Tratamiento del linfoma cutáneo de células T con ligandos selectivos del receptor retinoide X: alteraciones endocrinológicas y metabólicas / Treatment of cutaneous T-cell lymphoma with retinoid receptor x- selective ligands: endocrine and metabolic disorders

Los ligandos selectivos del receptor retinoide X se utilizan actualmente en el tratamiento de estadios avanzados del linfoma cutáneo de células T resistentes a otros tratamientos sistémicos, siendo el bexaroteno el primer fármaco de este grupo aprobado en Europa. Se han descrito numerosos efectos adversos asociados a su utilización, entre los que destacan las alteraciones endocrino-metabólicas. Presentamos a 2 pacientes con linfoma cutáneo de células T, tratados con bexaroteno, que desarrollaron hipotiroidismo central y dislipemia de forma precoz tras su inicio. Se describen también la respuesta de estas alteraciones al tratamiento y su remisión completa tras suspender el bexaroteno (AU)

The retinoid X receptor-selective ligands has been used for advanced stages of cutaneous T-cell lymphoma refractory to previous systemic therapy, being bexarotene the first drug in this group approved in Europe. Multiple drug-related adverse events has been reported such as endocrine-metabolic disorders. We report 2 patients with cutaneous T-cell lymphoma, treated with bexarotene, that developed central hypothyroidism and dyslipidaemia immediately after the beginning of this treatment. We also showed the successfully treatment response of these alterations and the total clinical remission after discontinuing the drug (AU)

[Treatment of cutaneous T-cell lymphoma with retinoid receptor X-selective ligands: endocrine and metabolic disorders]. / Tratamiento del linfoma cutáneo de células T con ligandos selectivos del receptor retinoide X: alteraciones endocrinológicas y metabólicas.

The retinoid X receptor-selective ligands has been used for advanced stages of cutaneous T-cell lymphoma refractory to previous systemic therapy, being bexarotene the first drug in this group approved in Europe. Multiple drug-related adverse events has been reported such as endocrine-metabolic disorders. We report 2 patients with cutaneous T-cell lymphoma, treated with bexarotene, that developed central hypothyroidism and dislipidaemia inmediately after the begining of this treatment. We also showed the successfully treatment response of these alterations and the total clinical remission after discontinuing the drug.

[99m-Tc sestamibi scintigraphy in primary hyperparathyroidism. Importance of lateral projections using a pin-hole collimator]. / Gammagrafía con sestamibi-Tc99m en el hiperparatiroidismo primario. Importancia de las proyecciones laterales con colimador pin-hole.

UNLABELLED: 99mTc-Sestamibi double-phase scintigraphy has been improved with digital and tomographic procedures as well as additional projections. Since two years ago, we have introduced additional early lateral views of neck to the conventional double-phase scintigraphy. We have tried to give anatomic data about the depth of the adenomas and to evaluate the possibility of obviating the late images of the double-phase study. METHOD: Two observers reviewed 50 studies performed for primary hyperparathyroidism in two different ways. The first one reviewed only conventional double-phase studies and the second one, with the additional report of the lateral views. RESULTS: in 32/50 patients (64 %) the report of the additional lateral views and the conventional early views was enough to diagnose parathyroid adenomas. No additional lesions were observed in the late views. These views did not provide any additional useful data and could have been obviated. Four ectopic adenomas were found, 1 mediastinal and 3 in paraesophagic area; three intrathyroidal focus; all of these atypical lesions were identified by lateral pinhole views. CONCLUSION: The performance of additional lateral projections of the parathyroids supplies additional information to the surgeon on the depth of the lesion in atypical sites and would have made it possible to obviate the late phase in more than half of the patients since this did not supply additional information to that of the early images that had reached a diagnosis.

Gammagrafía con Sestamibi-Tc99m en el HiperparatiroidismoPrimario. Importancia de las Proyecciones Laterales con ColimadorPin-Hole / 9Mtc-sestamibi scintigraphy in primary hyperparathyroidism

