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Biomedical subjects

J Weeke

Publications and source records attributed to J Weeke.

At least 55 records · Page 3Linked to original sources
PubMed1989

The cardiovascular effects of octreotide treatment in acromegaly: an echocardiographic study.

Nine acromegalic patients were treated by the somatostatin analogue SMS 201-995 octreotide (Sandostatin (octreotide), Sandoz, Basle, Switzerland] 250 micrograms/day in 4 divided s.c. injections (50 + 50 + 50 + 100 micrograms) for 1 month, 250 micrograms/24 has continuous s.c. infusions for another month and thereafter 200 micrograms three times daily as s.c. injections. Echocardiography was performed before the treatment, following 1 month of octreotide s.c. infusion/injection and after 6 and 12 months of octreotide treatment. No differences in serum growth hormone, heart rate, blood pressure, cardiac contractility or left ventricular wall mass or wall thickness were found between the infusion and the injection periods. As compared to the pretreatment levels serum growth hormone decreased by 62 and 66% respectively following 6 and 12 months octreotide treatment. The heart rate per minute (+/- SD) decreased from the pretreatment level of 75 +/- 12 to 63 +/- 13 (P less than 0.007) at month 12. The systolic and the diastolic blood pressure decreased from the pretreatment level of 121 +/- 8 and 79 +/- 5 mmHg respectively to 108 +/- 7 (P less than 0.0007) and 71 +/- 7 mmHg (P less than 0.0001) respectively at month 12.(ABSTRACT TRUNCATED AT 250 WORDS)

Acromegaly↗
PubMed1989

Effects of growth hormone therapy on thyroid function of growth hormone-deficient adults with and without concomitant thyroxine-substituted central hypothyroidism.

Administration of human GH to GH-deficient patients has yielded conflicting results concerning its impact on thyroid function, ranging from increased resting metabolic rate to induction of hypothyroidism. However, most studies have been casuistic or uncontrolled and have used pituitary-derived GH of varying purity, often contaminated with TSH. Therefore, we conducted a double blind, placebo-controlled cross-over study of the effect of 4 months of biosynthetic human GH therapy (Norditropin; 2 IU/m2.day) on thyroid function in GH-deficient adults (8 females and 14 males; mean +/- SE age, 23.8 +/- 1.2 yr). One group (I) was euthyroid without T4 substitution (n = 13), whereas the other (group II) received T4 (n = 9). Serum T4 (nanomoles per L) decreased in both groups after GH treatment [group I, 100 +/- 8 (mean +/- SE) vs. 89 +/- 8 (P less than 0.01); group II, 145 +/- 18 vs. 115 +/- 10 (P less than 0.05)]. Conversely, GH treatment caused an increase in serum T3 (nanomoles per L) in both groups [group I, 1.9 +/- 0.1 vs. 2.0 +/- 0.1 (P less than 0.1); group II, 1.7 +/- 0.1 vs. 1.9 +/- 0.1 (P less than 0.05)]. Similar changes were seen in serum free T4 and T3. The serum T3 level during the placebo period of group I was significantly lower than that in an age-matched reference group (P less than 0.02). Serum rT3 (nanomoles per L) was low in group I and decreased significantly, as in group II, after GH treatment [group I, 0.26 +/- 0.02 (placebo) vs. 0.20 +/- 0.02 (GH; P less than 0.01); group II, 0.38 +/- 0.05 (placebo) vs. 0.29 +/- 0.02 (GH; P less than 0.01)]. Serum TSH decreased in both groups during GH therapy, though not significantly. Serum thyroglobulin was unaltered and did not differ from that in the reference group. In conclusion, our data are consistent with a GH-induced enhancement of peripheral deiodination of T4 to T3. GH thus seems to play an important role, either directly or indirectly, in the regulation of peripheral T4 metabolism.

Adult↗
PubMed1988

A hyperkinetic heart in uncomplicated active acromegaly. Explanation of hypertension in acromegalic patients?

