Polirradiculopatía torácica diabética: un dolor olvidado / Diabetic thoracic polyradiculopathy: a forgotten pain

La polirradiculopatía torácica diabética (PTD) es una manifestación neuropáticainfrecuente que suele presentarse en pacientes con diabetes de larga evoluciónjunto a otras complicaciones crónicas microangiopáticas. Se manifiestacomo un cuadro doloroso que afecta a la región torácica o a la abdominaldependiendo de las raíces implicadas. El dolor puede llegar a ser de gran intensidade incapacitante, y a menudo el diagnóstico se retrasa al valorarseprimeramente otras causas más frecuentes de aquél. El diagnóstico se confirmamediante estudio electromiográfico, debiéndose descartar otras etiologíasorgánicas, en particular las tumorales. El tratamiento incluye los fármacos comúnmenteempleados en la neuropatía diabética dolorosa, precisándose aveces la administración de corticoides, la estimulación neural transcutánea ola plasmaféresis. Presentamos un caso de PTD en un paciente joven con diabetestipo 2 de reciente diagnóstico, de un tiempo de evolución indeterminadoy con severas manifestaciones microangiopáticas. Se exponen las característicasdel cuadro clínico, el planteamiento diagnóstico y la actitud terapéutica(AU)

The diabetic thoracic polyradiculopathy (DTP) is an uncommon neuropathicmanifestation that usually appears in patients with long evolution diabetes togetherwith microangiopathic chronic complications. It appears as a painfulpicture that affects the thoracic and abdominal region depending from the affectedroots. The pain can be of great intensity and disabling and very often thediagnosis is delayed when assessing other more frequent causes first. The diagnosisis confirmed through an electromyography, having to rule out otherorganic etiologies, specially the tumoral ones. The treatment includes the mostused drugs for painful diabetic neuropathy, being sometimes the administrationof corticosteroids, transcutaneous neural stimulation or plasmapheresis required.We present the case of DTP in a young patient with a recent diagnosedT2D with an undetermined evolution time and with serious microangiopathicmanifestations, standing out the characteristics of the medical profile, the diagnosticapproach and the therapeutic attitude(AU)

[Hungry bone syndrome related to hyperthyroidism]. / Síndrome del hueso hambriento relacionado con hipertiroidismo.

Hungry bone syndrome is a common clinical entity which is accompanying of hypocalcemia, hypomagnesemia, and hipophosphatemia, results from an increase in bone formation. It is related to a pathological scenario which causes an imbalance between osteoclast-mediated bone resorption and osteoblast-mediates bone formation, favouring the latter. Its classic presentation occurs after parathyroidectomy in hyperparathyroydism's patients. Its clinical features are largely due to plasmatic calcium levels reduction. Hungry bone syndrome is frequent in hyperparathyroid's patients who have development bone disease before surgery. Even less frequent, it has also been described after thyroydectomy in patients with hyperthyroidism. We hereby report a case of hungry bone syndrome in one patient who suffers a Graves' disease. Then, we will provide a brief review of pathogenesis and therapeutic features.

Síndrome del hueso hambriento relacionado con hipertiroidismo / Hungry bone syndrome related to hyperthyroidism

El síndrome del hueso hambriento es una entidad clínica que se caracteriza por la aparición de hipocalcemia, hipofosfatemia e hipomagnesemia secundaria a un aumento de su captación a nivel óseo. Es un proceso que se ha descrito en el contexto de enfermedades que actúan generando un disbalance entre la producción y la resorción, a favor de ésta última. La forma clásica de presentación, acontece tras la realización de una paratiroidectomia en pacientes con hiperparatiroidismo (HPT), siendo su clínica la relacionada fundamentalmente con la caída de los niveles plasmáticos de calcio. Aunque menos habitual, ha sido descrito tras tratamiento quirúrgico de entidades clínicas que cursan con un exceso de hormonas tiroideas, siendo la forma más frecuente la enfermedad de Graves-Basedow. Presentamos un caso de este síndrome tras tiroidectomía en un paciente con hipertiroidismo primario por enfermedad de Graves, realizando una breve revisión de los aspectos fisiopatológicos y manejo del cuadro

