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Biomedical subjects

J G Vieira

Publications and source records attributed to J G Vieira.

At least 19 recordsLinked to original sources

High prevalence of low bone mineral density in pre-dialysis chronic kidney disease patients: bone histomorphometric analysis.

UNLABELLED: Chronic kidney disease (CKD) leads to reduced bone mineral density (BMD) in pre-dialysis and dialysis patients. A few studies have used dual-energy x-ray absorptiometry (DEXA) to assess BMD in pre-dialysis CKD patients and have shown low BMD to be highly prevalent. Until now there have been no studies reporting the histological features of low BMD in pre-dialysis CKD patients. AIM: To determine the prevalence and histological features of low BMD in pre-dialysis CKD patients. METHOD: Pre-dialysis CKD patients (n = 103, 46 females/57 males), median creatinine clearance of 29 (10 - 78) ml/min/ 1.73 m2, were evaluated using biochemical analysis and DEXA. Bone biopsies were obtained from those with low BMD. RESULTS: Fifty (48.5%) out of the 103 patients had low BMD (LBD group) and 53 (51.5%) had normal BMD (NBD group). The risk for low BMD was increased in those patients with alkaline phosphatase levels above 190 U/l and intact-PTH (iPTH) below 70 pg/ml (p < 0.05). Demographic and biochemical parameters from both groups were comparable, except for lower body mass index (BMI) in LBD subjects (p = 0.04). Women who had been post-menopausal for at least 1 year comprised 65% (13/20) and 50% (13/26) of the LBD and NBD groups, respectively (p = NS). In 40 LBD patients, bone histomorphometry revealed adynamic bone disease (ABD, 52.5%), osteomalacia (OM, 42.5%) and mixed bone disease (MBD, 5%). Trabecular bone volume (BV/TV) was lower in ABD and OM patients. A nearly significant association was found between ABD and iPTH < or = 150 pg/ml (p = 0.056), whereas higher values of iPTH were associated with OM. Total alkaline phosphatase < or = 190 U/l was significantly associated with ABD, whereas higher values were associated with OM. No correlation was observed between BV/TV and BMD. CONCLUSION: Low BMD is frequent in pre-dialysis CKD patients, and low turnover bone disease, manifesting as ABD and OM, was the hallmark of this bone loss.

Absorptiometry, Photon↗

Pitfalls in pituitary diagnosis: peculiarities of three cases.

Due to the increasing availability and sensitivity of diagnostic methods, biochemical and imaging abnormalities of pituitary function and anatomy are becoming more frequent. Hyperprolactinaemia was found in three women without any prolactin (PRL) related clinical features. All three patients had normal libido, regular menses with evidence of ovulation, no galactorrhoea, and normal FSH, LH, TSH and free T4 serum levels. Magnetic resonance imaging (MRI) of the sellar region showed images that were compatible with pituitary microadenomas in all three cases. Due to the discordance between laboratory and clinical features, we searched for the presence of PRL aggregates with high molecular weight and low biological activity (macroprolactinaemia). Initially, we screened with a polyethylene glycol precipitation method, and then confirmed the presence of macroprolactinaemia by chromatography. All three cases screened positive for the presence of macroprolactinaemia. MRI alterations, compatible with pituitary microadenomas, may be due to true microincidentalomas, normal anatomical variations or imaging artefacts. In conclusion, we have described the presence of double diagnostic pitfalls that might lead to unnecessary medical or surgical intervention.

Adenoma↗

Circulating forms of parathyroid hormone detected with an immunofluorometric assay in patients with primary hyperparathyroidism and in hyperparathyroidism secondary to chronic renal failure.