Cardiac function was studied by echocardiography in 12 patients with active acromegaly and in 12 age- and sex-matched healthy control subjects. None of the patients had cardiovascular diseases or other endocrine diseases than acromegaly. The patients had a mean age of 39 +/- 5 years and were short-term acromegalic with a mean duration of disease of 6 +/- 3 years. Mean left ventricular mass was 163 +/- 43 g/m2 in the acromegalic group versus 120 +/- 24 g/m2 in the control group. Preload (the diastolic diameter of the left ventricle) was within normal limits, while afterload (end-systolic meridional wall stress) was significantly decreased in the acromegalic group. Myocardial contractility assessed as fractional shortening of the left ventricle was 39.9 +/- 3.6% in the acromegalic group versus 32.9 +/- 5.1% in the control group, and cardiac output was increased by 52% in the acromegalic group because of increased heart rate and stroke volume. We suggest that augmented peripheral blood flow is responsible for the condition of cardiac hyperkinesia in short-term acromegaly and involved in the development of hypertension, which is a frequent complication of long-term acromegaly.

Acromegaly↗
PubMed1988

Characterization of the insulin resistance of glucose utilization in adipocytes from patients with hyper- and hypothyroidism.

UNLABELLED: Insulin action on glucose utilization was characterized in adipocytes from 10 thyrotoxic patients, 6 hypothyroid patients and 10 age- and sex-matched control subjects. In thyrotoxic patients insulin binding at low insulin concentrations was reduced (P less than 0.05) and accompanied by impaired insulin sensitivity of glucose transport (P less than 0.02), glucose oxidation (P less than 0.05) and lipogenesis (P less than 0.05). Glucose transport and glucose oxidation rates also exhibited depressed maximal insulin responsiveness (P less than 0.05). In hypothyroid patients insulin binding was reduced, too, (P less than 0.05) and associated with impaired sensitivity to insulin of glucose transport (P less than 0.05). Both glucose transport and lipogenesis rates showed decreased maximal insulin responsiveness (P less than 0.05). IN CONCLUSION: In man, both hyper- and hypothyroidism are characterized by insulin resistance of adipocyte glucose utilization localized to insulin binding as well as to insulin-stimulated glucose transport and metabolism.

Adipose Tissue↗
PubMed1987

Continuous subcutaneous pump infusion of somatostatin analogue SMS 201-995 versus subcutaneous injection schedule in acromegalic patients.

Diurnal serum GH patterns were determined in 10 acromegalic patients before treatment, after 3 d continuous s.c. pump infusion and then after 3 d with three equal daily s.c. injections in both instances totalling 100 micrograms/24 h. Subcutaneous injections (33 micrograms) induced impressive suppression of serum GH lasting 3-6 h in eight patients followed by escape to pretreatment values before the next injection. In contrast, continuous infusion resulted in greater and more stable 24 h suppression to the levels reached at the nadir between injections. Suppression of mean 24 h serum GH below 5 ng/ml was achieved by pump treatment in four patients, while two patients had mean values between 5 ng/ml and 10 ng/ml. In four patients occasional or all levels were above 10 ng/ml (24 h average 12.4-102 ng/ml) implying either that adequate suppression by the SMS 201-995, was impossible during the 3 d pump infusion period, or that the dose administered was inadequate. Carbohydrate tolerance was unaffected in either regimen, indicating that reduction in insulin antagonistic hormones balanced inhibition of insulin release. Interestingly, and in contrast to somatostatin, SMS 201-995 did not inhibit TSH release. No untoward effects were observed at the moderate dosage and blood clinical chemistry was unchanged. Fairly constant diurnal serum SMS 201-995 values were obtained during pump infusion, while levels undulated inversely with serum GH during injection treatment. Average diurnal serum somatostatin-C immunoreactivity (all patients) decreased from 496 +/- 129 (mean +/- SD) to 385 +/- 100 ng/ml (P less than 0.003) during pump treatment and did not decrease further during the following 3 d injection treatment (363 +/- 76 ng/ml). The normal adult mean is 179 +/- 40 ng/ml. Computer tomographic (CT) scans of the sellar region were performed in all patients before and after the experimental week. Two patients had extracellular tumours whose size decreased from 8.2 to 4.1 cm3 and from 12.6 to 10.5 cm3. The results demonstrate that superior and stable suppression of GH secretion is obtained during continuous s.c. pump infusion of SMS 201-995.

Acromegaly↗
PubMed1987

Plasma growth hormone in acromegalic patients. Demonstration of highly reproducible diurnal profiles in individual patients.

