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D Micic

Publications and source records attributed to D Micic.

At least 19 recordsLinked to original sources
PubMed2003

Epstein-Barr virus-associated haemophagocytic lymphohistiocytosis in Wiskott-Aldrich syndrome.

UNLABELLED: A patient with Wiskott-Aldrich syndrome who developed Epstein-Barr virus-associated haemophagocytic lymphohistiocytosis (EBV-HLH) is described in this study. At 4 mo of age the patient developed fever associated with bicytopenia and splenomegaly. Analysis of a bone marrow specimen revealed extensive haemophagocytosis, and in situ hybridization for EBV of the bone marrow specimen using an EBV-encoded RNA probe was positive. Diagnosis of EBV-HLH was established and immunotherapy with HLH-94 protocol was started. HLH has been described in patients with other well-defined primary immunodeficiencies such as X-linked lymphoproliferative syndrome, Chediak-Higashi syndrome and Griscelli disease. Also, HLH was reported recently in severe combined immunodeficiency and DiGeorge syndrome. CONCLUSION: The possibility of an underlying primary immunodeficiency should be considered in paediatric patients who present with HLH during infancy.

Child, Preschool↗
PubMed2003

Ghrelin main action on the regulation of growth hormone release is exerted at hypothalamic level.

Ghrelin, a recently isolated hormone, seems to participate in the physiological regulation of GH secretion. Exogenously administered ghrelin stimulates GH discharge in all species so far tested including man, but whether this action is exerted at pituitary or alternatively at hypothalamic level is not known at present. To understand the point of ghrelin action a group of patients with organic lesion mainly in the hypothalamic area and matched controls were studied. Patients showed a severe GH deficiency after hypothalamic stimulation (ITT), but partial response after GHRH administration. Cases and controls were tested on three separate days by either ghrelin; GHRH; and ghrelin plus GHRH; always at 1 micro g/Kg iv. The mean GH peak after stimulation in the patients were: 0.4 +/- 0.1 micro g/L by ITT; 3.1 +/- 0.5 micro g/L after GHRH; 2.0 +/- 0.8 micro g/L after ghrelin; and 9.6 +/- 2.9 micro g/L after the combination of GHRH plus ghrelin. In the controls GHRH induced a GH peak of 21.2 +/- 7.5 micro g/L, and 75.1 +/- 16.0 micro g/L after ghrelin with a peak after GHRH + ghrelin of 103.5 +/- 26.4 micro g/L. These data indicate that when hypothalamic structures are not operative ghrelin, either alone or in combination with GHRH, is not able to significantly release GH. In addition to postulating a hypothalamic point of action for the ghrelin-induced GH secretion, these results suggests that ghrelin will not have significant clinical utility in patients with GH deficiency due to organic lesion.

Adult↗
PubMed2002

A single growth hormone (GH) determination is sufficient for the diagnosis of GH-deficiency in adult patients using the growth hormone releasing hormone plus growth hormone releasing peptide-6 test.

