[Addison's disease as a rare cause of chronically elevated liver enzymes]. / Morbus Addison als seltene Ursache für chronisch erhöhte Transaminasen.

Common causes of chronically elevated serum liver enzymes include fatty liver disease, chronic viral hepatitis, autoimmune hepatitis, or hereditary metabolic disorders. Adrenocortical insufficiency can also cause elevated liver enzymes. Since 1990 only 11 cases have been reported. We here report a 52-year-old man with elevated liver enzymes (1.5 x upper limit of normal) over the past 10 years. Furthermore, hyponatremia and hyperkalemia were noted. He complained of fatigue and low blood pressure over the past few years. At physical examination a dark complexion was noted. After ruling out chronic viral hepatitis, autoimmune disease, metabolic or hereditary disorders, rare causes of elevated liver enzymes were considered. The endocrinological work-up revealed Addison's disease as cause of serum electrolyte disturbance and elevated liver enzymes. The patient was successfully treated with hydrocortisol and fludrocortisol. After one week, liver enzymes, serum electrolytes and arterial blood pressure had normalized. In conclusion, for patients with constantly elevated liver enzymes also rare, extrahepatic diseases have to be considered. Addison's disease is a rare but fully reversible cause for elevated liver enzymes.

Variable bone mass recovery in hyperthyroid bone disease after radioiodine therapy in postmenopausal patients.

OBJECTIVES: Long-term follow-up of postmenopausal hyperthyroid females after radioiodine therapy, since hyperthyroidism is known to cause impressive bone loss which may increase the risk of bone fractures. METHODS: Bone mineral density (BMD) and biochemical parameters of bone metabolism in hyperthyroid postmenopausal patients were investigated before and 2 years after radioiodine therapy and compared with euthyroid age-matched controls. RESULTS: At baseline, the incidence of low BMD with t-scores more than 2.5 S.D. below normal was significantly higher in hyperthyroid patients (54%) than in controls (20%, P<0.001). Regardless of initial BMD values, osteocalcin (OC) was also higher in all hyperthyroid patients (P<0.0001). After 2 years, all treated patients were euthyroid and OC levels were in the upper normal range. In hyperthyroid patients with initially low BMD, bone density values had increased significantly by +6.5% (P<0.008) as compared with baseline values. In contrast, hyperthyroid patients with initially normal BMD showed a further decrease in lumbar BMD values of -4.3% despite radioiodine treatment. BMD in euthyroid controls decreased by -6.5% within 2 years. CONCLUSIONS: We conclude that hyperthyroid postmenopausal patients with generally increased bone turnover may show individual differences in bone loss and BMD recovery after radioiodine treatment. The mechanisms for this variable manifestation of osteoporosis have still to be elucidated, since this has implications for prophylactic and therapeutic strategies in these elderly patients.

Plasma levels of parathyroid hormone-related peptide are elevated in hyperprolactinemia and correlated to bone density status.

Osteopenia is an important clinical manifestation of hyperprolactinemia. Bone loss in these patients has mainly been attributed to concomitant deficiency of gonadal hormones rather than to hyperprolactinemia per se. Parathyroid hormone-related peptide (PTHrP) is expressed in human mammary tissue, and elevated circulating PTHrP levels as well as concomitant hypercalcemia have been described during lactation. We sought to determine circulating PTHrP levels in patients with long-standing hyperprolactinemia and whether PTHrP may exert possible systemic effects on bone and mineral metabolism. We studied 45 patients (30 women and 15 men) with persisting hyperprolactinemia 6 +/- 4 years (mean +/- SD) after trans-sphenoidal surgery for prolactin-producing pituitary adenomas. PTHrP levels in 117 healthy controls were 10.6 +/- 7.3 pmol-eq/l (mean +/- SD). In hyperprolactinemic patients, plasma PTHrP was elevated to 30.3 +/- 13.4 pmol-eq/l (p < 0.001, n = 45), and in patients with humoral hypercalcemia of malignancy PTHrP levels were 52.9 +/- 29.6 (p < 0.001 to controls and hyperprolactinemic patients). Fifty-three percent of hyperprolactinemic patients (n = 24) had clearly elevated PTHrP levels (> 2 SD). Retrospective immunocytochemical studies of the removed pituitary adenomas from 19 patients generally showed a higher degree of immunoreactivity for PTHrP (1-34) in all but one case when compared with normal pituitary tissue. Patients with elevated circulating PTHrP levels showed in most instances strong immunoreactivity to PTHrP in 70-100% of tumor cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Thyroid hormone excess and osteoporosis.

