Interference causes false high calcitonin levels with a commercial assay.
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Calcitonin↗
Biomedical subjects
H Vierhapper
Publications and source records attributed to H Vierhapper.
Adrenocortical tumors: clinical symptoms and biochemical diagnosis.
Patients who are suspected clinically to suffer from hypersecretory disorders of their adrenal(s) should undergo an appropriate endocrinological investigation to confirm or exclude the presence of such disorders prior to any radiological investigation. In those patients in whom an adrenal mass is found 'incidentally' on imaging clinical symptoms of hormonal activity should be carefully followed up. Asymptomatic patients should be screened biochemically for latent hormonal hypersecretion syndromes including pheochromocytoma (urine catecholamine excretion), hypercortisolism (overnight dexamethason suppression test) and aldosteronism (blood pressure and serum potassium). These investigations are mandatory in all patients scheduled for surgery. The decision to refer patients with inactive adrenal tumors to surgery is, in the absence of valid biochemical markers of malignancy, mainly influenced by tumor size but remains arbitrary. Patients who are not at first treated by surgery should be operated if follow-up indicates a progression in tumor size.
Adrenal Gland Neoplasms↗
The use of the pyridostigmine growth hormone-releasing hormone stimulation test to detect growth hormone deficiency in patients with pituitary adenomas.
The pyridostigmine (PD)/growth hormone-releasing hormone (GHRH) stimulation test was used to determine growth hormone (GH) secretion in patients with pituitary adenomas prior to (n = 55) and after (n = 72) transsphenoidal adenomectomy, as well as in 98 controls. In controls, maximum concentrations of GH showed a strong negative relationship both with body mass index (BMI) and age. Having calculated the 95% confidence intervals for maximum GH concentrations to be expected for any given age and BMI according to a statistical model, we compared these individually predicted ranges to GH concentrations actually observed in patients with pituitary disease during PD/GHRH stimulation. Preoperatively and postoperatively, a maximum GH concentration below the calculated confidence intervals was seen in 29 of 55 (52%) and in 57 of 72 (79%) of these patients, respectively. In the remaining patients, maximum GH concentrations were in or above the range defined by these confidence intervals. Our results indicate that maximum concentrations of GH during the PD/GHRH test depend to a large extent on the individuals' age and BMI. The results obtained with the PD/GHRH stimulation must, in each individual patient, be compared with a large control group taking into account both age and BMI. In individuals older then 55 years and with a BMI greater than 35 kg/(2), the diagnosis of GH deficiency cannot safely be made, at least not with this test.
Adenoma↗
Prevalence of hypergastrinemia in patients with hyper- and hypothyroidism: impact for calcitonin?
OBJECTIVES: To evaluate the prevalence of hypergastrinemia in patients with hyperthyroidism and hypothyroidism and to determine whether gastrin-induced hypercalcitonemia could explain the high prevalence of thyroid C-cell hyperplasia among patients with hyperthyroidism. METHODS: Concentrations of gastrin and of hCT were determined by commercially available radioimmunoassays. RESULTS: Elevated serum concentrations of gastrin were found in 17 of 161 (10.5%) patients with manifest hyperthyroidism (Graves' disease) and in 4 of 37 (10.8%) and 23 of 255 (9.0%) patients with manifest or subclinical hypothyroidism, respectively. Only 2 cases of hypergastrinemia of 255 subclinically hypothyroid patients (0.8%) could not be linked to thyroid autoimmune disease by either biochemical or sonographic criteria. Four patients with Graves' disease presented elevated plasma concentrations of calcitonin, but none of these patients also had an elevated serum gastrin. CONCLUSIONS: The prevalence of hypergastrinemia in autoimmune thyroid disease is about 10%. The determination of gastrin in subclinical hypothyroidism is not cost-effective in the absence of biochemical and/or sonographic markers of autoimmune thyroid disease. The determination of gastrin is of no use to predict the presence of C-cell hyperplasia commonly seen in patients with Graves' disease.
Aged↗
Complete thyroxine-binding globulin (TBG) deficiency in two families without mutations in coding or promoter regions of the TBG genes: in vitro demonstration of exon skipping.
