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Introduction Hurthle cells are modified follicular thyroid cells, whose development and proliferation have been related to different stimuli inducing cellular stress. Most thyroid aspirates containing Hurthle cells are classified as indeterminate, although the specific risk of malignancy for this subtype of atypia remains unclear. The aim of our study was to assess if the presence of Hurthle cells in indeterminate thyroid nodules correlates with the risk of malignancy. We further evaluated if this risk can be modified by the presence of an underlying Hashimoto's thyroiditis. Materials and methods We retrospectively analyzed all indeterminate thyroid nodules that were surgically treated at our institution between January 2010 and March 2019. For each nodule, we inferred the presence of Hurthle cells in the cytological report. Cytological findings were then correlated with histological reports. Results 354 indeterminate thyroid nodules were included in the study. The rate of malignancy resulted significantly lower in nodules exhibiting Hurthle cells compared to those negative for this cellular pattern (11.4% vs 22.5%, p = 0.01). Although there was no difference in the rate of malignancy in the whole population according to the presence or absence of Hashimoto's thyroiditis (21.5 vs 18.5%, p = 0.63), the significantly lower prevalence of malignant lesions in nodules with Hurthle cells was confirmed only in the presence of a histologically documented Hashimoto's thyroiditis (6.2% vs 32%, p = 0.005). Conclusions The finding of Hurthle cells in indeterminate thyroid nodules is associated with a low risk of malignancy in patients with an underlying Hashimoto's thyroiditis. The clinical management of these lesions may therefore be more conservative.

Context Several case reports of Graves’ disease (GD) occurrence after COVID-19 vaccination that are possibly related to the autoimmune syndrome induced by adjuvants (ASIA) were published recently. Objective The aim of our study was to evaluate possible distinctive features in the presentation and clinical course of patients with GD occurring early (within 4 weeks) after COVID-19 vaccination who attended our Endocrine Unit in 2021. Methods Patients with a first episode of GD attending a tertiary endocrine center between January 1, 2021, and December 31, 2021, were included. Results Sixty-four patients with a first episode of GD were seen in 2021: 20 (31.2%) of them had onset within 4 weeks following vaccine administration. Compared with the other 44 patients, the 20 patients with postvaccine early-onset (PoVEO) GD were older (median age 51 years vs 35 years, P = .003) and more likely to be male (40.0% vs 13.6%, P = .018). At diagnosis, the biochemical and immune profiles were similar between the 2 groups. However, at 3 months after starting methimazole, patients with PoVEO GD had significantly lower thyrotropin receptor antibody titer and were taking lower doses of methimazole than the other patients with GD. None in the PoVEO group had sustained free triiodothyronine elevation. Conclusion This relatively large series suggests that in 2021 PoVEO GD may be a new nosologic entity representing one-third of patients evaluated for new-onset GD in our center. Distinctive features included older age at onset, higher male prevalence, and a better initial biochemical and immunologic response to treatment. Further studies are warranted to clinically and biochemically differentiate these cases from sporadically occurring GD.

Purpose: The effects of growth hormone (GH) replacement on bone mass and body composition in adult with GH deficiency (AGHD) are still debated with regard to their persistence in the long term. Moreover, the impact of gender on the response to GH is controversial. Aim of this study was to evaluate the long-term effects of rhGH replacement on bone mass and body composition in a monocentric cohort of patients with AGHD.Methods: Data from 138 patients with AGHD (34.3 ± 14.3 years, 48 women and 90 men) treated with rhGH for a period of at least 3 years up to a maximum of 10 were retrospectively collected. Bone mineral density (BMD) at the lumbar spine, femur, and radius, and total and truncular body composition were evaluated by dual energy X-ray absorption (DXA) before and during treatment. Clinical and laboratory evaluations were performed before and during the treatment period on an annual basis.Results: Lumbar spine BMD consistently increased in males, while in females decreased after a transient improvement observed during the first 4 years of therapy. There were no significant changes in femoral BMD in either sexes, while a progressive increase at radius was observed only in males. Lean mass significantly increased in both sexes, while fat mass decreased only in males.Conclusions: In AGHD patients long-term rhGH replacement therapy induces a positive effect with regard to bone mass and body composition. A sexual dimorphism in the response to treatment is evident, with males displaying more favorable outcome.

Background. The 8th edition of the American Joint Committee on Cancer (AJCC) staging system changed the age cutoff for risk stratification of differentiated thyroid carcinoma (DTC), downgrading patients between 45 and 54 years to stage I or II. The aim of our study was to assess cancer-specific survival (CSS) in patients aged 45–54 years, in order to document the prognostic capability of the last edition of the staging system. Methods. We retrospectively reviewed the medical records of 172 patients that from January 1st, 2005, to May 31st, 2017, were diagnosed at our institution with DTC when aged 45–54 years. We restaged patients according to the 8th edition of the staging system and estimated CSS. Results. 101 out of 172 patients (58.7%) were reallocated to a lower stage. Of the 101 downstaged patients, 88 (88.9%) showed a high or intermediate American Thyroid Association (ATA) risk of recurrence. We recorded no cancer-specific deaths. Conclusions. Risk of cancer-specific mortality in patients aged 45–54 years with DTC is low, supporting the prognostic capability of the 8th edition of the staging system. However, we recommend to consider carefully the significant proportion of patients at intermediate or high risk of recurrence in this group of patients.

Background The 8th edition of the American Joint Committee on Cancer (AJCC) staging system changed the age cutoff for risk stratification of differentiated thyroid carcinoma (DTC), downgrading patients between 45 and 54 years to stage I or II. The aim of our study was to assess cancer-specific survival (CSS) in patients aged 45–54 years, in order to document the prognostic capability of the last edition of the staging system. Methods We retrospectively reviewed the medical records of 172 patients that from January 1st, 2005, to May 31st, 2017, were diagnosed at our institution with DTC when aged 45–54 years. We restaged patients according to the 8th edition of the staging system and estimated CSS. Results 101 out of 172 patients (58.7%) were reallocated to a lower stage. Of the 101 downstaged patients, 88 (88.9%) showed a high or intermediate American Thyroid Association (ATA) risk of recurrence. We recorded no cancer-specific deaths. Conclusions Risk of cancer-specific mortality in patients aged 45–54 years with DTC is low, supporting the prognostic capability of the 8th edition of the staging system. However, we recommend to consider carefully the significant proportion of patients at intermediate or high risk of recurrence in this group of patients.

Context Recombinant human growth hormone (rhGH) replacement therapy is often prescribed in patients with nonfunctioning pituitary adenoma (NFPA) or craniopharyngioma, Objective To study whether rhGH therapy in patients with adult growth hormone deficiency (AGHD) increases the risk of pituitary tumor recurrence. Design Retrospective, observational study. Setting Tertiary care center. Patients We studied 283 consecutive patients with AGHD due to NFPA or craniopharyngioma between 1995 and 2018. Intervention rhGH treatment at standard doses was initiated in 123 patients (43.5%). The remaining 160 patients served as controls. Main Outcome Measure Risk of tumor recurrence in rhGH-treated and control patients. Results In univariate analysis, recurrence of the pituitary tumor was less frequent in rhGH-treated patients (19.5%) than in controls (29.7%; hazard ratio [HR] 0.53, 95% confidence interval [CI] 0.32–0.86; P = .01). Multivariate Cox analysis demonstrated that the risk of tumor recurrence was associated with detection of residual disease at the baseline magnetic resonance imaging (HR 9.17; 95% CI, 4.88–17.22; P Conclusions We found no association between rhGH replacement and the risk of tumor recurrence in patients with AGHD caused by NFPA or craniopharyngioma. These data add to the mounting evidence that rhGH therapy has a neutral effect on the recurrence of pituitary tumors. Précis Replacement therapy with rhGH is prescribed to patients with adult growth hormone deficiency. Our study found no increased risk of pituitary tumor recurrence.

