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Biomedical subjects

F Roelfsema

Publications and source records attributed to F Roelfsema.

At least 73 records · Page 4Linked to original sources
PubMed1991

Pulsatile thyrotropin release and thyroid function in acromegalics before and during subcutaneous octreotide infusion.

The pulsatile secretion of TSH was studied in eight patients with active acromegaly before treatment and after 1 month of therapy consisting of the sc infusion of 300 micrograms octreotide/day. Mean GH levels decreased from 37.1 +/- 7.2 to 5.2 +/- 1.4 mU/L (P = 0.002). Insulin-like growth factor-I levels decreased from 82.9 +/- 8.8 to 37.8 +/- 9.8 nmol/L (P less than 0.01) and normalized in five of the eight patients. In one patient TSH levels were undetectable before and during octreotide therapy. In the other seven patients, Cluster analysis revealed 11.9 +/- 0.8 pulses/24 h, with a mean pulse width of 81 +/- 4.6 min, a mean pulse height of 1.33 +/- 0.42 mU/L, and a mean pulse increment of 0.36 +/- 0.12 mU/L. During octreotide therapy these pulse parameters remained unchanged. Pulse height and amplitude increased significantly during the night (i.e. from 2000-0800 h) in both untreated and treated patients. The acrophase was unchanged by therapy. During therapy T3 levels decreased from 2.05 +/- 0.17 nmol/L to 1.44 +/- 0.08 nmol/L (P = 0.001), while rT3 levels increased from 0.14 +/- 0.02 nmol/L to 0.19 +/- 0.03 nmol/L (P less than 0.05). Plasma T4 levels remained unchanged. From these studies we conclude that the TSH pulse generator is unchanged in active acromegaly and apparently unaffected by chronic octreotide infusions.

Acromegaly↗
PubMed1991

Octreotide treatment in acromegaly: a comparison between pen-treated and pump-treated patients in a cross-over study.

The effect of a schedule of three daily injections of 100 micrograms octreotide (pen treatment) compared with that of a continuous sc infusion of 300 micrograms/24 h on GH and IGF-I suppression, and other GH-dependent parameters was studied in 10 acromegalic patients in a cross-over study. Treatment was administered via a specially designed pen or a pump for 4 weeks. Following a washout period of a further 4 weeks, patients were switched to the other mode of delivery. Mean GH levels decreased from 26.2 +/- 4.7 to 9.9 +/- 3.1 mU/l (p = 0.007) during pen therapy and to 7.7 +/- 2.4 mU/l (p = 0.003) during pump treatment. IGF-I levels decreased from 75.6 +/- 9.5 to 42.0 +/- 9.3 nmol/l (p = 0.003) during pen treatment and to 32.5 +/- 2.5 nmol/l (p = 0.001) during pump treatment. There was a significant difference in IGF-I levels between pen and pump treatments (p = 0.03). In 7 patients the IGF-I levels normalized during pump treatment compared with 3 patients in the pen treatment group. There was no change in the free T4 index levels, but the free T3 index significantly decreased during therapy, without changes in plasma TSH. This study demonstrates that continuous infusion with octreotide results in a better control of GH oversecretion than the intermittent mode of delivery.

Acromegaly↗
PubMed1991

The interaction of GHRH with TRH in acromegaly: a controlled study.

In a single-blind placebo-controlled study, the effect of an iv bolus injection of 100 micrograms GHRH(1-29)NH2 on the response to 200 micrograms TRH was assessed in 10 untreated patients with acromegaly to determine whether GHRH interacts with TRH in acromegaly, as previously described in healthy subjects. The combination of GHRH(1-29)NH2 with TRH resulted in a larger increment of peak and of integrated plasma TSH and PRL levels than after TRH alone. GHRH alone had no effect on TSH secretion and only a modest effect on PRL secretion. These findings suggest that in acromegaly, like in healthy individuals, GHRH potentiates the TSH response to TRH and that the effects of GHRH and TRH on PRL secretion are additive.

