[Position paper on medication-related osteonecrosis of the jaw (MRONJ)]. / Positionspapier zur medikamentenassoziierten Osteonekrose des Kiefers (MRONJ).

It is now 12 years since the first article on medication-related osteonecrosis of the jaw (MRONJ) was reported in 2003. The recognition of MRONJ is still inconsistent between physicians and dentists but it is without doubt a severe disease with impairment of oral health-related quality of life. This position paper was developed by three Austrian societies for dentists, oral surgeons and osteologists involved in this topic. This update contains amendments on the incidence, pathophysiology, diagnosis, staging and treatment and provides recommendations for management based on a multidisciplinary international consensus. The MRONJ can be a medication-related side effect of treatment of malignant and benign bone diseases with bisphosphonates (Bp), bevacizumab and denosumab (Dmab) as antiresorptive therapy. The incidence of MRONJ is highest in the oncology patient population (range 1-15 %), where high doses of these medications are used at frequent intervals. In the osteoporosis patient population, the incidence of MRONJ is estimated to be 0.001-0.01 %, marginally higher than the incidence in the general population (< 0.001 %). Other risk factors for MRONJ include glucocorticoid use, maxillary or mandibular bone surgery, poor oral hygiene, chronic inflammation, diabetes mellitus, ill-fitting dentures as well as other drugs, including antiangiogenic agents. Prevention strategies for MRONJ include elimination or stabilization of oral disease prior to initiation of antiresorptive agents, as well as maintenance of good oral hygiene. In those patients at high risk for the development of MRONJ, including cancer patients receiving high-dose BP or Dmab therapy, consideration should be given to withholding antiresorptive therapy following extensive oral surgery until the surgical site heals with mature mucosal coverage. Management of MRONJ is based on the stage of the disease, extent of the lesions and the presence of contributing drug therapy and comorbidity. Conservative therapy includes topical antibiotic oral rinses and systemic antibiotic therapy. Early data have suggested enhanced osseous wound healing with teriparatide in those patients without contraindications for its use. The MRONJ related to denosumab may resolve more quickly with a drug holiday than MRONJ related to bisphosphonates. Localized surgical debridement is indicated in advanced nonresponsive disease and has proven successful. More invasive surgical techniques are becoming increasingly more important. Prevention is the key for the management of MRONJ. This requires a close teamwork for the treating physician and the dentist. It is necessary that this information is disseminated to other relevant health care professionals and organizations.

How long should women with postmenopausal osteoporosis be treated with a bisphosphonate?

Bisphosphonates are very frequently prescribed to women suffering from postmenopausal osteoporosis with or without fragility fractures. The present review was aimed to update the available information on the most efficient treatment duration. Studies on bisphosphonate treatment duration were identified by Medline up to January 2013. Bisphosphonates are very effective in the short as well as in the medium-term. However, the optimal duration of use has not been determined yet. Therefore, this review summarizes the long-term effects of bisphosphonates on surrogate parameters of fracture prevention, bone mineral density measurements, and bone turnover markers. An initial treatment period of 3-5 years is recommended. Then, the patient has to be re-evaluated for fracture risk, which depends on fracture status as well as on other health issues. Beyond that, life style factors such as regular physical activity as well as a sufficient intake of calcium and vitamin D or, if necessary supplementation of calcium and/or vitamin D play an essential part in fracture prevention.

Surgeons save bones: an algorithm for orthopedic surgeons managing secondary fracture prevention.