Objective The impact of growth hormone (GH) deficiency of the adult on cardiovascular function remains only partially elucidated. Purpose of this study was to test cardiac function in adult GH deficient patients using cardiac magnetic resonance (CMR). Design Cardiac magnetic resonance (CMR) techniques, including cardiac 31P MR spectroscopy and evaluation of gadolinium late-enhancement, were applied to assess simultaneously, in a cross-sectional fashion, morphological, functional, metabolic, and structural parameters of the left (LV) and right ventricle (RV) in 15 patients with adult onset GH deficiency. Fifteen healthy individuals served as controls. Results In GH deficient patients LV systolic function (EF%: 61 ± 1.7 vs 62.1 ± 0.8; p = .44) was not different in spite of a lower LV mass (83.2 ± 5.3 vs 145.3 ± 11.9 g; p = .001), a subclinical impairment of diastolic function (E/A peak ratio: 1.6 ± 0.2 vs 2.1 ± 0.2 p = .05), and a trend for lower PCr/ATP ratio (2.1 ± 0.8 vs 2.3 ± 0.1 p = .07). The RV showed reduced chamber size (end diastolic volume 123.8 ± 9 vs 147.9 ± 7.6 mL; p = .021) with preserved mass. No structural alterations of the LV and RV at late-enhancement were detected in these patients. Conclusions GH deficient patients represent a unique model of reduced LV myocardial mass in which major structural and metabolic alterations are lacking. Mal-adaptive mechanisms developing in the long term in response to GH deficiency and more severely affecting the LV remain to be elucidated.

Purpose: Gonadotroph adenomas are pituitary adenomas with inefficient and variable secretory characteristics, that is why they are usually considered as a subgroup of nonfunctioning pituitary adenomas (NFPA) and are recognized only at immunohistochemistry. When gonadotroph adenomas secrete active hormones, they may cause spontaneous ovarian hyperstimulation syndrome (OHSS) in premenopausal women. Aim of our study is to describe three women with OHSS diagnosed before the removal of the adenoma and to calculate the prevalence of OHSS in premenopausal women with a clinical diagnosis of NFPA. Methods: We reviewed clinical records of premenopausal women that underwent neurosurgery for NFPA at our centre between 1993 and 2014. OHSS was diagnosed in patients with high levels of FSH, suppressed LH, hyperestrogenism, abdominal symptoms, polymenorrhea, enlarged ovaries with cysts or previous surgery for ovarian cysts. Results: 171 women were included into the study; 62 (36.6%) had a gonadotroph adenoma diagnosed at immunohistochemistry. Two patients were retrospectively diagnosed as having OHSS due to gonadotroph adenoma and three had OHSS diagnosed before neurosurgery. The prevalence of OHSS was 2.9% in the overall group of patients with NFPA and 8.1% among patients with a gonadotroph adenoma detected at immunohistochemistry. Conclusions: Frequency of OHSS due to a gonadotroph adenoma is not negligible. Increased awareness of the characteristic clinical and hormonal picture should permit an early detection of this condition in premenopausal women with a pituitary adenoma.

BACKGROUND Hirsutism in females can be a source of considerable psychological distress and a threat to female identity. The aim of our study was to evaluate a possible relationship between facial, total body hair involvement and physical, mental and social well-being during 12 months of follow-up and treatment. Both objective and subjective methods of evaluating hirsutism were used: the Ferriman-Gallwey (FG) scoring method and the questionnaires General Health Questionnaire (GHQ)-12, Polycystic Ovary Syndrome Questionnaire (PCOSQ) and SF-12. METHODS The total of 469 female patients (mean age 27.61±7.63 years) was enrolled in 27 Italian centers participating in this study. Higher total body score was correlated to significant emotional discomfort. The correlation between the FG total body score, the facial score and physical/mental health was found to be significant in all the patients assessed by SF-12 questionnaire. The ongoing reduction of GHQ-12 score was found for the facial FG score at the first follow-up (T0-T1 period) and at the second one (T0-T2). No relationship was found between T1 and T2. At both 6 (T1) and 12 months (T2) follow-up an increase of PCOSQ Score (psychological improvement) was accompanied by a concomitant reduction of the FG Score (reduction of hirsutism). Physical health assessed by SF-12 questionnaire does not change at both 6- and 12-month follow-up, but mental health decreased at both T1 and T2. RESULTS The clinical improvement was achieved at 6 months regardless on treatment used and it was maintained for the next six-month follow-up. The clinical outcome could be assessed both by FG Score both through questionnaires administrated to each patient with hirsutism. CONCLUSIONS For the evaluation of psychopathological discomfort the most appropriate questionnaire was GHQ-12, because of it major sensitivity to identify the psychological discomfort in the hirsutism.

Objective To report the use of rituximab to treat thyroidassociated orbitopathy (TAO) in a patient with a concomitant B-cell organ-specific autoimmune disorder—the stiff person syndrome (SPS). Methods We present a case report and a review of the related literature. Results A 62-year-old man with SPS, latent autoimmune diabetes of the adult, and Graves-Basedow disease was referred to our medical center because of bilateral TAO. An ophthalmologic examination documented asymmetric bilateral NOSPECS (N = no signs or symptoms; O = only signs, no symptoms; S = soft tissue involvement; P = proptosis; E = extraocular muscle involvement; C = corneal involvement; and S = sight loss) class IV TAO (left eye > right eye) with a clinical activity score of 5 on a scale of 7. Magnetic resonance imaging of the orbits documented bilateral exophthalmos (left eye > right eye) due to retrobulbar fibroadipose infiltration, bilateral increase of extrinsic ocular muscle thickness, and enhancement of the left inferior rectus muscle on T2-weighted sequences. Because of concomitant incapacitating SPS and diet-controlled latent autoimmune diabetes of the adult, we excluded long-term corticosteroid therapy as an option and considered the use of rituximab, a mouse-human chimeric monoclonal antibody targeting the CD20 protein on pre-B and mature B lymphocytes. Rituximab was administered in accordance with the protocol for rheumatoid arthritis. During the subsequent 4 months, clinical signs and symptoms of TAO dramatically resolved (clinical activity score = 0 of 7) with a sustained improvement of the spastic paraparesis. The glutamic acid decarboxylase antibody titer remained high, and glycemic control and first-phase insulin secretion did not change. Conclusion Treatment of active TAO with rituximab should be considered when standard intravenous pulse glucocorticoid treatment is contraindicated or ineffective and when SPS or other organ-specific autoimmune disorders with involvement of humoral autoimmunity are present, inasmuch as more than 1 disease may benefit from the use of this chimeric monoclonal antibody. (Endocr Pract. 2010;16:677-685)