Acromegaly↗
PubMed1990

The influence of octreotide treatment on pulsatile growth hormone release in acromegaly.

The pulsatile release of GH was investigated in eight active acromegalic patients before and during a subcutaneous infusion of 300 micrograms octreotide/24 h for 4 weeks. The number of GH pulses increased from a basal value of 14.4/24h to 16.3/24h during octreotide therapy. At the same time the mean GH concentration, valley concentration, peak height and amplitude decreased significantly. The inhibitory effect of octreotide on pulse characteristics did not depend on the time of day. IGF-I levels also decreased significantly; in five patients normal levels were reached. IGF-I levels correlated significantly with the mean GH level (r = 0.714, P less than 0.001), mean valley concentration (r = 0.697, P less than 0.001) and, to a lesser extent, area under the curve (r = 0.436, P = 0.033), but not the number of pulses. Plasma octreotide levels did not correlate with pulse parameters. In all but one patient a circadian rhythm was present during both the basal study and octreotide therapy. Compared with surgically treated acromegalics, the number of GH pulses was higher in untreated and octreotide-treated patients. This study demonstrates the pulsatile release of GH in active acromegaly both before and during octreotide therapy. This result suggests that endogenous GHRH is important for the generation of GH pulses in this disease.

Acromegaly↗
PubMed1989

Circadian and pulsatile thyrotropin release in treated acromegalics.

We studied the 24-h TSH profiles of 16 treated male acromegalic patients (age range 26-68 yr) in clinical and biochemical remission. Eight had undergone transsphenoidal surgery, the others surgery and pituitary irradiation. Blood samples were taken at 20-min intervals; circadian rhythms were established by cosinor analysis, pulsatile release with the Cluster programme. All patients, except one irradiated subject, were euthyroid. TSH reserve was diminished preoperatively in 7 subjects and at the time of the profile study in 10 subjects, one of whom was biochemically hypothyroid. A significant circadian rhythm was present in 14 subjects and absent in the hypothyroid patient. The acrophase occurred at 2.46 +/- 0.51 h in nonirradiated patients and at 3.37 +/- 0.38 h in irradiated patients (NS). About 10 TSH pulses/24 h (range 6-13) were detected; there was no significant difference between irradiated and non-irradiated patients. With cross-correlation techniques synchronous release of TSH and PRL was demonstrated in 7 out of 8 nonirradiated patients in contrast to only 2 of the irradiated patients. This study demonstrates a qualitatively normal TSH secretion pattern for treated acromegalic patients, but the absolute TSH levels are clearly low compared with published data on normal subjects. The present findings can be explained by a diminished TSH cell mass; in addition radiation therapy causes a disturbance at the hypothalamic level, as indicated by the loss of synchronism between TSH and PRL release.

Acromegaly↗
PubMed1989

Prolactin and luteinizing hormone profiles of cured acromegalic subjects.

The 24-h PRL and LH hormone profiles were analysed of 16 cured male acromegalic patients who had undergone selective transsphenoidal surgery 4-9 years previously. Eight of these patients also underwent pituitary irradiation. Blood samples were taken at 20-min intervals; the PRL and LH data were analysed with the cluster program. ARIMA modelling, cross-correlation techniques, Fourier analysis, and cosinor analysis. About 10-11 PRL and LH peaks were demonstrated for both non-irradiated and irradiated patients. The absolute heights of PRL pulses and the mean valley levels were significantly greater for irradiated patients than for non-irradiated patients, but the increment in amplitude did not differ. A significant diurnal rhythm for PRL was found for all non-irradiated patients but for only one irradiated patient. LH pulse area and amplitude were lower in the group of irradiated patients. The incremental responses of LH and PRL to GnRH and TRH, respectively, were lower in irradiated patients than in non-irradiated patients. During the night (0200-0800 h) the number of PRL pulses decreased in non-irradiated patients but not in irradiated patients. Pulse nadirs and amplitudes increased during the evening and night in non-irradiated patients but were constant in irradiated subjects. Bivariate modelling of the data for 14 patients revealed significant cross-correlations between LH and PRL pulses in nine subjects. This study demonstrates that the pulsatile secretion of PRL and LH in treated acromegalics is basically normal. Additional radiation therapy, however, may lead to damage of the hypothalamus, as reflected by the absence of a circadian PRL rhythm. A direct influence on the pituitary by radiation is indicated by the decreased magnitude of LH pulses and the diminished response of LH and PRL after injection of GnRH and TRH, respectively.

