Height and bone mineral density in androgen insensitivity syndrome with mutations in the androgen receptor gene.

INTRODUCTION AND HYPOTHESIS: Androgen insensitivity syndrome (AIS) constitutes a natural model to study effects of androgens and estrogens on growth and bone density. We evaluated height and bone density in patients with AIS with mutations in the androgen receptor (AR) gene. METHODS: A retrospective analysis was conducted of eight subjects with complete AIS (CAIS) and four with partial AIS (PAIS) submitted to gonadectomy followed by estrogen replacement, and three with PAIS who did not undergo gonadectomy. Standing height and bone mineral apparent density (BMAD) by DXA were measured and compared with male (z (m)) and female (z (f)) reference populations. The z-scores were compared with a value of zero using the one-sample t-test. RESULTS: Final heights of patients with CAIS and PAIS were intermediate between those predicted for females and males. BMAD of the lumbar spine in CAIS and PAIS after gonadectomy and estrogen replacement (z (f) = - 1.56 +/- 1.04, P = 0.006, and z (m) = - 0.75 +/- 0.89, P = 0.04) indicated vertebral bone deficit, whereas BMAD at the femoral neck was normal. No patient reported fractures. CONCLUSION: Subjects with AIS had mean final height intermediate between mean normal male and female, and decreased bone mineral density in the lumbar spine. These data suggest an important role for androgens in normal male growth and bone density not replaced by estrogens.

Improvement of adynamic bone disease after renal transplantation.

Low bone remodeling and relatively low serum parathyroid hormone (PTH) levels characterize adynamic bone disease (ABD). The impact of renal transplantation (RT) on the course of ABD is unknown. We studied prospectively 13 patients with biopsy-proven ABD after RT. Bone histomorphometry and bone mineral density (BMD) measurements were performed in the 1st and 12th months after RT. Serum PTH, 25-hydroxyvitamin D, 1,25-dihydroxyvitamin D, and osteocalcin were measured regularly throughout the study. Serum PTH levels were slightly elevated at transplantation, normalized at the end of the third month and remained stable thereafter. Bone biopsies performed in the first month after RT revealed low bone turnover in all patients, with positive bone aluminum staining in 5. In the 12th month, second biopsies were performed on 12 patients. Bone histomorphometric dynamic parameters improved in 9 and were completely normalized in 6, whereas no bone mineralization was detected in 3 of these 12 patients. At 12 months post-RT, no bone aluminum was detected in any patient. We also found a decrease in lumbar BMD and an increase in femoral BMD. Patients suffering from ABD, even those with a reduction in PTH levels, may present partial or complete recovery of bone turnover after successful renal transplantation. However, it is not possible to positively identify the mechanisms responsible for the improvement. Identifying these mechanisms should lead to a better understanding of the physiopathology of ABD and to the development of more effective treatments.

Improvement of adynamic bone disease after renal transplantation

Low bone remodeling and relatively low serum parathyroid hormone (PTH) levels characterize adynamic bone disease (ABD). The impact of renal transplantation (RT) on the course of ABD is unknown. We studied prospectively 13 patients with biopsy-proven ABD after RT. Bone histomorphometry and bone mineral density (BMD) measurements were performed in the 1st and 12th months after RT. Serum PTH, 25-hydroxyvitamin D, 1,25-dihydroxyvitamin D, and osteocalcin were measured regularly throughout the study. Serum PTH levels were slightly elevated at transplantation, normalized at the end of the third month and remained stable thereafter. Bone biopsies performed in the first month after RT revealed low bone turnover in all patients, with positive bone aluminum staining in 5. In the 12th month, second biopsies were performed on 12 patients. Bone histomorphometric dynamic parameters improved in 9 and were completely normalized in 6, whereas no bone mineralization was detected in 3 of these 12 patients. At 12 months post-RT, no bone aluminum was detected in any patient. We also found a decrease in lumbar BMD and an increase in femoral BMD. Patients suffering from ABD, even those with a reduction in PTH levels, may present partial or complete recovery of bone turnover after successful renal transplantation. However, it is not possible to positively identify the mechanisms responsible for the improvement. Identifying these mechanisms should lead to a better understanding of the physiopathology of ABD and to the development of more effective treatments.

