Diffuse Neuroendocrine Hyperplasia with Obliterative Bronchiolitis and Usual Interstitial Pneumonia: An Unusual "Headcheese Pattern" with Nodules.

A 74-year-old non-smoker female presented to our attention with a history of dyspnea and cough. CT scan revealed multiple areas of patchy ground glass attenuation associated to a diffuse mosaic oligoemia. Scattered bilateral subcentimetric pulmonary nodules were also present. Patient underwent a surgical lung biopsy. Specimens showed features of diffuse neuroendocrine hyperplasia, microhoneycombing, fibroblast foci. A final diagnosis of diffuse neuroendocrine hyperplasia with obliterative bronchiolitis and UIP was rendered.

EBUS-guided cryobiopsy in the diagnosis of thoracic disorders.

BACKGROUND: Endobronchial Ultrasound (EBUS) has emerged as a crucial tool for diagnosing intrathoracic disorders, particularly in the staging of lung cancer. However, its diagnostic capabilities in the context of benign and rare diseases remain a subject of debate. AIM: to investigate the diagnostic yield and safety of EBUS-transbronchial mediastinal cryobiopsy (EBUS-TMC) in comparison to EBUS-transbronchial needle aspiration (TBNA) for a broad spectrum of intrathoracic diseases. METHODS: a single-centre retrospective observational study conducted on 48 patients who underwent both EBUS-TBNA and endobronchial ultrasound-transbronchial mediastinal cryobiopsy (EBUS-TMC) in the same procedure between August 2021 and October 2023. RESULTS: The overall diagnostic yield of EBUS-TMC surpassed that of EBUS-TBNA (95.8% vs 54.1 %), notably excelling in the diagnosis of sarcoidosis (92.8% vs 78.5 %), rare mediastinal disorders (100% vs 0 %), hyperplastic lymphadenopathy (100% vs 0 %), and lymphoproliferative disease (100% vs 0 %). No significant differences were observed in the diagnosis of NSCLC and SCLC. Samples obtained through EBUS-TMC facilitated the acquisition of NGS and immunohistochemical analyses more readily. CONCLUSION: EBUS-TMC may contribute to the precise diagnosis and subtyping of mediastinal diseases, especially lymphomas and rare mediastinal tumors, thereby reducing the number of non-diagnostic procedures.

Diagnostic yield and safety of transbronchial lung cryobiopsy for diffuse parenchymal lung diseases diagnosis: Comparison between 1.7-mm and 1.9-mm probes.

PURPOSE OF THE RESEARCH: transbronchial lung cryobiopsy has been recently accepted as a valid and less invasive alternative to surgical lung biopsy. The purpose of this randomized controlled study was to evaluate, for the first time, the quality and safety of biopsy specimens obtained by using the new disposable 1.7-mm cryoprobe compared with the standard re-usable 1.9 mm cryoprobe in the diagnosis of diffuse parenchymal lung diseases. METHODS: 60 consecutive patients were prospectively enrolled and randomly assigned to two different groups: 1.9 mm (group A) and 1.7 mm (group B); primary endpoints were pathological and multidisciplinary diagnostic yield, sample size and complication rate. PRINCIPAL RESULTS: the pathological diagnostic yield of cryobiopsy was 100% in group A and 93.3% in group B (p = 0.718); cryobiopsy median diameter was 6.8 mm in group A and 6.7 mm in group B (p = 0,5241). Pneumothorax occurred in 9 patients in group A and 10 in group B (p = 0.951); mild-to-moderate bleeding in 7 cases and 9 cases in group A and B respectively (p = 0.559). No death or severe adverse events were observed. CONCLUSIONS: there was no statistically significant difference between the two groups, regarding diagnostic yield, adverse events and sampling adequacy.

Idiopathic nonspecific interstitial pneumonia: an interstitial lung disease associated with autoimmune disorders?

