Concomitant thyroid disease in patients operated for primary hyperparathyroidism.

INTRODUCTION: Parathyroid and thyroid diseases are ones of the most common endocrine diseases, but simultaneous surgical treatment of both endocrine systems is still under discussion. METHODS: We retrospectively evaluated 1,574 patients operated for primary hyperparathyroidism at the 3rd Department of Surgery, 1st Faculty Medicine, Charles University and University Hospital Motol in Prague with the thyroid and parathyroid ultrasound reports available. The patients were divided into two groups - with and without thyroid surgery. RESULTS: Thyroid surgery was performed in 34% of patients with primary hyperparathyroidism. Group 2, where thyroid surgery was performed, showed a higher proportion of reported abnormal thyroid sonographic findings (74%), a higher proportion of bilateral throat exploration (69%) and a longer hospital stay (3.3 days). CONCLUSION: A patient indicated for surgery for parathyroid disease should also be indicated for possible thyroid surgery.

Measurement of intact parathormone during operation for primary hyperparathyroidism.

In this prospective study, the role of the intact parathormone (iPHT) levels for the verification of pathologic parathyroid tissue removal during parathyroidectomy, was analyzed in 441 patients diagnosed with primary hyperparathyroidism. The level of intact parathormone was obtained before the initial incision (baseline level) and 10 minutes after the pathologic parathyroid gland removal (control value). In 80 % of cases, the decrease of intact parathormone was more than 50 % of the baseline level. The comparison of preoperative and postoperative intact parathormone levels can also be used as marker of parathyroid hyperplasia or persistent hyperparathyroidism. This method is necessary mainly for performance of focused, miniinvasive approaches as well as in reoperations. This method is of significant benefit in cases of negative preoperative examination methods. The determination of intact parathormone level increases the success of parathyroidectomy (Ref. 26).

[Videothoracoscopic excision of mediastinal parathyroid adenoma in primary hyperparathyroidism]. / Videothorakoskopické odstranení mediastinálne ulozeného adenomu prístítného telíska pri primární hyperparathyreóze.

INTRODUCTION: Primary hyperparathyroidism is a disease caused by elevated secretion of parathyroid hormone from pathological parathyroid glands. After the diagnosis, the success of its surgical solution depends predominantly on surgical management and experience of the surgeons. A special group is formed by ectopic localizations of pathologically enlarged parathyroid glands in the mediastinum, which require a modified surgical approach. When the adenoma is deep in the mediastinum, sternotomy or thoracotomy is indicated; alternatively, a minimally invasive approach can be used - videothoracoscopic thymectomy. CASE REPORT: We present a case of a patient with normocalcemic recurrent primary hyperparathyroidism. This patient underwent a minimally invasive video-assisted thymectomy after scintigraphic confirmation of parathyroid adenoma in the mediastinum. CONCLUSION: The removal of parathyroid adenoma in the mediastinum using the videothoracoscopic method is safe. Compared to sternotomy, this method improves the postoperative period, reduces the length of stay and provides more comfort to patients. We recommend considering the videothoracoscopic method in cases where the pathologically enlarged parathyroid gland is localized in the inferior and anterior mediastinum. KEY WORDS: primary hyperparathyroidism adenoma of glandula parathyroidea - mediastinum miniinvasive.

[Repeated surgery for parathyroid carcinoma]. / Opakované operace pro karcinom prístítného telíska.

INTRODUCTION: Carcinoma of the parathyroid glands is a rare cause of primary hyperparathyroidism with an incidence of 1%. MATERIAL AND METHODS: This article presents an up-to-date review of the literature illustrated by three clinical cases in the form of case reports. RESULTS: Parathyroid carcinoma is usually not detected before the first operation. Symptoms of carcinoma of the parathyroid glands are similar to those of benign adenoma. Patients with parathyroid carcinoma usually have a higher level of calcium in serum and a higher level of parathormone. Imaging methods such as neck ultrasound and 99mTc sestamibi scan can help localize pathologically enlarged glands, but they are not capable of distinguishing malignant disease. Fine needle aspiration is not recommended due to the possible associated risk of tumour seeding along the needle track. The radical excision of the tumour together with the ipsilateral thyroid gland removal remains the standard of treatment. Local recurrence is frequent. CONCLUSION: Parathyroid carcinoma is a very rare disease and should be managed surgically in a specialized centre.

