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P M Zelissen

Publications and source records attributed to P M Zelissen.

At least 19 recordsLinked to original sources

[Role of prasterone (dehydroepiandrosterone) in substitution therapy for adrenocortical insufficiency].

Prasterone (dehydroepiandrosterone; DHEA) is a steroid hormone from the adrenal cortex with weak androgenic properties. It can be converted into stronger acting steroids with both androgenic and oestrogenic properties. DHEA also appears to have an affinity with certain receptors in the brain and can act as a neurosteroid. Patients with primary or secondary adrenocortical insufficiency exhibit a marked decrease in DHEA production and the added value of DHEA replacement in these patients has been investigated in three recently published trials. With a daily dose of 50 mg DHEA, the plasma levels of DHEAS (the sulphate of DHEA) increase to levels within the normal range and beneficial effects have been demonstrated for several psychological parameters such as mood, fatigue, general well-being and sexual function. The androgenic side effects on skin and hair appear to be both moderate and acceptable. For patients with adrenocortical insufficiency who function suboptimally despite adequate replacement therapy with glucocorticosteroids and (if indicated) mineralocorticosteroids, these results would seem to justify treatment with a replacement dose of DHEA.

Adrenal Insufficiency↗

Efficacy of high therapeutic doses of iodine-131 in patients with differentiated thyroid cancer and detectable serum thyroglobulin.

Serum thyroglobulin (Tg) is usually the best marker of residual or metastatic disease after treatment of differentiated thyroid cancer. We evaluated the effect of so-called blind therapeutic doses of iodine-131 in patients with detectable Tg during suppressive levothyroxine treatment (Tg-on), and in patients with a negative diagnostic scintigram but detectable Tg during the hypothyroid phase (Tg-off). Twenty-two patients with differentiated thyroid carcinoma underwent total thyroidectomy and radioiodine ablation. During the follow-up, six patients with detectable Tg-on and 16 patients with detectable Tg-off were identified. All patients were treated with a blind therapeutic dose of 7,400 MBq iodine-131. Diagnostic scintigrams were compared with post-treatment scintigrams. Tg-off was measured in 16 cases, 1 year after the administration of the blind therapeutic dose, at the time of the follow-up diagnostic scintigram. Six patients were followed up by Tg-on only. Post-therapy scintigrams revealed previously undiagnosed local recurrence or distant metastases in 13/22 cases (59%); the remaining nine post-therapy scintigrams were negative. At the time of the blind therapeutic doses, Tg-off values ranged from 8 to 608 microg/l. After 1 year of follow-up, Tg-off decreased in 14/16 (88%) patients. In all patients who were followed by Tg-on only (n=6), a decrease in Tg values was measured. It is concluded that blind therapeutic doses resulted in a decrease in Tg levels in the majority of patients with suspected recurrence or metastases. The post-treatment scintigrams revealed pathological uptake in 59% of patients.

Adult↗

Validity and reproducibility of ultrasonography for the measurement of intra-abdominal adipose tissue.

OBJECTIVE: We studied the validity and reproducibility of a new abdominal ultrasound protocol for the assessment of intra-abdominal adipose tissue. MEASUREMENTS: Intra-abdominal adipose tissue was assessed by CT, MRI, anthropometry and ultrasonography on a single day. By ultrasonography the distance between peritoneum and lumbar spine was measured using a strict protocol, including the location of the measurements, pressure on the transducer and respiration. All measurements were repeated after 3 months. RESULTS: The study population consisted of 19 overweight patients with a body mass index (BMI) of 32.9 kg/m(2) (s.d. 3.7), intra-abdominal adipose tissue on CT 140.1 cm(2) (s.d. 55.9), and a mean ultrasound distance of 9.8 cm (s.d. 2.5). There was a strong association between the CT and ultrasonographic measures: Pearson correlation coefficient was 0.81 (P<0.001). The correlation between ultrasound and waist circumference was 0.74 (P<0.001), the correlation between CT and waist circumference was 0.57 (P=0.01). Ultrasound appeared a good method to diagnose intra-abdominal obesity: the area under the ROC curve was 0.98. During the follow-up period of 3 months, the patients lost on average almost 3 kg of body weight. The correlation coefficient between changes in intra-abdominal adipose tissue assessed by CT and ultrasound was 0.74 (P<0.001). The correlation coefficient of the mean ultrasound distance assessed by two different sonographers at baseline was 0.94 (P<0.001), the mean difference 0.4 cm (s.d. 0.9), and the coefficient of variation 5.4%, indicating good reproducibility of the ultrasound measurements. CONCLUSIONS: The results of this validation study show that abdominal ultrasound, using a strict protocol, is a reliable and reproducible method to assess the amount of intra-abdominal adipose tissue and to diagnose intra-abdominal obesity.

