Recurrence following transsphenoidal surgery for acromegaly.

The long-term results of transsphenoidal adenomectomy and the incidence of possible recurrences were studied in 61 patients who had normal basal serum growth hormone (GH) levels 1 week after surgery. The patients were followed up for an average of 6.0 years (range: 1.5-14.0 years) by repeated measurements of GH, oral glucose tolerance testing (OGTT) and at the last follow-up visit also by assaying somatomedin C levels. In 4 of the patients, the basal GH levels had increased to values above 5 ng/ml. In 43 patients, a normal suppression of GH during an oral glucose load was observed shortly after surgery. In only 2 of these cases did a transiently inadequate suppression develop during the follow-up period, although clinical acromegaly did not recur and the somatomedin C levels remained normal. It is concluded that recurrence of active acromegaly is unlikely to occur in patients who achieve a normal glucose-induced suppression of GH levels shortly after adenomectomy. As such, an OGTT provides better prognostic information than basal human GH level measurements and may give a clearer and earlier indication of surgical success.     

Radioimmunoassay for insulin-like growth factor II (IGF-II)

Insulin-like growth factor II (IGF-II) levels in human plasma were measured in physiological and pathological conditions by radioimmunoassay (RIA) with biosynthetic IGF-II. This RIA was specific for IGF-II and cross-reactivity with IGF-I was 1%. The sensitivity was 15 pg/tube with 50% displacement at 50 pg/tube. The intra- and inter-assay coefficients of variation for IGF-II were 6.3 and 9.3%, respectively. The plasma IGF-II levels in normal adults, patients with hypopituitarism and patients with active acromegaly were 589.6 +/- 15.8, 800.9 +/- 45.6 and 330.3 +/- 24.3 ng/ml, respectively. After human growth hormone (hGH) treatment in hypopituitarism, IGF-II slightly increased, but not significantly. After adenomectomy in patients with acromegaly, IGF-II significantly decreased. These data indicate that IGF-II concentrations in plasma were partially GH dependent. This GH dependency was less than that of IGF-I. IGF-II was low in patients with anorexia nervosa and with liver cirrhosis and high in patients with renal failure. In two cases with extrapancreatic tumor-associated hypoglycemia, plasma IGF-II was increased to 1123.8 and 843.5 ng/ml, and returned to normal after tumor resection. These data showed that IGF-II was partly dependent on GH and nutritional conditions and that IGF-II was the most likely cause of some cases of hypoglycemia with extrapancreatic tumor. This specific and sensitive RIA of IGF-II would be useful in evaluating its physiological and pathological role in plasma and tissue.     

Pituitary surgery for the management of acromegaly

Active acromegaly is almost always the result of a benign growth hormone (GH)-secreting adenoma of the pituitary gland. Because the same pituitary stem cell can produce both GH and prolactin (PRL), many acromegalic patients also have hyperprolactinemia. The advantages of surgical excision of pituitary adenomas associated with acromegaly include: (1) prompt decrease in GH; (2) reliable and immediate relief of the mass effect from the tumor (decompression of the optic nerves and chiasm), and (3) the opportunity to obtain tumor tissue for characterization and investigative study. Currently, more than 97% of operations for removal of pituitary tumors associated with acromegaly are done using the transsphenoidal approach rather than craniotomy. Technical advances to make the surgery safer continue to evolve, and include endoscopic approaches, computer-guided image-based intraoperative visualization, and intraoperative magnetic resonance imaging. Criteria for satisfactory remission of acromegaly after surgery are the same as those used for medical management. They include normal insulin-like growth factor (IGF)-I and suppression of GH to undetectable levels (<1.0 ng/ml) during an oral glucose tolerance test (OGTT). Data from a recent series of 86 patients operated upon for acromegaly at the University of Virginia and followed for more than 1 year have been reviewed. In patients receiving surgery as the initial procedure, 67% had a normal IGF-I, and 52% suppressed to <1.0 ng/ml in an OGTT. There was one true recurrence of disease diagnosed 81 months after surgery. Results are best in patients with noninvasive microadenomas. Gamma knife radiosurgery has been a valuable adjunct in those patients who fail to achieve postoperative remission. Pathological evaluation of the tumors revealed that 16% expressed GH only, 25% stained for GH and glycoprotein hormones (follicle stimulating hormone, thyroid hormone, thyroid stimulating hormone, alpha-subunit), 21% for GH and PRL, and 33% for GH, PRL and glycoprotein hormones. There was one acidophil stem cell tumor and 10% had the mammosomatotroph subtype. This contemporary series was free of mortality or serious complications. One patient had a transient cerebrospinal fluid leak and 3 developed transient SIADH with hyponatremia. Surgical treatment remains an important aspect of the combined management of patients with acromegaly.     