Effect of PPAR-γ agonist rosiglitazone on bone mineral density and serum adipokines in C57BL/6 male mice.

Thiazolinediones (TZD) are widely used to treat type 2 diabetes, but their mechanism of action still remains only partially understood. Although the in vitro effects of TZD on osteoblastogenesis are well recognized, the in vivo consequences of these compounds on bone turnover are less understood and rather controversial. We demonstrate that a 9-week oral treatment with rosiglitazone in C57BL/6 male mice resulted in significant bone loss that was not dose dependent. The bones of the rosiglitazone-treated mice were characterized by reduction of bone density, and ash, calcium and phosphorus content. Rosiglitazone-treated mice had significantly thinner cortical widths. In contrast to serum TrACP expressed by action of osteoclasts, serum B-ALP activity, which serves as a marker of osteoblastic activity, was significantly lower in the rosiglitazone-fed animals. We did not find any differences in circulating levels of adipokines that could eventually explain rosiglitazone action. As the decrease in osteoblastic activity was demonstrated after rosiglitazone treatment, we anticipated changes in the haematopoietic stem cell pool. These cells seed in endosteal niches which comprise osteoblasts in order to maintain their stem cell function. In our study we did not see any significant influence of rosiglitazone administration on stem cells or any impairment in the lineage restrictions of rosiglitazone-treated stem cells. Our data demonstrate that rosiglitazone administration causes a loss of bone mass in cortical bone, possibly through a decrease in bone formation expressed by decreased B-ALP in male C57BL/6 mice. The levels of adipokines do not play any role.

[Surgical therapy of primary hyperparathyrodism in the context of orthopaedic diagnosis and treatment: our experiences in 441 patients]. / Chirurgická lécba primární hyperparathyreózy v kontextu ortopedické diagnostiky a lécby: nase zkusenosti u 441 pacientu

PURPOSE OF THE STUDY: Primary hyperparathyroidism is an endocrine disorder affecting calcium and phosphate metabolism. It is surgically treated by removing hyperfunctional parathyroid tissue. The aim of the study was to show, based on surgical results, that the introduction of serum calcium screening in orthopaedic therapy is effective. The detection of hypercalcemia and diagnosis of primary hyperparathyroidism allow for a good timing of endocrine surgery in relation to an orthopaedic procedure. MATERIAL AND METHODS: This retrospective study included 441 patients in the age range of 18 to 83 years who underwent parathyroidectomy between 2004 and 2007. Skeletal disorders were diagnosed by clinical, radiographic and densitometric examination; calcium levels were measured after surgery. Bone repair after parathyroidectomy was followed up by the endocrinologist for 1 year. RESULTS: Before surgery, 48 % of the patients had skeletal disorders. Adenoma was found in 87 %, double adenoma in 2 %, hyperplasia in 10 % and parathyroid carcinoma in 0.5 % of the patients. Complications involved transient paresthesia of the recurrent laryngeal nerve (1 %), transient hypocalcemia (0.5 %), transient post-operative arrhythmias (0.5 %), temporary psychological problems (0.7 %) and post-operative bleeding (0.5 %). None of the patients died. Serum calcium levels were as follows: 2.90 ± 0.01 mmol/L pre-operatively; 2.44 ± 0.01 mmol/L on the evening of surgery; 2.30 ±0.01 mmol/L on the 1st day; 2.19 ± 0.01 mmol/L on the 2nd day; and 2.18 ± 0.01 mmol/L on the 3rd post-operative day. On the 3rd post-operative day most of the patients were discharged from the hospital. Normal calcium levels were achieved in 98 % of the surgically treated patients. DISCUSSION AND CONCLUSIONS: The study provides evidence for the efficiency of calcium screening in primary hyperparathyroidism and shows the feasibility of involving endocrine surgery in the course of orthopaedic treatment.