Bone histomorphometry in Cushing's syndrome.

Bone involvement is a common finding in Cushing's syndrome. The actions of corticosteroids on bone have been studied quite intensively but only a few studies of bone histomorphometry in this syndrome have been published. In this paper we present histomorphometric measurements of bone activity in 7 patients with a postoperative reevaluation in two. The results show irregular alterations on histomorphometric parameters with an increased bone resorption and decreased bone formation rate. After surgery the abnormalities changed towards normal.

Effect of testosterone on bone mineralization of the hypophosphataemic rat.

Clinical observations in patients with X-linked hypophosphataemic rickets, that bone changes can be corrected during puberty, suggest that androgen can participate actively in the process of bone mineralization. In the present study we investigated the role of testosterone on the bone mineralization of male rats placed on a low phosphorus and vitamin D diet and kept in complete darkness after weaning. After 15 days the animals presented hypophosphataemia, rickets and osteomalacia, as assessed by histomorphometry of the tibia and seventh caudal vertebra calcification fronts respectively. Testosterone propionate administration for five days, while the animals were kept on the same rachitogenic diet, induced an improvement in the bone mineralization process of the hypophosphataemic rat independently of serum phosphate levels. Testosterone-treated rats were cured of rickets but not of osteomalacia, despite the reduction in osteoid seam area.

Bone mass in totally thyroidectomized patients. Role of calcitonin deficiency and exogenous thyroid treatment.

Calcitonin has an uncertain role in the preservation of bone mass. Since surgical thyroidectomy abolishes the calcitonin secretion in response to calcium, the bone mineral density at the radius shaft and lumbar spine was measured in 60 patients (5 men, 16 premenopausal, 34 postmenopausal euparathyroid and 5 postmenopausal hypoparathyroid women) who had undergone near total thyroidectomy for thyroid cancer 8.4 +/- 0.7 years before the study. All patients were maintained on suppressive doses of thyroid hormones. Bone mineral density values of the radius shaft (expressed as Z-score) of 34 postmenopausal euparathyroid women was significantly below the normal average (mean +/- SEM = -0.59 +/- 0.2; p = 0.01). Bone mineral density of the lumbar spine was also below the normal average although the difference only approached statistical significance (-0.36 +/- 0.2; 0.05 less than p less than 0.1). The bone mineral density of neither the radius nor the spine differed from normal levels in the premenopausal women and the postmenopausal hypoparathyroid women. Unexpectedly, the bone mineral density of the spine was significantly increased in the 5 thyroidectomized men. The results indicate that thyroidectomized women have a diminished bone mass after the menopause only if parathyroid function is normal. Since the patients were receiving thyroid hormone at suppressive doses, the present study is not able to separate the relative contributions of calcitonin deficit and exogenous thyroid on bone mass loss.

[Basedow-Graves' disease: analysis of various parameters in the prognosis of remission after clinical treatment]. / Doença de Basedow-Graves: análise de diferentes parâmetros na previsão de remissão após tratamento clínico.

Fifty patients with Graves' disease were evaluated in relation to their outcome following medical treatment: goiter size, T3/T4 ratio, TSH and TSAb plasma levels were studied. Patients were followed for 8-20 months of medical treatment with PTU and 24-36 months thereafter. Thirty patients were eliminated for abandoning treatment (50%) or due to PTU side-effects (10%). The 20 patients remaining presented similar remission/relapse rates regardless of their T3/T4 ratio, greater than 20 (21% vs. 79%) or less than 20 (16% vs. 84%). Patients with TSH levels greater than 0.10 uU/ml immediately after PTU withdrawal presented a slight increase of remission rate (30% vs. 10%). Patients with goiter size greater than 60 cm3 at the beginning of medical treatment presented a remission rate of 8%, while those with goiters less than or equal to 60 cm3 showed a remission rate of 50%. Finally, normalization of TSAb levels (less than 15%) occurred at a remission rate of 100%, while all patients who did not achieve this goal relapsed shortly after PTU withdrawal. Based on these results, the authors conclude that the determination of TSAb levels is a reliable parameter of predict remission of Graves' disease following medical treatment.