Recent evidence suggests that idiopathic nonspecific interstitial pneumonia (iNSIP) is a distinct clinical entity amongst other idiopathic interstitial pneumonias, and some data seem to suggest a possible pathogenetic role of autoimmunity. The aim of the present study was to assess if iNSIP might represent an early lung manifestation of an autoimmune disease. After initial review of cases found in the medical records database by searching for the term "NSIP" (n = 63), 37 iNSIP cases were identified, and were re-evaluated using a dynamic integrated multidisciplinary approach. 27 cases with iNSIP were selected for the study. Mean ± sd age at first respiratory symptom was 54.2 ± 8 yrs, 70% were females, and 59% were never-smokers. At follow-up (mean ± sd 59.7 ± 29 months, range 12-138 months), autoimmune diseases occurred in 14 (52%) patients, with seven (26%) cases of autoimmune thyroiditis, six (22%) of undifferentiated connective tissue disease and three (11%) of connective tissue disease. Patients developing autoimmune diseases were older and more frequently never-smoking females. In >50% of patients diagnosed with iNSIP, evidence of autoimmune diseases develops within 2 yrs, suggesting a probable link between the clinical entity of iNSIP and autoimmune disorders.

Prospective evaluation of drug-induced lung toxicity with high-resolution CT and transbronchial biopsy.

PURPOSE: This study compared the results of high-resolution computed tomography (HRCT) and cytohistology after transbronchial biopsy in the evaluation of drug-related interstitial lung disease (DR-ILD). MATERIALS AND METHODS: Patients with a clinical and imaging diagnosis of DR-ILD were prospectively included in a study protocol lasting 5 years. All patients were evaluated by bronchoscopy with transbronchial biopsy or bronchoalveolar lavage (BAL) following an HRCT examination that raised a suspicion of DR-ILD. Two radiologists (one senior and one junior), unaware of the diagnosis, reported the single HRCT findings, their distribution and predominant pattern. In the event of disagreement, the diagnosis was subsequently reached by consensus. Cytohistological examination was considered the gold standard in the diagnosis of DR-ILD. Patients who were unable to undergo the endoscopic procedure were excluded from the study. RESULTS: The study included 42 patients (25 men, 17 women; age range 20-84 years). Transbronchial biopsy was performed in all but four patients (one case of alveolar haemorrhage and three cases of lipoid pneumonia) in whom the diagnosis was established with BAL. Assessment of the HRCT images revealed the following patterns: noncardiogenic pulmonary oedema (n=13); organising pneumonia (OP) (n=9); hypersensitivity pneumonitis (HP) (n=2); alveolar haemorrhage (AH) (n=2); nonspecific interstitial pneumonia (NSIP) (n=5); lipoid pneumonia (LP) (n=1); sarcoid-like pattern (n=1). Cytohistological diagnosis revealed diffuse alveolar damage (DAD) in 11 patients, OP in seven, HP in three, AH in three, chronic interstitial pneumonia (CIP) in eight, LP in three and pseudosarcoidosis in one. Subdivision of the drugs into antineoplastic and nonantineoplastic agents showed that the most common patterns were CIP (n=6), DAD (n=2) and OP (n=2) in the antineoplastic group and DAD (n=9) and OP (n=5) in the nonantineoplastic group. Sensitivity and specificity of the radiological analysis was excellent, especially for patterns such as OP and DAD (sensitivity 0.86 and specificity 0.88 for OP; sensitivity 1 and specificity 0.93 for DAD). CONCLUSIONS: HRCT demonstrated excellent sensitivity and specificity. In cases in which its specificity was low, HRCT was nonetheless useful for biopsy planning and clinical-radiological monitoring after discontinuation of the drug treatment.

Pulmonary vein stenosis mimicking interstitial lung disease.

Pulmonary vein stenosis (PVS) is a rare condition, often difficult to diagnose and associated with poor prognosis at advanced stages. Lung parenchymal abnormalities are indirect evidence of PVS and can manifest as multifocal opacities, nodular lesions, unilateral effusions, and interstitial septal thickening. These can lead to erroneous diagnoses of airway disease, pneumonia, malignancies or interstitial lung disease. This review summarizes the current literature about the approach to, evaluation and management of these patients. Our case report demonstrates that PVS is an under-recognized complication of cardiovascular surgery and should be considered in all patients presenting with respiratory symptoms after a cardiac procedure.

Cathepsin-K is a sensitive immunohistochemical marker for detection of micro-granulomas in hypersensitivity pneumonitis.