La gammagrafía de paratiroides con sestamibi-Tc99m en dos fases se ha ido complementando con técnicas digitales, tomográficas y proyecciones adicionales. Desde hace dos años hemos incorporado la realización selectiva de proyecciones laterales con colimador pin-hole a 90° en las imágenes precoces en un intento sencillo de proporcionar información acerca de la situación en profundidad, por un lado, para complementar el diagnóstico intentando acortar la exploración y, por otro, para facilitar el abordaje quirúrgico al cirujano en las ectopias. Método: Dos observadores revisaron los estudios de 50 hiperparatiroidismos primarios de dos formas distintas: una a partir de las proyecciones anteriores convencionales en dos fases y otra con la información adicional de las proyecciones laterales. Resultados: En 32/50 pacientes (64 por ciento) la información de las proyecciones laterales adicionales fue suficiente para diagnosticar la presencia de adenomas paratiroideos sin que las imágenes tardías aportasen datos de interés pudiéndose obviar la fase tardía. No se observaron lesiones adicionales en las imágenes tardías. Se encontraron 4 adenomas ectópicos (3 paraesofágicos y 1 mediastínico). 3 captaciones nodulares intratiroideas fueron perfectamente localizadas por las proyecciones laterales. Conclusión: La realización de proyecciones laterales adicionales de paratiroides aporta información adicional al cirujano acerca de la profundidad de la lesión en localizaciones atípicas y hubiera permitido obviar la fase tardía en más de la mitad de los pacientes ya que ésta no aportó información adicional a la de las imágenes precoces que habían alcanzado un diagnóstico (AU)

[Spinal extradural lipomatosis. Revision of 108 cases. Case induced by exogenous contribution of ACTH]. / Lipomatosis estradural espinal. Revisión de 108 casos. Caso inducido por aporte exógeno de ACTH.

Authors present a male patient with Spinal Extradural Lipomatosis, previously treated of a cerebral astrocytoma with surgery and radiotherapy, after which he received ACTH for a long period of time. Clinical manifestations were rachialgia, paraparesia with pain and dysestesias in both lower extremities. Diagnosis was carried out by Magnetic Resonance imaging. After a progressive withdrawal of the treatment with ACTH, the patient achieved a complete recovery and neuroimaging studies showed the dissappearance of the compression caused by the lipomatosis. We carry out a revision of the literature showing data we consider of interest derived from the wide series subjected to study.

Lipomatosis extradural espinal. Revisión de 108 casos. Caso inducido por aporte exógeno de ACTH / Spinal extradural lipomatosis. Revision of 108 cases. Case induced by exogenous contribution of ACTH

Presentamos un caso de Lipomatosis extradural espinal en un paciente previamente tratado de un glioma anaplásico cerebral mediante cirugía y radioterapia, que recibió tratamiento con ACTH durante un largo período. Las manifestaciones clínicas fueron de raquialgia, paraparesia con dolor y disestesias en ambas extremidades inferiores. El diagnóstico se realizó mediante Resonancia Magnética. La retirada progresiva del tratamiento con ACTH hasta su supresión logró la recuperación clínica completa del paciente y la desaparición en los estudios de neuroimagen de la compresión provocada por la lipomatosis. Realizamos una revisión de la literatura aportando datos que consideramos de interés y que se derivan de la amplitud de la serie sometida a estudio (AU)

No disponible

[Primary adrenal insufficiency and primary antiphospholipid syndrome]. / Insuficiencia suprarrenal primaria y síndrome antifosfolípido primario.

Primary adrenal insufficiency (PAI) is a rare complication of antiphospholipid syndrome (APS). The hypercoagulable state in the APS may lead to adrenal vein thrombosis and subsequently to hemorrhagic necrosis of the adrenal glands. This complication of APS is important to recognize because it may be fatal if untreated. We describe one case of PAI and primary APS, with magnetic resonance studies consistent with hemorrhagic necrosis of the adrenal glands.

[Thyrotropin-producing hypophyseal adenomas]. / Adenomas hipofisarios productores de tirotropina.

Thyrotropin (TSH)-producing adenoma or TSH-oma is an uncommon entity. Most cases correspond to macroadenomas, and microadenomas are exceptional. The differential diagnosis should include mainly hypophyseal resistance to thyroid hormones, which can be difficult because of normal findings of imaging studies of the pituitary gland in some cases of TSH-oma and also because of the clinical and biochemical heterogeneity of both entities. Hypophyseal surgery is the treatment of choice for TSH-omas, although clinical and biochemical recovery of hyperthyroidism is not achieved in a considerable proportion of cases. When surgery fails or is contraindicated, radiotherapy and somatostatine analogues are therapeutic alternatives. We report here two cases of TSH-producing microadenoma which were confirmed after hypophyseal surgery.

[Ketoconazole in the control of arterial hypertension in Cushing's syndrome]. / Ketoconazol en el control de la hipertensión arterial en el síndrome de Cushing.

