Manejo multidisciplinario de la acromegalia / Multidisciplinary management of acromegaly

Acromegaly is a chronic disease caused in most cases by hypophysiary adenoma. It is of complex management due to the high variability of the causing lesion and its clinical repercussion. Surgical outcomes are poor with remission rates of 80 percent for microadenomas and 50 percent for macroadenomas. The author's experience in treating 38 patients with this pathology as well as the remission results of the illness and the complications are presented herein. Handling alternatives and associated complications are discussed and a clinical case is presented to show the therapeutical options in more complex cases.

La acromegalia es una enfermedad crónica causada en la mayoría de los casos por un adenoma hipofisario. Su manejo es complejo por la gran variabilidad de la lesión causante y su repercusión clínica. Los resultados quirúrgicos son pobres, con tasas de remisión de la enfermedad en promedio de un 80 por ciento en microadenomas y 50 por ciento en macroadenomas. Se presenta la experiencia del autor en el manejo de esta patología en 38 pacientes, los resultados de remisión de la enfermedad. Se discute las alternativas de manejo, complicaciones asociadas y se ilustra con un caso clínico para demostrar las opciones terapéuticas en los casos más complejos.

Hiponatremia grave como manifestación inicial de síndrome de Sheehan de diagnóstico tardío: caso clínico / Hyponatremia secondary to panhypopituirarism: report of one case

Hyponatremia is common among older people and its possible causes are not thoroughly investigated in this age group. We report a 69 years old female with a history of hypothyroidism in treatment that consulted for malaise, anorexia and a severe hyponatremia that required hospital admission. A new interrogation, revealed that the patient suffered an uterine hemorrhage in 1977, remaining with agalactia. She also referred asthenia since 1990. Her serum cortisol was below normal limits and a sella turcica magnetic resonance imaging revealed a pituitary atrophy. The patient was treated with cortisol and discharged in good conditions.

Cortisol plasmático basal matinal como predictor de indemnidad del eje hipotálamo hipófisis suprarrenal / Basal morning serum cortisol for the assessment of hypothalamic, pituitary adrenal axis function

The study of hypothalamic, pituitary adrenal axis function requires complex tests. However, themeasurement of basal morning serum cortisol levels may be a simple measure to evaluate this axis. AIM: To determine if an isolated morning measurement of basal serum cortisol levels in the absence of stress, may predict the indemnity of the hypothalamic, pituitary adrenal axis. MATERIAL AND METHODS: Morning cortisol levels in the basal period and 30 minutes after the injection of 50 ug ACTH were measured in 76 patients with a mean age of 52 years (48 females), operated of a pituitary tumor, without cushing syndrome and not using steroids or oral estrogens. Twenty healthy volunteers with a mean age of 30 years (11 males) were studied as controls. In this last group, the lower limit of normal stimulated cortisol levels was defined as the mean value less two standard deviations and corresponded to 17 ug/dL. RESULTS: Based on stimulated cortisol levels, 15 percent of operated patients had a hypothalamic, pituitary adrenal axis dysfunction. Using cut-off levels of less than 5, 7.5 and 10 ug/dL, basal cortisol levels had a sensitivity for the diagnosis of hypothalamic, pituitaryadrenal axis dysfunction of 64, 81 and 100 percent, respectively. The figures were 100, 95 and 66 percent for specificity respectively, 100, 75 and 34 percent for positive predictive value and 94, 97 and 100 percent for negative predictive value. CONCLUSIONS: A basal morning cortisol value over 10 ug/dL discards the presence of hypothalamic, pituitary adrenal axis dysfunction and a value lower than 5 ug/dL confirmed alteration in all of the cases.

Resultados Terapéuticos en pacientes acromegálicos: es tiempo de intervenir / Results of surgical treatment for acromegaly in 53 patients

Background: The treatment of choice for acromegaly is surgery that, according to the literature, is curative in 91 percent of pituitary microadenomas and 73 percent 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 percent of patients with pituitary microadenomas and 21 percent of patients with macroadenomas. In 47 percent 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 percent, persistent diabetes insipidus in 4 percent and cerebrospinal fluid fistula in 4 percent. 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 / Prophylactic thyroidectomy in children and young people with hereditary medullary thyroid carcinoma: A Chilean experience

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 first-degree 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.

