Helicobacter pylori CagA antibodies and thyroid function in latent autoimmune diabetes in adults.

OBJECTIVE: H. pylori infection is reportedly associated with autoimmune diseases such as chronic thyroiditis and autoimmune diabetes. The aim of this study is to determine the association between H. pylori infection and its virulent strain CagA with antibodies against thyroperoxidase (TPO Ab) and thyrotropin (TSH) in a cohort of latent autoimmune diabetes in adult (LADA) patients. PATIENTS AND METHODS: We included 234 LADA patients (53.8% women). Antibodies against H. pylori whole antigens and CagA, TPO Ab and TSH were assessed in all patients. RESULTS: Prevalence of IgG against H. pylori and GagA was 52.1% and 20.9% respectively. Antibodies against H. pylori were not associated with TPO Ab and TSH (rho = 0.067, p = 0.620 and rho = 0.156, p = 0.099, respectively). Antibodies against CagA showed a positive association with TSH and TPO Ab (respectively rho = 0.309, p = 0.036 and rho = 0.419, p = 0.037). Subjects with hypothyroidism (TSH ≥ 3.5 µU/ml) had an increased frequency of Ab anti CagA (p = 0.059). CONCLUSIONS: The infection by H. pylori strains expressing CagA is associated with increased TPO Ab and TSH levels in LADA patients, suggesting a possible mechanism involved in thyroid autoimmunity and dysfunction of the gland. Further research is needed to test this hypothesis.

No evidence of association between subclinical thyroid disorders and common carotid intima medial thickness or atherosclerotic plaque.

BACKGROUND AND AIMS: Increased carotid artery intima-media thickness (IMT) and the presence of plaques have been shown to be predictors of cardiovascular disease. The cardiovascular risk in patients with overt thyroid diseases is related to increased risk of atherosclerosis, but there has been no clear evidence about subclinical disorders. We have assessed whether subclinical thyroid dysfunction is associated with arterial thickening and plaque. METHODS AND RESULTS: The SardiNIA study is a population-based survey on the Italian island of Sardinia. We reviewed data from 5815 subjects (aged 14-102 years), none of whom had overt hyperthyroidism or hypothyroidism or was taking thyroid medication. Serum thyrotropin (TSH), free thyroxine, together with carotid ultrasound IMT and the presence of common carotid plaques were analysed in all subjects. Possible association of IMT and carotid plaques with thyroid parameters was evaluated by univariate and multivariate analyses. IMT was significantly associated with age, sex, smoking, low density lipoprotein cholesterol (LDL), high density lipoprotein cholesterol, pulse pressure (PP), history of arterial hypertension, diabetes, and previous cardiovascular events (p = 0.001 or lower, R(2) = 0.47). Carotid plaques were predicted by age, sex, LDL, PP, history of diabetes, previous cardiovascular events, and the use of statins (p = 0.029 or lower). Thyroid hormone was not predictive of carotid atherosclerosis when adjusted for confounders. CONCLUSION: Thyroid hormone is not associated with increased IMT or with the presence of carotid artery plaque. Our data do not support the idea that treating subclinical disorders might help to prevent arterial remodelling or carotid atherosclerosis.

Primary symptomatic adrenal insufficiency induced by megestrol acetate.

Megestrol acetate (MA) is a progestational agent for the treatment of metastatic breast cancer and endometrial cancer. MA has also been used to promote weight gain in malnourished elderly patients, in patients with immunodeficiency virus and in cancer-induced cachexia. In addition to thromboembolic disease, MA may induce hyperglycaemia, osteoporosis, suppression of the gonadal axis, and Cushing's syndrome. MA has also been shown to cause symptomatic suppression of the hypothalamic-pituitary-adrenal (HPA) axis owing to its intrinsic glucocorticoid-like effect. Three additional patients are presented who developed symptomatic adrenal insufficiency while they were receiving 160-320 mg MA daily. The patients were treated with cortisone acetate supplements, had clear evidence of HPA-axis suppression but recovered fully after MA was discontinued. Patients receiving MA might have an inadequate adrenal response during stressful conditions, possibly because 160-320 mg MA daily may not provide adequate protection to prevent the symptoms of adrenal insufficiency. The adverse MA effect on the HPA axis is probably not well recognised in clinical practice, and clinicians need an increased awareness of the endocrine complications secondary to MA treatment.