Postmenopausal osteoporosis has a big impact on health care budget worldwide, which are expected to double by 2050. In spite of severe medical and socioeconomic consequences from fragility fractures, there are insufficient efforts in optimizing osteoporotic treatment and prevention. Undertreatment of osteoporosis is a well known phenomenon, particularly in elderly patients. Treatment rates remain low across virtually all patient, provider, and hospital-level characteristics, even after fragility fractures. In-hospital initiation is one of the options to increase treatment rates and improve osteoporosis management. However, multiple factors contribute to the failure of initiating appropriate treatment of osteoporosis in patients with fragility fractures. These include a lack of knowledge in osteoporosis and an absence of a comprehensive treatment guideline among family physicians and orthopedic surgeons. Furthermore, orthopedic surgeons are hardly willing to accept their responsibility for osteoporosis treatment due to the fact that they are usually not familiar with the initiation of specific drug treatments. The presented algorithm offers trauma surgeons and orthopedic surgeons a safe and simple guided pathway of treating osteoporosis in postmenopausal women appropriately after fragility fractures based on the current literature. From our point of view, this algorithm is useful for almost all cases and the user can expect treatment recommendations in more than 90 % of all cases. Nevertheless, some patients may require specialized review by an endocrinologist. The proposed algorithm may help to increase the rate of appropriate osteoporosis treatment hence reducing the rates of fragility fractures.

A rare case of a 123I-MIBG SPECT/CT positive, but 68Ga-DOTA-TOC PET/CT negative pheochromocytoma of the bladder. / Caso infrecuente de feocromocitoma vesical positivo en la SPECT/TC con 123I-MIBG, pero negativo en la PET/TC con 68Ga-DOTA-TOC.

Pheochromocytoma (PHEO) is rare and belongs to the group of neuroendocrine tumours (NETs). These tumours can be found anywhere from the neck to the pelvis associated with sympathetic ganglia. Morphological imaging, for example CT, provides excellent anatomical detail and high sensitivity but lacks specificity as difficulties may occur when distinguishing between tumours derived from the sympathetic nervous system and other tumour entities. In contrast to anatomical imaging, functional imaging (123I-MIBG, 68Ga-DOTA-TOC PET) provides high sensitivity and specificity in detecting NETs. Early detection of PHEO is crucial and has a major effect on treatment and prognosis. This case report describes the important role of anatomical and functional imaging in a patient with a neuroendocrine tumour of unusual origin.

Levels and molecular properties of secretoneurin-immunoreactivity in the serum and urine of control and neuroendocrine tumor patients.

We have determined the levels of secretoneurin (SN), a novel 33-amino acid neuropeptide belonging to the class of chromogranins, in the serum and urine of healthy subjects and patients suffering from various tumors. SN serum levels averaged 22.1+/-1.1 fmol/mL. They were 5-fold higher in younger children and then declined continuously. SN levels were positively correlated with serum creatinine, suggesting an influence of renal function on the clearance of SN from the serum. In the urine 80.0 fmol/mL SN was present. In patients with endocrine tumors like gut carcinoids, endocrine pancreatic tumors, oat cell lung carcinomas, and pheochromocytomas, SN serum levels were elevated up to 45-fold. Patients suffering from neuroblastomas, insulinomas, pituitary adenomas including acromegaly, and solid nonendocrine tumors had concentrations in the normal range. In human serum, SN-immunoreactivity was confined to the free peptide SN; neither larger intermediate-sized forms nor the precursor secretogranin II were detected. An efficient removal of the small molecule SN from the serum by the kidney explains why SN serum levels are lower when compared to chromogranin A, which is present as large molecule in serum.

Molecular characterization of immunoreactivities of peptides derived from chromogranin A (GE-25) and from secretogranin II (secretoneurin) in human and bovine cerebrospinal fluid.

Chromogranin A and secretogranin II are members of the so-called chromogranins, the acidic proteins stored in neuroendocrine large dense-core vesicles. We characterized chromogranin A and secretogranin II immunoreactivities in cerebrospinal fluid by radioimmunoassays using synthetic peptides derived from these components (GE-25 for chromogranin A and secretoneurin for secretogranin II). In lumbar cerebrospinal fluid, high levels (more than 1000 fmol/ml) of these two components were found, whereas in ventricular cerebrospinal fluid the secretoneurin levels were relatively low. The cerebrospinal fluid/serum ratio for secretoneurin was close to 170. High-performance liquid chromatography revealed that in both cerebrospinal fluid and extracts from human brain secretoneurin was the predominant immunoreactive component. In cerebrospinal fluid chromogranin A immunoreactivity was present as intermediate-sized peptides with little intact chromogranin A and free GE-25 peptide. In human brain samples smaller peptides including GE-25 were more predominant. Analogous findings for secretoneurin and chromogranin A were obtained for bovine brain samples. We can conclude that chromogranins are present in cerebrospinal fluid in concentrations much higher than those of classical neuropeptides also stored in large dense-core vesicles. Therefore, their degree of proteolytic processing can be analysed with small samples of cerebrospinal fluid. A possible disturbance of proteolytic processing in large dense-core vesicles in various pathological conditions can now be discovered.