The influence of plasma triglycerides on human growth hormone response to arginine and insulin: a study in hyperlipemics and normal subjects.

Human growth hormone (HGH) response to arginine (25 gm IV in 30 min) and to insulin (0.1 U/kg B.W.) was studied in 12 male patients (mean age 36 +/- 2 years), with normal glucose tolerance and normal body weight, affected with Fredrickson's Type IV primary hyperlipemia. The patients were examined both when plasma triglycerides (TG) were elevated and following clofibrate (2 gm/die for 30-60 days) induced TG reduction. No variations in glucose or FFA behaviour or in body weight were observed after clofibrate. HGH response to arginine was absent, while that to insulin was only inhibited, when plasma TG were elevated. A significant increase in HGH peaks after arginine (from 1.99 +/- 0.59 to 9.34 +/- 1.58 ng/ml) and a slight increment in HGH peaks after insulin (from 23.09 +/- 7.19 to 31.46 +/- 7.95 ng/ml) were observed following reduction in plasma TG. Arginine test was carried out in 7 normal subjects during saline infusion and at the 3rd hour of lipid infusion (Intralipid 20%). HGH response to arginine was absent in all of the subjects during lipid infusion. The HGH response to insulin test, carried out in 9 other normal subjects during saline infusion and at the 3rd hour of lipid infusion (Lipiphysan 15%) was significantly inhibited during lipid infusion. Since lipid infusion provoked an increment, not only in plasma TG but also in FFA, the inhibition of HGH release could be correlated with the elevated plasma levels of both TG and FFA. The results obtained in both spontaneous and experimental hyperlipemia not only confirm the role played by FFA in the regulation of HGH secretion, but also support the hypothesis that elevated TG levels could inhibit HGH response to some stimuli.     

Acromegaly with 'normal' serum growth hormone levels. Clinical features, diagnosis and results of transsphenoidal microsurgery.

Among 216 consecutive patients with growth hormone secreting pituitary adenomas who underwent primary neurosurgical treatment at the University of Erlangen-Nürnberg, 8 cases of acromegaly with 'normal' basal growth hormone levels (less than or equal to 5 ng/ml) were seen. They all had the typical clinical features of acromegaly, exhibited an abnormal growth hormone secretion following an oral glucose load, and had markedly elevated somatomedin C levels. The GRH- and TRH/GnRH-tests were not found helpful in establishing the diagnosis. Neuroradiology could demonstrate a pituitary adenoma in all of the patients. Following transsphenoidal microsurgical resection of the tumours, growth hormone secretion during oral glucose tolerance testing was normalised in 7 of the 8 patients. Immunohistology and explant culture studies documented growth hormone secreting pituitary adenomas in all cases. The authors conclude that even the finding of repetitive 'normal' (less than or equal to 5 ng/ml) serum GH levels does not exclude active acromegaly and when the clinical diagnosis of acromegaly is suspected, dynamic endocrine testing may reveal abnormal secretion patterns of GH in these cases. Transsphenoidal microsurgical resection of a pituitary adenoma offers a good chance of clinical and endocrinological remission in these cases.     

Radioimmunoassay for insulin-like growth factor I (IGF-I) using biosynthetic IGF-I

We produced antiserum to insulin-like growth factor I (IGF-I), and developed a specific and sensitive radioimmunoassay (RIA) for IGF-I using the biosynthetic IGF-I. This antiserum to IGF-I was specific for IGF-I; no cross-reactivities with multiplication stimulating activity, porcine insulin or human growth hormone (hGH) were detected. The sensitivity was 10-25 pg/tube with 50% displacement at 125 pg/tube. The intra- and inter-assay coefficients of variation for IGF-I were 5.4 and 9.7%, respectively. The plasma IGF-I levels as determined by RIA in normal adults (N = 46), patients with active acromegaly (N = 31), and pituitary dwarfs (N = 31) were 21.6 +/- 1.0, 157.3 +/- 17.0, and 2.5 +/- 0.3 ng/ml (Mean +/- SEM), respectively, indicating the levels were GH-dependent. The plasma IGF-I levels were significantly increased from 2.2 +/- 0.2 to 26.5 +/- 3.2 ng/ml after hGH administrations for three consecutive days in five pituitary dwarfs. The IGF-I levels were low in patients with hypothyroidism and liver cirrhosis, but were normal in patients with chronic renal failure. These data confirm previous reports and this radioimmunoassay proves useful in evaluating plasma IGF-I levels.     

