High prevalence of morphometric vertebral fractures opportunistically detected on thoracic radiograms in patients with non-functioning pituitary adenoma.

PURPOSE: Vertebral fractures (VFs), the hallmark of skeletal fragility, have been reported as an emerging complication in patients with pituitary diseases associated with hormonal excess and/or deficiency, independently from bone mineral density. Non-functioning pituitary adenoma (NFPA) is amongst the most frequent pituitary adenomas; however, skeletal health in this context has never been investigated. We aimed at assessing the prevalence and the determinants of morphometric VFs in patients with NFPA. METHODS: We enrolled 156 patients (79 M/77F, mean age 55.75 ± 12.94 years) at admission in Neurosurgery Unit before trans-sphenoidal surgery and compared them with an age and sex-matched control group of subjects with neither history/risk factors for secondary osteoporosis nor pituitary disorders. We performed a vertebral morphometric evaluation of the thoracic spine on pre-operative X-ray images (MTRx) and collected biochemical, demographic, and clinical data from the entire cohort. RESULTS: The prevalence of thoracic VFs in patients with NFPA was significantly higher than the control group (26.3% vs. 10.3%; p < 0.001). In the NFPA group, 20 patients (48.8% of the fractured patients) showed multiple VFs, 14 (34.1% of them) showed moderate/severe VFs. Patients with VFs were significantly older and had lower serum free triiodothyronine (fT3) levels than non-fractured ones (p = 0.002 and p = 0.004; respectively). The prevalence of secondary male hypogonadism was higher among men with VFs as compared to those with no VFs (72% vs. 48.1%; p = 0.047). Consistently, total testosterone levels in males were significantly lower in fractured patients than in non-fractured ones (p = 0.02). The prevalence of gonadotroph adenomas was significantly higher among patients with VFs (p = 0.02). In multiple logistic regression analysis, older age and lower serum fT3 levels were independent factors predicting the risk for VFs. CONCLUSIONS: For the first time, we reported a high prevalence of thoracic radiological VFs in patients with NFPAs. Our data should prompt clinicians to proceed with a clinical bone fragility evaluation already during the diagnostic work-up, particularly in those with concomitant hypogonadism, or in those with older age and/or with lower fT3.

Novel approaches to bone comorbidity in Cushing's disease: an update.

Skeletal complications are frequent and clinically relevant findings in Cushing's disease (CD) since an uncoupled suppressed bone formation and enhanced bone resorption leads to a marked skeletal damage with a rapid increase of fracture risk. Reduced Bone Mineral Density (BMD) has been consistently reported and osteopenia or osteoporosis are typical findings in patients with CD. Vertebral Fractures (VFs) are frequently reported and may occur even in patients with an only mild reduction of BMD, representing nowadays a still under- or misdiagnosed comorbidity of these patients being frequently asymptomatic. A novel approach combining different available tools such as BMD evaluation and vertebral morphometry, in order to improve diagnosis, management, and follow-up of bone comorbidity in all patients affected by CD, is needed. This approach is foreseen to be a crucial part of management of patients with CD, particularly in Pituitary Tumor Center of Excellence since VFs, the landmark of the bone involvement, may occur early in the history of the disease and may represent a relevant risk factor for further fractures, reduced quality of life and survival and need for pharmacologic prevention and treatment.

The osteo-metabolic phenotype of COVID-19: an update.

CONTEXT: In the multifaceted COVID-19 clinical scenario characterized by a multi-system disorder with negative implications not only on respiratory function but also on cardiac, hematological, neurological and endocrine-metabolic systems, a distinctive osteo-metabolic phenotype with an independent influence on disease severity and recovery of patients affected was early reported. AIM: To summarize and update the main evidences regarding the distinct components of this phenotype in acute and Long COVID-19, reinforcing its clinical relevance and discussing the main pathophysiological and clinical-therapeutic implications of the most recent reported findings. RESULTS: This emerging phenotype is characterized by a widespread acute hypocalcemia and hypovitaminosis D with an impaired compensatory parathyroid hormone response, and a high prevalence of skeletal complications such as vertebral fractures. The clinical relevance of this osteo-metabolic phenotype on acute COVID-19 is well characterized, and novel seminal evidences are progressively highlighting its importance also in predicting patient's long-term outcomes and Long COVID-19 occurrence. CONCLUSIONS: These findings reinforced the central role of a multidisciplinary team, including endocrinologists, in evaluating these patients for a proactive search of each aspect of the osteo-metabolic phenotype components since they may represent suitable therapeutic targets to prevent SARS-CoV-2 infection, poor COVID-19 outcomes, Long COVID-19 occurrence and even possibly better responses to COVID-19 vaccination.

