Glucagon test in insulinoma: Is it useful?

Diagnosis of endogenous hyperinsulinism caused by insulinoma is based on confirmation of hypoglycemia during the symptoms associated to elevated insulin levels. Patients with insulinoma may demonstrate an excessive insulin response and subsequent hypoglycemia after 1 mg of glucagon iv injection. Glucagon test was performed in 11 patients with insulinoma before therapy and in 4 after therapy. Our study suggests that the presence of plasma glucose levels less than 55 mg/dl and below baseline at time 120 min of glucagon test strongly reinforce the diagnosis of insulinoma.

Magnetic resonance guided focused ultrasound surgery. Ablation of soft tissue at bone-muscle interface in a porcine model.

BACKGROUND: Pain management treatments of patients with bone metastases have either efficacy problems or significant side effects. Percutaneous radiofrequency ablation has recently proved to be of palliative value. Magnetic resonance guided focused ultrasound surgery (MRgFUS) uses focused ultrasonic energy to non-invasively create a heat-coagulated lesion deep within the body in a controlled, accurate manner. The surgeon can monitor and control energy deposition in real time. This technology represents a potential treatment modality in oncological surgery. We investigated the ability of two MRgFUS methods to accurately and safely target and ablate soft tissue at its interface with bone. MATERIALS AND METHODS: Heat-ablated lesions were created by MRgFUS at the bone-muscle interface of 15 pigs. Two different methods of energy delivery were used. Temperature rise at the target adjacent to bone was monitored by real time MR thermal images. Results were evaluated by MRI (magnetic resonance imaging), nuclear scanning and by histopathological evaluation. RESULTS: Soft tissue lesion sizes by both methods were in the range of 1-2 cm in diameter. Targeting the focus 'behind' the bone, achieved the same result with a single sonication only. Follow up MRI and histopathological examination of all lesions showed focal damage at its interface with bone and localized damage to the outer cortex on the side closer to the targeted tissue. There was no damage to non-targeted tissue. CONCLUSION: MRgFUS by both energy deposition methods can be used to produce controlled well-localized damage to soft tissue in close proximity to bone, with minimal collateral damage.

MR-guided focused ultrasound surgery (MRgFUS) for the palliation of pain in patients with bone metastases--preliminary clinical experience.

BACKGROUND: Magnetic resonance-guided focused ultrasound surgery (MRgFUS) is a noninvasive thermal ablation technique, shown to be clinically effective in the treatment of uterine fibroids and is being evaluated as a method of thermal ablation of benign and malignant breast tumors. To evaluate the safety and initial efficacy of MRgFUS for the palliation of pain caused by bone metastases, in patients for whom other treatments are either not effective or not feasible. MATERIALS AND METHODS: Thirteen patients suffering from symptomatic bone metastases underwent MRgFUS procedure. Treatment safety was evaluated by assessing the incidence and severity of device-related complications up to 6 months after treatment. Effectiveness of pain palliation was evaluated by visual analog scale, pain questionnaires and changes in the patients' medication. RESULTS: Fifteen procedures were carried out. Mean follow-up was 59 days. Twelve patients received adequate treatment and were available for follow-up. Two patients died due to disease progression during the first month after treatment. No severe adverse events were recorded. The remaining 10 patients reported prolonged improvement in pain score and/or reduced analgesic dosage. CONCLUSION: MRgFUS may provide a safe and effective noninvasive alternative for the palliation of pain, caused by bone metastases.

Novel vasopressin type 2 (AVPR2) gene mutations in Brazilian nephrogenic diabetes insipidus patients.