Abdomen↗

The atherogenic plasma remnant-like particle cholesterol concentration is increased in the fasting and postprandial state in active acromegalic patients.

BACKGROUND: Premature atherosclerosis is a clinical feature in untreated acromegaly. Increased postprandial lipoprotein remnant levels are associated with premature atherosclerosis. In most studies, remnants have been measured indirectly using retinyl esters (RE) as a chylomicron core label. Remnants can also be directly quantified by immunoseparation using monoclonal antibodies to apolipoprotein (apo) AI and apo B100 to remove nonremnant lipoproteins. Cholesterol is quantified in the remaining apo E-rich remnant fraction (RLP-C). OBJECTIVE: The aim of the present study was to investigate the role of postprandial lipaemia in patients with acromegaly to further define abnormalities leading to increased susceptibility for atherosclerosis. PATIENTS: In a case-control study, the plasma postprandial lipoprotein remnant fraction (RLP-C and RE) were analysed in six patients with active acromegaly [two females, four males; aged 53 +/- 9 years; body mass index (BMI), 29 +/- 4 kg/m2] and in six normolipidaemic control subjects (matched for age, gender, BMI and apo E genotype). They underwent an oral vitamin A fat loading test. RESULTS: Baseline plasma triglycerides (TG) were not significantly different in patients (1.75 +/- 0.71 mM) and controls (1.15 +/- 0.46 mM). Lipoprotein lipase activity was significantly lower in patients than in controls (108 +/- 21 vs. 141 +/- 19 U/l, respectively; P < 0.05). Baseline plasma apo E levels were higher in patients (60.8 +/- 7.9 mg/l) than in controls (48.3 +/- 5.9 mg/l; P < 0.05). No differences were found in the area under the postprandial TG curve (AUC-TG), the incremental AUC-TG (DeltaAUC-TG) and AUC-RE in the Sf < 1000 remnant fraction. However, fasting plasma RLP-C concentrations, isolated by immunoseparation, were increased in patients with active acromegaly (0.41 +/- 0.13 mM) compared to control subjects (0.20 +/- 0.07 mM; P < 0.05). Incremental postprandial RLP-C response (corrected for fasting values) was also significantly elevated in patients (2.14 +/- 1.19 mM/h/l) compared to controls (0.86 +/- 0.34 mM/h/l; P < 0.05). In both groups, the maximal RLP-C concentration was reached between 2 and 4 h. CONCLUSIONS: In conclusion, the atherogenic postprandial remnants, represented by RLP-C, were significantly elevated at baseline and in the postprandial period, whereas the larger-sized remnants, represented by retinyl esters (Sf < 1000), were not different from controls. The disturbances in the postprandial RLP-C response increased the susceptibility for premature atherosclerosis as observed in patients with acromegaly.

Acromegaly↗

GIP-dependent adrenal Cushing's syndrome with incomplete suppression of ACTH.

