[Hypocalcemia and convulsive syndrome in alcoholics--an association frequently not diagnosed]. / Hipocalcemia e síndrome convulsiva em alcoólatras--uma associação freqüentemente não diagnosticada.

UNLABELLED: Hypocalcemia can be a contributory factor for epilepsy and previous studies showed that ethanol decreases plasma calcium. PURPOSE: To establish the prevalence of hypocalcemia in the general convulsive population and to ascertain if there was a specific group of risk for hypocalcemia. METHODS: A prospective study of plasma ionized calcium measurement in 78 consecutive patients admitted owing to seizures at the Emergency Department of Escola Paulista de Medicina was performed. 22% of these patients were alcoholics. The plasma ionized calcium in 44 ambulatory non-convulsive alcoholics was also measured. RESULTS: A high prevalence of hypocalcemia was found in the alcoholic convulsive population (32%), in contrast with the non-alcoholic convulsive group and the alcoholic non-convulsive group (no calcium disturbance in both groups). The alcoholic convulsive group had values of ionized calcium statistically lower than the non-alcoholic convulsive group using the Mann-Whitney test (p < 0.05) [median value = 1.20 mmol/L; range = 1.04-1.32 mmol/L/median value = 1.24 mmol/L; range = 1.16-1.29 mmol/L respectively]. The alcoholic non-convulsive group had values of ionized calcium between 1.17 and 1.32 mmol/L with median value of 1.26 mmol/L; these values were not different from those obtained with the non-alcoholic convulsive patients, however they were higher than the calcium levels in the alcoholic convulsive group (p < 0.05). PTH levels, liver function tests, phosphatemia and amylasemia were normal in all patients. CONCLUSION: This study emphasizes the importance of serum calcium measurement in alcoholic patients presenting seizures and suggests that hypocalcemia correction might be important in these patients.

Hipocalcemia e síndrome convulsiva em alcoólatras: uma associaçäo frequentemente näo diagnosticada / Hypocalcemia and convulsive syndrome in alcoholics: an association frequently not diagnosed

Hipocalcemia é um fator importante contribuinte para a epilepsia, e estudos anteriores mostraram que o etanol diminui o cálcio plasmático. Objetivo. Estabelecer a prevalência de hipocalcemia na populaçao convulsiva em geral e identificar um subgrupo específico de risco para hipocalcemia. Métodos. Realizamos um estudo prospectivo de dosagem de cálcio ionizado plasmático em 78 pacientes consecutivos admitidos no Serviço de Emergência da Escola Paulista de Medicina devido à síndrome convulsiva. Desses pacientes, 22 por cento eram alcóolicas. Foi também dosado o cálcio ionizado plasmático numa populaçao de 44 alcoólatras nao-convulsivos em seguimento ambulatorial. Resultados. Uma alta prevalência de hipocalcemia foi encontrada na populaçao alcoólatra convulsiva (32 por cento), em contraste com os convulsivos nao-alcoólatras e o grupo alcoólatra nao-convulsivo (ambos os grupos sem distúrbio do cálcio). O cálcio ionizado plasmático do grupo de alcoólatras convulsivos teve valores significantemente menores que o grupo de convulsivos nao-alcoólatras (p<0,05) [mediana de 1,20; variaçao entre 1,04 e 1,32 mmoI/L/; mediana de 1,24; variaçao entre 1,16 e 1,29 mmol/L, respectivamente]. O grupo de alcoólatras nao-convulsivos apresentou valores de cálcio ionizado entre 1,17 e 1,32 mmol/L, com mediana de 1,26mmol/L. Estes valores nao diferiram dos obtidos nos convulsivos nao-alcoólatras, mas foram significantmente maiores que os do grupo de alcoólatras convulsivos (p<0,05). Os níveis de paratormônio sérico, funçao hepática, fosfatemia e amilasemia estavam normais em todos os pacientes estudados. Conclusao. Estes estudo mostra a importância da dosagem de cálcio plasmático em pacientes alcoólatras com síndrome convulsiva e sugere que a correçao da hipocalcemia possa ser medida importante a ser adotada nestes casos.

Parathyroid glands in uraemic patients with refractory hyperparathyroidism: histopathology and p53 protein expression analysis.

