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Biomedical subjects

H Vierhapper

Publications and source records attributed to H Vierhapper.

At least 19 recordsLinked to original sources

Serum calcium in thyroid disease.

Thyroid hormones are believed to influence calcium metabolism. In the present prospective study we investigated the influence of various thryroid diseases on serum calcium levels. In addition to screening for thyroid diseases we measured serum calcium concentrations (S-Ca) in individuals who came to our outpatient service for thyroid diseases from 1992 to 1998. 13,387 persons, among them 9017 patients with thyroid diseases and 4370 persons without thyroid dysfunction, were studied. S-Ca was found to be higher in patients with hyperthyroidism (2.36 +/- 0.11 mmol/L n = 1201, p < 0.05) than in those with subclinical hyperthyroidism (2.33 +/- 0.11 mmol/L, n = 494), with euthyroid goiter (2.32 +/- 0.10 mmol/l, n = 5599), with hypothyroidism (2.31 +/- 0.11 mmol/L, 344), with subclinical hypothyroidism (2.32 +/- 0.10 mmol/L, n = 1290) and in healthy persons (2.31 +/- 0.11 mmol/L, n = 4370). 173/13,387 persons had serum calcium levels < 2.1 mmol/L, among them 31 patients with hypoparathyroidism after strumectomy (31/592) and 2 patients with primary hypoparathyroidism. 106/13,387 persons showed a S-Ca of > 2.6 mmol/L, which in 30 cases was due to primary hyperparathyroidism. Of 55 persons with S-Ca of > 2.6 mmol/L and without any other reason for hypercalcaemia, 31 were found to be in a hyperthyroid state. In conclusion, a clinically not relevant influence on S-Ca was demonstrated in patients with hyperthyroidism as compared with other thyroid diseases and individuals with no thyroid diseases. Measurement of S-Ca in every patient being referred to a thyroid outpatient department is recommended because of the frequent occurrence of postoperative hypoparathyroidism and primary hyperparathyroidism in this setting.

Adolescent↗

Obesity in Austria: body mass index of 15 000 euthyroid men and women referred to a thyroid outpatient service between 1992 and 2000.

A mean body mass index (BMI) of 25.4 +/- 5.0 kg/m(2) was calculated in 15439 euthyroid patients newly referred to our thyroid outpatient department from January 1, 1992 until December 31, 1999. This patient population included 2916 men aged 50 +/- 16 years (BMI: 26.2 +/- 4.3 kg/m(2)) and 12563 women aged 47 +/- 17 years (BMI 25.3 +/- 5.1 kg/m(2) ). Mean BMI appeared to rise (p < 0.01) from 25.0 +/- 4.7 kg/m(2) (1992) to 25.6 +/- 5.0 kg/m(2) (1999) and the share of obese patients (BMI > 30 kg/m(2)) increased from 13.8% in 1992 to 17.2% in 1999. However these changes were parallelled by a rise (p < 0.01) in the mean age of newly referred patients from 45 +/- 16 years (1992) to 49 +/- 17 years (1999). When the whole population was subdivided into groups of different age no time-related trend was apparent in mean BMI or in the prevalence of obesity in any of these subgroups. Only in men and women beyond 60 years of age BMI of those referred in 1998 and 1999 was higher (p < 0.05) than in those individuals referred in 1992-1994. These data indicate that close to half of all euthyroid patients referred to a thyroid outpatient service in eastern Austria is overweight. From 1992 to the end of 1999 there was, however, no marked increase in the prevalence of obesity in this population.

Adult↗

FDG-PET in adrenocortical carcinoma.

Adrenal cortical carcinoma (ACC) is a rare malignant neoplasm with a poor prognosis. Radical surgery of the primary tumor and of local as well as of distant recurrence is the only effective treatment, and requires accurate and early localization of recurrent tumors. In this regard, we prospectively scanned 10 patients with ACC, 8 during follow-up and 2 at primary work-up. In all patients PET scans from the neck to the upper thighs were obtained 45 minutes after injection of 370 MBq [18F]FDG. Reading was done visually, with the investigator blinded to the results of other diagnostic modalities. All known sites of ACC lesions showed markedly increased FDG uptake. In 3 patients, previously unknown lesions were identified by PET in the lung (one lesion), the abdomen (3 lesions), and the skeleton (multiple), respectively. One false positive liver focus was shown by PET aside from the true positive lung metastases in the same patient. The sensitivity/specificity of PET based on different organs was 100/97%, that based on the number of PET-detected lesions (N = 23) was 100/95%. PET altered or influenced the tumor stage in 3/10 patients, modifying the subsequent therapeutic management in 2/10 patients. We conclude that FDG-PET is highly useful in ACC and should be included in the work-up for initial staging as well as for follow-up.