Number of autoantibodies and HLA genotype, more than high titers of glutamic acid decarboxylase autoantibodies, predict insulin dependence in latent autoimmune diabetes of adults.

OBJECTIVE: In latent autoimmune diabetes of adults (LADA), the progression into insulin-dependent diabetes is usually faster than in type 2 diabetes (T2D) but the factors influencing this progression are not completely known. In this study, we searched for sensitive markers associated with early development of insulin dependence. DESIGN: The screening of 5568 T2D patients for glutamic acid decarboxylase autoantibodies (GAD65Ab) identified 276 LADA patients (M=131; F=145) and in 251 of them, tyrosine phosphatase-2 (IA-2Ab) and thyroperoxidase autoantibodies (TPOAbs), some clinical features and genotype variation of the main type 1 diabetes (T1D) disease susceptibility loci (HLA-DRB1 and HLA-DQB1) were analyzed. RESULTS: Four years after the diagnosis of diabetes, high GAD65Ab titer was not significantly associated with faster progression toward insulin deficiency (P=0.104). Patients with GAD65Ab and TPOAb or IA-2Ab or triple positivity for both islet and TPOAbs (GAD65Ab/IA-2Ab/TPOAb) showed a significantly faster disease progression (P=0.002). Among 104 TPOAb-positive LADA patients, 10 received replacement therapy (l-thyroxine), 43 showed high TSH levels (62.7% developed insulin dependence), and 3 had hyperthyroidism treated with methimazole. Multivariate analysis revealed a significant effect on disease progression only for TPOAb (P=0.022), female gender (P=0.036), low body mass index (BMI; P=0.001), and T1D high/intermediate risk HLA-DRB1/DQB1 genotypes grouped (P=0.020). CONCLUSIONS: High GAD65Ab titers per se are not a major risk factor for disease progression in LADA, while the number of positive autoantibodies and HLA DRB1-DQB1 genotypes at high risk for T1D are significant predictors. Moreover, clinical characteristics such as low BMI and female gender are more likely to identify patients who will require insulin therapy within 4 years of diagnosis.

[Severe hypertriglyceridemia without organ complications in an alcoholic non-diabetic patient]. / Grave ipertrigliceridemia senza complicanza d'organo in un paziente alcolista non diabetico.

A case report of a non-diabetic alcoholic patient (ethanol intake >220 g/d) who experienced severe hypertriglyceridemia (12.679 mg/dL) without pancreatitis or detectable genetic factors responsible for severe dyslipidemia is described. Following the normalization of triglyceride and cholesterol levels, through lipid-free parenteral nutrition therapy, a regimen of alcohol withdrawal and a well-balanced diet with less than 10% saturated fat maintained a normal lipid profile without requiring any lipid-lowering drug. The absence of organ damage in the patient is likely to be attributed to the short duration of the elevated triglyceride peak. The treatment of this disorder does not necessarily require LDL-apheresis but can be simply managed by parenteral therapy provided that no other risk factors are present.

Activation of alpha1-adrenoceptors inhibits growth hormone secretion in humans.

In order to determine whether an alpha1-adrenergic mechanism is involved in the secretion of Growth Hormone (GH) in humans, we studied the effect of the alpha1-adrenergic-stimulating agent methoxamine on serum GH levels in twelve normal males (age range 22-32 years). Intravenous infusion of methoxamine (dose: 6 microg/kg/min; duration: 150 min) significantly reduced serum GH levels at time 120 and 150, and on integrated concentrations. These data suggest that alpha1-adrenergic receptors inhibit tonic GH secretion in humans.