BACKGROUND: The diagnosis of GH deficiency in adults is based on the provocative testing of GH secretion. When testing a patient with suspected GH deficiency, clinicians assess the whole secretory curve and select the GH peak as an index of secretory capability. This procedure is time consuming and the determination of GH in several samples is necessary. The combined administration of growth hormone releasing hormone (GHRH) plus growth hormone releasing peptide-6 (GHRP-6) is an effective test of GH secretion, and it has been unambiguously demonstrated that the elicited GH peak is capable of segregating normal GH secretion subjects from GH deficient patients on an individual basis. The GHRH + GHRP-6 test biochemically classifies patients into three groups; those with a stimulated GH peak >/= 20 micro g/l are considered normal and those with peaks at </= 10 micro g/l as GH deficient. The group comprising individuals between these parameters is considered uncertain, and the results are further interpreted according to clinical information, or by other tests. OBJECTIVE: As the GHRH + GHRP-6 test induces GH peaks consistently in the first 30 minutes, the working hypothesis assessed in this study was whether a single determination of GH 30 minutes after stimulus could provide the same clinical classification as the whole secretory curve. PATIENTS AND METHODS: Three hundred and forty-nine adult subjects (146 patients with organic pituitary disease and 203 healthy subjects) were studied. All were administered GHRH 1 micro g/kg i.v. plus GHRP-6 1 micro g/kg i.v. at 0 minutes, and blood samples were obtained at regular intervals. GH was determined in all samples. RESULTS: GHRH + GHRP-6-evoked GH peaks in controls and patients were not correlated with GH basal values, making this determination useless for test validation. In contrast, an excellent correlation was observed between GH values at 30 minutes and the GH peaks (r = 0.994, P < 0.0001). When comparing the 30-minute GH values against the peaks, the biochemical classification changed from normal toward uncertain in only five out of 203 control subjects, which is without clinical relevance according to Bayes theorem. Similarly, when the 30-minute value was used instead of the peak in GH deficient patients, only two out of 146 patients moved from the uncertain area toward the GH deficient one. Thus, better diagnostic classification was provided for patients. CONCLUSIONS: The GHRH + GHRP-6 test is a convenient, safe and reliable, provocative test of GH reserve in adults, which can be reduced to a single fixed GH determination 30 minutes after stimulus.

Adolescent↗
PubMed2001

Loss of gender difference in serum leptin levels and its slow recovery after successful surgery for Leydig cell tumours in two virilized females.

One of the factors that predicts serum leptin levels is gender. It has been shown that sex steroid hormones, in particular testosterone, play an important role in the regulation of serum leptin levels. We had the opportunity to examine the effects of acute and chronic changes in serum testosterone levels on serum leptin concentrations in two virilized females harbouring testosterone-secreting ovarian tumours, before and after curative surgery. Chronically elevated basal testosterone levels (46 nmol/l) were associated with suppressed serum leptin levels (1.46 microg/l and 2.56 microg/l) vs. 12 age- and BMI-matched healthy subjects 9.89 +/- 0.64 microg/l. Leptin levels were determined from pooled serum samples assayed by commercial radioimmunoassay. High testosterone levels abolished the well known sexual dimorphism of serum leptin levels. Two weeks after curative resection of these tumours serum leptin levels were unaltered and started to increase progressively after one month. One patient received parenteral conjugated oestrogens while the other resumed spontaneous menstrual cycles. Three months after curative surgery obvious changes in body composition were registered (DEXA). Six months later further rise in serum leptin concentrations occurred without further changes in body composition. In conclusion, leptin levels did not change in spite of rapid changes in the steroid milieu, but in the long term increase in body fat stores, new steroid milieu and maybe other factors are important determining factors of serum leptin levels.

Adult↗
PubMed2001

Physiology and possible pathology of growth hormone secretagogues.

Growth hormone segretagogues (GHS) are artificial molecules able to stimulate growth hormone (GH) secretion. They were discovered before the hypothalamic growth hormone-releasing hormone (GHRH). These molecules had a structure devoid of opiate activity, and GHRP-6 is the most representative compound. These compounds identified a new physiological system involved in GH regulation, and their action is independent of GHRH or somatostatin. Recently an endogenous ligand for the GHS receptor, ghrelin, was discovered, suggesting that this may be the third factor in the control of GH secretion. This peptide was isolated from the stomach and is characterized by the presence of an acylated group representing a new type of molecular hormonal structure; it is able to stimulate GH secretion in vitro and in vivo in the rat. As observed for the majority of GHS, ghrelin's action is not fully specific for GH release; the acute administration of ghrelin stimulates the release of significant amounts of PRL, ACTH and cortisol. Moreover, the presence of ghrelin in rat and human placenta has been reported, suggesting a possible role of this peptide in the local modulation of GH release and in maternal and fetal pituitary secretion. Ghrelin stimulates gastric acid secretion, is able to induce adiposity by activating a central mechanism for increasing food intake and decreasing fat utilization, and ghrelin mRNA and peptide are expressed in normal and adenomatous human pituitary tissue. Possible therapeutic applications of ghrelin remain to be assessed.