Nephrogenic diabetes insipidus (NDI) is an inherited disorder characterized by renal resistance to the antidiuretic effect of arginine vasopressin (AVP), resulting in polyuria, polydipsia, and hypoosmolar urine. In the vast majority of cases, NDI is associated with germ-line mutations in the vasopressin receptor type 2 gene (AVPR2) and in about 8% of the cases with the water channel aquaporin-2 gene (AQP-2) mutations. To date, approximately 277 families with 185 germ-line mutations in the AVPR2 gene have been described worldwide. In the present study, the AVPR2 gene was genotyped in eight unrelated Brazilian kindred with NDI. In five of these NDI families, novel mutations were noted (S54R, I130L, S187R, 219delT, and R230P), whereas three seemingly unrelated probands were found to harbor previously described AVPR2 gene mutations (R106C, R137H, R337X). Additionally a novel polymorphism (V281V) was detected. In conclusion, although NDI is a rare disease, the findings of mutations scattered over the entire coding region of the AVPR2 gene are a valuable model to determine structure function relationship in G-protein-coupled receptor related diseases. Furthermore, our data indicate that in Brazil the spectrum of AVPR2 gene mutations is "family specific".

Pituitary-adrenal dynamics after ACTH-secreting pituitary tumor resection in patients receiving no steroids post-operatively.

It has recently been suggested that the classical routine of glucocorticoid administration before and after transsphenoidal surgery (TSS) in Cushing's disease (CD) patients may not be necessary, since it is likely that peritumoral normal corticotrophs are not completely suppressed during this period. We compared the dynamics of ACTH and cortisol from a group of CD patients (cured and not cured), receiving no steroids post-operatively, with a control group of acromegalic patients who presented normal hypothalamic-pituitary-adrenal (HPA) axis. Blood samples for ACTH and cortisol determination were obtained immediately before, at the end of surgery and at 4, 8, 12, 16, 24, 48 and 72 h after surgery, in 8 cured CD patients (Group I), 9 not cured CD patients (Group II) and in 7 subjects with acromegaly (Group III) who presented normal HPA axis (control group). The mean ACTH level in Group I was significantly lower than in Group III from 4 to 12 h and lower than in Group II from 8 to 12 h post-operatively. The mean cortisol level in Group I was lower than in Groups II and III from 8 to 72 h after surgery. No difference in mean cortisol level was observed among Groups II and III during the evaluated period. The lowest cortisol value in Group II was 193 nmol/l (at 24 h after surgery) and in Group I patients, after 20 h post-operatively, the highest cortisol level was 165 nmol/l. Although all cured CD patients (Group I) presented serum cortisol level lower than 55 nmol/l until 72 h after surgery, none had significant complications related to adrenal insufficiency. Ours findings are in agreement with recent observations that there is probably no need for glucocorticoid administration until clinical and/or laboratorial data are suggestive of adrenal insufficiency. However, we have also shown that a subphysiological HPA axis response could be observed in cured CD patients after TSS, and a definitive conclusion about glucocorticoid management during and after this procedure could not be made on the ground of the few cases studied in the literature.

Outcome of revision hip arthroplasty in patients with a previous total hip replacement for developmental dysplasia of the hip.

Our aim was to determine if the height of the cup, lateralisation or the abduction angle correlated with functional outcome or survivorship in revision total hip replacement in patients with a previous diagnosis of developmental dysplasia of the hip. A retrospective investigation of 51 patients (63 hips) who had undergone revision total hip replacement was performed. The mean duration of follow-up was 119 months. Forty-one patients (52 hips) were available for both determination of functional outcome and survivorship analysis. Ten patients (11 hips) were only available for survivorship analysis. The height of the cup was found to have a statistically significant correlation with functional outcome and a high hip centre correlated with a worse outcome score. Patients with a hip centre of less than 3.5 cm above the anatomical level had a statistically better survivorship of the cup than those with centres higher than this. Restoration of the height of the centre of the hip to as near the anatomical position as possible improved functional outcome and survivorship of the cup.