Correlation between nasal mucociliary clearance time and gastroesophageal reflux disease: our experience on 50 patients.

OBJECTIVES: It is increasingly suggested that gastroesophageal reflux disease (GERD) could play an important role in chronic rhinosinusitis. The aim of our study was to evaluate the nasal mucociliary clearance time in GERD patients and if any correlations could be assumed. METHODS: Fifty GERD patients endoscopically diagnosed underwent an ear, nose and throat evaluation. The saccharin test and the 20-Item Sino-nasal Outcome Test (SNOT-20) were administered to 50 participants who correspond to our inclusion criteria. The saccharin test is a validated proof to verify the nasal mucociliary clearance time and the SNOT-20 is a disease-specific, health-related quality of-life questionnaire widely used for the assessment of rhinosinusitis. RESULTS: Thirty-seven (74%) patients showed a significant increment in their saccharin test values in comparison with the others subjects (23.79+/-5.58 vs 8.15+/-2.06min; P=0.0001). This group of patients reported only typical gastroesophageal symptoms (GES) without any other complaint. Gastroesophageal endoscopic findings revealed some interesting and unexpected results in this subgroup. The remainder of patients considered (13/50; 26%) showed normal values for nasal mucociliary clearance time and they referred only typical extraesophageal symptoms (EES). In any case and in both groups rhinosinusitis complaints were present. The SNOT-20 test results were normal in all patients even if a significant difference for GES group could be highlighted (19.3 vs 7.4; P<0.005). CONCLUSION: This study supports the assumption of possible and important correlations between nasal mucociliary clearance time and GERD. GERD could be an altering factor for nasal function also in absence of laryngo-pharyngeal symptoms although to verify this interesting hypothesis more validated data are necessary.

An inhibition of the hypothalamic somatostatinergic tone is not the cause of the enhanced growth hormone response to growth hormone-releasing hormone in patients with liver cirrhosis.

Animal models of liver cirrhosis (LC) display a reduced hypothalamic somatostatinergic tone. To test whether a similar mechanism could explain the enhanced Growth Hormone (GH) secretory response to GH-Releasing Hormone (GHRH), which is seen in human LC, we studied the effect of the cholinesterase inhibitor pyridostigmine (PD), which is able to reduce the release of hypothalamic somatostatin (SS), on the GHRH-stimulated GH secretion. We considered that if PD were unable to increase GH secretion, this would constitute evidence of an already inhibited endogenous somatostatinergic tone. If proved, this in turn could explain the enhanced GH response to GHRH seen in LC. Ten LC patients and nine controls were given GHRH (100 microg, intravenously), or PD (120 mg, orally) plus GHRH. After GHRH alone, the GH peak was four times higher in LC than in controls (40.85+/-15.7 ng/ml in LC and 9.35+/-2.5 ng/ml in controls). In LC, PD administration markedly increased the GH response to GHRH (GH peak: 98.0+/-19.7 ng/ml; +240% vs. GHRH alone). The ability of PD to increase the GH response in patients with LC suggests that in this condition the enhanced GH response to GHRH is not due to a completely inhibited endogenous somatostatinergic tone. SS appears instead to maintain its modulator role on GH secretion in human LC, in contrast with what observed in animal models.

Successful treatment of retrograde ejaculation with the alpha1-adrenergic agonist methoxamine: case study.