In patients with uremia, intact parathyroid hormone (PTH) measurement appears to overestimate the biologically active hormone in circulation. The recent description of the accumulation in these patients of a non-intact PTH form measured by the standard immunometric assays, re-opened the question. In this study we submitted serum samples from 7 patients with primary hyperparathyroidism (PHP) and from 10 patients with hyperparathyroidism secondary to chronic renal failure (SHP) to preparative HPLC in order to discriminate the molecular forms measured by our currently used immunofluorometric assay for intact PTH. The elution profile obtained with the HPLC system showed two clearly defined peaks, the first one corresponding to a lower molecular weight form, and the second to the intact PTH (1-84) form. In patients with SHP the area under the curve for the first peak (mean 29.5%, range 20.6 to 40.4%) was significantly greater than that observed for patients with PHP (mean 15.6%, range 5.6 to 21.9%). This confirms previous studies showing accumulation of molecular forms of slightly lower molecular weight, presumably PTH (7-84), in patients with SHP and, to a lesser extent, in patients with PHP. The real necessity of assays that discriminate between these two molecular forms is debatable.

Chromatography, High Pressure Liquid↗

Osteoporotic fractures of proximal femur: clinical and epidemiological features in a population of the city of São Paulo.

CONTEXT: It is believed that about 25% of menopausal women in the USA will exhibit some kind of fracture as a consequence of osteoporosis. Fractures of the proximal femur are associated with a greater number of deaths and disabilities and higher medical expenses than all the other osteoporotic fractures together. OBJECTIVE: To study the clinical and epidemiological features of patients with proximal femur fracture in hospitals in São Paulo. DESIGN: Transversal and retrospective study. LOCAL: Hospital São Paulo and Hospital Servidor Público Estadual "Francisco Morato Oliveira". PARTICIPANTS: Patients aged sixty-five years or more hospitalized because of proximal femur fracture, from March to November 1996 (N = 73). This group was compared to patients of the same age without fracture of the proximal femur. INTERVENTION: Evaluation of weight, height, body mass index; lifestyle habits (physical activity at home, ingestion of dairy calcium, drinking of coffee, smoking habit), gynecological history (ages at menarche and menopause, number of pregnancies and lactations), previous morbidity, use of medications, history of previous fractures, family history of osteoporosis. MEASUREMENT: The comparison of the different data regarding lifestyle habits between the two groups was made using the chi-squared test. Other data were analyzed using the Mann--Whitney test. P pound 0.05 was considered significant. RESULTS: We noted a predominance of proximal femur fracture among females in relation to males (a female/male ratio of 3.3:1) with a progressive increase in the frequency of proximal femur fracture with age in both sexes. The group with proximal femur fracture, in comparison with the control group, showed a lower body mass index, less physical activity, and a greater number of pregnancies and lactations. Other data were not different. CONCLUSION: In accordance with the literature, we found a predomination of proximal femur fracture in women in relation to men, and a favorable effect of higher body mass index and physical activity for decreasing the frequency of proximal femur fracture. We also discuss the role of pregnancies and lactation on the frequency of proximal femur fracture.

Age Distribution↗

Effect of hormone replacement therapy on the bone mass and urinary excretion of pyridinium cross-links.

CONTEXT: The menopause accelerates bone loss and is associated with an increased bone turnover. Bone formation may be evaluated by several biochemical markers. However, the establishment of an accurate marker for bone resorption has been more difficult to achieve. OBJECTIVE: To study the effect of hormone replacement therapy (HRT) on bone mass and on the markers of bone resorption: urinary excretion of pyridinoline and deoxypyridinoline. DESIGN: Cohort correlational study. SETTING: Academic referral center. SAMPLE: 53 post-menopausal women, aged 48-58 years. MAIN MEASUREMENTS: Urinary pyr and d-pyr were measured in fasting urine samples by spectrofluorometry after high performance liquid chromatography and corrected for creatinine excretion measured before treatment and after 1, 2, 4 and 12 months. Bone mineral density (BMD) was measured by dual energy X-ray absorptiometry (DEXA) before treatment and after 12 months of HRT. RESULTS: The BMD after HRT was about 4.7% (P < 0.0004); 2% (P < 0.002); and 3% (P < 0. 01) higher than the basal values in lumbar spine, neck and trochanter respectively. There were no significant correlations between pyridinium cross-links and age, weight, menopause duration and BMD. The decrease in pyr and d-pyr was progressive after HRT, reaching 28.9% (P < 0.0002), and 42% (P < 0.0002) respectively after 1 year. CONCLUSIONS: Urinary pyridinoline and deoxypyridinoline excretion decreases early in hormone replacement therapy, reflecting a decrease in the bone resorption rate, and no correlation was observed with the bone mass evaluated by densitometry.