Ghrelin↗
PubMed2000

GH-releasing hormone and GH-releasing peptide-6 for diagnostic testing in GH-deficient adults.

BACKGROUND: The diagnosis of growth hormone (GH) deficiency in adults is based on provocative testing of GH secretion. The insulin tolerance test (ITT), currently the favoured test for this diagnosis, has been criticised for poor reproducibility and inconvenience. Since the combined administration of GH-releasing hormone (GHRH) plus GH-releasing peptide-6 (GHRP-6) is the most potent stimulus of GH secretion, we did a multicentre study comparing GH peaks elicited by ITT with those elicited by the GHRH/GHRP-6 test in healthy controls and GH-deficient individuals (cases). METHODS: 125 adult patients with organic pituitary disease and 125 healthy individuals were studied. All cases and controls were given GHRH 1 microg per kg bodyweight intravenously plus GHRP-6 1 microg per kg intravenously at 0 min and blood samples were obtained during a subsequent 120 min period. 27 controls and all cases had an ITT. Inclusion criteria were severe GH deficiency--ie, a GH peak after ITT of < or = 3 microg/L. Results of the GHRH/GHRP-6 test were analysed by receiver-operating characteristic curve methodology. FINDINGS: GH peaks seen after the GHRH/GHRP-6 test did not result in any side-effects and were not affected by age, sex, amount of adipose tissue, or by the GH assay system used. The GH mean peak after the GHRH/GHRP-6 test was 59.2 microg/L (SD 2.2) for controls and 4.1 microg/L (0.3) for cases, whereas after ITT the mean peak was 14.3 microg/L (1.7) and 0.5 microg/L (0.06), respectively. The differential peak responses of controls and cases was greater (p<0.001), for GHRH/GHRP-6 test than for ITT. When individually analysed GH peaks were a continuum, from 139.0 microg/L to 0.01 microg/L, with a cut-off point of 15.0 microg/L. The GHRH/GHRP-6 test performed well under the ROC curve analysis. For clinical utility, it is then proposed that values > or = 20.00 microg/L be considered normal and < or = 10.00 microg/L as GH deficient. INTERPRETATION: The GHRH/GHRP-6 test is a convenient, safe and reliable test for adult GH deficiency and is not confounded by clinical factors known to alter GH secretory patterns. An evoked GH concentration of > or = 15.0 microg/L accurately distinguishes between healthy and GH-deficient adults.

Adolescent↗
PubMed1999

Growth hormone secretagogues: the clinical future.

Growth hormone (GH) releasing hexapeptide (GHRP)-6 and other peptidergic and non-peptidergic compounds collectively designated GH secretagogues (GHS) are potent releasers of GH in man. Their clinical future may be envisioned in three areas: therapy of GH-deficient (GHD) states, diagnosis of GHD, and non-endocrinological actions. As therapeutic agents and compared with GH itself, GHS have the disadvantage of lower potency but have a more physiological and safer profile of GH secretion. GHS administration could be indicated for states in which medium GH doses have been shown to be effective. As a diagnostic tool, the combined administration of GH releasing hormone plus GHRP-6, both at saturating doses, is currently the most powerful releaser of GH, devoid of side effects and convenient for the patient; it may also be an alternative to the insulin tolerance test for the diagnosis of GHD in adult patients. Their potential action at cardiovascular level is highly promising. Although the clinical future of GH releasing substances is appealing, probably the most relevant contribution has yet to be discovered. Once the endogenous ligand of the GHS receptor is identified, we will have an insight into the real hypothalamic control of GH secretion in man. With this knowledge it is likely that some diagnostic and therapeutic actions that are commonly undertaken will significantly change.

Animals↗
PubMed1998

Growth hormone secretion elicited by GHRH, GHRP-6 or GHRH plus GHRP-6 in patients with microprolactinoma and macroprolactinoma before and after bromocriptine therapy.

