Biomedical subjects

Jan W A Smit

Publications and source records attributed to Jan W A Smit.

At least 19 recordsLinked to original sources

PubMed2006

Efficacy of needle-free administration of recombinant human growth hormone in adults with growth hormone deficiency.

AIM: Needle-free administration of recombinant human growth hormone (rhGH) is effective in the treatment of growth hormone deficiency (GHD) in children, but has not been studied in adult patients. Therefore, we evaluated the efficacy of needle-free administration of rhGH in adults with GHD. METHODS: Insulin-like growth factor-I (IGF-I) concentrations were compared in newly diagnosed patients with GHD (n = 21) and in patients previously treated by subcutaneous injection of rhGH (switchers, n = 34), at baseline, 12 months and 24 months. RESULTS: In the new patients, IGF-I standard deviation scores (SDS) increased from - 1.82 +/- 0.46 to + 0.75 +/- 0.33 at 12 months and to + 0.65 +/- 0.41 at 24 months (P < or = 0.001 vs. baseline). In switchers, IGF-I SDS remained unchanged with values of + 0.98 +/- 0.32 at baseline, + 0.87 +/- 0.23 at 12 months and + 0.73 +/- 0.29 at 24 months (P = 0.696 vs. baseline). In new patients, the rhGH dose was 0.46 +/- 0.03 mg day(-1) at 12 months and 0.47 +/- 0.03 mg day(-1) at 24 months. In switchers, the rhGH dose was 0.53 +/- 0.04 mg day(-1) at baseline (s.c. injection), 0.52 +/- 0.03 mg day(-1) at 12 months and 0.48 +/- 0.03 mg day(-1) at 24 months (NS between the different time points). There was no difference in the dose of rhGH at 12 and 24 months between the two groups. Side-effects were generally minor and consisted of local tissue reactions. CONCLUSION: Administration of rhGH by needle-free, transdermal injection is effective in maintaining IGF-I concentrations in the normal range for age in adults with GHD, and is as effective as traditional subcutaneous injection of rhGH.

Adult↗

PubMed2005

Morbidity after long-term remission for acromegaly: persisting joint-related complaints cause reduced quality of life.

Active acromegaly is associated with significant comorbidity and reduced quality of life. However, the prevalence of comorbidity after long-term remission is not established. Therefore, we assessed the presence of comorbidity in 118 patients in long-term remission after surgery, radiotherapy, and/or somatostatin analog treatment according to strict biochemical criteria of serum GH and IGF-I concentrations and evaluated the impact of comorbidity on quality of life. The mean duration of remission was 12.0 +/- 7.4 yr, and mean actual IGF-I sd scores were 0.6 +/- 1.7. Self-reported joint problems occurred in 77% of patients, hypertension in 37%, a history of myocardial infarction in 9%, and diabetes mellitus in 11%. The presence of joint problems was not related to GH and IGF-I levels, active disease duration, or age. Joint complaints had significant negative impact on quality of life. Patients with a history of myocardial infarction had reduced scores for general health, depression, and fatigue, and diabetes mellitus was associated with reduced scores for anxiety and sleep. In conclusion, acromegalic patients had a high prevalence of joint-related comorbidity and hypertension despite long-term control of GH excess. Especially, joint complaints contributed to a reduced perceived quality of life in these patients.

Acromegaly↗

PubMed2005

Intravenous octreotide test predicts the long term outcome of treatment with octreotide-long-acting repeatable in active acromegaly.

