Endocrinological evaluation of sellar and suprasellar tumor cases (the sixth report)-on pituitary hormone secretion of acromegalic patients before treatment (author's transl)

1) Pituitary hormone secretion of 14 acromegalic patients was studied before treatment. Incidence of hyporeactive response was 0%, 43%, 29%, 71% and 9% in ACTH, LH, FSH, TSH and PRL respectively. 2) Relatively higher incidence of hyporeactive TSH response in TRH test seems to be characteristic in acromegalic patients. 3) Six of 13 acromegalic patients examined on blood PRL level revealed relatively high blood PRL level over 50ng/ml.     

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In 1985, Losa et al reported that an i.v. bolus injection of GH-releasing hormone (GHRH) was able to paradoxically stimulate PRL secretion in more than half of their acromegalic patients. However, this observation was not generally accepted since several other investigators have concluded that such an anomalous PRL response to GHRH was an extremely rare phenomenon in acromegaly. Therefore, in this study we examined a large number (51 patients) of active acromegalics in order to obtain more reliable data on the incidence of the paradoxical PRL response to GHRH in this disorder. Each patient underwent i.v. bolus injections of GHRH (100 micrograms) and thyrotropin-releasing hormone (TRH, 500 micrograms) on separate days, and plasma levels of GH and PRL were measured. The plasma PRL response to GHRH was considered positive (a paradoxical increase) when an increase over baseline of at least 50% occurred. We found that only 6 patients (12%) showed a positive PRL response to GHRH. These PRL-responders to GHRH had higher GH responses to this peptide than PRL-non-responders to GHRH. Although PRL-responders and non-responders to GHRH had a similar PRL responsiveness to TRH, the GH response to TRH was lower in PRL-responders to GHRH than PRL-non-responders to this peptide. In addition, PRL-non-responders to GHRH had lower basal GH and higher basal PRL levels than PRL-responders to GHRH.(ABSTRACT TRUNCATED AT 250 WORDS)     

Insulin-like growth factor-I in growth hormone-deficient adults: relationship to population-based normal values, body composition and insulin tolerance test

BACKGROUND: Although an insulin tolerance test (ITT) is the most commonly used method for detecting growth hormone (GH) deficiency (GHD) in adults, measurements of serum insulin-like growth factor-I (IGF-I) may also be of value. OBJECTIVE: To validate the use of serum IGF-I concentration in the diagnosis of GHD in adults. DESIGN: A cross-sectional study. PATIENTS: One hundred and four patients, 60 men and 44 women, with known pituitary disease and verified GHD based on ITT. MEASUREMENTS: Serum IGF-I was determined by radioimmunoassay after acid-ethanol extraction. Body composition was estimated with total body potassium combined with total body water assessments. RESULTS: According to age- and sex-adjusted population-based references values, 51 patients had serum IGF-I concentrations below -2 SD of the predicted values and 53 had concentrations within 2 SD. Fifty-seven per cent of the patients aged 41 years (25th percentile) or below and 39% of the patients aged 57 years (75th percentile) or above had serum IGF-I concentrations below -2 SD. Women had lower mean IGF-I SD scores than men (P < 0.01). Serum IGF-I was correlated with peak GH response during ITT (r = 0.40; P < 0.001), age (r = -0.27; P < 0.01), duration of hypopituitarism (r = -0.52; P < 0.001), number of pituitary hormonal deficiencies (r = -0.35; P < 0.001), body cell mass (r = 0.30; P < 0.01) and serum insulin (r = 0.21; P < 0.05). The peak GH response during ITT correlated with spontaneous GH secretion, duration (P = -0.48; P < 0.001) and number of deficiencies (r = -0.50; P 0.001). CONCLUSION: The measurement of serum IGF-I concentrations is not suitable as a single diagnostic test for growth hormone deficiency in adults. Even as a screening test, its use appears to be limited, especially in elderly subjects. The serum level of IGF-I was influenced by several factors in addition to GH, such as age, gender, anthropodometry and serum insulin level. The peak GH response during the insulin tolerance test appears to be influenced to a lesser degree by these factors.     