ACTH-independent Cushing's syndrome may be due to the development of ectopic hormone receptors in adrenal tissue. Thus, in food-dependent Cushing's syndrome the adrenals aberrantly express receptors for gastric inhibitory polypeptide (GIP). We present the case of a 60-year-old woman with food-dependent Cushing's syndrome whose cortisol levels increased after stimulation with CRH. In this patient with Cushing's syndrome the finding of low basal plasma cortisol levels in the late night and early morning as well as a paradoxical rise of plasma cortisol during a 7-h infusion with dexamethasone (carried out without any restriction in food intake), suggested that cortisol production was stimulated at times of food intake. Hourly measurements of plasma cortisol for 48 h revealed prominent meal-related peaks. A plasma cortisol response, elicited by oral glucose administration, could be prevented by octreotide. Plasma ACTH was low or undetectable. CRH administration was followed by a ACTH response from 3 to 16 ng/l and a plasma cortisol response from 230 to 680 nmol/l. Octreotide treatment for nearly five months induced a partial clinical and biochemical remission. Total bilateral adrenalectomy was performed. The left adrenal was grossly enlarged (7 x 5.5 x 4 cm) and the right adrenal was slightly enlarged (6 x 4 x 1.8 cm). Microscopy revealed bilateral nodular hyperplasia. Cell suspensions of adrenal tissue from the patient did respond in a dose-dependent fashion to stimulation with GIP and were very sensitive to stimulation with synthetic ACTH1-24. However, CRH had no significant effect on cortisol production in vitro. Using RT-PCR amplification and cDNA hybridization, GIP receptor was found to be overexpressed in the left and right adrenal tissues from this patient as compared to adrenal tissues from a normal individual or from non GIP-dependent adrenal Cushing's syndrome. There was no evidence of presence of adrenal CRH receptors. Thus, in this patient with food-dependent Cushing's syndrome, the CRH-induced plasma ACTH and cortisol response is probably mediated by an incomplete suppression of the HPA axis as a result of the intermittent food-dependent nature of Cushing's syndrome.

Adrenal Cortex↗

Fixed dosage of 131I for remnant ablation in patients with differentiated thyroid carcinoma without pre-ablative diagnostic 131I scintigraphy.

Differentiated thyroid cancer is treated by (near) total thyroidectomy followed by radioiodine (131I) ablation of the residual active tissue in the thyroid bed. Controversy remains concerning the use and the dose of pre-ablative diagnostic 131I scintigraphy. This study was designed to assess the efficacy of thyroid ablation by high-dose 131I without pre-ablative diagnostic 131I scintigraphy. Ninety-three patients were treated with (near) total thyroidectomy and with a high ablative dose of 131I (3700-7400 MBq). A preablative 131I diagnostic scintigram was not performed. To assess the efficacy of the treatment, all patients were studied with a diagnostic 131I scintigram and with thyroglobulin plasma assays 1 year later after withdrawal of L-thyroxine for 4-6 weeks. The main criterion for a successful ablation was the absence of thyroid bed activity. An additional criterion was a thyroglobulin value of <10 microg x l(-1). Successful ablation according to the main criterion was obtained in 88% of patients. Forty patients (43%) showed no neck uptake and had undetectable serum thyroglobulin. Twenty-two patients (25%) had serum thyroglobulin concentrations between 1 and 10 microg x l(-1). Twenty-six patients (27%) had thyroglobulin >10 microg x l(-1), 19 patients showing residual thyroid uptake or metastatic lesions. We conclude that high-dose radioiodine ablation without prior diagnostic scintigraphy results in a high rate of successful ablation, preventing repeat 131I treatment.

Adult↗

Fluorine-18 fluorodeoxyglucose dual-head positron emission tomography in the detection of recurrent differentiated thyroid cancer: preliminary results.

In the follow-up of patients with thyroid cancer, it may be very difficult to identify the site of recurrence in the presence of persistently elevated or rising thyroglobulin (Tg) levels and negative iodine-131 whole-body scintigraphy (WBS). The aim of this study was to assess the feasibility of employing fluorine-18 fluorodeoxyglucose and a dual-head positron emission tomography (PET) camera to detect recurrent thyroid cancer in patients with elevated Tg levels and negative 131I WBS. Eleven patients suspect of having recurrent thyroid cancer (five males, six females; mean age 47 years; range 26-73 years) were studied with both 131I WBS and FDG using a dual-head PET camera. The suspicion that these patients had recurrent thyroid cancer was based on elevated Tg levels. Thyroid stimulating hormone (TSH) and Tg levels as well as antibodies to Tg were measured 3 weeks after the withdrawal of tri-iodothyronine. In patients in whom pathological uptake was seen on the PET images but who had no signs of recurrent thyroid cancer on WBS, ultrasonography and/or computed tomography or magnetic resonance imaging was performed followed by fine-needle aspiration cytology. The mean Tg and TSH levels after discontinuation of L-thyroxine were 156 ng/ml (range 4-815 ng/ml) and 84 mU/l (range 43-159 mU/l), respectively. None of the patients had antibodies to thyroglobulin. In seven out of ten patients with negative 131I WBS, FDG PET showed focally increased uptake in the head and neck region. In one patient, the site of increased uptake on the PET images corresponded with the site of increased 131I uptake. Malignancies with a diameter less than 1 cm (n = 3) were not depicted by either CT or US. It is concluded that detection of recurrent thyroid cancer by means of FDG dual-head PET is feasible in patients with elevated Tg concentrations and negative 131I WBS. The results justify a prolongation of the study.