Absorptiometry, Photon↗

Increased hip bone mineral density in a woman with gluteal silicon implant.

Conditions and artifacts such as aortic calcification, osteophytes, hip prostheses, and metallic objects can mislead the results of dual energy X-ray absorptiometry (DXA) scanning of the spine and hip. Gluteal silicon implants increasingly are being used for aesthetic purposes by women in Brazil, some of whom are at an age of high risk for the development of postmenopausal osteoporosis. We herein report a case of a woman whose hip bone mineral density by DXA clearly increased after the placement of bilateral gluteal implants of silicon. This case demonstrates the importance of inquiring about the presence of this artifact to avoid unnecessary evaluation of hip bone densitometry in these situations.

Absorptiometry, Photon↗

Y-chromosome identification by PCR and gonadal histopathology in Turner's syndrome without overt Y-mosaicism.

OBJECTIVE: The frequency of gonadoblastoma is high in patients with Turner's syndrome bearing cells with Y or partial Y-chromosome. About 60% of patients with Turner's syndrome have a 45,X karyotype. In 30% of them a Y-sequence is disclosed by DNA analysis. To identify patients at risk of developing gonadoblastoma, a PCR based assay with SRY, ZFY and DYZ3 specific primers was carried out to detect different Y-sequences in the DNA of peripheral lymphocytes from patients with Turner's syndrome. DESIGN AND PATIENTS: Peripheral blood karyotypes from 36 patients with Turner's syndrome were studied. Patients with proven Y-chromosomal material were excluded. Genomic DNA was extracted from peripheral blood. SRY and ZFY genes and DYZ3 repetion of Y-chromosome were amplified by PCR. Patients with clinical signs of hyperandrogenism or with positive Y-sequences by PCR underwent gonadectomy. The gonadal tissues were examined for Y-sequences using PCR, morphology and immunohistochemical study. MEASUREMENTS: Turner's syndrome and signs of hyperandrogenism were evaluated both clinically and through laboratory tests. Haematoxylin and eosin staining was employed in gonadal morphology studies. The presence of testosterone was detected by immunohistochemistry using a monoclonal antibody. RESULTS: Two patients who had Y-positive blood samples and three hyperandrogenic (2 hirsutes, 1 virilized) Y-negatives underwent gonadectomy. PCR was carried out on their gonadal tissue. The tissue from the two patients without hyperandrogenism was Y-positive. The gonadal tissue from the three hyperandrogenics was Y-negative. Gonadal morphology disclosed hilus cell hyperplasia in the 3 hyperandrogenic Y-negatives and in one Y-positive patient; stromal luteoma and hyperthecosis in the virilized patient, cystadenofibroma in one hirsute patient and gonadoblastoma in one Y-positive. Testosterone was detected immunohistochemically in the hilus cell hyperplasia, stromal luteoma and hyperthecosis found in the hyperandrogenic patients. CONCLUSIONS: The molecular study was sensitive and useful in the evaluation of patients at risk of developing gonadoblastoma. Other nontumour, gonadotrophin-dependent and Y-independent mechanisms which deserve the same medical approach may be involved in the genesis of hyperandrogenic signs in Turner's syndrome.

Adolescent↗

Evaluation of bone metabolism after the use of an inhaled glucocorticoid (flunisolide) in patients with moderate asthma.