Factors determining the long-term outcome of surgery for acromegaly

Seventy-nine patients with acromegaly were investigated before and after transsphenoidal adenomectomy, to determine the immediate and late outcome, the pre-operative features associated with a good result, and the accuracy of post-operative testing in predicting outcome. Pre-operative evaluation included basal growth hormone (GH), GH response to oral glucose tolerance test (OGTT), GH response to thyrotrophin-releasing hormone (TRH), tests of pituitary reserve, and pituitary scanning to assess tumour size. A few weeks after surgery, these tests were repeated. The patients were recalled for late assessment 1-13 years (median 86 months) after the operation. At the immediate postoperative testing, minimum GH after oral glucose was < or = 2 mU/l in 48.7%, < 5 mU/l in 76.3% and < 10 mU/l in 84.2%. Only 12 patients had GH > 10 mU/l. Basal GH was < or = 2 mU/l in 21%, < 5 in 59.2%, < 10 in 73.6% and < 20 in 90.8%. A minimum GH of < or = 2 mU/l during an OGTT was achieved in 67.4% of patients with intrasellar tumours, compared with 27.3% with extrasellar tumours. Basal GH and post-glucose GH correlated with the late outcome. GH response to TRH showed no correlation with outcome. IGF-1, which could not be assessed in detail, correlated with GH but was not a reliable indicator of outcome. Transsphenoidal adenomectomy is thus a very satisfactory treatment for acromegaly. Postoperative levels of basal growth hormone < 5 mU/l and post-glucose GH < or = 2 mU/l can be regarded as a biochemical cure. Postoperative radiotherapy is not required in patients who achieve a good result. The preoperative factors which significantly influenced the final outcome were basal GH, post-glucose minimum GH, tumour size and impaired pituitary reserve.     

Delusions and hallucinations in patients with borderline personality disorder

OBJECTIVE: Heat exposure has been shown to stimulate GH release, but the specificity and the reproducibility have not been determined, and the test has not been compared with validated GH stimulation tests in adulthood. We therefore tested the specificity and the reproducibility of the heat exposure test in healthy subjects and compared the results with those obtained with the insulin-tolerance test (ITT). DESIGN: Ten healthy non-obese men, aged 31.3+/-4.80 years, underwent four GH stimulation tests in random order: two ITTs and two heat exposure tests. In the heat test, subjects were placed in a hot bath with water temperature at 40.3+/-0.11 degrees C for 45 min, resulting in an identical (P = 0.477) significant increase in tympanic temperature of 1.26+/-0.05 and 1.41+/-0.07 degrees C in the two tests. RESULTS: Peak GH response to the heat exposure test was less than the peak GH response to ITT (5.25+/-1.72 vs 15.5+/-3.17 microg/l, P = 0.006). Furthermore the specificity (arbitrary cut-off level = 3 microg/l) of the heat test was lower than of the ITT (8/17 vs 18/20, P = 0.006). The coefficient of variation did not differ between the two tests (heat test 0.31, ITT 0.36, P = 0.77). Peak GH values in the individual tests were highly correlated (heat, r = 0.908, P = 0.002; ITT, r = 0.815, P = 0.004). Reproducible increments in the circulating levels of stress hormones were observed during ITT. but these hormones remained largely unchanged during heat exposure. CONCLUSIONS: The heat exposure test is not a reliable GH stimulation test compared with the ITT in adults. This study documents that the ITT has a high specificity and reproducibility in the diagnosis of GH deficiency in adulthood. We propose that the heat exposure test is not used in the diagnosis of this condition in adulthood.     