Prevalence of celiac disease in Brazilian children of short stature

The aim of the present study was to determine the prevalence of celiac disease in children of short stature and to assess whether some of the routine laboratory examinations performed to determine the cause of short stature could suggest the presence of celiac disease. A total of 106 children of short stature and no gastrointestinal symptoms were studied. An extensive endocrine work-up had been negative for all of them and an additional investigation was performed by measuring the concentration of antiendomysial antibody. Patients who were positive for antiendomysial antibody ( > or = 1:10) or who exhibited IgA deficiency (less than 5 mg/dl) were referred for an endoscopic intestinal biopsy. We detected a pathological titer of antiendomysial IgA in six of these patients. Five of them showed histological abnormalities compatible with celiac disease and one had normal histology and was considered to have potential celiac disease. The prevalence of celiac disease in the population studied was 4.7 percent (with another 0.9 percent of the subjects being considered to have potential celiac disease). The children with celiac disease did not differ in any of the parameters tested when compared to those without celiac disease, though they showed an improvement in growth velocity after treatment with a gluten-free diet. We conclude that it is important to test all children with short stature for celiac disease by measuring antiendomysial IgA.

Prevalence of celiac disease in Brazilian children of short stature.

The aim of the present study was to determine the prevalence of celiac disease in children of short stature and to assess whether some of the routine laboratory examinations performed to determine the cause of short stature could suggest the presence of celiac disease. A total of 106 children of short stature and no gastrointestinal symptoms were studied. An extensive endocrine work-up had been negative for all of them and an additional investigation was performed by measuring the concentration of antiendomysial antibody. Patients who were positive for antiendomysial antibody (> or =1:10) or who exhibited IgA deficiency (less than 5 mg/dl) were referred for an endoscopic intestinal biopsy. We detected a pathological titer of antiendomysial IgA in six of these patients. Five of them showed histological abnormalities compatible with celiac disease and one had normal histology and was considered to have potential celiac disease. The prevalence of celiac disease in the population studied was 4.7% (with another 0.9% of the subjects being considered to have potential celiac disease). The children with celiac disease did not differ in any of the parameters tested when compared to those without celiac disease, though they showed an improvement in growth velocity after treatment with a gluten-free diet. We conclude that it is important to test all children with short stature for celiac disease by measuring antiendomysial IgA.

Glucocorticoid receptor gene polymorphisms in ACTH-secreting pituitary tumours.

OBJECTIVE: The inhibitory action of glucocorticoids on the hypothalamic-pituitary axis is disrupted in ACTH-secreting pituitary tumours. The molecular events leading to the development of these tumours and their relative resistance to glucocorticoids are unknown. We investigated the presence of mutations and polymorphisms of the glucocorticoid receptor (GR) gene in corticotropinoma and their possible relationship with the tissue-specific resistance to glucocorticoids. DESIGN AND METHODS: DNA or RNA was extracted from 18 corticotropinomas and the GR gene was amplified by the polymerase chain reaction (PCR) or reverse transcriptase-PCR followed by automated direct sequencing. RESULTS: We did not identify any mutation in the coding region and the exon-intron boundary regions of the GR gene. The polymorphism AAT > AGT at codon 363 (N363S) was found in 17% and the polymorphism AAT > AAC at codon 766 (N766N) in 11% of tumours, both in heterozygous state. The polymorphisms at codons 22 and 23, at introns 3 and 4, and at codon 618, previously described in normal population, were not observed. CONCLUSIONS: Our results show that GR gene mutations are rare and unlikely to contribute to the glucocorticoid resistance observed in corticotropinomas. Polymorphisms in the GR gene might confer a selective advantage to tumorigenesis in corticotropinoma. However, there was no relationship between GR gene polymorphism and clinical presentation, tumour size or surgery outcome, suggesting that tumour growth may not be directly related to alterations of the GR gene structure.

Adrenocorticotropin levels do not change during early recovery of transsphenoidal surgery for ACTH-secreting pituitary tumors.