Inherited thyroxine-binding globulin (TBG) deficiency is caused by mutations in the TBG gene located on the X-chromosome. We now describe two families (K and H) with X-linked complete TBG deficiency without mutations in the coding or promoter regions of the TBG gene. The propositi of both families presented with euthyroid hypothyroxinemia and were found to have undetectable TBG in serum. Affected females had approximately half the normal serum TBG concentration except for one woman who also had undetectable TBG (family H). All four of her children (two boys and two girls) were affected. Affected members of family K had no mutations in any of the five exons or in the minimal promoter region of the TBG gene. However, a G to A substitution, five base pairs downstream from exon 3, was associated to the phenotype of TBG deficiency (TBG-Jackson) and was not present in 100 normal alleles. In contrast to individuals without this mutation, no TBG mRNA could be detected in fibroblasts of the propositus, expressing solely TBG-Jackson. In vitro transcription of genomic DNA containing the mutant intron in an exon trapping system showed that this mutation, reducing the consensus value on the 5' donor splice site, affects the normal splicing process. The transcript of TBG-Jackson lacks exon 3 and is unstable. The deduced amino acid sequence has a frameshift and an early stop codon at position 325. Affected subject of family H had no mutations in the TBG gene including all exons, all introns, the minimal promoter, and the 3' untranslated sequence. However, an intragenic A/G polymorphism (125 bp upstream from exon 2) was identified. It allowed us to confirm a cosegregation of the phenotype to the TBG gene and to show that the single female with complete TBG deficiency was homozygous for the polymorphic TBG allele. The cause of TBG deficiency in this family remains unknown.
Adult↗
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↗
Sporadic versus familial medullary thyroid microcarcinoma: a histopathologic study of 50 consecutive patients.
By means of calcitonin screening programs, sporadic and hereditary medullary thyroid carcinoma (MTC) can be detected at an early stage. We investigated the histopathologic findings of 16 familial (mean age 32 +/- 21 years, female/male ratio 1.6:1) and 34 sporadic (mean age 58 +/- 15 years; female/male ratio 2.4:1) MTCs with stage T1 comparatively. Patients with hereditary tumors were younger. Hereditary tumors were more often found multifocal (13 of 16 vs 3 of 34; p < 0.001), bilateral (11 of 16 vs 3 of 34; p < 0.001), displaying desmoplastic stroma (14 of 16 vs 19 of 34; p = 0.02), and accompanied by C cell hyperplasia (16 of 16 vs 24 of 34; p = 0.01), but all of these factors were present in some sporadic patients. Only tumors with desmoplastic stroma showed lymph node metastasis, which was observed in eight of the 50 patients. After surgery all patients showed permanent normalization of calcitonin levels. We conclude that 1) morphologic parameters considered to indicate familial MTC risk are of no value in the individual patient, 2) many sporadic MTCs develop on the background of CCH, 3) tumors with desmoplastic stroma are more likely to develop lymph node metastasis, and 4) early detection of MTC permits curative surgery in the majority of patients.
Adolescent↗
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↗
Production rates of dihydrotestosterone in healthy men and women and in men with male pattern baldness: determination by stable isotope/dilution and mass spectrometry.
Production rates of dihydrotestosterone (DHT) were determined in healthy men (n = 8), in healthy women during the follicular phase of their menstrual cycle (n = 7), and in young men with male pattern baldness (n = 8) using the stable isotope dilution technique and mass spectrometry. [2,3,4-(13)C]DHT was infused for 10 h at doses of 15 microg/h (men) and 2 microg/h (women), and blood samples were obtained at 20-min intervals during the last 4 h of the observation period. Production rates estimated between April and June were 2.9 +/- 1.1 microg/h (women) and 17.8 +/- 6.2 microg/h (men). In men production rates of DHT were similar (16.2 +/- 7.7 microg/h) when the investigation was repeated between October and December. Mean production rates of DHT in young men with male pattern baldness (60 +/- 50 microg/h) were higher than those in healthy men (P < 0.005). Although this group included two individuals with normal production rates of DHT, the production rate of DHT was markedly elevated (range, 32.0-161.0 microg/h) in the remaining patients. Stable isotope-labeled infusions of DHT are suitable for clinical use in a routine setting to obtain analytically correct estimates of DHT production in vivo. In the majority of men with male pattern baldness endogenous production of DHT is markedly increased, providing a rationale for therapeutic 5 alpha-reductase inhibition in this disorder.
Adult↗
The stress of being a doctor: steroid excretion rates in internal medicine residents on and off duty.
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Adrenal Cortex Hormones↗
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↗
A novel mutation E179K of the MEN1 gene predisposes for multiple endocrine neoplasia-type 1 (MEN1).
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Adenoma↗
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↗