Hungry bone syndrome is a common clinical entity which is accompanying of hypocalcemia, hypomagnesemia, and hipophosphatemia, results from an increase in bone formation. It is related to a pathological scenario which causes an imbalance between osteoclast-mediated bone resorption and osteoblast-mediates bone formation, favouring the latter. Its classic presentation occurs after parathyroidectomy in hyperparathyroydism´s patients. Its clinical features are largely due to plasmatic calcium levels reduction. Hungry bone syndrome is frequent in hyperparathyroid´s patients who have development bone disease before surgery. Even less frequent, it has also been described after thyroydectomy in patients with hyperthyroidism. We hereby report a case of hungry bone syndrome in one patient who suffers a Graves´ disease. Then, we will provide a brief review of pathogenesis and therapeutic features

Diagnóstico y tratamiento del insulinoma: nuestra experiencia en 10 casos / Diagnosis and treatment of insulinoma: review of 10 patients

Objetivo Revisión de la presentación clínica, la sensibilidad y la especificidad de las diferentes técnicas de localización utilizadas y de los tratamientos empleados en pacientes con insulinoma. Pacientes y métodos Estudio restrospectivo y descriptivo de pacientes con diagnóstico de insulinoma intervenidos en nuestro centro durante el período de 1992 a 2004. Se evaluaron la edad, el sexo, la clínica, los valores de insulina y de glucosa, los resultados de estudios de localización, la técnica quirúrgica, las características anatomopatológicas y la morbimortalidad. Resultados Se estudió a 10 pacientes, un 60% mujeres, con una edad de 58 ± 14 años. La clínica fue de neuroglucopenia en el 90% y síntomas simpatoadrenérgicos en el 50%. En todos los casos se demostró una relación insulina/glucosa elevada. Las tasas de detección del tumor fueron, para la ecografía transabdominal del 22%, para la tomografía computarizada del 50%, para la resonancia magnética del 33% y para la gammagrafía con octreótido marcado del 25%; con estas técnicas se localizó el 50% de los tumores. La arteriografía con inyección de calcio y la ecografía intraoperatoria identificaron el tumor en todos los casos en los que se realizaron. Dos pacientes tenían insulinomas malignos con metástasis ganglionares. La cirugía fue la enucleación en 5 casos, resección distal del páncreas en 3 y duodenopancreatectomía cefálica en 2. En ningún caso el insulinoma se asoció a neoplasia endocrina múltiple tipo 1. No existió mortalidad postoperatoria. Todos los pacientes estaban asintomáticos, al menos, 6 meses tras la cirugía. Conclusiones La arteriografía con inyección intraarterial de calcio es la prueba de localización preoperatoria más sensible, pero debido a su complejidad debe reservarse para pacientes con insulina sin diagnóstico de localización previo. La alta sensibilidad y el bajo coste de la ecografía intraoperatoria la convierten en una técnica sencilla y muy útil durante el procedimiento quirúrgico, tanto para la localización del tumor como para la valoración de su extensión (AU)

Objective To evaluate clinical features, the sensitivity and specificity of preoperative imaging techniques, and treatment in patients with insulinoma. Patients and methods All patients treated in our institution for surgically proven insulinoma between 1992 and 2004 were retrospectively reviewed. Age, sex, symptoms, insulin and glucose levels, imaging studies, surgical technique, pathological results, morbidity and mortality were analyzed. Results Ten patients with pancreatic insulinomas were included. The mean age was 58 ± 14 years and 60% were women. Clinical findings included neuroglycopenia in 90% and/or sympathoadrenal symptoms in 50%. In all patients, a high insulin/glucose ratio was demonstrated. The detection rates were 22% for transabdominal ultrasonography, 50% for computed tomography (CT), 33% for magnetic resonance imaging and 25% for 111-In-octreotide imaging. Using these techniques, 50% of the tumors were detected. Selective arterial calcium stimulation with hepatic venous sampling and intraoperative ultrasonography identified the tumor in all patients who underwent these techniques. Two patients had malignant insulinomas with nodal metastases. Surgical procedures included enucleation of insulinoma in five patients, partial distal pancreatectomy in three patients and the Whipple procedure in two patients. None of the patients had associated multiple endocrine neoplasia type 1. There was no postoperative mortality. All patients were symptom-free for at least 6 months after surgery. Conclusions Selective arterial calcium stimulation is the most sensitive preoperative test but, due to its complexity, it should be reserved for difficult cases. Because of its high sensitivity and low cost, intraoperative ultrasonography is a very useful intraoperative technique to evaluate localization and/or extension of the insulinoma (AU)