OBJECTIVE: To determine the usefulness of ketoconazole for the control of arterial hypertension (AH) in Cushing syndrome (CS) as temporary treatment. PATIENTS AND METHODS: Fifteen cases of CS were collected (eleven cases of Cushing disease, two cases of ectopic secretion of ACTH, one case of adrenal adenoma, and one case of adrenal carcinoma). The clinical characteristics as well as laboratory data of patients with AH and the response to therapy were studied. RESULTS: Six patients (40%) had AH. A significant difference was observed of an older age, a higher frequency of association with diabetes mellitus and a higher 24 hour free urine cortisol (FUC) for patients with AH compared with non hypertensive patients. Ketoconazole was efficient for controlling AH in five cases, and in all of them the return to normal levels of 24 hour FUC was achieved. A failure of AH control under treatment with ketoconazole occurred in the only case of adrenal carcinoma. There was no significant secondary adverse reaction to ketoconazole. CONCLUSIONS: Ketoconazole is an efficient drug for the control of AH in CS and is well tolerated. In our series, the return to normal levels of FUC was associated with control of AH.

[Cushing's syndrome: clinical study of fifteen cases]. / Síndrome de Cushing: estudio clínico de quince casos.

OBJECTIVE: To study the epidemiological and clinical features and diagnostic tests of Cushing's syndrome (CS) of non-iatrogenic etiology, because of there are few similar studies in the last ten years. METHODS: Fifteen cases of CS were diagnosed from 1992 to 1997 at our hospital. We describe the epidemiological, clinical, biochemical, radiologic, therapeutic and evolutive characteristics. RESULTS: Both diabetes mellitus and hypertension were observed in 40% of patients. The frequency of etiologies was: Cushing's disease, 66.6%; ectopic ACTH syndrome, 13.3%; adrenal adenoma, 6.6%; adrenal carcinoma, 6.6%; and undiagnosed, 6.6%. The 24-hour urine free cortisol (UFC) and the overnight 1 mg oral dexamethasone suppression test yielded 93.3 and 100% diagnostic sensitivity for CS, respectively. The overnight 8 mg oral dexamethasone suppression test, the metyrapone test and the 7 mg intravenous dexmethasone test had 75, 50 and 60% diagnostic sensitivity for Cushing's disease, respectively. Ketoconazole treatment had success in to normalize the 24-hour UFC in all patients, except for the case of adrenal carcinoma. CONCLUSIONS: The Cushing's disease was the most common form of CS. The 24-hour UFC and overnight 1 mg oral dexamethasone suppression test were good screening studies. Ketoconazole was successful in normalizing the adrenal cortex function.

[Advances in pharmacological treatment of pituitary adenomas]. / Avances en el tratamiento farmacológico de los adenomas hipofisarios.

In last years, advances in endocrinological and neuroradiological research have lead to an earlier recognition and more effective management of pituitary tumours. At the same time, pharmacological investigation has allowed the development of useful drugs in the treatment of pituitary adenomas, either as an exclusive therapy or as an aid to surgery and radiotherapy. In this article we review indications and dosage of recently developed drugs for different types of hormone-secreting pituitary adenomas.

[Subtotal thyroidectomy. A treatment to keep in mind in amiodarone-induced thyrotoxicosis]. / Tiroidectomía subtotal. Un tratamiento a tener en cuenta en la tirotoxicosis inducida por amiodarona.

Amiodarone is an antiarrhythmic drug, frequently used in cardiology, which may produce secondary effects on the thyroid function. These effects can range from subtle changes in peripheral hormones without clinical manifestations, to severe forms of hypothyroidism or hyperthyroidism. The evolution of amiodarone-induced-hyperthyroidism can be mild, requiring only the withdrawal of the drug, or very severe, requiring an aggressive therapy with multiple drugs which may in some cases be fatal in spite of this therapy. Recently, the increase in the usage of this drug has produced reports of severe amiodarone-induced-thyrotoxicosis requiring surgery in some cases (subtotal or total thyroidectomy). A case of amiodarone-induced-thyrotoxicosis in its more aggressive form, which required intensive pharmacological treatment ultimately combined with surgery, is presented here.

[Effectiveness of serotonergic agonists in the treatment of obese patients]. / Efectividad de los agonistas serotoninérgicos en el tratamiento de pacientes obesos.

