Disease control of acromegaly does not prevent excess mortality in the long term: results of a nationwide survey in Italy.

OBJECTIVE: This study aimed to assess the long-term outcome of patients with acromegaly. DESIGN: This is a multicenter, retrospective, observational study which extends the mean observation period of a previously reported cohort of Italian patients with acromegaly to 15 years of follow-up. METHODS: Only patients from the centers that provided information on the life status of at least 95% of their original cohorts were included. Life status information was collected either from clinical records or from the municipal registry offices. Standardized mortality ratios (SMRs) were computed comparing data with those of the general Italian population. RESULTS: A total of 811 patients were included. There were 153 deaths, with 90 expected and an SMR of 1.7 (95% CI 1.4-2.0, p < 0.001). Death occurred after a median of 15 (women) or 16 (men) years from the diagnosis, without gender differences. Mortality remained elevated in the patients with control of disease (SMR 1.3, 95% CI 1.1-1.6). In the multivariable analysis, only older age and high IGF1 concentrations at last available follow-up visit were predictors of mortality. The oncological causes of death outweighed the cardiovascular ones, bordering on statistical significance with respect to the general population. CONCLUSIONS: Mortality remains significantly high in patients with acromegaly, irrespectively of disease status, as long as the follow-up is sufficiently long with a low rate of patients lost to follow-up. Therapy strategy including radiotherapy does not have an impact on mortality. Oncological causes of death currently outweigh the cardiovascular causes.

Protein kinase C delta mediates Pasireotide effects in an ACTH-secreting pituitary tumor cell line.

PURPOSE: Clinical control of corticotroph tumors is difficult to achieve since they usually persist or relapse after surgery. Pasireotide is approved to treat patients with Cushing's disease for whom surgical therapy is not an option. However, Pasireotide seems to be effective only in a sub-set of patients, highlighting the importance to find a response marker to this approach. Recent studies demonstrated that the delta isoform of protein kinase C (PRKCD) controls viability and cell cycle progression of an in vitro model of ACTH-secreting pituitary tumor, the AtT-20/D16v-F2 cells. This study aims at exploring the possible PRKCD role in mediating Pasireotide effects. METHODS: It was assessed cell viability, POMC expression and ACTH secretion in AtT20/D16v-F2 cells over- or under-expressing PRKCD. RESULTS: We found that Pasireotide significantly reduces AtT20/D16v-F2 cell viability, POMC expression and ACTH secretion. In addition, Pasireotide reduces miR-26a expression. PRKCD silencing decreases AtT20/D16v-F2 cell sensitivity to Pasireotide treatment; on the contrary, PRKCD overexpression increases the inhibitory effects of Pasireotide on cell viability and ACTH secretion. CONCLUSION: Our results provide new insights into potential PRKCD contribution in Pasireotide mechanism of action and suggest that PRKCD might be a possible marker of therapeutic response in ACTH-secreting pituitary tumors.

Investigation of COVID-19 infection in subjects with Klinefelter syndrome.

PURPOSE: COVID-19 has worse clinical outcomes in males compared with females and testosterone may determine gender differences. Hypogonadism and supernumerary X chromosome may have a role in the SARS-CoV-2 infection in Klinefelter syndrome (KS). Aim of the study was evaluating COVID-19 frequency and severity in KS. METHODS: Participants were invited to complete a retrospective self-administered questionnaire containing multiple choice and open-ended answers. RESULTS: COVID-19 was detected in 10% of the evaluated KS subjects; none was hospitalized. 44.4% of COVID-19 patients had one cohabitant-infected versus 3% of non-infected (p < 0.01). Testosterone levels in infected patients were lower compared to those of non-infected subjects (3.1 ± 1.2 ng/ml vs. 5.2 ± 2 ng/ml, p < 0.05). CONCLUSIONS: The frequency of SARS-CoV-2 infection among KS subjects was 10%. All infected patients showed mild symptoms. The presence of one affected cohabitant significantly associated with SARS-CoV-2 infection. An association between SARS-CoV-2 and hypogonadism was confirmed.

GH/IGF-1 axis in a large cohort of ß-thalassemia major adult patients: a cross-sectional study.