The postoperative stress response and its reflection in cytokine network and leptin plasma levels

The objective of the present report was to clarify the postoperative stress response of some inflammatory markers, namely of proinflammatory cytokines and leptin levels during uncomplicated postoperative periods. The results were compared with the dynamics of these parameters during intraabdominal sepsis. We followed 20 patients after a planned resection of colorectal cancer in stage Ib-IV with uncomplicated healing and 13 obese men after laparoscopic non-adjustable gastric banding. These were compared to 12 patients with proven postoperative sepsis. The control group consisted of 18 healthy men. The observed parameters included serum levels of cytokines, tumor necrosis factor-alpha (TNFalpha), interleukin-1 beta (IL-1 beta), interleukin-1 receptor antagonist (IL-1 ra), IL-6, IL-8, soluble receptor of interleukin-2 (sIL-2R) and leptin. It was found that during the first 24 h after resection there was a significant increase in the serum concentration of IL-6 up to 1125+/-240 ng/l, which declined within the next 48-72 h. Serum concentration of TNFalpha was highest 18-24 h after resection (205+/-22 ng/l) and after banding (184+/-77 ng/l). IL-1 beta had a stable serum concentration without significant elevation. Serum concentration of IL-8 after resection rose to 520+/-200 ng/l after 36-48 h. Maximal cytokine levels after gastric banding were quantitatively lower (IL-6 414+/-240 ng/l, TNFalpha 184+/-77 ng/l) than after resection. We found significant elevation of plasma leptin concentration (32+/-10 ng/ml) 24 h after banding compared with preoperative values (18+/-5 ng/ml, p 0.05). Leptin levels 48 and 72 h after banding rapidly returned to the level before operation. During abdominal surgery leptin shows to be an acute phase reactant. Proinflammatory cytokines can be main regulatory factors of leptin during this period. Significant correlation between leptin and TNFalpha (similarly demonstrated by other authors in models of bacterial inflammation) indicates that TNFalpha can be the crucial regulator of leptin generation in the early postoperative period. On the basis of our results we recommend to observe IL-6 and IL-8 at 24-72 h after the surgery in patients with a high risk of early postoperative septic complications.     

Evaluation of a new radioimmunological assay for the determination of the B subunit of creatine kinase enzyme

We used a new radioimmunological (RIA) kit for the assay of B subunit of creatine kinase enzyme (CK). This RIA system uses a specific antisera against the B subunit as ligant, human CK-BB labelled with 125I as tracer, and purified human CK-BB isoenzyme as standard. The mean (+/- SD) sensitivity obtained was 0.25 +/- 0.16 ng/tube and the between assay variability was about 9-10%. Serum levels of 113 normal subjects was not normally distributed. The 95% of values was found below 5 ng/ml. This new RIA is usefull in clinical practice when serum levels of CK-BB isoenzyme must be determined. This method is quickly and it is characterized by a good degree of precision, but the CK-MB isoenzyme cross-reacts for about 40% in this RIA system. Therefore, for the clinical diagnosis by means of this RIA it is necessary to rule out the concomitant elevations of serum CK-MB values.     

Hypercalcemia and Acromegaly-Clarifying the Connections: A Case Report and Review of the Literature

