in families with multiple endocrine neoplasia type 2

Medullary thyroid carcinoma occurs sporadically or as a part of the inherited cancer syndrome multiple endocrine neoplasia (MEN) type 2. The MEN 2 gene has been identified as the RET proto-oncogene on chromosome 10. In MEN 2A, RET mutations are detectable in one of five cysteine codons within exons 10 and 11 and in MEN 2B in codon 918 (exon 16). Direct DNA testing for RET proto-oncogene mutations is the method of first choice in presymptomatic screening of MEN 2 families. Gene carriers should be offered prophylactic thyroidectomy. The process of DNA analysis for RET proto-oncogene mutations is demonstrated in one family with hereditary medullary thyroid carcinoma. RET mutations were detectable in five of the nine family members at risk.Abbreviations MEN Multiple endocrine neoplasia - MTC Medullary thyroid carcinoma - FMTC Familial medullary thyroid carcinoma - PCR Polymerase chain reaction - C-cells Calcitonin-producing parafollicular cells     

Diagnostik des Schilddrüsenkarzinoms

Most thyroid cancers are well differentiated, grow slowly, and have a good prognosis. They account for less than 1% of all malignancies with an incidence of 3 per 100,000. Clinical presentation of thyroid cancer is a late event induced by local infiltration and the development of cervical lymph nodes. The problem of early diagnosis of thyroid cancer is the high prevalence rate of thyroid nodules in the German population (30%) and the low malignancy rate (1–2%). Diligent work-up is necessary including evaluation of risk factors, routine ultrasonography of the thyroid, thyroid scintigraphy and in all hypoechogenic, cold nodules >1 cm diameter fine-needle aspiration as well as fine-needle aspiration in all rapidly growing nodules. Calcitonin determination in all thyroid nodules and if slightly elevated a pentagastrin stimulation test is recommended for early detection of medullary thyroid carcinoma. A familial variant occurs in 25% of medullary thyroid carcinomas which can be confirmed by RET mutation analysis. Further family studies identify asymptomatic gene carriers who can be cured by early prophylactic thyroidectomy, which improves the overall mortality rate and prognosis.     

Difference in development of medullary thyroid carcinoma among carriers of RET mutations in codons 790 and 791

Objectives Hereditary medullary thyroid carcinoma (MTC) is caused by germ‐line mutations in the RET proto‐oncogene. Our study addresses the difference in development of MTC between rare mutations in RET codons 790, 791 and 804. Design We evaluated tumour stage, calcitonin levels, biochemical cure rates and associated endocrinopathies in 153 German/Austrian patients with RET 790 (n = 47), 791 (n = 56) and 804 mutations (n = 50), divided into index‐ and screening groups. Results Age at diagnosis in index‐patients did not differ significantly among the three codon groups (medians of 57, 61 and 53 years). Tumour stage at diagnosis was significantly less advanced with codon 791 (n = 22) than 790 (n = 16) and 804 (n = 16) mutations (P = 0·001). In screening patients, age at diagnosis did not differ significantly among the three groups (medians 19, 24 and 32 years). Tumour stage at diagnosis was also significantly less advanced with codon 791 (n = 34) than 790 (n = 31) and 804 (n = 34) (P = 0·032). Preoperative basal calcitonin levels were significantly lower in codon 791 carriers compared to codon 790 carriers, and cure rates were significantly higher in both index (75%vs. 31%; P = 0·03) and screening patients (100%vs. 75%; P = 0·015). Additional endocrinopathies were observed only with codon 791 carriers (four pheochromocytomas and two hyperparathyroidism). Conclusion There is a significant difference in MTC development with less extensive C‐cell disease, higher cure rate and more frequent additional endocrinopathies in carriers of RET codon 791 mutations compared with carriers of codons 790 and 804 mutations. This information should be considered when age of prophylactic thyroidectomy is discussed.     