Current thinking and available clinical data on the relationship between hyperthyroidism and bone disease are discussed. Data are also presented on TSH-suppressive and non-suppressive thyroid hormone therapy and its effect on bone. Although these data are clearly inconsistent, some risk factors for thyroid hormone induced osteopenia seem to be accepted: long standing, clinically manifest hyperthyroidism (a very rare disorder today because of early diagnosis and appropriate therapy), old age, menopause and total thyroidectomy. Thyroid hormone therapy (whether TSH-suppressive or not) has not been proven so far to lead to manifest osteoporosis.

The effect of treatment with levothyroxine or iodine on thyroid size and thyroid growth stimulating immunoglobulins in endemic goitre patients.

OBJECTIVE: We assessed the effect of levothyroxine or iodine on thyroid size and on thyroid growth stimulating immunoglobulins in endemic goitre patients. DESIGN: Levothyroxine or iodine was given orally in an open randomized prospective study (100 and 200 micrograms respectively). PATIENTS: Thirty-seven euthyroid patients with diffuse iodine deficiency goitres and thyroid growth stimulating immunoglobulins were studied. MEASUREMENTS: Thyroid size, thyroid growth stimulating immunoglobulins (mitosis arrest assay), basal TSH, free T3, free T4, thyroid anti-microsomal antibodies, antithyroglobulin antibodies, anti-TSH receptor antibodies and urinary iodine excretion were measured. RESULTS: Thyroid size decreased significantly in both groups, in the levothyroxine group more than in the iodine treated group. Thyroid growth stimulating immunoglobulins levels also decreased significantly in both groups. Between groups there was no statistically significant difference. A statistically significant correlation between thyroid growth stimulating immunoglobulins reduction profiles and goitre size reduction could not be established. TSH levels became suppressed in the levothyroxine group while the T4 values rose; in the iodine treated group TSH levels stayed constant as did T4. None of the patients developed thyroid microsomal or thyroglobulin auto-antibodies and/or hyperthyroidism during the treatment. CONCLUSIONS: Levothyroxine as well as iodine was effective in reducing thyroid size as well as thyroid growth stimulating immunoglobulins levels in endemic goitre patients. Since in both groups TSH levels were not related to thyroid size reduction, other factors than TSH suppression must be responsible for the observed thyroid size reduction. Iodine itself by virtue of its antiproliferative action on thyrocytes may have had a direct action on the goitre reduction during iodine treatment; however, the levothyroxine dose, containing less iodine, had a similar effect. A complicated picture hence emerges with regard to factors involved in the shrinkage of iodine deficiency goitre during thyroxine or iodine therapy. These findings indicate that TSH and thyroid growth promoting immunoglobulins are not the only influences on the size of endemic goitres, although it cannot be excluded that these two factors contribute to influence the pathogenetic process.

Enhancing in vivo effect of propranolol on human lymphocyte function is not due to stereospecific beta-adrenergic blockade.

Immunoenhancing in vivo effects of beta-adrenergic blockers have been previously ascribed to a reduced beta-receptor-mediated immunosuppression. In the present study using a whole blood stimulation assay, the effects of a five-day treatment with the purified (R)- or (S)-isomer of propranolol (3 x 40 mg/day) on the polyclonal in vitro responsiveness of peripheral blood lymphocytes (PBL) of normothyroid and hyperthyroid persons were assessed. It is shown that both isomers likewise exhibit a significant enhancing effect on the proliferative response of PBL to T and B cell mitogens, which strongly argues for nonspecific effects of propranolol to be responsible rather than a specific beta-adrenergic receptor blockade.

[Clinical value of the various methods of ACTH determination]. / Klinische Wertigkeit unterschiedlicher ACTH-Bestimmungsmethoden.

We determined 293 plasma-ACTH levels out of 49 patients. In 12 patients with various pituitary diseases 168 samples were collected during a standardized pituitary stimulation test. For this purpose we used the following kits: the DYNOtest ACTH and LUMItest ACTH and Allegro HS-ACTH test. Additionally, morning ACTH levels were analyzed from 49 patients using Allegro HS ACTH test and DYNOtest ACTH. Regarding ACTH concentrations during pituitary stimulation the clinical usefulness of the 3 named tests were comparable. Pair differences of morning ACTH levels were not statistically significant. In a setting of a wide range of ACTH levels all 3 trials proved appropriate for making a diagnosis. Practicability of all 3 tests was similar. For all 3 methods incubation can be done overnight which saves time. Reagents can be reused when frozen immediately after reconstitution.

Involvement of the immune system in iodine deficient goiter.

Iodine deficient goiters were studied by immunohistochemistry and showed extensive presence and typical arrangement of dendritic cells, known to have excellent antigen presenting capacity. These cells were positive for all MHC-class II epitopes and for ICAM-1. Epithelial follicle lining cells were also seen to be class II positive but lacked ICAM-1. Thyroglobulin seemed not to be iodinated at the C-terminal hormogenic site, as shown by reactions with monoclonal antibodies. Iodine therapy, as well as thyroxine therapy were effective in reducing thyroid size. Both forms of therapy were found to decrease the pretreatment levels of circulating thyroid growth stimulating immunoglobulins (TGI).