ObjectiveHypercalcemia in patients with acromegaly is rare and usually due to co-existent primary hyperparathyroidism. The etiology of hypercalcemia directly related to acromegaly is debated.MethodsWe present a case report of 1,25(OH)2D3-mediated hypercalcemia in a patient with acromegaly and discuss potential pathophysiological mechanisms contributing to the development of hypercalcemia late in the course of the disease.ResultsA 67-year-old female presented with classical features of acromegaly. A review of her previous photographs suggested a disease duration of approximately 10 years, and her serum calcium (Ca) was normal during this period. A biochemical work up confirmed a combined growth hormone (GH-) and prolactin (PRL-) cosecreting tumor with a GH level of 92.03 ng/mL (normal 0-3.61), an insulin-like growth factor-1 (IGF-1) level of 1,498 ng/ mL (59-225), and a PRL level of 223.3 ng/mL (2-17.4). Magnetic resonance imaging (MRI) of the pituitary showed a 1.9-cm macroadenoma. Her preoperative work up revealed new onset hypercalcemia with a corrected serum Ca level of 10.7 mg/dL (8.5-10.5), an ionized Ca level of 1.37 mmol/L (1.08-1.30), a parathyroid hormone (PTH) level of 13.0 pg/mL (10-60), and a high 1,25(OH)2D3 level of 72.6 pg/mL (15-60). She underwent resection of the pituitary adenoma with normalization of GH and PRL levels, and her IGF-1 level decreased to 304 ng/mL. Her serum Ca (9.3 mg/dL), ionized Ca(1.22) and 1,25(OH)2D3 levels (38.6 pg/mL) normalized after surgery.ConclusionWhile overt hypercalcemia in acromegaly is rare, it tends to occur late in the disease course. The hypercalcemia is mediated by elevated 1,25(OH)2D3 levels rather than PTH. (Endocr Pract. 2014;20:e86-e90)     

Determination of insulin-like growth factor-I in normal subjects and in patients with growth hormone disorders by radioimmunoassay using biosynthetic homologous peptide

A highly sensitive and specific RIA for IGF-I has been developed using recombinant DNA-derived IGF-I of very high purity and specific antiserum to it. This assay system could detect IGF-I at as low concentrations as 20-30 ng/ml. The intra-assay and interassay coefficients of variation at various concentrations of IGF-I were 4.9 to 6.5% and 5.4 to 8.0%, respectively. The recovery rate of pure IGF-I added to plasma was 77.0 +/- 3.7%. The antiserum did not cross-react with porcine insulin, biosynthetic human insulin, hGH, hEGF, the synthetic C-domain of IGF-I or that of IGF-II, but reacted equally with an analog, Thr59-IGF-I. Plasma IGF-I was extracted by the acid-ethanol method before assay to separate IGF-I from its binding protein. When plasma IGF-I was assayed without extraction, the inhibition curves of serial dilution of plasma samples from several individuals were not parallel to the standard curve of IGF-I. The plasma concentration of IGF-I was 147 +/- 49 ng/ml (mean +/- SD) in 156 normal adults aged from 20-59 years. As reported by others, the IGF-I levels were low in cord plasma (41.8 +/- 23.5 ng/ml) and plasma of patients with GH deficiency (64.6 +/- 42.0 ng/ml), while its levels were high in normal children of pubertal ages (12-13 yr, 365 +/- 126 ng/ml) and in patients with active acromegaly (562 +/- 115 ng/ml). This RIA system is a simple and useful method for determining plasma IGF-I in normal and diseased states.     

A screening test to detect HGH-antibodies in pituitary dwarfs treated with HGH preparation by the radio-immunoassay with double antibody technique

Sixty-four blood samples, obtained from 25 pituitary dwarfs treated with KABIHGH preparation, were checked for serum HGH concentration by a double antibody radioimmunoassay and for antibodies against HGH by the method of propylethyleneglycol separation. Antibodies to HGH were detected in the samples whose HGH concentration was falsely estimated to be more than 5 ng/ml, but not in those whose HGH concentration was 5 ng/ml or less. The measurement of HGH concentration by a double antibody technique in the serum obtained from pituitary dwarfs 3-4 days after the last injection can be used to screen the presence of antibodies to HGH peparation used.     

Development of time-resolved immunofluorometric assays for rat follicle-stimulating hormone and luteinizing hormone and application on sera of cycling rats