AIMS: Refractory hyperparathyroidism is a state of parathyroid hyperfunction and hypercalcaemia in uraemic patients with previous secondary hyperplasia. We studied histopathological features and p53 expression in 49 parathyroid glands of uraemic patients (n = 21) with refractory hyperparathyroidism in order to investigate whether p53 abnormalities could be present in parathyroid hyperplasias of chronic renal failure. METHODS AND RESULTS: Nodular hyperplasia was found in 77.5% of the glands (n = 38). The proportion of oxyphil cells and acinar cell arrangements was higher in nodular hyperplasia than in diffuse hyperplastic glands P < 0.001). Duration of renal disease and haemodialysis treatment tended to be longer in patients with nodular hyperplasia. There was no correlation between serum intact PTH (iPTH), calcium and hyperplasia pattern. A trend for a higher glandular mass was found in nodular type hyperplasia (1.88 +/- 2.13 g) than in diffuse type hyperplasia (0.87 +/- 1.28 g; P = 0.06). Nuclear p53 immunoreactivity was shown in 55% of the hyperplastic glands, whereas it was not detected in 12 normal parathyroid glands used as controls. p53 staining was present in c. 82% of the diffuse hyperplastic glands and in 47% of the nodular hyperplastic glands (P = 0.08). CONCLUSIONS: Nodular type hyperplasia was the predominant histopathological pattern in uraemic patients with refractory hyperparathyroidism in our study. Nodular hyperplastic glands characteristically had higher percentage of oxyphil cells, acinar cell arrangements and mass than diffuse hyperplastic glands. A high prevalence of p53 protein expression was found in hyperplastic glands of uraemic patients. Our results suggest that p53 abnormalities might be involved in the pathogenesis of parathyroid hyperplasia in chronic renal failure.

A comparative study of p53 immunoexpression in parathyroid hyperplasias secondary to uremia, primary hyperplasias, adenomas and carcinomas.

OBJECTIVE: To investigate immunoexpression of p53 in parathyroid tumors and hyperplasias and correlate it with the histopathological diagnosis and severity of hyperparathyroidism. DESIGN: A total of 102 parathyroid tissues from archival paraffin-embedded specimens or obtained at surgery between 1988 and 1997 from 65 consecutive individuals with hyperparathyroidism were studied. METHODS: p53 immunoexpression, gland mass, preoperative serum calcium and intact parathyroid hormone (PTH) were analyzed; 14 normal parathyroid glands were used as controls. RESULTS: The histopathological findings were: adenomas (n = 28), primary hyperplasias (n = 12), secondary nodular and diffuse hyperplasias (patients with uremia, n = 57), carcinomas (n = 4) and carcinomatous metastatic tissue (n = 1). Nuclear p53 was detected in 36% of the adenomas, 42% of the primary hyperplastic glands, 72% of the diffuse hyperplasias, 44% of nodular hyperplasias and 40% of the carcinomatous tissues, and was absent from normal glands. p53 expression was significantly more frequent in diffuse hyperplasias than in adenomas (P = 0.037). Serum ionized calcium tended to be higher in p53-positive glands in all histopathological groups; however, the difference was only significant in nodular hyperplasias (P = 0.018). The same trend was observed for serum intact PTH levels of adenomas and nodular hyperplastic glands. Gland mass was not significantly different according to p53 staining. CONCLUSIONS: p53 immunoexpression was not useful in differentiating between the histopathological parathyroid subgroups. p53 immunodetection was particularly frequent in secondary hyperplastic glands of uremic patients. Our study suggests that p53, whether wild-type or mutant, is regulated in parathyroid tumors and hyperplasias. Changes in wild-type p53 may be part of a cellular response to a hyperproliferative condition.

Prospective bone mineral density evaluation in patients with insulin-dependent diabetes mellitus.

The bone mineral density (BMD) in patients with insulin-dependent diabetes mellitus (IDDM) was evaluated prospectively to assess the course of osteopenia in IDDM. We measured BMD in the lumbar spine, femoral region, and total body calcium in 23 patients aged 21-53 years with IDDM for 2.3 to 20 years using a dual energy X-ray absorptiometry. A second BMD measurement was done after 26.5+/-4.1 months in all patients. The blood glucose control, insulin dosage, and disease duration were also assessed. Eleven patients had osteopenia (1 Z-score below the mean values of normal gender- and age-matched individuals). These patients had a longer IDDM duration (8.6+/-5.1 years in osteopenics versus 4.6+/-3.75 years in non-osteopenics; p=0.03). The blood glucose control and insulin dosage were not significantly different throughout the study. The mean spinal BMD was higher in the second evaluation in both osteopenics (0.91+/-0.12 g/cm2 and 0.96+/-0.09 g/cm2, p=0.035) and non-osteopenics (1.24+/-0.15 g/cm2 and 1.29+/-0.16 g/cm2; p=0.02). In the end of the study, however, the osteopenic group persisted with lower subnormal BMD values than the non-osteopenic group (p < 0.001). The small BMD increment observed in the spine did not correlate with changes in the metabolic control or with IDDM duration, but occurred mainly in patients younger than 30 years old. There was no significant change in the femoral BMD or total body calcium. None of the patients developed or significantly worsened the osteopenia. We conclude that diabetic osteopenia, despite being a complication of high prevalence in IDDM, seems to be non-progressive in the majority of patients. In some patients, the spinal BMD increased during observation and may have been due to achievement of peak bone mass.