Studies on the TRH test on the patients with Graves' disease during the treatment with antithyroid drug (author's transl)

A study was performed to observe serum TSH response following TRH injection (TRH test) in 79 cases of Graves' disease (male 23, female 56, aged 16-70 years old), before and during treatment by antithyroid drug, in a total of 244 occasions. Treatment was mostly the daily administration of methyl-mercaptoimidazole (MMI), and in one case of propylthiouracil (PTU). TRH test was conducted by i.v. administration of 500 mug synthetic TRH, and subsequent 6 blood drawing until 2 hours. Serum TSH was measured by radioimmunoassay in each serum, and serum T4, T3, RT3U and cholestrol were measured in the serum before TRH injection. In some cases, the results of TRH test were compared with those of T3 131I thyroidal uptake suppression test, using the 131I uptake values at 20 min. and 24 hours. Results were obtained as follows: 1) Some cases showed positive TRH test at the early stage of treatment when the patients were in eumetabolic states, while many patients showed no TSH response in spite of their long maintenance at eumetabolic states. 2) When both serum T4 and T3 were high, all cases showed no response of TSH. When serum T4 alone was high, all cases except one case showed no response;whereas when serum T3 alone was high, 5 cases showed normal response. When both serum T4 and T3 were below normal, 2 cases showed no response. When serum T4 was low, all cases showed response; whereas when serum T3 alone was low, 6 cases showed no response. Thus, there was no positive correlation between TSH reactivity and serum concentrations of thyroid hormones. 3) No correlation was observed between TSH reactivity and the period after the onset of hyperthyroidism. 4) In 57 cases of Graves' disease, who were under treatment and in eumetabolic states, a comparison was made between TSH reactivity and the results of T3 suppression test. In T3 suppressed group, 19 showed response, and 3 showed no response; whereas in T3 non-suppressed group, 18 showed response and 17 showed no response. In the group of T3 non-suppression as well as in the group of T3 non-suppression plus TRH no response, there was a significant elevation of serum T3 compared with the control group. 5) TRH test does not appear to be an appropriate test as a predictive method to know the permanent remission of Graves' disease.     

A case of traumatic pseudoaneurysm of the middle meningeal artery treated with endovascular surgery

Thyrotropin-releasing hormone (TRH) has been found in the gastrointestinal tract, where it mainly exerts an inhibitory action. We used oral TRH, a stable and powerful formulation, to explore the glucoregulatory response of oral glucose tolerance test (OGTT) on obese patients with impaired glucose tolerance (IGT). Seven obese patients with IGT and eight controls were investigated. Three tests were performed on three separate days. On day 1, An oral TRH test: a 40 mg TRH tablet, was given. Blood samples for blood glucose (BG), proinsulin (PI), insulin (INS), C-peptide (CP), thyroxine (T4), triiodothyronine (T3), and thyrotropin (TSH) were collected every 30 minutes for 3 hours. On day 2, an OGTT with 75 g glucose was performed. On day 3, an oral TRH test was administered 30 minutes before the OGTT, and blood was collected every 30 minutes for 3 hours. Oral-TRH had no effect on basal BG and on pancreatic hormone secretion. Oral TRH, coupled with OGTT in both controls and obese patients, led to a significant inhibition of BG (p < 0.01), of CP (p < 0.001), and of INS (p < 0.001) during the first hour of administration, and afterward, there was only a very slight increase, compared with levels after only OGTT treatment. After OGTT, PI peaked at 90 minutes (9.4+/-3 ng/mL) in controls and at 60 minutes (12.7+/-2.5 ng/mL) in obese patients. TRH application prior to OGTT inhibited PI secretion for 90 minutes in controls, whereas in obese patients PI levels were decreased, not inhibited, during the OGTT. The mechanism of the inhibitory TRH action on OGTT-induced increase of BG and pancreatic hormone secretion is not clear. It could be due to inhibition of gastric motility, and on a paracrine effect that enhances secretion of somatostatin that then suppresses INS, CP, and possibly PI levels. The partial escape of PI from the TRH blockade in obese patients with IGT might indicate a diminished functioning capability of beta-cells and that TRH cannot affect the INS processing within the beta-cells in these patients.     

Serum concentrations of thyroid hormones during egg laying in two types of Japanese quail (Coturnix coturnix japonica)

In the present investigation a lighter white egg-type (L) and a heavier wild meat-type (M) of female Japanese quails were compared with respect to egg production, body growth, abdominal fat pad, serum thyroxine (T4) and triiodothyronine (T3) concentrations, TRH sensitivity and T4 5'-monodeiodinase activity in liver homogenates. During the investigation period L type layed considerably more eggs and M type was heavier in body weight. Abdominal fat pad in L type quails was significantly higher than in M type ones. L type quails had lower serum T4 and T3 concentrations than M type ones and the liver T4 5'-monodeiodinase activity was higher in M type than in L type quails. Following TRH administration serum T4 and T3 concentrations increase was higher in L type quails than in M type ones. Our results suggest that lower T4 and T3 observed in L type quails reflect a possible metabolic adaptation to egg production. Different activities of 5'-monodeiodinase and of response to TRH may be inherent to these two types of quail.     

