The impact of obstructive sleep apnea syndrome on renin and aldosterone.

OBJECTIVE: Obstructive Sleep Apnoea Syndrome (OSAS) is a respiratory disorder characterized by recurrent airflow obstruction caused by total or partial collapse of the upper airway. OSAS is an established independent factor of cardiovascular risk together with other risk factors such as smoking and increased lipids. The aim of our study was to measure serum levels of aldosterone and renin in OSAS patients that did not suffer from arterial hypertension and compare them to matched healthy subjects in order to reveal the impact of chronic intermittent hypoxia on the renin-angiotensin-aldosterone system. PATIENTS AND METHODS: The patients that enrolled in this study were 19 OSAS patients who had undergone overnight polysomnography and had an Apnoea Hypopnoea Index (AHI) greater than 10 events/hour. They were compared to 20 healthy non-OSAS closely matched controls. Serum aldosterone and direct renin concentration were measured by radioimmunoassay. RESULTS: Aldosterone concentration follows a diurnal variation; therefore, all blood samples were obtained at the same time (6 AM). There were no significant differences in serum aldosterone levels between the two studied groups of OSAS patients and the healthy subjects group (140.6 pg/ml ± 25.2 vs. 133.2 pg/ml ± 18.5 with p = 0.223). Similar were the results for the renin levels (25.0 ± 6.9 vs. 24.9 ± 4.4 with p = 0.360). CONCLUSIONS: Our study suggests that patients with OSAS, but without existing hypertension have aldosterone and renin levels similar to healthy subjects. According to our findings a direct connection between OSAS and the development of arterial hypertension may not be established via sympathetic system activation.

The influence of intensive physical training on salivary adipokine levels in Elite Rhythmic Gymnasts.

Exercise challenges homeostasis and establishes a new dynamic equilibrium. Elite Rhythmic Gymnasts (RG's) begin exercise at an early age, undergo physical and psychological stress, and adopt negative energy balance to retain a lean physique. The aim of the present study was to evaluate the effect of negative energy balance, acute and chronic exercise on salivary adiponectin, resistin and visfatin levels and their interaction with salivary cortisol, and insulin levels in elite RG's. This study is unique in character, as all variables were assessed on the field of competition. The study included 51 elite RG's participating in "Kalamata 2010 World Cup" in Kalamata, Greece on April 2010. Twenty-seven healthy age-matched girls were used as controls. Anthropometric values were assessed; baseline and post exercise salivary cortisol, insulin, adiponectin, resistin, and visfatin levels were measured. Comparisons regarding hormonal features between RG's and controls were adjusted for BMI and body fat percentage. Salivary adiponectin levels were higher (p<0.05) and visfatin lower (p=0.094) in RG's compared with controls, while no significant changes were observed regarding salivary cortisol, insulin, and resistin levels. In elite RG's acute intensive anaerobic exercise led to increased salivary insulin levels (p<0.001), reduced salivary adiponectin (p<0.001) and visfatin levels (p<0.05), and no changes in salivary resistin levels. Moreover, diurnal variation of salivary cortisol was lost. In elite RG's salivary adiponectin is upregulated and salivary visfatin is downregulated after chronic intensive exercise and negative energy balance, while both salivary adiponectin and visfatin levels are suppressed after short term intensive anaerobic exercise.

Chronic hepatitis C virus infection without cirrhosis induces insulin resistance in patients with alpha-thalassaemia major.