Background: Clinical studies on the effect of growth hormone (GH) on thyroid function in patients with GH deficiency are contradictory. Further, the majority of published observations are limited to the first 6-12 months of GH replacement therapy. The aim of our study was to estimate the incidence of clinically relevant hypothyroidism in a cohort of patients with adult GH deficiency (AGHD) during long-term therapy with recombinant human GH (rhGH). Methods: The study was designed as a retrospective collection of data on thyroid function in 49 AGHD patients of whom 44 (90%) had multiple hormone deficiency. Thirty-seven patients (76%) were on stable levothyroxine (LT4) replacement therapy (HYPO), and 12 (24%) were euthyroid (EUT). Therapy with rhGH was started at a dose of 3.5 μg/kg body weight and adjusted according to insulin-like growth factor-I (IGF-I) levels. At baseline, 6 months, 12 months, and yearly thereafter we measured free triiodothyronine (fT3), free thyroxine (fT4), thyroid-stimulating hormone, and IGF-I. Study outcome was fT4 level below the normal range (9 pmol/L), irrespectively of fT3 or thyroid-stimulating hormone levels. Results: During a follow-up of 115 patient-years, mean fT4 level decreased significantly, although remaining within the normal range (p = 0.0242; month 48 vs. baseline). The largest decrease was between baseline and month 6, when fT4 decreased of 1.43 pmol/L (95% confidence interval, 0.33-2.53) per 1 unit (μg/kg body weight) increase in rhGH dose. The incidence of hypothyroidism was 1.2 (HYPO group) and 6.7 (EUT group) events per 100 patient-years. Conclusion: We confirm that in patients with AGHD, rhGH therapy is associated with a small, although significant, decrement of fT4 in the first 6 months of replacement therapy. However, the incidence of hypothyroidism is low. Monitoring of thyroid function during rhGH therapy is advisable, particularly in the first year of therapy when the largest decrease in fT4 occurs. © Copyright 2008, Mary Ann Liebert, Inc.

ObJEctIVE: some extra-thyroid actions of thyroid stimulating hormone (tsH), such as an in vitro action on bone, have been described. Our aim was to evaluate in vivo the acute effect of a recombinant human tsH (rhtsH)-induced tsH surge on Osteoprotegerin (OPG) and receptor activator of the nuclear factor-κb (r ANK-L) levels in patients under levo-thyroxine (L-t4) therapy. DEsIGN: 24 patients with differentiated thyroid carcinoma (Dtc) were studied. s tandard rhts H testing was performed. OPG, r ANK-L, ts H, thyroid hormones, thyroglobulin and several parameters of bone metabolism were evaluated. rE su Lts: baseline OPG and rANK-L levels were in the range of our reference population. An inverse correlation between OPG and spinal Z-score (p=0.029) and between r ANK-L and age (p=0.018) or urinary calcium/creatinine ratio (p=0.011) was detected. After rhtsH administration, a significant (p

OBJECTIVE - Aims of this study were 1) to assess sexual function and endocrine profile among fertile type 1 diabetic women during the follicular and luteal phases of the menstrual cycle, 2) to compare these results with those obtained among healthy fertile women who served as control subjects, and 3) to explore the correlations between sexual function and endocrine milieu among patients and control subjects during the follicular and luteal phases of the menstrual cycle. RESEARCH DESIGN AND METHODS - Fifty fertile women with type 1 diabetes and 47 healthy control subjects completed a semistructured medical interview and filled in self-administered validated instruments to evaluate sexual function, depression, and sexual distress. Venous blood samples were drawn to measure glycated hemoglobin and an endocrine profile during either the follicular or the luteal phase of the menstrual cycle. RESULTS - Type 1 diabetic women had decreased sexual function and increased sexual distress compared with control subjects during the luteal, but not the follicular, phase of the menstrual cycle. During the follicular phase, patients had lower estrogenic basal tone, lower "weak" androgen (namely Delta(4)-androstenedione and dehydroepiandrosterone sulfate) production, and lower free-triiodothyronine and free-thyroxine levels compared with control subjects. During the luteal phase, total testosterone levels were higher in patients than control subjects, while 17 beta-estradiol and progesterone levels were lower in patients than control subjects. CONCLUSIONS - Among type 1 diabetic women, sexual function and sexual distress vary according to the phase of the menstrual cycle. This finding may have implications on the clinical assessment of sexual function in type 1 diabetic women, OBJECTIVE - Aims of this study were 1) to assess sexual function and endocrine profile among fertile type 1 diabetic women during the follicular and luteal phases of the menstrual cycle, 2) to compare these results with those obtained among healthy fertile women who served as control subjects, and 3) to explore the correlations between sexual function and endocrine milieu among patients and control subjects during the follicular and luteal phases of the menstrual cycle. RESEARCH DESIGN AND METHODS - Fifty fertile women with type 1 diabetes and 47 healthy control subjects completed a semistructured medical interview and filled in self-administered validated instruments to evaluate sexual function, depression, and sexual distress. Venous blood samples were drawn to measure glycated hemoglobin and an endocrine profile during either the follicular or the luteal phase of the menstrual cycle. RESULTS - Type 1 diabetic women had decreased sexual function and increased sexual distress compared with control subjects during the luteal, but not the follicular, phase of the menstrual cycle. During the follicular phase, patients had lower estrogenic basal tone, lower "weak" androgen (namely Delta(4)-androstenedione and dehydroepiandrosterone sulfate) production, and lower free-triiodothyronine and free-thyroxine levels compared with control subjects. During the luteal phase, total testosterone levels were higher in patients than control subjects, while 17 beta-estradiol and progesterone levels were lower in patients than control subjects. CONCLUSIONS - Among type 1 diabetic women, sexual function and sexual distress vary according to the phase of the menstrual cycle. This finding may have implications on the clinical assessment of sexual function in type 1 diabetic women

OBJECTIVE: Osteoprotegerin (OPG), a glycoprotein belonging to the tumor necrosis factor receptor family, is an endogenous inhibitor of osteoclastogenesis produced by cells of the osteoblast lineage. OPG is a key cytokine involved in the regulation of osteoblast/osteoclast cross-talk. Since GH replacement therapy in GH deficiency (GHD) activates bone remodeling and increases bone mass, we investigated if short-term GH replacement therapy affects plasma OPG levels. DESIGN AND METHODS: Eighteen adults with GHD, ranging from 17 to 51 Years (nine childhood-onset and nine adult-onset) were enrolled in the study. All subjects were on stable replacement therapy, especially sex hormones. The starting dose of GH replacement therapy was 4 microg/kg per day x 7 days/week, and was progressively increased according to the serum IGF-I values. Biochemical parameters of bone and mineral metabolism were measured before and after 6 Months of GH replacement therapy. Bone mass density (BMD) was monitored at three skeletal sites (lumbar vertebrae, femur, radius) by dual-energy X-ray absorptiometry. RESULTS: After 6 Months of therapy, ionized calcium, parathyroid hormone and 25-OH vitamin D did not change, whereas total serum calcium and urinary calcium excretion increased significantly (P

We report a patient with a meningioma presenting with Cushing's syndrome, an unprecedented paraneoplastic presentation. Molecular studies, bioassay, and high-performance liquid chromatography of tumor specimens demonstrated the synthesis and secretion of bioactive corticotropin-releasing hormone. To our knowledge, this appears to be the first report of a hormone-secreting meningioma and, further, the first clearly proven case of Cushing's syndrome due to ectopic corticotropin-releasing hormone secretion without concomitant corticotropin production.

