Spanish consensus for the management of patients with anaplastic cell thyroid carcinoma.

Anaplastic thyroid cancer (ATC) is the most aggressive solid tumor and almost uniformly lethal in humans. The Boards of the Thyroid Cancer Group of the Spanish Society of Endocrinology and Nutrition and the Grupo Español de Enfermedades Huérfanas e Infrecuentes of the Spanish Society of Oncology requested that an independent task force draft a more comprehensive consensus statement regarding ATC. All relevant literature was reviewed, including serial PubMed searches together with additional articles. This is the first, comprehensive Spanish consensus statement for ATC and includes the characteristics, diagnosis, initial evaluation, treatment goals, recommendations and modalities for locoregional and advanced disease, palliative care options, surveillance, and long-term monitoring. Newer systemic therapies are being investigated, but more effective combinations are needed to improve patient outcomes. Though more aggressive radiotherapy has reduced locoregional recurrences, median overall survival has not improved in more than 50 years.

Consensus on the management of advanced radioactive iodine-refractory differentiated thyroid cancer on behalf of the Spanish Society of Endocrinology Thyroid Cancer Working Group (GTSEEN) and Spanish Rare Cancer Working Group (GETHI).

Thyroid cancer is the single most prevalent endocrine malignancy; differentiated thyroid cancer (DTC) accounts for more than 90 % of all malignancies and its incidence has been rising steadily. For more patients, surgical treatment, radioactive iodine (RAI) ablation, and thyroid-stimulating hormone (TSH) suppressive therapy achieve an overall survival (OS) rate of 97.7 % at 5 years. Nevertheless, locoregional recurrence occurs in up to 20 % and distant metastases in approximately 10 % at 10 years. Two-thirds of these patients will never be cured with radioactive iodine therapy and will become RAI-refractory, with a 3-year OS rate of less than 50 %. Over the last decade, substantial progress has been made in the management of RAI-refractory DTC. Given the controversy in some areas, the Spanish Task Force for Thyroid Cancer on behalf of Spanish Society of Endocrinology Thyroid Cancer Working Group (GTSEEN) and the Spanish Rare Cancer Working Group (GETHI) have created a national joint task force to reach a consensus addressing the most challenging aspects of management in these patients. In this way, multidisciplinary management should be mandatory and nuclear medicine targeted therapy, novel molecular targeted agents, and combinations are currently changing the natural history of RAI-refractory DTC.

Consensus on management of advanced medullary thyroid carcinoma on behalf of the Working Group of Thyroid Cancer of the Spanish Society of Endocrinology (SEEN) and the Spanish Task Force Group for Orphan and Infrequent Tumors (GETHI).

BACKGROUND: Of all thyroid cancers, <5 % are medullary (MTC). It is a well-characterized neuroendocrine tumor arising from calcitonin-secreting C cells, and RET gene plays a central role on its pathogeny. METHODS: The electronic search was conducted using MEDLINE (PubMed), EMBASE and Cochrane Central Register of Controlled Trials. Quality assessments of selected current articles, guidelines and reviews of MTC were performed. RESULTS: This consensus updates and summarizes biology, treatment and prognostic considerations of MTC. CONCLUSIONS: Multidisciplinary teams and specialized centers are recommended for the management of MTC patients. In the metastatic setting, those patients with large volume of disease are candidates to start systemic treatment mainly if they are symptomatic and the tumor has progressed in the last 12-14 months. Wait and see strategy should be offered to patients with: disseminated disease with only high levels of calcitonin and no macroscopic structural disease, low burden and absence of progression.

Actualización de las recomendaciones para la evaluación y tratamiento de la osteoporosis asociada a enfermedades endocrinas y nutricionales. Grupo de trabajo de osteoporosis y metabolismo mineral de la SEEN / Update of recommendations for evaluation and treatment of osteoporosis associated to endocrine and nutritional conditions. Working Group on Osteoporosis and Mineral Metabolism of the Spanish Society of Endocrinology