Combination chemotherapy of advanced medullary and differentiated thyroid cancer

Summary A group of 20 patients with advanced medullary (MTC) or differentiated thyroid carcinoma (DTC) received a combination chemotherapy of doxorubicin (50 mg/m²), cisplatin (60 mg/m²) and vindesine (3 mg/m²). In the 18 (10 MTC, 8 DTC) evaluable patients only 1 partial remission (in a patient with MTC) and 3 minor responses (in 3 patients with DTC) were observed. These responses lasted for 15, 9, 13, and 22 months, respectively. Three MTC patients suffered from progressive disease and no change was seen in the other 11 patients. Toxicity, including 1 severe case of cardiomyopathy, was considerable. Thus, the combination chemotherapy of doxorubicin, cisplatin and vindesine has failed to prove superior to the commonly applied doxorubicin monotherapy in patients with advanced medullary or differentiated thyroid carcinoma.Abbreviations MTC, DTC medullary and differentiated thyroid carcinoma This study was supported by a grant of the German Cancer Research Center (Tumorzentrum Heidelberg/Mannheim)     

Investigation of Historical Hard Rubber Ornaments of Charles Goodyear

Charles Goodyear discovered the vulcanization process of natural rubber in the middle of the 19th century. In this paper, original ornaments produced by Charles Goodyear are investigated. Additionally, for comparison, a sample is produced according to Goodyear's patent (US 3633) as reference. Contrary to expectation, it is found that Charles Goodyear did not prepare the ornaments using the formulation of his patent, thus he excluded the white lead. Due to this, another reference sample is produced like the other but without white lead. It is proven that by artificial aging, natural rubber samples can get properties similar to the 150 years old rubber sample.

     

Clinical relevance of RET variants G691S, L769L, S836S and S904S to sporadic medullary thyroid cancer

Background Based on reports of higher frequencies among patients with sporadic medullary thyroid cancer (MTC) relative to external controls, the RET (REarranged during Transfection) variants G691S, L767L, S836S and S904S have been considered disease modifiers, suggesting greater lifetime risks of MTC. Other studies, employing different external controls, failed to confirm this association. Using a complementary approach, this study aimed at exploring differences in clinico‐pathological characteristics among patients with sporadic MTC carrying no (wildtype), one (heterozygotes) or both (homozygotes) homologue RET variants in the germline, with wildtype cases acting as internal controls. Methods Included in this investigation were 150 patients with complete genetic information on G691S, L769L, S836S and S904S RET alleles operated on for sporadic MTC at a tertiary referral centre. Results Not one statistically significant dose–response relationship was identified between any RET variant (wildtype vs RET heterozygotes vs homologue RET homozygotes) and patient age at MTC diagnosis, gender, primary tumour size, extrathyroidal extension, numbers of involved and removed lymph nodes, or distant metastasis. L769L and S836S homozygotes, unlike G691S and S904S homozygotes, were either rare or absent, limiting the analyses to comparisons of heterozygosity versus wildtype. On time‐to‐event analysis, G691S, L769L, S836S or S904S carriers and noncarriers developed MTC at similar rates. Conclusions In carriers and noncarriers of the RET variants G691S, L767L, S836S and S904S, sporadic MTC appeared clinically and pathologically indistinguishable. This observation, along with the inconclusive evidence of previous association studies, calls for larger longitudinal association studies with age‐ and sex‐matched external controls and additional functional studies of RET biology.     

Initial Results after Implementation of a Multimodal Treatment for Peritoneal Malignancies

Introduction : Peritoneal carcinomatosis represents a clinical condition with a limited perspective concerning long term survival. The combination of surgical cytoreduction and hyperthermic intraperitoneal chemotherapy (HIPEC) represents a complex multimodal therapeutic management concept with promising results for prolongation of survival. For the identification of pitfalls during implementation of the HIPEC procedure into clinical practice an observational study was conducted.

Methods : Between 2005 and 2009 data from all patients treated with cytoreductive surgery and HIPEC for peritoneal carcinomatosis was prospectively collected and analysed.

Results : During the observational interval a total of 42 patients underwent surgical treatment for peritoneal carcinomatosis. In 34 patients the complete procedure with surgical cytoreduction and HIPEC was performed. Perioperative mortality (6%) and morbidity (35%) was similar to other reported series. Twenty-five patients (76%) survived the 18 months follow-up period after complete procedure.

Conclusion : The multimodal therapeutic treatment concept of surgical cytoreduction and following HIPEC leads to promising results for patients suffering from peritoneal carcinomatosis. However this treatment concept is afflicted with a relevant risk of postoperative complications.