Acromegaly↗
PubMed1989

The effect of calcitonin on growth hormone secretion in acromegaly.

To determine whether human calcitonin inhibits GH secretion in acromegaly, as previously described for healthy subjects, the effect of an i.v. bolus injection of calcitonin or saline on GH levels in patients with active acromegaly was studied and compared to that of an i.v. bolus injection of the synthetic somatostatin analogue, octreotide. After the injection of calcitonin, GH levels decreased by 46% of initial values, whereas octreotide reduced GH levels by 87% and saline had no significant effect. Administration of calcitonin to acromegalics did not cause the transient rise in plasma PRL and TSH levels seen in normal subjects. Octreotide induced a decrease in plasma PRL in three out of seven patients. It is concluded that human calcitonin suppresses GH secretion in acromegaly, but not to normal levels; moreover the effect is less than that found for octreotide. In addition, acromegalic patients did not exhibit the PRL and TSH-releasing activity of calcitonin found in normal subjects, while octreotide inhibited PRL secretion in some acromegalic patients.

Acromegaly↗
PubMed1989

Bromocriptine therapy for non-functioning pituitary adenoma.

Over a 6-year period, 25 patients with non-functioning pituitary adenomas were treated with bromocriptine, while 18 other patients with this condition underwent surgery as the first therapeutic modality. The medically treated group, consisting of those patients without alarming eye symptoms, was analysed in retrospect. Eight of these patients had previously undergone surgery and radiotherapy. Bromocriptine was used in a dose of 5 to 22.5 mg per day; the mean duration of treatment was 18 months. For 11 patients, radiological findings obtained during the year before treatment with bromocriptine revealed progression in five cases and stable tumour size in the others. Three of the five patients with progression showed tumour size reduction during bromocriptine therapy while no further growth occurred in the other two. When medication was stopped in one responding patient, the tumour grew again. One other patient, without pretreatment radiological investigation, exhibited tumour size reduction during bromocriptine therapy, and one patient exhibited radiological progression during the study period. In one case visual fields improved and in one other deteriorated without parallel changes in tumour size on computerized tomography. The favourable reactions were equally divided between the groups with and without previous radiotherapy. We conclude that bromocriptine is rarely capable of reducing the size of non-functioning pituitary adenomas (16% in this series). However, pituitary adenomas exhibiting recent growth may be sensitive to this drug, leading to size reduction or growth arrest.

Adenoma↗
PubMed1989

Plasma growth hormone profiles and sleep: a study of 13 treated acromegalics.

The plasma growth hormone profiles and sleep patterns of 13 treated male acromegalic patients, aged 29-67 years, were studied. All patients had undergone selective pituitary transsphenoidal surgery 4-9 years previously; five patients had also undergone supplemental pituitary irradiation. Blood samples were taken at 20-min intervals; the sleep patterns were obtained by EEG. GH reserve was assessed after insulin-induced hypoglycaemia and GHRH (1-44) with and without pyridostigmine. The profiles were analysed with the aid of the Pulsar program. Seven out of eight non-irradiated patients had 1-3 nocturnal GH peaks; in the irradiated group only one patient had a normal profile. The GH reserve after insulin-induced hypoglycaemia was normal in seven out of eight non-irradiated patients, and subnormal in all five irradiated patients. In the latter group the GH reserve was diminished when tested with GHRH. One patient from each group had a severe apnoea syndrome; in both cases there was no nocturnal GH increase. The percentage sleep stage 1 was lower for irradiated patients when compared with non-irradiated patients, but the 14 other sleep parameters did not differ. From this study we conclude that the physiological regulation of GH secretion is restored in surgically treated patients. Radiation therapy may lead to pituitary and hypothalamic damage, which could affect spontaneous GH secretion.