Objetivo: Actualizar las recomendaciones previas formuladas por el Grupo de trabajo de osteoporosis y metabolismo mineral de la Sociedad Española de Endocrinología y Nutrición (SEEN) para la evaluación y el tratamiento de la osteoporosis asociada a diferentes enfermedades endocrinas y alteraciones nutricionales. Participantes: Miembros del Grupo de trabajo de osteoporosis y metabolismo mineral de la SEEN. Métodos: Las recomendaciones se formularon de acuerdo al sistema Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) para establecer tanto la fuerza de las recomendaciones como el grado de evidencia. Se realizó una búsqueda sistemática en PubMed de las nuevas acerca de cada enfermedad usando las siguientes palabras clave asociadas al nombre de cada proceso patológico: AND osteoporosis, fractures, bone mineral density, bone markers y treatment. Se revisaron artículos escritos en inglés con fechas de inclusión comprendidas entre el 18 de octubre de 2011 y el 30 de octubre de 2014. Tras la formulación de las recomendaciones estas se discutieron de forma conjunta por el Grupo de trabajo.Conclusiones: Esta actualización resume los nuevos datos acerca de la evaluación y tratamiento de la osteoporosis en las enfermedades endocrinas y nutricionales que se asocian a baja masa ósea o a un aumento del riesgo de fractura.(AU)

Objective: To update previous recommendations developed by the Working Group on Osteoporosis and Mineral Metabolism of the Spanish Society of Endocrinology and Nutrition for the evaluation and treatment of osteoporosis associated to different endocrine and nutritional diseases. Participants: Members of the Working Group on Osteoporosis and Mineral Metabolism of the Spanish Society of Endocrinology and Nutrition. Methods: Recommendations were formulated according to the GRADE system (Grading of Recommendations, Assessment, Development, and Evaluation) to describe both the strength of recommendations and the quality of evidence. A systematic search was made in MEDLINE (Pubmed) using the following terms associated to the name of each condition: AND "osteoporosis", "fractures", "bone mineral density", and "treatment". Papers in English with publication date between 18 October 2011 and 30 October 2014 were included. The recommendations were discussed and approved by all members of the Working Group. Conclusions: This update summarizes the new data regarding evaluation and treatment of osteoporosis associated to endocrine and nutritional conditions.(AU)

[Hypophosphatemia in parenteral nutrition: prevention and associated risks factors]. / Hipofosfatemia en nutrición parenteral: prevención y factores de riesgo asociados.

AIM: To determine the incidence of hypophosphatemia in parenterally fed patients, the phosphate amount necessary to prevent this complication and associated risks factors. SETTING: Observational study, not controlled, in a third level hospital. PATIENTS: In-patients with parenteral nutrition with at least a complete laboratory work-up. INTERVENTION: For a complete year, days on parenteral nutrition, administered phosphate and plasmatic ionised calcium levels, y-glutamiltranspeptidase, glucose, phosphate, pre-albumin, urea, and leukocytes were recorded. A multiple stepwise regression analysis and logistic regression are used for data analysis. RESULTS: Eight hundred and twenty seven determinations, corresponding to 401 patients, were included. Significant variables (p < 0.05) were: administered phosphate and ionised calcium serum levels, glucose, pre-albumin, and urea; regression coefficients were 0.004 (95%CI: 0.002 to 0.006), -0.156 (95%CI: -0.270 to 0.037), -0.014 (95%IC: -0.022 to 0.009), 0.005 (95%CI: 0.002 to 0.009) and 0.019 (95%CI: 0.016 to 0.022), respectively; the constant was 1.0735 (95%CI: 0.939 to 1.2079). The risk for developing hypophosphatemia decreased from 0.65 (95%CI: 0.33 to 1.26) to 0.16 (95%CI: 0.078 to 0.35) when administered phosphate varied from the span 7.5-17.5 mmol to values higher than 27.5 mmol. CONCLUSIONS: It is necessary to routinely supplement nutrition with phosphate since its content in commercially available lipidic emulsions is not sufficient to prevent hypophosphatemia in the majority of patients with parenteral nutrition. Phosphate intake must be sufficient to restore the intracellular phosphate deficit and to compensate for the plasmatic phosphate fall, with special attention to poorly nourished, hyperglycaemic or with renal failure patients. Phosphate intakes around 27-37 mmol dramatically decrease the incidence of hypophosphatemia in studied patients, with no recorded cases of severe hypophosphatemia.

Utilidad del tratamiento con yodo radiactivo en el bocio multinodular normofuncionante / Utility of radioactive iodine treatment in multinodular goiter with normal function

No disponible

[Anthropometry and the reference values of body composition by bioelectrical impedance in the adult population of L'Hospitalet de Llobregat]. / Antropometría y valores de referencia de la composición corporal por bioimpedanciometría en la población adulta de L'Hospitalet de Llobregat.