AIM: The aim of this study was to investigate the cause of increased incidence of impaired glucose tolerance and diabetes mellitus in patients with alpha-thalassaemia major and chronic hepatitis C virus (HCV) infection without cirrhosis of the liver. PATIENTS AND METHODS: The study included 28 alpha-thalassaemic multi-transfused patients (14 females and 14 males; age, 25.7 +/- 6.3 years) with normal fasting glucose levels. Sixteen were seropositive for HCV and they had biopsy proven chronic hepatitis C without cirrhosis. An oral glucose tolerance test (OGTT) was performed. Glucose, insulin and C-peptide levels were measured every 30 min for 2 h. Fasting insulin resistance index (FIRI) was calculated according to the formula: FIRI = (fasting glucose x fasting insulin)/25. RESULTS: All patients had a normal OGTT except for two HCV positive and two HCV negative patients who had impaired glucose tolerance. HCV positive patients had higher fasting insulin levels (P = 0.02), higher fasting insulin/fasting glucose ratio (P = 0.017) and higher FIRI (P = 0.016) than HCV negative patients. During the OGTT, peak insulin levels occurred at 30 min in HCV negative patients but at 60 min in HCV positive. HCV infected patients had higher mean value of insulin at 60 (P = 0.017), 90 (P = 0.04), and 120 min (P = 0.04), and higher mean increment above basal at 60 (P = 0.015), 90 (P = 0.018) and 120 min (P = 0.05). The area under the curve (AUC) of insulin was also greater in HCV positive patients as compared to HCV negative (P = 0.04), although the AUC of glucose and the glucose levels at all time points of the OGTT were similar in both groups. CONCLUSIONS: The findings of this study show that alpha-thalassaemic patients with HCV infection without liver cirrhosis are more insulin resistant and have delayed insulin secretion compared to HCV negative alpha-thalassaemic patients. These changes in insulin action and secretion are evident before the development of impaired glucose tolerance and may explain the higher prevalence of diabetes mellitus in this group.

Novel application of IGF-I and IGFBP-3 generation tests in the diagnosis of growth hormone axis disturbances in children with beta-thalassaemia.

OBJECTIVE: Children with beta-thalassaemia major (beta-thal) frequently have growth retardation in the presence of low serum IGF-I and a normal GH response to pharmacological stimulation suggesting that they have GH insensitivity (GHIS). This study was carried out to study the cause of their growth retardation. DESIGN: We studied IGF-I and IGFBP-3 generation after exogenous GH administration for four days, in 15 prepubertal controls (C) and 41 prepubertal beta-thal patients divided into three groups according to their growth status: (Group 1) 15 with normal growth (N-thal) (Group 2) 16 with decelerated growth (D-thal) and (Group 3) 10 with short stature (S-thal), in order to determine whether GHIS is the cause of their growth retardation. MEASUREMENTS: IGF-I and IGFBP-3 were measured daily, before and for 4 days after daily administration of 0.1 IU/kg hGH, in 3 groups of prepubertal beta-thal patients and normal controls. RESULTS: N-thal and C had similar basal serum IGF-I (142 +/- 52 and 196 +/- 56 ng/ml, respectively) and IGFBP-3 concentrations (2.07 +/- 0.49 and 2.66 +/- 0.41 mg/l, respectively) as well as a similar percent increase of IGF-I (101 +/- 23% and 104 +/- 37%, respectively) and IGFBP-3 (52 +/- 36%, and 38 +/- 14%, respectively) during the generation tests. S-thal and D-thal had significantly lower basal IGF-I and IGFBP-3 concentrations (85 +/- 42 and 101 +/- 36 ng/ml; and 1.60 +/- 0.49 and 1.79 +/- 0.52 mg/l, respectively) as compared to N-thal and C (P < 0.001 and P < 0.005, respectively), and a significantly higher percent increase of IGF-I and IGFBP-3 during the generation tests (249 +/- 43 and 161 +/- 76%; and 121 +/- 99 and 73 +/- 35%, respectively) as compared to N-thal and C (P < 0.0001 and P < 0.01, respectively). Twenty-five percent of the growth retarded patients had classic GH deficiency (GHD) and percent increases of IGF-I and IGFBP-3 in the generation tests (164 +/- 86% and 80 +/- 49%, respectively) which were similar to those of the remaining growth-retarded children. CONCLUSION: The greater percent increases of IGF-I and IGFBP-3 in the generation tests of the growth retarded beta-thal patients, both with and without GHD, strongly suggest impaired GH secretion rather than GHIS as the cause of their growth retardation. We conclude that the IGF-I and IGFBP-3 generation tests are useful tools for the study not only of GHIS but also of GH secretory disorders in patients with beta-thal and short stature that can easily be performed in an outpatient setting as an initial test to identify the patients that may benefit from GH therapy.