Osteopenia occurs in a minority of patients with acromegaly and is predominant in the spine.

Acromegaly may induce abnormalities in bone metabolism; however, there are limited data related to bone mineral density (BMD) in this condition. To evaluate the effects of an excess of growth hormone/ insulin-like growth fractor I (GH/IGF-I) in the skeleton, we measured the BMD in spine and femoral region, total body calcium and body composition in 45 patients (24 females and 21 males) aged 21-77 years (median 43 years) with acromegaly for 11.4 +/- 7.5 years (range 0.5-26 years) using a dual-energy X-ray absorptiometer (Lunar DPX). Thirty-four patients had had hypogonadism for 8.6 +/- 6.5 years (1-24 years). Mean serum GH and IGF-I levels were respectively 159 +/- 183 micrograms/l and 843 +/- 497 micrograms/l. Total body calcium was increased in the acromegalics (males: 1272 +/- 217 g, range 916-1816 g; females: 1041 +/- 223 g, range 739-1609 g) when compared with normal individuals (males: 1115 +/- 144 g, range 856-1398 g; females: 909 +/- 144 g, range 511-1311 g; p = 0.01). The lean body mass was significantly higher in acromegalic patients (p < 0.001) compared with normal individuals. There was a tendency for a lower fat percentage in the acromegalics; however, this difference was not significant. Osteopenia (1 Z-score below the mean) was found in the spine in 20% (n = 9) of the patients, while BMD was decreased in the femoral region in only 8.8% (n = 4). The group with osteopenia had a greater duration of hypogonadism than the normal BMD group (14 +/- 11 years vs 4.4 +/- 4.0 years; p = 0.01). A negative correlation was also found between the duration of hypogonadism and BMD in spine (r = -0.4; p = 0.003) and femoral region (r = -0.37; p = 0.013). The hypogonadal patients had a lower BMD in spine (p < 0.005), but not in other regions analyzed. No correlation was found between duration of hypersomatotropism, GH/IGF-I levels and BMD. We conclude that the majority of patients with acromegaly have preserved BMD despite the presence of hypogonadism.

Conservative management of pituitary apoplexy: a prospective study.

A prospective study was conducted to evaluate the usefulness and limitations of conservative treatment in patients with pituitary apoplexy. Twelve patients presenting sudden headache, visual impairment, or ophthalmoplegia had the diagnosis of pituitary apoplexy established by computerized tomographic scans. Initially, 11 patients received iv dexamethasone (2.0-16.0 mg/day). Surgery was indicated when dexamethasone failed to improve visual or consciousness impairment. Among the 7 patients who were treated conservatively, ophthalmoplegia recovered completely in 6 and improved in 1. Follow-up computerized tomographic scans showed resolution of the tumor in 4 patients and residual masses in 3 patients who were treated conservatively. Five patients had surgery and experienced improvement of vision and consciousness. Follow-up computerized tomographic scans showed residual masses in all surgical patients. Recurrences were observed in 2 patients, one in each group. The prevalence of pituitary deficiencies in the conservative group (9 of 17) was similar to that of the surgical group (3 of 14), but when only patients whose tumors were resolved by the apoplexy were analyzed, a significantly higher prevalence (8 of 12) was observed (P = 0.02). A retrospective analysis of presenting clinical and computerized tomography data on the basis of the response to dexamethasone showed that visual impairment did not improve during treatment with dexamethasone, whereas the presence of a large hypodense area within the tumor predicted complete tumor resolution. These results support conservative management of pituitary apoplexy in patients who are selected on the basis of clinical and tomographic findings.