Effect of endothelin-1 in man--impact on basal and stimulated concentrations of luteinizing hormone, follicle-stimulating hormone, thyrotropin, growth hormone, corticotropin, and prolactin

The effect of endothelin-1 on basal and stimulated serum (plasma) concentrations of luteinizing hormone (LH), follicle-stimulating hormone (FSH), thyrotropin (TSH), prolactin (PRL), growth hormone (GH), and corticotropin was investigated in healthy male volunteers (n = 5). Intravenous (IV) administration of endothelin-1 (5 ng/kg/min for 15 minutes, followed by 2.5 ng/kg/min for 105 minutes) induced an increase in basal plasma concentrations of corticotropin. Serum concentrations of PRL, TSH, LH, FSH, and GH remained unchanged. The increase in serum concentrations of these pituitary hormones induced by IV administration of LH-releasing hormone ([LH-RH] 100 micrograms), thyrotropin RH ([TRH] 400 micrograms), GH-RH (100 micrograms), and corticotropin-releasing factor ([CRF] 100 micrograms) was suppressed in regard to PRL (P < .01) and GH (P < .01) and enhanced in regard to corticotropin (P < .01). Stimulated serum concentrations of LH and FSH also tended to be higher following administration of endothelin-1 (P < .05), whereas the increase in serum concentrations of TSH remained unchanged. Thus, when administered in pharmacological doses, endothelin-1 influences pituitary hormone secretion in man.     

Effects of growth hormone secretagogues on prolactin release in anesthetized dwarf (dw/dw) rats

In addition to stimulating GH release, GH secretagogues such as GH-releasing peptide-6 (GHRP-6) stimulate small amounts of ACTH and PRL release. Although the effects on ACTH have recently been studied, there is little information about the effects of GHRP-6 on PRL. We have now studied GHRP-6-induced GH and PRL release and their regulation by estrogen (E2) in anesthetized male and female rats and in GH-deficient dwarf (dw/dw) rats that maintain high pituitary PRL stores and show elevated hypothalamic GH secretagogue receptor expression. Whereas GHRP-6 (0.1-2.5 microg, i.v.) did not induce PRL release in normal male or female rats, significant PRL responses were observed in dw/dw females. These responses were abolished by ovariectomy and could be strongly induced in male dw/dw rats by E2 treatment. These effects could be dissociated from GHRP-6-induced GH release in the same animals, but not from PRL release induced by TRH, which was also abolished by ovariectomy and induced in males by E2 treatment. However, the effects of GHRP-6 on PRL were unlikely to be mediated by TRH because in the same animals, TSH levels were unaffected by GHRP-6 whereas they were increased by TRH. The increased PRL response could reflect an increase in GH secretagogue receptor expression that was observed in the arcuate and ventromedial nuclei of E2-treated rats. Our results suggest that the minimal PRL-releasing activity of GHRP-6 in normal rats becomes prominent in GH-deficient female dw/dw rats and is probably exerted directly at the pituitary; these GHRP-6 actions may be modulated by E2 at both hypothalamic and pituitary sites.     