Increased sensitivity to the inhibitory effect of excess iodide on thyroid function in patients with beta-thalassemia major and iron overload and the subsequent development of hypothyroidism.

OBJECTIVE: Patients with beta-thalassemia frequently develop primary hypothyroidism and other endocrine disorders due to iron overload. We studied whether administration of excess iodide to patients with apparently normal thyroid function could uncover an underlying thyroid disease. DESIGN AND METHODS: Twenty-five patients, 10 prepubertal (mean age 11+/-3 years) and 15 adults (mean age 23+/-5 years) with normal thyroid hormone and TSH levels, a normal response of TSH to TRH and negative thyroid peroxidase antibodies received 20mg iodide three times daily for three weeks, and thyroid hormone and TSH levels were measured weekly during, and for three weeks after, iodide administration and every 3 months thereafter for the next 5 years. RESULTS: During iodide administration there was a significant decrease in thyroid hormone concentrations which remained within normal levels, and a significant increase in TSH concentrations which in 14 out of 25 (56%) patients reached the hypothyroid level. Baseline TSH values were higher in those patients who developed subclinical hypothyroidism (2.31+/-0.71mU/l vs 1. 34+/-0.64mU/l, P=0.0016). Subclinical hypothyroidism developed in 70% of prepubertal and in 47% of adult patients. Serum ferritin was elevated in all patients. Nine of the fourteen patients (64.3%) who developed subclinical hypothyroidism during iodide administration developed hypothyroidism during the 5-year follow-up compared with only one of the eleven patients with a normal response to iodide (P=0.004). CONCLUSIONS: Patients with beta-thalassemia should not be exposed to excess iodide due to increased sensitivity to its inhibitory effects on thyroid function. The susceptible individuals frequently develop permanent hypothyroidism in the following years.

Beneficial effects of growth hormone and insulin-like growth factor I on intestinal bacterial translocation, endotoxemia, and apoptosis in experimentally jaundiced rats.

BACKGROUND: This study was undertaken to investigate the effect of growth hormone (GH) and insulin-like growth factor I (IGF-I), two well-known growth factors, on bacterial translocation, endotoxemia, enterocyte apoptosis, and intestinal and liver histology in a model of experimental obstructive jaundice in rats. STUDY DESIGN: One hundred six male Wistar rats were divided into five groups: I (n = 21), controls; II (n = 22), sham operated; III (n = 22), bile duct ligation (BDL); IV (n = 21), BDL and GH treatment; and V (n = 20), BDL and IGF-I administration. By the end of the experiment, on day 10, blood bilirubin was determined, and mesenteric lymph nodes, liver specimens, and bile from the bile duct stump were cultured. Endotoxin was measured in portal and aortic blood. Tissue samples from the terminal ileum and liver were examined histologically and apoptotic body count (ABC) in intestinal mucosa was evaluated. Mucosal DNA and protein content were also determined. RESULTS: Bilirubin increased significantly after BDL (p < 0.001). Bile from the bile duct was sterile. In group III, MLN and liver specimens were contaminated by gut origin bacteria (significant versus group I and II, p < 0.001, respectively). GH reduced significantly positive cultures (p < 0.01), and IGF-I had no effect. BDL resulted in significant increase in portal and aortic endotoxemia (p < 0.001); treatment with GH and IGF-I reduced it (p < 0.001). Mucosal DNA and protein content were reduced in animals with BDL and after treatment with GH or IGF-I; an increase to almost normal levels was noted in DNA, but not in protein. Overall the ileal architecture remained intact in all animal groups. The ABC increased after BDL. After GH and IGF-I administration, the ABC decreased significantly, and there was no difference between GH and IGF-I treated animals. After BDL, liver biopsies displayed typical changes of biliary obstruction, which were significantly improved after administration of GH and IGF-I. CONCLUSIONS: Treatment with GH and IGF-I in rats with experimental obstructive jaundice reduces endotoxemia, and it improves liver histology. Apoptosis, in the intestinal epithelium, may serve as a morphologic marker of the ileal mucosal integrity, demonstrating the proliferative potential of GH and IGF-I in cases of obstructive jaundice, and this might be of potential value in patients with such conditions.