OBJECTIVE: To compare the effectiveness of two interventions in the treatment of obese patients: hypocaloric diet and hypocaloric diet plus serotoninergic medication. DESIGN: Randomised clinical trial. SETTING: Primary Care. Out-patient Endocrinology clinic. PATIENTS: The trial included 60 obese adults, assigned at random to two groups of 30 each. Both groups were comparable for sex, age, weight and Body Mass Index. Weight controls were performed at 2, 4 and 6 months. RESULTS: There were no significant differences in weight losses at the times studied (2, 4 and 6 months) between the Control (Hypocaloric diet) and Study (Hypocaloric diet plus medication) groups. There were significant weight losses in both groups analysed between 2 and 4 months, with a Body Mass Index which went down from 36.2 to 34.12 and from 35.52 to 33.57 (p < 0.001) in the Control and Study groups, respectively. CONCLUSIONS: No significant differences were observed in the results obtained for obese patients between a hypocaloric diet supplemented by serotoninergic medication and a hypocaloric diet.

[Serum osteocalcin in insulin-dependent diabetic patients]. / Osteocalcina sérica en pacientes diabéticos insulinodependientes.

Serum osteocalcin (BGP) is the currently most reliable marker of osteoblastic activity and of the bone formation index. To investigate its state in patients with insulin-dependent diabetes mellitus (IDDM) we measured the BGP level in 82 individuals divided in two groups. The control group (CG) consisted of 26 healthy volunteers (16 males and 10 females: mean age 25.6 +/- 2.8 years). The diabetic group (DG) consisted of 56 patients with IDDM (36 males and 20 females; mean age 23.2 +/- 6 years). The DG was, in its turn, subdivided in four subgroups (A, B, C, D) depending on the time from the diagnosis (TE) (less than 2, 2-5, 5-10, and greater than 10 years). The DG had a significantly lower BGP than CG (3.01 +/- 1.5 vs 3.9 +/- 1.7 ng/nl; p = 0.024). BGP levels were also lower in the subgroups C (2.4 +/- 1.0 ng/ml; p = 0.006) and D (1.7 +/- 0.9 ng/ml; p = 0.000) than in CG. When they were compared between them, the subgroups A (3.6 +/- 1.1 ng/ml) and B (4.5 +/- 1.4 ng/ml) had BGP levels significantly higher than subgroups C (2.4 +/- 1.0 ng/ml; p = 0.009 and p = 0.000) and D (1.7 +/- 0.9 ng/ml; p = 0.000 and p = 0.000). There were no differences between subgroups A and B, on the one hand, and C and D, on the other. There was a highly significant lineal correlation between TE and the BGP levels (r = 0.5196; p = 0.000). The patients with IDDM have reduced BGP levels; this reduction becomes apparent after 5 years of clinical evolution and shows a correlation with the time since the diagnosis.

[Parathormone, cyclic AMP, 1,25 dihydroxyvitamin D and osteocalcin in hypercalciuric renal lithiasis]. / Parathormona, AMP cíclico, 1,25 dihidroxivitamina D y osteocalcina en la litiasis renal hipercalciúrica (LRH).

A study was undertaken in 46 subjects; 21 patients diagnosed as having HRL and 25 volunteers patients. Biochemical and hormonal analyses were performed in the study population, including determination of Ca, P, Mg, Cr in blood and urine, phosphate tubular resorption (PTR), maximum tubular phosphate resorption (MTPR), fasting calcium secretion (FCS), alkaline phosphatase (AP), hydroxyprolinuria (HPR), osteocalcin (BGP), parathormone (PTH), cAMP, and 1-25(OH)2D. The stone formers showed lower calcemia values (p less than or equal to 0.005d), higher phosphaturia, and magnesiuria (p less than or equal to 0.0005), higher FCS (P less than or equal to 0.005) and higher values for PTH (p less than or equal to 0.01) and cAMP (p less than or equal to 0.0025). No significant differences were observed for the other parameters evaluated. Classification of the patient group into 2 subgroups (renal SbR and absorptive SbA) according to FCS values greater or lower that 0.16 mg/dl, the SbR patient group revealed a higher PTH and 1-25(OH)2D values (p less than or equal to 0.05). There appears to be no increase of bone resorption since AP, HPR, and BGP values in our patients fell within normal ranges. The 1-25(OH)2D levels were also normal and, with respect to the control group, were only elevated for the SbR patient group, whose PTH levels were also observed to be elevated. These increments appear to be related and may result in intermediate forms between renal and absorptive hypercalciuria.