Vertebral fractures at hospitalization predict impaired respiratory function during follow-up of COVID-19 survivors.

PURPOSE: Morphometric vertebral fractures (VFs) have been recently reported as an important component of the endocrine phenotype of COVID-19 and emerging data show negative respiratory sequelae at long-term follow-up in COVID-19 survivors. The aim of this study was to evaluate the impact of VFs on respiratory function in COVID-19 survivors. METHODS: We included patients referred to our Hospital Emergency Department and re-evaluated during follow-up. VFs were detected on lateral chest X-rays on admission using a qualitative and semiquantitative assessment and pulmonary function tests were obtained by Jaeger-MasterScreen-Analyzer Unit 6 months after discharge. RESULTS: Fifty patients were included. Median age was 66 years and 66% were males. No respiratory function data were available at COVID-19 diagnosis. VFs were detected in 16 (32%) patients. No differences between fractured and non-fractured patients regarding age and sex were observed. Although no difference was observed between VF and non-VF patient groups in the severity of pneumonia as assessed by Radiological-Assessment-of-Lung-Edema score at admission, (5 vs. 6, p = 0.69), patients with VFs were characterized as compared to those without VFs by lower Forced Vital Capacity (FVC, 2.9 vs. 3.6 L, p = 0.006; 85% vs. 110% of predicted, respectively, p = 0.001), Forced Expiratory Volume 1st s (FEV1, 2.2 vs. 2.8 L, p = 0.005; 92% vs. 110% of predicted, respectively, p = 0.001) and Diffusing Capacity of the Lungs for Carbon Monoxide (DLCO 5.83 vs. 6.98 mmol/min/kPa, p = 0.036, 59% vs. 86.3% of predicted, respectively, p = 0.043) at 6-month follow up. CONCLUSIONS: VFs, expression of the endocrine phenotype of the disease, appear to influence medium-term impaired respiratory function of COVID-19 survivors which may significantly influence their recovery. Therefore, our findings suggest that a VFs assessment at baseline may help in identifying patients needing a more intensive respiratory follow-up and patients showing persistent respiratory impairment without evidence of pulmonary disease may benefit from VFs assessment to preventing the vicious circle of further fractures and respiratory deterioration.

High Prevalence of Vertebral Fractures Associated With Preoperative GH Levels in Patients With Recent Diagnosis of Acromegaly.

CONTEXT: Osteopathy and morphometric vertebral fractures (VFs) are emerging complications in acromegaly. However, the prediction of VFs in this clinical setting is still a matter of uncertainty, and it is debated whether they are an early event in the natural history of the disease. OBJECTIVE: We aimed to evaluate the prevalence and determinants of morphometric VFs in patients with recently diagnosed acromegaly. METHODS: We enrolled 92 patients (43 men/49 women) on admission to the neurosurgery unit before transsphenoidal surgery, and compared them with control individuals without secondary forms of osteoporosis and pituitary disorders. We performed a VF assessment on preoperative chest x-ray images and collected biochemical, demographic, and clinical data. RESULTS: We detected a significantly higher prevalence of VFs (33.7%) in patients with acromegaly than in controls (P = .001). Among the patients with acromegaly and VFs, 12 (38.7%) showed multiple VFs, and 5 (16.1%) showed moderate/severe VFs. Patients with VFs had higher random serum growth hormone (GH) levels than those with no VFs (P = .03), but there was no difference in insulin-like growth factor-1 (IGF-1) (P = .07) and IGF-1/Upper Normal Limit ratio (P = .08). Free 3,5,3'-triiodothyronine was slightly lower in patients with acromegaly and VFs than in those without VFs (P = .05). In multiple logistic analysis, GH was independently associated with risk for VFs (P = .003). The preoperative serum GH cutoff value that predicted VFs was 12 ng/mL. CONCLUSION: For the first time, high prevalence of radiological VFs is reported in patients with recent diagnosis of acromegaly. Therefore, we can hypothesize that VFs are an early phenomenon of acromegaly and related to GH levels. VF assessment should be included in the workup at the diagnosis of acromegaly.