Abdominal Neoplasms↗

Mutational spectrum of the steroid 21-hydroxylase gene in Austria: identification of a novel missense mutation.

This study attempted an analysis of the mutational spectrum of 21-hydroxylase deficiency in 79 unrelated Austrian patients with classical and nonclassical forms of congenital adrenal hyperplasia and their respective 112 family members. Apparent large gene deletions/conversions were present in 31% of the 158 unrelated congenital adrenal hyperplasia alleles, whereas the most frequent point mutations were intron 2 splice (22.8%), I172N (15.8%), V281L (12%), and P30L (7.6%), in line with the frequencies reported for other countries. In 5 of the 12 congenital adrenal hyperplasia alleles carrying a P30L mutation the aberration is based on a single base substitution, whereas the remaining 7 represent part of a CYP21B conversion (1 allele) or CYP21B/21A hybrid gene (6 alleles), the latter characterized by a junction site before intron 2 as indicated by Southern blot, PCR, and sequence analyses. Previously described mutations were not present in 1.2% of unrelated congenital adrenal hyperplasia alleles, including one female patient presenting with severe genital virilization. Sequence analysis of the complete functional 21-hydroxylase gene revealed an as yet undescribed mutation in exon 10-Arg(426)His, which has not yet been described to represent a common pseudogene sequence. In vitro expression experiments showed the Arg(426)His mutant to exhibit only low enzyme activity toward the natural substrate 17-hydroxyprogesterone corresponding to the degree of disease manifestation in the patient in whom it was found.

Adrenal Hyperplasia, Congenital↗

Successful treatment of high turnover osteoporosis in a patient with adrenocortical insufficiency.

We present a case of high-turnover osteoporosis associated with substituted adrenocortical insufficiency (Addison's disease) and its successful treatment with calcitonin and calcitriol. A 43-year-old man presented with markedly reduced bone mineral density (BMD) (lumbar spine BMD -3.46 SD below healthy young adults) after thirteen years of glucocorticoid substitution. Interestingly, his osteocalcin levels indicated an unusually high bone turnover and his alkaline phosphatase levels were also increased. Combination treatment with calcitriol and calcitonin was started. Re-evaluation after twelve months revealed a substantial increase in BMD (+6.8% for the lumbar spine, +15% for the left hip). Alkaline phosphatase levels had normalised and osteocalcin was nearly down to normal. In spite of a thorough evaluation, no other cause of osteoporosis was detected. We discuss these findings in view of the existing literature.

Addison Disease↗

Prevalence of paradoxically normal serum cholestrol in morbidly obese women.

The paradox that cholesterol may be lower in extremely obese subjects versus those who are less overweight, although originally observed more than 40 years ago, has never been documented in a systematic fashion. We have therefore prospectively determined the body mass index (BMI) and serum cholesterol concentration in 3,312 women. The percentage of women with serum cholesterol in the normal range (<200 mg/dL) decreased with an increasing BMI, from 55% in women with a BMI less than 20 kg/m2 to 28% in those with a BMI of 30 to 35 kg/m2. Serum cholesterol greater than 300 mg/dL was found in only 2% of individuals with a BMI less than 20 kg/m2 but in 6% of the group with a BMI between 30 and 35 kg/m2. However, among morbidly obese women (BMI >40 kg/m2, n = 46), 39% presented with serum cholesterol less than 200 mg/dL and only one woman had serum cholesterol more than 300 mg/dL. With the BMI, the fitted regression model shows an increase in cholesterol for low BMIs, while cholesterol appears to decrease with larger values for the BMI. The age-dependent increase in cholesterol is more evident in younger women versus older women, where it tends to disappear. It is concluded that among morbidly obese women (BMI >40 kg/m2), there is a substantial subgroup with normal serum cholesterol.

Adult↗

production rates of testosterone in patients with Cushing's syndrome.

