A. Orsatti

Prevalence of metabolic syndrome in long-term survivors of hematopoietic stem cell transplantation

Our purpose was to determine the prevalence and features of metabolic syndrome (MS) in a series of long-term hematopoietic stem cell transplantation (HSCT) survivors. We assessed the clinical, metabolic and endocrinological data, and plasma TNF, leptin, resistin and adiponectin levels relating to 85 HSCT recipients. MS was diagnosed on the basis of the National Cholesterol Education Program-Adult Treatment Panel III criteria. Its prevalence was compared with that observed in an Italian population, and its relationship with the clinical and laboratory parameters was assessed univariately and multivariately. Twenty-nine HSCT recipients had MS instead of the 12.8 expected (P<0.0001), with hypertriglyceridemia being the most common feature. Univariate analysis indicated that high insulin and leptin levels, low-adiponectin levels and hypogonadism were significantly related to a diagnosis of MS; multivariate analysis indicated plasma leptin, insulin resistance, age and hypogonadism. We conclude that HSCT recipients are at increased risk of a form of MS that has particular clinical features. Plasma leptin levels are independently related to MS, thus suggesting that leptin resistance may play a role as a pathogenetic clue, as in other conditions in which MS occurs as a secondary phenomenon. MS deserves consideration as a life-threatening complication in patients who are probably cured of their underlying disease.

Plasma ACTH-response to the corticotropin releasing factor in patients with Cushing's disease. Comparison with the lysine-vasopressin test

In three female patients with Cushings disease, 100 micrograms of synthetic ovine corticotropin releasing factor (CRF) were administered before surgery and 1 week after transsphenoidal microadenomectomy. In these patients a test with lysine-vasopressin (LVP), 10 U intramuscularly, was also performed before and after pituitary surgery. Before surgery, both stimuli induced a clear increase in plasma ACTH and cortisol in all patients; the response of ACTH to CRF was of greater magnitude. Postoperatively, the responses were virtually absent in two patients, but were still present in the third one in whom the removal of adenoma had been partially unsuccessful. The CRF test was also performed in a female patient with Cushings syndrome due to adrenal adenoma; in this patient no responses of plasma ACTH and cortisol to CRF were recorded. This paper demonstrates that pituitary microadenomas causing Cushings disease may retain the ability to respond to CRF; this stimulus may be useful in the differential diagnosis between ACTH-dependent and independent Cushings syndrome; the lack of response after microadenomectomy indicates successful removal of the tumor. CRF is more potent than LVP in releasing ACTH at the doses employed.

Neuropsychological functions and metabolic aspects in subclinical hypothyroidism: the effects of L-thyroxine.

Thyroid hypofunction is a slowly progressing graded phenomenon [Vanderpump MP, Tunbridge WM, French JM, Appleton D, Bates D, Clark F, et al. The incidence of thyroid disorders in the community: a twenty-year follow-up of the Whickham Survey. Clin Endocrinol (Oxf) 1995;43(1):55-68]; subclinical forms (SCH) often represent a laboratory diagnosis in apparently asymptomatic patients. In the absence of adequate parameters for thyroid hormone action in tissues, the level of TSH increase corresponding to negative effects remains unsettled. We studied a wide range of physiological processes in a strictly selected population of 38 female patients (56.4+/-12.6 years) with minor forms of SCH (TSH 6.6+/-1.8 mIU/L), after exclusion of neurological, psychiatric and somatic disorders or confounding conditions. The investigations, performed at admission and after 6 months of l-thyroxine (LT4) treatment, included metabolic evaluation, health status perception and an extensive battery of neuropsychological tests and psychological rating scales. Lipid metabolism improved after LT4 (total cholesterol: 231.9+/-49.6 mg/dl pre- vs 221.0+/-40.0 mg/dl post-treatment; LDL cholesterol: 183.1+/-62.9 vs 162.7+/-53.7 mg/dl; apolipoprotein A1: 183.5+/-64.5 vs 160.9+/-50.3 mg/dl; p<0.05 for all comparisons), while glucose metabolism was unchanged. Health status perception was favourably influenced by the treatment (total SF-36 score 97.8+/-18.4 pre- vs 108.5+/-14.8 post-, p<0.0001); in a matched control group with euthyroid goiter, tested to examine the effects of medical care in the absence of treatment, no significant differences were found in the SF-36 scores at admission and after 6 months (109.3+/-15.1 vs 109+/-14.2, p=0.9). Attention performance improved after LT4; HRSD and HRSA scores did not significantly change, but negative correlations were found between FT3 levels and affective scores at admission, and between the post-treatment changes of affective scores and of FT3. In our study subtle disturbances of health status perception, attention and lipid metabolism associated to SCH of mildest degrees were reverted by LT4 replacement, reinforcing reports of unfavourable consequences of marginal thyroid disease.