The aim of this study was to develop time-resolved immunofluorometric assays (TR-IFMA) for measuring rat (r)FSH and rLH. The advantages of these IFMAs are higher sensitivity due to lower background values, higher specificity as only intact molecules of FSH and LH can be measured, and a very long shelf life of the nonradioactive biotin antigens compared with radiolabeled iodine antigens. For rFSH, IFMAs are lacking, while for rLH, if present, the resources for antibodies are scarce or the mouse monoclonal antibodies (mMAbs) against LHalpha are inactive with FSH. Thus specific antibodies need to be obtained. With the final TR-IFMAs, rFSH and rLH levels were assessed during the estrous cycle and compared with those obtained with the more classical RIAs and fluoroimmunoassays (FIAs). Two IFMAs for rFSH were developed with mMAbs against the recombinant human (rec h)FSHbeta subunit (FSH56A) attached to the wall and two different rabbit polyclonal antibodies (PAbs) against the alpha subunit of rec hFSH (R93-2705) or recombinant rat (rec r)LH (R95-2715) conjugated with biotin as signal antibody. With both IFMAs, rFSH holo-molecules can be measured. Rat FSH standards could be assessed between 0.02 and 10 ng/ml with a detection limit of 0.05 and 0.24 ng/ml in buffer and serum, respectively. These detection limits in four IFMAs were 8- to 16-fold lower than those in RIAs and FIAs. This detection level allowed the measurement of FSH levels in serum of hypophysectomized (HYPEX) rats at 0.18 ng/ml. In serum of cycling rats, the FSH levels of the IFMA were 2-fold lower than those of the FIA, while in ovariectomized (OVX) rats the IFMA levels were comparable. A peak level of FSH was found during proestrus of Day 2 and gestation with both RIA and FIA, but with IFMAs at gestation only. An IFMA for rLH was set up with mMAb (hCG77A) reacting with rLHbeta as capture and rabbit PAb to rec rLHalpha (R95-2712) as signal antibody. Rat LH standard could be assessed between 0.001 and 10 ng/ml with a detection limit of 0.012 and 0.1 ng/ml in buffer and serum, respectively, which was 8-fold lower than that in RIA/FIA. In serum of HYPEX rats, LH was undetectable (< 0.04 ng/ml), whereas a high background level of 2.5 ng/ml was measured in the FIA. In serum of cycling rats, only a very low LH level of 0.14 ng/ml was measured, which strongly deviated from the level of 3.46 ng/ml with an FIA. The load of LH in serum of OVX rats was 2.91 ng/ml, which was 12-fold lower than that for the FIA. The peak level of LH was detected on proestrus Day 2 with RIA, FIA, and IFMA. In conclusion, two IFMAs for rFSH and one for rLH have been developed with high sensitivity and specificity for intact gonadotropins. The LH pattern during the estrous cycle was comparable between IFMA, RIA, and FIA, although the overall level in the IFMA was much lower, as were HYPEX levels. The FSH pattern differed only on proestrus Day 2 in the IFMA from that of RIA/FIA, showing a peak level with RIA/FIA and a basal level with the IFMA. This implies that in RIA/FIA measurements, proteins other than intact FSH and LH interfere with the analysis at proestrus Day 2 for FSH and in HYPEX, cycling, and OVX rats for LH.     

Dynamics of injected somatostatin in blood of patients with hepatic failure and acromegaly

Plasma somatostatin levels were measured by radioimmunoassay (RIA) at various times after rapid injection into the blood of 4 patients with acromegaly, 4 patients with hepatic failure, and 4 healthy subjects. In contrast to the single peak found in normal and acromegalic individuals, two distinct peaks were observed in each patient with liver failure. The first occurred at about the same time as that observed in the other two groups, but the second occurred about 3 min later. This second peak could not be distinguished immunologically from the intact somatostatin tetradecapeptide. The half-time disappearance of somatostatin in patients with hepatic failure was significantly longer than in the normal subjects. Acromegalic subjects tended to have the shortest half-time disappearance of the injected somatostatin and the highest peak level. The results are consistent with the possibility that altered metabolism and/or binding of somatostatin occurs in hepatic failure and in acromegaly.     

Radioimmunoassay of serum medroxyprogesterone acetate (Provera) in women following oral and intravaginal administration.