UNLABELLED: Hypersensitivity Pneumonitis (HP) is an interstitial lung disease that occurs upon exposure to a variety of inhaled organic antigens. The presence of small non-caseating granulomas and isolated giant cells is not specific, but is considered a relevant histological feature for HP. The detection of granulomas is widely considered as easy on standard histological stains, but microgranuloma detection can be difficult and/or time consuming, especially in chronic HP cases. Cathepsin K (Cath-K) is a potent cysteine protease expressed at high levels in activated macrophages (osteoclasts, and epithelioid cells in granulomas), but is not expressed in resident macrophages thus representing a promising marker to rapidly detect and quantitatively evaluate microgranulomas in interstitial lung diseases. We analyzed the expression of Cath-K by immunohistochemistry in 22 subacute and chronic HP cases, using semi-quantitative scores. Control samples included normal lung tissue, and a variety of interstitial lung diseases: 3 Wegener's granulomatosis, 3 sarcoidosis, 3 tuberculosis, 1 berylliosis, 20 idiopathic pulmonary fibrosis (IPF), 2 Langerhans' cell histiocytosis, 5 nonspecific-interstitial pneumonia (NSIP), 5 cryptogenic organising-pneumonia (COP), 2 Airway-Centered Interstitial Fibrosis (ACIF), 5 desquamative interstitial pneumonia (DIP), 3 respiratory bronchiolitis interstitial lung disease (RB-ILD). Intense expression of Cath-K was demonstrated in epithelioid and giant cells in all cases containing granulomas (HP, sarcoidosis, Wegener's granulomatosis, berylliosis, tuberculosis). Among HP cases 19/22 (86.3%) contained granulomas that could be semiquantitatively evaluated. In all HP and control cases alveolar macrophages did not express Cath-K, including cases characterised by large collections of alveolar macrophages such as DIP and RB-ILD. CONCLUSIONS: Cath-K represents a sensitive and specific marker to detect and quantitate granulomatous reactions in interstitial lung diseases, and is particularly useful in chronic HP cases.

The role of transbronchial lung biopsy for the diagnosis of diffuse drug-induced lung disease: a case series of 44 patients.

At present, no studies have evaluated the role of bronchoscopic transbronchial lung biopsy (TBLB) in the diagnosis of diffuse drug-induced lung disease (DILD), and there is no consensus for a definite diagnostic workup approach for this rare clinical entity. The aim of the present study was to evaluate the clinical usefulness of TBLB in diffuse DILD. This study was a retrospective analysis of patients with diffuse DILD, who underwent bronchoscopy. The role of TBLB was assessed to determine whether the histological results are useful for the final diagnosis. Over a 5-yr period, 44 patients underwent bronchoscopy, and all had a bronchoalveolar lavage (BAL). Thirty-three of the 44 patients underwent TBLB (75%), and the results of TBLB were diagnostically helpful in 25 (75.7%) of the procedures. No histopathologic abnormality was identified in 6 (18%) of the 33 patients. In 2 patients (6%) the obtained samples were not adequate, since no lung parenchyma was obtained. No severe complications related to bronchoscopic procedures occurred. In conclusion, TBLB is a safe procedure, and is diagnostically helpful in the majority of cases of patients with diffuse DILD. Histological data obtained by TBLB further corroborate clinical, laboratory, radiologic and BAL results for a definitive diagnosis of diffuse DILD.

The 2015 World Health Organization Classification of lung tumors: new entities since the 2004 Classification.

In the last few years different new pulmonary neoplastic lesions have been recognised and some of them, namely NUT carcinoma, PEComatous tumors, pneumocytic adenomyoepithelioma, pulmonary myxoid sarcoma, myoepithelial tumors/carcinomas entered in the last 2015-WHO classification of lung tumors. In addition angiomatoid fibrous histiocytoma and ciliated muconodular papillary tumor have been morphologically and genetically characterized albeit not yet included in the 2015-WHO classification.In the present paper we summarised the clinical, morphological, immunohistochemical and molecular features of these new entities. The knowledge of key histologic and molecular characteristics may help pathologists in achieving a correct diagnosis thus leading to an adequate therapeutic approach.