In patients with ACTH-secreting pituitary tumor the peri-tumoral normal corticotrophs were supposed to be suppressed by cronic hypercortisolemia since frequently they develop transient secondary adrenal insufficiency after pituitary tumor resection and during early postoperative days. We evaluated the ACTH dynamics during transsphenoidal surgery in 16 patients with ACTH-secreting pituitary tumors (6 cured by surgery, 8 not cured Cushing's disease patients and 1 cured by surgery and 1 not cured Nelson's syndrome patients) and tested the hypothesis that in these patients, ACTH secretion from the peri-tumoral normal corticotrophs is inhibited and hence removal of the entire tumor should result in subtle postoperative reduction in plasma ACTH. Blood samples for ACTH determination were obtained from 14 Cushing's disease patients immediately before pituitary gland manipulation and 10, 30, 60, 90, 120, 150 and 300 min after pituitary tumor resection and on postoperative day one. In Nelson's syndrome patients the blood sample was obtained only after tumor removal. All patients received intravenous hydrocortisone during surgery and on the first postoperative day. Patients were considered cured by surgery if they presented adrenal insufficiency after hydrocortisone withdrawal. Mechanical pituitary manipulation induced increase in ACTH level. In all 14 Cushing's disease patients (cured and not cured), mean plasma ACTH levels were significantly greater 10 min after pituitary tumor resection (54.4+/-12.8 pmol/l) than in the premanipulation period (ACTH=26.3+/-5.3 pmol/l) (p=0.005). In Cushing's disease patients, the ACTH levels did not change significantly until 300 min after pituitary tumor resection either in those 6 patients cured by surgery (at 10 min after pituitary tumor resection ACTH was 54.4+/-12.8 pmol/l for all 14 Cushing's disease patients and at 300 min after tumor removal ACTH was 39.0+/-12.6 pmol/l for cured and 41.3+/-15.7 pmol/l for not cured Cushing's disease patients). The ACTH level also persisted high until 300 min after complete pituitary tumor resection in one cured patient with Nelson's syndrome. ACTH level does not change in the early recovery period after ACTH-secreting pituitary tumor, even in those cured patients, and probably peri-tumoral normal corticotrophs are not completely suppressed by cronic hypercortisolemia (and acute glucocorticoid administration) when these patients are under intense stress, like transsphenoidal surgery. Mechanical pituitary manipulation may induce ACTH release in patients with ACTH-secreting pituitary tumors but probably does not interfere in the maintenance of high ACTH-levels during the early postoperative period, since ACTH half-life is only 8-15 min. In patients with ACTH-secreting pituitary tumors, the behavior of the human hypothalamic-pituitary-adrenal system during transsphenoidal surgery does not conform to the specifications of a negative feedback mechanism.

Adrenocortical carcinoma: clinical and laboratory observations.

BACKGROUND: The clinical features and natural history of adrenocortical carcinoma are highly dependent on the type of center reporting their experience. Observations from oncology services suggest a high incidence of nonfunctioning tumors, whereas reports from endocrine clinics emphasize excessive corticoid and androgen production in the majority of tumors. The incidence rate and natural history of childhood adrenal carcinoma generally has been under emphasized. METHODS: Over the past 17 years, the authors have evaluated and treated 47 patients with adrenocortical carcinoma referred to the University of Sao Paulo, 22 of whom were children. RESULTS: There is a bimodal age incidence of adrenal carcinoma, with the disease peaking in the first and fourth decades of life. Childhood adrenal carcinoma is characterized by a high rate of incidence of virilization, marked overproduction of androgens, and a less aggressive clinical course, and appears to be more amenable to surgical and other therapeutic modalities. By contrast, adrenocortical carcinoma occurring in adults presents more commonly as a mixed Cushing and virilizing syndrome, with overproduction of corticoids and androgens and a far more aggressive clinical course, leading to rapid death within months or years. Nonfunctioning adrenocortical carcinoma is less common; it generally occurs in older adults and exhibits a rapid downhill course. Modern day imaging methods have improved the diagnosis and staging of adrenal carcinoma greatly. In the authors' experience, the histologic criteria of Weiss appeared to predict tumor prognosis most accurately, whereas immunologic markers, cytoskeletal markers, DNA ploidy, cell phase markers, and oncogenic probes have yielded inconsistent results to date. Surgical removal of a localized tumor remains the best hope for long term survival. Medical therapy with mitotane and its successors in patients with Stage III or IV (MacFarlane system as modified by Sullivan et al.) disease appear to have added little to longevity or quality of life. CONCLUSIONS: When diagnosed in children, adrenal carcinoma is associated with virilism and a less aggressive natural history; however, when it occurs in adults, the disease presents more commonly as a mixed Cushing-virilizing syndrome and has a virulent course. The Weiss histologic criteria appear to correlate best with disease prognosis, but other histochemical, cell cycle, and genetic markers have not, to date, aided in disease management.