[Kala-azar acquired in Croatia]. / In Kroatien erworbene Kala-Azar.

Six weeks after his return from a two-week vacation in Croatia a 52 year-old janitor from Graz complained of loss of appetite, fever, headache, and a 9-kg weight loss. The spleen was enlarged to 16cm as measured by sonography. Laboratory tests revealed pancytopenia, a prolonged prothrombin time and elevation of serum LDH concentration. While repeated bone marrow biopsy showed no signs of leishmaniasis, high antibody titers against leishmania antigen led to the diagnosis of kala-azar. The indirect immunofluorescent antibody test (1:128) and a haemagglutination-inhibition test (1:512) showed diagnostic elevations of titers. Therapy with pentostam led to prompt defervescence and resulted in a full recovery of the patient. After six weeks a marked decrease of antibody titers in the haemagglutination-inhibition test (1:16) could be observed. Leishmaniasis has to be considered in patients with fever of unknown origin who return from Mediterranean countries. Despite a negative bone marrow biopsy a diagnosis is possible on the basis of serological tests. This is important because effective therapy is available as illustrated by this patient and because of the fact that the disease runs a lethal course if the diagnosis is missed.

[Sonography and cytology of cold thyroid nodules]. / Sonographie und Zytologie von kalten Schilddrüsenknoten.

270 patients with a scintigraphically cold thyroid nodule of sonographically increased (n = 34), diminished (n = 72) or neutral (n = 86) echogenity or cystic criteria (n = 78) were subjected to fine needle aspiration biopsy. This revealed unequivocal malignancy in 8 and follicular neoplasia in another 30 patients, 10 of whom proved to have malignomas on further evaluation. A total of 12 papillary and 2 follicular carcinomas, 2 non-Hodgkin lymphomas, 1 sarcoma and the metastasis of a breast carcinoma were diagnosed. The most sensitive criteria for malignancy were diminished echogenity, an inhomogeneous echo pattern and the occurrence of a solitary nodule. The incidence of malignancy was increased among males but not among especially young persons. There was no sonographic feature that would permit omission of fine needle aspiration.

[Pharmacology and dosage of thyrostatic drugs]. / Pharmakologie und Dosierung der Thyreostatika.

The iodine organification in thyroid gland was inhibited by application of Thyrostatic (Methimazole, Carbimazole) and consequently, thyroid hormone production and excretion were diminished. Carbimazole is converted to Methimazole in vivo and in vitro. Equivalent doses of Carbimazole and Methimazole are 0.6 to 1.0. Methimazole penetrates through the placenta, therefore established therapy with Methimazole (or Carbimazole) and thyroid hormone are contradicted in states of gravidity. In hyperthyroidism, preferred therapy strategy is accepted as Methimazole and/or Carbimazole only and in low doses, respectively (40-60 mg Methimazole as first step, consequently to doses down to 5-10 mg daily); accompaning rates of hematopoetic damage are dose responded.

[Successful treatment of autoimmune hemolytic anemia with cyclosporin A]. / Erfolgreiche Behandlung einer autoimmunhämolytischen Anämie mit Cyclosporin A.

A sixty-year-old patient suffering from an idiopathic immunohemolytic anemia was treated by 3 plasma exchanges (with 31 exchange-volume) and following by Ciclosporin A (3 mg/kg body weight) after the monotherapy of prednisone has been unsuccessful. Ciclosporin A promptly effected a continuous remission of the autoimmune hemolysis. The mode of action of Ciclosporin A in immunhemolytic anemia depending on incomplete warm-auto-antibodies is discussed.

[Diagnostic significance of immunoradiometric serum TSH determination]. / Diagnostische Bedeutung der immunradiometrischen TSH-Bestimmung im Serum.

TSH measurements using sensitive TSH-IRMA method makes differentiation of euthyroidism and hyperthyroidism possible without TSH stimulation after TRH. TSH-basal values less than 0.1 mU/L proof pituitary TSH suppression (clinical overt and latent hyperthyroidism, thyroid hormone therapy etc.). TSH-basal values between 0.4 and 4.0 mU/L are found in euthyroidism. TSH-basal values greater than 4.0 mU/L indicate latent or manifest hypothyroidism. With basal TSH values between 0.1 and 0.4 mU/L (borderline values between euthyroidism and "relative pituitary hormone excess") a TRH-test ist still necessary as it is not possible to predict stimulated TSH values from basal TSH concentrations with adequate accuracy. TSH measurements using sensitive IRMA methods may be recommanded as a screening test of thyroid function.