OBJECTIVE: Depot formulations of somatostatin analogues are increasingly used in the treatment of active acromegaly. A priori knowledge of the efficacy of these drugs in controlling GH excess is clinically relevant, because only approximately 60% of the patients respond with adequate control of GH (GH levels < 5 mU/L) and/or IGF-1 levels upon this treatment. Therefore, we assessed the acute responses of serum GH levels to a new octreotide test (intravenous administration of 50 microg) in 98 consecutive patients with active acromegaly and we measured the predictive value of this test for the efficacy of chronic octreotide-long acting repeatable (octreotide-LAR) treatment in 18 patients. DESIGN: Serum GH concentrations were measured before and at 20, 30, 45, 60, 90, 120, 150 and 180 min following 50 microg i.v. octreotide. The minimal achieved GH was used for analysis. Octreotide-LAR was individually titrated aiming at a normal serum IGF-I for age and a serum GH < 5 mU/L. The mean of 3-6 monthly serum GH and IGF-I measurements after individual dose adjustment was used for evaluating the efficacy of chronic therapy. RESULTS: Octreotide decreased GH levels to values below 5 mU/L in only 49% of unselected consecutive patients and the response was inversely related to basal GH levels. In patients with baseline GH above 50 mU/L, 50 microg i.v. octreotide reduced GH to < 5 mU/L in only 15% of cases (n = 41), whereas in patients with baseline GH levels below 50 mU/L this goal was achieved in 77% of cases. The fractional decrease in GH levels upon octreotide injection was similar in microadenomas and macroadenomas. The minimally achieved serum GH concentration during the intravenous octreotide test was a good predictor for the GH concentrations during long-term octreotide-LAR treatment as assessed in 18 patients. The intravenous octreotide test, using a minimal GH level of < 5 mU/L, had a sensitivity, positive and negative predictive value of 100% for prediction of GH suppression to below 5 mU/L during long term octreotide-LAR treatment. For predicting the response of IGF-I during long-term treatment, the test performed with a sensitivity of 73% and a positive predictive value of 73%. CONCLUSION: Intravenous octreotide reduces GH to concentrations < 5 mU/L in approximately 50% of consecutive patients with active acromegaly, which predicts a good response to chronic octreotide-LAR treatment.

Acromegaly↗

PubMed2005

High prevalence of long-term cardiovascular, neurological and psychosocial morbidity after treatment for craniopharyngioma.

INTRODUCTION: The treatment of craniopharyngiomas is associated with long-term morbidity. AIM OF THE STUDY: To assess the long-term functional outcome and mortality rates after treatment for craniopharyngiomas, we audited our data with special focus on cardiovascular, neurological and psychosocial morbidity. PATIENTS AND METHODS: Between 1965 and 2002, 54 consecutive patients underwent surgery for craniopharyngiomas at the Leiden University Medical Centre (LUMC). Fifteen patients (25%) received additional postoperative radiation therapy. The median follow-up period was 10 years (range 1-37 years). RESULTS: Long-term cure rate was 82% and long-term recurrence rate 18%. Visual fields/visual acuity stabilized or improved in 74% of cases. The long-term prevalence rate of hypopituitarism was 89%. In addition, long-term cardiovascular, neurological and psychosocial morbidity rates were high: 22% (risk factors 57%), 49% and 47%, respectively. Female sex was an independent predictor of increased cardiovascular, neurological and psychosocial morbidity (odds ratio 3.78, P = 0.031). Ten patients (18%) died during an 828 person-year follow-up. The actuarial patient survival rates 5, 10 and 20 years after the initial operation were 95, 85 and 85%, respectively. The standardized mortality ratio (SMR) was 2.88 [95% confidence interval (CI) 1.35-4.99]. CONCLUSION: Craniopharyngioma is associated with excessive long-term multisystem morbidity and mortality, especially in female patients, despite a high cure rate. These observations indicate that dedicated long-term follow-up of these patients is required. The purpose of the follow-up should be: first, to look for recurrences and to ensure appropriate endocrine replacement, especially oestrogen replacement in premenopausal females; and second, to achieve intensive control of glucose, lipids, blood pressure and weight, as in any other patient with increased risk for cardiovascular disease.

Adolescent↗

PubMed2004

Indium-111 octreotide scintigraphy for the detection of non-functioning metastases from differentiated thyroid cancer: diagnostic and prognostic value.

In this prospective study, we evaluated the diagnostic and prognostic value of (111)In-octreotide scintigraphy (SRS) in papillary and follicular thyroid carcinoma (DTC) with increasing thyroglobulin (Tg) levels but no response to treatment with (131)I. Twenty-three consecutive patients (13 female, 10 male; mean age 55 years, range 13-81 years) with progressive DTC were selected for the study. All patients had non-functioning metastases, defined by no or slight uptake of (131)I in metastases. Diagnosis of tumour progression was based on rising Tg levels during follow-up and was confirmed by radiological examination. Uptake on SRS was scored from 0 to 4. Data on initial tumour stage, histology, age, gender, Tg values, TSH levels, (131)I treatment doses, intervals and survival were gathered. Seven patients died during follow-up. The overall sensitivity for the detection of metastases was 74%. The sensitivity was better in patients in whom (131)I whole-body scintigraphy did not show any abnormal uptake (82%; 14/17) than in patients with faint (131)I uptake (50%; 3/6). The 10-year survival rate was significantly different between patients with an uptake score of 0 or 1 (100%) and those with an uptake score of 2, 3 or 4 (33%) ( P=0.001). Gender, log Tg and uptake on SRS significantly correlated with survival, but in stepwise analysis, (111)In-octreotide uptake was selected as the most prognostic independent variable (hazard rate 6.25, P=0.006). We conclude that (111)In-octreotide scintigraphy is a valuable clinical tool for the detection of non-functioning DTC metastases. The uptake seems to correlate with prognosis and survival.