OBJECTIVE: Growth hormone-releasing peptides (GHRPs) are potent GH releasers which act at both pituitary and hypothalamic levels through specific G-protein coupled receptors, recently cloned. A synergistic effect from the simultaneous administration of GHRH + GHRP-6 on GH release is observed in normal subjects, while it is absent in patients with hypothalamo-pituitary disconnection. We studied the effects of GHRH, GHRP-6 and both secretagogues on GH release in patients harbouring pituitary tumours that may be reduced in size by medical treatment. DESIGN: Analysis of peak GH response to GHRH, GHRP-6 and GHRH plus GHRP-6 in patients with micro- and macroprolactinomas. Integrated GH response over 2 hours calculated as AUG-GH mU/l x 120 min. Analysis of delta PRL above the basal level in response to the same GH releasers. PATIENTS: Eleven patients with macroprolactinomas aged 41.2 +/- 4.8 years (range 24-75), nine patients with microprolactinomas aged 31.5 +/- 3.4 (range 22-53) and 13 healthy subjects aged 42.1 +/- 4.7 years (range 22-64) were studied. Prolactinoma patients were then treated with bromocriptine (15-20 mg orally) for 6-24 months. Tests were repeated when there was evidence of tumour shrinkage and normalized plasma prolactin concentrations. RESULTS: Peak GH response before treatment in macroprolactinoma patients was 4.9 +/- 0.9 mu/l after GHRH, 8 +/- 4 mU/l after GHRP-6 and 18 +/- 5 mU/l after GHRH + GHRP-6. Synergism was absent. AUC were 390 +/- 90; 500 +/- 100 and 1100 +/- 300 mU/l x 120 min respectively. These values were all significantly different (P < 0.05) from normal subjects and patients with microprolactinomas with peak GH 16.8 +/- 0.9 mU/l after GHRH; 43 +/- 6 mU/l after GHRP-6 and 130 +/- 10 mU/l after GHRH + GHRP-6. AUC-GH was 1200 +/- 400 after GHRH, 2200 +/- 400 after GHRP-6 and 9000 +/- 1000 mU/l x 120 min after GHRH + GHRP-6. As in normal subjects, synergism was preserved in patients with microprolactinoma (P > 0.05). After treatment with bromocriptine peak GH in patients with macroprolactinoma was 8 +/- 4 mU/l after GHRH, 22 +/- 5 mU/l after GHRP-6 and 70 +/- 20 mU/l after GHRH + GHRP-6. AUC-GH was 800 +/- 300, 1100 +/- 300 and 3500 +/- 800 mU/l x 120 min, respectively. The response of GH after GHRP-6 and GHRH + GHRP-6 improved significantly (P < 0.05) in treated patients with macroprolactinoma. There was no significant change in GH response in microprolactinoma patients after treatment with bromocriptine. Peak GH after GHRH was 30 +/- 20 mU/l, after GHRP-6 it was 75 +/- 8 mU/l and after GHRH + GHRP-6 it was 200 +/- 30 mU/l. AUC-GH was 1500 +/- 700 after GHRH, 4500 +/- 500 after GHRP-6 and 15,100 +/- 600 mU/l x 120 min. Delta prolactin after GHRP-6 did not change before and after bromocriptine treatment in patients with macroprolactinoma or microprolactinoma. CONCLUSION: GH release after GHRP-6 or GHRH + GHRP-6 is fully preserved in patients with microprolactinomas and does not differ before and after treatment with bromocriptine. Patients with macroprolactinoma have blunted responses of GH after GHRH and GHRP-6 and synergism is severely compromised. GH responsiveness to and synergistic interaction between GHRH and GHRP-6 recovers after shrinkage of macroprolactinoma with bromocriptine. Prolactin release stimulated by intravenous administration of GHRP-6 in healthy subjects was not seen in patients with micro- or macroprolactinomas.

Adult↗
PubMed1998

Increased incidence of neoplasia in patients with pituitary adenomas. The Pituitary Study Group.