[The use of suprarenal scintigraphy in the differential diagnosis of suprarenal incidentaloma]. / Utilidad de la gammagrafía suprarrenal en el diagnóstico diferencial del incidentaloma suprarrenal.

OBJECTIVES: To assess the usefulness of adrenal scintigraphy for clinical evaluation of adrenal incidentalomas, and its relation with pathological diagnosis and follow-up. PATIENTS AND METHODS: We have studied 46 patients with unilateral adrenal incidentaloma of size between 10 and 100 mm (average 30.5 +/- 19 mm). The lesions were discovered with abdominal computerized tomography in the study of a primary tumor (22%) or in the evaluation of benign pathology (78%). Adrenal scintigraphy assessed uptake in adrenal incidentaloma. Hormonal study included urinary catecholamines, plasma cortisol after dexamethasone, adrenal androgens, and renin and aldosterone in hypertensive patients. Five patients were operated, FNAB was carried out in three patients, and in the rest average follow-up was 29 +/- 21 months. Adrenal incidentaloma was considered nonfunctional if the lesion did not modified its size nor showed analytical alterations along a follow-up higher than 8 months. RESULTS: Of 46 adrenal lesions, seven didn't show uptake (three metastases, one cyst, one adrenal carcinoma, one pheochromocytoma, and one angiomyolipoma), 34 showed excessive uptake (29 nonfunctional adrenal nodules and 5 hyperfunctional adrenal nodules), and five had normal uptake (nonfunctional adrenal nodules). Adrenal scintigraphy was compatible in all cases with cytological study or the response to chemotherapy. Along the follow-up, growth of the lesion was demonstrated in 23%, and reduction or disappearance of the lesion in 11%, with no hormonal significant changes. CONCLUSIONS: Detection of a lesion with no uptake in adrenal scintigraphy forces to carry out complementary explorations in order to rule out malignant pathology. A lesion with excessive uptake is indicative of a benign process and should be assessed with hormonal determinations.

Utilidad de la gammagrafía suprarrenal en el diagnóstico diferencial del incidentaloma suprarrenal / Role of adrenal scintigraphy in the management of adrenal incidentaloma

Objetivos. Valorar la utilidad de la gammagrafía suprarrenal en el estudio de los incidentalomas suprarrenales y su relación con el diagnóstico patológico y el seguimiento posterior. Pacientes y métodos. Hemos estudiado 46 pacientes con incidentaloma suprarrenal unilateral de tamaño entre 10 y 100 mm (media: 30,5 ± 19 mm). Las lesiones se localizaron mediante tomografía computarizada abdominal durante el estudio de un tumor primario (22%) o de patología benigna (78%). La gammagrafía suprarrenal valoró la existencia o no de captación en el incidentaloma suprarrenal. El estudio hormonal incluyó catecolaminas urinarias, cortisol plasmático tras dexametasona, andrógenos adrenales y renina y aldosterona en pacientes hipertensos. Cinco pacientes fueron operados, en tres se realizó punción-aspiración con aguja fina y en los restantes seguimiento medio de 29 ± 21 meses. Se consideró incidentaloma suprarrenal no funcionante si la lesión no modificaba su tamaño ni mostraba alteraciones analíticas en el seguimiento superior a 8 meses. Resultados. De las 46 lesiones suprarrenales 7 fueron hipocaptadoras (tres metástasis, un quiste, un carcinoma suprarrenal, un feocromocitoma y un angiomiolipoma), 34 hipercaptadoras (29 nódulos suprarrenales no funcionantes y 5 hiperfuncionantes) y 5 normocaptadoras (nódulos suprarrenales no funcionantes). La gammagrafía suprarrenal fue concordante con estudio citológico o la respuesta a quimioterapia en todos los casos. Durante el seguimiento se demostró un crecimiento de la lesión en el 23% y reducción o desaparición de las lesiones en el 11% y no se encontraron cambios significativos hormonales.Conclusiones. Una lesión hipocaptadora en gammagrafía suprarrenal hace necesaria la realización de exploraciones complementarias para descartar patología maligna. Una lesión hipercaptadora es indicativa de proceso benigno y debe ser valorada con determinaciones hormonales