Improvement of hypertension after parathyroidectomy of patients suffering from primary hyperparathyroidism.

Background. Primary hyperparathyroidism (PHPT) is one of the most common endocrine conditions and is accompanied by hypertension and increased cardiovascular mortality. The purpose of this study was to evaluate the effect of parathyroidectomy on systolic and diastolic blood pressure (BP) in hypertensive patients with PHPT and whether hypertension occurs more frequently in PHPT than in control group. Methods. A total of 1020 patients with proved PHPT who underwent surgery were compared with with 1020 age, sex, BMI, and smoking status matched controls. We evaluated changes in serum calcium, parathyroid hormone (PTH), uric acid, and BP before and 6 months after surgery. Results. Parathyroidectomy corrected PHPT and resulted in a substantial fall in both mean systolic (150 ± 3.8 to 138 ± 3.6 mmHg) and mean diastolic pressures (97 ± 3 to 88 ± 2.8 mmHg) of the hypertensive subjects; P < .01. In these patients, PTH, calcium, and uric acid normalized. 726 patients from 1020 with PHPT (69.8%) were found to be hypertensive whilst only 489 (47.8%) from 1020 of our control group. Conclusion. Parathyroidectomy in hypertensive patients reduces systolic and diastolic BP. PHPT is accompanied by a variety of metabolic complications, which are a risk factor for hypertension, and parathyroidectomy can improve these metabolic complications.

The effect of chronic alcohol administration on bone mineral content and bone strength in male rats.

Alcohol use has been identified as a risk factor for the development of osteoporosis. Eight male Wistar rats at two months of age were alcoho-fed (7.6 g 95 % ethanol/kg b.w. per day) to evaluate the effects of long-term administration (three months) of alcohol in drinking water. We have used a dose which is considered to be comparable to a dose of 1 liter of wine or 2.5 liters of 12(°) beer used in male adults daily. The bones were tested mechanically by a three-point bending test in a Mini Bionix (MTS) testing system. The bones from alcohol-fed rats were characterized by a reduction in bone density as well as in ash, calcium and phosphate content. In alcohol-fed rats the reduction in bone mineral density (10 %) was reflected by about 12 % reduction of mechanical strength of femur (158+/-5.5 vs. 178+/-3.2 N/mm(2)). Alcohol significantly altered femoral cortical thickness. In our experiment alcohol itself did not exert any antiandrogenic effect and it did not produce changes in the weight of seminal vesicles. Liver function test (GGT, ALP, AST) did not differ between alcohol-fed rats and control rats. Alcohol-induced bone loss is associated with increased bone resorption and decreased bone formation. These results document the efficacy of alcohol at the dose of 7.6 g 95 % ethanol/kg b.w. to cause bone loss and loss of bone mechanical strength in intact rats. The results of the present study may be interpreted as supporting the hypothesis of alcohol as a risk factor for osteoporosis.

The late-stage foetal liver microenvironment is essential for later sensitivity of B-lymphopoiesis to suppression by oestrogens.

B-lymphopoiesis in FL differs notably from that of adult B-lymphopoiesis in being resistant to suppression by oestrogens due to the lack of expression of oestrogen receptors in B-cell progenitors and precursors. We have transplanted middle-stage FL cells (E14.5) to adult male mice and demonstrated that B-lymphopoiesis derived from FL cells remained resistant to suppression by exogenous oestrogen for several months compared to adult BM cells. This significant difference strongly suggests that the latestage FL environment exerts an inductive action on the haematopoietic stem cells and is mandatory for later sensitivity of B-lymphopoiesis to suppression by oestrogens. The results also provide the first in vivo functional confirmation of a differential responsiveness of FL- and adult BM-derived B-lymphopoiesis to suppression by oestrogens.

[Differential diagnosing of hypercalcemias]. / Diferenciální diagnostika hyperkalcemií.