Effects of growth hormone (GH) replacement on bone metabolism and mineral density in adult onset of GH deficiency: results of a double-blind placebo-controlled study with open follow-up.

It is known that GH stimulates bone turnover and that GH-deficient adults have a lower bone mass than healthy controls. In order to evaluate the influences of GH replacement therapy on markers of bone turnover and on bone mineral density (BMD) in patients with adult onset GH deficiency, a double-blind placebo-controlled study of treatment with recombinant human GH (rhGH; mean dose 2.4 IU daily) in 20 patients for 6 months and an extended open study of 6 to 12 months were conducted. Eighteen patients, fourteen men and four women, with a mean age of 44 years with adult onset GH deficiency were evaluated in the study. Compared with placebo, after 6 months serum calcium (2.39 +/- 0.02 vs 2.32 +/- 0.02 mmol/l, P = 0.037) and phosphate (0.97 +/- 0.06 vs 0.75 +/- 0.05 mmol/l, P = 0.011) increased and the index of phosphate excretion (0.03 +/- 0.03 vs 0.19 +/- 0.02, P < 0.001) decreased significantly, and there was a significant increase in the markers of bone formation (osteocalcin, 64.8 +/- 11.8 vs 17.4 +/- 1.8 ng/ml, P < 0.001; procollagen type I carboxyterminal propeptide (PICP), 195.3 +/- 26.4 vs 124.0 +/- 15.5 ng/ml, P = 0.026) as well as those of bone resorption (type I collagen carboxyterminal telopeptide (ICTP), 8.9 +/- 1.2 vs 3.3 +/- 0.5 ng/ml, P < 0.001; urinary hydroxyproline, 0.035 +/- 0.006 vs 0.018 +/- 0.002 mg/100 ml glomerular filtration rate, P = 0.009). BMD did not change during this period of time. IGF-I was significantly higher in treated patients (306 +/- 45.3 vs 88.7 +/- 22.5 ng/ml, P < 0.001). An analysis of the data compiled from 18 patients treated with rhGH for 12 months revealed similar significant increases in serum calcium and phosphate, and the markers of bone turnover (osteocalcin, PICP, ICTP, urinary hydroxyproline). Dual energy x-ray absorptiometry (DXA)-measured BMD in the lumbar spine (1.194 +/- 0.058 vs 1.133 +/- 0.046 g/cm2, P = 0.015), femoral neck (1.009 +/- 0.051 vs 0.936 +/- 0.034 g/cm2, P = 0.004), Ward's triangle (0.881 +/- 0.055 vs 0.816 +/- 0.04 g/cm2, P = 0.019) and the trochanteric region (0.869 +/- 0.046 vs 0.801 +/- 0.033 g/cm2, P = 0.005) increased significantly linearly (compared with the individual baseline values). At 12 months, BMD in patients with low bone mass (T-score < -1.0 S.D.) increased more than in those with normal bone mass (lumbar spine 11.5 vs 2.1%, P = 0.030, and femoral neck 9.7 vs 4.2%, P = 0.055). IGF-I increased significantly in all treated patients. In conclusion, treatment of GH-deficient adults with rhGH increases bone turnover for at least 12 months. BMD in the lumbar spine and the proximal femur increases continuously in this time (open study) and the benefit is greater in patients with low bone mass. Therefore, GH-deficient patients exhibiting osteopenia or osteoporosis should be considered candidates for GH supplementation. However, long-term studies are needed to establish that the positive effects on BMD are persistent and are associated with a reduction in fracture risk.