We treated two patients affected by retrograde ejaculation (RE) with the pure alpha1-adrenergic agonist methoxamine; the drug was self-administered intramuscularly by the patients 30 min prior to intercourse or masturbation. A previous trial with oral imipramine had been ineffective in both patients. Sperm count increased substantially, particularly in the first patient who had insulin-dependent diabetes and was seeking fertility. In this patient, total ejaculated sperm increased from 22 millions to 488 and 419.5 millions on two different occasions, with good motility; two clinical pregnancies were obtained in the partner of this patient after 3 and 4 months of treatment, respectively. The second patient did not desire fertility. In both patients, no side effects were seen except for slight piloerection; blood pressure values increased slightly, and heart rate was unchanged. We conclude that self-administered methoxamine can be a useful, noninvasive and inexpensive treatment of RE, when oral agents are ineffective.

Serum prolactin levels after administration of the alimentary opioid peptide gluten exorphin B4 in male rats.

Gluten Exorphins are opioid peptides identified in enzymatic digests of gluten. The effects of Gluten Exorphins are still largely unknown. It has been shown that Gluten Exorphin B5 (Tyr-Gly-Gly-Trp-Leu) stimulates Prolactin secretion in male rats. In this study, we have evaluated the Prolactin response to Gluten Exorphin B4, another exorphin whose structure (Tyr-Gly-Gly-Trp) is identical to that of the NH(2)-terminal sequence of Gluten Exorphin B5. To this aim, five groups of male rats were given the following intravenous treatments: vehicle, Gluten Exorphin B5 3 mg kg-1 body weight, Gluten Exorphin B4 at the doses of 3, 6 and 9 mg kg-1 body weight. At the dose of 3 mg kg-1 body weight, Gluten Exorphin B5 induced a significant increase in Prolactin levels. Gluten Exorphin B4 could not modify Prolactin secretion, even when administered at doses three times higher than those effective for Gluten Exorphin B5. The present study: (1) indicates that Gluten Exorphin B4 does not modify Prolactin secretion in male rats; (2) confirms the ability of Gluten Exorphin B5 to exert a stimulatory action on Prolactin release; (3) suggests that the presence of the carboxy-terminal leucine in Gluten Exorphin B5 is essential for its action on Prolactin secretion.

Furosemide and 11beta-hydroxysteroid dehydrogenase activity, in man.

Mineralocorticoid receptors possess the same affinity for aldosterone and for cortisol and preferential binding of aldosterone is modulated by the 11 beta-hydroxysteroid dehydrogenase (11 beta-OHSD) enzyme, which converts cortisol to its inactive metabolite cortisone. Several endogenous or exogenous compounds able to inhibit the enzyme have been described and, as a consequence, produce the syndrome of apparent mineralocorticoid excess (AME) characterized by hypertension, hypokalemia, volume repletion and suppression of the renin-angiotensin-aldosterone system. High doses of furosemide, a diuretic that works in the luminal surface of the thick ascending limb of Henle's loop, have been reported to inhibit 11 beta-OHSD activity to the same extent as licorice in vivo and in vitro, in rat. The aim of our study was to verify the effect of the drug on 11 beta-OHSD activity in man at the doses currently used in clinical practice. We tested the activity of 11 beta-OHSD following both acute and protracted administration of furosemide. In the acute study, the drug was administered at low (40 mg i.v. in bolo) and high doses (infusion of 10 mg/kg bw i.v for six hours); the protracted furosemide administration consisted in 50 mg/day for 20 days, by mouth. The ratios between the cortisol metabolites tetrahydrocortisol plus allo-tetrahydrocortisol to tetra-hydrocortisone and urinary free cortisol to urinary free cortisone were used to measure the activity of 11 beta-OHSD. Urinary cortisol, cortisone and their metabolites were tested by a gas-chromatographic/mass spectrometric method. Neither acute nor prolonged administration of furosemide did affect the activity of 11 beta-OHSD although the drug was able to modify plasma aldosterone and PRA secretion and to determine hypokalemia. Our results suggest that furosemide does not play a significant role in 11 beta-OHSD modulation in humans, at least at the dosage used in clinical practice.

Neuroendocrine-immune (NEI) circuitry from neuron-glial interactions to function: Focus on gender and HPA-HPG interactions on early programming of the NEI system.