Primary hyperparathyreosis and tumour diseases are the two most frequent causes of hypercalcaemia. Surgical removal of parathyroid adenoma is the permanent solution for hypercalcaemia. Hypercalcaemia may occur in 20-30% of patients with cancer in the course of the disease. It causes progressive deterioration of the overall condition of the patient which culminates in a coma-like state with renal failure and means a bad prognosis for the affected person. Evaluation of clinical condition and obtaining the immunoreactive parathormone level data are of extreme importance for correct diagnosis. Normal or even low parathormone levels almost surely exclude primary hyperparathyreosis as the source of hypercalcaemia. Additional, less frequent causes of hypercalcaemia should also be taken into consideration, such as diseases caused by the granulomatose tissue, familial benign hypocalciuric hypercalcaemia, drug provoked hypercalcaemia, high thyroid hormone doses and patient dehydration. Fast replenishment of liquids and administration of bisphosphonates are the cornerstones of hypercalcaemia therapy.

Risedronate has no adverse effects on mouse haematopoiesis.

Bisphosphonates are commonly used for treatment of osteoporosis. They inhibit osteoclast activity and thus bone resorption. It was shown that they also affect some other cell types including tumour and endothelial cells. The effects of risedronate on bone marrow microenvironment were not studied yet. As endothelial cells are integral part of bone marrow microenvironment, it is important to know whether prolonged administration of bisphosphonates does not affect haematopoietic stem cells and bone marrow haematopoiesis. We fed mice two weeks with risedronate. We found no effect of risedronate treatment on bone marrow stem cells using the method of congenic bone marrow repopulation. Risedronate administration in the dose which is considered to be comparable to a dose of risedronate used for treatment of osteoporosis in women seems to be safe in terms of effects on mouse haematopoiesis.

The effect of chronic nicotine administration on bone mineral content and bone strength in normal and castrated male rats.

Tobacco, containing nicotine as the principal pharmacologically active chemical, has been identified as being a risk factor for the development of osteoporosis. Thirty-two male Wistar rats of two months of age were castrated or sham operated to evaluate the effects of long-term administration (four months) of nicotine in drinking water (9.0 mg/kg/day). The presence of cotinine in urine confirmed successful delivery of nicotine. The bones were tested mechanically by a three point bending test in a Mini Bionix (MTA) testing system. The bones from castrated rats were characterized by a reduction in bone density as well as ash, calcium and phosphate content. Castration significantly altered mechanical properties of bone (9%) and femoral cortical thickness. When intact rats were treated with a high dose of nicotine, nicotine had negative effect on tibial bone density as well as ash, calcium, phosphate content and significantly altered the mechanical properties of bone (12%) and femoral cortical thickness compared to intact animals. Nicotine itself does not exert any anti-androgenic effect and does not produce changes in the weight of seminal vesicles. Nicotine-induced bone loss is associated with high bone turnover in the male rats as expressed by increased TrACP and B-ALP. When castrated rats were treated with the high dose of nicotine the changes in bone density resulting from castration were not further potentiated. These results document the efficacy of nicotine at high doses to cause bone loss and loss of bone mechanical strength in intact rats. The results of the present study may be interpreted as supporting the hypothesis of nicotine as a risk factor for osteoporosis.

Raloxifen prevents bone loss in castrated male mice.

Raloxifen is a selective estrogen receptor modulator which prevents bone loss in ovariectomized female mice in a fashion similar to estrogens. Since testosterone-deficient male mice also lose bone mass, we were interested in testing the effects of raloxifen on bones in intact and castrated male mice. Bone density was significantly reduced in castrated animals (1.36+/-0.04 g/ml) as compared to intact animals (1.42+/-0.03 g/ml) (p<0.01). When castrated mice with extraordinarily low concentrations of testosterone and with reduced weight of seminal vesicles were treated with raloxifen, the changes in bone density and bone minerals resulting from castration (1.36+/-0.04 g/ml) were entirely prevented (1.40+/-0.01 g/ml). Cortical bone was lost in orchidectomized mice, and this decrease in cortical thickness of the femur was prevented by raloxifen administration. Raloxifen in a dose used in humans for treatment of osteoporosis decreased the weight of seminal vesicles, an organ which is highly sensitive to the androgenic effect, decreased the concentration of testosterone (12.5+/-2.8 micromol/l) (p<0.01) but not to the same level as in the case of castrated animals (0.6+/-0.3 micromol/l), and did not have any effect on bone density or mineral content in intact mice. The results of the present study may thus be interpreted as supporting the hypothesis that raloxifen is an effective agent against the deleterious effects of castration-induced osteopenia in male mice and also support the hypothesis that estrogens may have physiological skeletal effects in male mice.