Testosterone production rates were determined in 16 patients with Cushing's syndrome (4 men and 12 women) using the stable-isotope dilution technique and mass spectrometry. 1alpha,2alpha-D-Testosterone was infused for 10 hours at a dose of 20 microg/h (men) and 0.4 microg/h (women) and blood samples were obtained at 20-minute intervals during the last 4 hours of the observation period. Estimated production rates in men with Cushing's syndrome were 27, 73, 150, and 180 microg/h (mean, 106 +/- 70 microg/h; healthy men [n = 12], 210 +/- 70 microg/h). In the 12 women with Cushing's syndrome, testosterone production rates were 0.3 to 22.3 microg/h (healthy women [n = 5], 4.3 +/- 1.9 microg/h). There was no difference in testosterone production rates in female patients with central (n = 8) versus adrenal (n = 4) Cushing's syndrome. In summary, testosterone production rates are subnormal or low-normal in male patients with endogenous hypercortisolism, but not in female patients with the same disorder. We conclude that testosterone production in men, but not in women, is predominantly of gonadal origin and hence susceptible to a glucocorticoid-induced suppression of gonadotropin secretion.

Adult↗

Relative hypoleptinemia in patients with type 1 and type 2 diabetes mellitus.

OBJECTIVE: To determine the relation between plasma leptin concentrations and metabolic control in human diabetes mellitus. DESIGN AND SUBJECTS: Cross sectional study consisting of 156 patients with diabetes mellitus type 1 (n=42), type 2 (n=114), and non-diabetic subjects (n=74). RESULTS: Plasma leptin concentrations were lower (P<0.05) in type 1 (8.3+/-1.7 ng/ml) and type 2 diabetic (14.9+/-1.8 ng/ml) than in non-diabetic humans (18.3+/-1.9 ng/ml). Only female type 1 and type 2 diabetic subjects also had decreased leptin/BMI ratios (P<0.05 vs non-diabetic females). The log rank test identified age-adjusted correlation of plasma leptin concentration with sex (P<0.0004) and body mass index (P<0.0218), but not with glycosylated haemoglobin A1c (P>0.5) in all groups. Plasma leptin was correlated with age (P<0.0058) and serum triglycerides (P<0.0199) in type 1 diabetic patients, and with serum cholesterol (P<0.0059) and LDL (P<0.0013) in type 2 diabetic patients. CONCLUSIONS: Defective leptin production and/or secretion might be present independently of metabolic control in female patients with type 1 or type 2 diabetes mellitus.

Adult↗

Spuriously high serum concentrations of TSH due to the use of an automatic pipetting device.

In a clinically hyperthyroid patient a TSH-value of 0.75 mU/L was measured. Upon retesting TSH was <0.1 mU/L. The patient's sample initially had been preceded, in the pipetting device, by a grossly hypothyroid patient's sample. Analogous problems were subsequently documented in 10 cases when samples of other hyperthyroid patients were preceded by samples with modestly to markedly elevated TSH. The spurious elevation of TSH (0.12 to 1.18 vs. <0.1 mU/L) appears to be due to a carryover effect from the respective previous sample within the used automatic pipetting system. This carryover was much larger than previously suggested, and occurred unpredictably.

Artifacts↗

Risk factors for malignancy of thyroid nodules initially identified as follicular neoplasia by fine-needle aspiration: results of a prospective study of one hundred twenty patients.

Indeterminate or suspicious findings on fine-needle aspiration (FNA) of nodular thyroid disease (i.e., findings that neither give immediate indication for surgery nor lead to clear-cut conservative management) have been the key diagnostic problem in thyroid cytology for which the inability to differentiate cytologically benign from malignant follicular growth has been one reason. The aim of this cohort study of 120 consecutive (103 females, 17 males) patients with palpable nodular thyroid disease diagnosed as follicular neoplasia (FN) by FNA (defined by the triad of high numbers of follicular cells, microfollicular arrangement, and scanty or absent colloid) was to identify patients at high risk for malignancy based on the prospective evaluation of clinical features and to characterize the histologic entities of FN. Based on a 100% surgery rate we found an 18% malignancy rate (12 papillary carcinomas, 9 follicular carcinomas). Previously suggested factors with elevated risk for malignancy such as extremes of age, male gender, and large nodule size were not associated with increased risk as were cold nodules by 99mTc-scintigraphy (relative risk: 1.2, 95% confidence interval [CI] 0.4-3.3). However, hard lesions to palpation (relative risk 2.6, 95% CI: 1.2-5.6), solitary (relative risk: 2.6, 95% CI: 1.7-4.0), and hypoechoic FNs (relative risk: 3.4, 95% CI: 2.0-5.7) by ultrasound showed elevated risks of malignancy. In summary, suspicious palpation or ultrasound results may help to define a subgroup of patients with elevated risk of malignancy when FNA indicates the diagnosis of follicular neoplasm of the thyroid.