Acromegaly↗
PubMed1989

Changes in basal and stimulated TSH and other parameters of thyroid function in acromegaly after transsphenoidal surgery.

T1 and T3 levels, TSH response to TRH and somatomedin-C levels in 63 patients with acromegaly, were measured before transsphenoidal surgery and during a 4-year follow-up period. Criteria for cure were: mean GH level less than 5 mU/l, suppression of GH by oral glucose tolerance test below 2.5 mU/l and normalization of paradoxical GH reaction to TRH. Nine patients underwent radioiodine studies to assess the renal and thyroid clearance of iodide, plasma inorganic iodine level and absolute iodine uptake. Among the patients 40% had goitre, with a male preponderance. T1 and T3 levels were in the normal range both before and after surgery. A transient decrease in T3 levels was found in the immediate postoperative period. Before treatment a diminished or absent TSH response to TRH was exhibited by 64% of the goitre patients and 34% of the non-goitre groups (p less than 0.05). Despite normalization of GH and somatomedin-C levels and normal T4 and T3 levels no improvement of the TSH response was found during follow-up. No correlation between the incremental response of TSH to TRH and circulating T4 or T3 levels, basal TSH, GH or tumour size was found. There was, however, a negative correlation (r = -0.765, p less than 0.05) between the incremental TSH response to TRH and somatomedin-C levels for females with goitre. Somatomedin-C levels were higher in patients with goitre than in those without goitre (95 +/- 26 vs 75 +/- 30 nmol/l; mean +/- SD, p = 0.05). Radioiodine studies showed an increased renal clearance of iodide which was related to the increase in creatinine clearance.(ABSTRACT TRUNCATED AT 250 WORDS)

Acromegaly↗
PubMed1988

Plasma growth hormone half-life after selective removal of adenoma in acromegalics determines the outcome of surgery.

We measured plasma GH levels during transsphenoidal surgery in eight patients with acromegaly. After removal of the adenoma GH levels fell monoexponentially in six subjects while they were still under general anaesthesia, but no decrease was noted for two other subjects. Normal postoperative GH and Somatomedin-C levels were found for those patients who exhibited a reduction in GH during surgery. During follow-up studies one patient with a normal GH level exhibited a paradoxical reaction to TRH, attributed to tumour remnants. The plasma half-life found for five patients was 18-33 min; for another cured subject it was longer, i.e. 58 min. The major fraction of the circulating GH, as determined by gel-chromatography, was mol. wt 22,000; this applied for six subjects, while the patient with the long plasma half-life appeared to have a mol. wt 33,000 variant. From this study we conclude that a clear drop in the plasma GH level after removal of the adenoma predicts a favourable outcome of surgery; however, if some tumour remnants are left behind, paradoxical reactions may occur despite normal basal GH levels.

Acromegaly↗
PubMed1988

The effect of calcitonin on growth hormone secretion in man.

To determine whether human calcitonin inhibits GH secretion in man, as has been described for salmon calcitonin, the effect of an i.v. bolus of human calcitonin or saline on GH release after either insulin-induced hypoglycaemia or the administration of GH-releasing hormone (GHRH) or saline was studied. After the injection of calcitonin, no spontaneous GH surges were seen; the GH response to hypoglycaemia was diminished and the response to GHRH almost completely suppressed. Administration of calcitonin also caused a small and transient rise in plasma PRL and TSH but not LH levels, and no change in the integrated PRL or TSH response. Calcium and magnesium levels did not change. It is concluded that human calcitonin suppresses GH secretion in man, but not by suppressing GHRH and probably not by increasing somatostatin release. In addition, calcitonin has limited PRL and TSH-releasing activity.