Endobronchial-ultrasound needle aspiration and endoscopic ultrasound-fine-needle aspiration in thoracic diseases.

EBUS-TBNA and EUS-FNA are minimally invasive techniques rapidly gaining ground in the non-surgical invasive diagnostic approach to thoracic diseases due to their high accuracy and low morbidity and mortality compared to surgical techniques. Moreover, in the diagnosis and staging of lung cancer the combination of the two techniques is superior to either test alone. In this review we focus on the role of EBUS-TBNA and EUS-FNA in both malignant and non-malignant thoracic diseases.

Interstitial lung disease preceding primary biliary cirrhosis in a male patient.

A 47-year-old male was admitted with subacute onset of dry cough and fever. Chest tomography demonstrated multifocal areas of consolidation and ground glass attenuation. Cytological analysis of bronchoalveolar lavage revealed lymphocytosis and eosinophilia and anatomopathological exam of transbronchial cryobiopsy showed poorly formed non-caseous granulomas associated to interstitial lympho-plasmocitary infiltrate. The diagnosis of idiopathic granulomatous lung disease (GLD) was assumed and the patient started oral prednisolone, presenting clinical, functional and radiological improvement. Two years later, the patient was diagnosed with primary biliary cirrhosis (PBC). At this time, it was possible to associate GLD with the autoimmune hepatobiliary disease. Clinical, epidemiological and pathological aspects of this uncommon case of interstitial lung disease as first presentation of PBC in a male patient are discussed.

Galanin is released by adrenocorticotropin-secreting pituitary adenomas in vivo and in vitro.

Galanin, a brain-gut peptide, is also synthesized and released by the pituitary. In man, galanin-like immunoreactivity and galanin messenger RNA have been detected specifically in normal and tumoral corticotropes, but little is known about the production and release of galanin by the human pituitary. We evaluated galanin release by 5 ACTH-secreting pituitary adenomas in culture and plasma galanin concentrations in the inferior petrosal sinuses (IPSs) of 15 patients with Cushing's disease before and after CRH administration. For comparison, the galanin response to CRH was evaluated in 8 normal controls. Galanin secretion by pituitary tumor cultures ranged from 30-230 pmol/4 h. Incubation with CRH induced an increase in galanin concentrations (100 pM CRH: 151 +/- 32%; 1 nM CRH: 232 +/- 43%; 10 nM CRH: 246 +/- 35%; and 100 nM CRH: 270 +/- 44% unstimulated levels at 24 h, P < 0.05). The stimulatory effect of CRH seemed to be dose-dependent. Basal and CRH-stimulated ACTH and galanin concentrations also exhibited a strong positive correlation in single tumor cultures. At IPS sampling, mean basal plasma galanin concentrations in the dominant IPS were somewhat higher than those registered at the periphery (18.6 +/- 1.94 vs. 15.8 +/- 1.60 pmol/L, P = 0.05). Administration of CRH induced a modest but significant increase in galanin concentrations at all three sampling sites. No correlations were found between ACTH and galanin levels in the IPSs and at the periphery. Different from what was observed in patients with Cushing's disease, CRH did not modify plasma galanin concentrations in normal subjects. In conclusion, this study demonstrates that galanin is released by human tumoral corticotropes and responds to CRH. The role of locally produced galanin is, as yet, unknown but may possibly be that of a autocrine/paracrine modulator.

Long-lasting prolactin-lowering effect of cabergoline, a new dopamine agonist, in hyperprolactinemic patients.

The new long-acting ergoline derivative cabergoline was given orally in a single dose of 300 micrograms to 15 hyperprolactinemic patients (including 4 acromegalic patients, 2 of whom were dopamine responsive). Serum PRL and GH levels were determined before and 3, 4, and 6 h and 1, 2, 3, 4, 5, 6, and 7 days after treatment. A control test with a single oral dose of 2.5 mg bromocriptine was also performed; serum PRL and GH levels were measured at the same time intervals for 2 days. Cabergoline induced a marked fall in serum PRL which began within 3 h and continued for 7 days. The maximal decrease ranged between -49.2% and -55.2% and occurred after 2-5 days. This maximal effect was only slightly less than that 6 h after bromocriptine treatment (-63.8%). After cabergoline treatment, serum GH levels did not change significantly in either nonacromegalic or acromegalic patients, whereas the two dopamine-responsive acromegalic patients had a marked GH fall after bromocriptine. A moderate blood pressure decrease, more evident in the standing position, occurred after both cabergoline and bromocriptine treatments. The only symptomatic side-effect was orthostatic hypotension after cabergoline in an elderly woman. These data indicate that cabergoline has potent and prolonged dopaminergic activity and may prove suitable for once weekly treatment of hyperprolactinemic patients.

