Overt hypothyroidism in pregnancy and language development in offspring: is there an association?

PURPOSE: Overt hypothyroidism during pregnancy is linked to various obstetric complications, such as premature birth and fetal death. While some studies have shown that maternal hypothyroidism can impact a child's Intelligence Quotient (IQ) and language development, findings are controversial. The aim of this study was to explore the connection between treated maternal hypothyroidism during pregnancy and offspring neurodevelopment, focusing on learning and language and examining related maternal obstetric complications. METHODS: Group 1 included 31 hypothyroid women with elevated thyroid stimulating hormone (TSH) (> 10 mU/L, > 10 µIU/mL) during pregnancy, and Group 2 had 21 euthyroid women with normal TSH levels (0.5-2.5 mU/L, 0.5-2.5 µIU/mL). Children underwent neuropsycological assessments using the Griffiths-II scale. RESULTS: Pregnancy outcome showed an average gestational age at delivery of 38.2 weeks for hypothyroid women, compared to 40 weeks for controls, and average birth weight of 2855.6 g versus 3285 g for controls, with hypothyroid women having children with higher intrauterine growth restriction (IUGR) prevalence and more caesarean sections. The 1-min APGAR score was lower for the hypothyroid group's children, at 8.85 versus 9.52. Neuropsychological outcomes showed children of hypothyroid mothers scored lower in neurocognitive development, particularly in the learning and language subscale (subscale C), with a notable correlation between higher maternal TSH levels and lower subscale scores. CONCLUSION: Fetuses born to hypothyroid mothers appeared to be at higher risk of IUGR and reduced APGAR score at birth. Neurocognitive development seemed to affect language performance more than the developmental quotient. This alteration appeared to correlate with the severity of hypothyroidism and its duration.

The treatment of neuroendocrine tumors with long-acting somatostatin analogs: a single center experience with lanreotide autogel.

The aim of this retrospective study was to evaluate the efficacy, safety, and tolerability of lanreotide autogel given to metastatic well-differentiated (WD) neuroendocrine tumors (NET) patients observed in our Institute between 2005 and 2008. Patients with metastatic NET referred to our tertiary referral center were given lanreotide autogel 120 mg/month by deep sc injection for a period of at least 24 months. The efficacy was evaluated by the relief of disease symptoms, behavior of tumor markers and response rate in terms of time to tumor progression. Safety and tolerability were evaluated by assessing the onset of adverse events and treatment feasibility. Twenty-three patients (13 males), median age 62 yr (range 32-87) were considered for the study. All patients were affected by WD metastatic NET and had tumor progression in the last 6 months before the enrolment in the study. Median duration of response was 28 months (range 6-50 months). Fourteen patients (60.9%) showed flushing and diarrhea which improved by 85.7% and 55.6%, respectively, bronchoconstrinction and abdominal pain also ameliorated. A complete, partial or no-changed response in the tumor markers behavior was observed, respectively, in 42.9%, 22.9%, and 17.1% of cases. According to RECIST (Response Evaluation Criteria In Solid Tumors) criteria (version 1.1), there were 2 partial regression (8.7%) and 15 stable disease (65.3%); 6 patients (26.0%) progressed. No patient complained from any severe adverse reaction. The results of our study suggest that lanreotide autogel is effective in the symptoms, biochemical markers, and tumor progression control of WD metastatic NET and confirm that the treatment is well tolerated.

Levothyroxine therapy in preventing nodular recurrence after hemithyroidectomy: a retrospective study.

AIM: To determine the effect of levothyroxine (L-T4) therapy on the recurrence rate of nodular disease in patients previously treated with lobectomy for benign nodular goiter. METHODS: Two hundred and thirty-tree patients (38 males, 195 females; age 49.9+/-13.1 yr) with no post-surgical evidence of nodular disease in the remnant, were followed- up yearly with serum TSH and ultrasound (US). Nodular recurrence was defined as a lesion of at least 5 mm at US. Patients were divided in 2 groups based on whether or not they had been treated with L-T4 after surgery: Group 1 (45 patients) who did not receive any L-T4, and Group 2 (188 patients) treated with L-T4. Group 2 was further subdivided in Group 2a (123 patients) receiving L-T4 substitutive therapy (TSH>or=0.5 and

Dexamethasone inhibition of interferon-alpha 2-induced stimulation of cortisol and growth hormone secretion in chronic myeloproliferative syndrome.