A comparison between metabolic syndrome post-hematopoietic stem cell transplantation and spontaneously occurring metabolic syndrome

Background: Hematopoietic stem cell transplantation (HSCT) is used in the treatment of several hematological and non-hematological disorders. An increasing number of long-term survivors recover from their primary disease, but they are at risk of adverse late effects, including metabolic syndrome (MS), which seems to be common in long-term survivors of HSCT. Aim: To compare common metabolic parameters and adipohormone profiles in post-transplant and spontaneously occurring or “classic” MS patients. Subjects and methods: Post-transplant MS patients (15 women and 14 men; 49.8±9.3 yr) were compared to “classic” MS patients (15 women and 14 men; 52.9±8.0 yr). For each subject a record of conventional clinical parameters was made; moreover, serum leptin, insulin, quantitative C-reactive protein (CRP), tumor necrosis factor-α [TNF-α], and adiponectin concentrations were measured. Results: The patients with post-HSCT MS had significantly higher levels of leptin, CRP, and TNF-α than the patients with “classic” MS. A generalized linear model comprising serum insulin (p=0.022), body mass index (p<0.001), gender (p<0.001), and group (i.e. healthy, post-HSCT with MS, or suffering from “classic” MS; p<0.001) explained serum leptin variability (adjusted R2=0.741). Serum leptin concentrations and BMI were related in the patients with “classic” MS but not in those with post-HSCT MS. Conclusions: A possible pathogenetic mechanism in the development of MS after HSCT could be hyperleptinemia. A potential interaction among circulating leptin, components of MS, and immune function might explain the role of this adipokine in mediating cardiovascular risk after HSCT.

A singular case of graves' disease in congenital thyroid hemiagenesis

We report the observation of an unusual case of Graves’ disease associated with thyroid hemiagenesis. A 41-year-old woman who presented with symptoms and clinical signs of hyperthyroidism was discovered to have thyroid hemiagenesia of the left lobe. Thyroid ultrasound scan showed enlargement of the right lobe with a single nodule, and absence of the left lobe; isotope scan showed homogeneous uptake in the single lobe and nodule. Ophthalmopathy, which was absent at presentation, developed after two years; after a further 2 years the patient developed decompensated hypothyroidism requiring thyroxine replacement. This is the first case of Graves’ disease in thyroid hemiagenesis evolved to hypothyroidism, and a rare case of thyroid ophthalmopathy accompanying this condition.

Increased growth hormone response to growth hormone releasing hormone induced by erythropoietin in uraemic patients

This study was designed to assess the response of growth hormone (GH) to growth hormone releasing hormone (GHRH) and the possible interaction of acutely administered recombinant human erythropoietin (rhEPO) on GH response to GHRH in a group of uraemic patients. Eight patients on maintenance haemodialysis, not previously treated with rhEPO, and six healthy controls were tested with GHRH (100 μg i.v. in bolus), and with GHRH (100 μg i.v. in bolus) plus rhEPO (40 U/kg in constant infusion for 30 min) on different days. GHRH injection provoked a GH release in five out of eight uraemic patients; the overall mean response did not differ significantly from the GH response obtained in controls (P = 0.30). Erythropoletin infusion significantly increased GH release after GHRH (P > 0.01 at 15, 30, 45, 60 min after GHRH injection) in uraemic patients; in controls, on the contrary, stimulation with GHRH plus rhEPO did not induce a greater increase of OH release compared with that observed after GHRH alone (mean GH peak 37.66 |Mp 7.68 mU/I after GHRH; and 38.0 |Mp 9.18 mU/I after GHRH plus rhEPO; P < 0.5). In this study acutely administered rhEPO significantly potentiated the GH response to GHRH in uraemic patients whereas the same effect was not demonstrable in subjects with normal renal function.