BACKGROUND: The aim of the present study was to assess the anthropometric variables and the reference values of body composition in the adult population of L'Hospitalet de Llobregat, due to the lack of epidemiological studies on this matter in Spain. PATIENTS AND METHODS: We studied 234 normal subjects, 134 males, mean age 41.4 years, and 134 females, mean age 40.7 years, selected from the census of L'Hospitalet de Llobregat and representative of its population in sex and age. We determined anthropometric characteristics, body weight, height, body mass index, waist-hip ratio and body composition parameters: total body water, free fat mass, fat mass and body fat by bioelectrical impedance analyzer. RESULTS: Twenty-four males and 33 females were obese, and out of them 2 males and 4 women presented morbid obesity. The body mass index was higher either in males (p = 0.017) or in females (p = 0. 0001) in the last decades in relation to first decade, and in women was as consequence of higher fat mass (p = 0.0001). The waist-hip ratio was 0.93 (0.08) in male and 0.79 (0.07) in female, and it was high in males in the last decades. CONCLUSION: The present study points out the high prevalence of obesity in our city and the anthropometric characteristics and reference values of body composition in the normal population of L'Hospitalet de Llobregat, remarking the high body mass index in the last decades, especially in women due to an increase of fat mass. The waist-hip ratio was high in males in the last decades.

[Changes in body composition in adult patients with hypopituitarism after substitutive treatment with growth hormone]. / Modificaciones de la composición corporal en pacientes adultos con hipopituitarismo después del tratamiento sustitutivo con hormona del crecimiento.

BACKGROUND: Adult growth hormone (GH) deficiency is associated with changes in body composition, with lower total body water (TBW) and fat free mass (FFM) and higher fat mass (FM). These changes can be modified after sustitutive treatment with GH. PATIENTS AND METHODS: We studied 20 patients, 14 males and 6 females with hypopituitarism and GH deficiency, the mean age was 40.3 years, as well as 20 comparable controls. The diagnosis of GH deficiency was based on the lack of GH response after an hypoglycemic test. We determined body composition by bioelectrical impedance. An initial 6 month double-blind placebo controlled phase was followed by an open treatment phase ending when the patients had received GH for 18 or 24 months. The initial dose was 0.125 U/kg/week during the first month and after 0.25 U/kg/week. RESULTS: The patients showed lower TWB and FFM and higher BF in relation to controls and after 3 months of GH treatment an increase of the TBW, FFM and a decrease in BF and waist/hip ratio was observed with a steady state in the changes of body composition after 3 months that continued 6 months after the GH treatment withdraw. Two patients presented maleolar oedema, 4 arterial hypertension that was settled with GH dose reduction and in the fourth patient the treatment had to be withdraw. Three patients presented carpal tunnel syndrome. In 4 patients the treatment was withdrawn. CONCLUSIONS: In patients with adult GH deficiency, we can observe differences in the body composition that can be significantly modified by GH treatment.

Tumor necrosis factor system activity is associated with insulin resistance and dyslipidemia in myotonic dystrophy.