This study investigated the acute effects of interferon-alpha 2 (IFN-alpha 2) on hormonal secretion in adult patients affected by a chronic myeloproliferative syndrome and tried to shed some light on the mechanism by which IFN-alpha 2 stimulates cortisol and GH secretion in humans. We compared the pattern of IFN-alpha 2-induced cortisol and GH release with that elicited after the same challenge given subsequent to pretreatment with dexamethasone (Dex). We studied eight patients affected by a chronic myeloproliferative syndrome (thrombocythemia) who had been selected for treatment with IFN-alpha 2. Four sets of experiments were performed: 1) 2 mL iv saline was given at 0800 h in eight cases; 2) 3 x 10(6) IU iv IFN-alpha 2 was given at 0800 h in eight cases; 3) 3 x 10(6) IU iv IFN-alpha 2 was given at 0800 h after pretreatment with 1.5 mg Dex (1 mg at midnight the previous night and 0.5 mg at 0700 h on the day of the test) in six cases; and 4) 2 mL iv saline was given at 0800 h after the same Dex pretreatment in four cases. Cortisol and GH were measured in plasma samples drawn at 30-min intervals between 0800 and 1300 h. Acute iv administration of IFN-alpha 2 stimulated the release of both cortisol and GH in each patient with a significant increment vs. control values, as assessed by areas under the curve. The administration of Dex significantly decreased basal plasma cortisol secretion and abolished cortisol response to IFN-alpha 2 administration. These data suggest that the stimulatory action of IFN-alpha 2 on cortisol release is mediated via a modulation of the activity of the hypothalamic-pituitary axis rather than through a direct effect at the level of the adrenal cortex. After Dex plus saline administration, no significant effect was observed on plasma GH levels, which remained low. Dex administration significantly decreased GH response to IFN-alpha 2. These data suggest that a hypothalamic or pituitary stimulation (or both) is involved in the mechanism of IFN-alpha 2-induced GH secretion. It remains to be established whether IFN-alpha 2 directly stimulates pituitary somatotropic cells or whether the cytokine exerts a stimulatory action on GH secretion by indirectly modulating the hypothalamic or pituitary activity. In conclusion, acute iv administration of IFN-alpha 2 represents a potent stimulus for cortisol and GH secretion in adult human subjects.(ABSTRACT TRUNCATED AT 400 WORDS)

Sexual dimorphism of pyridostigmine potentiation of growth hormone (GH)-releasing hormone-induced GH release in humans.

Sex differences in the neuroregulation of GH secretion are not now known in humans. To investigate whether activation of cholinergic tone by pyridostigmine could cause a sex-related difference in the pituitary responsiveness to GH-releasing hormone (GHRH), we have studied the GH response to GHRH in 16 normal subjects (8 men and 8 women) tested after oral placebo or different doses of pyridostigmine (30, 60, and 120 mg). Each subject presented a normal response after iv administration of 50 micrograms GHRH and placebo. In men each dose of pyridostigmine induced a significant increase in the GH response to GHRH, as assessed by both the maximal GH peak and the area under GH curve. In women, on the contrary, the GH response to GHRH was not potentiated by pretreatment with pyridostigmine at any given dose. Only five female subjects were tested with 120 mg pyridostigmine because of the severe side-effects of the drug at this dosage. Our present data strongly suggest that in humans there is a sex-related difference in the neuroregulation of GH secretion and this is probably expressed through a different cholinergic tone.

Corticotropin-releasing hormone inhibition of growth hormone-releasing hormone-induced growth hormone release in man.