[Two generations of FT4-radioimmunoassays--results in euthyroid patients and in patients on thyroid hormone therapy]. / Zwei Generationen FT4-Radioimmunoassays--Ergebnisse bei Euthyreosen und bei Patienten unter Schilddrüsenhormontherapie.

In accordance with the TRH-test two generations of FT4-immunoassays were checked in order to find a substitute for the free thyroxine index. The euthyroid reference range of FT4 was between 0.69-1.91 ng/dl using GammaCoat (Clinical Assays) and 0.94-2.29 ng/dl using Amerlex (Amersham), respectively. In the euthyroid range, FT4 as measured by Amerlex was, on the average, 47% higher than the value obtained by using GammaCoat. During treatment by thyroid hormones and TSH-suppression following TRH application, Amerlex FT4 values were up to 59% higher than the GammaCoat FT4 values. During replacement therapy, the FT4 values obtained by Amerlex were within the euthyroid reference range so that a differentiation between substitution and suppression appears to be possible by means of determining FT4. An overdose was assessed by simultaneous determination of T3 and FT4. According to our results Amerlex FT4 meets the requirements of a modern radioimmunoassay and is suitable as a substitute for the free thyroxine index. For this purpose the earlier method of determining FT4 (GammaCoat) does not seem suitable.

Proof of the linearity of the pharmacokinetics of alinidine in man.

The pharmacokinetics of alinidine was investigated in two groups of volunteers: Group I (N=5) received on two occasions single doses of 14C-labelled drug given orally (40 mg) or intravenously (10 mg); Group II (N=6) received single oral doses 10, 30, or 90 mg dissolved in 20 ml water. The samples from Group I were analysed by two different and independent methods (RIA and counting total radioactivity). The results obtained by the two methods were identical, since the compound was not metabolized. The plasma concentrations and renal excretion data obtained from both groups were individually fitted to an open three compartment model. Independent of the route of administration and of the doses given, similar pharmacokinetic parameters were calculated for each group and each trial. The half lives of the distribution and elimination phases were t1/2 alpha: 36-41s, t1/2 beta: 9.9-11.1 min and t 1/2 gamma: 2.7-3.8h. There was a linear relationship between the dose administered and the resulting areas under the plasma concentration curves (AUC). Following a lag period (tau =0.19-0.22h), the peak plasma concentration was reached 0.6-1.2h after oral administration. Oral alinidine was 100% bioavailable.

[Growth hormone determination in a combined adenohypophyseal stimulation test (author's transl)]. / Die Wachstumshormonbestimmung mit einem kombinierten Stimulationstest der Adenohypophyse.

The authors sought the simplest but still reliable method for evaluation of the functional reserve of the anterior lobe of the pituitary gland. The proposed test is stimulation of those various functions by injection of insulin, gonadotropin releasing hormone (LH-RH = GnRH) and thyrotropin releasing hormone (TRH). The test fulfils the clinical requirements. Furthermore it forms a valuable first step for the classification of more scientific problems.

[Thyroxine in an amount of 150 micrograms daily for the prevention of the recurrence of goiter]. / Thyroxin in einer Dosis von 150 micrograms täglich zur Strumarezidivprophylaxe.

24 patients, who had undergone a subtotal thyroidectomy, were given 150 micrograms thyroxine daily for 6 weeks for prevention of goiter recurrency. 14 patients had been included in an earlier reported study using 75 micrograms thyroxine daily. Prior to this trial 10 patients had 100 micrograms thyroxine daily; the 14 above mentioned patients had had no therapy for 4 weeks. A significant decrease of the TSH response to TRH is observed when compared with the prestudy regimen. According to this parameter the incidence of hyperthyroidism is increased and the incidence of euthyroidism and hypothyroidism decreased. 2 patients however remained hypothyroid. The before mentioned hyperthyroid patients had only an abnormal TSH-response and were euthyroid when determined by clinical signs or ETR-values. It is concluded, that the dosage of 150 micrograms thyroxin is indicated in patients when reduction of goiter size is desired or a high demand for thyroid replacement is suspected. This (and every comparable) regimen needs a clinical and biochemical control.

[Thyroxine in the treatment of euthyroid goiter and the prevention of goiter recurrence]. / Thyroxin in der Behandlung der euthyreoten Struma und der Prophylaxe des Strumarezidivs

Patients with non-toxic goitre, or patients after an operation of non-toxic goitre, were given 75 mug thyroxine daily. The level of TSH decreased significantly only for the non-toxic goitre group. The TSH-TRH-test showed a high percentage of abnormal results, even after several months of treatment. An index for free thyroxine increased a little, but significantly. The neck sizes decreased only in the post-operative group significantly. The final scans showed a high percentage of goitres. 75 mug thyroxine is too small a dosage in these patients and 100 to 150 mug daily seem to be indicated in the above mentioned states.