Adenocarcinoma, Follicular↗

Increased lead excretion correlates with desoxypyridinoline crosslinks in hyperthyroid patients.

Lead is a widespread toxic metal that accumulates predominantly in human bone. Altered bone metabolism in hyperthyroidism is characterized mainly by bone resorption. Thus, we speculated that lead excretion could be increased in hyperthyroid patients. In 12 hyperthyroid patients (43.3 +/- 16.1 years) who were not previously occupationally exposed to lead, lead concentrations in blood (PbB), spot urine samples corrected by urine creatinine (PbUs), and in 24-hour urine samples (PbU24) were determined in the hyperthyroid state and after euthyroidism had been induced by therapy. Serum osteocalcin (OC) and desoxypyridinoline crosslinks (Pyr) served as specific markers for bone metabolism. After induction of euthyroidism (duration of antithyroid therapy: mean 17.3 +/- 6.9 weeks) PbB was reduced (3.7 +/- 2.6 vs. 5.7 +/- 4.7 microg/dL, p = 0.041) as was PbUs (0.39 +/-0.27 vs. 0.61 +/- 0.32 microg/mg Cr, p = 0.005). A fourfold decrease of PbU24 was associated with a 3.3-fold decrease of Pyr, and moreover there was a significant correlation between Pyr and PbUs (r = 0.58, p = 0.047). Concentration of total triiodothyronine correlated with Pyr (r = 0.66, p = 0.018), but not with PbB or PbUs. OC showed only a tendency to be increased before antithyroid medication, and did not correlate with either thyroid hormone or Pyr. Our results indicate that in hyperthyroid patients, even when not previously exposed to lead, lead excretion is increased due to bone resorption.

Adult↗

Prevalence of C-cell hyperplasia in patients with normal basal and pentagastrin-stimulated calcitonin.

The prevalence of thyroid C-cell hyperplasia (CCH) was investigated prospectively in 57 patients with normal preoperative pentagastrin-stimulated plasma concentrations of calcitonin (hCT, range, 1-60 pg/mL; normal, 100 pg/mL) who subsequently underwent total thyroidectomy due to thyrotoxicosis (n = 18) or to nodular thyroid disease in the presence (n = 9) or absence (n = 30) of cytological follicular neoplasia. CCH was seen in 28 of 57 (49%) of all patients. CCH was more common in hyperthyroid (12/18 [66%]) than in euthyroid (16/39 [41%] patients. No age- or gender-related differences in the occurrence of CCH was seen. There was no histological evidence of medullary thyroid carcinoma (MTC) in any patient. CCH classified histologically as neoplastic was encountered in two instances. It was concluded that CCH may be expected in almost 50% of normocalcitonemic patients with various thyroid disorders. Although the potential clinical importance of this histological finding and specifically its neoplastic variety remains unknown, these results are in keeping with the assumption that pentagastrin-stimulated plasma concentrations of hCT within the normal range do not exclude the presence of CCH.

Adult↗

Low-density lipoprotein cholesterol in subclinical hypothyroidism.

The significance of subclinical hypothyroidism in regard to ensuing hyperlipidemia remains unclear. Because an unfavorable lipid profile would provide a possible explanation for the reported association of coronary-heart disease with this syndrome, we have evaluated the relationship of thyrotropin (TSH) with total cholesterol, low-density-lipoprotein (LDL) cholesterol, and triglycerides in patients with normal thyroid function (n = 4886) as well as subclinical (n = 1055) and manifest (n = 92) hypothyroidism. Serum concentrations of LDL cholesterol were similar in euthyroid persons (134+/-39 mg/dL) and in patients with subclinical hypothyroidism (137+/-40 mg/dL) but were higher (178+/-70 mg/dL, p < 0.01) in overt hypothyroidism. Within the group of subjects with subclinical hypothyroidism there was no apparent relationship between serum concentrations of TSH ranging from 4.0 to 49.0 microU/mL and concentrations of LDL cholesterol. Thus, there is no "threshold value" of TSH in these patients per se necessitating substitution therapy with thyroxine.