Recent studies in the rat have shown that intracerebroventricular administration of CRH inhibited spontaneous pulsatile GH secretion and prevented GH-releasing hormone (GHRH)-induced GH release. We have studied the effect of CRH on GHRH-induced GH release in man. In the first study, CRH was injected iv at three different doses (100, 50, or 25 micrograms) at 0800 h together with 50 micrograms GHRH in six men and six women. In a second study, 100 micrograms CRH were given iv at 0800 h, 1 h before the administration of 50 micrograms GHRH in five men and five women. Each subject demonstrated a normal GH response after the administration of 50 micrograms GHRH plus saline. All doses of CRH administered simultaneously with GHRH significantly inhibited GHRH-induced GH release in women [peak value +/- SE after GHRH plus saline, 28.9 +/- 2.9 micrograms/L; after GHRH plus 100 micrograms CRH, 9.9 +/- 0.7 micrograms/L (P less than 0.001); after GHRH plus 50 micrograms CRH, 8.7 +/- 0.8 micrograms/L (P less than 0.001); after GHRH plus 25 microgram CRH, 9.5 +/- 1.6 microgram/L (P less than 0.001]). In contrast, in men, while a dose of 100 micrograms CRH was capable of suppressing GHRH-induced GH secretion (peak value +/- SE, 8.1 +/- 0.6 vs. 20 +/- 2.9 micrograms/L; P less than 0.001), no inhibition was observed after 50- and 25-micrograms doses. When 100 micrograms CRH were injected 1 h before the administration of 50 micrograms GHRH, it strongly inhibited GHRH-induced GH secretion in both men (peak value +/- SE, 6.2 +/- 2.8 vs. 24.6 +/- 5.9 micrograms/L; P less than 0.02) and women (peak value +/- SE, 14.2 +/- 4.5 vs. 37.8 +/- 6.7 micrograms/L; P less than 0.005), and this inhibition lasted up to 2 h post-CRH administration. These results demonstrate that CRH is capable of inhibiting GHRH-induced GH release in both men and women. Furthermore, the findings suggest that a sexual dimorphism in the neuroregulation of GH secretion may be present in man. In view of the inhibitory action of CRH on GH secretion, simultaneous administration of CRH and GHRH for testing should be avoided in clinical practice.

Effect of acute and chronic administration of tamoxifen on GH response to GHRH and on IGF-I serum levels in women with breast cancer.

Tamoxifen, an estrogen antagonist, is usually employed in the treatment of breast cancer. Its mechanism of action is not well known because an antiproliferative effect of the drug has been shown also in estrogen receptor negative tumors, most likely mediated by the inhibition of local growth factors and particularly IGF-I. However, the action of tamoxifen on the GH-IGF-I axis is still open to investigation. We have investigated the influence of acute and chronic treatment with tamoxifen on GH response to GHRH and IGF-I serum levels in six postmenopausal women with metastatic breast cancer. A GHRH test (50 microg i.v. at time 0, GH determinations at 0, 15, 30, 60, 90 and 120 min) was performed (a) basally, (b) 3 h after 40 mg oral administration of tamoxifen and (c) after 8 weeks of 20 mg twice a day oral tamoxifen treatment. IGF-I was measured basally and after chronic tamoxifen therapy. No significant modifications in GH response to GHRH were observed after acute or chronic treatment with tamoxifen vs the basal test. On the contrary, chronic tamoxifen treatment induced a significant decrease in serum IGF-I levels. Basal pretreatment levels of 123+/-18 microg/l were suppressed to 65+/-11 microg/l (mean suppression 47%, P < 0.001). These preliminary data confirm the inhibitory effect of tamoxifen on IGF-I production but seem to exclude the possibility that this effect may be due to an inhibition of GH secretion.

Corticotropin-releasing hormone inhibition of paradoxical growth hormone response to thyrotropin-releasing hormone in insulin-dependent diabetics.

A paradoxical growth hormone (GH) response to thyrotropin-releasing hormone (TRH) has been observed in type 1 diabetic patients and was hypothetically attributed to a reduced hypothalamic somatostatin tone. We have previously reported that corticotropin-releasing hormone (CRH) inhibits GH response to growth hormone-releasing hormone (GHRH) in normal subjects, possibly by an increased release of somatostatin. To study the effect of CRH on anomalous GH response to TRH, we tested with TRH (200 micrograms intravenously [IV]) and CRH (100 micrograms IV) + TRH (200 micrograms IV) 13 patients (six males and seven women) affected by insulin-dependent diabetes mellitus. A paradoxical GH response to TRH was observed in seven of 13 patients, one man and six women. In these subjects, the simultaneous administration of CRH and TRH significantly reduced the GH response to TRH, as assessed by both the maximal GH mean peak +/- SE (2.18 +/- 0.67 v 9.2 +/- 1.26 micrograms/L, P less than 0.005) and the area under the curve (AUC) +/- SE (187 +/- 32 v 567 +/- 35 micrograms.min/L, P less than .001). CRH had no effect on TRH-induced thyroid-stimulating hormone (TSH) release. Our data demonstrate that the paradoxical GH response to TRH in patients with type 1 diabetes mellitus is blocked by CRH administration. This CRH action may be due to an enhanced somatostatin release. Our data also show that exogenous CRH has no effect on TSH response to TRH, thus suggesting the existence of separate pathways in the neuroregulation of GH and TSH secretion.

