Tratamiento médico de la acromegalia con antagonistas del receptor de GH / Medical treatment of acromegaly with growth hormone (GH) receptor antagonists

Los pacientes con acromegalia presentan una morbilidad y mortalidad entre 2 y 3 veces superior a la de la población general, especialmente por enfermedad cardiovascular. A pesar de los tratamientos disponibles actualmente (cirugía transesfenoidal, radioterapia, agonistas dopaminérgicos y análogos de somatostatina), un porcentaje importante de pacientes con acromegalia no alcanza un buen control de su enfermedad. Pegvisomant es el primero de un nuevo grupo de fármacos para el tratamiento de la acromegalia, son antagonistas del receptor de la hormona del crecimiento, que no actúan directamente sobre el adenoma hipofisario, sino que bloquean la acción de la hormona de crecimiento en los tejidos periféricos. Los estudios publicados hasta el momento muestran que se trata del fármaco más eficaz y específico para el tratamiento de la enfermedad, consiguiendo la normalización de los valores de factor de crecimiento similar a la insulina tipo I (IGF-I) en más del 90% de los pacientes, con independencia de las características del tumor. Pegvisomant ha sido bien tolerado hasta la fecha, con apenas efectos secundarios, entre los que destaca la hepatotoxicidad. Datos extraídos de los primeros estudios publicados parecen demostrar un efecto beneficioso de pegvisomant sobre la resistencia a la insulina, en comparación con los análogos de somatostatina. Su alto coste, los dilemas planteados por la necesidad de utilizar el IGF-I como único marcador de la actividad de la enfermedad y la posibilidad de crecimiento tumoral son los principales inconvenientes del tratamiento. En la actualidad pegvisomant es un tratamiento de segunda línea eficaz en el tratamiento de la acromegalia, especialmente útil en los pacientes resistentes a otras alternativas terapéuticas (AU)

Morbidity and mortality in patients with acromegaly is between 2 and 3 times higher than in the general population, especially that due to cardiovascular disease. In a substantial percentage of patients, currently available treatments (transphenoidal surgery, radiotherapy, dopaminergic agonists and somatostatin analogs) fail to adequately control the disease. Pegvisomant is the first of a new group of drugs for the treatment of acromegaly, GH receptor antagonists, which do not act directly on the pituitary adenoma but rather block the action of GH in the peripheral tissues. Studies published to date show that pegvisomant is the most effective and specific drug for the treatment of acromegaly, achieving a return to normal insulin-like growth factor (IGF)-I values in more than 90% of patients, independently of the characteristics of the tumor. So far, this drug has been well tolerated, with few adverse effects, the most important of which is hepatotoxicity. Data from the first published studies seem to demonstrate a beneficial effect of pegvisomant on insulin resistance in comparison with somatostatin analogs. The main disadvantages of this treatment are its high cost, the dilemmas posed by the need to use IGF-I as the only marker of disease activity and the possibility of tumoral growth. Currently, pegisomant is a second-line drug in the treatment of acromegaly and is especially useful in patients who do not respond to other therapeutic alternatives (AU)

Treatment of invasive growth hormone pituitary adenomas with long-acting somatostatin analog SMS 201-995 before transsphenoidal surgery.

The purpose of this study was to determine whether the long-acting somatostatin analog SMS 201-995 (octreotide) shrinks growth hormone (GH)-secreting adenomas and improves the results of subsequent transsphenoidal surgery. Ten previously untreated active acromegalic patients (nine women and one man) with invasive tumors were treated with SMS 201-995 (100 micrograms subcutaneously every 8 hours) for 6 weeks prior to transsphenoidal surgery. The clinical activity, mean GH secretion, insulin-like growth factor (IGF)-I concentration, and tumor volume were measured under basal conditions and on Days 14, 28, and 42 of treatment. The SMS 201-995 improved the symptoms of acromegaly in all patients. Mean levels of both GH and IGF-I (+/- standard deviation) were significantly decreased by Day 14 (from 92.9 +/- 30.5 to 44.9 +/- 20.3 micrograms/liter and from 10.6 +/- 7.4 to 5.9 +/- 2.6 U/ml, respectively), after which there were only slight further decreases. Six (60%) of the 10 patients experienced tumor shrinkage ranging from 9% to 78% (mean 30%). When it occurred, tumor shrinkage was significant by Day 14 (7.9 +/- 6.3 to 6.5 +/- 5.1 cu cm) and no further shrinkage was achieved by longer administration. Transsphenoidal surgery reduced postoperative GH levels to less than 2 micrograms/liter and IGF-I to less than 1.5 U/ml in six patients (60%). This percentage of cure is higher than expected from the literature and the authors' previous experience. However, an investigation of the influence of this drug on several parameters, such as reduction of tumor size or GH and IGF-I concentrations, has failed to prove any relationship. Only pretreatment size of the tumor was of predictive value with respect to the surgical outcome.

[Nelson's syndrome concomitant with Cushing's syndrome]. / Síndrome de Nelson concomitante con síndrome de Cushing.

A case is presented of Nelson's Syndrome concomitant with Cushing's Syndrome in a female patient who underwent five years earlier bilateral adrenalectomy due to Cushing's Disease. Together with hyperpigmentation, very elevated ACTH, and intrasellar mass in CT scan, plasma cortisol levels without rythm and not suppressible were observed as well as increased cortisol in urine. The macroadenoma was resected though the sphenoid and later hypophysis radiotherapy was given, with a clinical remission and biochemical improvement of the syndrome. At the present time, slightly elevated ACTH levels persist, with panhypopituitarism and empty sella turcica. The clinical picture is described and a literature search is carried out.

[Description of Wolfram syndrome (DIDMOAD) on the basis of a new case]. / Descripción del síndrome de Wolfram (DIDMOAD) a partir de un nuevo caso.

We present a new clinical case of a 25-year-old man with Wolfram's syndrome. Partial central diabetes insipidus was found to cause polyuria, polydipsia and enuresis. The patient had diabetes mellitus for the last 18 years, controlled with diet and/or chlorpropamide during 10 years and showed no typical complications of the disease. The patient was also shown to have a dilated urinary tract and perceptive hypoacusis for high frequencies. The fifth classical component of this syndrome, primary optic atrophy, was not found. Based on the report of this case, Wolfram's syndrome is briefly described.