Bidirectional communication between the neuroendocrine and immune systems during ontogeny plays a pivotal role in programming the development of neuroendocrine and immune responses in adult life. Signals generated by the hypothalamic-pituitary-gonadal axis (i.e. luteinizing hormone-releasing hormone, LHRH, and sex steroids), and by the hypothalamic-pituitary-adrenocortical axis (glucocorticoids (GC)), are major players coordinating the development of immune system function. Conversely, products generated by immune system activation exert a powerful and long-lasting regulation on neuroendocrine axes activity. The neuroendocrine-immune system is very sensitive to preperinatal experiences, including hormonal manipulations and immune challenges, which may influence the future predisposition to several disease entities. We review our work on the ongoing mutual regulation of neuroendocrine and immune cell activities, both at a cellular and molecular level. In the central nervous system, one chief compartment is represented by the astroglial cell and its mediators. Hence, neuron-glial signalling cascades dictate major changes in response to hormonal manipulations and pro-inflammatory triggers. The interplay between LHRH, sex steroids, GC and pro-inflammatory mediators in some physiological and pathological states, together with the potential clinical implications of these findings, are summarized. The overall study highlights the plasticity of this intersystem cross-talk for pharmacological targeting with drugs acting at the neuroendocrine-immune interface.

Enhancement of the peripheral sensitivity to growth hormone in adults with GH deficiency.

OBJECTIVE: Adults with severe GH deficiency (GHD) need recombinant human growth hormone (rhGH) replacement to restore body composition, structure functions and metabolic abnormalities. The optimal rhGH dose for replacement has been progressively reduced to avoid side effects. The aim of the present study was to define the minimal rhGH dose able to increase both IGF-I and IGF binding protein (BP)-3 levels in GHD and to verify the possible change in GH sensitivity. DESIGN AND PATIENTS: To this goal, we studied the effect of 4-day treatment with 3 rhGH doses (1.25, 2.5 and 5.0 microg/kg/day) on IGF-I and IGFBP-3 levels in 25 panhypopituitary adults with severe GHD (12 males and 13 females, age: 44.5+/-3.0 years, body mass index (BMI): 27.0+/-0.9 kg/m(2)) and 21 normal young adult volunteers (NV, 12 males and 9 females, age: 30.5+/-2.0 years, BMI: 20.8+/-0.5 kg/m(2)). RESULTS: Basal IGF-I and IGFBP-3 levels in GHD were lower (P<0.001) than in NV. In NV the 1.25 microg/kg dose of rhGH did not modify IGF-I levels. The dose of 2.5 microg/kg rhGH significantly increased IGF-I levels in men (P<0.001) but not in women, while the 5.0 microg/kg dose increased IGF-I levels in both sexes (P<0.001). IGFBP-3 levels were not modified by any of the administered rhGH doses. In GHD patients, all rhGH doses increased IGF-I levels 12 h after both the first (P<0.01) and the fourth rhGH dose (P<0.001). At the end of treatment percentage increases in IGF-I were higher (P<0.001) in GHD patients than in NV. In contrast with NV, in GHD patients the IGF-I response to short-term stimulation with rhGH was independent of gender. Moreover, GHD patients showed increases in IGFBP-3 after the fourth administration of both 2.5 and 5.0 microg/kg rhGH. CONCLUSION: The results of the present study demonstrate that the minimal rhGH dose able to increase IGF-I and IGFBP-3 levels in GHD patients is lower than in normal subjects, at least after a very short treatment. This evidence suggests an enhanced peripheral GH sensitivity in GH deprivation.

Prevalence of silent celiac disease in patients with autoimmune thyroiditis from Northern Sardinia.