Intracranial and spinal dissemination of an ACTH secreting pituitary neoplasia. Case report and review of the literature.

We report a case of a 52-year-old woman presenting with a recurrence of a large pituitary adenoma with suprasellar extension and an overt Cushing's clinical picture, five years after successful transsphenoidal treatment. After transfrontal ablation of the tumour, followed by external radiotherapy, she was asymptomatic for six years before she exhibited epileptic seizures. A left frontal intracranial neoplasm was diagnosed and removed, and at histological examination it was found to be constituted by a localization of the pituitary ACTH secreting neoplasia. One month later she exhibited spinal dissemination of the ACTH secreting neoplasia which was only partially removed. After four months a Magnetic Resonance Image (MRI) revealed recurrence of the intracranial localization and further spinal dissemination. Because of compressive symptoms, spinal masses with the same histologic features, were partially removed again in three successive surgical operations. Several medical treatments for obtaining the control of corticoid excess, caused by the ACTH overproduction, were tried, but none were satisfactory. Finally a bilateral adrenal venous embolization was performed thus obtaining a critical transient fall of serum cortisol. Five months later the patient died. At necroscopy bilateral adrenal enlargement was found, spinal disseminations were confirmed, and no metastatic lesions were discovered.

[Immunogenetic and functional study of first-degree relatives of patients with type I diabetes mellitus for identifying prediabetic subjects]. / Studio immunogenetico e funzionale dei consanguinei di I grado di pazienti affetti da diabete di tipo I per l'identificazione dei soggetti prediabetici.

Insulin dependent diabetes mellitus is an autoimmune disease with HLA-related genetic susceptibility. There is a latent phase before overt disease. During this phase islet cell antibodies (ICA) as a marker of humoral autoimmunity are detected and i.v. glucose tolerance test (IVGTT) is decreased. The aim of our work was to correlate IVGTT, HLA typing and ICA testing in all siblings of IDDM patients in order to identify high risk subjects (HRS). IVGTT showed significantly lower insulin levels in siblings vs controls (P less than 0.0001). This phenomenon could be caused by HLA unrelated genetic predisposition to low insulin secretion. Insulin level values of ICA+ siblings were lower than those of ICA- siblings, even if the difference was not significant.

Consensus and variable region PCR analysis of Helicobacter pylori 3' region of cagA gene in isolates from individuals with or without peptic ulcer.

The clinical outcome of Helicobacter pylori infection may be associated with the cagA bacterial genotype. To investigate the cagA status of H. pylori-infected patients and the relationship between cagA and peptic ulcer disease, gastric biopsy specimens from 103 Caucasian patients in Brazil were analyzed by PCR. Since allelic variation in cagA exists and distinct H. pylori subgenotypes may circulate in different regions, PCR using primers for a variable 3' region of the cagA gene according to a Japanese methodology and for a consensus cagA 3' region used in Western methods was used for cagA detection. cagA was present in 53 (71%) of 75 H. pylori-positive cases when analyzed by the consensus region method and was associated with duodenal ulcer disease (P = 0.02), but not with gastric ulcer (P = 0.26), when compared to patients with duodenitis or gastritis. The variable region PCR method was able to detect 43 (57%) cagA-positive cases within the same group of H. pylori-positive patients and showed three subtypes of cagA (A, B/D, and C) that were not associated with clinical outcome. However, in 8 (18%) of the cases, more than one subtype was present, and an association between patients with multiple subtypes and disease outcome was observed when compared to patients with isolated subtypes (P = 0.048). cagA was a marker of H. pylori strains for duodenal ulcer disease in our population, and in spite of the differences in the 3' region of the cagA gene, the Japanese methodology was able to detect the cagA status in most cases. The presence of multiple subgenotypes of cagA was associated with gastric ulcer.