PURPOSE: GH deficit (GHD) could represent an endocrine issue in ß-Thalassemia Major (ßTM) patients. GH/IGF-1 axis has not been extensively explored in ßTM adults, so far. We aim to assess GHD and IGF-1 deficiency prevalence in ßTM adult population, focusing on the relationship with liver disease. METHODS: Cross-sectional multi-centre study conducted on 81 adult ßTM patients (44 males, mean age 41 ± 8 years) on transfusion and chelation therapy. GHD was investigated by GHRH + arginine test. IGF-1 levels, routine biochemical exams, Fibroscan, Hepatic Magnetic Resonance Imaging (MRI) and pituitary MRI were collected. RESULTS: Eighteen patients were affected by GHD and 63 were not (nGHD) according to GHRH + arginine test, while basal GH levels did not differ. GHD was associated with a higher BMI and a worse lipid profile (p < 0.05). No significant differences were observed regarding liver function between the two groups. Pituitary MRI scan was normal except for one case of empty sella. The 94.4% and 93.6% of GHD and nGHD, respectively, presented lower IGF-1 levels than the reference range, and mean IGF-1 SDS was significantly lower in GHD patients. CONCLUSION: GHD is frequent in adult ßTM patients and is associated with higher BMI and worse lipid profile. nGHD patients present lower IGF-1 levels as well. There was no relationship between IGF-1 levels and liver disease. Further, multicentric studies with larger cohorts and standardized diagnostic protocols are needed.

Functional hypothalamic and drug-induced amenorrhea: an overview.

BACKGROUND: Functional hypothalamic amenorrhea (FHA) is a form of chronic anovulation not due to identifiable organic causes and with adverse health consequences. The identification of women with this disorder or the precocious identification of women at risk is based on the knowledge of lifestyle risk factors or behaviors such as stress, weight loss, and excessive physical exercise that are known to negatively impact gonadal axis activity. METHODS: In this overview, we described the most common forms of FHA, in particular stress-induced amenorrhea and overtraining-induced amenorrhea. In addition, although its mechanisms can differ from those involved in FHA, we reviewed the available literature on drug-induced amenorrhea, highlighting the clear connection between this condition and psychoactive drugs such as antipsychotics, antidepressants and anti-epilectics thus raising concern about the role that the abuse of substances such as opioids or alcohol can possibly have on the growing unexplained infertility of the female population.

Dopamine receptor subtype 2 and somatostatin receptor subtype 5 expression influences somatostatin analogs effects on human somatotroph pituitary adenomas in vitro.

Dopamine (DA) and somatostatin (SRIF) receptor agonists inhibit growth hormone (GH) secretion by pituitary adenomas. We investigated DA subtype 2 receptor (DR2) and SRIF receptor (sst) subtypes 2 and 5 expression in 25 GH-secreting pituitary adenomas and tested in primary culture the effects on GH and prolactin (PRL) secretion of sst agonists selectively interacting with sst2 (BIM-23120), sst5 (BIM-23206), and sst2 and sst5 (BIM-23244). All adenomas expressed sst2; eight adenomas expressed both sst5 and DR2, eight sst5 but not DR2, and eight DR2 but not sst5. One tissue lacked expression of DR2 and sst5. GH secretion was inhibited by BIM-23120 in all samples, while it was reduced by BIM-23206 only in adenomas not expressing DR2. BIM-23120's inhibitory effects correlated with sst2 and DR2 expression, whereas DR2 expression correlated inversely with BIM-23206 inhibitory effects on GH secretion. In seven mixed GH-/PRL-secreting pituitary adenomas, PRL secretion was inhibited in sst5-expressing tumors by BIM-23206, but not by BIM-23120. BIM-23244 reduced PRL secretion only in adenomas expressing sst2, sst5 and DR2. sst5 and DR2 expression correlated directly with BIM23206 inhibitory effects on PRL secretion. Our results suggest that adenomas expressing DR2 are less likely to respond to clinically available SRIF analogs in terms of GH secretion inhibition. Therefore, drugs interacting also with DR2 might better control secretion of pituitary adenomas.

Diurnal rhythm of plasma catecholamines in acromegaly.