Vitamin D Levels Are Associated With Blood Glucose and BMI in COVID-19 Patients, Predicting Disease Severity.

CONTEXT: A high prevalence of vitamin D (VD) deficiency in COVID-19 patients has been reported and hypothesized to increase COVID-19 severity likely because of its negative impact on immune and inflammatory responses. Furthermore, clear associations between hypovitaminosis D and fat body mass excess and diabetes, factors associated with COVID-19 severity, have been widely recognized. OBJECTIVE: The aim of this study was to evaluate in COVID-19 patients the relationship between VD levels and inflammatory response, body mass index (BMI), blood glucose (GLU), and disease severity. METHODS: Patients admitted to San Raffaele-Hospital for COVID-19 were enrolled in this study, excluding those with comorbidities and therapies influencing VD metabolism. 25-Hydroxyvitamin D levels, plasma GLU levels, BMI, and inflammatory parameters were evaluated at admission. RESULTS: A total of 88 patients were included. Median VD level was 16.3 ng/mL and VD deficiency was found in 68.2% of patients. VD deficiency was found more frequently in male patients and in those affected by severe COVID-19. Regression analyses showed a positive correlation between VD and PaO2/FiO2 ratio, and negative correlations between VD and plasma GLU, BMI, neutrophil/lymphocyte ratio, C-reactive protein, and interleukin 6. Patients with both hypovitaminosis D and diabetes mellitus, as well those with hypovitaminosis D and overweight, were more frequently affected by a severe disease with worse inflammatory response and respiratory parameters, compared to those without or just one of these conditions. CONCLUSION: We showed, for the first-time, a strict association of VD levels with blood GLU and BMI in COVID-19 patients. VD deficiency might be a novel common pathophysiological mechanism involved in the detrimental effect of hyperglycemia and adiposity on disease severity.

Hypocalcemia in COVID-19: Prevalence, clinical significance and therapeutic implications.

COVID-19 extra-pulmonary features include several endocrine manifestations and these are becoming strongly clinically relevant in patients affected influencing disease severity and outcomes.At the beginning of COVID-19 pandemic no population data on calcium levels in patients affected were available and in April 2020 a first case of severe acute hypocalcemia in an Italian patient with SARS-CoV-2 infection was reported. Subsequently, several studies reported hypocalcemia as a highly prevalent biochemical abnormality in COVID-19 patients with a marked negative influence on disease severity, biochemical inflammation and thrombotic markers, and mortality. Also a high prevalence of vertebral fractures with worse respiratory impairment in patients affected and a widespread vitamin D deficiency have been frequently observed, suggesting an emerging "Osteo-Metabolic Phenotype" in COVID-19.To date, several potential pathophysiological factors have been hypothesized to play a role in determining hypocalcemia in COVID-19 including calcium dependent viral mechanisms of action, high prevalence of hypovitaminosis D in general population, chronic and acute malnutrition during critical illness and high levels of unbound and unsaturated fatty acids in inflammatory responses.Since hypocalcemia is a frequent biochemical finding in hospitalized COVID-19 patients possibly predicting worse outcomes and leading to acute cardiovascular and neurological complications if severe, it is reasonable to assess, monitor and, if indicated, replace calcium at first patient hospital evaluation and during hospitalization.

Radiological Thoracic Vertebral Fractures are Highly Prevalent in COVID-19 and Predict Disease Outcomes.