Tumor-related arthrodesis. Reconstruction of the shoulder contour using a free TRAM (Transverse Rectus Abdominis Musculocutaneous) flap]

We evaluated growth hormone binding protein (GHBP) activity in a group of obese children (12 boys and 12 girls, age 3.1-14.7 years, BMI 21.1-33.3, 11 prepubertal and 13 early pubertal) and in 26 age-matched normal weight children (14 boys and 12 girls, age 2.1-16.0 years, BMI 14.2-21.4, 18 prepubertal and 8 early pubertal). All children were of normal stature. GHBP activity was significantly higher in the obese (39.1 +/- 1.1%) than in the control children (28.3 +/- 1.0%, p < 0.0001). Mean serum GHBP was not different between boys and girls or between prepubertal and pubertal subjects. A positive correlation was found between BMI and GHBP levels only in the normal weight children (r = 0.425, p < 0.05). Baseline insulin concentrations in the obese children were 97.6 +/- 7.9 pmol/l (normal values, 45.0 +/- 18.6 pmol/l), and the mean insulin AUC following OGTT in the obese was 811.3 +/- 160.7 pmol/l (normal values, 373.1 +/- 150.1 pmol/l). Serum GHBP activity in the obese was not correlated with baseline serum insulin concentrations or with the insulin AUC following OGTT. In conclusion, we found that obese children have elevated GHBP activity, and speculate that this phenomenon may serve to compensate for their reduced GH secretion and accelerated GH clearance.     

Hypothalamic dysfunction in "cured" acromegaly is treatment modality dependent

The current definition of cure after treatment for acromegaly stipulates a reduction in GH levels to less than 2 ng/mL (< 5 mU/L), as such GH concentrations are believed to be associated with normalization of long term survival. We sought to further define the nature of the cure in such patients, when cure has been achieved by alternative therapeutic modalities, in the expectation that hypothalamic neuroregulatory control of GH secretion might be affected differently by radiotherapy or surgery. In particular we wished to determine the effect of therapy modality on endogenous somatostatin (SMS) tone, using the GH response to i.v. arginine as a paradigm. We studied 20 patients with cured acromegaly (mean 24-h GH concentration, < 2 ng/mL). Eight patients had been cured by surgery only (S; 4 women and 4 men; mean +/- SEM age, 52 +/- 5 yr), and 12 patients had been cured by radiotherapy (R; 4 women and 8 men; age, 52 +/- 3 yr). Sixteen healthy subjects were studied as a control group (C; 6 women and 10 men; age 53 +/- 3]. The median (range) GH during 24-h profiles was similar in each group: S, 1.3 (0.7-1.8) ng/mL; R, 0.6 (0.4-1.8) ng/mL; and C, 0.7 (0.4-3.2) ng/mL (P = 0.57). The median incremental GH responses to arginine were significantly lower in the R group compared with those in the S and C groups: S, 6.4 (2.1-16.6) ng/mL; R, 0.1 (0-1.7) ng/mL; and C, 9.2 (0-16.1) ng/mL (P = 0.0002; S vs. R, P < 0.01; S vs. C, P > 0.05; R vs. C, P < 0.001). We conclude that in acromegalic patients deemed to be cured (GH, < 2 ng/mL), the mode of therapy has considerable influence on the remaining hypothalamic-somatotroph function. In view of the putative mechanism by which arginine releases GH, we suggest that radiotherapy leads to a reduction or complete loss of endogenous SMS tone. This may have implications for the treatment of those acromegalic patients who are not cured (GH, > 2 ng/mL) and who require SMS analog therapy.     

Hot water swallows improve symptoms and accelerate esophageal clearance in esophageal motility disorders

The mechanism of action of the synthetic growth hormone (GH)releasing peptide hexarelin is not yet fully understood. Although a direct effect on pituitary cells has been demonstrated, the peptide is also active at hypothalamic level, where specific binding sites have been found. The observation that hexarelin acts synergistically with GH-releasing hormone (GHRH) in releasing GH has suggested that it might suppress endogenous somatostatin secretion. As somatostatin is also inhibitory on TSH secretion, to verify the occurrence of modifications of the somatostatinergic tone induced by hexarelin, we studied its effects on TRH-induced TSH secretion. Seven normal subjects (4 women and 3 men aged 24-29 years) underwent the following tests on 3 different days: a) TRH (200 micrograms/l i.v.) + placebo; b) hexarelin (1 microgram/Kg bw i.v.) + placebo c) combined TRH + hexarelin administration. Hexarelin induced significant and similar increases in serum GH levels when given in combination either with placebo or with TRH (1217 +/- 470 vs 986 +/- 208 micrograms/min/l p:NS), while no modifications of GH levels were seen after TRH + placebo. Serum TSH levels were unmodified by hexarelin + placebo injection. The TSH increase elicited by hexarelin + TRH was superimposable to that elicited by TRH + placebo (1124 +/- 530 and 1273 +/- 380 mU/min/l respectively). Circulating PRL levels slightly increased after hexarelin + placebo too (897 micrograms/min/l), and the PRL response to hexarelin + TRH was slightly, although not significantly, greater than that observed after TRH + placebo (2680 +/- 1517 and 2243 +/- 1108 micrograms/min/l, respectively). In conclusion, our data show that hexarelin does not alter basal and TRH-stimulated TSH secretion, thus suggesting that it does not inhibit somatostatin release. Furthermore a modest PRL-releasing effect of this peptide has been confirmed.     