OBJECTIVE: We have investigated the effects of the inhaled corticosteroid flunisolide on bone metabolism and adrenal function in patients with moderate asthma. SUBJECTS AND DESIGN: Twenty ambulatory patients (13 females, 7 males, mean age +/- SD of 36.4 +/- 12.4 years) with moderate asthma were recruited. None had taken corticosteroids for at least 1 month. Flunisolide 500 microg was given twice a day for 10 weeks, without any other medication. Blood and urine were collected before and at the end of treatment course. Cortisol (basal and 1 h after ACTH 250 microg i.v.) was measured to evaluate adrenal function. A peak cortisol response of 496 nmol/l was considered an adequate response. Serum ionized calcium, intact PTH, plasma osteocalcin (OC) and urinary pyridinoline (Pyr) and deoxy-pyridinoline (D-Pyr) were measured to evaluate bone metabolism. Wilcoxon paired test was performed for statistical analysis. Results are expressed as mean +/- SD. RESULTS: In most patients (85%), there was no difference after treatment with flunisolide on basal and stimulated cortisol levels. We found a significant decrease of OC (3.55 +/- 1.42 to 2.97 +/- 1.05 nmol/l) and Pyr (66.4 +/- 20.0 to 59.5 +/- 24.9 pmol/micromol creatinine) levels after treatment (P < 0.05). We also observed a positive correlation between the variations seen in pre and post treatment values of OC and Pyr/D-Pyr. CONCLUSIONS: The use of inhaled flunisolide 1000 microg/day for 10 weeks had no suppressive effect on adrenal function in the majority of asthmatic patients studied. However, the effects seen on bone and mineral metabolism, evidenced by the significant fall in osteocalcin and pyridinoline levels, may indicate a possible systemic effect of this drug. Clinical consequences of long-term treatment with flunisolide need to be further evaluated.

Administration, Inhalation↗

Pituitary glycoprotein hormone a-subunit secretion by cirrhotic patients.

Secretion of the alpha-subunit of pituitary glycoprotein hormones usually follows the secretion of intact gonadotropins and is increased in gonadal failure and decreased in isolated gonadotropin deficiency. The aim of the present study was to determine the levels of the alpha-subunit in the serum of patients with cirrhosis of the liver and to compare the results obtained for eugonadal cirrhotic patients with those obtained for cirrhotic patients with hypogonadotropic hypogonadism. Forty-seven of 63 patients with cirrhosis (74.6%) presented hypogonadism (which was central in 45 cases and primary in 2), 7 were eugonadal, and 9 women were in normal menopause. The serum alpha-subunit was measured by the fluorimetric method using monoclonal antibodies. Cross-reactivity with LH, TSH, FSH and hCG was 6.5, 1.2, 4.3 and 1.1%, respectively, with an intra-assay coefficient of variation (CV) of less than 5% and an interassay CV of 5%, and sensitivity limit of 4 ng/l. The serum alpha-subunit concentration ranged from 36 to 6253 ng/l, with a median of 273 ng/l. The median was 251 ng/l for patients with central hypogonadism and 198 ng/l for eugonadal patients. The correlation between the alpha-subunit and basal LH levels was significant both in the total sample (r = 0.48, P < 0.01) and in the cirrhotic patients with central hypogonadism (r = 0.33, P = 0.02). Among men with central hypogonadism there was a negative correlation between alpha-subunit levels and total testosterone levels (r = -0.54, P < 0.01) as well as free testosterone levels (r = -0.53, P < 0.01). In conclusion, although the alpha-subunit levels are correlated with LH levels, at present they cannot be used as markers for hypogonadism in patients with cirrhosis of the liver.

Adult↗

Specific insulin and proinsulin secretion in glucokinase-deficient individuals.

Glucokinase (GCK) is an enzyme that regulates insulin secretion, keeping glucose levels within a narrow range. Mutations in the glucokinase gene cause a rare form of diabetes called maturity-onset diabetes of the young (MODY). An early onset (less than 25 years), autosomal dominant inheritance and low insulin secretion stimulated by glucose characterize MODY patients. Specific insulin and proinsulin were measured in serum by immunofluorimetric assays (IFMA) during a 75-g oral glucose tolerance test (OGTT). Two kindreds (SA and LZ) were studied and compared to non-diabetic unrelated individuals (control group 1) matched for age and body mass index (BMI). In one kindred, some of these subjects were also obese (BMI > 26 kg/m2), and other family members also presented with obesity and/or late-onset NIDDM. The MODY patients were also compared to a group of five of their first-degree relatives with obesity and/or late-onset NIDDM. The proinsulin profile was different in members of the two MODY kindreds. Fasting proinsulin and the proinsulin/insulin ratio were similar in MODY members of kindred LZ and subjects from control group 1, but were significantly lower than in MODY members of kindred SA (P < 0.02 and P < 0.01, for proinsulin and proinsulin/insulin ratio, respectively). Moreover, MODY members of family SA had higher levels of proinsulin and proinsulin/insulin ratio, although not significantly different, when compared to their first-degree relatives and to subjects from control group 2. In conclusion, we observed variable degrees of proinsulin levels and proinsulin/insulin ratio in MODY members of two different kindreds. The higher values of these parameters found in MODY and non-MODY members of kindered SA is probably related to the obesity and late-onset NIDDM background present in this family.