The effects of the selective alpha 2-adrenoreceptor antagonist idazoxan on diurnal variations in plasma growth hormone levels were studied in acromegalic patients. Seven patients entered the study; six patients had been unsuccessfully treated with either pituitary adenotomy, bromocriptine or other drug therapy or a combination of the two procedures. Plasma growth hormone levels were measured at hourly intervals over a period of 24 h under control conditions and following 4 days treatment with either placebo or idazoxan (20 mg po, three times a day); the comparison of idazoxan with placebo was a double blind cross-over study. Except in one patient, the diurnal growth hormone plasma profiles were virtually superimposable under control conditions and following either placebo or idazoxan; each patient had a characteristic profile. Four patients had impressive nocturnal elevations ranging from about 40 to 200 per cent above average daytime levels. Only one had definite paradoxical early postprandial peaks. These observations are contrary to accepted views on growth hormone levels in acromegalic patients. The majority of our patients thus had profiles reminiscent of the normal diurnal plasma growth hormone pattern albeit at a higher level indicating some preserved central drive. The rather high prevalence in the present study of patients having relapses after adenomectomy may indicate that a selection had been made of cases with hypothalamic aetiology. Administration of the selective alpha 2-adrenoreceptor antagonist idazoxan did not modify plasma growth hormone profiles in these patients.

Acromegaly↗
PubMed1986

Goitre size and outcome of medical treatment of Graves' disease.

One hundred and twenty-four patients with newly diagnosed hyperthyroidism received a combined thionamid-thyroxine medical therapy for approximately 2 years. According to the estimated goitre size before therapy and the type of goitre the patients were divided into 4 groups: Graves' disease no goitre (n = 19), Graves' disease small goitre (n = 57), Graves' disease medium or large goitre (n = 23), multinodular goitre (n = 25). The median follow-up period after cessation of medication was 64 (range 11-141) months. The remission rates in the different groups during follow-up were calculated using life table analysis. Graves' patients with no goitre or a small goitre had a significantly better outcome (remission % after 5 years 82.5 +/- 15.4 (SE) and 71.5 +/- 7.8, respectively) than Graves' patients with a medium size or large goitre (remission % after 5 years 37.0 +/- 11.1)(P less than 0.025). Most patients with multinodular goitre had a relapse within the first year after stop of medication (remission % after 5 years 15.5 +/- 10.1). Hence patients with Graves' disease having a small thyroid gland should be treated medically while surgery or radioiodine may be a more reasonable choice in Graves' patients with medium size or large goitres. Medically treated patients with toxic multinodular goitres have a very small chance of prolonged remission if medication is stopped.

Adult↗
PubMed1986

Ultrafiltration method for direct radioimmunoassay measurement of free thyroxine and free tri-iodothyronine in serum.

Ultrafiltration at physiological pH and temperature of undiluted serum followed by direct radioimmunological determination of T3 and T4 in the protein-free ultrafiltrate offers the best possible approach towards estimation of in vitro plasma levels of free T3 and free T4. The major technical difficulties in meeting this apparently simple proposition are: establishing adequately sensitive radioimmunoassays; avoidance of adhesion to ultrafilters and glassware; removal from the ultrafilters of compounds which would cross-react or interfere in the radioimmunoassays; and avoidance of co-filtration of thyroid hormone binding proteins in serum, which would obviously imply spurious data. This methodological study describes the magnitude and significance of each of these obstacles and how to circumvent them. Practically all other available methods, including equilibrium dialysis, imply dilution of serum samples with buffer often leading to alterations in ionic composition to which thyroid hormone binding to proteins is peculiarly sensitive. Dilution itself alters the fraction of free thyroid hormones in serum especially when pharmaca or compounds are present which compete for the binding sites. These pitfalls are avoided in ultrafiltration of undiluted serum. This is illustrated through measurements on serum containing therapeutic concentrations of Fenclofenac which was found to displace 120% more T4 in undiluted than in diluted (1:28) serum. Using the described technique FT3 was 8.8 +/- 1.7 pmol/l and FT4 30.8 +/- 8.2 (SD) pmol/l in serum from 29 normal subjects. Pregnant women in their third trimester had lower levels: FT3 7.1 +/- 2.1 and FT4 17.6 +/- 5.8 pmol/l (SD, n = 24).

Female↗
PubMed1985

A comparison of the effects of propylthiouracil and methimazol on circulating thyroid hormones and various measures of peripheral thyroid hormone effects in thyrotoxic patients.