The effects of chronic ill health and treatment with sulphasalazine on fertility amongst men and women with inflammatory bowel disease in Leicestershire

Our aim was to investigate the effect of GnRH-agonist (GnRH-a) induced suppression of plasma sex steroids on serum GH, insulin like growth factor-I (IGF-I) and insulin levels after an oral glucose load (OGTT) in women with polycystic ovary syndrome (PCOS). Serum insulin, GH and IGF-I levels during a 75-g 4-h OGTT were measured in 3 nonobese and 7 obese hyperandrogenic women with PCOS and normal glucose tolerance before and after 10 weeks of treatment with the GnRH-a triptorelin (3,75 mg im every 28 days). Basal estrogen and androgen levels were also measured at time 0 of the first and the second OGTT. After the therapy serum estrogens and androgens were significantly suppressed. Body weight remained unchanged. Basal GH significantly increased after the treatment while fasting IGF-I and insulin levels decreased from (mean +/- SE) 349.3 +/- 31.8 to 278.7 +/- 33.2 ng/mL and from 22.4 +/- 4.1 to 18.8 +/- 4.4 microU/mL, respectively. The insulin response to OGTT (area under curve) was also reduced (from 16,017 +/- 2598 to 11,736 +/- 2317 microU/mL/240 min). Our results suggest that the GnRH-a induced suppression of ovary secretion may modify the serum GH and IGF-I levels and the insulin response to an OGTT in women with PCOS.     

Normal growth hormone secretory reserve in men with idiopathic osteoporosis and reduced circulating levels of insulin-like growth factor-I

Many men with idiopathic osteoporosis have reduced circulating insulin-like growth factor-I (IGF-I) levels. The major source of circulating IGF-I is GH-mediated production by the liver. The known anabolic effects of GH on the skeleton raised the possibility of GH deficiency in these men. We sought to test this hypothesis in this study. Fourteen men (mean age, 52.1 +/- 3.2 yr, range 31-68) with idiopathic osteoporosis were studied. Mean lumbar spine bone mineral density (BMD) was 0.723 g/cm2, T score -3.5; femoral neck BMD was 0.642 g/cm2, T score, -3.07; distal (1/3) radius BMD was 0.708 g/cm2, T score, -2.05. Eleven of 14 (79%) had frank reductions in serum IGF-I levels compared with age and sex-matched values (158.5 +/- 50 SD vs. 180 +/- 45 SD). GH secretion was stimulated by iv arginine infusion (30 g) over 30 min followed 1 h later by oral L-dopa (500 mg). Serum GH was measured at time (t) = -15, 0, 30, 45, 60, 90, 120, 150, and 180 min. All patients responded to at least one stimulus with the majority (n = 9) responding to both. Five patients responded either to arginine or to L-dopa but not to both. Baseline GH for the entire group was 0.77 + 0.08 ng/mL (SEM). Peak GH following arginine (t = 45-60 min) was 14.0 +/- 2.8 ng/mL, a 17.7 +/- 2.8-fold rise. Peak GH following L-dopa (t = 120-180 min) was 5.7 +/- 1.0 ng/mL, a 9.2 +/- 2.2-fold rise. No difference in maximal secretion was observed between those with low or normal IGF-I levels. Neither IGF-I nor IGF binding protein-3 concentrations changed significantly during the short period of GH stimulation. These data suggest that men with osteoporosis and reduced IGF-I levels do not appear to have a deficiency in the GH axis. Other hormonal or local factors may be important in regulating IGF-I expression. Deficiencies of IGF-I production at skeletal sites may be important in the pathogenesis of this syndrome.     

