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The isolated ACTH deficiency is a scarcely diagnosed disease of heterogeneous nature. Two patients with isolated deficiency of ACTH in whom the initial diagnosis was of primary suprarrenal failure are reported. In the first case this diagnosis was performed after hospital admission for deterioration of the level of consciousness and the development of an acute suprarrenal crisis in the course of nosocomial pneumonia. In the second case the clinical manifestations began as weakness, anorexia, weight loss and lymphocytosis with eosinophilia. In both patients an increase in the thyrotropic hormone was detected leading to suspicion of the existence of associated primary hypothyroidism. Finally, several studies were carried out (basal measurements of cortisol and ACTH, stimulation with continual perfusion of ACTH, insulinic hypoglycemia, global study of adenohypophysary function, ACTH CRF release factor test, computerized tomography of the pituitary region) in both patients leading to the definitive diagnosis of isolated ACTH deficiency of idiopathic cause of possible pituitary origin without the existence of other associated hormonal deficiencies.

The effect of corticosteroids on beta cell function and humoral immune response in type 1 diabetes was tested in a 2-month trial conducted on 32 newly diagnosed patients (age 22.8 +/- 1.4 years, mean +/- S.E.M.). Prednisone was administered at immunosuppressive dosage (1 mg.kg-1.day-1) during the initial 10 days and at a maintenance dosage (0.3 mg.kg-1.day-1) for 50 days. Patients (n = 32) were enrolled within 6 weeks after diagnosis and matched in pairs for age, sex, presence of islet cell antibodies (ICA) and glucagon stimulated C-peptide levels. Insulin discontinuation was not contemplated. All the patients who received prednisone became ICA during treatment but in some (4 out of 10) this effect was only transient. Insulin antibodies (IA) were significantly lower in the prednisone group at second and third month (P < 0.05). No patient experienced complete remission but in 10 prednisone and 4 control patients the insulin requirements were below 0.3 IU/kg (P < 0.05). With similar glycemia the fasting C-peptide levels were higher in the treated patients. The profile of the insulin requirements during the follow-up was different in the two groups and at 9 months the prednisone group needed less insulin than the control (P < 0.05). Interestingly, within the prednisone-treated group and after 6 months, the levels of stimulated C-peptide improved significantly among the ICA+ patients while they were steady or declined in ICA- (P < 0.01). The analysis of variance covariance confirmed a positive interaction between ICA and the administration of prednisone on the outcome of beta cell function.(ABSTRACT TRUNCATED AT 250 WORDS)

We have studied a family with an autosomal dominant inheritance of primary localized cutaneous amyloidosis (PLCA) and familial medullary thyroid carcinoma (MTC). Ten family members were screened for multiple endocrine neoplasia (MEN) 2; five were found to have MTC and two had C-cell hyperplasia. None had evidence of phaeochromocytoma or parathyroid abnormalities. Five of these seven patients presented characteristic interscapular hyperpigmented lesions, showing dermal amyloid deposits in two of the four patients in which a biopsy was performed. The data are analysed in the light of two recent reports of MEN 2A associated with identical lesions. We conclude that PLCA should be sought in MTC patients, even if no other endocrinopathies are present. This may be informative of the familial character of MTC in index cases and also of the tumour gene status in family members who are being screened.

The HLA haplotype and its relationships with clinical, biological and immunological parameters were analyzed in a group of 87 Spanish type 1 diabetic patients at the clinical onset of the disease. The frequency of HLA-B18, DR3 and DR4 antigens was significantly increased whereas DR2, DR5 and DR7 were decreased in comparison with 189 healthy unrelated controls without family history of diabetes. DR3 showed a maximum relative risk for diabetes (5.5) whereas DR4 had a lower one (4.0). HLA-DR4 patients were younger at the time of diagnosis than DR4 negative (16.7 vs 21.4 years). We found no statistically significant relationship between HLA antigens and the other variables studied including the presence of islet cell antibodies, complement fixing islet cell antibodies, insulin autoantibodies, organ-specific antibodies, fasting and maximal glucagon stimulated C-peptide levels, initial glycemia and glycosylated hemoglobin.

Primary empty sella is a neuroanatomical condition which is more common in middle aged obese multiparous females with long-standing hypertension. Usually there are no symptoms, but occasionally nonspecific headache may be present. Hormone studies are commonly normal in these patients, although several functional hypothalamic and pituitary abnormalities have been reported. We report a 64-year-old female with primary empty sella in whom Cushing's disease was diagnosed. The association of both disorders is exceptional.

A patient presented with post-traumatic hypopituitarism, where transient diabetes insipidus, high prolactin levels and prolonged and delayed TSH rise after TRH suggested a hypothalamic lesion. Although there was no gonadotropin response to LHRH as one could have expected, following repeated administration of LHRH, the LH response returned to normal, thus confirming a hypothalamic cause for his hypogonadism.