Progestagens androgenic action on the bone of male castrated mice.

It has been suggested that some progestagens could have an androgenic stimulatory effect on bone formation. The androgenic effects of progestagens were tested in vivo in the absence of androgens and estrogens in the castrated male mice, species extraordinary responsive to the withdrawal or administration of androgens. Three progestagens (norethisterone, uterogestan and medroxyprogesterone acetate were compared as to their androgenic activity. Tissues especially sensitive to androgens, the seminal vesicles and kidney of the mice fell significantly after castration and all three progestagens did not affect their weights. The present results confirm the well known fact that castration leads to osteopenia in mice. Uterogestan micronized progesterone and MPA have no effect on the bone density or mineral content of the tibia of tested mice. Only in the case of NETA we observed slight statistically significant (p < 0.05) increase in bone density. Progestagens do not appear to have the androgenic effect on the skeleton and NETA has been suggested as one of the exception. Our results indicate that only NETA at the dose which is used in hormonal therapy for prevention of osteoporosis has a slight protective effect against bone mineral loss in castrated mice.

The impact of diabetes mellitus on skeletal health: an established phenomenon with inestablished causes?

Diabetes mellitus and osteoporosis affect a large proportion of older adults. In this context, diabetes may influence the bone in multiple pathways, some with contradictory effects. These mechanisms include changes in insulin and insulin-like growth factors levels, hypercalciuria associated with glycosuria, reduced renal function, obesity, higher concentrations of advanced glycation end products in collagen, angiopathies, neuropathies and inflammation. Although it is assumed that the decreased bone strength in diabetes may contribute to fracture risk, a very high number of available clinical and/or epidemiological studies as well as animal model studies brought about heterogeneous or even contradictory results on the skeletal involvement in patients with diabetes mellitus. In addition, bone mineral density (BMD) is a convenient predictor for fracture and the type 1 diabetes is associated with modest reductions in BMD. However, type 2 diabetes can be related to the elevated BMD. The immediate improvement in these discrepancies is to consider the complex pathophysiology of diabetes as well as influences of gender, age, treatment and duration of the disease. It is important also to improve further the choice of investigated biochemical markers and the standardization of the bone mass measurements. Along these lines, several recent cohort studies undeniably indicated that diabetes itself is associated with increased risk of osteoporosis.

Effect of alendronate administration on bone mineral density and bone strength in castrated rats.

Castration of male rats leads to increased bone turnover and osteopenia. This study was conducted to examine the effects of the aminobisphosphonate alendronate on castration-induced bone changes. Bisphosphonates are drugs that inhibit bone turnover by decreasing the resorption. Since they suppress bone remodeling, they may also prevent the repair of microdamage and decrease bone strength. Although the mechanical properties of bones are directly related to the determination of fracture risk, bisphosphonate effects on the related variables have scarcely been investigated. Twenty-four male Wistar rats at two months of age were castrated or sham-operated to evaluate the effects of long-term administration (six months) of sodium alendronate at a dose of 1 mg/kg/day. The bones were tested mechanically by a three-point bending test in a Mini Bionix (MTS) testing system. High bone remodeling seen in castrated rats expressed by increased TrACP and B-ALP was suppressed by alendronate administration. Bone from castrated rats was characterized by a reduction in bone density as well as ash, calcium and phosphate content. Castration significantly altered mechanical properties of bone and femoral cortical thickness. When castrated rats were treated with high dose of alendronate, the changes in bone density resulting from castration were entirely prevented, and mechanical analysis revealed preserved mechanical strength of femur and cortical thickness. We conclude that castration induces cortical bone loss associated with high bone turnover in the male rat, and this bone loss can be prevented by alendronate through the inhibition of osteoclastic activity, while preserving the mechanical properties of bone. These results document the efficacy of alendronate, even at high doses, in preventing bone loss, loss of bone mechanical strength, and the rise in biochemical bone turnover indicators due to castration in rats, and raises the possibility that a alendronate could be equally effective in humans.