Objetives. To assess the usefulness of adrenal scintigraphy for clinical evaluation of adrenal incidentalomas, and its relation with pathological diagnosis and follow-up. Patients and methods. We have studied 46 patients with unilateral adrenal incidentaloma of size between 10 and 100 mm (average 30.5 ± 19 mm). The lesions were discovered with abdominal computerized tomography in the study of a primary tumor (22%) or in the evaluation of benign pathology (78%). Adrenal scintigraphy assessed uptake in adrenal incidentaloma. Hormonal study included urinary catecholamines, plasma cortisol after dexamethasone, adrenal androgens, and renin and aldosterone in hypertensive patients. Five patients were operated, FNAB was carried out in three patients, and in the rest average follow-up was 29 ± 21 months. Adrenal incidentaloma was considered nonfunctional if the lesion did not modified its size nor showed analytical alterations along a follow-up higher than 8 months. Results. Of 46 adrenal lesions, seven didn't show uptake (three metastases, one cyst, one adrenal carcinoma, one pheochromocytoma, and one angiomyolipoma), 34 showed excessive uptake (29 nonfunctional adrenal nodules and 5 hyperfunctional adrenal nodules), and five had normal uptake (nonfunctional adrenal nodules). Adrenal scintigraphy was compatible in all cases with cytological study or the response to chemotherapy. Along the follow-up, growth of the lesion was demonstrated in 23%, and reduction or disappearance of the lesion in 11%, with no hormonal significant changes. Conclusions. Detection of a lesion with no uptake in adrenal scintigraphy forces to carry out complementary explorations in order to rule out malignant pathology. A lesion with excessive uptake is indicative of a benign process and should be assessed with hormonal determinations

Una causa rara de diabetes insípida aislada / An infrequent cause of isolated diabetes insipidus

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Growth hormone responses to oral glucose and intravenous thyrotropin-releasing hormone in acromegalic patients treated by slow-release lanreotide.

The aim of this study was to assess GH response to oral glucose tolerance test (OGTT) and TRH stimulation test in a group of 10 patients with active post-operative acromegaly before and after long-term slow-release (SR) lanreotide therapy (30 mg im every 10-14 days). Seven patients (2 males, 5 females, 29-71 yr), who during therapy maintained plasma GH and IGF-I concentrations under 5 microg/l and 450 microg/l, respectively, were considered as responders and studied for 24 (1 patient) to 36 months (6 patients). Three patients (1 male, 2 females, 46-61 yr) with levels of GH and IGF-I above those values were studied for 12 months. The OGTT (75 g po) and TRH test (400 microg iv) were repeated before and after 6, 12, 24 and 36 months. The GH response to OGTT was abnormal (nadir: >2 microg/l) at 6 and 12 months in poorly responsive patients. This response was normalized in all responsive patients. Nonetheless, 2 responsive patients showed abnormal GH values after OGTT once each throughout the 36-month study period. The GH response to TRH was characterized by great variability and exhibited unpredictable behavior throughout the study period both in responsive and in poorly responsive patients. Only 2 patients in the responsive group showed persistent normal GH levels (peak: < or =5 microg/l) after TRH for 3 yr. In conclusion, SR lanreotide treatment gave rise to a correct control of GH hypersecretion and to a normalization of GH response to oral glucose in 7 out of 10 patients, although it did not abolish the paradoxical reaction of GH to TRH in all responders. The effect of SR lanreotide on GH response to glucose tolerance test was not paralleled by GH response to TRH.