Effect of gamma-aminobutyric acid on growth hormone and prolactin secretion in man: influence of pimozide and domperidone.

To investigate the possibility that GH release induced by gamma-aminobutyric acid (GABA) in man is mediated by a dopaminergic mechanism(s), we evaluated the effect of two antidopaminergic compounds, pimozide and domperidone, on the plasma GH response to acute GABA administration (5 g, orally). Only the former compound can freely cross the blood-brain barrier. In 9 normal volunteers, GABA caused a significant increase of plasma GH levels (P < 0.0001 vs. GH levels in a group of 14 controls). In these subjects, pimozide (6 mg/day, orally, for 4 days) significantly blunted the GH elevation induced by GABA (P < 0.01). Unlike pimozide, in 8 additional subjects, domperidone (4 mg injected iv immediately before GABA administration) did not influence the GABA-induced GH response. GABA did not alter either baseline or pimozide-stimulated plasma PRL levels. Likewise, it did not significantly modify the brisk PRL rise after domperidone injection. These findings are consistent with the hypothesis that GABA-stimulated GH secretion is mediated via dopamine release at a suprapituitary level. With regard to PRL secretion, no GABA-dopamine interactions are readily apparent.

Cabergoline in the treatment of early Parkinson's disease: results of the first year of treatment in a double-blind comparison of cabergoline and levodopa. The PKDS009 Collaborative Study Group.

Cabergoline is a potent D2 receptor agonist with a half-life of 65 hours that may provide continuous dopaminergic stimulation administered once daily. In this study, we randomized de novo Parkinson's disease (PD) patients to treatment with increasing doses of cabergoline (0.25 to 4 mg/d) or levodopa (100 to 600 mg/d) up to the optimal or maximum tolerated dose. Decreases of > 30% in motor disability (Unified Parkinson's Disease Rating Scale Factor III) versus baseline were considered indicative of clinical improvement. If 30% improvement was not achieved, levodopa/ carbidopa could be added on an open basis. Of the 208 patients entered in the cabergoline group, 175 remained in the study for 1 year at a mean dose of 2.8 mg/d; in the levodopa group, 176 of the 205 patients entered were still on study after 1 year at a mean dose of 468 mg/d. The proportion of patients requiring additional levodopa/carbidopa increased in the cabergoline group from 18% at 6 months to 38% at 1 year versus 10% (p = 0.05) at 6 months and 18% (p < 0.01) at 1 year in the levodopa group. The proportion of patients showing clinical improvement did not differ significantly between the two groups, or between the subgroups on monotherapy, at any endpoint. Irrespective of levodopa/carbidopa addition, 81% of patients in the cabergoline group and 87% of patients in the levodopa group were clinically improved at 1 year (p = 0.189); the corresponding figures for the subgroup on monotherapy were 79% in the cabergoline-treated patients and 86% in the levodopa-treated patients (p = 0.199). The mean difference versus baseline in Unified Parkinson's Disease Rating Scale Factor III scores in patients who remained on monotherapy up to 1 year was 12.6 (95% confidence interval [CI]: 10.8, 14.3) in the cabergoline group and 16.4 (95% CI: 14.8, 18.0) in the levodopa group. Adverse events occurred in 76% of patients on cabergoline and in 66% of patients on levodopa. The severity profile for reported events was similar for the two agents. The results of this study indicate that cabergoline treatment for up to 1 year is only marginally less effective than levodopa in the proportion of patients who can be treated in monotherapy. More than 60% of de novo PD patients could be managed on cabergoline alone up to 1 year. In the patients in whom levodopa/carbidopa was needed, the combination therapy provided efficacy similar to that obtained with levodopa alone, with a relevant sparing of levodopa.