Polimorfismos G691S, L769L y S836S del proto-oncogen RET no se asocian a mayor riesgo de cáncer medular tiroideo esporádico en pacientes chilenos / G691S, L769L and S836S ret proto-oncogene polymorphisms are not associated with higher risk to sporadic medullary thyroid carcinoma in Chilean patients

Background: Medullary thyroid carcinoma (MTC) may occur either as sporadic or as hereditary. Even though the sporadic form corresponds to the majority of cases, the pathogenesis is still unclear. Several polymorphisms of the ret proto-oncogene, including those located in exon 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. Aim: To evaluate the allele frequencies of these variants in Chilean patients and controls and to determine if these polymorphisms would be associated with the development of sporadic MTC from a different genetic population base. Subjects and Methods: Fifty sporadic MTC patients and 50 normal subjects were tested for G691S, L769L, S836S and S904S polymorphisms. The extracted genomic DNA was initially analyzed by direct sequencing of PCR products in patients. The presence or absence of each polymorphism was also assessed in patients and in control by restriction digestion. Results: The allele frequencies showed a similar level of the G691S, L769L and S904S variants in both groups. Of interest, we found an under-representation of S836S polymorphism in the sporadic MTC group but this number was not statistically significant (p=0.141). Conclusions: We did not find an over representation of the G691S, L769 and S836S. These results argue against the validity of the association of these polymorphisms as contributing factors in the development of sporadic MTC based on a Chilean population and raise questions about the importance of these polymorphisms overall.

Consenso de diagnóstico y manejo de los nódulos tiroideos no palpables / Consensus report on the diagnosis and management of non palpable thyroid nodules

With the availability of new diagnostic techniques, numerous alterations are found, whose real importance for health is uncertain. The term <>, is used for non apparent tumors found in diagnostic procedures. In Endocrinology, the incidental finding of thyroid nodules is common. The occurrence of those incidental nodules requires a review of the <> statements for the management of palpable nodules. The most important issue is to rule out the presence of cancer. The Chilean Society of Endocrinology, Metabolism and Nutrition appointed a group of experts to generate a consensus on tbe management of non palpable nodules. These experts reviewed international literature, and the local experience, analyzed the 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, considering that a unique and optimal approach is still lacking.

Determinación del anticuerpo antirreceptor de TSH: experiencia en pacientes con patología tiroídea y controles / Determination of TSH antireceptor antibody: experience in patients with thyroid pathology and controls

In order to measure TSH receptor antibodies (TRAb) we tried to set up a radioreceptor assay using human thyroid membranes. Due to lack of appropriate binding activity of the material obtained, we decided to use a kit which provides solubilized porcine membrane-receptors to TSH instead of human membranes, as well as calibrators that have been standarized in a receptor assay against MRC LATS std B. With these reactives we have measured TRAb in sera from 7 normal controls (C), 54 thyrotoxic patients (43 diffuse goiters [BDH], 8 multinodular goiters [BDH] and 3 subacute Thyroiditis [TSA], 3 patients with Hashimoto's Thyroiditis (TH) and 6 non-hyperthyroid Graves ophtalmopathy patients. Measurement were initially performed using calibrators and the results expressed as U/L; since a very good correlation between the expression U/L and the calculated inhibition Index (I.I.) was found (r=0.99, n=15, p<0,001), results are shown using latter. In C mean ñ SD value for I.I. was 3.4 ñ 2.37 percent so we decided to use, as cut off criteria for differentiating between normal and abnormal results, the figure 11 percent which represents the mean ñ 3 SD. According to this, 93 percent of BDH has elevated TRAb activity while only slightly more than one third of MBH had elevated values, this difference being highly significant (p<0,0001); both TSA and TH patients showed low TRAb activity while all Graves ophtalmopathy pts had elevated values, thus suggesting that they had a latent disease. We concluded that the methodology that is adequate and practical for clinical purposes. Our results show that measurement of TRAb activity is very useful in stablishing the etiology of hyperthyroidism in an individual patient. Also it provides help inthe differential diagnosis of patients with exoftalmus od unknown etiology. Its usefulness remains to be proved in the follow-up of BDH pts after been treated with antithyroid drugs

Evaluación de la tiroglobulinemia en el seguimiento del carcinoma diferenciado del tiroides tratado / Thiroglobulinemia evaluation in the treated thyroid differential carcinoma follow up

Se analizan 110 pacientes con cáncer diferenciado del tiroides luego de ser tratados y en los cuales se realiza un seguimiento con tirogloobulinemia en forma periódica durante los últimos 10 años. En un grupo de ellos se realiza estudio comparativo con la cintigrafía de cuerpo entero. Al analizar la evaluación se concluye que la Tg es un excelente marcador tumoral con una sensibilidad de 92,8 por ciento y una especificidad de 88,5 por ciento , constituyéndose en el mejor método para el seguimiento y control de este tipo de pacientes, con la ventaja de la cintigrafía que no necesita la suspensión de la terapia sustitutiva y que es capaz de detectar lesiones no funcionantes desde el punto de vista isotópico