ABSTRACT
BACKGROUND AND AIMS: Ghrelin is an orexigenic hormone produced in the stomach and in other organs, exerting a wide range of metabolic functions, including stimulation of GH secretion. Ghrelin secretion is decreased by iv or oral glucose load as well as during euglycemic-hyperinsulinemic clamp and hypoglycemia. We evaluated the circulating ghrelin levels in GH-deficient (GHD) and in GH-sufficient (GHS) patients during GHRH plus arginine test. MATERIALS AND METHODS: The study group comprised 35 patients, including 20 with pituitary tumors, 12 with empty sella, 2 with short stature, and 1 with post-traumatic isolated GH deficiency. According to the results of GHRH plus arginine test, 14 patients were defined as GHD and 21 as GHS. Patients with central hypothyroidism, hypocorticism, and hypogonadism had been on replacement therapy for at least 3 months at the moment of the study. Blood samples were collected every 20 min up to 60 min after GHRH and arginine administration. RESULTS: By definition, GH response to GHRH plus arginine was higher in GHS than GHD group (p<0.0001). Basal serum ghrelin levels were not different in the two groups and did not correlate with body mass index, GH, IGFI and insulin concentrations. After GHRH plus arginine, serum ghrelin decreased significantly in both groups, with percent decreases ranging 13.3-66.6% in GHD patients (p=0.001) and 7.2-42.2% in GHS patients (p=0.004), with no significant difference in the two groups (p=0.12). CONCLUSION: Our results show that ghrelin secretion is not modulated by acute GH increase observed in GHS subjects during GHRH plus arginine infusion. The similar decrease of serum ghrelin after GHRH plus arginine stimulation in both GHS and GHD subjects demonstrated that there is no negative feedback of GH on ghrelin secretion.
Subject(s)
Arginine/administration & dosage , Empty Sella Syndrome/drug therapy , Ghrelin/blood , Growth Disorders/drug therapy , Growth Hormone-Releasing Hormone/administration & dosage , Human Growth Hormone/blood , Pituitary Neoplasms/drug therapy , Adolescent , Adult , Aged , Body Composition , Body Mass Index , Empty Sella Syndrome/blood , Empty Sella Syndrome/pathology , Feedback, Physiological , Female , Glucose/metabolism , Growth Disorders/blood , Growth Disorders/pathology , Human Growth Hormone/deficiency , Humans , Insulin/metabolism , Male , Middle Aged , Pituitary Neoplasms/blood , Pituitary Neoplasms/pathology , Radioimmunoassay , Young AdultABSTRACT
Cyclic Cushing's disease is an unusual disorder characterised by ACTH-dependent periodical increase of serum cortisol levels, clinically accompanied by peripheral edema, abnormalities of cardiac rhythm and hypokalemia. The condition may be unrecognised for years, since the typical features of Cushing's disease are usually absent due to the intermittent and brief duration of cortisol hypersecretion. We describe the case of a 42-yr-old man with Cyclic Cushing's disease due to an ACTH-producing pituitary macroadenoma, who presented two episodes of hypercortisolism in a 3-yr-period, clinically characterised by peripheral edema, hypokalemia and arrhythmia. The diagnosis was suspected because of a paradoxical increase of plasma ACTH and cortisol after dexamethasone administration during an asymptomatic period and was confirmed by pituitary imaging and by final histology after transphenoidal resection of the pituitary adenoma. After surgery, the patient resumed a normal pituitary-adrenal function with restoration of the normal ACTH and cortisol suppression after dexamethasone. Cyclic Cushing's disease should be considered in the differential diagnosis of several conditions characterised by recurrent episodes of idiopathic edema, hypokalemia or unexplained cardiac arrhythmia. In such patients, the pituitary-adrenal axis should be tested possibly during the acute phase of their disease or using the dexamethasone suppression test during asymptomatic intervals.