Bioactivity of human growth hormone in serum: validation of an in vitro bioassay

GH, in clinical practice, is determined by RIA, but RIA estimates may not accurately reflect serum GH bioactivity. The available measures of GH bioactivity lack either sensitivity, specificity, or a physiologically relevant end point. The objective of this research was to develop a physiologically relevant GH bioassay which would not only measure the bioactivity of purified GH preparations, but would also have sufficient sensitivity to measure GH bioactivity in human serum. The method consisted of incubating murine 3T3-F442A adipocytes in serum-free medium containing BSA, 14C-glucose, and increasing concentrations of GH or test materials for 24 h, followed by measurement of conversion of glucose to lipid. Interference by nonspecific serum factors was reduced by the addition of 10 micrograms/liter insulin, 25 nM dexamethasone, and 37 nM estradiol to the medium. In the presence of 10 micrograms/liter insulin, 50 micrograms/liter insulin-like growth factor-1 did not alter the ability of GH to suppress lipid accumulation. Epinephrine and glucagon could suppress lipid accumulation but only at concentrations greatly in excess of the physiological range in serum. Twenty two thousand dalton hGH produced dose-dependent suppression of lipid accumulation which was linear between 0.625 and 10 micrograms/liter (r = 0.926; P = 0.0001) with a half-maximal response of 3.0 +/- 0.2 micrograms/liter (n = six experiments). The intra- and interassay coefficients of variation were 7% and 19%, respectively. The assay was specific for GH since addition of human PRL produced suppression of lipid accumulation only at concentrations where contamination of the preparation by GH became a significant factor. ACTH also suppressed lipid accumulation but only at doses of 1000 micrograms/liter or greater. Human placental lactogen and hLH, hFSH, and hTSH did not cross-react with GH in this assay. Addition of human serum did not alter the slope of ED50 of the GH dose-response curve. Pools of serum from prepubertal and pubertal boys and girls, subjects treated with arginine or insulin, a diabetic girl, and a boy with gigantism who had a serum GH content of 80 micrograms/liter by RIA and 40 micrograms/liter by bioassay, produced dose response curves parallel to that of the GH standard curve. Serum from patients with hypopituitarism did not produce significant suppression of lipid accumulation in any assay. Recovery of 5 micrograms/liter GH added to human serum was 94%. Twenty thousand dalton GH also suppressed lipid accumulation in this assay, but was 2-fold less potent than 22,000 dalton GH.(ABSTRACT TRUNCATED AT 400 WORDS)     

Esterase D polymorphism: phenotype- and gene frequencies in Northern Germany (Schleswig-Holstein) (author''s transl)]

We have observed an apparent hypoglobulinemia in 17 of 35 patients (48.6%) with acromegaly. This unexpected finding was persistent and reproducible up to six years for five acromegalic patients, and more than one year for nine other patients. Serum globulin was analyzed by three different methods, and the deficiency was most noticeable in the alpha globulin fraction (alpha1 greater than alpha2). When hypoglobulinemia occurred in control hospital in-patients (11%) it was associated with chronic or severe illnesses, and limited nutritional intake, but similar medical problems were absent in the acromegalic patients. There was no correlation of the hypoglobulinemia in the 35 acromegalic patients to their growth hormone (GH) concentration (r = 0.07), ages, sex, treatment status, or to the seriousness or duration of the acromegaly. The pathophysiology of the apparent hypoglobulinemia in acromegaly is unknown, but may be related to transport and/or disposal of excess growth hormone, or a defect in protein synthesis.     