[Tumor markers in bronchus cancer]. / Tumormarker beim Bronchuskarzinom.

Small cell lung cancers are neuroendocrine tumours and therefore produce a lot of peptide hormones (calcitonin, ACTH, ADH), as well as the neuropeptide chromogranin A, which are all useful tumour markers. Furthermore, the tumour-associated antigens CEA and TPA, as well as the enzymes neuron specific enolase (NSE) and creatine kinase BB are used as markers in small cell lung cancer. At present, NSE appears to be the best marker for small cell lung cancer; elevated serum NSE levels are found in 65 to 85% of the patients. The serum level of the tumour markers is related to the stage of the tumour. When tumour regression occurs following therapy, elevated pretreatment levels decrease to the normal range. If the marker level increases again, tumour progression is indicated and this can be an early and sensitive sign denoting recurrence. Metastases in the central nervous system can be detected early by marker determination in the cerebrospinal fluid. At present, CEA appears to be the most valuable tumour marker for non-small cell lung cancer, but TPA may also be a useful marker.

[Treatment of hypertension with a drug combination, consisting of bemetizide, triamterene, dihydralazine and bupranolol (author's transl)]. / Hypertoniebehandlung mit einem Kombinationspräparat, bestehend aus Bemetizid, Triamteren, Dihydralazin und Bupranolol.

The optimal daily dose and dose regimen of a new drug combination (Pertenso), consisting of 10 mg bemetizide, 20 mg triamterene, 20 mg dihydralazine and 20 mg bupranolol were tested in 14 hypertensive outpatients (WHO I to III) in a single blind crossover trial. The mean blood pressure before treatment was 183/107 +/- 5/2 mm Hg (+/-SEM) and was lowered to a mean blood pressure of 147/89 +/- 4/4 mm Hg (+/- SEM; p less than 0,005) during a multiple dose regimen and to 141/84 +/- 3/3 mm Hg (+/- SEM; p less than 0,005) during a single dose regimen. The results indicate that even in hypertension which requires a combination of diuretics, vasodilators and beta-adrenergic blocking agents for treatment, a fixed combination of these substances could be given for effective blood pressure control. The data suggest the possibility of a single dose regimen of the fixed drug combination.

Changes in the volume of residual pituitary adenomas in patients with adult-onset growth hormone deficiency during replacement therapy with the recombinant human growth hormone.

In the course of a prospective study concerning recombinant human growth hormone replacement therapy in adult-onset growth hormone deficiency, we determined the volumes of residual tumors in six patients with pituitary macroadenomas who had formerly been treated with surgery alone or surgery and external radiotherapy. Pituitary CT scans in direct coronal views were obtained at baseline, and at 6, 12 and 18 months. The volumes of the residual tumors were calculated from the tumor diameters assuming that the tumors had an ellipsoid shape. Tumor volumes did not change in one patient and were reduced in two patients. In three patients, clinically non-significant tumor expansion by a median of 23.6 +/- 13.2% (range, 21.1-62.0%) was noted after 12 to 18 months. This tumor expansion did not cause signs or symptoms of a mass effect and did not influence further treatment. One of the six patients discontinued treatment and no further change in tumor size, as determined by MRT, was noted over a mean follow up of 34 months. Treatment was continued for up to 38 months in five patients. In four of these five patients no further change in tumor size was detected. However, treatment with the growth hormone was stopped in one patient since a 30% expansion in tumor volume, elevating the optic chiasm, was noted on MRT. None of the patients developed deterioration of visual fields. Interestingly, tumor invasion of the cavernous sinus had been present initially in all three who displayed tumor expansion while on rhGH. This first study in which diameters of residual pituitary adenomas in patients on growth hormone replacement therapy were prospectively and carefully measured, permits no conclusion regarding a causal relationship between growth hormone and tumor expansion, owing to the small number of patients. However, the observed incidence is not much different from that in former studies without growth hormone replacement therapy. Nevertheless, a close observation of the pituitary by imaging studies at regular intervals appears to be mandatory, particularly in patients with invasive residual adenomas.