We investigated the 24-h profiles of the circulating levels of norepinephrine (NE) and epinephrine (E), blood pressure (BP), and heart rate in 14 acromegalic patients, before (A) and 3-6 months after transsphenoidal surgery (C-A, cured; A-A, active), and in 8 age-matched normal subjects (N). In addition, the responses of NE, E, PRA, and aldosterone to upright posture were investigated. No significant differences in the mean 24-h plasma NE and E levels were observed between either group of acromegalics and the N subjects. Analysis of the 24-h profiles indicated a statistically significant 24-h rhythm of both NE and E in N subjects. No evidence of a 24-h rhythm of plasma NE and E and BP was found in A patients. After surgery, a statistically significant 24-h rhythm of NE was detected in the patients with acrophase (13.54 and 13.45 h in C-A and A-A patients, respectively) and mesor (1019.8+/-45.1 and 1017.8+/-54.7 pmol/L in C-A and A-A patients, respectively) similar to those observed in N subjects (acrophase, 13.21 h; mesor, 942.3+/-42.5 pmol/L). After surgery, the plasma concentration of E clearly fluctuated throughout the 24 h in both C-A and A-A patients, even if cosinor analysis failed to reveal a 24-h significant rhythm. A statistically significant 24-h rhythm of BP was restored only in C-A patients. The mean 24-h heart rate was slightly, but significantly (P<0.05), higher in A than in N subjects and decreased after surgery. No significant differences in upright-stimulated NE, E, and plasma aldosterone levels were observed between each group of acromegalics and N subjects. However, basal and upright-stimulated PRA levels were significantly (P<0.001) lower in A patients. In conclusion, our study demonstrates the lack of a clear circadian variation in catecholamine levels and BP in active acromegaly and the return of a significant 24-h rhythm of NE and BP after pituitary surgery, concomitant with the reduction in GH and insulin-like growth factor I serum levels.

Stress-induced activation of sympathetic nervous system is attenuated by the delta-opioid receptor agonist deltorphin in healthy man.

To examine the role of delta-opioid receptors in the regulation of the sympathoadrenomedullary system, the effects of the highly selective delta-opioid receptor agonist deltorphin (DT) on plasma catecholamine responses to insulin-induced hypoglycemia (IIH) and cold pressor test (CPT) have been investigated in normal subjects in two separate studies. DT failed to modify basal plasma levels of both norepinephrine (NE) and epinephrine (E). DT completely suppressed the IIH-evoked elevation of NE, whereas it attenuated the E response by 20%, with the DT-induced decrease in E release failing to achieve statistical significance. DT completely blocked the release of both NE and E elicited by CPT. We conclude that specific delta-opioid receptor stimulation exerts an inhibitory effect on NE release induced by both IIH and CPT. These findings provide evidence that delta-opioid receptors may influence the autonomic sympathetic reactivity.

Modulatory effect of the renin-angiotensin system on the plasma levels of calcitonin gene-related peptide in normal man.

Calcitonin gene-related peptide (CGRP) has positive chronotropic and inotropic effects in animals and humans, and produces the most potent vasodilation known for an endogenous peptide. Yet, a physiological role for CGRP in the regulation of vascular tone and blood pressure has not been demonstrated. We studied the effects of 1) assumption of the upright position and 2) iv infusion of angiotensin-II (sequential doses of 8, 16, and 32 ng/kg.min, each dose for 20 min) in eight normal subjects (four men). Serial venous blood samples were taken to determine the plasma CGRP, epinephrine, norepinephrine, and aldosterone levels and PRA. Blood pressure and heart rate were continuously monitored at the finger with a Finapres 2300 instrument. After assumption of the upright posture, a quick rise in plasma CGRP levels was observed together with the expected increases in plasma norepinephrine and aldosterone and PRA. A transient increment was also observed for diastolic blood pressure and heart rate. Angiotensin-II infusion caused dose-dependent increases in plasma CGRP and aldosterone concentrations, already significant at the lowest infusion rate and parallel with the blood pressure rise. Plasma catecholamines significantly increased only at higher infusion rates. Our data demonstrate that modifications of plasma CGRP concentrations are part of the normal response to postural and vasomotor changes. These findings suggest a physiological role for CGRP in regulation of the peripheral vascular tone and possibly blood pressure in man.

Blood growth hormone-binding protein levels in premenopausal and postmenopausal women: roles of body weight and estrogen levels.