OBJECTIVE: The goal of our study was to determine the rate of neoplasms in patients with other pituitary adenomas (non-functioning and prolactinomas) in comparison with acromegaly which is known to favour the development of neoplasia. DESIGN AND PATIENTS: We reviewed clinical records for 220 patients with acromegaly, 151 patients with non-functioning pituitary adenoma (NF) and 98 patients with prolactinomas. Incidence rates of cancer for patients with pituitary tumours were calculated per person-years of follow-up study. These rates were then compared with sex and age adjusted incidence rates reported by National Tumour Registry. An internal control group of 163 subjects with a non-neoplastic condition, i.e. Graves' disease followed chronically in the same clinic was also studied. The ratios observed to expected were expressed as standardized incidence rates (SIR). The only significant difference between the acromegalic and other pituitary tumours patients was in hypopituitarism, present in 18.2% (acromegaly) 47% (NF) and 18.6% (prolactinomas). RESULTS: Twenty-three malignant tumours were registered in 19 acromegalics (1 Hodgkin disease, 1 myelogenous leukaemia, 1 lymphocytic leukaemia, 3 papillary thyroid carcinomas, 1 ovarian carcinoma, 2 colorectal carcinoma, 1 renal cell carcinoma, 4 cervical carcinoma, 2 skin cancers, 2 pancreatic carcinoma, 4 breast carcinoma, 1 bladder carcinoma). Three acromegalics harboured two malignancies. Patients with acromegaly had a 3.39-fold increased rate of malignant tumours compared with the general population and a 3.21-fold increased rate compared with our internal control group. Eleven malignant tumours were found in patients with NF-pituitary adenomas and 2 in prolactinoma patients (1 lymphoma, 1 multiple myeloma, 1 colonic cancer, 1 renal cell cancer, 1 stomach cancer, 2 lung cancers, 1 cervix carcinoma, 1 breast cancer, 1 testicular carcinoma and 3 melanoma). Patients with NF pituitary adenomas had a 3.91-fold increased rate of malignant tumours compared with the general population and 4.07-fold increase compared with the internal control group. Patients harbouring prolactinomas did not have an increased incidence rate of malignancy compared with the general population or our internal controls. Female patients with acromegaly and male patients with NF-pituitary adenoma had higher incidences of neoplasia. CONCLUSION: We have demonstrated that the overall incidence of malignant tumours in patients with non-functioning pituitary adenomas and acromegaly is significantly higher than expected for general population and for our internal control group.

Acromegaly↗
PubMed1998

Preserved growth hormone (GH) secretion in aged and very old subjects after testing with the combined stimulus GH-releasing hormone plus GH-releasing hexapeptide-6.

Either spontaneous or pharmacological stimulated GH secretion is reduced with advanced age. This observation is an added difficulty for the biochemical diagnosis of GH deficiency in adults. Furthermore, the combined administration of saturating doses of GH-releasing hormone (GHRH) plus GH-releasing hexapeptide (GHRP)-6 is nowadays the most effective GH-releasing stimulus tested in a variety of settings related to altered somatotroph function. To understand whether the GH discharge elicited by the combined stimulus declines with age, 26 normal subjects of both sexes, divided into 3 age groups [adults 19-40 yr; aged 46-65 yr; and very old (75-96 yr) subjects] were studied. They were administered i.v., as bolus and in combination, 90 micrograms GHRH plus 90 micrograms GHRP-6. In the three groups, the combined administration of GHRH plus GHRP-6 elicited a GH area under the curve (microgram/L per 120 min) of 3,127 +/- 262, 3,409 +/- 573, and 4,655 +/- 737 for adults, aged, and very old subjects, respectively (nonsignificant differences). The mean GH peak was 47.5 +/- 4.5 micrograms/L for adults, 52.9 +/- 8.4 micrograms/L for aged subjects, and 76.0 +/- 11.7 for very old subjects (nonsignificant differences). Individually examined, there were no nonresponders to the combined stimulus, and all subjects (independently of age) showed a GH peak over 25 micrograms/L (the lowest peak was 27.3 micrograms/L, and the highest peak was 119.2 micrograms/L). In conclusion, the GHRH plus GHRP-6-induced GH release is well preserved in aged and very old subjects, which suggests that the GH secretory capability of the combined test is not reduced by age. This combined test may be useful for the diagnosis of GH-deficient states in adults.