Pro-inflammatory cytokines play a key role in the inflammatory response and contributing to producing local hyperalgesia. It is known that pentoxifylline inhibits inflammatory cytokine production. Therefore, the aim of this study was to find out, using a behavioural test and neuronal Fos expression, if this drug had some antinociceptive effect decreasing nociresponsive neuron activation in the spinal cord after nociceptive inflammation (injection of formalin in the hind paw). Our data showed that formalin induced a great number of Fos-positive neurons in the dorsal horn of the lumbar spinal cord mainly in the ipsilateral I and II laminae. The local pre-treatment with pentoxifylline before the formalin injection, decreased the nociceptive response in the formalin test and the number of Fos positive neurons in the spinal cord. This finding suggests that pentoxifylline is involved in decreasing the activation of nociceptive neurons in the spinal cord playing a role in local anti-nociception.

Objective. Laparoscopic adrenalectomy is now a standard procedure for the vast majority of patients with surgical adrenal disease. Herein, we evaluate various techniques employed during laparoscopic adrenalectomy, and assess the current role of laparoscopic adrenalectomy, and possible future developments. Materials and Methods: We reviewed large series of reports presenting the results of laparoscopic transperitoneal and retroperitoneal adrenalectomy and we compared the data of different series and authors, adding our experience. Results: Laparoscopic adrenalectomy is a safe, reproducible and effective procedure with low complication rates. With increasing worldwide experience, the indications for laparoscopic adrenalectomy are expanding. When retrospectively compared to open surgery, laparoscopic adrenalectomy is superior in terms of postoperative pain, hospital stay, return to normal activity and complications. Conclusions. Laparoscopic adrenalectomy is a safe and effective option for most surgical adrenal pathologies. Moreover, laparoscopic adrenalectomy is associated with a superior patient tolerance profile. It is safe to say that today, laparoscopy must be considered the first choice procedure for excision of benign surgical adrenal lesions. Copyright (C) 2001 S.Karger AG, Basel.

We have recently presented experimental evidence indicating that insulin has a physiologic inhibitory effect on growth hormone (GH) release in healthy humans. The aim of the present study was to determine whether in obesity, which is characterized by hyperinsulinemia and blunted GH release, insulin contributes to the GH defect. To this aim, we used a simplified experimental protocol previously used in healthy humans to isolate the effect of insulin by removing the interference of free fatty acids (FFAs), which are known to block GH release. Six obese subjects (four men and two women; age, 30.8 +/- 5.2 years; body mass index, 36.8 +/- 2.8 kg/m2 [mean +/- SE]) and six normal subjects (four men and two women; age, 25.8 +/- 1.9 years; body mass index, 22.7 +/- 1.1 kg/m2) received intravenous (i.v.) GH-releasing hormone (GHRH) 0.6 microg/kg under three experimental conditions: (1) i.v. 0.9% NaCl infusion and oral placebo, (2) i.v. 0.9% NaCl infusion and oral acipimox, an antilipolytic agent able to reduce FFA levels (250 mg at 6 and 2 hours before GHRH), and (3) euglycemic-hyperinsulinemic clamp (insulin infusion rate, 0.4 mU x kg(-1) x min(-1)). As expected, after placebo, the GH response to GHRH was lower for obese subjects versus normals (488 +/- 139 v 1,755 +/- 412 microg/L x 120 min, P < .05). Acipimox markedly reduced FFA levels and produced a mild reduction of insulin levels; under these conditions, the GH response to GHRH was increased in both groups, remaining lower in obese versus normal subjects (1,842 +/- 360 v 4,871 +/- 1,286 microg/L x 120 min, P < .05). In both groups, insulin infusion yielded insulin levels usually observed under postprandial conditions and reduced circulating FFA to the levels observed after acipimox administration. Again, the GH response to GHRH was lower for obese subjects versus normals (380 +/- 40 v 1,075 +/- 206 microg/L x 120 min, P < .05), and in both groups, it was significantly lower than the corresponding response after acipimox. In obese subjects, as previously reported in normals, the GH response to GHRH was inversely correlated with the mean serum insulin (r = -.70, P < .01). In conclusion, our data indicate that in the obese, as in normal subjects, the GH response to GHRH is a function of insulin levels. The finding that after both the acipimox treatment and the insulin clamp the obese still show higher insulin levels and a lower GH response to GHRH than normal subjects suggests that hyperinsulinemia is a major determinant of the reduced GH release associated with obesity.

Background: We performed bilateral laparoscopic adrenalectomies on four patients (three women and one man) with Cushing's disease (pituitary-dependent Cushing's syndrome) showing persistent hypercortisolism after transsphenoidal surgery. Methods: The technique for bilateral transperitoneal laparoscopic adrenalectomy was derived from the one previously adopted by our group for unilateral adrenalectomy and previously described. Eight trocars were used, of which two were used for both left and right adrenalectomy. Results: Bilateral laparoscopic adrenalectomy was performed in a one-stage procedure in the three women and, because of the abundant abdominal fat of the patient, in a two-stage procedure (after a 1-week interval) in the man. Operating times for the three women were 255 minutes, 230 minutes, and 220 minutes , and for the man 170 minutes for right adrenalectomy and 140 minutes for left adrenalectomy. No surgical or anesthesiologic complications were encountered. All patients were discharged from the hospital within 5 days after operation. At present, after follow-up periods of 23, 8, 6, and 18 months, all patients show remission of Cushing's disease and undetectable cortisol levels. Conclusions: Our experience suggests that bilateral laparoscopic adrenalectomy is a safe and effective procedure and a valid therapeutic option in patients with Cushing's disease showing persistent hypercortisolism after transsphenoidal surgery. However, the decision to remove both adrenal glands in such patients needs to be weighed against the risk of their having Nelson's syndrome or other long-term complications. (Surgery 1998;123:144-50.)

OBJECTIVES: To compare extraocular muscles (EOMs) T2, post-contrast T1 (T1Gad) signal intensity ratios (SIRs) and normalized-apparent diffusion coefficient (n-ADC) values in patients with thyroid-associated orbitopathy (TAO) at different phases of activity and severity and correlate MRI modifications to clinical evolution during follow-up. METHODS: A total of 74 TAO patients were classified as active or inactive on the basis of the clinical activity score (CAS). Severity of EOM impairment was evaluated by assigning a functional score to each rectus. T2, T1Gad SIRs and n-ADC of EOMs were compared in patients with active inflammation, those with inactive disease and 26 healthy controls, and correlated with clinical scores. MRI parameter variation was correlated with clinical modifications during follow-up. RESULTS: All MRI parameters in TAO EOMs were significantly higher than in healthy subjects and correlated with muscle dysfunction and CAS. EOMs of active patients showed higher T2 and T1Gad SIRs than those with inactive disease. The T2 SIR and n-ADC of normally functioning TAO EOMs were higher than those of healthy controls. SIRs decreased in clinically improved and clinically stable EOMs after therapy. CONCLUSIONS: T2 SIR, T1Gad SIR and n-ADC are objective measures of activity and severity of EOMs in TAO patients. MRI shows clinically silent muscle involvement and modifications. KEY POINTS: • MRI and DWI measures are objective, quantitative parameters of TAO activity and severity • MRI and DWI measures significantly correlate with clinical scores in TAO patients • MRI and DWI can identify clinically silent inflammation of deep orbital structures • MRI and DWI can depict subclinical modifications during follow-up • MRI and DWI may aid clinicians in choosing the most appropriate