A substantial proportion of GH circulates bound to high affinity GH-binding protein (GHBP), which corresponds to the extracellular domain of the GH receptor. Current evidence indicates that nutritional status has an important role in regulating plasma GHBP levels in humans. In the present study the relationship among plasma GHBP levels, body composition [by bioelectrical impedance analysis (BIA) and dual energy x-ray absorptiometry (DEXA)] and serum estradiol (E(2)) was evaluated in premenopausal (n = 92) and postmenopausal (n = 118) healthy women with different body weight [three groups according to body mass index (BMI): normal, 18.5-24.99; overweight, 25-29.99; obese, 30-39.99 kg/m(2)]. Plasma GHBP levels were measured by high pressure liquid chromatography gel filtration. GH and insulin-like growth factor I levels were determined by immunoradiometric assay and RIA, respectively. GHBP levels were significantly higher in premenopausal women with BMI above 25 kg/m(2) (overweight, 3.789 +/- 0.306 nmol/L; obese, 4.372 +/- 0.431 nmol/L) than those observed in postmenopausal women (overweight, 1.425 +/- 0.09 nmol/L; obese, 1.506 +/- 0.177 nmol/L). No significant differences were found between normal weight premenopausal (1.741 +/- 0.104 nmol/L) and postmenopausal (1.524 +/- 0.202 nmol/L) women. In premenopausal women GHBP levels correlated positively with BMI (r = 0.675; P < 0.001), fat mass (FM; r = 0.782; P < 0.001; by BIA; r = 0.776; P < 0.001; by DEXA), truncal fat (TF; r = 0.682; P < 0.001), waist to hip circumference ratio (WHR; r = 0.551; P < 0.001), and E(2) (r = 0.298; P < 0.05), whereas no significant correlation was found in postmenopausal women between GHBP levels and BMI, FM, TF, WHR, or E(2). In normal weight pre- and postmenopausal women GHBP levels did not change between the ages of 20 and 69 yr. No statistically significant correlation was found between GHBP and age for all groups studied. Moreover, in two distinct subgroups of pre- and postmenopausal women, aged 40-49 yr, the direct relationship between GHBP levels and all indexes of adiposity were only observed in premenopausal women [BMI: r = 0.836; P < 0.001; FM: r = 0.745 (BIA) and r = 0.832 (DEXA); P < 0.001; TF: r = 0.782; P < 0.001; WHR: r = 0.551; P < 0.05], but not in postmenopausal women. In conclusion, the present data indicate a strong direct correlation between GHBP and body fat in premenopausal, but not in postmenopausal women, whereas they failed to detect a relationship between GHBP and age. Therefore, these results suggest that endogenous estrogen status may be an important determinant of the changes in GHBP levels in women with different body weights.

Human galanin reduces plasma norepinephrine levels in man.

The neuropeptide galanin (GAL) is widely distributed in the peripheral and central nervous systems, where it often coexists with catecholamines. To gain insight into the action of human GAL on sympathetic nervous system activity in man, we investigated the effects of a 60-min infusion of human (h) GAL (80 pmol/kg.min) or saline on peripheral norepinephrine (NE) and epinephrine concentrations, heart rate (HR), and systolic and diastolic blood pressure (BP) in the supine position as well as after assumption of the upright posture (UP) in eight healthy male volunteers. hGAL depressed supine plasma NE (0.84 +/- 0.06 vs. 0.33 +/- 0.02 nmol/L) and blunted the NE response to assumption of the UP (1.68 +/- 0.03 vs. 0.44 +/- 0.03 nmol/L), but caused a significant enhancement of the epinephrine response to assumption of the UP (0.22 +/- 0.02 vs. 0.65 +/- 0.06 nmol/L). hGAL significantly increased supine HR (70 +/- 2 vs. 99 +/- 4 beats/min) and potentiated the HR response to assumption of the UP (82 +/- 3 vs. 107 +/- 4 beats/min). hGAL did not alter supine systolic and diastolic BP, but caused a significant decrease in the systolic (121 +/- 3 vs. 98 +/- 2 mm Hg) and diastolic (74 +/- 2 vs. 62 +/- 2 mm Hg) BP responses to assumption of the UP. Our data show that hGAL decreases supine position- and UP-stimulated release of NE, suggesting an inhibitory modulation of hGAL on sympathetic outflow in man. The finding that hGAL induces an increase in HR, both in the supine position and after UP, and an inhibition of the systolic and diastolic BP response to UP provides further support for an involvement of hGAL in regulation of the cardiovascular and autonomic nervous systems in man.

Serum thyroglobulin concentrations and (131)I whole-body scan results in patients with differentiated thyroid carcinoma after administration of recombinant human thyroid-stimulating hormone.