Adolescent↗

PubMed2004

Radioiodine-131 in differentiated thyroid cancer: a retrospective analysis of an uptake-related ablation strategy.

In our hospital, a 24-h radioiodine-131 ((131)I) uptake-related ablation strategy is used in patients with differentiated thyroid cancer to destroy thyroid remnants after primary surgery. In this strategy, low doses of (131)I are used, but data in the literature on its efficacy are conflicting. Therefore, we performed the present study to evaluate the clinical outcome of this ablation strategy. In this study, patients ( n=235) were selected who underwent thyroidectomy for differentiated thyroid cancer, followed by an ablative dose of (131)I. Approximately 6 months after ablation, treatment efficacy was evaluated using radioiodine scintigraphy and thyroglobulin (Tg) measurements. Successful ablation was defined as the absence of radioiodine uptake in the neck region (criterion 1). Tg values were determined 3-12 months after ablation (criterion 2). Based on criterion 1, unsuccessful ablation was found in 43.0% of cases. Pre-treatment uptake values were statistically significantly lower ( P=0.003) in successfully ablated patients (mean 5.4%) than in unsuccessfully ablated patients (mean 8.2%). Based on criterion 2, unsuccessful ablation was found in 52.4% of patients. The uptake-related ablation strategy, using low doses of (131)I, shows a relatively high treatment failure rate. Based on these results it is suggested that a lower ablation failure rate could be achieved by applying higher (131)I doses in the ablation of thyroid remnants in differentiated thyroid carcinoma patients. In the case of lymph node metastases a further dose adjustment may be advisable.

Adolescent↗

PubMed2004

Genes differentially expressed in thyroid carcinoma identified by comparison of SAGE expression profiles.

To identify transcripts that distinguish malignant from benign thyroid disease serial analysis of gene expression (SAGE) profiles of papillary thyroid carcinoma and of normal thyroid are compared. Of the 21,000 tags analyzed, 204 tags are differentially expressed with statistical significance in the tumor. Thyroid tumor specificity of these transcripts is determined in silico using the tissue preferential expression (TPE) algorithm. TPE values demonstrate that 42 tags of the 204 are thyroid tumor specific. BC013035, a cDNA encoding a novel protein, is up-regulated from 0 to 24 tags in the thyroid tumor SAGE library. In a tissue panel of 30 thyroid tumors and 12 controls, it has an expression pattern similar to thyroid peroxidase, indicating possible involvement of BC013035 in thyroid differentiation. A tag coding for extracellular matrix protein 1 (ECM1) is absent in the normal thyroid SAGE library and present 55 times in the tumor. ECM1, a protein recently associated with angiogenesis and expressed in metastatic breast carcinoma, is up-regulated in 50% of all thyroid carcinoma and absent in normal controls and follicular adenoma. In conclusion, SAGE analysis and subsequent determination of TPE values facilitates the rapid distinction of genes specifically expressed in cancer tissues.

Adenocarcinoma, Follicular↗

PubMed2004

Six-months of recombinant human GH therapy in patients with ischemic cardiac failure.