Surgical contribution to the management of primary hyperparathyroidism.

Surgical management of primary hyperparathyroidism is a very effective method. The target is to cure primary hyperparathyroidism and to reach normal calcium levels. This results in an improvement of health condition and resolution or at least moderation of symptoms. Complications are infrequent and mortality is very low. Surgical management is definite, safe and effective. Authors of this article address the diagnosis of primary hyperparathyroidism, clarify bone, metabolic and biochemical syndromes and present series of 151 patients that have been operated on at the 3rd Department of Surgery of the Motol University Hospital, Prague, with the diagnosis of primary hyperparathyroidism. The survey is focused on the primary hyperparathyroidism concomitant diseases and on the possible sequelae in the postoperative period.

The influence of nitric oxide synthase inhibitor L-NAME on bones of male rats with streptozotocin-induced diabetes.

The pathophysiological processes underlying the development of diabetic osteopenia has not hitherto been elucidated. Induction of streptozotocin diabetes leads in our experiments to decrease of bone density, ash, mineral content and to thinner cortical width compared to control male rats. In order to investigate the pathogenetic role of bone resorption by osteoclasts in streptozotocin-induced diabetes, we determined the circulating levels of tartrate-resistant acid phosphatase (TRAP), a biochemical marker for bone resorption. Plasma TRAP values in diabetic rats did not differ from their corresponding controls. Streptozotocin diabetes by itself did not have any effect on the weight of seminal vesicles which are highly testosterone-dependent. Low doses of nitric oxide cause bone resorption, but higher doses of NO inhibit bone resorbing activity. We examined the effect of L-NAME (inhibitor of nitric oxide production) after six weeks of administration to diabetic rats. There was no further significant loss of bone mineral density, ash and mineral content or tibia weight in diabetic rats treated with L-NAME. L-NAME itself did not decrease bone metabolism. In our study no evidence of an increased bone resorption was found. Our results have indicated that a predominance of bone resorption over bone formation is not involved in the pathogenesis of diabetes-associated osteopenia. Inhibition of NO neither increased osteoclastic activity (TRAP) nor induced osteopenia in L-NAME-treated rats. This suggests a possibility that NO is not involved in the pathogenesis of diabetic osteopenia.

Effects of triiodothyronine and estrogen administration on bone mass, mineral content and bone strength in male rats.

Experimental hyperthyroidism had a negative effect on bone mineral density, but did not significantly alter mechanical properties of femur and femoral bone thickness. Estradiol at a dose used in humans for the treatment of osteoporosis decreased seminal vesicle weight and concentration of testosterone but increased bone density in male rats compared to intact animals. In these rats, the mechanical analysis revealed an increased mechanical femur strength higher than the increase in bone density and femoral cortical thickness. When hyperthyroid male rats with low bone density were treated with estradiol in spite of a low plasma testosterone, the changes in bone density resulting from hyperthyroidism were entirely prevented. Estrogens protect the male skeleton against resorbing action of T (3). Treatment with estradiol in male rats with hyperthyroidism did not increase mechanical bone strength or femoral cortical thickness as it did with estradiol administration alone. Our results suggest that exogenously administered estrogens may have therapeutic value in preventing bone loss accompanying triiodothyronine administration, even in male rats with a low testosterone levels. At the concentration studied, estradiol increased in spite of low plasma testosterone, bone mineral density, mechanical strength of femur, and femoral cortical thickness.