Two groups of patients with newly diagnosed thyrotoxicosis were treated with propylthiouracil (PTU) 400 mg every 6 h for 4 days followed by methimazol (MMI) 40 mg every 6 h for 4 days or by MMI for 4 days followed by PTU for 4 days. The shift from MMI to PTU induced a considerable decrease in serum T3 while shift from PTU to MMI led to an increase in serum T3. Serum T4 decreased gradually during the whole treatment period. The opposite variations in serum T3 were accompanied by similar opposite variations in basal metabolic rate (BMR) (P less than 0.001). Hence the rapid variations in serum T3 which can be induced by PTU in thyrotoxic patients, are followed by rapid alterations in the thyrotoxic state as evaluated by BMR.

Achilles Tendon↗
PubMed1985

Evaluation of pituitary-adrenal function after pituitary surgery.

A short overnight metyrapone test and a 30-min ACTH test were performed in ten patients after pituitary surgery. At the initial testing 2 weeks after surgery the 30-min ACTH test was abnormal in two patients while normal increases in s-cortisol were observed in eight patients. These eight patients also had normal responses to ACTH when re-tested after 6-19 months. The short metyrapone test was a much more sensitive indicator of functional disturbances in pituitary/adrenal function. Two weeks after surgery the test was abnormal in seven of the patients. After 6-19 months some normalization of the short metyrapone test had occurred, probably due to disappearance of postoperative oedema and haematoma. However, the test was still abnormal in three patients having normal responses during the 30-min ACTH test. It is suggested that both tests are performed in such patients to specify a high risk group, i.e. both tests abnormal, and a low risk group with a normal 30-min ACTH test but subnormal responses during the short metyrapone test. This would be of help in the decision on cortisol supplementation and offer a high degree of safety for the patients.

17-alpha-Hydroxyprogesterone↗
PubMed1984

Changes in blood chemistry in hypertensive patients during propranolol therapy.

Propranolol induced changes in blood plasma chemistry were followed in thirty hypertensive patients (WHO I-II) who were seen each week during 14-15 weeks. The initial 4 weeks were a drug free period and the next 2 weeks were a drug adjustment period. After that the patients were on an unchanged propranolol dose for 8 weeks (40, 80 or 160 mg four times daily). For all observed changes the correlation was studied to (1) dose, (2) free and total simultaneously determined plasma concentration and (3) free and total average plasma concentration of unchanged drug during the preceding 24 h period. Total protein and albumin did not change significantly. After 4 and 8 weeks on the final dose orosomucoid was increased significantly (by 10%) compared with the value from the end of the drug free period. Creatinine rose significantly during the initial 4-6 weeks therapy to remain at the same level during the last 4 weeks. Urate was increased at the two lowest dose levels. Total cholesterol fell significantly (5%) while triglycerides increased significantly (16%). T4 rose significantly, T3 fell and r-T3 rose significantly in a dose dependent way. Interindividually r-T3 was the only biochemical change showing a significant relationship to the propranolol plasma concentration. The relationship reached the highest level of significance to the average 24 h free concentration.

Adult↗
PubMed1984

TRH immunoreactivity in the thyroid gland.

Methanol extracts of dog and pig thyroid tissue contained considerable amounts of thyrotropin releasing hormone immunoreactivity (iTRH): 2.98 +/- 1.38 and 1.83 +/- 0.58 pmol/g thyroid wet weight, respectively (mean +/- SD). This iTRH was not due to ether extractable materials and behaved like TRH standard in dilution experiments, during gel filtration on Sephadex G-25 and during thin layer chromatography on a silica gel plate. Cation exchange chromatography on SP-Sephadex C-25 revealed that the iTRH in methanol extract was heterogeneous. However, part of the iTRH applied on the column was eluted as synthetic TRH: 0.209 +/- 0.046 and 0.052 +/- 0.021 pmol/g dog and pig thyroid, respectively. During incubation with rat serum, the SP-Sephadex purified iTRH disappeared in parallel with TRH. These studies indicate that the thyroid contains small amounts of iTRH which behaves identically to synthetic TRH.

Animals↗
PubMed1983

Fenclofenac-secondary effects upon the pituitary thyroid axis.