Effects of acute infusion of erythropoietin on paradoxical responses of growth hormone to thyrotropin-releasing hormone in acromegalic patients.

OBJECTIVE: Our aim has been to evaluate the effects of i.v. infusion of recombinant human erythropoietin (rhEPO) on the responses of growth hormone (GH), prolactin (PRL) and thyrotropin (TSH) to thyrotropin-releasing hormone (TRH) stimulation in acromegalic patients. METHODS: We studied 16 patients (8 females, aged 29-68 years) with active acromegaly and 12 control subjects (7 females, 24-65 years). All participants were tested with TRH (400 microg i.v. as bolus) and with TRH plus rhEPO (40 U/kg at a constant infusion rate for 30 min, starting 15 min before TRH injection) on different days. Blood samples were obtained between -30 and 120 min for GH and PRL determinations, and between -30 and 90 min for TSH determinations. Hormone responses were studied by a time-averaged (area under the secretory curve (AUC)) and time-independent (peak values) analysis. RESULTS: Twelve patients exhibited a paradoxical GH reaction after TRH administration with great interindividual variability in GH levels. When patients were stimulated with rhEPO plus TRH there were no changes in the variability of GH responses or in the peak and AUC for GH secretion. Infusion with rhEPO did not induce any significant change in GH secretion in normal subjects. Baseline and TRH-stimulated PRL concentrations in patients did not differ from those values found in controls. When TRH was injected during the rhEPO infusion, a significant (P<0.05) increase in PRL concentrations at 15-120 min was found in acromegalic patients. Accordingly, the PRL peak and the AUC for PRL secretion were significantly increased in patients. Infusion with rhEPO had no effect on TRH-induced PRL release in control subjects. Baseline TSH concentrations, as well as the TSH peak and the AUC after TRH, were significantly lower in patients than in controls. Infusion with rhEPO modified neither the peak TSH reached nor the AUC for TSH secretion after TRH injection in acromegalic patients and in healthy volunteers. CONCLUSION: Results in patients with acromegaly suggest that (i) the paradoxical GH response to TRH is not modified by rhEPO infusion, (ii) rhEPO has no effect on TRH-induced TSH release, and (iii) acute rhEPO administration increases the TRH-induced PRL release in acromegalic patients.

Long-term effects of recombinant human erythropoietin therapy on growth hormone secretion in uremic patients undergoing peritoneal dialysis.

Recombinant human erythropoietin (rhEPO) is being successfully used for the treatment of uremic anemia. Short-term studies have proved that correction of anemia with rhEPO therapy is accompanied by several changes in growth hormone (GH) secretion in uremic patients. The present study aimed to assess the influence of long-term rhEPO therapy on baseline and stimulated GH concentrations in a group of uremic patients undergoing continuous ambulatory peritoneal dialysis (CAPD). Seven well-nourished and clinically stable CAPD patients were studied. Ten normal subjects were studied as controls. GH responses to direct pituitary stimulation with GH-releasing hormone (GHRH) (100 microg intravenously [i.v.]) and indirect hypothalamic stimulation with insulin-induced hypoglycemia (0.1 U/kg body weight i.v.) and clonidine (0.15 mg/m2 orally), were assessed before and after 3, 6, and 12 months of subcutaneously administered rhEPO therapy. After rhEPO administration, an increase of the hemoglobin concentration was observed in all patients and maintained at about 12 g/dL throughout the study period. rhEPO therapy did not induce any significant change in baseline concentrations of GH and insulin-like growth factor I. Correction of the anemia was accompanied by a clear increase in the area under the curve (AUC) and the area above the baseline (AAB) of GH secretion in response to GHRH stimulation. These changes were statistically significant after 3 and 6 months of therapy, although at 12 months no significant differences in relation to pretreatment values could be observed. rhEPO treatment was associated with a progressive decrement in the GH AUC and AAB in response to hypoglycemic challenge, reaching statistically significant values at months 6 and 12. On the other hand, compared with the control group, GH responses to clonidine were blunted at the start of the study in CAPD patients, and rhEPO therapy was not accompanied by any modification. In conclusion, long-term treatment with rhEPO in CAPD patients is associated with complex and profound effects on somatotrope cell function, characterized by diverse effects on GH responses to stimuli that release GH through different mechanisms. Some of these rhEPO-induced alterations in somatotrope function are dependent on the duration of treatment.