Growth hormone therapy in patients with idiopathic dilated cardiomyopathy and ischemic cardiac failure has revealed varying effects on systolic function, probably related to the response in serum insulin-like growth factor I (IGF-I) levels. As diastolic function has not been studied thoroughly, we studied the effects of 6 months of recombinant human growth hormone (rh GH) treatment on systolic and diastolic function in patients with ischemic cardiac failure, using cardiovascular magnetic resonance (MR) imaging. Nineteen patients with ischemic cardiac failure (left ventricular ejection fraction (LVEF), <40%) were studied in a randomized trial. Nine patients received 6 months treatment with growth hormone (2 IU/day). Systolic and diastolic function were assessed at baseline and after 26 weeks by cardiovascular MR imaging. No differences were found in systolic and diastolic function between rh GH treated patients and controls. No change was observed in left ventricular mass index (LVMI), end-diastolic volume, end-systolic-volume and ejection fraction. The treated patients showed no clinical improvement. Six months of treatment with growth hormone therapy in ischemic cardiac failure has no favorable effects on LVMI, on systolic and diastolic function.

Aged↗

PubMed2004

Six month follow-up after 111In-DTPA-octreotide therapy in patients with progressive radioiodine non-responsive thyroid cancer: a pilot study.

BACKGROUND AND AIM: 111In-DTPA-octreotide is internalized by thyroid and neuroendocrine cancer cells via somatostatin receptor subtypes and can cause DNA damage by the emission of conversion and Auger electrons. The aim of the study was to determine the effect of 111In-DTPA-octreotide therapy in patients with progressive radioiodine non-responsive thyroid cancer in relation to 111In-DTPA-octreotide uptake by tumour localizations assessed on pre-treatment diagnostic octreotide scans. METHODS: Eleven consecutive patients, selected on positive pretreatment diagnostic scans, were treated with fixed doses of approx. 7400 MBq of 111In-DTPA-octreotide with an interval of 2-3 weeks between the doses. In one patient, the dose was adjusted because of sickle-cell disease. To assess the effects during treatment with 111In-DTPA-octreotide thyroglobulin levels were gathered from 2 years before treatment, during treatment and up to 1 year after treatment. A computed tomography scan was performed 3 months after the last treatment. RESULTS: Two patients died during and shortly after the treatment course. Death was due to a sepsis and an insulin overdose, respectively. In 44% of the patients, stable disease was achieved up to 6 months after the first treatment according to both criteria. All four had relative low pretreatment thyroglobulin values (mean value 275 microg.l), representing limited metastasized disease. In two patients biochemical stable disease was observed, whereas computed tomography showed tumour progression. CONCLUSION: Treatment with high doses of 111In-DTPA-octreotide in differentiated thyroid cancer results in a stable disease in a subgroup of patients. Our results suggest that a low pre-treatment thyroglobulin value, representing a small tumour load, may be a selection criterion for treatment.

Adult↗

PubMed2004

Increased prevalence of regurgitant valvular heart disease in acromegaly.

Cardiac involvement is common in acromegaly, but the prevalence of valvular abnormalities in patients with acromegaly has not been documented and is the topic of this study. In a prospective study design, 40 consecutive patients with acromegaly and 120 control subjects (matched for age, sex, hypertension, and left ventricular systolic function) were studied. All patients and controls were evaluated using conventional two-dimensional and Doppler echocardiography. Significant valve disease was more prevalent in acromegalics compared with controls (22% vs. 6.7%, respectively; P = 0.005). Aortic valve regurgitation (>/=>trace severity) was present in 30% of patients vs. 7% of controls (P < 0.001), and mitral regurgitation (>/=moderate severity) was absent in controls but present in 5% of acromegalics (P = 0.014 vs. controls). Binary logistic regression analysis showed a significant impact only for disease duration on valvular disease, with an odds ratio of 1.19 (95% confidence interval, 1.028-1.376; P = 0.019). Acromegaly is associated with an increased prevalence of regurgitant valvular heart disease. This is dependent on the duration of exposure to increased GH concentrations, with a 19% increase in odds per year. This increased prevalence of occult valvular disease indicates that these patients require appropriate follow-up care and monitoring, especially patients with inadequate control of GH overproduction.

Acromegaly↗

PubMed2004

Decreased quality of life in patients with acromegaly despite long-term cure of growth hormone excess.