UNLABELLED: The use of recombinant human thyroid-stimulating hormone (rhTSH) has recently become available as an alternative diagnostic tool to assess the persistence and recurrence of differentiated thyroid carcinoma (DTC) in patients on thyroid hormone-suppressive therapy (THST) after near-total or total thyroidectomy and ablative doses of (131)I. We report the results of rhTSH administration in patients who were monitored for DTC. METHODS: Thirty-three adult DTC patients (13 men, 20 women; mean age +/- SE, 45.6 +/- 2.31 y; age range, 21-65 y) underwent diagnostic follow-up after rhTSH administration at a dose of 0.9 mg once a day for 2 d. Whole-body scanning and serum thyroglobulin (Tg) measurement were performed after rhTSH administration. Patients were divided into 2 groups depending on serum Tg concentrations on THST: 29 patients had Tg concentrations of <2 ng/mL (group A) and 4 patients had Tg values of >2 ng/mL (group B). RESULTS: In group A, Tg values remained at <2 ng/mL in 25 patients and increased from 1.1 +/- 0.14 ng/mL to 22.0 +/- 5.75 ng/mL (mean +/- SE) in 4 patients after rhTSH administration. Whole-body scanning did not reveal any uptake of (131)I in the 25 patients without an increase in Tg, whereas (131)I uptake was evident in 2 of the 4 patients with a rise in Tg. In group B, Tg values increased in all 4 patients from 17.3 +/- 6.35 ng/mL to 55.3 +/- 12.75 ng/mL, and (131)I uptake was evident in 3 of the 4 patients. No major adverse effects were reported after rhTSH administration. CONCLUSION: Our results show that the measurement of serum Tg concentrations after rhTSH has a higher diagnostic value than whole-body scanning in detecting the persistence of thyroid tissue. Therefore, rhTSH should be administered in TSH-suppressed patients with basal serum Tg concentrations of <2 ng/mL because the increment in serum Tg concentrations may reveal the persistence of thyroid tissue in these patients.

Effect of human galanin on the response of circulating catecholamines to hypoglycemia in man.

Human galanin (hGAL) is a neuropeptide with 30 amino acid residues that has been found in the peripheral and central nervous system, where it often co-exists with catecholamines. In order to clarify the possible role of hGAL in the regulation of sympathoadrenomedullary function, the effect of a 60-min infusion of hGAL (80 pmol.kg-1.min-1) on plasma epinephrine and norepinephrine responses to insulin-induced hypoglycemia in nine healthy subjects was investigated. Human GAL administration significantly reduced both the release of basal norepinephrine and the response to insulin-induced hypoglycemia, whereas it attenuated the epinephrine response by 26%, with the hGAL-induced decrease in epinephrine release failing to achieve statistical significance. Human GAL significantly increased the heart rate in resting conditions and clearly exaggerated the heart rate response to insulin-induced hypoglycemia, whereas it had no effect on the blood pressure. We conclude that GAL receptor stimulation exerts an inhibitory effect on basal and insulin-induced hypoglycemia-stimulated release of norepinephrine. These findings provide further evidence that GAL may modulate sympathetic nerve activity in man but that it does not play an important role in the regulation of adrenal medullary function.

Evaluation of hormonal function in a series of incidentally discovered adrenal masses.

The discovery of an asymptomatic adrenal mass (incidentaloma) during the investigation of an unrelated condition is relatively common. In this study, we report the clinical, radiologic, and endocrine evaluation of 38 patients (22 women and 16 men aged 24 to 84 years) with adrenal incidentaloma (size, 1 to 12 cm). The patients underwent basal and dynamic evaluation of the hypothalamic-pituitary-adrenal (HPA) axis, renin-angiotensin-aldosterone system, and adrenomedullary function. Moreover, computed tomograpy (CT) scan and 131I-6beta-iodomethyl-19-norcholest-5(10)-en-3beta-ol(NP-59) and/or 131I-metaiodobenzylguanidine (MIBG) scintigraphy were performed. The endocrine evaluation indicated two cases of pheochromocytoma and four cases of preclinical Cushing's syndrome, three of which underwent surgery with histologic diagnosis of two adrenocortical adenomas and one carcinoma. Low levels of serum dehydroepiandrosterone sulfate (DHEA-S), associated with a markedly increased 17-hydroxyprogesterone (17-OHP) response to a corticotropin (ACTH) test, were found in patients with incidentaloma. On the basis of endocrine and morphologic data, 13 patients underwent surgical treatment: five adrenocortical adenomas (two functioning), two pheochromocytomas, two ganglioneuromas, one cortisol-secreting adrenal carcinoma, one lymphangiomatous cyst, one myelolipoma, and one hemorrhage were found. Careful diagnostic assessment of incidentally discovered adrenal masses must be performed to exclude the presence of malignant and/or functioning lesions and to verify the possibility that patients with incidentaloma have a genetic or acquired deficit of adrenal steroidogenic activity.

Differential effects of deltorphin on arginine and galanin-induced growth hormone secretion in healthy man.