Corticotrophin-releasing activity of desmopressin in Cushing's disease: lack of correlation between in vivo and in vitro responsiveness.

Desmopressin (DDAVP), an arginine vasopressin analogue, markedly stimulates ACTH secretion in patients with Cushing's disease, in contrast to its minimal effect in normal subjects. However, little is known about the mechanisms underlying this action and it appeared to be of interest to evaluate the effect of DDAVP on ACTH-secreting pituitary adenomas in vitro, in comparison with its effect in the same patients in vivo. Pituitary adenomas from 14 patients with Cushing's disease were incubated with DDAVP, corticotrophin-releasing hormone (CRH) and DDAVP together with vasopressin receptor antagonists or CRH. Incubation with DDAVP induced a modest dose-dependent increase in ACTH concentrations which appeared maximal at 10 nM. CRH stimulated ACTH to a greater extent compared with DDAVP and potentiated the effect of DDAVP alone. The DDAVP-induced ACTH increase appeared blunted by vasopressin V(2) and V(3) receptor antagonists. V(3) receptor gene expression was detected by RT-PCR in all adenoma samples except for two which were not responsive to DDAVP in vitro but responsive to the peptide in vivo. Surprisingly, no difference in the in vitro ACTH secretory response was observed between in vivo DDAVP-responsive (ACTH peak>150% baseline) and -unresponsive (ACTH peak<120% baseline) patients, suggesting that the pituitary adenoma is not the sole mediator of the ACTH-releasing effect of DDAVP. In conclusion, the marked stimulatory effect of DDAVP observed in patients with Cushing's disease appears to be mainly dependent on an extrapituitary action, possibly the inhibition of a corticotrophin release-inhibitory factor.

Lack of growth hormone response to acute administration of dexamethasone in anorexia nervosa.

High plasma growth hormone (GH) levels, associated with abnormal hormone responses to provocative stimuli, point to an altered GH secretion in anorexia nervosa. The GH-releasing effect of acutely administered glucocorticoids, firmly established in normal subjects, has not been reported in these patients. In this study, acute iv administration of 4 mg of dexamethasone, compared with saline, increased plasma GH in nine normal-weight women (AUC 848.2 +/- 127.95 vs 242.8 +/- 55.35 micrograms.l-1.min-1, p < 0.05, respectively) but was ineffective in 11 anorectic patients (AUC 3271.8 +/- 1407.11 vs 2780.0 +/- 1162.04 micrograms.l-1.min-1, NS). After dexamethasone, a significant lowering of plasma cortisol was observed in normal women (AUC 25367.0 +/- 3128.43 vs 47347.1 +/- 4456.61 nmol.l-1.min-1, after dexamethasone and saline, respectively, p < 0.05), but not in anorectic patients (AUC 77809.3 +/- 8499.92 vs 78454.9 +/- 7603.62 nmol.l-1.min-1, NS). In both groups, plasma adrenocorticotrophin (ACTH) displayed a significant decrease after dexamethasone (AUC 523.6 +/- 92.08 vs 874.2 +/- 115.03 pmol.l-1.min-1, p < 0.05, after dexamethasone and saline, respectively, in anorectic patients and 377.5 +/- 38.41 vs 1004.9 +/- 200.51 pmol.l-1.min-1, p < 0.05, in controls). However, when considering the hormonal decremental areas, a significant dexamethasone-induced ACTH inhibition, compared to saline, was evidenced in normal (delta AUC -414.4 +/- 65.75 vs 222.9 +/- 42.40 pmol.l-1.min-1, p < 0.05) but not in anorectic women (delta AUC -254.2 +/- 96.92 vs 2.9 +/- 132.32 pmol.l-1.min-1, NS).(ABSTRACT TRUNCATED AT 250 WORDS)

Salivary cortisol measurement in normal-weight, obese and anorexic women: comparison with plasma cortisol.