Prevalence and magnitude of osteopenia associated with insulin-dependent diabetes mellitus.

The authors evaluated the prevalence, magnitude, and contributing factors for osteopenia in insulin-dependent diabetes mellitus (IDDM). We measured bone mineral density (BMD) in the lumbar spine and femoral region in 90 patients aged 18-54 years with IDDM using dual-energy x-ray absorptiometry. The blood-glucose control, insulin dosage, duration of disease, and presence of chronic complications of diabetes were evaluated. Serum ionized calcium, magnesium, phosphorus, alkaline phosphatase (ALP), 25-hydroxycholecalciferol, immunoreactive parathyroid hormone (iPTH), and urinary calcium, phosphorus, and hydroxyproline were also analyzed. Thirty-one patients (34%) were classified as having a reduced BMD (less than 2 SD below the mean). The comparison between normal and low BMD patients showed that the osteopenics had a tendency to be younger (median, 28 years versus 32 years), showed a higher mean plasma glucose (15.5 +/- 5.0 mmol/L versus 12.9 +/- 3.8 mmol/L; p = 0.018), longer duration of disease (11.2 +/- 2.1 years versus 5.0 +/- 1.3 years; p = 0.004), and needed a higher insulin dosage (56 +/- 17 U/day versus 43 +/- 16 U/day; p < 0.001). There was a positive correlation between mean glucose levels, duration of disease, insulin dosage, and bone-mass decrease. A higher incidence of chronic complications, mainly retinopathy (58% versus 25%) and neuropathy (52% versus 22%) was found in the low BMD group. There was no alteration of serum calcium, phosphorus, iPTH, 25-hydroxycholecalciferol, and urinary calcium and phosphorus. The ALP levels were significantly higher in the osteopenic group, and magnesium and hydroxyproline levels were lower in the whole diabetic group, but these measurements did not correlate with BMD reduction.(ABSTRACT TRUNCATED AT 250 WORDS)

Prevalence and magnitude of osteopenia in patients with prolactinoma.

1. The association between hypogonadism and osteoporosis has been reported. We conducted a study to establish the prevalence and magnitude of osteopenia in patients with prolactinoma and the relationship of bone loss with the duration of hypogonadism. 2. We measured the bone mineral density (BMD) of spine and femur (a site that has not been analyzed earlier) in 35 patients with prolactinoma using a dual-energy X-ray absorptiometer. The patients were classified as normal BMD and low BMD (osteopenics). 3. Seventeen patients (48%) showed osteopenia. The mean bone loss in the different regions was: spine, 13%; femoral neck, 15%; trochanter, 11%; Ward's, 22%. This difference was only significant when the spine and Ward's region were compared. The duration of hypogonadism was significantly greater in the low-BMD group (11.3 vs 4.9 years) when compared to the normal BMD group. There was a positive relationship between the duration of hypogonadism and magnitude of bone loss in both spine and femur (P = 0.04; r = 0.6). 4. A high prevalence of osteopenia in both spine and femur was found in patients with prolactinoma, and was highly associated with the duration of hypogonadism. Early treatment of this condition seems important to prevent bone loss.

Prevalence and magnitude of osteopenia in patients with prolactinoma

1. The association between hypogonadism and osteoporosis has been reported. We conducted a study to establish the prevalence and magnitude of osteopenia in patients with prolactinoma and the relationship of bone loss with the duration of hypogonadism. 2. We measured the bone mineral density (BMD) of spine and femur (a site that has not been analyzed earlier) in 35 patients with prolactinoma using a dual-energy X-ray absorptiometer. The patients were classified as normal BMD and low BMD (osteopenics). 3. Seventeen patients (48 per cent ) showed osteopenia. The mean bone loss in the different regions was: spine, 13 per cent ; femoral neck, 15 per cent ; trochanter, 11 per cent ; Ward's, 22 per cent . This difference was only significant when the spine and Ward's region were compared. The duration of hypogonadism was significantly greater in the low-BMD group (11.3 vs 4.9 years) when compared to the normal BMD group. There was a positive relationship between the duration of hypogonadism and magnitude of bone loss in both spine and femur (P = 0.04; r = 0.6). 4. A high prevalence of osteopenia in both spine and femur was found in patients with prolactinoma, and was highly associated with the duration of hypogonadism. Early treatment of this condition seems important to prevent bone loss

Do impaired glucose tolerance and diabetes mellitus interfere with the interpretation of the growth hormone response to the oral glucose tolerance test?