Adult↗
PubMed1998

Serum leptin and insulin concentrations in patients with insulinoma before and after surgery.

Inferential studies suggest that circulating insulin concentrations positively regulate leptin secretion by adipocytes. In humans, however, insulin requires prolonged periods of time, and relatively artificial set-ups before a relationship with leptin can be observed. In the present work, serum leptin concentrations were measured in five patients with insulinoma before and one month after surgery and in five control subjects matched by sex and body mass index (BMI). The control subjects presented a mean serum leptin concentration of 6.7+/-1.5 microg/l and a BMI of 24.9+/-1.1. The mean serum leptin concentration in patients with insulinoma was 11.8+/-3.1 microg/l (P < 0.05 vs controls), with a BMI of 26.3+/-1.9. After surgery, there was a non-significant reduction in BMI (25.8+/-1.7), and a clear reduction in serum leptin concentration (5.6+/-2.4 microg/l, P < 0.05 vs pre surgical values and no difference vs control subjects). The fasting area under the curve (AUC) of insulin concentration (in mU/l per 120 min) before surgery was 14421+/-4981 and after surgery was 1306-/+171 (P < 0.05). Before surgery, serum leptin concentrations significantly correlated with BMI (r = 0.71) and AUC of insulin (r = 0.82), a correlation that was lost after surgery. In conclusion, serum leptin concentrations are significantly elevated in patients with chronically high insulin levels due to insulinoma. After surgical treatment and normalization of insulin values, leptin levels return to normal.

Adult↗
PubMed1997

Absence of desensitization by hexarelin to subsequent GH releasing hormone-mediated GH secretion in patients with anorexia nervosa.

OBJECTIVE: Both the basal levels and the neuroregulation of GH secretion are perturbed in patients with anorexia nervosa. It is unknown if these alterations are due to severe undernutrition or if they reflect basic neurotransmitter alterations of the patient's neural pathways. On the other hand, prior administration of the GH secretagogue hexarelin in normal subjects blocks the GH-releasing capability of GH releasing hormone (GHRH) administered 2 hours later. In the present work a sequential test was performed using the administration of hexarelin as first stimulus followed 120 minutes later by GHRH. The two aims of the study were: (a) to evaluate the interaction of GHRH and hexarelin, and (b) to further understand the alterations in GH neuroregulation in patients with anorexia nervosa. DESIGN: The GH stimuli used were hexarelin (1 micrograms/kg i.v.), a GH stimulus whose main action is hypothalamic, followed 120 minutes later by GHRH (1 micrograms/kg i.v.) as a pituitary stimulus. Each woman was tested once. PATIENTS: Thirty-two woman matched for age participated in the study: six normal-weight women as controls, 14 women with anorexia nervosa, seven women with secondary amenorrhoea due to voluntary weight loss for aesthetic reasons, and five normal-weight women after 72 hours of a controlled hypocaloric diet (800 cal/day). MEASUREMENTS: Plasma GH levels were measured by time-resolved fluoroimmunosasay, each value shown is the mean +/- SE in mU/l. RESULTS: The administration of hexarelin to the normal-weight women induced a clear-cut GH secretion (expressed as mean +/- SE of GH peak in mU/l of 77.5 +/- 21.8, but blocked the GH-releasing capability of GHRH administered 120 minutes later (6.6 +/- 2.8, P < 0.05). In contrast, the women with anorexia nervosa showed a normal GH response after the two stimuli: hexarelin 64.8 +/- 9.2. GHRH 71.1 +/- 14.2. The absence of heterologous desensitization was specific to anorexia nervosa, because the women with amenorrhoea due to voluntary weight loss but with a normal energy intake showed a pattern similar to the controls (GH after hexarelin 60.3 +/- 9.5 and to GHRH 120 minutes later 6.2 +/- 1.0 (P < 0.05)). Similarly, the women after the short-term hypocaloric diet showed a hexarelin-mediated GH secretion of 99.6 +/- 17.8, which blunted the subsequent administration of GHRH (GH mean peak of 9.9 +/- 2.9, P < 0.05 vs hexarelin). CONCLUSIONS: In the normal subjects, the administration of hexarelin induced clear-cut GH secretion, but inhibited the action of GHRH when administered 120 min later, while this heterologous desensitization was not observed in the patients with anorexia nervosa. This sequentially delayed test may be of some value in the clinical setting for assessing the status of patients with anorexia nervosa.