Opioid compounds, such as morphine, induce powerful analgesic effects and are extensively used clinically to treat a wide variety of pain. The aim of our study was to evaluate the impact of opioid therapy on phenotype and function peripheral blood NK cells. The patients were referred to three Italian pain therapy centers (Milan, Pavia, Piacenza) for chronic pain in neuropathic or mixed somatic components. The patients were between 18 and 75 years old and were of Caucasian ethnicity. We studied the expression of activating and inhibitory NK receptors to discriminate NK subsets with different CD56 surface expression intensities (CD56(bright) and CD56(dull) NK cells). The flow cytometry analysis of the NK cells was at normal levels in peripheral blood lymphocytes with fewer CD56(bright) compared to the CD56(dull) NK cell subset when compared to blood from drug free donors. Furthermore, the cytolytic activity of in vitro patient NK cells analyzed was not lower, as would be expected from the regular expression of activating NK receptors for both subsets. Taken together, these data indicate that NK cells from opioid treated patients do not show any signs of NK cell immune-suppression.

GH induces lipolysis in vivo, increasing plasma free fatty acid (FFA) levels; in turn, FFA are able to reduce GH release, and acipimox, a nicotinic acid analog able to block lipolysis, enhances in normal subjects the GH response to GHRH. Obesity and old age are characterized by a blunted GH response to several stimuli, including GHRH; reports also indicate high plasma FFA levels in obesity and sometimes in the elderly. The aim of this study was to evaluate the possible role of FFA in GH release in obese and elderly subjects. According to a randomized, single blind, cross-over protocol, six healthy subjects, six obese subjects, and six elderly subjects received on 2 different days, with a 1-week interval, placebo or acipimox (250 mg, orally) at 0700 and 1100 h; GHRH [GHRH-(1-44)NH2; 50 micrograms in healthy subjects and in elderly subjects, 100 micrograms in obese subjects] was injected iv at 1300 h, and blood samples for evaluation of plasma FFA, blood glucose, serum insulin (IRI), and serum GH levels were taken from 1200 to 1500 h. Plasma FFA levels were always lower (P0.05) after acipimox than after placebo (0.03 +/- 0.01 vs. 0.13 +/- 0.02 g/L in healthy subjects, 0.09 +/- 0.01 vs. 0.27 +/- 0.02 g/L in obese, 0.02 +/- 0.005 vs. 0.17 +/- 0.01 g/L in elderly subjects); serum IRI levels were also lower (P0.05) after acipimox than after placebo in the three groups of subjects (16 +/- 3 vs. 30 +/- 5, 120 +/- 30 vs. 181 +/- 32, and 21 +/- 3 vs. 49 +/- 9 pmol/L); both FFA (P0.05) and IRI levels (P0.05) were higher in obese than in healthy or elderly subjects after placebo and acipimox. Blood glucose levels were not different in the three groups of subjects after either placebo or acipimox. The integrated GH response to GHRH-(GH delta area) was always greater (P0.05) after acipimox than after placebo (4677 +/- 633 vs. 1599 +/- 373 in healthy, 1469 +/- 230 vs. 343 +/- 114 in obese, 2304 +/- 759 vs. 325 +/- 133 micrograms/L.120 min in elderly subjects); after both placebo and acipimox, the GH delta area was greater (P0.05) in healthy subjects than in obese or elderly subjects. The GH delta area of elderly and obese subjects after acipimox was not different from the GH delta area of healthy subjects after placebo. Changes in GH delta areas were not significantly related to changes in FFA or IRI induced by acipimox; in contrast, absolute values of FFA and IRI as well as basal GH levels were all significantly related to the GH delta area. At multiple regression analysis, FFA was the only significant predictor of GH delta area. These data indicate that acute pharmacological reduction of plasma FFA levels restores the blunted GH response to GHRH commonly observed in obese and elderly subjects: however, when lipolysis is blocked to a similar extent, healthy subjects still show a higher GH delta area than obese or elderly subjects. As FFA are the best predictor of the GH delta area, we suggest that in obesity, the blunted GH release is due to high FFA levels, whereas in the elderly there might be an abnormal sensitivity to normal FFA levels.

In acromegaly, high GH levels are primarily attributable to GH hypersecretion, but the contribution of GH clearance is still under debate and is difficult to assess. In the present study, GH plasma clearance rate (PCR), half-life (t1/2), and volume of distribution (VD) were assessed in seven acromegalic patients and seven normal lean subjects, after suppression of endogenous GH release by octreotide, with use of a constant GH infusion. An octreotide sc infusion was started the night before the day of the test (2100 h) and maintained throughout the study. On the day of the test, exogenous GH was constantly infused iv for 6 h (0900-1500 h) in order to achieve a new steady state of GH levels. After the cessation of GH infusion, the decay curve of serum GH levels was monitored for 1 h. In both groups, GH PCR was calculated from the steady state serum GH levels, and GH t1/2 was estimated from the monoexponential analysis of the GH disappearance curve. Estimates of VD were derived from PCR and t1/2. In acromegalic patients, GH PCR was 2.5 +/- 0.2 mL/kg.min-1, and GH t1/2 and VD were 15.7 +/- 1.0 min and 54.9 +/- 5.5 mL/kg, respectively. GH PCR and GH t1/2 of acromegalic patients were higher and lower, respectively, than those of normal subjects (PCR, 1.7 +/- 0.2 mL/kg.min-1, P < 0.02; t1/2, 18.4 +/- 0.6 min, P < 0.05). VD was not significantly different in the two groups. In summary, in acromegalic patients GH kinetic parameters can be reliably assessed by using a constant GH infusion after suppression of endogenous GH release by octreotide. Our results also indicate that the increased circulating GH levels observed in acromegaly are attributable only to GH overproduction and do not depend on an alteration in the processes of GH distribution or disappearance.

Cushing's syndrome may remain unrecognized among patients referred for metabolic syndrome; thus, a proactive screening has been suggested in certain patient populations with features of the disorder. However, conflicting data have been reported on the prevalence of Cushing's syndrome in patients with type 2 diabetes.Our aim was to evaluate the prevalence of unsuspected Cushing's syndrome among outpatients with type 2 diabetes.This was a cross-sectional prospective study in 24 diabetes clinics across Italy.Between June 2006 and April 2008, 813 patients with known type 2 diabetes without clinically overt hypercortisolism were evaluated. Follow-up of the study was closed in September 2010. Patients were not selected for characteristics conferring a higher pretest probability of hypercortisolism. Patients underwent a first screening step with the 1-mg overnight dexamethasone suppression test.Forty patients failed to suppress serum cortisol less than 5.0 μg/dl (138 nmol/liter) and underwent a standard 2-d, 2-mg dexamethasone suppression test, after which six patients (0.6% of the overall series) failed to suppress cortisol less than 1.8 μg/dl (50 nmol/liter), receiving a definitive diagnosis of Cushing's syndrome that was adrenal dependent in five patients. Four patients were cured, being able to discontinue, or reduce, the glucose-lowering agents.The present data do not support widespread screening of patients with type 2 diabetes for Cushing's syndrome; however, the disorder is less rare than previously thought when considering epidemiology of type 2 diabetes. Our results support a case-finding approach in patients with uncontrolled diabetes and hypertension despite appropriate treatment.