CONTEXT AND OBJECTIVE: COVID-19 has become the most relevant medical issue globally. Despite several studies that have investigated clinical characteristics of COVID-19 patients, no data have been reported on the prevalence of vertebral fractures (VFs). Since VFs may influence cardiorespiratory function and disease outcomes, the aim of this study was to assess VFs prevalence and clinical impact in COVID-19. DESIGN AND PATIENTS: This was a retrospective cohort study performed at San Raffaele Hospital, a tertiary health care hospital in Italy. We included COVID-19 patients for whom lateral chest x-rays at emergency department were available. VFs were detected using a semiquantitative evaluation of vertebral shape on chest x-rays. RESULTS: A total of 114 patients were included in this study and thoracic VFs were detected in 41 patients (36%). Patients with VFs were older and more frequently affected by hypertension and coronary artery disease (P < 0.001, P = 0.007, P = 0.034; respectively). Thirty-six (88%) patients in VFs+ group compared to 54 (74%) in VFs- group were hospitalized (P = 0.08). Patients with VFs more frequently required noninvasive mechanical ventilation compared with those without VFs (P = 0.02). Mortality was 22% in VFs+ group and 10% in VFs- group (P = 0.07). In particular, mortality was higher in patients with severe VFs compared with those with moderate and mild VFs (P = 0.04). CONCLUSIONS: VFs may integrate the cardiorespiratory risk of COVID-19 patients, being a useful and easy to measure clinical marker of fragility and poor prognosis. We suggest that morphometric thoracic vertebral evaluation should be performed in all suspected COVID-19 patients undergoing chest x-rays.

Hyperprolactinemia and bone.

Prolactin (PRL) has direct and indirect effects on bone metabolism. Experimental studies showed that in the presence of high PRL levels bone resorption was increased as well as bone formation was suppressed. Increased PRL levels in humans caused a reduction in sex hormone levels which turn may have detrimental effects on bone. Patients with hyperprolactinemia did have often decreased bone mineral density as well as an increased risk of fractures. Since PRL control may be relevant to bone health it is a clinical open issue the inclusion of skeletal health in future guidelines as indication to proactive screening, prevention and treatment particularly in high risk patients such as hyperprolactinemic women after menopause and patients with drug induced hyperprolactinemia.

Skeletal fragility: an emerging complication of Ehlers-Danlos syndrome.

Ehlers-Danlos syndrome (EDS) is an emerging cause of skeletal fragility. Mechanism of bone damage are probably multifactorial in line with the different skeletal phenotypes that can be found in clinical practice. A structured approach to clinical management of bone metabolic complication in EDS is proposed.

High Prevalence of Radiological Vertebral Fractures in Patients With TSH-Secreting Pituitary Adenoma.

BACKGROUND: Bone loss and high risk of fractures have been reported in patients with primary hyperthyroidism, whereas data on skeletal health in TSH-secreting adenoma (TSH-oma) are scant, and the risk of fractures in this specific clinical context has not been investigated so far. In this cross-sectional study, we aimed at evaluating for the first time, to our knowledge, the prevalence and determinants of radiological vertebral fractures (VFs) in patients with TSH-oma. METHODS: Twenty-two patients (10 males, 12 females; median age 47 years) with TSH-oma and 44 patients (20 males, 24 females; median age 49 years) with nonfunctioning pituitary adenoma (NFPA) were retrospectively evaluated for thoracic VFs using a morphometric approach on lateral chest X-ray routinely performed in the presurgical diagnostic workup. RESULTS: The prevalence of VFs was significantly higher in TSH-oma vs NFPA (59.1% vs 22.7%; P = 0.003), the difference being still significant (odds ratio, 10.5; P = 0.005) after correction for the size of pituitary adenomas and biochemical parameters. In TSH-oma, the prevalence of VFs was significantly associated with older age (P = 0.007) and higher serum free T4 values (P = 0.02). In 20 patients, data on presurgical medical therapies of TSH-oma were available. All patients not treated with somatostatin receptor ligands were fractured compared with 25% of those who were treated with these drugs (P = 0.001). No significant (P = 0.25) association between VFs and treatment with methimazole was found. CONCLUSIONS: This study provides the first evidence, to our knowledge, that patients with TSH-oma may develop VFs in close relationship with severity of hyperthyroidism.

Growth hormone deficiency in treated acromegaly and active Cushing's syndrome.