A radioimmunoassay (RIA) method for measuring medroxyprogesterone acetate (MPA, Provera) in serum has been developed utilizing benzene:iso-octane extraction, 3H-MPA to assess procedural losses, goat anti-MPA-3-(0-carboxymethyl) oxime-bovine serum albumin serum and dextran-coated charcoal separation. Control serum blanks were undetectable, 200 pg/ml of MPA was measurable with a high reliability, and intra- and interassay coefficients of variation were 6 and 13 percent, respectively. MPA added to control serum was quantitatively recovered. Serum MPA levels measured in 2 women after ingestion of 10 mg MPA rose to 3.4 to 4.4 ng/ml within 1 to 4 hours after oral intake and fell rapidly thereafter to 0.3 to 0.6 ng/ml within 24 hours. Insertion of Silastic intra-vaginal rings (IVRs), containing 100 or 200 mg of MPA, into 4 women for periods of 3 weeks resulted in a rapid rise of serum MPA after insertion, rather stable MPA levels of 0.9 to 1.6 ng/ml while the IVRs were in place, and a rapid decline of serum MPA following IVR removal. Serum estradiol-17beta and progesterone concentrations, measured about 3 times a week in these patients, indicated that ovulation was consistently inhibited. The serum MPA levels observed in this study were approximately 5 times lower than those reported by other investigators using a double-antibody RIA of MPA in unextracted serum.     

Ectopic growth hormone-releasing hormone (GHRH) syndrome in a case with multiple endocrine neoplasia type I

A 36-yr-old man with multiple endocrine neoplasia (MEN) type I had an ectopic growth hormone-releasing hormone (GHRH) syndrome due to a GHRH-secreting pancreatic tumor. The immunoreactive (IR)-GHRH concentration in his plasma ranged from 161 to 400 pg/ml (299 +/- 61 pg/ml, mean +/- SD; normal, 10.4 +/- 4.1 pg/ml), and a significant correlation was found between his plasma IR-GHRH and GH (r = 0.622, p less than 0.02). After removal of the pancreatic tumor, the high plasma GH concentration returned to nearly the normal range (42.2 +/- 31.3 to 9.6 +/- 3.8 ng/ml). These changes paralleled the normalization of his plasma IR-GHRH (16.1 +/- 3.8 pg/ml) and some of his symptoms related to acromegaly improved. However, plasma GH (7.7 +/- 1.3 ng/ml) and IGF-I (591 +/- 22 ng/ml) concentrations were high at 12 months after surgery, suggesting adenomatous changes in the pituitary somatotrophs. Before surgery, exogenous GHRH induced a marked increase in plasma GH, and somatostatin and its agonist (SMS201-995) completely suppressed GH secretion, but not IR-GHRH release. No pulsatile secretion of either IR-GHRH or GH was observed during sleep. An apparent increase in the plasma GH concentration was observed in response to administration of TRH, glucose, arginine or insulin, while plasma IR-GHRH did not show any fluctuation. However, these responses of plasma GH were reduced or no longer observed one month and one year after surgery. These results indicate that 1) a moderate increase in circulating GHRH due to ectopic secretion from a pancreatic tumor stimulated GH secretion resulting in acromegaly, and evoked GH responses to various provocative tests indistinguishable from those in patients with classical acromegaly, and 2) the ectopic secretion of GHRH may play an etiological role in the pituitary lesion of this patient with MEN type I.     

大熊猫生殖生物学研究:Ⅰ.大熊猫发情期血清和尿液中促黄体素、孕酮和17β-雌二醇含量的变化

作者用放射免疫法和生物测定法对4只大熊猫发情期血清和尿液中的促黄体素、孕酮和17β-雌二醇的含量进行分析。结果表明:3只大熊猫在发情高峰期均出现雌二醇和促黄体素高峰;LH峰值出现在E_2峰值之后。根据雌兽在发情期血清和尿液中这二种激素含量的变化可为选择人工授精的最佳时间提供可靠的理论依据。     

Growth hormone in urine: development of an ultrasensitive assay applicable to plasma and urine

A radiometric assay for human growth hormone (HGH) was developed based on a polyclonal goat anti-HGH antiserum covalently coupled to nonsedimenting polyacrylamide particles. HGH can be specifically immunoextracted from sample volumes of up to 10 ml. Subsequently, bound HGH is identified and quantitatively measured by a 125I-labelled monoclonal anti-HGH antibody. The assay is insensitive to plasma proteins from 10 to greater than 90%, to changing NaCl and urea molarities and to pH ranges from 6 to 8. The sensitivity in the second incubation is 2 pg/tube, corresponding to a maximum sensitivity of 300 fg/ml of a sample volume of 10 ml (urine) or of 40 pg/ml, if a volume of 50 microliter (plasma) is assayed. In healthy children, a mean HGH excretion of 6.5 ng/24 h was found with a large interindividual range from undetectable to 37.4 ng. An important intraindividual night-to-night variation of HGH excretion was found in several subsequent first morning void samples in healthy children. The mean excretion in 13 HGH-deficient children was 0.9 ng/24 h off therapy and increased to a mean of 6.9 ng/24 h on therapy. In acromegalic patients, the excreted HGH amounted to 73-208 ng/24 h. Preliminary results suggest that the ultrasensitive assay applied to plasma and urine could be a considerable improvement of diagnosis and follow-up of disorders of HGH secretion.     