Adult↗
PubMed1987

Somatomedin-C levels in treated and untreated patients with acromegaly.

With the aid of a recently developed commercially available radioimmunoassay for Somatomedin-C (Sm-C) we measured the Sm-C levels in 38 controls, 24 untreated acromegalics, 45 inactive acromegalics and five pituitary dwarfs. With the exception of the dwarfs, the age and sex distributions for the various groups were similar. In inactive acromegalics the basal GH level (calculated as the mean of four blood samples taken during the day) was less than 5 mU/l; it was depressed to, or less than, 2.5 mU/l during the 100 g oral glucose tolerance test. The mean Sm-C level found for control subjects was 20.4 +/- 5.1 nmol/l and for untreated patients 85.6 +/- 25.7 nmol/l (mean +/- SD, P less than 0.001). The mean Sm-C level for inactive patients who had undergone surgery and invariably showed a normalized paradoxical reaction to TRH was 18.2 +/- 7.1 nmol/l (NS) vs 16.1 +/- 8.2 nmol/l (NS) for those who underwent surgery plus postoperative pituitary radiation therapy. Only one out of 45 inactive acromegalics exhibited an increased Sm-C level. The Sm-C levels correlated significantly not only with the log GH levels (r = 0.82) but also with the fasting insulin/glucose ratio the integrated incremental insulin levels, the maximal insulin increase and the integrated glucose levels during the oral glucose tolerance test as well as the 24-h urinary excretion of calcium and hydroxyproline.(ABSTRACT TRUNCATED AT 250 WORDS)

Acromegaly↗
PubMed1986

Circadian urinary excretion rhythms in adrenalectomized rats.

The impact of the adrenal system on urinary rhythms was investigated in adrenalectomized (ADX) rats under various experimental conditions. During a 12:12 light-dark cycle the acrophases were shifted in ADX rats with respect to control rats. Under constant light conditions ADX rats displayed free-running rhythms, similar to those of control rats. The periods were stable in blind rats but not in rats maintained on a constant light cycle. The abrupt change in period, which occurred after approximately 8 days, suggests a stage of internal desynchronization. A 6-h delay in the administration of corticosterone to ADX rats caused a delay shift of the acrophases. A single intraperitoneal injection of corticosterone in blind free-running ADX rats caused delay or advance shifts so that we could construct phase-response curves for the various excretory rhythms. These observations indicate that the adrenals are not essential for the establishment of the urinary rhythms; however, corticosterone influences the phase setting of these rhythms. The site of action is probably the X pacemaker (controlling the body temperature rhythm), although we cannot totally exclude an additional effect on secondary (renal) oscillators.

Adrenalectomy↗
PubMed1986

Conversion of thyroxine to 3,5,3'-triiodothyronine in several rat tissues in vivo: the effect of hypothyroidism.

The local conversion of thyroxine (T4) to 3,5,3'-triiodothyronine (T3) has been recognized as a source of T3 at various sites in euthyroid rats. The present study was designed to evaluate the effect of hypothyroidism on the source and quantity of T3 at several of these sites (liver, cerebral cortex (Cx), thymus, testis, brown adipose tissue). For this purpose intact euthyroid rats and radiothyroidectomized (RTx) rats received a continuous iv infusion of [125I]T4 and [131I]T3 until isotopic equilibrium was attained. In addition to the labelled iodothyronines, RTx rats received a continuous iv infusion of 0.75 microgram T4/day, in order to maintain a defined hypothyroid state. At the end of the infusion period the animals were bled and perfused, and homogenates of the various organs were prepared. The mean plasma T4 and T3 levels in T4-maintained RTx rats, as measured by RIA, were 1.5 micrograms/dl and 15 ng/dl (euthyroid values: 5.2 micrograms/dl and 48 ng/dl, respectively). The plasma and tissue homogenates were processed for thin layer chromatography and the [125I]T4, [125I]T3 and [131I]T3 levels determined. From these data the concentrations of T4, total T3 and T3 derived from local T4 to T3 conversion (LcT3(T4)) in tissue could be calculated. The relative mean contribution of LcT3(T4) to the total T3 in Cx (75%), thymus (31%), testis (43%) and brown adipose tissue (65%) from hypothyroid rats was higher than that determined for euthyroid animals (66%, 19%, 29% and 27%, respectively). The reverse was found for the liver (15% vs 39%).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1985

