Nelson Wohllk G

[G691S, L769L and S836S ret proto-oncogene polymorphisms are not associated with higher risk to sporadic medullary thyroid carcinoma in Chilean patients].

Medullary thyroid carcinoma (MTC) may occur either assporadic or as hereditary. Even though the sporadic form corresponds to the majority of cases, thepathogenesis is still unclear. Several polymorphisms of the RET proto-oncogene, including those located inexon 11, 13, 14 and 15 have been described in the general population and some of them seem to be over-represented in sporadic MTC patients from European countries, especially G691S, L769L and S836S.

Mutaciones de línea germinal del proto-oncogen ret en pacientes chilenos con cáncer medular tiroideo hereditario y esporádico

Background: Medullary thyroid carcinoma (MTC) may occur either as a sporadic or familial disease. Multiple endocrine neoplasia (MEN) type 2, inherited as an autosomal dominant disease, is characterized by MTC only (FMTC) or coexistence of MTC with other endocrine neoplasia (NEM 2A, 2B). Germline mutations of the RET proto-oncogene (cRet) are found in the inherited forms and in some apparently sporadic MTC cases. Aim: To study RET mutations in 8 families with MEN 2. Material and methods: RET mutations were screened in peripheral blood DNA from 18 patients and 87 high risk carriers belonging to 8 MEN 2 families and 52 sporadic MTC. Exons 10, 11, 13, 14, 15 and 16 of the c-Ret were amplified by polymerase chain reaction (PCR) and examined by direct sequencing of PCR products and/or restriction enzyme analysis. Results: Five MEN 2A and one FMTC families with a germline mutation at codon 634, one MEN 2A and one FMTC family carrying a mutation at codon 620 were identified. Mutations were found in 23 out of 87 high risk carriers. In addition, we detected a S891A (exon 15) germline mutation in a sporadic MTC patient and in one out of her three sons and V804M (exon 14) in another sporadic MTC case and in one out of his six relatives, indicating in both cases the presence of a sporadic misclassified familial disease. Conclusions: These results underscore the importance of routine application of c-Ret testing in all cases of MTC either familial or sporadic. (Rev Med Chile 2001; 129: 713-8).

Consenso de diagnóstico y manejo de los nódulos tiroideos no palpables

With the availability of new diagnostic techniques, numerous alter-ations are found, whose real importance for health is uncertain. The term «incidentalomas», isused for non apparent tumors found in diagnostic procedures. In Endocrinology, the incidentalfinding of thyroid nodules is common. The occurrence of those incidental nodules requires a re-view of the «classical» statements for the management of palpable nodules. The most important is-sue is to rule out the presence of cancer. The Chilean Society of Endocrinology, Metabolism andNutrition appointed a group of experts to generate a consensus on the management of non palpa-ble nodules. These experts reviewed international literature, and the local experience, analyzedthe value of thyroid ultrasound examination and the efficiency of fine needle aspiration biopsy.This consensus is a clinical guide for the management of non palpable thyroid nodules, consider-ing that a unique and optimal approach is still lacking (Rev Med Chile 2004; 132: 1249-55).(

Neoplasias endocrinas múltiples: un modelo clínico para aplicar técnicas de genética molecular

Multiple endocrine neoplasias (MEN) are syndromes inherited as autosomal dominant. The application of the techniques of molecular biology has made possible the identification of the genes causing MEN 1 and 2. The gene responsable for MEN 1 belongs to the family of tumor suppressor genes and encodes for a protein named MENIN whose function remains to be elucidated. The identification of mutant MEN 1 gene carriers who are at risk of developing this syndrome requires frequent biochemical screening for the development of endocrine tumors. MEN 2 is a consequence of mutations in the Ret proto- oncogene (c-Ret). This gene encodes for a tyrosine kinase receptor thought to play a role in the development of neural crest- derived tissue. Members of kindred with either MEN 2A or MEN 2B should be screened by direct DNA testing early in life for mutations in c-Ret. Those with the mutation should be advised to have thyroidectomy at five years of age in children with MEN 2A and earlier in children with MEN 2B . Some cases of sporadic MTC are actually MEN 2A or Familial MTC after c-Ret testing is done, therefore routine application of this test is recommended in all cases of apparent sporadic MTC (Rev Med Chile 2000; 128: 811-20).