The influence of bariatric surgery on calcium homeostasis and biochemical markers of bone turnover in patients with morbid obesity

INTRODUCTION: Obese patients may have abnormal calcium homeostasis because of unbalanced diet and decreased sun exposure. Bariatric surgery itself may lead to disturbances in calcium homeostasis (and in consequence changes in bone mass) or increase preexisting metabolic derangements. The aim of the study was: 1. To assess calcium homeostasis and biochemical markers of bone turnover in patients with morbid obesity. 2. To determine the impact of bariatric surgery on parameters mentioned above. 3. To establish recommendations for supplementation with calcium and vitamin D in morbidly obese patients after bariatric surgery. MATERIAL AND METHODS: Serum calcium, parathormone (PTH), vitamin D (25(OH)D), biochemical markers of bone turnover (beta-CrossLaps as a marker of bone resorption and osteocalcin as a marker of bone formation) and urine calcium as well as fat mass, lean mass and bone mineral content (by DXA) were measured before bariatric surgery of the stomach (VBG or GBP) in 57 morbidly obese patients (48 women, 9 men; mean age 35.9 y). The same procedures were repeated six months after operation in 28 of them (24 women, 4 men). Daily calcium intake was also determined based on food questionnaire. RESULTS: Biochemical findings in the group of patients before bariatric surgery were as follows: serum calcium, beta-CrossLaps and urine calcium were within normal range, PTH concentration was increased to 81.0 pg/ml and 25(OH)D as well as osteocalcin concentration decreased (4.9 ng/ml and 13.6 ng/ml, respectively). Six months after bariatric surgery there was no change in serum and urine calcium, PTH concentration decreased to normal level (46.8 pg/ml), 25(OH)D concentration increased to 6.5 ng/ml (not significant) and still remained below normal range. Markers of bone turnover--both resorption and formation--increased (beta-CrossLaps over normal range to 0.594 ng/ml, osteocalcin to normal range 26.8 ng/ml). Daily calcium intake was below RDA before and after bariatric procedure. CONCLUSIONS: 1. Patients with morbid obesity have secondary hyperparathyroidism and deficiency of vitamin D. 2. Abrupt weight loss after bariatric surgery is accompanied by the regression of secondary hyperparathyroidism, decrease of the deficiency of vitamin D and increase in bone turnover. 3. Supplementation with vitamin D and calcium is recommended for patients with morbid obesity after bariatric surgery.     

Effect of Fenfluramine on Human Growth Hormone Release

In order to investigate the effect of fenfluramine on hormonal and metabolic changes with exercise, five normal volunteers have been studied during and after 20 minutes of steady exercise on a bicycle ergometer after injection of fenfluramine (20 mg intravenously). Fenfluramine abolished the rise of plasma human growth hormone (HGH) which occurred in control investigations. Fenfluramine also affected plasma insulin, blood glucose, and ketone body levels.The acute effect of fenfluramine on the release of growth hormone was examined further by studying its effect in patients with acromegaly. A marked depression of growth hormone occurred both at rest and with exercise. These observations indicate that fenfluramine has a direct effect on pathways controlling growth hormone release. We also suggest that this action may have practical use in the medical treatment of acromegaly.     

Ovarian activity and peripheral plasma levels of oestrogens and progesterone in the lactating sow

Ten gilts were examined for peripheral plasma levels of progesterone and oestrogens 3 weeks before and up to 8 weeks after parturition. The sows were slaughtered at different intervals after parturition and the ovaries were examined. Peripheral plasma levels of progesterone decreased dramatically from about 8ng/ml two days before parturition to about 2 ng/ml on the day before parturition. After parturition the mean progesterone level was about 1.5 ng/ml. Maximum oestrone levels of about 7 ng/ml were obtained two days before parturition. After parturition the level dropped to below 0.1 ng/ml. Three sows showed high levels of oestradiol (75–440 pg/ml) without signs of heat during the lactation. In no case were ovulated follicles or periodic corpora lutea registered.