Adult↗

High-affinity growth hormone (GH)-binding protein (GHBP), body fat mass, and insulin-like growth factor-binding protein-3 predict the GHBP response to GH therapy in adult GH deficiency syndrome.

The study objective was to investigate which baseline factors can accurately predict plasma high-affinity growth hormone (GH)-binding protein (GHBP) levels after GH replacement therapy in patients with GH deficiency (GHD). The study group consisted of 36 GHD patients (22 men and 14 women; mean age, 43.1 years; (range, 21 to 60) known to have adult-onset GHD for many years (range, 4 to 22). They were randomly divided into a GH-treated group (n = 19) and a placebo group (n = 17). Body composition (assessed by bioelectrical impendance analysis [BIA]), plasma GHBP (fast protein liquid chromatography [FPLC] size-exclusion gel chromatography), insulin-like growth factor-I (IGF-I), and IGF-binding protein-3 ([IGFBP-3] radioimmunoassays) were measured before and after 6 months. A stepwise multiple linear regression analysis with the plasma GHBP level after 6 months as the dependent variable was used to unravel significant explanatory (or predictor) variables. In contrast to placebo therapy, GH replacement therapy increased the mean plasma levels of IGF-I and IGFBP-3 to the normal range, whereas a small but statistically significant increase in plasma GHBP was observed. The combination of baseline plasma GHBP, body fat mass, and IGFBP-3 predicts posttreatment GHBP levels accurately (adjusted R2 = .97), indicating that baseline variables such as age, gender, fat-free mass, and IGF-I have no contribution. Furthermore, reliability analysis showed that the observed and predicted values for GHBP fit a strict parallel model. These findings indicate that the variations in body fat mass and IGFBP-3 among adult GHD subjects explain the reported variable response of GHBP to GH replacement therapy.

Adipose Tissue↗

Acromegaly: report of two patients with an unusual presentation.

The presenting features of functionally active pituitary tumours depend on the specific hormone which is overproduced. Growth hormone (GH) producing tumours usually present with the clinical manifestations of acromegaly due to excessive GH secretion or symptoms resulting from mass effects of the enlarging tumour. The changes in physical features and the increase in tumour size are usually insidiously slow and therefore, recognition of the disease is delayed. In this report two patients with acromegaly are described with an atypical presentation due to acute onset of symptoms. The first patient presented with central diabetes insipidus. The diagnosis acromegaly was made on physical examination. The second patient presented with a generalized seizure during sleep. On CT-scanning a large tumour protruding into the left temporal lobe connected to the pituitary gland was seen. Immunohistochemistry of the tumour after partial transcranial resection confirmed the clinical diagnosis of acromegaly. At a later stage transsphenoidal resection of the pituitary tumour was performed with full recovery and without loss of pituitary function.

Acromegaly↗

Undetectable serum thyroglobulin in a patient with metastatic follicular thyroid cancer.

The case of a 54-year-old woman with metastatic follicular thyroid cancer and undetectable serum thyroglobulin is presented. Many years after the patient had a subtotal thyroidectomy for a large goiter that had no clear evidence of malignancy, metastatic bone disease developed. When the bone metastases were detected and during the follow-up period, serum thyroglobulin values remained undetectable, but radioiodine uptake in the metastases was abundant. This case indicates that the combination of 1-131 scintigraphy and serum thyroglobulin values is superior to the measurement of serum thyroglobulin alone in detecting well-differentiated, metastatic thyroid cancer.

Adenocarcinoma, Follicular↗

Three novel mutations at serine 314 in the thyroid hormone beta receptor differentially impair ligand binding in the syndrome of resistance to thyroid hormone.