Acromegalic cardiomyopathy: an echocardiographic study

Thirty eight acromegalic patients (A) and a control group (C) of subjects without heart disease, were studied with echocardiography. Acromegalies were divided in two groups, A1 and A2, who had increase or normal serum growth hormone (GH) levels respectively after treatment (pituitary adenectomy and/or bromocriptine), at the time of the study. In acromegalic patients (A) mean left ventricular (LV) dimensions were normal while LV wall and septal thickness, LV mass and left atrial (LA) dimension were increased compared to control subjects. LVH was present in 79% of acromegalic patients. Asymmetric septal hypertrophy (ASH) was found in 10,5% of our patients. In group A1, IVS, LVPW, LVMM/m2 were significantly increased as compared to group A2. Fractional shortening (FS), ejection fraction (EF), mean velocity of circumferential fibre shortening (Vcf), frequency-normalized Vcf (Vcfn), posterior left ventricular wall velocity (PWV), and normalized PWV (PWVn) were normal in both groups. In patients with active acromegaly (Al) IVS and LVMM/m2 correlated well with the total duration of the disease (r=0.550 p less than 0.01 for IVS; r=0.624 p less than 0.01 for LVMM/m2) and with the duration of acromegaly before treatment (r=0.568, p less than 0.01 for IVS; r=0.500 p less than 0.01 for LVMM/m2). Furthermore a positive correlation was found between IVS and GH levels (r=0,550 p less than 0.01). Concomitant coronary artery disease and or hypertension did not seem to play any role in causing the above mentioned echocardiographic changes. Echocardiography is useful in assessing the cardiac involvement in patients with acromegaly.     

Role of protein degradation in the growth of livers after a nutritional shift

Four patients with idiopathic pituitary dwarfism were shown to have growth hormone (GH), adrenocorticotropin (ACTH), and luteinizing hormone (LH) deficiencies. Basal levels of thyrotropin (TSH) were within normal range in three patients and slightly elevated in one. Exaggerated and delayed responses were obtained after TSH-releasing hormone (TRH) stimulation. Serum thyroxine (T4) values were low (2.3 +/- 0.4 mug/100 ml), while triiodothyronine (T3) levels were in the normal range (1.22 +/- 0.25 ng/ml), both rising substantially after exogenous TSH and consecutive TRH administration. Their hypothyroid state was, therefore, probably due to TRH deficiency. To examine the dose of L-T4 necessary to produce inhibition of the TSH response to TRH, 50 mug/m2/day of L-T4 was administered to these patients. At the end of 4 weeks of replacement, serum T4 rose to 5.2 +/- 0.5 mug/100 ml, whereas T3 was unchanged from the previous levels, after which TSH responses to TRH were completely suppressed in all patients. As a control group, six patients with primary hypothyroidism received gradually increasing doses of L-T4 for 4-week periods, and TSH response to TRH was tested at the end of each dosage of L-T4, until complete inhibition of TSH release was obtained. The primary hypothyroid patients required approximately 150 mug/m2/day of L-T4 for suppression of TSH response to TRH. At this dosage, serum T4 and T3 levels were 8.5 +/- 0.9 mug/100 ml and 2.34 +/- 0.5 ng/ml respectively, which were significantly higher than those levels in the pituitary dwarfs (P less than 0.001 for T4 and P less than 0.01 for T3). These observations indicate that the set point of TSH release in feedback inhibition by throxine is low in idiopathic hypopituitarism with TRH deficiency, and TRH seems to control the pituitary sensitivity to feedback regulation of thyroid hormones.     

Accumulation of zinc in rainbow trout (Oncorhynchus mykiss) after waterborne and dietary exposure

An acromegalic patient with nontoxic autonomous goiter was sequentially treated with octreotide and bromocriptine. Before therapy, serum GH, PRL and insulin-like growth factor-I (IGF-I) levels were increased. Free T3 and free T4 were within the normal range with suppressed TSH levels, whereas 123Iodine-uptake of thyroid was 5.6% after 24 h. During treatment with octreotide and bromocriptine, serum GH, PRL, and IGF-I became normal and free T3 and free T4 were slightly but significantly decreased, but TSH levels remained very low. After thyroidectomy, thyroglobulin, free T3 and free T4 were further decreased, and the TSH levels were recovered to normal. These findings suggested that octreotide and bromocriptine inhibit the release of thyroid hormones from the autonomous thyroid gland directly or indirectly through the decline in IGF-I.