Thyrotoxicosis due to ectopic retrotracheal adenoma treated with radioiodine.

Ectopic thyroid tissue is rarely found in the cervical retrotracheal region and its functional autonomy with suppression of the normal gland can be considered unusual. We report a case of thyrotoxicosis in a patient who had no palpable goitre in the neck but was found to have a solitary toxic thyroid nodule behind the trachea. US and CT scanning confirmed that the nodule was retrotracheal and apparently was not continuous or contiguous with the normal thyroid gland. The toxic adenoma showed avid uptake of iodine-131 (131I), and using thallium-201-chloride (201Tl)-SPECT the normal thyroid gland together with the retrotracheal autonomous nodule was demonstrated. The patient underwent radiometabolic therapy with 666 MBq of 131I and a 131I scan performed 6 months later showed only the previously suppressed normal thyroid gland.

Giant prolactinomas in men: efficacy of cabergoline treatment.

OBJECTIVE: The term 'giant prolactinoma' can be used for tumours larger than 4 cm in diameter and/or with massive extrasellar extension. Cabergoline (CAB), a long-lasting dopamine agonist (DA), safe and well tolerated, is effective in normalizing PRL levels and inducing tumour shrinkage in micro- and macroprolactinomas. The purpose of this prospective study was to evaluate the efficacy and safety of CAB also for giant prolactinomas. PATIENTS AND METHODS: Ten men with giant prolactinomas with a median age of 44.8 years were treated with CAB. Before CAB, four patients had previously undergone transsphenoidal surgery without modifying the parasellar extension of the tumour or their visual defects. Pretreatment serum prolactin (PRL) levels ranged between 1230 and 22 916 micro g/l (mean +/- SEM: 5794 +/- 1996) and tumour volume was between 21.8 and 105.5 cm3 (mean +/- SEM: 50.7 +/- 8.8). CAB was administered at an initial low dose of 0.5 mg three times a week and, in five patients who did not achieve serum PRL normalization, the dose was progressively increased up to 10.5 mg/week. The duration of treatment was 13-68 months (mean 38.9). PRL levels and pituitary target organ hormones were assayed before, after 30 days and then every 3 months after the beginning of CAB treatment. Magnetic resonance imaging (MRI) was carried out before, after 1-3 months, after 6 months and then every 10-12 months to evaluate tumour shrinkage. RESULTS: In every patient, a significant PRL decrease (P = 0.0086) of at least 96% of the pretreatment values occurred (from 5794 +/- 1996 to 77 +/- 38, mean +/- SEM); a persistent normalization of PRL levels was achieved in five out of 10 patients (50%) beginning from the first 3-6 months of CAB treatment (only one patient needed 12 months of therapy). A significant tumour shrinkage (P = 0.0003) was achieved after 12 months of therapy in nine out of 10 patients (90%), with a volume reduction greater than 95% in three, of 50% in four and 25% in two patients. Tumour volume decreased from 50.7 +/- 8.8 to 28.6 +/- 9.4 and then to 22.3 +/- 8.8 cm3 (mean +/- SEM) after 6 and 12 months of CAB treatment, respectively. An improvement of visual field defects (VFD) was obtained in six of the seven patients presenting visual impairment before CAB treatment. Among the eight patients presenting libido and potency (L-P) failure, five normalized their PRL levels. In two of these a complete restoration of libido and potency was observed. Three patients with secondary hypoadrenalism and a patient with secondary hypothyroidism were treated with substitutive therapy during all the study time. The drug was well tolerated by all patients and no one discontinued the therapy. CONCLUSIONS: These data suggest that, in giant, aggressive prolactinomas, CAB represents a first-line therapy effective in reducing PRL levels and determining tumour shrinkage.

A chitinase encoding gene (chit1 gene) from the entomopathogen Metarhizium anisopliae: isolation and characterization of genomic and full-length cDNA.