Adult↗

Vitamin D receptor gene polymorphism: correlation with bone mineral density in a Brazilian population with insulin-dependent diabetes mellitus.

Patients with insulin-dependent diabetes mellitus (IDDM) are at higher risk of developing osteoporosis. Among the genetic factors related to the development of osteoporosis, a possible association between vitamin D receptor (VDR) gene polymorphism and bone mineral density (BMD) has been described in some populations. We characterized the VDR gene polymorphism in a healthy adult Brazilian population and in a group of patients with IDDM and correlated these findings with densitometric values in both groups. The Brazilian population is characterized by an important racial heterogeneity and therefore is considered an ethnically heterogeneous population. We recruited 94 healthy adult Brazilian volunteers (63 women and 31 men), mean (+/- SD) age 32.4 +/- 6.5 years (range 18-49 years), and 78 patients with IDDM (33 women and 45 men) diagnosed before 18 years of age, mean (+/- SD) age 23.3 +/- 5.5 years (range 18-39 years). VDR genotype was assessed by polymerase chain reaction amplification followed by BsmI digestion on DNA isolated from peripheral blood leukocytes. Statistical analysis included Bonferroni t-test to compare densitometric values within different genotypes in both groups and multiple regression analysis of bone density adjusted for potential confounding factors. The IDDM group had a lower BMD compared with the control group. The VDR genotype distribution in the control group was 43 Bb (45.7%), 39 bb (41.5%) and 12 BB (12.8%). This distribution did not differ from that observed in the IDDM group: 39 Bb (50%), 26 bb (33.3%) and 13 BB (16.7%). In the IDDM group, patients with the Bb genotype had a higher body weight when compared with the BB genotype (p = 0.02). However, when diabetic patients were controlled for age, sex and body mass index, BB genotype was associated with a lower mean BMD at lumbar spine and femoral neck than in Bb and bb patients. BB patients had a shorter duration of IDDM than bb and Bb patients. These findings suggest a small influence of VDR gene polymorphism on BMD of a racially heterogeneous population with IDDM.

Adolescent↗

Changes in renal hemodynamics and tubular function of surgically cured primary hyperparathyroid patients are probably due to chronic hypercalcemic nephropathy.

To understand the mechanisms responsible for the persistent hypercalciuria and reduced glomerular filtration rate (GFR) previously found in 6 of 10 patients surgically cured of primary hyperparathyroidism (PHPx), the tubular handling of lithium, sodium, calcium, and phosphate as well as the renal hemodynamics were evaluated in these 10 PHPx patients, in 10 control subjects, and in 5 patients with renal hypercalciuria (RH), during fasting and after an oral calcium load. A positive correlation between the fractional excretions of calcium and sodium was found in all groups, but the PHPx patients excreted more calcium for the same amount of sodium than control subjects. The fractional proximal sodium reabsorption (FPRNa), distal delivery, and fractional phosphate reabsorption were similar in all groups; a significant positive correlation was found between the fractional calcium reabsorption and the FPRNa, indicating that proximal tubular function was preserved and that the urinary calcium losses in RH and in the hypercalciuric PHPx patients (h-PHPx) occurred in the distal nephron. However, only h-PHPx patients had reduced renal plasma flow, renal blood flow, and GFR, as well as a high renal vascular resistance, which was even more evident after the calcium challenge. These findings lead us to conclude that RH and h-PHPx patients are very different, as far as kidney dysfunction is concerned, and that a hypercalcemic nephropathy is the most probable cause of the alterations in distal calcium reabsorption and renal hemodynamics found in the h-PHPx patients.

Adenoma↗

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.

Adenoma↗

Fractures of the proximal femur: correlation with vitamin D receptor gene polymorphism.