The long-term impact of acromegaly on subjective well-being after treatment of GH excess is unclear. Therefore, we evaluated quality of life by validated questionnaires in a cross-sectional study of 118 successfully treated acromegalic patients. The initial treatment was transsphenoidal surgery in most patients (92%), if necessary followed by radiotherapy or octreotide. All patients were in remission at the time of assessment (GH, <1.9 mug/liter; normal IGF-I for age). General perceived well-being was reduced compared with controls for all subscales (P < 0.001) as measured by the Nottingham Health Profile and the Short Form-36. Acromegalic patients also had lower scores on fatigue (Multidimensional Fatigue Index) and anxiety and depression (Hospital Anxiety and Depression Scale). Radiotherapy was associated with decreased quality of life in all subscales except for the Hospital Anxiety and Depression Scale, and worsened quality of life significantly, according to the fatigue scores. Somatostatin analog treatment was not associated with improved quality of life. Independent predictors of quality of life were age (physical subscales and Nottingham Health Profile), disease duration (social isolation and personal relations), and radiotherapy (physical and fatigue subscales). In conclusion, patients cured after treatment for acromegaly have a persistently decreased quality of life despite long-term biochemical cure of GH excess. Radiotherapy especially is associated with a reduced quality of life.

Acromegaly↗

PubMed2004

Genetically defined hyperlipidemia.

The unraveling of genetic defects associated with disorders in lipid metabolism has contributed to the understanding of lipoprotein metabolism and the pathophysiological consequences of a particular mutation. The translation, however, of a single genetic defect into the individual's risk of cardiovascular disease and subsequent treatment strategies is an extremely complex issue that involves the identification of multiple additional determinants, including genetic, metabolic and environmental factors. The discovery of these factors, including genetic determinants of drug efficacy, provides insight into the interaction between regulatory systems traditionally thought to be unrelated and may, in the future, lead to a more complete diagnostic and therapeutic appreciation of the individual patient.

Animals↗

PubMed2004

Differential effects of natural flavonoids on growth and iodide content in a human Na*/I- symporter-transfected follicular thyroid carcinoma cell line.

OBJECTIVE: Natural flavonoids (plant pigments) have been shown to inhibit thyroid peroxidase (TPO) in vitro and the growth of thyroid cancer cell lines. We have studied the role of flavonoids on the iodide transport and the growth of the human follicular thyroid cancer cell line (FTC133) which was stably transfected with the human Na(+)/I(-) symporter (hNIS). DESIGN AND METHODS: Cells were treated with flavonoids (0.5-50 microM) for 0, 2, 4 and 6 days; (125)I content and (125)I efflux of the cells and DNA content were measured. RESULTS: Cell growth was inhibited significantly at day 6 by most flavonoids. Eight out of ten flavonoids decreased the (125)I content of the cells at day 4. Morin did not influence the (125)I content of the cells and, surprisingly, myricetin increased the (125)I content of the cells. Kaempferol, apigenin, luteolin and F21388 decreased NIS mRNA expression after 15, 29 and 48 h; after 96 h NIS mRNA returned to normal. CONCLUSION: As TPO is not present in this cell line, the effects of the flavonoids on the iodide uptake are not related to organification. Myricetin was the only flavonoid studied that increased the influx and decreased the efflux of iodide. The effect of myricetin (decreased growth and increased retention of iodide) can be of therapeutic value in the radioiodide treatment of thyroid carcinoma.

Adenocarcinoma, Follicular↗

PubMed2003

Diastolic dysfunction is associated with altered myocardial metabolism in asymptomatic normotensive patients with well-controlled type 2 diabetes mellitus.

OBJECTIVES: This study evaluated myocardial function in relation to high-energy phosphate (HEP) metabolism in asymptomatic patients with uncomplicated type 2 diabetes mellitus using magnetic resonance (MR) techniques. BACKGROUND: Myocardial dysfunction may occur in patients with type 2 diabetes mellitus in the absence of coronary artery disease or left ventricular (LV) hypertrophy. The mechanisms underlying this diabetic cardiomyopathy are largely unknown, but may involve altered myocardial energy metabolism. METHODS: We assessed myocardial systolic and diastolic function and HEP metabolism in 12 asymptomatic normotensive male patients with recently diagnosed, well-controlled type 2 diabetes and 12 controls, using MR imaging and phosphorus-31-nuclear MR spectroscopy (31P-MRS) on a 1.5 T clinical scanner; 31P-MR spectra were quantified, and myocardial HEP metabolism was expressed as phosphocreatine to adenosine-triphosphate (PCr/ATP) ratio. RESULTS: No differences were found in LV mass and systolic function between patients and controls. However, early (E) acceleration peak, deceleration peak, peak filling rate, and transmitral early-to-late diastolic peak flow (E/A) ratio, all indexes of diastolic function, were significantly decreased in patients compared with controls (p < 0.02). In addition, myocardial PCr/ATP in patients was significantly lower than in controls (1.47 vs. 1.88, p < 0.01). Inverse associations were found between myocardial PCr/ATP and E acceleration peak, E deceleration peak, and E peak filling rate (all, p < 0.05). CONCLUSIONS: These results indicate that altered myocardial energy metabolism may contribute to LV diastolic functional changes in patients with recently diagnosed, well-controlled and uncomplicated type 2 diabetes.