Growth hormone deficiency (GHD) in adults is characterized by reduced quality of life and physical fitness, skeletal fragility, increased weight and cardiovascular risk. It may be found in (over-) treated acromegaly as well as in active Cushing's syndrome. Hypopituitarism may develop in patients after definitive treatment of acromegaly, although the exact prevalence of GHD in this population is still uncertain because of limited awareness, and scarce and conflicting data so far available. Because GHD associated with acromegaly and Cushing's syndrome may yield adverse consequences on similar target systems, the final outcomes of some complications of both acromegaly and Cushing's syndrome may be further affected by the occurrence of GHD. It is still largely unknown, however, whether GHD in patients with post-acromegaly or active Cushing's syndrome (e.g. pharmacologic glucocorticoid treatment) may benefit from GH replacement. We review the diagnostic, clinical and therapeutic aspects of GHD in adults treated for acromegaly and in those with active Cushing's syndrome.

Incidence of morphometric vertebral fractures in adult patients with growth hormone deficiency.

Cross-sectional studies showed an elevated prevalence of clinical and morphometric vertebral fractures (VFs) in adult patients with growth hormone deficiency (GHD). However, no data are available on incidence and determinants of radiological VFs in this clinical setting. In this prospective study, we investigated the incidence and risk factors of radiological VFs in adults with GHD. Forty patients with GHD (28 males, 12 females; median age 44 years, range 19-82) were studied for incident VFs using quantitative morphometric approach on spine X-ray at baseline and after 6 years of follow-up. GHD patients were also studied for bone mineral density (BMD) measured by DXA at lumbar spine. After 6 years of follow-up, 12 patients (30 %) experienced incident VFs. Patients with incident VFs had more frequently untreated GHD and prevalent VFs at baseline, as compared to patients who did not experience incident VFs. Untreated GHD patients were significantly older as compared to treated GHD (50 years, range 19-82 vs. 36 years, range 19-75; p = 0.003), but the correlation between high risk of VFs and untreated GHD remained significant even after adjustment for the age of patients (odds ratio 6.8, CI 95 % 1.1-41.8; p = 0.037). In GHD patients experiencing incident VFs, lumbar spine BMD decreased significantly whereas it did not change in patients not developing VFs. This is the first prospective study confirming the hypothesis suggested by cross-sectional studies that untreated GHD may cause high risk of VFs in adult patients and that recombinant human GH treatment may effectively decrease such a risk.

Growth hormone deficiency in treated acromegaly.

Growth hormone deficiency (GHD) of the adult is characterized by reduced quality of life (QoL) and physical fitness, skeletal fragility, and increased weight and cardiovascular risk. Hypopituitarism may develop in patients after definitive treatment of acromegaly, but an exact prevalence of GHD in this population is still uncertain owing to limited awareness and the scarce and conflicting data available on this topic. Because acromegaly and GHD may yield adverse consequences on similar target systems, the final outcomes of some complications of acromegaly may be further affected by the occurrence of GHD. However, it is still largely unknown whether patients with post-acromegaly GHD may benefit from GH replacement. We review the diagnostic, clinical, and therapeutic aspects of GHD in adult patients treated for acromegaly.

Influence of diabetes mellitus on vertebral fractures in men with acromegaly.

Acromegaly is frequently complicated by fragility vertebral fractures and diabetes mellitus. Since type 2 diabetes mellitus is a cause of secondary osteoporosis in the general population, in this cross-sectional study we aimed at investigating the association between diabetes mellitus and vertebral fractures in males with acromegaly. Fifty-seven patients (median age 47 years, range: 24-85) with active (21 cases) and controlled (36 cases) acromegaly and 57 control subjects were evaluated for bone mineral density (BMD) by DXA and vertebral fractures by a quantitative morphometric analysis. Diabetes mellitus was found in 18 patients and 18 control subjects. The prevalence of vertebral fractures was higher in acromegalic patients as compared with the control subjects (50.9 vs. 10.5%; χ(2): 21.8; P < 0.001). Acromegalic patients with fractures had serum IGF-I values significantly higher (P = 0.009), longer duration of active disease (P < 0.001) and higher prevalence of active acromegaly (P = 0.007) and diabetes mellitus (P = 0.04) as compared to patients who did not fracture. When acromegaly was active, the prevalence of vertebral fractures was high independently of the coexistent diabetes mellitus. On the contrary, when acromegaly was controlled the prevalence of vertebral fractures was significantly higher in patients with diabetes as compared to patients without diabetes (62.6 vs. 28.0%; P = 0.04). In both diabetic and non diabetic patients, vertebral fractures occurred independently of BMD. In conclusion, this study suggests that diabetes mellitus may be associated with an increased prevalence of vertebral fractures in males with acromegaly. However, this effect seems to be relatively attenuated in the presence of persistent GH hypersecretion.