1. The ability of glucose to suppress growth hormone (GH) secretion is well known and the glucose test is widely used for the diagnosis of acromegaly. However, when suspected acromegaly is associated with diabetes mellitus (DM) or impaired glucose tolerance (IGT) the interpretation of the GH response to the oral glucose tolerance test (OGTT) may be difficult. Recently, Hattori et al. (Journal of Clinical Endocrinology and Metabolism, 70: 771-778, 1990), using a highly sensitive (1.5 ng/l) polyclonal antibody-based immunoenzymometric assay, found no differences in the GH response to glucose load among control, IGT and DM patients. 2. We employed a less sensitive (100 ng/l) but monoclonal antibody-based immunoenzymometric assay to measure the serum GH levels of 19 normal subjects, 11 patients with DM and 11 patients with IGT to determine the effect of glucose intolerance on the GH response to the OGTT. 3. Complete suppression of GH (< 0.1 microgram/l) was achieved in 73% of the controls with a mean nadir of 0.17 +/- 0.16 microgram/l (range, < 0.1-0.6 microgram/l). GH was completely suppressed in 82% of the diabetics with a mean nadir of 0.58 +/- 1.21 micrograms/l (range, < 0.1-4.0 micrograms/l). However, complete suppression occurred in only 27% of the IGT patients with a nadir of 1.09 +/- 2.08 micrograms/l (range, < 0.1-7.0 micrograms/l), which was statistically higher than observed for controls and diabetics. 4. We conclude that plasma GH levels after glucose loading of IGT patients should be interpreted with caution because an abnormal response can be detected when some sensitive immunometric assays are employed.

Do impaired glucose tolerance and diabetes mellitus interfere with the interpretation of the growth hormone response to the oral glucose tolerance test ?

The ability of glucose to suppress growth hormone (GH) secretion is well known and the glucose test is widely used for the diagnosis of acromegaly. However when suspected acromegaly is associaterd with diabetes mellitus (DM) or impaired glucose tolerance (IGT) the interpretation of the GH response to the oral glucose tolerance test (OGTT) may be difficult. Recently, Haltori et al. (Journal of clinical endocrinology and metabolism, 70: 771-778, 1990), using a highly sensitive (1.5 ng/l) polyclonal antibody-based immunoenzymometric assay, found no differences in the GH response to glucose load among control, IGT and DM patients. We employed a less sensitive (100 ng/l) but monoclonal antibody-based immunoenzymometric assay to measure the serum GII levels of 19 normal subjects, 11 patients with DM and 11 patients with IGT to determine the effect of glucose intolerance on the GH response to the OGTT. Complete suppression of GH (<0.1 ug/l) was achieved in 73% o9f the controls with a mean nadir of 0.17 ñ 0.16 ug/l (range, <0.1-0.6 ug/l). GH was completely suppressed in 82% of the the diabetes with a mean nadir of 0.58 ñ 1.21 ug/l (range, <0.1-4.0 ug/l). However, complete suppression occurred in only 27% of the IGT patients with a nadir of 1.09 ñ 2.08 ug/l (range, 0.1-7.0 yg/l), which was statisticaly higher than observed for controls and diabetics. We conclude that plasma GH plasma GH levels after glucose loading of IGT patients should be interpreted with caution because an abnormal response can be detected when some sensitive immunometric assays are employed

Giant aneurysms of the sellar region simulating pituitary adenomas: a diagnosis to be considered.

Aneurysms of the sellar region are commonly mistaken for pituitary adenomas, since they have similar clinical, endocrinological and neurological symptoms. The authors describe three patients with giant aneurysms of the internal carotid artery which were initially diagnosed as pituitary tumors. In all patients the clinical presentation was nonspecific, and consisted mainly of neurological symptoms such as headaches and visual field defects. Endocrine abnormalities were also found in the three cases. Patient no. 1 had short stature, lack of GH response to clonidine stimulation, low IGF-1 levels and blunted TSH response to TRH. Patient no. 2 had gonadotropin deficiency and patient no. 3 had hyperprolactinemia. CT scans showed a densely enhanced lesion in all patients, which was heterogeneous in one case and homogeneous in the remaining. Carotid angiography confirmed the diagnosis of aneurysm. Preoperative angiographic studies are necessary for the differential diagnosis of an aneurysm from a pituitary tumor. Furthermore, these studies could prevent the serious consequences of a transsphenoidal surgical approach in misdiagnosed cases.