Adenosine Triphosphate↗

PubMed2003

Dietary flavonoids and iodine metabolism.

Flavonoids have inhibiting effects on the proliferation of cancer cells, including thyroidal ones. In the treatment of thyroid cancer the uptake of iodide is essential. Flavonoids are known to interfere with iodide organification in vitro, and to cause goiter. The influence of flavonoids on iodine metabolism was studied in a human thyroid cancer cell line (FTC-133) transfected with the human sodium/iodide transporter (NIS). All flavonoids inhibited growth, and iodide uptake was decreased in most cells. NIS mRNA expression was affected during the early hours after treatment, indicating that these flavonoids can act on NIS. Pendrin mRNA expression did not change after treatment. Only myricetin increased iodide uptake. Apeginin, luteolin, kaempferol and F21388 increased the efflux of iodide, leading to a decreased retention of iodide. Instead myricetin increased the retention of iodide; this could be of use in the radioiodide treatment of thyroid cancer.

Cell Division↗

PubMed2003

Sandostatin LAR in acromegaly: a 6-week injection interval suppresses GH secretion as effectively as a 4-week interval.

INTRODUCTION: Depot preparations of long-acting somatostatin analogues are being used increasingly in the treatment of GH hypersecretion in patients with acromegaly, either as primary treatment or as secondary treatment following incomplete surgery. In 60% of these patients, Sandostatin long-acting release (LAR), the depot preparation of octreotide, achieves effective suppression of serum GH (< 5 mU/l) and IGF-I levels. The advice is to administer Sandostatin LAR at 4-week intervals. After injection, serum octreotide shows an initial peak and thereafter maximal values between 14 and 42 days. There have been suggestions that the dose interval of this preparation could be increased, resulting in reduced costs, although this concept has not been confirmed by studies. AIM OF THE STUDY: We performed a prospective, cohort study in patients with active acromegaly but with normal serum GH and IGF-I levels during Sandostatin LAR treatment to assess whether the dose interval could be safely increased from 4 to 6 weeks, without significant effect on serum GH concentrations or other biochemical and clinical markers of GH hypersecretion. PATIENTS AND METHODS: Fourteen patients (seven males) with GH concentrations below 5 mU/l during Sandostatin LAR treatment entered an 8-week withdrawal study following an injection. Subsequently, during an interval study patients received injections at 6-week intervals (t = 0, 8, 14, 20, 26, 32, 38 and 44 weeks). Study parameters (fasting GH, average GH of eight plasma samples, IGF-I, and octreotide concentrations, symptoms score and quality-of-life score) were assessed 2, 4, 6 and 8 weeks following the first injection (withdrawal) and at 26 and 44 weeks (interval study) before the next injection. RESULTS: During the withdrawal study, mean serum GH concentration increased significantly from 1.68 +/- 0.3 at 4 weeks to 2.57 +/- 0.5 mU/l at 6 weeks (P = 0.04, 4 vs. 6 weeks) and to 2.89 +/- 0.4 mU/l at 8 weeks (P < 0.001, 4 vs. 8 weeks). Mean serum GH concentration was below 5 mU/l in all patients at all time points, except for one patient at 8 weeks, and IGF-I levels remained normal in all patients. During withdrawal up to 8 weeks there was no significant change in serum IGF-I concentration, symptoms score or quality-of-life score. Mean serum octreotide decreased significantly from 1610 +/- 355 ng/l at 2 weeks to 1045 +/- 272 ng/l at 6 weeks (P = 0.002, 2 and 4 vs. 6 weeks) and to 559 +/- 147 ng/l at 8 weeks. In the interval study, one patient had mean serum GH above 5 mU/l associated with an increase in symptoms at 26 weeks and she was withdrawn from the study. The remaining 13 patients completed the 6-weekly injection study protocol and in the long term no significant changes in mean serum GH concentration, IGF-I concentration or symptom scores were observed (6 vs. 26 and 44 weeks). All patients had a mean serum GH concentration < 5 mU/l and serum IGF-I remained normal in 11 out of 14 patients at 26 weeks and nine out of 13 patients at 44 weeks. Moreover, the mean octreotide concentrations measured 6 weeks after a Sandostatin LAR injection did not decrease in the long term. CONCLUSION: On the basis of serum GH concentrations, most patients with serum GH levels < 5 mU/l during Sandostatin LAR treatment using a 4-weekly schedule can be effectively treated with 6-weekly injections. However, during long-term treatment with 6-weekly injections, discordant IGF-I and GH results were observed in 30% of the patients and careful clinical monitoring is therefore required.