There are no reports to date of entire gene sequences coding for chitinolytic enzymes from entomopathogenic fungi, even though these enzymes act synergistically with proteolytic enzymes to solubilize insect cuticle during the key step of host penetration, having considerable importance in the biological control of some insect pests. This paper reports the complete nucleotide sequence and analysis of the chromosomal and full-length cDNA copies of the regulated gene (chit1) coding one of the chitinases produced by the biocontrol agent Metarhizium anisopliae. Degenerated primers, encompassing conserved regions of other fungal chitinases, were used to amplify a 650-bp DNA fragment, which was used to isolate genomic and cDNA clones from M. anisopliae. Albeit at least two different chitinases are characterized in this fungus, only one chit gene was isolated. The chit1 gene is interrupted by three short typical fungal introns and has a 1,521-bp ORF, which encodes a protein of 423 amino acids with a stretch of 35 amino acid residues displaying characteristics of signal peptide. The deduced sequence of the mature protein predicts a 42-kDa protein with pI of 5.8. Southern analysis of genomic DNA indicates a single copy of chit1 in the M. anisopliae genome.

Incidentally discovered adrenal masses: a functional and morphological study.

In the last two years we have examined 17 consecutive patients (11 females and 6 males, 20-66 years old) in whom an unsuspected adrenal mass was discovered by ultrasonography or computed tomography performed for unrelated reasons. Pathological diagnosis was available in 11 cases based on surgical excision in 9 (2 pheochromocytomas of 5 and 12 cm in diameter; 2 ganglioneuromas of 5 and 6 cm; and 5 benign cortical adenomas between 3 and 5 cm), autopsy in 1 (a disseminated malignant pheochromocytoma of 16 cm) and fine-needle biopsy in 1 (a pseudo-adrenal mass of 6 cm, that was a regenerative hepatic nodule). The remaining 6 non histologically diagnosed masses were less than 3 cm in diameter. Endocrine studies showed elevated urinary excretion of catecholamines, vanillylmandelic acid and metanephrines in the pheochromocytomas and borderline high values in ganglioneuromas. A low plasma renin activity was encountered in 2 operated cortical adenomas and 3 non operated incidentalomas. In 2 of the latters aldosterone serum levels were elevated and the final diagnoses respectively were Conn's adenoma and dexamethasone-suppressible hyperaldosteronism with bilateral nodular hyperplasia. An inappropriate cortisol secretion was documented in a cortical adenoma removed. Radio-cholesterol scintiscan showed unilateral or increased uptake on the side of adrenal mass (concordant uptake) in the 5 benign cortical adenomas removed and in 4 non operated incidentalomas. A decreased uptake on the side of the adrenal mass (discordant uptake) was found in the 2 ganglioneuromas while an indeterminate bilateral uptake was found in the 2 remaining non operated incidentalomas and in the pseudo-adrenal mass.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute complications in the course of "mild" hyperparathyroidism.

It is generally accepted that some patients affected by mild asymptomatic primary hyperparathyroidism need not be treated with surgery, but may be medically managed without risk. However, our experience regarding 5 of these cases observed in the last two years, suggests a different approach. These patients, initially diagnosed as having mild hyperparathyroidism based on only moderately elevated serum concentrations of calcium and followed medically for years, were referred to us for a sudden worsening of their clinical course. One 35-year-old man presented hemorrhagic gastritis with severe anemia and type II AV block with syncopal attacks. Three women, aged 51, 64 and 65 years, presented with severe hypercalcemia associated with renal failure in two and with marked bone disease in another. In all these cases parathyroid neoplasms were preoperatively localized (by ultrasonography, CT scan and radioactive 201-Tl 99-Tc scan) and surgically removed. Histological examination showed a parathyroid carcinoma in the male patient and single gland enlargements in the three females. A fifth patient, a 65-year-old woman, was referred to us in critical condition: severe hypercalcemia, osteopenia with femur fracture, myocardial infarction and renal failure. She died in a few days, in spite of intensive medical care. These cases suggest that patients with hyperparathyroidism initially diagnosed as "mild" need close medical observation and preferably, in our opinion, should undergo surgery.

Activation of cholinergic tone by pyridostigmine reverses the inhibitory effect of corticotropin-releasing hormone on the growth hormone-releasing hormone-induced growth hormone secretion.