Recombinant human growth hormone therapy in malnourished dialysis patients: a randomized controlled study.

Recombinant human growth hormone (rhGH; Saizen, Serono, Spain) has been recently used as an anabolic agent in several catabolic states, including malnourished chronic dialysis patients. However, up-to-date, comparative studies with control groups of dialysis patients have not been reported. The aim of the present study was to assess the effects of rhGH on nutritional status in a group of malnourished adult chronic dialysis patients undergoing both continuous ambulatory peritoneal dialysis (CAPD) and hemodialysis (HD). The patients were randomly assigned to the control group (nine patients; 6 women, 3 men; mean age, 58.3 +/- 5.6 years; seven undergoing CAPD, two undergoing HD) or the rhGH group (eight patients; three women, five men; mean age, 63.9 +/- 3.1 years; four undergoing CAPD, four undergoing HD). Both groups were similar at baseline. All patients were given dietary prescriptions (35 kcal/kg/d and 1 g protein/kg ideal body weight/d) during 4 weeks. In the rhGH group, rhGH was administered at 0.2 IU/kg/d subcutaneously (SC) during this period. Anthropometric and analytic parameters were assessed before (0 weeks) therapy and at 2 and 4 weeks after starting therapy. The rhGH group showed an increase of 1.238 kg in body weight from 64.3 +/- 4.3 (mean +/- standard error of the mean [SEM]) to 65.6 +/- 4.9 kg (P < 0.05). Serum insulin-like growth factor type 1 (IGF-1) concentrations increased from 216.6 +/- 42.5 to 581.2 +/- 171.5 ng/mL (4 weeks; P < 0.01) and transferrin levels increased from 271.2 +/- 16.3 to 314.5 +/- 21.2 mg/dL (4 weeks; P < 0.05). A significant reduction in blood urea nitrogen (BUN) level was observed (62.1 +/- 1.8 v 46.8 +/- 3.8 mg/dL; 4 weeks; P < 0.05). Mean daily protein intake, determined by individual dietary survey, at 0 and 4 weeks, remained constant in both groups. In conclusion, weight gain and IGF-1 and transferrin level increases and BUN level decreases, despite the constant oral intake, suggest that short-term rhGH administration is associated with an anabolic reaction in malnourished dialysis patients.

Efficacy of octreotide in the regression of a metastatic carcinoid tumour despite negative imaging with In-111-pentetreotide (Octreoscan).

We present the case of a 52-year old patient diagnosed with carcinoid tumour of the rectum with liver metastases in which treatment with somatostatin analogues (octreotide) proved very effective in the disappearance of the symptomatology and dramatic efficacy in the regression of the tumour. Imaging by octreoscan was always negative. The role of octreotide in the treatment of carcinoid tumour and the usefulness of In-111-pentetreotide (octreoscan) in the localization and prediction of the response to treatment with octreotide is discussed. We conclude that the negative result of the scintigraphic image with octreoscan does not necessarily suppose the inefficacy of octreotide treatment. We believe that this may constitute an important issue since some patients may be denied octreotide treatment in the absence of a positive octreoscan result.

Spontaneous recovery from post-traumatic hypopituitarism.