Molecular analyses of the vasopressin type 2 receptor and aquaporin-2 genes in Brazilian kindreds with nephrogenic diabetes insipidus.

Nephrogenic diabetes insipidus (NDI) is associated with germline mutations in two genes: vasopressin receptor type 2 (V2(R)) in X-linked NDI, and the water channel aquaporin-2, in autosomal-recessive disease. Genetic heterogeneity is further emphasized by reports of phenotypically abnormal individuals with normal structural genes. We analyzed both genes in five Brazilian families and the aquaporin-2 gene in two Swedish families with clinical and laboratory diagnosis of NDI, by a combination of denaturing gradient gel electrophoresis (DGGE) and direct DNA sequencing. A novel polymorphism in the aquaporin-2 gene (S167S), but no disease-associated mutations in any tested individual from all seven families, was detected. In two Brazilian families, frameshift mutations were detected in the V2(R) gene: one leading to a premature stop after codon 36 and the other to a longer peptide (462 aa instead of the 373 aa wild-type protein). In two other Brazilian families, probable disease-associated missense mutations were detected: an alanine to proline at codon 163 (A163P) and an asparagine to aspartic acid at codon 85 (D85N). In one Brazilian family, both genes were structurally normal and the aquaporin-2 gene was also normal in the two Swedish kindreds. This report further extends the mutational spectrum of NDI and suggests that there are other mutational or epigenetic events inactivating the two known genes or even novel genes that underlie NDI.

[Subclinical apoplexy in pituitary tumors]. / Apoplexia subclínica em tumores pituitários.

Acute pituitary apoplexy is a rare event, even in patients with pituitary macroadenomas. On the other hand, the presence of necrotic/hemorrhagic areas, especially in macroadenomas, seems to be more common than earlier reported in the CT period. After the introduction of MR in the presurgical workup of these patients, these apopleptic areas have been more easily diagnosed preoperatively. Forty consecutive patients with pituitary macroadenomas were studied with high-resolution 1.5 T T1 coronal, sagittal and axial slices over the sellar region. Special attention was paid in the detection of necrotic, cystic and hemorrhagic areas within these tumors. Ten patients had hemorrhagic/necrotic areas within their tumors, without any sign or symptom of acute apoplexy. These areas varied from small (2 mm) to very large (30 mm) ones. Seven patients had non-secreting tumors, 2 GH and 1 prolactin secreting tumors, which is the same profile of secretory pattern for the whole series (40 patients). The clinical picture included (other than that caused by endocrine secretion) slowly progressive (but not acute) visual loss (n = 8) and headache (n = 3). After surgical decompression of the surrounding structures and visual apparatus, which was facilitated by the presence of the necrotic areas, there was visual improvement in 6 patients and headache resolution in 2. The presence of asymptomatic apopletic areas in these macroadenomas and their absence in microadenomas as can be seen in the literature suggest that they are related more to the size of the tumor than to its endocrine secretion pattern. This is in agreement with a vascular insufficiency hypothesis in the pathogenesis of these lesions.

[Identical twins discordant for Cushing's disease: case report[]. / Gêmeas idênticas discordantes para a doença de Cushing. Relato de caso.