Previous studies have shown that corticotropin-releasing hormone (CRH) is capable of inhibiting growth hormone (GH) secretion in response to GH-releasing hormone (GHRH). In an attempt to clarify the mechanism of the CRH action, we have studied the effect of enhanced cholinergic tone induced by pyridostigmine on the CRH inhibition of the GH response to GHRH in a group of six normal men and six normal women. All subjects presented a normal GH response to 50 micrograms i.v. GHRH administration (mean peak +/- SEM plasma GH levels 20 +/- 2.9 micrograms/l in men and 28.9 +/- 2.9 micrograms/l in women) with a further significant increase after pyridostigmine pretreatment (60 mg orally given 60 min before GHRH) in men (GH peaks 43.1 +/- 6.9 micrograms/l, p less than 0.005) but not in women (GH peaks 39.2 +/- 3.0 micrograms/l). In the same subjects, peripherally injected CRH (100 micrograms) significantly inhibited the GH response to GHRH (GH peaks 8.1 +/- 0.6 micrograms/l in men, p less than 0.005 and 9.9 +/- 0.7 micrograms/l in women, p less than 0.005). Pyridostigmine (60 mg) given orally at the same time of CRH administration (60 min before GHRH) reversed the CRH inhibition of GHRH-induced GH secretion (GH peaks 35.3 +/- 8.2 micrograms/l in men and 35 +/- 3.3 micrograms/l in women) with a response not significantly different to that seen in the pyridostigmine plus GHRH test. Our data confirm that pyridostigmine is capable of potentiating the GHRH-induced GH release in normal male but not female subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of sex and age on pyridostigmine potentiation of growth hormone-releasing hormone-induced growth hormone release.

Previous studies have shown that pyridostigmine (PD) is capable of increasing the growth hormone (GH) response to GH-releasing hormone (GHRH) in young healthy subjects. In order to investigate the influence of age and sex on the PD potentiation of GHRH-induced GH release, we have studied the GH response to GHRH (50 micrograms i.v.) 1 h after oral administration of placebo or PD (60 mg) in 8 young healthy men (aged 19-28 years) and 8 age-matched young women (aged 18-25 years) during the follicular phase of the menstrual cycle, as well as in 8 postmenopausal women (aged 57-62 years) and 8 age-matched elderly men (aged 56-64 years). In the same subjects the effect of PD alone (60 mg p.o.) was also studied. Furthermore, in 6 postmenopausal women and 6 elderly men, the effect of a 30-mg PD oral dose on GH secretion and GH response to GHRH was evaluated with a similar protocol. The GH responses (mean +/- SE) to GHRH + placebo were similar in young men (peak 20.1 +/- 2 ng/ml, AUC 1,250 +/- 113 ng/ml/min) and women (peak 29.3 +/- 2.3 ng/ml, AUC 1,769 +/- 305 ng/ml/min). PD 60 mg was capable of significantly increasing the GH response to GHRH in young men (peak 43.5 +/- 5.1 ng/ml, AUC 3,734 +/- 472 ng/ml/min, p less than 0.005) but not in women (peak 39 +/- 2.3 ng/ml, AUC 2,479 +/- 205 ng/ml/min).(ABSTRACT TRUNCATED AT 250 WORDS)

Paroxystic hypertension in a long-term hemodialyzed patient. Successful adrenalectomy for a dopamine-producing pheochromocytoma.

Pheochromocytoma (Pheo) is an uncommon neoplasm producing blood pressure troubles and it may be undiagnosed in chronic dialyzed patients in whom hypertension is a common finding. The symptoms in Pheo syndrome depends on the prevalent catecholamine released, the most common being epinephrine (E) and norepinephrine (NE). Recently, a particular clinical picture has been described for dopamine (DA)-producing Pheos, in whom a normo-hypotensive status is more often observed. The authors report a case of mainly dopamine-producing Pheo in a long-term dialyzed patient, successfully treated with adrenalectomy. The main steps in diagnosis and preoperative management are described and debated also in view of the particular background produced by the end-stage renal failure. The common imaging techniques adopted for adrenal medullary neoplasms (US, CT, MIBG scintiscan) confirmed to be decisive for diagnosis; HPLC assay of plasma catecholamines is the only biochemical test available in these patients although its significance is questionable due to the poor knowledge of catecholamine metabolism in chronic renal failure. The clinical findings observed in this case seem in disagreement with those already reported in DA producing Pheos. Pheo in hemodialyzed patients is a rare event and it may be hidden by other more common causes of hypertension. However, more awareness from the medical staff allows to diagnose the neoplasm correctly by the currently available methods and to plan a safe surgical therapy also in high-risk patients.