High prevalence of radiological vertebral fractures in women with prolactin-secreting pituitary adenomas.

Hyperprolactinemia may cause bone loss but data on fractures are scanty. The aim of this study was to evaluate the prevalence of vertebral fractures in women with prolactin (PRL)-secreting adenoma. In this cross-sectional study, 78 women (median age 45.5 years, range: 20-81) with PRL-secreting pituitary adenoma (66 with microadenoma and 12 with macroadenoma) and 156 control subjects, with normal PRL values and with comparable age to patients with hyperprolactinemia, were evaluated for vertebral fractures by a morphometric approach and for bone mineral density (BMD) by a dual-energy X-ray absorptiometry at lumbar spine. Vertebral fractures were shown in 25 patients with PRL-secreting adenoma (32.6%) and in 20 controls (12.8%, P < 0.001). Fractured patients were significantly older (P < 0.001) and had lower BMD T-score (P < 0.001), longer duration of disease (P < 0.001), higher serum PRL (P = 0.004) and lower serum IGF-I (P < 0.001) values as compared to patients who did not fracture. The prevalence of vertebral fractures was significantly (P < 0.001) higher in post-menopausal women with PRL-secreting adenoma as compared to pre-menopausal patients. Fractures occurred more frequently (P = 0.01) in patients with untreated hyperprolactinemia versus patients treated with cabergoline. Logistic regression analysis demonstrated that duration of disease maintained a significant correlation with vertebral fractures (odds ratio 1.16, C.I. 95% 1.02-1.33) even after correction for age, menopausal status, treatment with cabergoline, BMD, serum IGF-I and serum PRL values. Hyperprolactinemia is associated with high prevalence of radiological vertebral fractures in women with PRL-secreting adenoma.

Vertebral fractures in males with type 2 diabetes treated with rosiglitazone.

OBJECTIVE: To investigate the relationship between osteoporotic vertebral fractures and rosiglitazone treatment and the influence on this association of bone mineral density (BMD) and duration of diabetes. RESEARCH DESIGN AND METHODS: In this cross-sectional study, we evaluated BMD by DXA and the prevalence of radiological vertebral fractures identified by a quantitative morphometric analysis in 43 males with type 2 diabetes under metformin alone (22 cases) or associated with rosiglitazone (21 cases) and in 22 control non-diabetic subjects attending an out-patient bone clinic. RESULTS: Vertebral fractures were found in 46.5% of diabetic males (p=0.06 vs. control subjects) with higher prevalence in patients treated with rosiglitazone plus metformin as compared with those under treatment with metformin alone (66.7% vs. 27.3%; p=0.01). The patients on rosiglitazone plus metformin were significantly younger and with greater body mass index (BMI). Multivariate logistic regression analysis demonstrated that rosiglitazone plus metformin treatment maintained the significant correlation with the occurrence of vertebral fractures (odds ratio 6.5, C.I. 1.3-38.1, p=0.03) even after correction for age and BMI. Within the rosiglitazone-exposed group, the occurrence of vertebral fractures was not correlated with BMD, age, duration of diabetes, duration of medical treatment, dose of rosiglitazone, serum glycosylated hemoglobin and total testosterone values. CONCLUSIONS: The use of rosiglitazone is associated with an increased prevalence of vertebral fractures in males with type 2 diabetes. These findings call for a wide screening of bone status in diabetic patients treated with rosiglitazone and the use of spine X-ray in combination with DXA in this assessment.

Neuroendocrine tumors secreting growth hormone-releasing hormone: Pathophysiological and clinical aspects.