Cushing's disease is rare in children and its occurrence in identical twins is extremely rare. This paper reports on identical twins discordant for Cushing's disease. One of them first presented with a cushingoid phenotype by the age of 10. Her evaluation showed an increased urinary free-cortisol and serum ACTH. Her pattern in the dexametazone suppression tests was compatible with Cushing's disease. MRI disclosed a pituitary macroadenoma which was removed by the transesphenoidal approach. Immunohistochemical studies of the tumor showed the presence of ACTH-producing cells. The patient went into clinical and laboratorial remission after surgery. She re-started to grow after the disappearance of the Cushing's phenotype but she is still shorter than her healthy sister. The latter remains disease-free 4 years after her sister's diagnosis. This represents the third such case reported in the literature. Our findings suggest that acquired factors may be responsible for the genesis of Cushing's disease.

[Pituitary apoplexy followed by endocrine remission. Report of two cases]. / Apoplexia pituitária seguida de remissão endócrina. Relato de dois casos.

Pituitary apoplexy is rare and endocrine remission in patients with apopletic secreting pituitary adenomas is even rarer. This study reports on two patients with pituitary macroadenomas (one with Cushing's disease and the other with acromegaly) in whom endocrine remission occurred after apoplexy. The first patient had Cushing's disease and had an ictus of headache and vomiting after which she started a progressive remission of hypercortisolism. A post-apoplexy MRI disclosed persistence of a sellar and supra-sellar mass. She was submitted to transesphenoidal surgery. An hypertensive hemorrhagic cyst was found with no tumor. The second patient had acromegaly. While performing a LHRH-stimulation test he had an ictus of headache, vomiting, no visual loss and appearance of diabetes insipidus. A CT scan disclosed an intrasellar hematoma. Despite the size of the tumor and since there was no visual impairment, this patient was followed up without surgery. Imaging follow-up showed a progressive shrinkage and disappearance of the mass, which was corroborated by endocrine remission. A high rate of recurrence is reported in such patients in the literature. Both patients are being currently followed-up on a long-term basis.

Cavernous sinus invasion by pituitary macroadenomas. Neuroradiological, clinical and surgical correlation.

The classical imaging gold-standard for this diagnosis is the presence of tumor lateral to the carotid artery. Seventeen patients with pituitary macroadenomas with intraoperative confirmation of cavernous sinus invasion were studied with MRI. Only 8 patients had tumor lateral to the carotid artery; 13 had tumor within the carotid syphon and all lacked the ring enhancement of the medial wall of the cavernous sinus. In 10 patients, widening of the posterior double leaflets of the cavernous sinus could be. All patients were operated by the transesphenoidal route. Only one patient was cured by surgery alone. Only 3 patients disclosing the above mentioned MRI features were identified in a series of 250 patients and did not have cavernous sinus invasion. The present criteria proved to be useful in the pre-operative diagnosis of cavernous sinus invasion and patients' counselling. Pre-operative diagnosis of cavernous sinus invasion of pituitary tumors has a great impact in the management of such patients.

Autosomal recessive deficiency of combined pituitary hormones (except ACTH) in a consanguineous Brazilian kindred.

Familial hypopituitarism represents a clinically and genetically heterogeneous disorder. In a subset of these families, defects in Pit-I, a transcription factor essential for proper pituitary development have been identified as underlying molecular cause. These patients present extreme short stature, GH, PRL and TSH deficiency but intact ACTH, LH and FSH secretion. The pituitary is usually hypoplastic. In this report we describe a consanguineous family (the parents are first cousins) with thirteen siblings. Of the ten living siblings, four (two males and two females) have panhypopituitarism with severe growth failure. They had evidence of growth hormone, prolactin and gonadotropin deficiencies and developed central hypothyroidism late in life. ACTH secretion was normal. Bone age was retarded and dual-photon bone densitometry indicated severe osteoporosis. Combined provocative tests for pituitary hormones indicated blunted responses for GH, LH, FSH and a modest rise in serum PRL and TSH. A clonidine-test failed to induce pituitary GH response. A corticotropin-releasing factor (CRF) provocative test was conducted after 6 months without the use of prednisone with a normal ACTH response after CRF in the affected sibling. Plasma IGF-I and IGF-BP3 were below normal levels. Serum E2 (females) and serum testosterone (males) levels were very low. MRI evaluation of the pituitary indicated pituitary aplasia in all subjects. The phenotype described in this kindred is different from families reported with Pit-1 mutations. However, it resembles previously published kindreds with similar clinical and biochemical findings. The relative preservation of ACTH suggests a genetic defect early in pituitary gland development.