Age Factors↗

Value of peptide receptor scintigraphy using (123)I-vasoactive intestinal peptide and (111)In-DTPA-D-Phe1-octreotide in 194 carcinoid patients: Vienna University Experience, 1993 to 1998.

PURPOSE: To report our experience with both (123)I-vasoactive intestinal peptide (VIP) and (111)In-DTPA-D-Phe(1)-octreotide for imaging to identify primary and metastatic tumor sites in carcinoid patients. PATIENTS AND METHODS: One hundred ninety-four patients with a verified or clinically suspected diagnosis of a carcinoid tumor were injected with (111)In-DTPA-D-Phe(1)-OCT for imaging purposes, while 133 patients underwent scanning with both (123)I-VIP and (111)In-DTPA-D-Phe(1)-OCT in random order. Imaging results were compared with computed tomography scans, results of conventional ultrasound, endosonography, and endoscopy, and results of surgical exploration in case of inconclusive conventional imaging. RESULTS: Primary or recurrent carcinoid tumors could be visualized with (111)In-DTPA-D-Phe(1)-OCT in 95 (91%) of 104 patients; metastatic sites were identified in 110 (95%) of 116 patients. In 11 (51%) of 21 patients with suggestive symptoms but without identified lesions by conventional imaging, focal tracer uptake located the carcinoid tumor. In addition, metastatic disease was demonstrated in three patients after resection. In a direct comparison in the 133 patients who underwent both imaging modalities, (111)In-DTPA-D-Phe(1)-OCT was found to be superior to (123)I-VIP, with 35 (93%) of 38 versus 32 (82%) of 38 scans being positive in primary or recurrent tumors, 58 (90%) of 65 versus 53 (82%) of 65 being positive in patients with metastatic sites, and seven (44%) of 16 versus four (25%) of 16 being positive in patients with symptoms but otherwise negative work-ups. Overall, additional lesions not seen on conventional imaging were imaged in 43 (41%) of 158 versus 25 (25%) of 103 scans with (111)In-DTPA-D-Phe(1)-OCT and (123)I-VIP, respectively. CONCLUSION: Both peptide tracers have a high sensitivity for localizing tumor sites in patients with ascertained or suspected carcinoid tumors, with (111)In-DTPA-D-Phe(1)-OCT scintigraphy being more sensitive than (123)I-VIP receptor scanning. Both, however, had a higher diagnostic yield than conventional imaging, as verified by surgical intervention or long-term follow-up. The combination of both peptide receptor scans does not seem to further enhance diagnostic information.

Adult↗

Medical therapy of Graves' disease: effect on remission rates of methimazole alone and in combination with triiodothyronine.

In a prospective, randomized study of 135 newly diagnosed patients with hyperthyroidism due to Graves' disease we compared the effect on remission rates of additional triiodothyronine (T3) with conventional antithyroid drug therapy. To this end 114 patients were followed for at least 12 months (15.7+/-4.9, mean+/-s.d.) after the discontinuation of any therapy. After return of thyroid function to normal (8.5+/-7.4 weeks, mean+/-s.d.) patients were maintained on antithyroid medication for 9.0+/-2.5 months. They were then randomly assigned to one of three groups: group 1 (n=44) stopped methimazole, groups 2 (n=39) and 3 (n=31) continued with exogenous T3 (not exceeding 75 microgram/day in any patient) for a further 6 months either with (group 2) or without (group 3) a fixed dose of 10mg methimazole daily. The T3 dose was kept variable to keep TSH suppressed (<0. 1mU/l), which could be achieved in 82% of patients on 100% of their monthly visits. No serious side-effect requiring the discontinuation of the study occurred in any patient. Total T3, TSH-receptor antibodies and some previously suggested potential predictors of relapse including thyroid size by ultrasound, 24h urinary iodine excretion, history of cigarette smoking and ophthalmopathy were determined at the outset of the study and subsequently every 6 months (and total T3 every 4 weeks). No significant difference (P>0.05, Chi square) was seen in relapse of hyperthyroidism after a mean follow-up of 16 months (range: 12-31 months; groups 1:52%, 2:44% and 3:42%) in an area of low-to-moderate iodine intake (prevalence of 24h urinary iodine excretion <100 microgram/24h: 17 and 25% at two different measurements respectively). Concomitantly, no predictor of recurrence of disease could be identified, irrespective of treatment modality.

Adolescent↗