Recently the spontaneous development of insulin autoantibodies (IAA) has been detected in patients at diagnosis of Type I diabetes mellitus before the beginning of insulin treatment. The present study was undertaken to investigate if the presence of IAA at clinical onset of IDDM may act as a new marker of the beta cell function. The results obtained showed that IAA were present in 44% of newly diagnosed diabetic patients before therapy. Patients without IAA displayed a higher C-peptide secretion than those with IAA, at six months (12.11 +/- 5.08 versus 5.88 +/- 3.25 ng/ml/10 min.)(X +/- SD) and at twelve months (10.45 +/- 3.05 versus 4.90 +/- 5.25 ng/ml/10 min)(X +/- SD) of the follow up period. HbA1 levels, and insulin requirements were similar in both groups (IAA+ and IAA-). We conclude that the presence of insulin autoantibodies at clinical diagnosis, before initiating insulin treatment, may well predict the loss of the beta cell function.

A 26-yr-old male was submitted to bilateral adrenalectomy in 1977 for Cushing's syndrome. Some months later he developed intense skin hyperpigmentation together with increased ACTH levels (149 to 4000 ng/l). The sellar region was always normal in X-ray studies. In April 1985, when the patient complained of chest pain, a chest x-ray showed a polycyclic mass in the upper left lobe of the lung. ACTH ranged from 20,000 to 100,000 ng/l, with no response to CRF or cyproheptadine administration. Urinary 5-OH-indolacetic acid was negative. Thoracotomy was performed in July 1985 with resection of two intrapulmonary masses. Histologic study demonstrated a carcinoid tumor, with positive neuron-specific enolase and ACTH immunochemical stain. ACTH concentration in tumoral tissue was 91 pg/g tissue. After surgery ACTH fell dramatically to 37 ng/l, and has remained at this level since then, associated with resolution of the skin hyperpigmentation.

Erythromelalgia is a syndrome characterized by erythema, burning pain and increased skin temperature of the affected extremities. It can be either primary (idiopathic) or secondary, but both forms require a critical temperature between 32-36 degrees C to provoke the crisis. Among the secondary forms, its association with diabetes mellitus is infrequent and its significance is little known. The histological studies have been fundamentally performed in patients with this syndrome affected by thrombocythemia; vascular thrombosis and fibromuscular intimal arteriolar proliferation were the prominent findings not corroborated in patients with the primary form. We studied one patient with acute diabetic neuropathy who developed erythromelalgia. We noted the absence of histopathological lesions, suggesting a disorder in vascular motility regulation favored by the severe neuropathy, without being able to discount a possible immunomediated mechanism. We describe the favourable evolution of the patient after treatment with aspirin and methysergide.

A 24 years old male with pseudohermaphroditism due to a deficiency in 17-ketosteroid reductase activity is described. Plasma delta 4 is 21 times higher than normal for an adult male, delta 4/T is greater than 6, both E1 and F2 are elevated and E1/E2 = 3. There is very slight modification of delta 4 on administration of ACTH, dexamethasone, hCG and fluoxymesterone. Steroid concentrations in the spermatic veins and arteries confirm the testicular origin of the increased secretion of delta 4 and E1 and show a lower secretion by the cryptorchidic testis. In vitro testicular tissue incubation and fibroblast studies confirm the 17-ketosteroid reductase deficiency and rule out any other anomaly as the cause of the ambiguous genitalia. Psychologically the patient seemed to be identified with a female social and sexual role in spite of her advanced degree of virilization.

Five obese patients were studied during 7 days, 750 mg of tolbutamide, per os, was given. Blood samples were drawn at basal state and at 3, 5, 7 days during the treatment and 6 days after it. The values of transglutaminase activity (that in the basal state were similar to that in the controls) decreased significantly at the seventh day of treatment (72.3%). This decrease was transient and rapidly returned to the basal values when the drug was suspended. The results suggest that sulfonylureas exert in part their hypoglucemic effect by modificating the insulin receptor binding through the inhibition of transglutaminase activity.

The effectiveness of ketoconazole for the therapy of Cushing's syndrome, both of adrenal and pituitary origin, was retrospectively evaluated. To this end, the clinical and hormonal results in 5 patients were assessed. There were 4 females and one male, with ages ranging between 17 and 64 years. Three of them, who had Cushing's disease, received sustained treatment with ketoconazole when other therapeutic measures had failed. The two remaining patients (one with Cushing's disease and the other with adrenal adenoma) were treated with this drug in the preoperative period to alleviate the deterioration in the clinical condition caused by hypercortisolism. The clinical evolution of the patients is described, as well as the plasma adrenocorticotropin (ACTH) and the free cortisol in 24 hour urine in the subsequent controls. In view of the study results, we feel that ketoconazole is an effective treatment for the long term control of Cushing's syndrome. In addition, it may be also useful as preoperative therapy in those patients severely deteriorated by the sustained hypercortisolism.