Fractures are the feared consequences of osteoporosis and fractures of the proximal femur (FPF) are those that involve the highest morbidity and mortality. Thus far, evaluation of bone mineral density (BMD) is the best way to determine the risk of fracture. Genetic inheritance, in turn, is one of the major determinants of BMD. A correlation between different genotypes of the vitamin D receptor (VDR) and BMD has been recently reported. On this basis, we decided to determine the importance of the determination of VDR genotype in the presence of an osteoporotic FPF in a Brazilian population. We studied three groups: group I consisted of 73 elderly subjects older than 65 years (78.5 +/- 7.2 years) hospitalized for nonpathological FPF; group II consisted of 50 individuals older than 65 years (72.9 +/- 5.2 years) without FPF and group III consisted of 98 young normal Brazilian individuals aged 32.6 +/- 6.6 years (mean +/- SD). Analysis of VDR gene polymorphism by restriction fragment length polymorphism (RFLP) was performed by PCR amplification followed by BsmI digestion of DNA isolated from peripheral leukocytes. The genotype distribution in group I was 20.5% BB, 42.5% Bb and 37% bb and did not differ significantly from the values obtained for group II (16% BB, 36% Bb and 48% bb) or for group III (10.2% BB, 47.6% Bb and 41.8% bb). No differences in genotype distribution were observed between sexes or between the young and elderly groups. We conclude that determination of VDR polymorphism is of no practical use for the prediction of FPF. Other nongenetic factors probably start to affect bone mass, the risk to fall and consequently the occurrence of osteoporotic fractures with advancing age.

Age Factors↗

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.

Adolescent↗

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.

Absorptiometry, Photon↗

Increased thyrotrophin levels and loss of the nocturnal thyrotrophin surge in Sheehan's syndrome.

OBJECTIVE: Since panhypopituitarism in patients with Sheehan's syndrome is due to massive pituitary necrosis with only minor hypothalamic involvement, we hypothesized that serum TSH levels would be low but its circadian rhythm preserved in these patients. DESIGN AND PATIENTS: Basal and TRH-stimulated mean afternoon (1500-1700 h) and nocturnal (0100-0300 h) TSH levels were determined in 10 patients with Sheehan's syndrome before and during T4/glucocorticoid replacement and in seven controls. MEASUREMENTS: Serum concentrations of T3, T4, free T4 (fT4) and cortisol were measured by radio-immunoassay; TSH, GH, PRL and LH were determined by immunofluorimetric assay. RESULTS: Afternoon TSH levels were markedly increased in Sheehan's syndrome patients compared with controls (3.3 +/- 1.0 vs 0.5 +/- 0.15 mU/l, respectively, P = 0.002). At night, TSH levels remained unchanged in Sheehan's syndrome patients (3.3 +/- 1.1 mU/l) but rose significantly in controls (1.1 +/- 0.34 mU/l, P = 0.016). The nocturnal TSH increment was significantly higher in controls than in patients (143 vs approximately 4.9%, respectively, P = 0.0001). In eight patients with normal serum fT4 levels during treatment, basal TSH levels decreased to 0.16 +/- 0.05 mU/l (P < or = 0.008), being barely detectable or undetectable in four patients. In the six patients with detectable TSH during treatment, nocturnal TSH increments were normal in four and blunted in two. There was a strong correlation between pre- and post-treatment basal TSH (r = 0.82, P = 0.012) and between pre- and post-treatment peak TSH after TRH (r = 0.91, P = 0.0017), but no significant correlation between TSH and thyroid hormone levels. The per cent ratio of peak TSH after TRH between treated patients and controls, an estimate of the relative size of the functional thyrotroph pool in Sheehan's syndrome patients, was 7%. CONCLUSIONS: Loss of TSH rhythm in Sheehan's syndrome is usually secondary to hormonal deficiency and results from maximally increased secretory activity of a decreased pool of thyrotrophs. The paradox of increased TSH levels and decreased thyroid function in Sheehan's syndrome could result from decreased TSH bioactivity and/or from a critically reduced thyrotroph population that fails to sustain sufficient TSH secretion in the face of rising serum thyroid hormone levels.

Adult↗