Growth hormone and insulin-like growth factor I protect intestinal cells from radiation induced apoptosis.

We studied whether programmed cell death (or apoptosis) is the predominant mechanism in radiation-induced cell damage to rat intestinal mucosa and investigated the mechanism of the protective effect of GH and IGF-I in the same model. Male albino Wistar rats were divided into four groups: controls, radiation, radiation plus GH and radiation plus IGF-I. Radiation was administered on the first day and on day 4. All animals were sacrificed and segments of the terminal ileum were stained with hematoxylin-eosin. Apoptosis of the epithelial cells was identified at the cellular level by the TUNEL stain and was distinguished from necrosis by the characteristic morphology of the cells (cytoplasmic shrinkage, marginal chromatin condensation and generation of nuclear apoptotic bodies). Apoptotic cells in the control animals were few and detected only at the tips of the villi while in the irradiated animals almost all the epithelial cells were apoptotic, distributed from the crypts to the tips of the villi and the mucosa showed severe epithelial atrophy and ulceration. The histologic picture of the mucosa in the GH and IGF-I treated animals was similar to normal controls and apoptotic cells were restricted only at the tips of the villi. DNA and RNA from the mucosa cells were isolated and analyzed by electrophoresis. DNA fragmentation and RNA 28s band ribonuclease cleavage was observed only in the irradiated animals. We have shown that abdominal radiation causes intestinal epithelial cell damage mainly through the induction of apoptosis and the treatment with GH and IGF-I inhibits apoptosis of the cells and preserves the mucosal integrity.

High prevalence of diabetes mellitus among adult beta-thalassaemic patients with chronic hepatitis C.

AIM: The aim of this study was to assess the prevalence of diabetes mellitus in patients with hepatitis C virus (HCV) chronic hepatitis and secondary haemochromatosis as a consequence of beta-thalassaemia major. This group of patients was studied in order to reveal subtle effects of early stages of HCV infection on glucose metabolism, made more apparent by the coexistence of the diabetogenic effect of haemochromatosis. PATIENTS AND METHODS: The study included 108 beta-thalassaemic multitransfused patients, 55 females and 53 males, age 26.8+/-9 years. Sixty-four patients were seropositive for HCV by ELISA-3 (61/64 HCV-polymerase chain reaction-positive by Amplicor). In 51 of these, chronic hepatitis C was documented by liver biopsy, which also showed incomplete cirrhosis for eight and cirrhosis for four patients. Diabetes was diagnosed according to the criteria of the National Diabetes Data Group of the National Institutes of Health. RESULTS: (1) Patients with thalassaemia and HCV infection were diabetic more often than thalassaemic patients without HCV infection (45.3% versus 11.3%; P<0.001). This highly significant difference was also found when patients with definite cirrhosis or incomplete cirrhosis were excluded (41% versus 11.3%; P<0.01). (2) The high frequency of diabetes in thalassaemic patients with HCV chronic hepatitis is not related to body mass index or iron load, but it seems especially evident in patients over 25 years of age (50% of HCV-positive were diabetic versus 9.5% of HCV-negative; P<0.01). CONCLUSION: The frequency of diabetes in adult thalassaemic patients is significantly increased by HCV infection, even in the absence of cirrhosis. It is probable that the coexistence of haemochromatosis makes the effect of HCV infection on glucose metabolism clinically evident, even in the stage of chronic hepatitis.

Technetium-99m-tetrofosmin for parathyroid scintigraphy: comparison to thallium-technetium scanning.