Recovery of the pituitary function from post-traumatic hypopituitarism is an exceptional event. We present the case of a 32 year-old man who was involved in a road traffic accident in which he suffered a severe head injury. Four days following the trauma the patient developed post-traumatic central diabetes insipidus and desmopressin was started. At discharge of the intensive care unit, the patient was referred to us for endocrine assessment. Three months after the head injury, the hormonal evaluation of the hypothalamic-pituitary axis by means of insulin stress test with the simultaneous administration of TRH and GnRH resulted in reduced responses of GH, cortisol, TSH, FSH, and LH with low baseline serum concentrations of free T4 and testosterone. Both serum basal and stimulated PRL concentrations were normal. Magnetic resonance imaging demonstrated deformity of the sella turcica with displacement of the pituitary gland by a post-traumatic retention cyst. A new evaluation of the pituitary function performed 6 months after the trauma showed spontaneous recovery of the gonadal, thyroid and adrenal function. However, GH response was reduced both to insulin-induced hypoglycemia, clonidine and GHRH tests. Presence of normal serum PRL levels, normal PRL response to TRH and reduced GH responses to pituitary and hypothalamic stimuli suggests both hypothalamic and pituitary damage. The present case shows an unusual case of partial spontaneous resolution of a post-traumatic hypopituitarism. Based on this clinical observation we recommend periodic evaluation of the pituitary function in these kind of patients.

Growth hormone responses to growth hormone-releasing hormone and clonidine before and after erythropoietin therapy in CAPD patients.

Correction of anemia with recombinant human erythropoietin (rhEPO) in patients with end-stage renal disease has been associated with improvement of several abnormalities in hypothalamo-hypophyseal functions. The aim of the present work was to evaluate the growth hormone (GH) responses to GH-releasing hormone (GHRH) and clonidine stimulation, as well as the baseline concentrations of insulin-like growth factor I(IGF-I), before and after the correction of anemia with rhEPO in a group of uremic patients undergoing continuous ambulatory peritoneal dialysis (CAPD). Nine clinically stable patients (1 male, 8 female; mean age 55.4 years; mean duration of CAPD 14.1 months) were studied. Twelve normal volunteers were studied as controls. GHRH and clonidine stimulation tests were performed prior to starting rhEPO and again after partial correction of anemia with rhEPO therapy (60-130 U/kg/week, s.c., for 12 weeks). Blood samples for GH were collected during 2 h after GHRH (100 micrograms i.v. in bolus) or clonidine (0.15 mg/m2, p.o.) administration. In basal plasma samples IGF-I concentrations were also measured. Mean (+/- SEM) blood hemoglobin concentration rose from 5.32 +/- 0.25 to 7.22 +/- 0.25 mmol/l (p < 0.001) after rhEPO treatment. GH responses to GHRH were characterized by marked differences in single patients when compared with the control group. However, the GH peak and the area under the secretory curves (AUC) of GH responses in CAPD patients (9.89 +/- 4.01 micrograms/l and 15.06 +/- 6.02 micrograms.h/l, respectively) did not differ from those obtained in control subjects (14.58 +/- 3.25 microgram/l and 16.94 +/- 4.31 microgram.h/l, respectively). The study after correction of anemia showed an evident potentiation of GH values that reached statistically significant values at 60 and 90 min. GH AUC after rhEPO therapy rose to 25.61 +/- 9.25 micrograms.h/l (p = 0.01). In control subjects, clonidine administration was followed by a GH release that reached a maximum at 90 min (7.67 +/- 2.24 micrograms/l). However, CAPD patients exhibited a blunted response to clonidine both before (2.00 +/- 0.78 microgram/l) and after (2.78 +/- 0.76 microgram/l, NS) correction of the anemia with rhEPO. On the other hand, IGF-I concentrations after rhEPO therapy (32.05 +/- 5.52 nmol/l) were not significantly different from those found prior to starting therapy (38.13 +/- 8.44 nmol/l). In conclusion, these results suggest that correction of the anemia with rhEPO therapy potentiates GH responses to direct pituitary stimulation with GHRH although it is unable to restore the blunted response of GH to clonidine that is found in CAPD patients.