Sociodemographic profile, health-related behaviours and experiences of healthcare access in Italian transgender and gender diverse adult population.

PURPOSE: Information on the general health of transgender and gender diverse (TGD) individuals continues to be lacking. To bridge this gap, the National Institute of Health in Italy together with the National Office against Racial Discriminations, clinical centres, and TGD organizations carried out a cross-sectional study to define the sociodemographic profile, health-related behaviours, and experiences of healthcare access in Italian TGD adult population. METHODS: A national survey was conducted by Computer-Assisted Web Interviewing (CAWI) technique. Collected data were compared within the TGD subgroups and between TGD people and the Italian general population (IGP). RESULTS: TGD respondents were 959: 65% assigned female at birth (AFAB) and 35% assigned male at birth (AMAB). 91.8% and 8.2% were binary and non-binary TGD respondents, respectively. More than 20% of the TGD population reported to be unemployed with the highest rate detectable in AMAB and non-binary people. Cigarette smoking and binge drinking were higher in the TGD population compared with IGP (p < 0.05), affecting TGD subgroups differently. A significant lower percentage of AFAB TGD people reported having had screening for cervical and breast cancer in comparison with AFAB IGP (p < 0.0001, in both cases). Over 40% was the percentage of AFAB and non-binary TGD people accessing healthcare who felt discriminated against because of their gender identity. CONCLUSIONS: Our results are a first step towards a better understanding of the health needs of TGD people in Italy in order to plan the best policy choices for a more inclusive public health.

Italian association of clinical endocrinologists (AME) position statement: drug therapy of osteoporosis.

Treatment of osteoporosis is aimed to prevent fragility fractures and to stabilize or increase bone mineral density. Several drugs with different efficacy and safety profiles are available. The long-term therapeutic strategy should be planned, and the initial treatment should be selected according to the individual site-specific fracture risk and the need to give the maximal protection when the fracture risk is highest (i.e. in the late life). The present consensus focused on the strategies for the treatment of postmenopausal osteoporosis taking into consideration all the drugs available for this purpose. A short revision of the literature about treatment of secondary osteoporosis due both to androgen deprivation therapy for prostate cancer and to aromatase inhibitors for breast cancer was also performed. Also premenopausal females and males with osteoporosis are frequently seen in endocrine settings. Finally particular attention was paid to the tailoring of treatment as well as to its duration.

Biochemical evaluation of patients with active acromegaly and type 2 diabetes mellitus: efficacy and safety of the galanin test.

The oral glucose tolerance test, which is considered the gold standard for the diagnosis of active acromegaly, should not be performed in the presence of basal hyperglycemia. Moreover, false-positive responses may occur in patients with diabetes mellitus. Galanin has previously been demonstrated to induce paradoxical inhibition of growth hormone (GH) secretion in most patients with active acromegaly. In this study, we assessed GH response to galanin infusion in a series of 17 consecutive patients with active acromegaly, 7 of whom had coexistent type 2 diabetes mellitus and 10 were without either diabetes mellitus or impaired tolerance to glucose. 6 acromegalic patients with diabetes mellitus (85.7%) and 7 without diabetes (70.0%) showed a decrease in serum GH values during galanin infusion (chi2 0.9; p = 0.6). The GH nadir occurred at a comparable time in the two groups of acromegalic patients. Moreover, the two groups showed no significant difference (p = 0.45) in DeltaGH during galanin infusion. Galanin infusion did not induce any significant change in plasma glucose levels in both diabetic and non-diabetic patients with acromegaly. The results of our study provide evidence that the galanin test may be of value for the diagnosis of acromegaly in patients with type 2 diabetes mellitus.

Growth hormone deficiency in the adult.