Growth hormone (GH) replacement in adulthood results in variable bone responses as a function of the gonadic hormonal milieu. We performed a retrospective analysis of a large cohort of adult males and females with confirmed GH deficiency (GHD) prior to treatment and during 3 years of replacement therapy. Potential confounders and effect modifiers were taken into account. Sixty-four adult patients with GHD (20 females and 44 males; mean age 34 years, range 18-64) were included in the analysis. GH replacement induced a different effect on bone in males compared to females. Bone mineral content increased in males and decreased in females at the lumbar spine, total femur, and femoral neck; bone mineral density showed a similar trend at the lumbar spine and femoral neck. There was no significant gender difference in bone area at any measured bone site. In both sexes we observed a similar trend for serum markers of bone remodeling. Sex predicted bone outcome on multivariate analysis, as did age, onset of GHD (childhood/adulthood), pretreatment bone mass, baseline body mass index (BMI), and BMI change during GH replacement. Serum IGF-I levels during treatment did not show any relationship with bone outcome at any measured site. This study confirms that bone responsiveness to GH replacement in adult GHD varies as a function of sex even after controlling for potential confounders and highlights the importance of other cofactors that may affect the interaction between GH replacement therapy and bone remodeling. © 2011 Springer Science+Business Media, LLC.

Women’s sexual dysfunction (SD) is defined as a disorder of sexual desire, arousal, orgasm, and/or sexual pain, which results in significant personal distress and may have a negative effect on a woman’s health and quality of life. Although previously published data suggest that sexual complaints are highly prevalent among women with diabetes mellitus (DM), the scientific community has scarcely investigated the potential correlation between diabetes mellitus and women’s SD. In case-control studies, SD was reported at a significantly greater rate in women with DM type 1 (DM1) than among controls – arousal difficulties being most common. Interestingly, sexual complaints were not isolated in occurrence, because women with DM often reported at least two sexual problems. Sexual disorders are also highly prevalent in women with DM type 2 (DM2), with low sexual desire being most commonly reported. Few treatment options and no specific compounds have been investigated to address the various types of SD in women with diabetes.

Methionyl-GH (met-GH) infusions inhibit the GH response to GH-releasing hormone (GHRH). Met-GH infusions induce lipolysis with a rise of plasma FFA that are known to suppress GH release, but the met-GH inhibition of the GH response to GHRH occurs also when lipolysis is pharmacologically blocked by acipimox. In addition, the inhibition of GH release might be due to an enhanced release of hypothalamic somatostatin. The aim of this study was to evaluate the effect of a met-GH infusion on the GH response to GHRH when lipolysis and hypothalamic somatostatin release are pharmacologically blocked. Twelve normal subjects, randomly allocated to two groups (A and B), received GHRH (50 micrograms, iv) at 1300 h after a 4-h saline infusion or met-GH infusion (80 ng/kg.min). To block lipolysis and hypothalamic somatostatin release, subjects in group B received acipimox, an antilipolytic agent (500 mg), and pyridostigmine, an acetylcholinesterase inhibitor (60 mg), during the 6 h before iv GHRH. GHRH induced a clear GH release during saline infusion in both groups, significantly higher in group B (43.6 +/- 4.8 micrograms/L) than in group A (20.1 +/- 6.1 micrograms/L; P less than 0.02 vs. A), and only a slight increase during met-GH infusions (10.4 +/- 4.1 micrograms/L in group A; 16.7 +/- 4.2 micrograms/L in group B; P = NS). These data indicate that the GH response to GHRH is inhibited by met-GH infusions when peripheral lipolysis and hypothalamic somatostatin release are pharmacologically blocked, suggesting the possibility of autoinhibition of GH at the pituitary level.

Patients with growth hormone deficiency (GHD) are known to have reduced life expectancy due to increased cardiovascular and cerebrovascular events. An increase in asymmetric dimethylarginine (ADMA) levels previously found in GHD patients could promote premature atherosclerosis. The aim of this study was to determine whether 6-month growth hormone (GH) replacement therapy was able to decrease ADMA levels and ameliorate endothelial dysfunction. Thirty-one GHD patients were studied before and after 6 months of GH (4 microg/[kg d], daily) replacement therapy. Reduced pretreatment levels of serum insulin-like growth factor (IGF) 1 were normalized during GH treatment (88.2 +/- 62.5 to 191.7 +/- 80.3 ng/mL, P < .0001). After 6 months of GH replacement, plasma cyclic guanosine monophosphate levels significantly increased (2.14 +/- 0.52 to 3.54 +/- 1.2 ng/mL, P < .0001), serum ADMA levels were significantly decreased (0.65 +/- 0.1 vs 0.59 +/- 0.11 mumol/L, P < .05), and arganine (Arg) to ADMA ratio was significantly higher (155 +/- 53 vs 193 +/- 61, P < .01). No changes were observed for plasma nitric oxide end products (nitrite and nitrate) levels after GH treatment (21.9 +/- 14.9 vs 24.1 +/- 19.0 mumol/L, not significant). Basal forearm blood flow remained unchanged, whereas reactive hyperemia increased from 7.30 +/- 5.31 mL/100 mL forearm per minute before GH therapy to 13.18 +/- 7.30 mL/100 mL forearm per minute after 6 months of therapy (P < .001). There was a positive correlation between IGF-1 and cyclic guanosine monophosphate (r = 0.73, P < .0001), IGF-1 and reactive hyperemia (r = 0.63, P < .0001), and IGF-1 and Arg/ADMA ratio (r = 0.44, P < .01). Conversely, a negative correlation was found between IGF-1 and ADMA levels (r = -0.41, P < .02). At the end of the study period, fat-free mass, plasma glucose, and hemoglobin A(1c) levels significantly increased, even if they were still in the reference range, suggesting moderate alteration of glucose metabolism. In conclusion, in GHD patients, GH replacement contributes to decreased, to some extent, cardiovascular risk, reducing ADMA levels and improving Arg/ADMA ratio and endothelial dysfunction.

Objective: To evaluate the safety and effectiveness of lanreotide Autogel on growth hormone and insulinlike growth factor 1 (IGF-1) concentrations and tumor size in patients with acromegaly. Methods: Between September 2004 and March 2006, patients with active acromegaly who had not previously been treated with somatostatin analogues or received irradiation were enrolled in a 1-year, prospective, open, multicenter study. Lanreotide Autogel was injected subcutaneously starting with 90 mg every 4 weeks for 2 cycles and then individually titrated, aiming for safe growth hormone concentrations (

It is presently thought that osteoprotegerin (OPG) is a cytokine involved in the regulation of osteoblast/osteoclast crosstalk and maintenance of bone mass. Recent studies showed that GH replacement therapy in GH-deficient patients was able to induce a significant increase of OPG in the plasma, as well as in the cortical and the trabecular bone. In order to determine whether GH could directly modulate OPG secretion, the effect of GH on human osteoblast-like cells (hOB) in primary culture was studied. After detecting the presence of the mRNA for the GH receptor (GHR) by RT-PCR, hOB were exposed to increasing concentrations of GH, from 0.1 to 25 ng/ml, for 24 h. The results showed that GH exposure was able to stimulate OPG secretion in a concentration-dependent manner. In addition, the OPG mRNA levels were increased, indicating that the hormone has a stimulatory effect on gene expression. The stimulatory effect on OPG expression and production was prevented by exposing the cells to tyrphostin AG490 (10 μM), an inhibitor of Janus kinase 2, which is one of the kinases involved in the intracellular pathway activated by the binding of GH to its receptor. Similar results were obtained when the cells were exposed to a receptor antagonist of GH, pegvisomant at 50 nM. GH exposure neither induced an increase in IGF-I expression nor secretion in hOB. These results suggest that the stimulation of OPG production induced by GH in hOB is specific and receptor mediated and further support the view that GH is able to modulate bone remodeling by directly influencing osteoblast-osteoclast crosstalk. © 2007 Society for Endocrinology.