[Diagnosis of osteoporosis using dual photon densitometry]. / Diagnóstico de osteoporose através da densitometria de dois fótons.

Osteoporosis is often diagnosed after fracture occurrence, when therapy is less effective. The dual photon densitometry has been the proposed method for osteoporosis early diagnosis. In the present study is presented our experience on the lumbar vertebral and femoral neck bone mass measurement by utilizing a Lunar DP-3 densitometer in normal young 82 volunteers and 103 women with radiologically and clinically diagnosed osteoporosis. The values found in osteoporotical patients were significantly lower when compared to those normals either in lumbar vertebrae (L2-L4) or in the femoral neck. The method's coefficient of variation was less than 0.5%, when determinated with a synthetic phantom aid and less than 1.5% repeating the exam in 10 normal volunteers. These results show that dual photon densitometry is a simple, sensitive and non-invasible method for early diagnosis and therapeutic follow-up of osteoporotical patients.

Conversion of thyroxine (T4) to T3 and rT3 in human leucocyte suspension: its application to clinical investigation.

The generation of T3 and rT3 from added nonradioactive T4 in human polymorphonuclear leucocytes was measured. The amounts of the T3 and rT3 generated were estimated by radioimmunoassay in healthy volunteers and patients suffering of thyroidal and nonthyroidal diseases. Under the incubation conditions employed an increase of in vitro generation of T3 and rT3 was observed in suspensions of hyperthyroid patients, while a significant decrease was found when leucocytes from hypothyroid patients were employed. These alterations were apparently due to either the excess or lack of thyroid hormones, respectively, since they could be restored in both cases by specific clinical treatment. Furthermore, the patients suffering from nonthyroidal illnesses showed decreased T3 generating activity in their leucocyte suspensions, while increased amounts of rT3 could be detected in the same test tube. These results showed that the leucocyte incubation system is a suitable method for investigations of the extrathyroidal metabolism of thyroid hormones in humans.

Insulinoma: consideracoes sobre os aspectos clinicos e cirurgicos. / Insulinoma: considerations on clinical and surgical aspects

E apresentado um caso de insulinoma em doente idosa, com historia de dez anos de evolucao. O diagnostico clinico foi confirmado pela determinacao da relacao insulina/glicemia de jejum, ultrasonografia e tomografia computadorizada. O tumor era grande, localizado na regiao cefalica do pancreas, tendo sido enucleado. Sao discutidos os diferentes aspectos clinicos e cirurgicos dos tumores pancreaticos produtores de insulina

Conversao de tiroxina (T4) em 3,5,3'triiodotironina (T3) e 3,3',5-triiodotironina (reverso T3) em suspensoes de leucocitos humanos. Estudo nos estados de hiper e hipotiroidismo. / Thyroxine (T4) to 3,5,3'-triiodothyronine (T3) and 3,3',5-triiodothyronine (reserve T3) conversion in human leukocyte suspensions. Study in hyper and hypothyroidism states

O metabilismo periferico dos hormonios tiroidianos foi estudado em suspensoes de leucocitos humanos, determinando-se, por radioimunoensaio, agestao in vitro de T3 e rT3 a partir de T4 nao radioativo. Pode-se evidenciar, nas suspensoes de leucocitos provenientes de pacientes portadores de hipertiroidismo, maior geracao in vitro de T3 e rT3, enquanto que diminuicao significativa foi observada nos pacientes com hipotiroidismo. Essas alteracoes sao aparentemente devidas ao excesso e a falta de hormonios tiroidianos, respectivamente, ja que em ambos os casos elas puderam ser revertidas pelo tratamento clinico adequado