Celiac disease (CD) is frequently associated with other autoimmune diseases such as Type 1 diabetes mellitus, autoimmune thyroiditis (AT), and Addison's disease. The frequency of these associations varies with the populations studied. We conducted this study to ascertain the prevalence of CD in patients with AT from Sardinia, an area with a very high prevalence of CD. To this aim, 297 consecutive patients with AT (as defined by elevated antithyroid antibody levels and a positive ultrasound scan) were studied. Immunoglobulin A and G-class antigliadin antibodies were assayed in serum; if either or both were positive, antiendomysium antibodies were determined. If two markers were positive, serum ferritin, folate, and vitamin B12 levels were measured and jejunal biopsy was suggested. Thirteen out of the 14 patients who showed at least two positive markers consented to jejunal biopsy and all of them showed histological features of CD. The prevalence of CD in AT patients was 4-fold greater than that observed in the general population (4.37 vs 1.06%, p<0.0001). Ferritin was low in 6 and vitamin B12 in 2 out of 13 patients; serum folates were normal in all patients. Molecular typing of HLA class II alleles showed an increased frequency of the extended haplotype DRB1*0301/DQA1*0501/DQB1*0201. None of our patients had a history of gastrointestinal symptoms. We confirm the increased prevalence of silent CD in patients with AT. Patients with AT ought to be regarded as a high-risk group for CD and should be screened routinely for it; if negative, screening tests should be repeated at regular intervals.

Congenital deficiency of 11beta-hydroxysteroid dehydrogenase (apparent mineralocorticoid excess syndrome): diagnostic value of urinary free cortisol and cortisone.

The syndrome of apparent mineralocorticoid excess (AME) is an inherited form of hypertension. This disorder results from an inability of the enzyme 11beta-hydroxysteroid dehydrogenase (11beta-OHSD) to inactivate cortisol to cortisone. The diagnosis of AME is usually based on an elevated ratio of cortisol to cortisone reduced metabolites in the urine [tetrahydrocortisol plus allotetrahydrocortisol to tetrahydrocortisone (THF+alloTHF/THE)]. The principal site of "A" ring reduction is the liver, but AME arises from mutation in the gene encoding 11beta-OHSD2 in the kidney. We used a gas chromatographic/mass spectrometric method to measure the urinary free cortisol (UFF) and free cortisone (UFE) in 24 patients affected by the two variants of AME [19 with the classical form (type I) and 5 with the mild form called AME type II] in order to provide a more reproducible in vivo measure of the renal enzymatic activity. Type I patients were divided into two groups: children under 12 and adults. UFF levels (microg/24 h) did not differ between under-12 controls and AME type I children (mean+/-SD, 9+/-4 and 15+/-12, respectively), but was significantly higher in affected adults compared to controls: (62+/-32 vs 29+/-8, p<0.01). No differences were found between adult controls and AME type II patients (29+/-8 and 37.0+/-14, respectively). UFE was undetectable in 63% of AME type I and significantly lower in AME type II (p<0.05). As a consequence UFF/UFE ratio was significantly higher in AME type I patients both in children and adults compared to controls (AME children: 5.1+/-2.6; normal children: 0.43+/-0.2, p<0.01; AME type I adults: 17.7+/-19.6; normal adults: 0.54+/-0.3 p<0.01). For AME type II, where UFE was detectable in every case, the UFF/UFE ratio was significantly higher than adult controls (2.75+/-1.5 vs 0.54+/-0.3, p<0.01). In conclusion, our study indicates that UFE and UFF/UFE ratio are sensitive markers of 11beta-OHSD2, directly reflecting the activity of the renal isozyme and readily identifying patients with AME. The presence of an altered UFF/UFE ratio in both types of AME, although with different degree of severity, calls for re-evaluation and the classification of AME as a single disorder.

Decreased nocturnal urinary antidiuretic hormone excretion in enuresis is increased by imipramine.