Adult↗
PubMed1997

Neuropharmacological assessment of growth hormone secretion.

The biochemical diagnosis of individuals who are either deficient in growth hormone (GH) or who have alterations in the normal pattern of GH secretion is difficult. The uncertainty surrounding diagnosis reflects the lack of a thorough understanding of the physiology of GH secretion and of the hypothalamic hormones involved. At least three hormones are implicated: GH-releasing hormone (GHRH), somatostatin and the endogenous ligand of the GH secretagogue receptor, although the role that each plays in the release of GH is not clear from the available experimental evidence. In such a situation, most of the dynamic tests of GH secretory capacity in humans need to undergo a 'trial and error' process before being validated. The search for the 'gold standard' test of GH secretion is ongoing, and the combination of GHRH plus GH secretagogues will probably play an important role in future clinical diagnosis.

Growth Hormone↗
PubMed1997

Growth hormone secretagogues in pathological states: diagnostic implications.

The identification and cloning of the receptor for synthetic growth hormone (GH) secretagogues, even before the endogenous ligand has been identified or its precise physiological role established, suggests that there is a novel target of action for this class of drug. In an attempt to select patients who will benefit from GH treatment, GH secretagogues are being evaluated for their usefulness in diagnosing GH deficiency. The effects of GH-releasing peptides (GHRPs) on GH release as a function of age and metabolic status, and in different neuroendocrine pathologies, are described, as are the different mechanisms of action, potency and reproducibility of the response to GHRPs compared with GH-releasing hormone (GHRH). GHRPs offer the advantage over GHRH in natural models of deranged GH secretion in that, in various metabolic states (e.g. obesity, anorexia nervosa and non-insulin-dependent diabetes mellitus), the GH response to GHRH is more impaired than it is to GHRPs. However, in some neuroendocrine pathologies, the reverse is true. Thus, both secretagogues provide separate information on the physiological status of somatotrophs.

Anorexia Nervosa↗
PubMed1996

Role of the new growth hormone-releasing secretagogues in the diagnosis of some hypothalamopituitary pathologies.

Growth hormone (GH)-releasing hormone (GHRH) and somatostatin have a dominant role in regulating GH secretion. However, results of studies using the new class of GH secretogogues, particularly GHRP-6, indicate that there may also be other, as yet undefined, hypothalamic mechanisms involved. Studies in adults with hypothalamopituitary disconnection (functional pituitary stalk transection), show GHRP-6-mediated GH release to be completely blocked, indicating a main action at the hypothalamic rather than the pituitary level. The synergistic effect of GHRH plus GHRP-6 administration on GH release seen in normal adults (and virtually unaffected by age, obesity, or sex) is also absent in these patients, providing further support for this conclusion. Studies of the effects of GHRP-6 in children with GH deficiency due to perinatal pituitary stalk transection have produced similar findings. It is suggested that the combined GHRH plus GHRH-6 test should be a promising tool for diagnosing GH deficiency states in both children and adults, and may identify a subgroup of patients with GH deficiency caused by interruption of the hypothalamopituitary connection.

Adult↗