The syndrome of resistance to thyroid hormone is associated with diverse mutations in the ligand-binding domain of the thyroid hormone beta receptor, localizing to three clusters around the hormone binding cavity. Here, we report three novel resistance to thyroid hormone mutations (S314C, S314F, and S314Y), due to different nucleotide substitutions in the same codon, occurring in six separate families. Functional characterization of these mutant receptors showed marked differences in their properties. S314F and S314Y receptor mutants exhibited significant transcriptional impairment in keeping with negligible ligand binding and were potent dominant negative inhibitors of wild-type receptor action. In contrast, the S314C mutant bound ligand with reduced affinity, such that its functional impairment and dominant negative activity manifest at low concentrations of thyroid hormone, but are more reversible at higher T3 concentrations. The degree of functional impairment of mutant receptors in vitro may correlate with the magnitude of thyroid dysfunction in vivo. Modelling these mutations using the crystal structure of thyroid hormone receptor beta shows why ligand binding is perturbed and why the phenylalanine/tyrosine mutations are more deleterious than cysteine.

Adolescent↗

[Diagnosis and therapy of patients with adrenocortical insufficiency].

Most symptoms and signs of adrenocortical insufficiency are aspecific. For a definitive diagnosis a stimulation test is often needed. In case of secondary adrenocortical insufficiency glucocorticoid substitution nearly always suffices. Patients with primary adrenocortical insufficiency need substitution not only with glucocorticoids but also with mineralocorticoids. A standard daily dose of 30 mg hydrocortisone as glucocorticoid substitution is too high for many patients, while for some a standard daily dose of 0.1 mg fludrocortisone as mineralocorticoid substitution is too low. Patients with adrenocortical insufficiency need adequate instructions about what to do in case of stress, such as a (febrile) illness or trauma. Duration and severity of the suppression of the pituitary-adrenal axis by the use of pharmacological amounts of glucocorticoids are highly variable. When pharmacological amounts of glucocorticoids (> 7.5 mg prednisone daily) are used for 3 weeks or longer, a clinically relevant suppression of the pituitary-adrenal axis is possible, and this may persist for one year after discontinuing the use of glucocorticoids.

Addison Disease↗

Reverse discordant scintigraphy in diffuse goiter.

Both Tc-99m pertechnetate and radioactive iodine (I-123 NaI or I-131 NaI) are useful in thyroid scintigraphy. These radiopharmaceuticals yield similar functional information in most patients. Occasionally, however, discordant results have been reported in the literature (warm or hot on the pertechnetate image and cold on the radioiodide image). Most of these reports have concerned the solitary thyroid nodule. A case is presented here with diffusely decreased Tc-99m pertechnetate uptake and normal I-131 NaI uptake in a patient with a diffuse goiter and subclinical hyperthyroidism, so-called reverse discordant behavior.

Goiter↗

Visceral adipose tissue is associated with circulating high affinity growth hormone-binding protein.

Recent data show that body fat distribution, specifically visceral fat accumulation, is associated with the regulation of GH secretion. To our knowledge no studies have been performed with regard to the relationship between plasma high affinity GH-binding protein (GHBP) levels and fat distribution in humans. To address this question, we measured plasma GHBP and insulin-like growth factor I levels as well as visceral, sc abdominal, and hip adipose tissue (AT) areas by using magnetic resonance imaging scanning in 12 patients with GH deficiency (GHD) and in 12 age- and sex-matched healthy subjects. The GHD patients were subsequently treated with GH replacement therapy. Regardless of the GH status of the subjects, body mass index and visceral AT area were positively correlated to plasma GHBP (r = 0.70; P < 0.01 and r = 0.73; P < 0.01, respectively), whereas the sc AT areas at the abdominal level tended to correlate positively with GHBP levels, but did not reach significance (r = 0.44; P = 0.07). The sc AT areas at the hip level were not correlated with plasma GHBP levels. In the GHD patients the pretreatment visceral and abdominal sc AT areas were positively correlated with the change in GHBP levels after GH replacement (r = 0.82; P < 0.01 and r = 0.75; P < 0.01, respectively). The pretreatment sc AT area at the hip level was not associated with the therapy-induced changes in plasma GHBP (r = 0.28; P > 0.10). In summary, this study shows that visceral fat is associated with circulating GHBP levels, suggesting that visceral fat mass may be involved in the regulation of the plasma GHBP level. Further, the amount of abdominal fat in GHD patients may partially determine the plasma GHBP response to GH replacement therapy.