UNLABELLED: The efficacy of 99mTc-tetrofosmin for the detection of parathyroid lesions was investigated prospectively in patients with hyperparathyroidism referred for surgical treatment. METHODS: Twenty-seven patients with primary and 18 with tertiary hyperparathyroidism were studied. Twelve patients had undergone one or more previous neck explorations. Static imaging with 201Tl was performed first, immediately followed by a 30-min 99mTc-tetrofosmin dynamic study. Delayed views of up to 3 hr postinjection were also obtained. Technetium-99m-pertechnetate was used for thyroid delineation. The tetrofosmin/99mTc-pertechnetate subtraction scan (TF/TC), the single-tracer washout technique and the thallium/technetium subtraction (TL/TC) were compared. Quantification of relative uptakes of tracers in the thyroid and abnormal parathyroids was accomplished by measuring activity within regions of interest. Kinetics of tetrofosmin in the thyroid and abnormal parathyroids were studied by evaluating the plots of the parathyroid to thyroid ratios against time as well as by calculation of the half-clearance times from the slow component of the time-activity curves. RESULTS: The overall sensitivity, specificity and accuracy of TF/TC and TL/TC were 76%, 92% and 83% and 52%, 85% and 65%, respectively. The respective sensitivities were 87% and 70% for adenomas and 72% and 46% for hyperplasia. The parathyroid-to-thyroid activity ratios of tetrofosmin were significantly higher than those of thallium (p < 0.001). The tetrofosmin single-tracer washout study was less accurate than the subtraction technique (overall sensitivity and specificity, 70% and 69%, respectively). The washout properties of tetrofosmin in abnormal parathyroids were not substantially different from those in the thyroid, with a few exceptions (p = 0.4). No correlation of half-clearance times with parathyroid size, degree of early uptake, parathyroid hormone levels or histology could be established. Comparing adenomas to hyperplasia in respect to tetrofosmin retention, a statistically significant difference was observed (p = 0.005). CONCLUSION: Technetium-99m-tetrofosmin is suitable for parathyroid imaging. The kinetic properties of this agent in parathyroid and thyroid tissues do not warrant differential washout protocols. The diagnostic impact of the observed difference in tetrofosmin kinetics between parathyroid adenomas and hyperplasia requires further investigation.

Nonabsorbable antibiotics reduce bacterial and endotoxin translocation in hepatectomised rats.

There is increasing evidence that septic complications, occurring after major hepatectomies, may be caused by gram negative bacteria, translocating from the gut. We investigated in rats, the effect of extended hepatectomy on the structure and morphology of the intestinal mucosa as well as on the translocation of intestinal bacteria and endotoxins. We also examined the effect of nonabsorbable antibiotics on reducing the intestinal flora and consequently the phenomenon of translocation by administering neomycin sulphate and cefazoline. Hepatectomy was found to increase translocation, while administration of nonabsorbable antibiotics decreased it significantly. In addition, hepatectomy increased the aerobic cecal bacterial population, which normalised in the group receiving antibiotics. Among the histological parameters evaluated, villus height demonstrated a significant reduction after hepatectomy, while the number of villi per cm and the number of mitoses per crypt, remained unchanged. Our results indicate that administration of nonabsorbable antibiotics presents a positive effect on bacterial and endotoxin translocation after extended hepatectomy, and this may be related to reduction of colonic bacterial load as an intraluminal effect of antibiotics.

Oral ornithine a-ketoglutarate accelerates healing of the small intestine and reduces bacterial translocation after abdominal radiation.