OBJECTIVE: To assess the role of integrated nocturnal antidiuretic hormone (ADH) secretion in children with enuresis, and possible modifications induced by treatment with imipramine. PATIENTS AND METHODS: The morning plasma ADH and nocturnal urinary ADH integrated concentrations were measured in 18 consecutive enuretic children (patients) and 21 age- and sex-matched controls admitted for minor treatment. Diurnal and nocturnal urine production, and plasma and urinary osmolality were also determined; lumbosacral radiography and uroflowmetry were undertaken in the patients. The assessments were repeated after 14 days of treatment with imipramine hydrochloride (orally, 20 mg/night). RESULTS: Half the patients had occult spinal malformations but the uroflowmetry results were all within the normal range. The median (95% confidence interval, CI) urinary ADH integrated concentrations were markedly lower in patients, at 29.7 (22.1-37.3) vs 63.0 (35.1-90.8) pg/mL/h (P = 0.03) than in controls. Plasma ADH levels were significantly increased by imipramine (0.64 to 1.47 pg/mL, 95% CI, 0.40-0.89 vs -0.26-3.2; P < 0.001), as were nocturnal urinary ADH integrated concentrations, at 29.7 (22.1-37.3) vs 59.0 (37.3-80.6) pg/mL/h (P < 0.001), and morning plasma osmolality decreased, from 298.5 (294.5-302.5) to 294.9 (292.4-297.3) mosmol/kg (P = 0.003), as was the 24-h fluid intake, from 983 (721-1245) to 666 (435-897) mL (P = 0.004). CONCLUSIONS: We conclude that enuretic children have a lower nocturnal ADH excretion; imipramine restores nocturnal ADH excretion, increases morning plasma ADH levels, and causes consistent changes in other biochemical variables.

Does kidney transplantation normalise cortisol metabolism in apparent mineralocorticoid excess syndrome?

The syndrome of apparent mineralocorticoid syndrome (AME) results from defective 11beta-hydroxysteroid dehydrogenase 2 (11beta-HSD2). This enzyme is co-expressed with the mineralocorticoid receptor (MR) in the kidney and converts cortisol to its inactive metabolite cortisone. Its deficiency allows the unmetabolized cortisol to bind to the MR inducing sodium retention, suppression of PRA and hypertension. Thus, the syndrome is a disorder of the kidney. We present here the first patient affected by AME cured by kidney transplantation. Formerly, she was considered to have a mild form of the syndrome (Type II), but progressively she developed renal failure which required dialysis and subsequent kidney transplantation. To test the ability of the transplanted kidney to normalise the patient's cortisol metabolism, we gave, in two different experiments, 25 and 50 mg/day of cortisone acetate or 15 and 30 mg/day of cortisol after inhibition of the endogenous cortisol by synthetic glucocorticoid (methylprednisolone and dexamethasone). The AME diagnostic urinary steroid ratios tetrahydrocortisol+5alphatetrahydrocortisol/tetrahydrocortisone and cortisol/cortisone were measured by gas chromatography/mass spectrometry. Transplantation resulted in lowering blood pressure and in normalization of serum K and PRA. After administration of a physiological dose of cortisol (15 mg/day), the urinary free cortisol/cortisone ratio was corrected (in contrast to the A-ring reduced metabolites ratio), confirming that the new kidney had functional 11beta-HSD2. This ratio was abnormally high when the supra-physiological dose of cortisol 30 mg/day was given. After cortisone administration, the tetrahydrocortisol+5alphatetrahydrocortisol/tetrahydrocortisone ratio resulted normalised with both physiological and supra-physiological doses, confirming that the hepatic reductase activity is not affected. As expected, the urinary free cortisol/cortisone ratio was normal with physiological, but increased after supra-physiological doses of cortisone. The described case indicates a normalisation of cortisol metabolism after kidney transplantation in AME patient and confirms the supposed pathophysiology of the syndrome. Moreover, it suggests a new therapeutic strategy in particularly vulnerable cohorts of patients inadequately responsive to drug therapy or with kidney failure.