OBJECTIVE: To compare salivary, plasma and urinary free cortisol (UFC) measurements in patients with anorexia nervosa, in whom an overdrive of the hypothalamic-pituitary-adrenal (HPA) axis is well established but information on salivary cortisol is lacking, in viscerally obese patients in whom subtle abnormalities of cortisol secretion and metabolism are postulated, and in normal-weight healthy women. PARTICIPANTS AND EXPERIMENTAL DESIGN: Measurement of salivary cortisol offers a convenient way to assess the concentrations of free, biologically active cortisol in plasma in different physiopathological settings. Forty-seven drug-free, newly diagnosed women with active restrictive anorexia nervosa, 30 restrictive anorexic women undergoing chronic psychopharmacological treatment, 47 women with mild-to-moderate visceral obesity, 103 women with severe central obesity and 63 normal-weight healthy women entered the study. Salivary and blood samples were collected at 0800 h, 1700 h and 2400 h, together with three consecutive 24-h urine specimens for UFC determination. In controls and patients with anorexia nervosa (n=83), salivary and plasma cortisol were also measured after a 1-mg overnight dexamethasone suppression test (DST). In patients with anorexia nervosa, mood was rated by the Hamilton scale for anxiety and depression. RESULTS: Untreated patients with anorexia nervosa showed increased plasma and salivary cortisol and UFC concentrations (all P<0.001 compared with controls), and decreased cortisol suppression after DST in plasma and saliva (P<0.0001 and P<0.005 respectively compared with controls). These alterations were less pronounced, although still statistically significant, in treated patients with anorexia nervosa. Salivary cortisol was highly correlated with paired plasma cortisol in the whole population and after splitting the participants by group (P<0.0001). However, for plasma cortisol values greater than 500 nmol/l (the corticosteroid-binding globulin saturation point), this parallelism was lost. Taking plasma cortisol as a reference, the level of agreement for post-dexamethasone salivary and plasma cortisol was 58.9% among suppressors and 77.8% among non-suppressors (chi2 test: P<0.01). Decreased 0800 h/2400 h cortisol ratios were observed in plasma and saliva in drug-free patients with anorexia nervosa (P<0.005 and P<0.05 respectively compared with controls), and in saliva in severely obese patients (P<0.05 compared with controls). Depression and anxiety scores were unrelated to cortisol concentrations in any compartment. CONCLUSIONS: Salivary cortisol measurement is a valuable and convenient alternative to plasma cortisol measurement. It enables demonstration of the overdrive of the HPA axis in anorexia nervosa and subtle perturbations of the cortisol diurnal rhythm in women with visceral obesity. With the establishment of more specific and widely acceptable cut-off values for dynamic testing, measurement of salivary cortisol could largely replace plasma cortisol measurement.

Induction of follicle maturation and ovulation by gonadotropin administration in women with beta-thalassemia.

The objective of this paper was to assess the ability of gonadotropin administration to induce ovarian steroidogenesis, follicle maturation and ovulation in hypogonadal women affected by beta-thalassemia. Thirteen hypogonadal thalassemic women underwent a test with gonadotropin-releasing hormone (GnRH), with estimation of serum follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels. They were then administered human menopausal gonadotropin (hMG) for a period ranging from 11 to 15 days with a total dose variable from 3,300 to 4,200 IU. In each patient, the initial dosage of 300 IU daily, adopted for the first 9 days, was modified subsequently according to the ovarian morphology, as shown by serial echographic examinations and by serum estradiol levels. In those patients in whom a dominant follicle was evidenced and the occurrence of pregnancy could be excluded, induction of ovulation was attempted by administration of 10,000 IU of human chorionic gonadotropin (hCG). All patients displayed a reduced LH and FSH rise in response to GnRH. Upon hMG administration, they exhibited echographic evidence of follicular growth with a clear-cut increase of serum estradiol, which peaked between the 9th and the 16th day from the start of treatment. In two out of three patients in whom a dominant follicle developed, ovulation was induced successfully by hCG injection, as shown by the increase of serum progesterone and by the ultrasonographic demonstration of a corpus luteum. This study has shown that, by proper pharmacological stimulation, the steroidogenic function of the gonads and even ovulation can be reinstated in hypogonadal thalassemic women.(ABSTRACT TRUNCATED AT 250 WORDS)