The effect of dietary ornithine a-ketoglutarate (OKG) on intestinal mucosal integrity and bacterial translocation was studied in rats following administration of a single dose of abdominal radiation (1100 cGy). Following the radiation injury the rats were randomized to receive a nutritionally incomplete diet which contained only water and OKG or a control diet with water and the non-essential amino-acid glycine. Four days after radiation, rats were anaesthetized and a laparotomy was performed. Cultures from mesenteric lymph nodes were taken and two tissue samples from the terminal ileum were also taken for light microscopy, protein and DNA determination. We examined the following parameters: number of villi per cm (V/cm), villus height (Vh), number of mitoses per crypt (M/c) and we measured the mucosal protein and DNA content. Nine of 16 rats who received the OKG-free diet had positive cultures but only 3 of 18 rats who received the OKG-enriched diet (P= 0.002). The group on the OKG-enriched diet had a better intestinal mucosal architecture than the group on the OKG-free diet and the studied parameters of the gut mucosa were significantly better: (V/cm: 130 +/- 8.1 vs 99 +/- 7.9, P = 0.001. Vh(mm): 0.40 +/- 0.03 vs 0.24 +/- 0.05, P= 0.002. M/c: 1.71 +/- 0.03 vs 0.34 +/- 0.2, P= 0.001, Protein (mg/cm): 2.300 +/- 0.033 vs 1.207 +/- 0.014, P = 0.002. DNA (microg/cm): 203 +/- 6.41 vs 130 +/- 4.94, P = 0.001. We conclude that OKG-enriched diet prevents the deleterious effects of radiation on intestinal mucosal morphology and integrity, abolishing thus, the increased bacterial translocation observed after abdominal radiation.

Evidence for two insulin-like growth factor I receptors with distinct primary structure that are differentially expressed during development.

We have previously presented evidence for two IGF I receptor species in rat skeletal muscle. One form of IGF I receptor is selectively expressed in fetal and early postnatal life, and the second is present in both fetal and adult animals. These two IGF I receptors were shown to have similar tryptic phosphopeptide maps but to differ in beta subunit molecular weight (105,000 for the fetal vs. 95,000 for the adult type receptor). In this study, we have used specific antibodies to investigate the structural relationships between the two IGF I receptors. Anti-IGF I receptor beta subunit antibodies were generated against synthetic peptides corresponding to residues 1284-1293 and 1308-1318 of the cloned human IGF I receptor, and the capacity of these antibodies to interact with the two IGF I receptors was investigated. Both anti-peptide antibodies selectively immunoprecipitated the higher molecular weight fetal receptor and not the adult receptor from rat muscle. Human placenta and muscle were shown to contain two receptors similar to those observed in rat muscle. In human muscle, the anti-peptide antibodies and the human-specific monoclonal alpha subunit antibody alpha-IR3 also selectively immunoprecipitated the fetal type receptor. The presence of a 95,000 M(r) IGF I receptor beta subunit distinct from the insulin receptor beta subunit in human muscle was confirmed by the demonstration of an IGF I sensitive receptor with a beta subunit of this size after insulin receptor immunodepletion. These data strongly support the conclusion that the fetal and adult type IGF I receptors differ in primary structure. The fetal receptor corresponds to the cloned and sequenced IGF I receptor, and the primary structure of the adult type receptor has not yet been established.

A novel fetal insulin-like growth factor (IGF) I receptor. Mechanism for increased IGF I- and insulin-stimulated tyrosine kinase activity in fetal muscle.

Insulin and insulin-like growth factor (IGF) I receptors from fetal and adult rat skeletal muscle were compared in order to gain insight into the evolving functions of the hormones during development. Basal, insulin-stimulated, and IGF I-stimulated receptor phosphorylation and tyrosine kinase activity are severalfold higher in partially purified receptor preparations from fetal muscle in comparison with equal numbers of receptors from adult muscle. There are distinct insulin and IGF I receptors with Mr 95,000 beta subunits in adult muscle, as evidenced by hormone dose-response curves, immunoprecipitation with specific antibodies, binding to insulin and IGF I affinity columns, and analysis of tryptic phosphopeptides. In addition to these two receptor species, fetal muscle contains a receptor with a Mr 105,000 beta subunit. The fetal receptor is structurally more closely related to the IGF-I receptor than the insulin receptor on the basis of its precipitation with specific antibodies, binding to an IGF I affinity column, and tryptic phosphopeptide map. The fetal receptor does not appear to bind insulin but, unlike the IGF-I receptor, its phosphorylation is stimulated by low physiological concentrations of both insulin and IGF I. This could be explained by the cross-phosphorylation of fetal receptors by activated insulin receptors. Expression of the fetal receptor is highest in the fetus and decreases markedly during the first 2 weeks of postnatal life. The fetal receptor appears to account for the high tyrosine kinase activity of fetal muscle and may be an important mediator of responses to both insulin and IGF I early in development.