[Trans-septo-sphenoidal operation for pituitary adenoma in 92 patients: results and follow-up endocrine studies]. / Transseptosphenoidale Operation von Hypophysenadenomen bei 92 Patienten: Ergebnisse und endokrine Verlaufskontrolle.

The short- and long-term therapeutic results of transseptosphenoidal adenomectomy were studied retrospectively in 92 patients with pituitary tumors (42 nonsecreting adenomas, 21 GH-, 15 PRL-, 10 ACTH-, 2 TSH-, and 2 FSH-secreting adenomas). Severe surgically related complications were not observed. The early remission rate was 53.7% in nonsecreting, 57.1% in GH-secreting, 60% in PRL-secreting, 88.9% in ACTH-secreting, and 75% in TSH- or FSH-secreting adenomas. The recurrence rate in patients with nonsecreting adenomas was 47.1%, with GH-secreting adenomas 10%, with ACTH-secreting adenomas 25%, and with TSH- or FSH-secreting adenomas 66.7%, respectively. A long-term cure rate of 69.2% was observed in prolactinomas in combination with a facultative dopamine agonist therapy. More patients had normal pituitary function concerning TSH, ACTH, and LH/FSH post-operatively (48.9% versus 46.6% preoperatively). These data confirm that transseptosphenoidal surgery is a safe and selective treatment for pituitary adenomas with efficient preservation of the normal pituitary gland.

Current controversies in clinical management of postmenopausal osteoporosis.

Osteoporosis is a frequent disease in postmenopausal women. Despite the fact that fragility fractures cause many problems - a bio-psycho-social burden for the individual and an economic burden for the society - osteoporosis is still underdiagnosed and undertreated. Controversies exist concerning assessment with different tools for initiating a disease-specific treatment, patient monitoring with bone turnover markers, and treatment duration due to potential side effects in long-term treatment. This manuscript outlines and discusses these controversies and the presented cases, representatives for frequent clinical problems, may give guidance for the clinician in deciding how and how long to treat his/her patient. Re-evaluations of the patients on a regular basis are essential to warrant the necessity of treatment continuation and may improve patients' compliance.

Bone mineral density and bone metabolism in patients with major depressive disorder without somatic comorbidities.

BACKGROUND: Major depressive disorder (MDD) has been linked with accelerated bone loss leading to the development of low bone mineral density (BMD). Several mechanisms have been discussed as causative factors, e.g. lifestyle, selective serotonin reuptake inhibitor (SSRI) intake, or the influence of proinflammatory cytokines. METHODS: In a cross-sectional study of in-patients with a current episode of MDD, without somatic comorbidities, we determined various parameters of bone metabolism, inflammatory parameters and parameters of depression. BMD was measured by dual x-ray absorptiometry. RESULTS: Of 50 patients, only one had low BMD in any of the measure sites. Body mass index (BMI) correlated positively with Z-scores. 83.3% of the examined patients had elevated osteoprotegerin (OPG) levels. SSRI intake did not have an effect on BMD. BMD in the femoral neck was significantly lower in smokers. We also found a positive correlation between the level of physical activity and osteocalcin levels. CONCLUSIONS: In our sample, young to middle-aged, somatically healthy, and acutely depressed patients with a history of MDD showed no reduction of BMD. This could be due to compensatory mechanisms, as suggested by elevated OPG levels. Physical activity and high BMI could also have served as protective factors. Still, as patients with MDD often suffer from comorbidities or take medication with a negative effect on bone, this population should be appreciated as a high-risk group for the development of osteopenia and osteoporosis.

[Androgen therapy from the viewpoint of the internal medicine physician]. / Androgentherapie aus der Sicht des Internisten.