Cushing’s Syndrome due to Unilateral Adrenal Nodular Hyperplasia with Incomplete Inhibition of the Contralateral Gland

A 57-year-old woman was demonstrated to be affected by adrenocorticotropic hormone (ACTH)-independent Cushings syndrome. Computed-axial tomography of the abdomen demonstrated an expansion of the left adrenal. In apparent contrast with these findings, adrenal scintigraphy demonstrated radiocholesterol uptake also by the right gland. At surgery, the left adrenal was found to be hard and enlarged and was excised, while the right gland was found of normal appearance and left in place. Histologic examination of the excised gland demonstrated nodular hyperplasia. Early after surgery, plasma cortisol returned to normal values with a normal circadian rhythm and complete inhibition by low dose dexamethasone; the response of plasma cortisol to ACTH was normal. The patient represents a rare case of unilateral adrenal nodular hyperplasia. Radiocholesterol uptake by the contralateral gland and early recovery from adrenal atrophy after surgery are exceptional findings and suggest incomplete inhibition of endogenous ACTH.

Gonadotropin releasing hormone elicits abnormal hormone responses in schizophrenia

We studied the non-specific responses of GH and PRL to gonadotropin releasing hormone (GnRH) in eleven male patients aged 18-30 in whom a diagnosis of acute schizophrenia was made according to Crows criteria. GnRH administration was followed by a significant increase in plasma GH in five patients; plasma PRL increased in two patients. The two prolactin responders were also GH responders. Non-specific GH response was confirmed on repeated testing in two patients in whom GnRH stimulation was performed twice. During saline control, non-specific hormone responses were not observed. The abnormal hormone responses observed in acute schizophrenia are probably due to the disordered monoamine regulation characteristic of this condition.

The impact of long-term hemodialysis on pituitary-adrenocortical function.

The activity of the hypothalamic-pituitary-adrenal axis in hemodialyzed (HD) patients has been investigated, with conflicting results. Different results are reported concerning both basal ACTH and cortisol concentration and the responses to different stimulating agents, in chronic hemodialyzed patients. The present study was performed in order to asses whether the length of the hemodialytic treatment may affect the pituitary and adrenocortical response to stimulation with ovine CRH (oCRH) and with exogenous ACTH in a group of patients on chronic HD for more than 10 years. Ten uremic patients (aged 38-71, 6 males and 4 females) on chronic hemodialysis for at least 10 years and 7 healthy subjects matched for age and sex were studied. The patients were tested on the day preceding dialysis session. Each subject received on different non-consecutive days oCRH (100 micrograms i.v. in bolus) and ACTH (Synacthen 0.25 mg i.v. in bolus), and blood samples were obtained at appropriate intervals. Basal ACTH and cortisol levels of HD patients were in the upper limit of normal range (ACTH 39.21 +/- 11.11 pg/mL in HD patients vs. 26.88 +/- 14.12 pg/mL in controls; cortisol 19.96 +/- 5.07 in HD patients vs. 12.66 +/- 4.44 in controls); however, the means were not significantly different compared with controls. Following oCRH administration a net increase of ACTH and cortisol was observed in every patient tested (ACTH peak 83.81 +/- 28.49 in HD vs. 78.73 +/- 22.87 pg/mL in controls; cortisol peak 30.73 +/- 19.31 in HD vs. 20.05 +/- 3.19 micrograms/dL in controls).(ABSTRACT TRUNCATED AT 250 WORDS)

Gonadotropin response to gonadotropin releasing hormone in acute schizophrenia.

To evaluate hypothalamic-pituitary-gonadal axis in acute schizophrenia, plasma FSH and LH concentrations were estimated both in basal conditions and after stimulation with gonadotropin releasing hormone (GnRH, 200 micrograms i.v.) in 14 young male patients with acute schizophrenia and in a age-matched group of 14 healthy male controls. Basal plasma PRL and testosterone levels were also measured. The mean basal levels of LH and FSH were slightly lower in schizophrenics, while the mean testosterone and prolactin levels were similar in the two groups. The FSH response to GnRH was significantly reduced in patients with acute schizophrenia, while the response of LH was similar in schizophrenics and in the controls. The possible significance of these findings is discussed in the contest of the complex neuroendocrine regulation of gonadotropin secretion and the overactivity of dopaminergic systems in acute schizophrenia.