Background: Exaggerated insulin resistance was described as the major metabolic abnormality in myotonic dystrophy type 1 (DM1). We reported recently that the severity of the impairment in insulin-stimulated glucose metabolism in these patients was overestimated. Objective: The aim was to dissect out insulin action with respect to whole-body energy homeostasis and glucose, protein, and lipid metabolism in patients with DM1 to assess the relevance of insulin resistance to the heterogeneous clinical manifestations of this syndrome. Design: Ten nondiabetic patients with DM1 and 10 matched healthy control subjects were studied by means of 1) dual-energy X-ray absorptiometry; 2) a euglycemic-hyperinsulinemic clamp (40 mil·m-2·tmin -1) combined with a primed, continuous infusion of [6,6-d 2]glucose and [1-13C]leucine; J) indirect calorimetry; and 4) localized 1H magnetic resonance spectroscopy of the calf muscles. Results: Patients with DM1 had less lean body mass, greater fat mass, and greater intramyocellular lipid contents than did healthy control subjects. Energy expenditure and glucose and lipid metabolism did not differ significantly between the groups. In contrast, markers of proteolysis were higher in DM1 patients in the postabsorptive and insulin-stimulated conditions and were associated with lower plasma concentrations of insulin-like growth factor 1 (P < 0.03) and higher plasma concentrations of tumor necrosis factor a receptor 2 (P = 0.04). Conclusions: Despite greater body fat and intramyocellular lipid contents in patients with DM1, insulin sensitivity was not significantly different between patients and control subjects. In contrast, the loss of lean body mass in patients with DM1 was associated with abnormal postabsorptive and insulin-stimulated regulation of protein breakdown. Lower plasma insulin-like growth factor 1 concentrations and higher tumor necrosis factor system activity might be involved in the muscle wasting of DM1. © 2004 American Society for Clinical Nutrition

OBJECTIVE—Myotonic dystrophy (MyD), the most common adult form of muscular dystrophy, is often complicated by diabetes. MyD is dominantly inherited and is due to heterozygosity for a trinucleotide repeat expansion mutation in a protein kinase gene able to induce derangement of RNA metabolism responsible of an aberrant insulin receptor expression. RESEARCH DESIGN AND METHODS—To assess insulin sensitivity and secretion before the onset of diabetes, we studied 10 MyD patients, 10 offspring of type 2 diabetes (OFF), and 10 healthy subjects with no family history of diabetes (control subjects) with dual X-ray energy absorption, euglycemic-hyperinsulinemic clamp (40 mU/[m2 · min]) combined with infusion of [6,6-d2]-glucose and oral glucose tolerance test (OGTT). RESULTS—MyD had reduced lean body mass, but peripheral insulin sensitivity was not different to that of control subjects in contrast to OFF, which showed insulin resistance. Insulin secretion, obtained by deconvolution of OGTT data, was also shown to be comparable with that of OFF and control subjects (index of β-cell function = Φ; P = 0.91) even if increased parameters of insulin secretion were found during the first 30 min (Φ30; P = 0.05) of the oral glucose challenge. Fasting plasma proinsulin concentrations (P = 0.01) and the ratio to insulin (P = 0.01) were increased in MyD patients. The proinsulin levels also failed to be suppressed during the clamp and showed exaggerated response after the OGTT. Increased proinsulin levels were shown to be peculiar of MyD patients when compared with OFF. CONCLUSIONS—In nondiabetic, young MyD patients, insulin sensitivity was preserved, and an increased early secretory response to oral glucose was detected. Abnormal plasma proinsulin levels in the fasting state, during the clamp, and during the OGTT were shown to be secretory dysfunctions peculiar of MyD patients and may be more important than insulin resistance in determining the high risk to develop diabetes in these patients.

The effects of an ayurvedic compound (MAK-5) alone or together with nerve growth factor (NGF) on the neurite outgrowth of PC12 cells was studied. PC12 cells treated with NGF alone showed a clear neurite outgrowth with a decrease of the proliferation at the dose higher than 5 ng/ml. MAK-5 alone does not induce significant neurite outgrowth in the PC12 cells and does not decrease the proliferation. The PC12 cells treated with NGF supplemented with MAK-5 showed a well-evident morphological differentiation also at low doses of NGF (less than 5 ng/ml), however, the proliferation does not decrease. We suggest that MAK-5 could contain some differentiating agents that are able to potentiate NGF inducing neuronal differentiation in PC12 cells without decreasing the cell proliferation.

A novel high-performance liquid chromatographic (HPLC) method for the quantification of diclofenac in human plasma was set up. Samples, added with ibuprofen (used as internal standard) were purified by solid-phase extraction using Abselut Nexus cartridges (Varian) not requiring pre-conditioning. Drugs of interest were eluted directly into the autosampler vials and injected. The recovery of diclofenac was 92%, the analysis lasted 7 min with a sensitivity of 5 ng/ml and intra- and inter-day RSDs of 3 and 8%, respectively. The pharmacokinetics of diclofenac after oral and rectal administration in 10 healthy volunteers are reported.

Purpose: Laparoscopic adrenalectomy is currently the technique of choice for removing benign adrenal lesions. Various laparoscopic techniques and approaches have been reported using the transperitoneal or retroperitoneal approach. We present our 8-year experience with and longterm results of transperitoneal laparoscopic adrenalectomy. Materials and Methods: Between October 1992 and October 2000, 161 laparoscopic approaches to the adrenal gland were performed, including 145 unilateral and 10 bilateral adrenalectomies, and 6 conservative operations. Patients were placed in the 60-degree flank position with the bed flexed to increase the surgical field. To avoid hypertensive crisis, especially in patients with pheochromocytoma, the first step involved early ligation of the adrenal vein. Results: The laparoscopic procedure was succesfully completed in all except 4 cases, which were converted to open surgery. Mean operative time was 160 minutes in the unilateral, 245 in the bilateral and 90 in the conservative group. Delayed complications included hemoperitoneum in 3 patients, which was drained surgically, severe blood loss in 3 treated with blood transfusion and wound infection in 2. Patients were ambulatory on the morning of postoperative day 1 and were discharged home 2.8, 5 and 1.8 days after unilateral, bilateral and conservative surgery, respectively. Conclusions: Laparoscopic transperitoneal adrenalectomy is a safe, effective, minimally invasive approach in patients with benign functioning or nonfunctioning adrenal masses. This technique involves low morbidity, minimal postoperative analgesic requirements and a short hospital stay.