A study of patients with Nelson's syndrome.

OBJECTIVE: The prevalence of Nelson's syndrome has varied greatly, at least in part because of the variability of the diagnostic criteria employed by different authors. We define Nelson's syndrome as the presence of an enlarging pituitary tumour associated with elevated fasting plasma ACTH levels and hyperpigmentation in patients with Cushing's disease after bilateral adrenalectomy. We have compared patients with Cushing's disease who developed Nelson's syndrome after bilateral adrenalectomy with those who did not. Our objective was to find differences between the two groups which might predict the development of Nelson's syndrome. PATIENTS AND METHODS: We have reviewed the records of 30 patients with Cushing's disease after adrenalectomy, and divided them into two groups; I: 14 who developed Nelson's syndrome and II, 16 who did not. The two groups of patients were compared in their clinical, laboratory and imaging data as well as in the therapeutic procedures that preceded the adrenalectomy. RESULTS: The comparison between the two groups of patients demonstrated a highly significant difference in relation to the development of cutaneous hyperpigmentation (100% in group I and 19% in group II) and neuro-ophthalmological symptoms (21% in group I and 0% in group II) after adrenalectomy. There were no significant differences in laboratory data before adrenalectomy. After adrenalectomy, plasma ACTH levels increased significantly in the patients of both groups, but to much higher levels in those who developed Nelson's syndrome. Plasma ACTH concentrations above 154 pmol/l occurred only in the subjects with Nelson's syndrome. Before adrenalectomy, a pituitary tumour was more frequent in the patients who developed Nelson's syndrome (55% vs. 33% at transsphenoidal pituitary exploration). Pituitary surgery and irradiation were undertaken before adrenalectomy in approximately equal numbers of patients in each group. DISCUSSION: The prevalence of Nelson's syndrome was 47% in our series of 30 patients with Cushing's disease after bilateral adrenalectomy. No clinical or laboratory data before adrenalectomy predicted the development of the syndrome. The value of prophylactic pituitary irradiation could not be evaluated from our clinical material. However, after adrenalectomy, the presence of hyperpigmentation and ACTH levels above 154 pmol/l had positive predictive value for the development of Nelson's syndrome. In this situation magnetic resonance imaging (MRI) of the pituitary is mandatory and, if no tumour is detected, MRI should be repeated at intervals.

Oral glucose ingestion increases endurance capacity in normal and diabetic (type I) humans.

The effects of an oral glucose administration (1 g/kg) 30 min before exercise on endurance capacity and metabolic responses were studied in 21 type I diabetic patients [insulin-dependent diabetes mellitus (IDDM)] and 23 normal controls (Con). Cycle ergometer exercise (55-60% of maximal O2 uptake) was performed until exhaustion. Glucose administration significantly increased endurance capacity in Con (112 +/- 7 vs. 125 +/- 6 min, P < 0.05) but only in IDDM patients whose blood glucose decreased during exercise (70.8 +/- 8.2 vs. 82.8 +/- 9.4 min, P < 0.05). Hyperglycemia was normalized at 15 min of exercise in Con (7.4 +/- 0.2 vs. 4.8 +/- 0.2 mM) but not in IDDM patients (12.4 +/- 0.7 vs. 15.6 +/- 0.9 mM). In Con, insulin and C-peptide levels were normalized during exercise. Glucose administration decreased growth hormone levels in both groups. In conclusion, oral glucose ingestion 30 min before exercise increases endurance capacity in Con and in some IDDM patients. In IDDM patients, in contrast with Con, exercise to exhaustion attenuates hyperglycemia but does not bring blood glucose levels to preglucose levels.