Recently we demonstrated the inhibitory action on Growth Hormone (GH) secretion of an opioid heptapeptide, deltorphin (DT), that is highly selective in binding delta-opioid receptors. To investigate the possible mechanism leading to the decrease in GH secretion by specific activation of delta-opioidergic pathway in man, we compared, in normal subjects, the effect of DT on GH secretion responses to two different GH secretagogues, namely arginine (ARG) and galanin (GAL). DT completely blunted the GH response to ARG, whereas it attenuated the GH response to GAL, but not at a statistically significant level. We suggest that the specific activation of delta-opioid receptors in man may exert an inhibitory influence on GH secretion principally by modulating endogenous hypothalamic somatostatin (SRIH) release.

Interrelationships between calcitonin gene-related peptide and sympathoadrenomedullary system: effects of administration of epinephrine and norepinephrine in healthy man.

To investigate the influence of the sympathoadrenomedullary system on the modulation of the circulating levels of calcitonin gene-related peptide (CGRP), the effects of epinephrine (E) and norepinephrine (NE) were studied in 8 normal subjects (4 females and 4 males). The mean basal levels of CGRP in normal subjects were 10.2 +/- 1 pmol/l. After the infusion of E (20 ng/kg per min for 30 min), a significant rise (P < 0.005) in plasma CGRP levels was observed with the expected increases in systolic blood pressure (BP), heart rate (HR) and plasma renin activity (PRA), and decrease in diastolic BP, whereas plasma aldosterone (PA) levels did not significantly change. The infusion of NE (40 ng/kg per min for 30 min) induced an increase in systolic and diastolic BPs, whereas it failed to modify CGRP, HR, PA and PRA. Our data demonstrate that the sympathoadrenomedullary system may modulate CGRP release in man perhaps via the beta-adrenergic pathway. It is likely that the modifications of plasma CGRP levels may be part of the acute vasal response to E.

Predictors of morbidity and mortality in acromegaly: an Italian survey.

OBJECTIVE: To describe demographic and hormonal characteristics, comorbidities (diabetes mellitus and hypertension), therapeutic procedures and their effectiveness, as well as predictors of morbidity and mortality in a nationwide survey of Italian acromegalic patients. DESIGN: Retrospective multicenter epidemiological study endorsed by the Italian Society of Endocrinology and performed in 24 tertiary referral Italian centers. The mean follow-up time was 120 months. RESULTS: A total of 1512 patients, 41% male, mean age: 45±13 years, mean GH: 31±37 µg/l, IGF1: 744±318 ng/ml, were included. Diabetes mellitus was reported in 16% of cases and hypertension in 33%. Older age and higher IGF1 levels at diagnosis were significant predictors of diabetes and hypertension. At the last follow-up, 65% of patients had a controlled disease, of whom 55% were off medical therapy. Observed deaths were 61, with a standardized mortality ratio of 1.13 95% (confidence interval (CI): 0.87-1.46). Mortality was significantly higher in the patients with persistently active disease (1.93; 95% CI: 1.34-2.70). Main causes of death were vascular diseases and malignancies with similar prevalence. A multivariate analysis showed that older age, higher GH at the last follow-up, higher IGF1 levels at diagnosis, malignancy, and radiotherapy were independent predictors of mortality. CONCLUSIONS: Pretreatment IGF1 levels are important predictors of morbidity and mortality in acromegaly. The full hormonal control of the disease, nowadays reached in the majority of patients with modern management, reduces greatly the disease-related mortality.

Prevalence of hypopituitarism in patients with cerebrovascular diseases.

Stroke is one of the main causes of death and disability in the adult population. Changes in pituitary hormone secretion may be observed during the acute phase of stroke, representing part of the adaptive response to injury. However, reduced pituitary hormone secretion, caused by pituitary and/or hypothalamus damage, may also occur. Hypopituitarism has been observed in 19% of patients with ischemic stroke and 47% of patients with subarachnoid hemorrhage, presenting as an isolated deficiency in most cases. Diabetes insipidus is very rare. Low IGF-I levels, during the acute phase of stroke, have been associated with poor outcome and high mortality. During rehabilitation, higher IGF-I levels have been observed in patients with better outcome, suggesting a neuroprotective role of IGF-I. Accurate evaluation and long-term follow-up of all patients with stroke are necessary to define the prevalence of hypopituitarism, and its relationship with type, severity, and outcome from stroke. Discovery and adequate treatment of possible endocrine deficiencies may improve outcome and quality of life of patients with stroke.