Aluminium (Al) exposure is neurotoxic and is considered a possible etiological factor for many neurodegenerative disorders. Since it is known that Al impairs the glutamate-nitric oxide-cGMP pathway in neurons, this study was carried out to monitor the expression of NADPH-d in some central nervous system areas of rats after chronic administration of Al in drinking water. We tested three different nervous areas known to contain NADPH-diaphorase positive neurons: two cortical area (somatosensory cerebral cortex and cerebral cortex), a deep brain area (dorsolateral periaqueductal gray matter) and a spinal area (lumbar enlargement of the spinal cord). Our data showed that Al significantly decreased NADPH-d positive neurons in the cerebral cortex and the NADPH-d staining of many granular neurons in the cerebellum. We also found that Al did not cause neuron loss or apoptosis in the cerebral cortex. These findings suggest that the cortical nitroxidergic neurons and granule cells were a specific target of Al neurotoxicity.

Free fatty acids (FFA) physiologically regulate GH release via a negative feedback. The aim of this study was to examine whether such feedback is preserved in acromegaly, a condition in which alterations in other regulatory mechanisms of GH release occur. Eight acromegalic patients (group 1: five women and three men, 43.0 +/- 4.2 yr old, mean +/- SE) received per os on two different days, at a 3 day-interval, in a random order, placebo or 250 mg of acipimox, an inhibitor of lipolysis analogous to nicotinic acid, at 0700 and 1100 h. In both tests GHRH (1-29 NH2), 50 microg, was administered i.v. at 1300 h. Blood samples for GH, FFA, immunoreactive insulin (IRI), and glucose were taken from 0900 to 1500 h, and the time period considered for statistical analysis was 1200-1500 h, representative of steady-state condition for FFA, IRI, and glucose. Mean plasma FFA levels (1200-1500 h) were significantly lower after acipimox than after placebo (0.05 +/- 0.01 vs. 0.17 +/- 0.01 g/L, P < 0.01). In contrast, both mean basal GH levels (1200-1300 h) and the mean GH response to GHRH (GH delta area, 1300-1500 h) were significantly higher after acipimox than after placebo (12.0 +/- 1.9 vs. 7.8 +/- 1.2 microg/L, P < 0.01; 2937 +/- 959 vs. 1154 +/- 432 microg/L x 120 min, P < 0.01). The increase in both basal GH levels and GH delta area occurred in all eight patients. Acipimox also reduced mean serum IRI (83 +/- 12 vs. 112 +/- 14 pmol/L) and blood glucose (5.1 +/- 0.1 vs. 5.7 +/- 0.1 mmol/L) levels, as compared with placebo (P < 0.03 or less). Eight acromegalic patients (group 2: six women and two men, 46.6 +/- 5.7 yr old) underwent a constant i.v. 10% lipid infusion (150 mL/h), started at 0900 h and continued until 1500 h. Mean plasma FFA levels (1200-1500 h) were significantly higher during lipid infusion than after placebo (0.27 +/- 0.01 vs. 0.16 +/- 0.01 g/L, P < 0.02); in contrast, mean basal GH levels (1200-1300 h) were reduced by lipid infusion, as compared with placebo (9.9 +/- 3.1 vs. 16.6 +/- 4.4 microg/L, P < 0.01), and the same occurred for the GH delta area after GHRH (2498 +/- 1643 vs. 4512 +/- 1988 microg/L x 120 min, P < 0.01). Serum IRI and blood glucose levels were similar after placebo and during lipid infusion. These data indicate that, in acromegaly, the acute reduction of circulating FFA levels results in increased GH release, whereas the increase in circulating FFA levels is accompanied by a reduced GH release. Taken together, these findings suggest that, in acromegaly, the control of FFA on GH release is preserved.

In our retrospective study we compare the effectiveness and safety of transperitoneal laparoscopic versus open adrenalectomy in 40 patients with benign hyperfunctioning unilateral adrenal tumors. Patients 1 to 20 underwent open adrenalectomy between July 1988 and July 1992, and patients 21 to 40 underwent the laparoscopic procedure between September 1992 and January 1994. Student's t test for unpaired data was used to compare intraoperative and postoperative results, and morbidity observed in the 2 groups. The affected adrenal gland was successfully removed in all cases. Mean operative time was significantly longer for laparoscopy, although it shortened progressively due to the learning curve effect. Blood loss was significantly less with laparoscopy, while only 3 patients undergoing open surgery required blood transfusions. Overall invasiveness and analgesic requirement were significantly lower with laparoscopy. The intervals to oral intake and ambulation, hospital stay and return to preoperative normal activity were shorter with laparoscopy. Major complications were noted only in open surgery patients. At 3 months all patients in both groups were cured of the underlying adrenal disease. We conclude that transperitoneal laparoscopic adrenalectomy is equally effective and less invasive than open surgery, and that it should be considered the first choice therapy for benign hyperfunctioning adrenal tumors.

A laparoscopic approach was used to remove the adrenal gland in 7 patients with aldosterone-producing adenoma (Conn’s disease), 2 with corticosteroid-producing adenoma (pituitary-independent Cushing’s syndrome) and 2 with pheochromocytoma. The affected gland was on the right side in 3 patients and on the left side in 8. Mean operative time was 3hours 10minutes (range 140 to 370minutes). The operation was uneventful in all patients and blood transfusions were never required. Mean postoperative hospitalization was 2.9 ± 0.8 days (standard error). Only minimal doses of analgesics were used postoperatively. All patients returned to work within 10 days postoperatively (mean 8.4 ± 1.2 days). Two months postoperatively no patient had clinical, biochemical or hormonal evidence of recurrent or persistent disease. We conclude that laparoscopic adrenalectomy is a safe and effective, minimally invasive approach for patients with benign adrenal neoplasms.

Obesity is associated with blunted growth hormone (GH) levels and pulsatility and elevated plasma free fatty acids (FFA) levels. To evaluate whether the two phenomena are correlated, in the present study we investigated the effects of an acute pharmacologic blockade of lipolysis on nocturnal GH levels and pulsatility in 10 obese and 10 control subjects. At 9pm on two different nights with a 1-night interval in between, all subjects received either a single oral tablet of placebo or acipimox slow release (ACX-SR, 500 mg) in randomized order. Blood samples were drawn from 10pm to 6am for evaluation of FFA, glycerol, GH, immunoreactive insulin (IRI), glucose, and insulin-like growth factor-I (IGF-I) levels. After placebo, FFA and glycerol levels were higher (P < .02) and GH levels, areas, peak amplitude, and peak increment (assessed by the Cluster algorithm) were lower in obese than in control subjects (P < .01). After ACX-SR, FFA and glycerol levels were reduced in both groups (P < .02 v placebo), and in obese subjects they became similar to those observed in control subjects after placebo. ACX-SR had no effect on GH levels and pulsatility in control subjects. GH levels, areas, peak amplitude, peak increment, and interpeak valley levels were all increased after ACX-SR in obese subjects (P < .05 or less v placebo) and became similar to those observed in normal subjects after placebo, but no correlation was found between the reduction in FFA levels and the increase in GH levels and pulsatility. IRI levels were significantly higher in obese than in control subjects after placebo (P < .05), and were significantly decreased by ACX-SR in both groups (P < .02 v placebo). IGF-I levels were lower in obese than in control subjects after placebo, and remained unchanged after ACX-SR. In conclusion, our data show that following acute pharmacologic blockade of lipolysis, nocturnal GH levels and pulsatility are reversed to normal in obese subjects.