Growth hormone deficiency (GHD) in adults may be of either adult or childhood onset and may occur as isolated GHD or as multiple hormone deficiencies. Adult-onset GHD (AoGHD) usually results from damage to the pituitary gland or hypothalamus. GH is frequently undetectable in normal subjects and thus GHD cannot be distinguished from the normal state using a single random GH measurement. In general, a stimulation test is required to recognize GHD. Insulin tolerance test (ITT) has been considered the gold standard by the most important scientific societies, although alternative tests, in particular GHRH plus arginine have been proposed as valuable alternative to ITT. The clinical syndrome associated with AoGHD is characterized by a wide array of symptoms and important chronic complications, such as cardiovascular complications, which may be responsible for an increased mortality. The rationale for GH replacement in adults GHD patients is justified by the beneficial effects on some clinical end-points, such as quality of life (QoL) and cardiovascular risk factors, whereas the effects on mortality risk are still controversial. Over the recent years, guidelines on the use of rhGH as a substitution treatment in adult hypopituitarism have been issued by international (Growth hormone research society-GRS, Endocrine Society) and relevant national (National Institute of Clinical Excellence-UK, NICE) institutions. The aim of the paper is to review and discuss these guidelines.

Hyperinsulinemia in the physiologic range is not superior to short-term fasting in suppressing insulin secretion in obese men.

The negative-feedback control exerted by plasma insulin on beta-cell insulin release in normal-weight and obese subjects is still a matter of debate. Subjects submitted to a euglycemic insulin clamp undergo a suppression of insulin secretion that is due to both the infused insulin and the 2- to 3-hour fast during the procedure. We elected to elucidate the role of physiologic hyperinsulinemia per se in the insulin negative autofeedback in obese men. Ten men with massive uncomplicated obesity (age, 18 to 37 years; body mass index [BMI], 41 +/- 1.15 kg/m2) and 6 normal-weight healthy men (age, 22 to 30 years; BMI, 22 +/- 0.28 kg/m2) underwent 2 studies in random order: (1) a euglycemic-hyperinsulinemic glucose clamp with an insulin infusion rate of 1 mU/kg/min and (2) a control study with saline infusion. Serum C-peptide concentrations were significantly higher in obese versus control subjects at baseline (2.54 +/- 0.178 v 1.63 +/- 0.256 ng/mL, P < .05). Exogenous insulin infusion significantly suppressed serum C-peptide at steady state ([SS] last 30 minutes of insulin or saline infusion) in controls (mean of the last 4 measurements from 120 minutes to 150 minutes, 0.86 +/- 0.306 ng/mL, P < .05 vbaseline) but not in obese patients (2.03 +/- 0.26 ng/mL, nonsignificant [NS] v baseline). During the saline infusion studies, C-peptide levels slightly and similarly declined over time in both groups (2.71 +/- 0.350 at baseline v 2.31 +/- 0.300 ng/mL at SS in obese patients, NS, and 1.96 +/- 0.189 v 1.62 +/- 0.150 ng/mL in controls, NS). This study shows that in obese men hyperinsulinemia within the postprandial range is not superior to a 2.5-hour fast for the suppression of beta-cell activity, suggesting an impairment of the insulin negative autofeedback in this clinical condition.

[Growth hormone secretion in heart failure]. / La secrezione dell'ormone della creascita nello scompenso cardiaco.

Growth hormone is a pituitary polypeptide hormone regulating growth in paediatric age as well as inducing anabolic actions directly or IGF-I mediated in adult age. Particularly, in many animals GH and IGF-I receptors were observed in cardiac myocyte membrane. GH modifies left ventricle structure and function. As concerns spontaneous GH secretion, some data suggest that pituitary gland can have a compensatory role on endocrine response to heart failure. Heart failure stage was directly correlated to nocturnal GH levels. All GH spontaneous night secretion parameters as well as IGF-I levels showed a range between normal people and very high spontaneous secretion. Therefore in these patients there are either a GH peripheric resistance or a reduction of the activity of GH/IGF-I axis. Anyhow in our patients, GH 24 hour infusion was inducing a 5 fold increase in GH concentration and a 50% increase in basal IGF-I levels. Anker et al. suggested to evaluate nutritional state in heart failure patients, observing no differences in non-cachectic patients vs controls, while cachectic patients presented a typical GH resistance syndrome. Interestingly, cardiovascular effects of GH administration seem to be only marginally correlated to hemodynamic basal state. On the other hand basal hormonal setting of the patient seems to correlate to the GH-induced cardiovascular response. In fact, low basal IGF-I but high basal GH patients presented the worst endocrine and cardiovascular response to GH infusion. In literature there are controversial data about GH treatment in patients with chronic heart failure. The heterogeneity of the population could be the reason for this discrepancy. Besides very different IGF-I responses to GH have been reported. Therefore, as there is good clinical evidence that GH acute infusion can improve heart failure, it seems to be necessary firstly to evaluate the basal endocrine status of the patients. Particularly attention should be given to those patients that present a peripheric GH resistance. On the other hand, those patients with a reduced pituitary GH reserve are supposed to have very beneficial effects from GH treatment.