Hypothalamic GHRH is secreted into the portal system, binds to specific surface receptors of the somatotroph cell and elicits intracellular signals that modulate pituitary GH synthesis and/or secretion. Moreover, GHRH is synthesized and expressed in multiple extrapituitary tissues. Excessive peripheral production of GHRH by a tumor source would therefore be expected to cause somatotroph cell hyperstimulation, increased GH secretion and eventually pituitary acromegaly. Immunoreactive GHRH is present in several tumors, including carcinoid tumors, pancreatic cell tumors, small cell lung cancers, endometrial tumors, adrenal adenomas, and pheochromocytomas which have been reported to secrete GHRH. Acromegaly in these patients, however, is uncommon. The distinction of pituitary vs. extrapituitary acromegaly is extremely important in planning effective management. Regardless of the cause, GH and IGF-1 are invariably elevated and GH levels fail to suppress (<1 microg/l) after an oral glucose load in all forms of acromegaly. Dynamic pituitary tests are not helpful in distinguishing acromegalic patients with pituitary tumors from those harbouring extrapituitary tumors. Plasma GHRH levels are usually elevated in patients with peripheral GHRH-secreting tumors, and are normal or low in patients with pituitary acromegaly. Unique and unexpected clinical features in an acromegalic patient, including respiratory wheezing or dyspnea, facial flushing, peptic ulcers, or renal stones sometimes are helpful in alerting the physician to diagnosing non pituitary endocrine tumors. If no facility to measure plasma GHRH is available, and in the absence of MRI evidence of pituitary adenoma, a CT scan of the thorax and abdominal ultrasound could be performed to exclude with good approximation the possibility of an ectopic GHRH syndrome. Surgical resection of the tumor secreting ectopic GHRH should be the logical approach to a patient with ectopic GHRH syndrome. Standard chemotherapy directed at GHRH-producing carcinoid tumors is generally unsuccessful in controlling the activated GH axis. Somatostatin analogs provide an effective option for medical management of carcinoid patients, especially those with recurrent disease. In fact, long-acting somatostatin analogs may be able to control not only the ectopic hormonal secretion syndrome, but also, in some instances, tumor growth. Therefore, although cytotoxic chemotherapy, pituitary surgery, or irradiation still remain available therapeutic options, long-acting somatostatin analogs are now preferred as a second-line therapy in patients with carcinoid tumors and ectopic GHRH-syndrome.

Cardiac and metabolic effects of chronic growth hormone and insulin-like growth factor I excess in young adults with pituitary gigantism.

Chronic growth hormone (GH)/insulin-like growth factor I (IGF-I) excess is associated with considerable mortality in acromegaly, but no data are available in pituitary gigantism. The aim of the study was to evaluate the long-term effects of early exposure to GH and IGF-I excess on cardiovascular and metabolic parameters in adult patients with pituitary gigantism. Six adult male patients with newly diagnosed gigantism due to GH secreting pituitary adenoma were studied and compared with 6 age- and sex-matched patients with acromegaly and 10 healthy subjects. Morphologic and functional cardiac parameters were evaluated by Doppler echocardiography. Glucose metabolism was assessed by evaluating glucose tolerance and homeostasis model assessment index. Disease duration was significantly longer (P<.05) in patients with gigantism than in patients with acromegaly, whereas GH and IGF-I concentrations were comparable. Left ventricular mass was increased both in patients with gigantism and in patients with acromegaly, as compared with controls. Left ventricular hypertrophy was detected in 2 of 6 of both patients with gigantism and patients with acromegaly, and isolated intraventricular septum thickening in 1 patient with gigantism. Inadequate diastolic filling (ratio between early and late transmitral flow velocity<1) was detected in 2 of 6 patients with gigantism and 1 of 6 patients with acromegaly. Impaired glucose metabolism occurrence was higher in patients with acromegaly (66%) compared with patients with gigantism (16%). Concentrations of IGF-I were significantly (P<.05) higher in patients with gigantism who have cardiac abnormalities than in those without cardiac abnormalities. In conclusion, our data suggest that GH/IGF-I excess in young adult patients is associated with morphologic and functional cardiac abnormalities that are similar in patients with gigantism and in patients with acromegaly, whereas occurrence of impaired glucose metabolism appears to be higher in patients with acromegaly, although patients with gigantism are exposed to GH excess for a longer period.