Glucose tolerance and plasma immunoreactive insulin levels in acromegalics before and after selective transsphenoidal surgery.

The glucose and immunoreactive insulin (IRI) responses to a 100 g oral glucose tolerance test (oGTT) administered to 23 acromegalic patients before and after transsphenoidal adenomectomy and to a sex and age-matched control group were studied. The preoperative growth hormone levels, ranging from 11 to 360 mU/l, had normalized (i.e. less than or equal to 5 mU/l) after surgery in all cases. Before surgery paradoxical increases in the GH level, either after i.v. TRH injection or during the oGTT were seen in 14 patients. After surgery, the paradoxical reaction to the oGTT had normalized in all cases and the increase measured after the TRH injection normalized in nine out of 12 cases. The disturbed glucose tolerance (either impaired tolerance or frank diabetes) was cured by surgery. The plasma glucose levels determined 1 and 2 years after surgery did not differ from those found for the control group. Preoperative plasma IRI levels were significantly elevated, whereas after surgery the IRI levels had decreased. Fasting levels were normalized in all patients. Two years after surgery, eight patients still showed some abnormalities of the insulin secretion (as revealed by the integrated sum and the maximum increment in IRI levels during the oGTT) despite the presence of normal circulating GH levels and a normalized paradoxical reaction to TRH. The data show that after normalization of GH levels in acromegalics, increased insulin secretion may still occur after glucose ingestion in some patients. It is suggested that this abnormality could be the result of an increased pancreatic islet beta-cell mass, as a persisting abnormality of the acromegalic state, although peripheral insulin resistance cannot be excluded totally.

Acromegaly↗
PubMed1985

Long-term results of transsphenoidal pituitary microsurgery in 60 acromegalic patients.

Sixty patients with clinically and biochemically active acromegaly were treated by transsphenoidal surgery. All patients underwent a full assessment of pituitary function both preoperatively and postoperatively; these studies were repeated 6 months after surgery and every year, when possible. The mean follow-up period was 3.3 years (range 0.5-7 years). The GH level normalized in 62% of patients after surgery. A paradoxical reaction of GH to TRH was present in 35 patients before surgery and had normalized in 17 after surgery. Large tumours were associated with higher GH levels than smaller tumours. A prognostic factor in terms of normalization of both the GH level and an eventual paradoxical reaction to TRH or a glucose challenge was a low preoperative GH level. Three out of seven patients with either a positive postoperative TRH test but a normal GH level, or a slightly elevated GH level suffered a biochemical and clinical recurrence and two of them underwent reoperation. In contrast, when the TRH test had normalized (always in association with normal GH levels) no recurrence was found. The impact of surgery on the other pituitary functions was generally slight and the numbers of patients with preoperative and postoperative impairment were about equal. Postsurgical radiation therapy was administered to patients with an elevated GH level, a non-normalized TRH test irrespective of whether the GH level had normalized, or local invasion of the tumour. In 11 out of 17 patients with elevated GH levels after surgery, normalization was achieved by radiation therapy after a mean period of 2.7 years. The incidence of pituitary failure after irradiation appeared to be high; gonadal function in men and the GH reserve function were especially vulnerable. From this study we conclude that in many cases the adenoma can be removed effectively, without compromising the other pituitary functions. However, a substantial number of the patients require additional radiation therapy, leading to an inevitable loss of other pituitary functions.

Acromegaly↗