Developmental expression of receptors for insulin, insulin-like growth factor I (IGF-I), and IGF-II in rat skeletal muscle.

Insulin and insulin-like growth factors (IGFs) stimulate responses in skeletal muscle that include effects on carbohydrate and fat metabolism, protein turnover, growth, and differentiation. To gain insight into the relative importance of insulin and IGFs at different stages of development, the expression of their specific receptors was evaluated in skeletal muscle of rats from the late fetal period through 40 weeks of age. Distinct receptors for insulin. IGF-I and IGF-II are present in crude membrane preparations and wheat germ agglutinin-purified extracts of hindlimb muscle from rats at all ages, but each of the three receptors follows a different pattern of expression during development. There is a marked predominance of IGF-II receptors in fetal muscle (80- and 55-fold more abundant than insulin and IGF-I receptors, respectively) and a rapid decline in IGF-II receptors in early postnatal life. IGF-I receptors are more abundant than insulin receptors in the term fetus, remain constant in number until approximately 4 weeks of age, and then gradually decline to adult levels. Insulin receptor number rises 2- to 3-fold postnatally, peaks at approximately 4 weeks, and decreases to levels in the adult that are slightly lower than those in the term fetus. Although binding affinities and receptor specificity did not change during development, the relatively large number of IGF-II receptors in the fetus resulted in significant binding of IGF-I to receptors for both IGF-II and IGF-I. There was a modest increase in apparent mol wt of all three receptor types during development, suggesting a change in a common pathway, such as posttranslational glycosylation. The marked changes in number and distinct patterns of expression of the insulin, IGF-I, and IGF-II receptors in muscle during development are consistent with evolving functions of the three hormones determined by alterations in both receptor number and hormone concentrations.

The sulpiride test in panhypopituitarism.

The results obtained with a new test of prolactin (PRL) release in six panhypopituitary patients as compared to fourteen normal subjects (eight females and six males) are presented. The test consists of the i.m. administration of 100 mg of sulpiride and the measurement of plasma PRL by a double antibody radioimmunoassay techniques at--15, 0, 15, 30, 45, 60, 75, 90, 105 and 120 min. Mean baseline PRL values were not significantly different in the three groups. After sulpiride a 800-4200% increment of prolactin over control values was noted in the females and 1200-3500% increment in the males. The peak values were obtained at 15 or 30 min (6030+/-670 mu/l +/-SEM in the females and 5550+/-870 mu/l in the males). The mean values were not significantly different in the two sexes until the sixtieth minute but were significantly higher (P less than 0.05) in the female thereafter. In the hypopituitary patients a complete failure of response was noted. These results show that the sulpiride test possesses a considerable potential as a screening procedure in the diagnosis of pituitary insufficiency.

Assessment of prolactin release in pituitary dwarfism with the sulpiride test.

We report here the results obtained with a new test of prolactin (PRL) release in six normal pre-pubertal boys, eleven children with short stature of non-pituitary origin and in thirteen pituitary dwarfs. The test consists of the administration of 100 mg of sulpiride i.m. and the measurement of PRL in serum samples up to 120 min after injection. Baseline PRL concentrations were not clearly different in the three groups. After sulpiride a marked increase (3--10 times over control values) in PRL was noted in all normal and short children without pituitary disease. A complete failure of response was observed in ten of the thirteen pituitary dwarfs. It is concluded that sulpiride has considerable potential in the differential diagnosis of children with stunted growth.