Myotonic dystrophy (MyD) is a multisystem autosomal dominant disorder associated with progressive muscle wasting and weakness. The striking metabolic abnormality in MyD is insulin resistance. The mechanism by which target tissues are insensitive to insulin action remains uncertain. In a recent study, plasma soluble tumor necrosis factor receptor (sTNFR)2 levels were found to be associated with muscle tissue mass and insulin resistance. Given these associations, we speculated that disorders of the muscle cell membrane could lead simultaneously to insulin insensitivity and sTNFR2 leakage in MyD. To test this hypothesis, we measured the levels of circulating sTNFR1 and sTNFR2 and insulin resistance in MyD patients. We studied 22 MyD patients and 24 age-, BMI-, and fat mass-matched control subjects. Both MyD men and women showed higher plasma insulin levels in the presence of comparable glucose concentrations than did control subjects. sTNFR2, but not sTNFR1, levels were approximately 1.5-fold higher in MyD patients. In parallel with these findings, the fasting insulin resistance index (FIRI) was also higher in MyD patients. In fact, in the whole population, fasting insulin and FIRI strongly correlated with sTNFR2 in both men (r = 0.77 and r = 0.81, P<0.0001, respectively) and women (r = 0.67 and r = 0.64, P = 0.001, respectively). sTNFR2 levels were also associated with the insulin sensitivity index (S(I)), calculated from an oral glucose tolerance test (OGTT) according to the method by Cederholm and Wibell (r = -0.43, P = 0.006). We constructed a multiple linear regression to predict FIRI, with BMI, waist-to-hip ratio, and sTNFR2 as independent variables. In this model, both BMI (P = 0.0014) and sTNFR2 (P = 0.0048) levels contributed independently to 46% of the variance of FIRI. In another model, in which FIRI was substituted for S(I) from the OGTT, both BMI (P = 0.0001) and sTNFR2 (P = 0.04) levels contributed independently to 48% of the variance of S(I) from the OGTT. Plasma cholesterol and triglyceride concentrations were significantly increased in MyD patients. sTNFR1 and sTNFR2 levels were found to be strongly associated with plasma cholesterol, LDL cholesterol, and triglycerides. sTNFR1 and sTNFR2 also correlated with serum creatine kinase activity in MyD patients (r = 0.57, P = 0.006; r = 0.75, P<0.0001, respectively). In conclusion, here we describe, for the first time to our knowledge, a relationship between insulin action and plasma sTNFR2 concentration in MyD patients. We have also found increased concentrations of plasma triglycerides and cholesterol levels in parallel with sTNFR1 and sTNFR2 concentrations in MyD patients. We speculate that the latter associations are dependent on, and secondary to, increased tumor necrosis factor (TNF)-alpha action. Whether TNF action is implicated in the pathogenesis of MyD or is a simple marker of disease activity awaits further studies.

[Changes in the lipid profile and thyroid function in adult patients with hypopituitarism after substitutive treatment with growth hormone]. / Modificaciones del perfil lipídico y de función tiroidea en pacientes adultos con hipopituitarismo tras tratamiento sustitutivo con hormona del crecimiento.

BACKGROUND: Adult growth hormone (GH) deficiency is associated with changes in serum lipid levels that can modify after GH substitution. METHODS: We studied 18 patients with GH deficiency treated with GH for 18 or 24 months. RESULTS: A decrease of total cholesterol, LDL with an increase in HDL without triglycerides changes was observed. T4 levels decreased and T3 increased. CONCLUSIONS: The GH substitution treatment in patients with GH deficiency improves the lipid profile and promotes the T4 to T3 conversion.

[Results of treatment of Graves-Basedow disease with 131I at low calculated doses]. / Resultados del tratamiento de la enfermedad de Graves Basedow con 131I a dosis bajas calculadas.

OBJECTIVE: To evaluate the results of treatment of Graves' disease with 131I at low calculated doses. METHODS: A total of 333 patients with Graves' disease were treated with low calculated doses of 131I on the basis of thyroid size and 131I uptake (mean doses = 6.6 +/- 1.9 mCi). The mean follow-up was 24.4 months (range 12-145). RESULTS: The accumulated likelihood of hypothyroidism at 145 months of follow-up was 89.8% (Kaplan-Meier method) and relapse 26%. Pretreatment levels of T3 above 9 nmol/l were associated with a lower incidence of hypothyroidism (p = 0.049, Mantel-Cox method). Pretreatment levels of T4 above 300 nmol/l were associated with a higher risk of therapy failure (odds ratio 3.27; 95% confidence interval = 1.3-8.2, Cox method). Age, sex, previous therapy with anti-thyroid agents or surgery, 131I uptake, initial and total dose of 131I, number of administered doses and development of transient hypothyroidism were not predictive of the evolution of thyroid function. CONCLUSION: Therapy of hyperthyroidism (Graves' disease) with low calculated doses of 131I shows a high incidence of hypothyroidism, also increasing the cost involved in estimating the dose and long-term follow-up.

[Autoimmune thyroid pathology in recently diagnosed diabetes mellitus type 1]. / Patología tiroidea autoinmunitaria en diabetes mellitus tipo 1 de reciente diagnóstico.