The partial androgen deficit of the ageing male is an essential part of the age-related changes of the endocrine system. Clinically relevant disturbances (co-) caused by a relative testosterone-deficit are: changes of body composition (increase of fat mass, decrease of lean tissue mass), decrease of muscle strength and mass, changes of the lipid profile, cardiovascular disease, osteoporosis and anemia. Controlled studies revealed a positive effect of testosterone substitution on body composition, muscle strength, bone metabolism and erythropoesis. Moreover, a protective effect on the development of coronary artery disease could be demonstrated by an improvement of the lipid profile, decrease of obesity and insulin resistance and by a direct effect on the coronary vessels. Clinically evident hypogonadism is a clear indication for testosterone-substitution also in the ageing male, whereas in the case of the partial testosterone-deficit in the absence of sufficient data at this time no general recommendation for substitution can be given; one has to decide about a (experimental) therapy in the individual patient. In every case the contraindications of a testosterone-supplementation (carcinoma of the prostate, elevated PSA-values, polyglobulia, sleep-apnea-syndrome) have to be observed, a continuous survey of the therapy, especially of the prostate is essential. A general recommendation for a substitution with dehydroepiandrosterone (DHEA) can not be given.

[Severe intoxication after combined chemotherapy of a sigma-adenocarcinoma with peptichemio and 5-fluorouracil (author's transl)]. / Schwere Intoxikation nach kombinierter Chemotherapie eines Sigma-Adenokarzinoms mit Peptichemio und 5-Fluorouracil.

After perioperative adjuvant chemotherapy of a sigma-adenocarcinoma with 400 mg peptichemio and 500 mg 5-fluorouracil a 61-year-old woman developed a severe intoxication: myelosuppression with pancytopenia, gastroenteritis and ulcerative proctitis, toxic hepato- and myocardiopathy, impaired renal function and alopecia. As a result of reduced resistance pneumonias, urinary tract infection, sepsis, cytomegaly infection and candidiasis of the oral mucosa occurred. The toxic effects are attributed mainly to the high dose of peptichemio.

[Systematic diagnostic workup: differential diagnosis of various forms of osteoporosis]. / Rationale Befunderhebung: Differentialdiagnose verschiedener Osteoporoseformen.

The objects of a rational approach to the diagnosis of osteoporosis are the identification of patients with osteopenia/osteoporosis by radiological methods, investigations concerning the etiology of the disease and an assessment of bone turnover by biochemical markers. Current classifications of osteoporosis are explained. The WHO classification of osteoporosis and a clinical classification according to severity are based on bone densitometry and fractures. In accordance with pathogenetic aspects a division in osteoporosis without or with known causes is possible (primary/secondary), moreover several regional forms of osteoporosis are mentioned. A classification in "low-" or "high-turnover" osteoporosis is possible by an assessment of the rate of bone loss. The diagnostic procedures in osteoporosis include the patients' history (pain, skeleton, risk factors for osteoporosis and for falls) and an exact physical examination. Essential radiological investigations are radiographs of thoracic and lumbar spine and a bone mass measurement (dual X-ray absorptiometry--DXA or quantitative computerized tomography--QCT, possibly also a quantitative ultrasonography). Basic laboratory tests, including markers of bone turnover are routinely performed, whereas additional specific tests are optional, according to the clinical situation. Scintigraphy and bone biopsy are seldom used in the diagnostic procedure. Practical guidelines for the diagnosis of osteoporosis in patients with or without pain are discussed. Diagnostic investigations should only be performed, if the patients gain benefit from it concerning prophylaxis or therapy.

Lactose absorption, milk consumption, and fasting blood glucose concentrations in women with idiopathic osteoporosis.

Lactose tolerance tests were performed in 33 women with osteoporosis and 33 control women matched for age. A questionnaire was used to elicit any history of milk intolerance and the subjects' daily intake of calcium derived from milk and dairy products. Eleven patients and four controls gave a history of milk intolerance (p less than 0.01); 13 patients had lactose malabsorption compared with four controls (p less than 0.01). The daily intake of calcium derived from milk was significantly lower in patients (125 (SEM 20) mg v 252 (43) mg; p less than 0.05). Curves of blood glucose concentrations during the lactose tolerance test in subjects with lactose malabsorption were significantly flatter in patients than controls (p less than 0.05). The fasting blood glucose concentration was higher (5.44 (0.17) mmol/l (98 (3) mg/100 ml) in the patients than the controls (4.88 (0.11) mmol/l (88 (2) mg/100 ml); p less than 0.05), although body weight was significantly lower (61.6 (2.2) kg v 66.3 (1.6) kg; p less than 0.05). Absorption of lactose is significantly impaired in women with "idiopathic" osteoporosis; this combined with low consumption of milk and a subclinical disorder of glucose metabolism may be a major factor in the development of idiopathic osteoporosis in women.