Resultados terapéuticos en pacientes acromegálicos: es tiempo de intervenir

Retrospective review of medical records of all patientswith acromegaly, operated between 1984 and 2004. When necessary, patients were contactedby telephone to complete information or to perform biochemical or imaging studies. A normalvalue of insulin like growth factor I (IGF-1) for age and sex, a growth hormone (GH) nadir ofless than 1 ng/ml during a glucose tolerance test or a basal GH of less than 2.5 ng/ml, allassessed three months after surgery, were considered as criteria for cure.BACKGROUND The treatment of choice for acromegaly is surgery that, according to the literature, is curative in 91% of pituitary microadenomas and 73% of macroadenomas. AIM To report the results of surgical treatment in 53 patients with acromegaly. MATERIAL AND METHODS Retrospective review of medical records of all patients with acromegaly, operated between 1984 and 2004. When necessary, patients were contacted by telephone to complete information or to perform biochemical or imaging studies. A normal value of insulin like growth factor I (IGF-1) for age and sex, a growth hormone (GH) nadir of less than 1 ng/ml during a glucose tolerance test or a basal GH of less than 2.5 ng/ml, all assessed three months after surgery, were considered as criteria for cure. RESULTS Biochemical cure was achieved in 67% of patients with pituitary microadenomas and 21% of patients with macroadenomas. In 47% of patients with neuro-ophtalmological involvement, a partial or total recovery in the visual field defect was achieved. The most common surgical complications were transient diabetes insipidus in 19%, persistent diabetes insipidus in 4% and cerebrospinal fluid fistula in 4%. A lower size of the tumor and lower preoperative growth hormone levels were associated with a better chance of cure. CONCLUSIONS The cure rates obtained in this group of patients are clearly lower than those reported abroad. These results stress the importance of having a national registry of acromegaly and the need to train neurosurgeons in the treatment of pituitary tumors.

Tiroidectomía profiláctica en niños y jóvenes con cáncer medular tiroideo hereditario: Experiencia chilena

Background: With the availability of the RET proto-oncogene genetic testing, it is possible to perform prophylactic total thyroidectomy among carriers of RET mutation. Aim: To evaluate the histological findings and the effects of the prophylactic total thyroidectomy in firstdegree relatives of Chilean patients with multiple endocrine neoplasia type 2 (MEN 2) based on the Ret proto-oncogen analysis. Subjects and Methods: Nineteen patients belonging to 11 MEN 2 families underwent total thyroidectomy. Of these, 16 either with C cell hyperplasia (CCH) or microscopic medullary thyroid carcinoma (MTC) were selected for the final analysis. Results: The age at the moment of thyroidectomy ranged from 3 to 24 years (median 9.5). The most common mutation was located in codon 634 (69%) followed by codon 620 (25%). Histopathology revealed MTC in 13 patients (81%, youngest 3 years, oldest ones 19 and 24 years) and CCH in 3. A significant correlation was observed between basal preoperative serum calcitonin/tumor size (r= 0.53, P <0.05) and age/tumor size (r= 0.56, P <0.03), but not between basal preoperative serum calcitonin and age. Stimulated preoperative calcitonin levels were confounding and not useful for differentiating CCH from MTC. None of patients in whom cervical dissection was done (9/16) presented lymph node metastases, including the oldest ones. All patients but the older ones were biochemically cured after a mean of 5 years of follow-up. Conclusion: Prophylactic total thyroidectomy should be done early in life because there is an age-dependent progression from HCC to MTC. MTC often precedes biochemical detection of the disease (Rev Med Chile 2005; 133: 1029-36). (Key Words: Multiple endocrine neoplasia type 2; Thyroidectomy; Thyroid neoplasms)

Tratamiento con radioyodo del bocio difuso hipertiroideo: influencia del pretratamiento con propiltiuracilo

BACKGROUND To stabilize Graves disease and deplete the preformed hormone, the use of antithyroid drugs prior 131I therapy has been suggested, specially in those patients with severe thyrotoxicosis and in the elderly. However, PTU may reduce the effectiveness of 131I. AIM To study the effects of PTU pretreatment before 131I administration. SUBJETS AND METHODS: A retrospective analysis of the medical records of patients with Graves disease treated with 131I from 1989 to 1997 was made. Of 244 patients with adequate follow-up for at least 12 months after 131I treatment, 142 had not been pretreated and 102 had received PTU prior to 131I therapy. Pretreated patients were distributed according to the number of days that PTU was discontinued before receiving 131I, forming four groups (a = 5 d, b = 6-14 d, c = 15-30 d and d = 31-60 d). Radioiodine was delivered according to our protocol of 120 microCi per gram of thyroid tissue, as estimated by clinical examination. Therapy was considered successful when laboratory evidence of euthyroidism or hypothyroidism after one year of treatment was obtained and as a failure when undetectable TSH values persisted after 12 months of treatment with 131I. RESULTS All groups were comparable as to age, gender, goiter size, and 24 h radioiodine uptake. Control of hyperthyroidism was achieved in 76% of the non pretreated group. A similar percentage was observed in groups (b), (c) and (d). However, the disease was controlled in only 50% of group (a) patients (p < 0.003). CONCLUSIONS The therapeutic efficacy of 131I is significantly reduced when the PTU is stopped for only a few days prior to the use of radioiodine. We postulate that PTU has to be discontinued for at least 10 days before radioiodine administration.