OBJECTIVE: To analyze the prevalence of autoimmune thyroid disease among adult patients with recently diagnosed diabetes mellitus type I and its possible correlation with beta-cell autoimmunity markers (ICA, GAD, and IA 2) and with the presentation characteristics of diabetes mellitus. PATIENTS AND METHODS: A total of 100 patients diagnosed from 1992 to 1996 were included and anti-thyroid antibodies (Ac), anti-thyroglobulin (aTG) and antiperoxidase (aTPO) were measured. A comparison followed of the clinical characteristics, biochemical markers, and beta-cell immunity markers between the group of patients with positive and negative antibody determinations. Differences between groups were compared by the Student "t" test and non-parametric tests were used for cases not fulfilling the application conditions. RESULTS: Among the 100 patients, 25 had Ac+, two with previously known thyroid pathology and eight diagnosed at that moment. The group with Ac+ was characterized by a predominance of females (68% vs 32%; p = 0.001), lower bicarbonate levels (18.6 +/- 6.1 vs 21.3 +/- 6.4; p = 0.026) and higher requirements for insulin at discharge (0.77 +/- 0.22 vs 0.59 +/- 0.25 IU/kg; p = 0.002). Among patients in the Ac+ group, patients with thyroid pathology were characterized by a higher prevalence of females (90% vs 53.3%; p = 0.05) and a higher percentage of individuals with high anti-TPO titres (80% vs 33.3% higher than 400 IU/ml; p = 0.02). ICAs (66.6% vs 26.6% higher than 40 U JDF; p = 0.05) and IA2 (44.4% vs 0% higher than 12 IU/ml, p = 0.01). CONCLUSIONS: There is a high prevalence of thyroid pathology prevalence among our adult population with recently diagnosed DMI. Patients with thyroid autoimmunity have higher antibody titres to beta-cell and a somewhat more severe clinical presentation form. Prospective studies are required to determine the long term relevance of these differences.

[Prevalence and significance of lymphocyte infiltration in papillary carcinoma of the thyroid gland]. / Prevalencia y significado de la infiltración linfocitaria en el carcinoma papilar del tiroides.

OBJECTIVE: We have investigated the prevalence, signification and prognostic value of lymphocytic infiltration associated to differentiated thyroid carcinoma in our series of differentiated carcinoma of the thyroid. METHODS: We studied the presence of lymphocytic infiltration in 223 patients effected of differentiated thyroid carcinoma, 138 of them were papillary carcinoma. The diagnostic was made with optic microscopy and we studied antithyroid antibodies in these patients. In survival analysis we studied all the variables of the patients and the event used as end point was death due to thyroid carcinoma, summarized in Kaplan-Meir curve and Cox method. RESULTS: We found eight patients with differentiated thyroid carcinoma, six with papillary carcinoma, and lymphocytic thyroiditis and in three cases, antithyroid antibodies were present at low levels. We did not found any difference between the two groups and the survival rate was similar. CONCLUSIONS: These data support that in our series the prevalence of lymphocytic infiltration was low and probably without prognostic signification.

Expression of ICAM-1 in distant metastatic thyroid carcinoma.

Distant metastasis from follicular thyroid carcinoma developed in a 48-year-old woman 11 yr after the resection of the primary tumor. Distant metastasis consisted in invasion of the left infraspinatus muscle by malignant thyroid cells. After its surgical removal, in the following 6-8 months multiple metastasis to distant skeletal muscle and brain appeared, and despite chemotherapy and local radiotherapy, the patient finally died. Intercellular adhesion molecule-1 (ICAM-1), a single chain transmembrane glycoprotein, was detected on the surface of cells of the metastatic tissue. Although ICAM-1-positive staining has been recently described in primary tumors such as papillary adenocarcinoma, and metastatic tumors from skin, brain, thymus, liver, adrenal gland and prostate, to our knowledge its expression on distant metastasis from thyroid carcinoma has not been previously reported.

[The COMBELL project. Analysis of the medical clinical competence]. / El proyecto COMBELL. Un análisis de la competencia clínica médica.

BACKGROUND: The most frequent tests for evaluate medical education in Spain, do not analyze clinical competence. The aims of this project was to introduce a method for the assessment of clinical skills using the simulation methodology with standardized patients. METHODS: All 83 first-year medical residents were evaluated. Three evaluation exercises were used in all study. The first was 10 standardized patients encounters, the second was 100 multiple choice questions, and the third 60 clinical images. Sixty-four last year medical students were evaluated using the same 10 standardized patients. RESULTS: The global mean score for the residents was 56.7% for all the encounters, and was lower in physical examination and patients notes. The global mean score for the students was 57.1% and was also lower in physical examination. We did not find correlations between clinical competence assessment, multiple choice-questions, MIR exam and clinical images. CONCLUSIONS: Our results show that: this assessment method was successful; the clinical competence levels of our residents and students, and the lack of statistical correlation between this method and other methods, which, basically analyze cognitive capacities.