[Follow-up of patients with pituitary tumors before and after operation, medical treatment and radiotherapy (author's transl)]. / Verlaufskontrollen bei Patienten mit Hypophysentumoren vor und nach Operation, medikamentöser Behandlung und Strahlentherapie.

From 1976 till 1981 56 patients with pituitary tumors were observed. From a total of 51 adenomas 17 prolactinomas (33.3%), 15 acromegalies (29.4%), 4 Cushing-syndromes (7.8%), 1 TSH-producing adenoma (1.9%) and 14 hormone-inactive adenomas (27.4%) were found. In addition there were 4 craniopharyngeomas and 1 intrasellar meningeoma. For the individual types of adenomas prae-and postoperative hormonal data after transcranial resp. transsphenoidal adenomectomy are listed. Prolactinomas responded well to bromocriptine therapy in some cases, whereas acromegalies showed no remission after bromocriptine. After radiotherapy of 4 recidive-adenomas remission in one case was seen. Problems and objects of long-term-care of patients with pituitary tumors are discussed.

Low-sodium diet versus low-sodium/high-potassium diet for treatment of hypertension.

In 21 patients with essential hypertension the effects of moderate sodium restriction from the usual 200 mmol Na/day to 80 mmol/day over 4 weeks were compared with the effects of a combined low-sodium/high-potassium intake (80 mmol Na/120 mmol K) which was also given over 4 weeks in an open crossover trial. Systolic blood pressure in nine untreated patients with essential hypertension decreased significantly by between 5 and 7 mm Hg during moderate sodium restriction; no further decrease of blood pressure occurred during the combined low-sodium/high-potassium diet. In 12 treated patients with essential hypertension moderate sodium restriction or the combined low-sodium/high-potassium diet enabled a marked reduction of anti-hypertensive therapy in eight patients without impairment of blood pressure control (beta-blockers by an average of 32%, saluretics by an average of 27% and vasodilators by an average of 24%). Here there were also no substantial differences between low-sodium intake and the combined low-sodium/high-potassium intake. It is concluded that sodium restriction to 80 mmol/day is effective in lowering systolic blood pressure but that a combined low-sodium/high-potassium diet does not further improve blood pressure control if the usual potassium intake is at least 80 mmol/day. Considerable reduction of anti-hypertensive therapy may be achieved by practical moderate sodium restriction.

Adrenocortical carcinoma evolving after diagnosis of preclinical Cushing's syndrome in an adrenal incidentaloma. A case report.

A 43-year-old female patient underwent abdominal ultrasonography and CT scan because of uncharacteristic abdominal pain. A 3-cm homogeneous adrenal tumor was diagnosed. The endocrine tests revealed an adrenal preclinical Cushing's syndrome (PCS). Due to the latent hormone excess we decided to operate on the adrenal tumor. Since the tumor was small, laparoscopic adrenalectomy was performed. Histological evaluation showed an adrenocortical tumor of undetermined nature. Four months later the patient presented with a metastasizing cortisol- and androgen-producing adrenocortical carcinoma (ACC). After pretreatment with ketoconazole to suppress the biosynthesis of adrenal steroids under substitution with hydrocortisone, we reduced the tumor load by surgery. Postoperatively we continued ketoconazole and started o, p'-dichlorodiphenyldichloroethane as well as chemotherapy with doxorubicin and suramin. However, the patient died from ACC 7 months after adrenalectomy. It is known from several reports that PCS may persist clinically silently or may progress to full-blown Cushing's syndrome. This is the first time a malignant course of PCS is described. Independent of the initial therapeutic strategy of PCS, i. e. surgery or regular follow-up visits, we must be aware that also relatively small adrenal tumors can harbor malignancy.