To elucidate the mechanism of suppression of TSH responsiveness to TRH induced by the initiation of fenclofenac therapy, the early period of drug administration was examined in detail and the effect of the drug during a thyrotrophin releasing hormone infusion was assessed. In addition, the effect of fenclofenac upon the response of ACTH, cortisol, growth hormone and prolactin to insulin-induced hypoglycaemia was examined. The effect of fenclofenac upon an equilibrium dialysis method for estimating free thyroid hormones was evaluated and was found to be insignificant within the therapeutic concentration range of the drug. A sharp, short-lived rise in free thyroxine (21.7 +/- 2.0 to 26.8 +/- 1.9 pmol/l; P less than 0.03) was observed 60 min after the first dose of fenclofenac. Repeated peaks of free thyroxine during chronic fenclofenac treatment, superimposed upon the previously described steady decline of free and total serum thyroxine, are postulated to cause the observed suppression of TSH release which is present only until free and total serum thyroxine levels reach their nadir. The time course of the changes seen during thyrotrophin releasing hormone infusion suggested that the pituitary suppression was secondary to a rise in free thyroxine. The responses to hypoglycaemia of those pituitary hormones examined were not affected by fenclofenac.

Adult↗
PubMed1983

The effect of heating and central cooling on serum TSH, GH, and norepinephrine in resting normal man.

The effects of central cooling and exterior heating on serum concentrations of thyrotropin (TSH), growth hormone (GH), and norepinephrine were studied in 10 normal males under resting conditions. Cooling was induced by ingestion of ice while the subjects were immersed in water of a temperature prone to elicit only minor cutaneous thermal reflexes. TSH and thyroid hormones changed neither during cooling nor during heating. Cooling induced a virtually complete suppression of GH-secretion whereas heating had the opposite effect: pronounced increase, also without previous cooling. Plasma norepinephrine rose by a factor of 2.5 and 1.7 during cooling and heating, respectively. It is concluded that the pituitary-thyroid system does not take part in short-term thermoregulation in man--as opposed to the situation in some smaller mammals. The mechanisms and the physiological role of the GH-responses to cooling and heating are as yet unknown, but the latter stimulus is an advantageous tool in clinical and pathophysiological studies of pituitary function as it is both safe and convenient.

Adult↗
PubMed1982

A longitudinal study of serum TSH, and total and free iodothyronines during normal pregnancy.

Serum T4, T3, rT3, free T4, free T3 and TSH were measured during and after normal pregnancy in 20 women. Special methodological precautions were taken to avoid interference of other hormones and protein alterations in the assays. Serum T4 and T3 were steadily increasing during the last part of the 1st trimester, and remained high and nearly stable during the 2nd and 3rd trimester of the gestation period. The high levels were approximately 1.5 times the values measured 10 weeks post-partum. Serum rT3 was elevated already during the last part of the 1st trimester and remained high throughout pregnancy, compared to the post-partum value. Serum free T4 and free T3 were slightly elevated in early pregnancy. The values decreased gradually during pregnancy and were slightly depressed during the 3rd trimester. A gradual increase in serum TSH was observed during pregnancy and the 2nd and 3rd trimester values were significantly higher than the post-partum value. The mean values for serum TSH, free T4 and free T3 remained always well within the normal range. Thus small variations in serum free iodothyronines and TSH occur during normal pregnancy, the alterations observed in the last trimester of the gestation period resembling those of a slight thyroid insufficiency. These trends in variation of the reference values are worth to remember in the diagnosis of borderline hypo- or hyperthyroidism and in the balanced treatment of pregnant women with thyroid dysfunction.

Adult↗
PubMed1981

Dynamics of inhibition of iodothyronine deiodination during propylthiouracil treatment of thyrotoxicosis.

Serum 3,3',5'-triiodothyronine (rT3), 3,5,3'-triiodothyronine (T3), thyroxine (T4) and propylthiouracil (PTU) were measured before and at short intervals for 8 hours after oral administration of 200 mg PTU to six patients with untreated thyrotoxicosis. The study was repeated on the 4th day of treatment with 200 mg PTU every 8 hours. Six other patients with untreated thyrotoxicosis were studied after a single administration of 800 mg PTU. The results indicated that PTU inhibition of T4 deiodination to T3, evaluated by the fall in serum T3, was of the same duration as the PTU inhibition of rT3 deiodination, evaluated by the increase in serum rT3. After 200 mg PTU inhibition was maximal for only a few hours, and there was no cumulative effect of PTU during the first four days of treatment, when 200 mg PTU was given every 8 hours. After 800 mg PTU the full effect was maintained for the 9 hour period studied, after which serum T3 had fallen to 65 +/- 2% of the pretreatment level (mean +/- SE). Thus, to obtain a permanent full effect of PTU on iodothyronine deiodination during the treatment of thyrotoxicosis it is necessary to use large doses or frequent administration.

Adult↗