[An evaluation of the clinical competence of a population of specialist physicians educated by the medical internship and residency system]. / Evaluación de la competencia clínica de una población de médicos especialistas formados por el sistema MIR.

BACKGROUND: The quality of physicians who have undergone resident official training (MIR) should logically be better than that of the remaining physicians who were not able to enter into this official training. The present study was designed with the aim of verifying this hypothesis. METHODS: A sample of physicians who underwent the MIR examination in 1982 and who upon passing the same were permitted to initiate the MIR training in 1983 was selected. The group was subdivided into MIR and no MIR and according to the specialty followed. When the physicians were practicing as specialists two types of surveys were carried out with one being by telephone and the other personal in which the personal characteristics, preparation for the MIR test, professional satisfaction and personal motivation were analyzed. The pharmaceutic prescriptions of both groups were analyzed according to indicators of the Servei Català de la Salut (Catalonian Health Service) and the opinion of colleagues of each of the members of each group was evaluated with another questionnaire. The written resolution of hypothetical clinical cases were given to each of the individuals included. A level of global competence defined as a percentage for the following components was identified using: curricular evaluation (10%), professional satisfaction (20%), personal motivation (10%), hypothetical case resolution (35%) and peer opinion (25%). RESULTS: The global competence of the physicians trained under the MIR system was greater than that of the no MIR group (p < 0.01). On analysis by sections the differences of greatest note were observed in the resolution of hypothetical cases (p < 0.0001), curricular evaluation (p < 0.0001) and the quality of pharmaceutical prescription (p < 0.0001). The differences were less of note in comparison of personal motivation (p < 0.02) and professional satisfaction (p < 0.02). No differences were observed in peer opinion. CONCLUSIONS: The professional quality of physicians trained by MIR who presented for the 1982 examination in Catalonia and practiced in medical specialties is greater than that of a comparable group with regard to professional practice.

Pituitary apoplexy into nonadenomatous tissue: case report and review.

Pituitary apoplexy into nonadenomatous tissue is extremely rare. The authors describe a 20-year-old woman with symptomatic pituitary hemorrhage into an apparently intrasellar malignant teratoma, which caused headache, visual impairment, involvement of III, IV, VI, and 1st division of the V cranial nerves, and hypopituitarism. Diabetes insipidus had developed previously. Magnetic resonance scans had a high-intensity signal in the pituitary on T1- and T2-weighted images, and lack of the signal of the posterior pituitary. Transsphenoidal approach, radiotherapy, and chemotherapy management did not preclude a fatal outcome.

[Postgraduate training in urology]. / La formación postgrado en urología.

Presentation of an updated protocol for training of In-house Urologists. Preparation of this protocol was the result of a pilot program undertaken in our Hospital by the Teaching Committee. The protocol contemplates in an comprehensive way all the activity developed by In-house physicians during their training, at the end of which the Teaching Committee prepares a curriculum approved by the Urology Tutor and the Consultant. With this a better assessment of the knowledge, capacities and attitudes of trained urologists can be obtained.

Study on growth hormone and insulin secretion in myotonic dystrophy.

Growth hormone (GH) levels were measured in 12 patients with myotonic dystrophy (MD; 7 men and 5 women, aged 21-49 years) and 14 volunteers after administration of 100 micrograms GH-releasing hormone (GHRH; 1-29). A 75-g oral glucose tolerance test was carried out to determine glucose, insulin, plasma C-peptide, and urinary C-peptide. The GH level in six MD patients responded normally to GHRH (group I), with a peak of 17.1 +/- 1.46 micrograms/l, compared with controls (27.8 +/- 19.6 micrograms/l, NS), and that in the other six patients responded subnormally, with a peak of 3.15 +/- 1.46 micrograms/l, lower than in controls and in group I patients (P < 0.001). In group I the insulin response to the glucose tolerance test showed hyperinsulinism and was lower than that in group II patients; stimulated C-peptide was also higher in group II than in group I and in controls; urinary C-peptide levels were parallel to those in previous data. In all MD patients there were a negative correlation between absolute values of GH response to GHRH and insulin response to glucose tolerance test (r = -0.79, P < 0.001). Our data suggest that the failure in GH release and peripheral insulin action is due to a generalized defect in cellular membrane function in MD patients.