Adipose Tissue↗

Iodine-131 therapy in sporadic nontoxic goiter.

UNLABELLED: The effect of radioiodine in the treatment of nontoxic goiter is seldom evaluated quantitatively. The aim of this study was threefold: (a) to assess the effect of 131I on goiter volume, (b) to establish a relationship between CT volume reduction and the amount of radioactivity taken up by the thyroid and (b) to assess the precision of scintigraphic thyroid volume measurements. METHODS: In 27 patients with sporadic nontoxic goiter, the thyroid volume was estimated from a [99mTc]pertechnetate scintigram. Two different models (cylinder model and surface model) were applied. The 131I dosage varied between 507 and 3700 MBq. In all patients, noncontrast CT scanning of the neck was performed before therapy and 1 yr after therapy. RESULTS: The mean CT thyroid volume before therapy was 194 +/- 138 ml. A reduction was obtained in all patients and averaged 34% +/- 17%. The volume reduction measured by CT correlated well with the amount of 131I in the thyroid (r = 0.70). In thyroids larger than 200 ml, both scintigraphic volume estimation methods were imprecise. For smaller volumes, the surface model was superior. Hypothyroidism developed in 14% of the patients. No other side effects occurred. CONCLUSION: Iodine-131 therapy for volume reduction in nontoxic goiter is a safe and effective treatment. For scintigraphic estimation of thyroid gland volumes smaller than 200 ml, the surface model is preferred.

Adult↗

Cortisol secretory patterns in Cushing's disease and response to cyproheptadine treatment.

To investigate whether cortisol secretory patterns are associated with a response to cyproheptadine treatment in Cushing's disease, we studied two patients with a hyperpulsatile pattern and one patient with a hypopulsatile pattern before and during chronic cyproheptadine therapy (24 mg daily). In the two patients with a hyperpulsatile cortisol secretory pattern, pituitary magnetic resonance imaging with gadolinium did not reveal a pituitary adenoma, whereas in the patient with a hypopulsatile cortisol secretory pattern, a microadenoma was identified. Plasma cortisol levels were measured every 30 min for 24 h. In the two patients with a hyperpulsatile cortisol secretory pattern, chronic treatment with cyproheptadine resulted in sustained clinical and biochemical improvement and normalization of the median of absolute and relative increments in cortisol spikes. In the patient with a hypopulsatile cortisol secretory pattern, only a reduction of cortisol spikes was noticed during treatment. These results suggest that patients with Cushing's disease who are characterized by a hyperpulsatile cortisol secretory pattern and in whom no pituitary lesion can be identified by magnetic resonance imaging, cyproheptadine treatment may be useful.

Adenoma↗

High-affinity growth hormone binding protein, insulin-like growth factor I and insulin-like growth factor binding protein 3 in adults with growth hormone deficiency.

The high-affinity growth hormone binding protein (GHBP) circulates in human blood and represents the extracellular domain of the growth hormone (GH) receptor. The effects of GH deficiency on GHBP in adults are not clear. The aim of this study was to evaluate serum GHBP levels in adults with GH deficiency and to assess whether GHBP measurement may contribute to the diagnosis of adult GH deficiency, based on a two-step model. We measured insulin-like growth factor I (IGF-I), IGF binding protein 3 (IGFBP-3) and GHBP levels in serum samples of 36 patients with adult-onset GH deficiency. The GHBP levels were measured by FPLC size-exclusion chromatography; IGF-I and IGFBP-3 levels were measured by RIA. Serum GHBP levels were elevated above the upper limit of the 95% confidence interval in 26 patients, whereas IGF-I and IGFBP-3 levels were low in 10 patients and in 16 patients, respectively. The combination of low serum IGF-I and low IGFBP-3 levels was found in 10 patients. In nine patients, serum IGF-I levels were low, with elevated GHBP levels. Low serum IGF-I, low IGFBP-3 and elevated GHBP levels were found in five patients. Only four out of 36 patients had serum IGF-I, IGFBP-3 and GHBP levels that were within the 95% confidence interval of the control values. We conclude that adults with acquired GH deficiency have elevated GHBP levels in comparison to healthy subjects. We suggest that measurement of GHBP levels might contribute to the diagnosis of adult GH deficiency, though further research is required to study the additional value of GHBP measurements.

Adult↗