Acromegaly↗

PubMed2003

Effects of low-iodide diet on postsurgical radioiodide ablation therapy in patients with differentiated thyroid carcinoma.

OBJECTIVE: Most patients with differentiated thyroid carcinoma (DTC) undergo total thyroidectomy followed by routine radioiodide thyroid remnant ablation. Most centres that routinely perform radioiodide ablation prescribe a low-iodide diet (LID) to increase the radioiodide accumulation in thyroid remnants. The efficacy of an LID on thyroid remnant ablation, however, has never been demonstrated convincingly. DESIGN AND METHODS: In a retrospective study, we studied two groups of DTC patients without distant metastases, who had received either a standard diet or an LID during ablation (LID group, n = 59, and control group, n = 61). Both groups were compared for radioiodide uptake in thyroid remnants during ablation and efficacy parameters of remnant ablation, 6 months after ablation. A subgroup without extrathyroidal tumour growth was analysed separately (stages T1-3, N0). RESULTS: In the total group, the LID during ablation decreased the 24-h urinary iodide excretion to 26.6 micro g compared with 158.8 micro g in controls whereas radioiodide uptake in thyroid remnants was increased by 65% (P < 0.001). Six months after ablation, patients were investigated after thyroid hormone withdrawal. In the total group, no significant effects of the LID during ablation were observed on thyroglobulin (Tg) or the percentage of patients with persistent neck activity after 185 MBq 131I. However, in the LID group, 65% of patients without Tg antibodies had undergone successful ablation (defined by absent neck activity and Tg < 2 micro g/l) compared with 48% in the control group (P < 0.001). In the subgroup (T1-3, N0), 8% of the patients who had undergone the LID had Tg >/= 2 micro g/l vs. 32% in the control group (P = 0.012), whereas successful ablation was achieved in 71% of patients without Tg antibodies in the LID vs. 45% in the control group (P < 0.001). CONCLUSION: We conclude from this study that a low-iodide diet during thyroid remnant ablation improves the efficacy of this treatment.

Adult↗

PubMed2003

Long-term predictive value of postsurgical cortisol concentrations for cure and risk of recurrence in Cushing's disease.

We assessed the value of postoperative plasma cortisol concentrations to predict cure and recurrence of Cushing's disease after transsphenoidal surgery (TS). Seventy-eight of 80 consecutive patients treated by TS for Cushing's disease were evaluated. TS cured 72% (n = 56) of the patients. Two weeks after surgery, patients with plasma cortisol levels below 138 nmol/liter (n = 50; three macroadenomas) and eight (27%) of 30 patients (nine macroadenomas) with cortisol greater than 138 nmol/liter were cured. Six (five with a macroadenoma) of these eight patients had cortisol values less than 50 nmol/liter 3 months after surgery. Therefore, the optimal cut-off value of cortisol predicting remission was 138 nmol/liter, measured 3 months after surgery (positive and negative predictive values 87 and 90%, respectively). Five patients (9%) had recurrent Cushing's disease during a median follow-up of 7 yr. Recurrence occurred in four of 24 (17%) patients with a follow-up of more than 10 yr. Therefore, cortisol levels above 138 nmol/liter, obtained 2 wk after TS, should be repeated, because they do not predict persistent Cushing's disease in 27% of those patients. Postoperative cortisol levels do not positively predict recurrence of disease during long-term follow-up of initially cured patients.

Adolescent↗