Prevention and treatment of glucocorticoid-induced osteoporosis.

Glucocorticoid-induced osteoporosis (GIO) is the most common form of secondary osteoporosis with fractures occurring in as many as 30-50% of patients receiving chronic glucocorticoid therapy. Calcium and vitamin D are important measures in the primary prevention of GIO. However, vitamin D and calcium alone do not allow to prevent fractures. Estrogens and androgens should be used in patients with documented hypogonadism. Bisphosphonates are the most effective of the various therapies that have been assessed for the management of GIO. These drugs need to be started early in order to correct the increase in bone resorption occurring in the first weeks of glucocorticoid treatment. Anabolic therapeutic strategies are under investigation. Teriparatide seems to be also efficacious for the treatment of patients with GIO.

Resistance to somatostatin analogs in acromegaly: an evolving concept?

The aim of acromegaly treatment is to control the disease by suppressing GH hyperactivity and reducing the size or impeding the growth of the pituitary GH secreting mass. Over recent years, many studies have emphasized the role of SS analogs in the treatment of acromegaly. In fact, SS analogs have been demonstrated to be an effective tool not only in the control of GH hypersecretion but also more recently in the control of tumor growth, in a relevant number of acromegalic patients both as primary or adjunctive treatment. In this context, the therapeutic failure of medical treatment with SS analogs needs to be accurately defined particularly when they are used as primary treatment but also when they are given to patients previously operated upon, since other effective therapeutic options are nowadays available. Current definition of resistance to SS analogs is based on their efficacy to control GH and IGF-I. However, due to the emerging significance of the shrinkage effect of SS analogs on pituitary adenomas as well as to the apparent dissociation between this effect and the biochemical effects of treatment with these analogs, an evolution in the concept of SS resistance is likely to be occurring. In this review, we will discuss the biological basis of the discordance between biochemical and volumetric effects of SS analogs, and we will address the intriguing clinical and therapeutic aspects related to a possible redefinition of the resistance to SS analogs.

Diagnosis and treatment of acromegaly and its complications: consensus guidelines.

In February 1999, May 2000 and April 2002, three workshops were held in Cortina, Montecarlo and Versailles, respectively, to develop a consensus defining the diagnosis and treatment of acromegaly and its complications. The workshops were sponsored by the Pituitary Society and European Neuroendocrine Association. Invited international participants included endocrinologists, neurosurgeons and radiotherapists skilled in the management of acromegaly. This review paper summarizes the main points of the three consensus statements published following these three workshops.

Cardiovascular risk in aging and obesity: is there a role for GH.

GH has significant impact in adults. In fact, patients with the GH deficiency (GHD) syndrome are now recognized as having an increased cardiovascular risk. The effects of human aging on GH secretion have been evaluated by a number of researchers. Studies of 24 h secretion of GH have shown variable reductions in most 24-h GH secretory parameters in middle-aged and in older men and women, resulting in a decrease in plasma levels of its anabolic mediator IGF-I. Obesity is also associated with several endocrine and metabolic abnormalities. These include decreased serum GH concentrations, reduced GH half-life, frequency of GH secretory episodes and daily GH production rate. The mechanism of the low GH in obesity is not completely understood nor is it clear whether its relationship with visceral adiposity is causal. The aim of this article will be to review the available clinical data concerning the potential involvement of "subclinical" or perhaps better "functional" GHD, which is observed in aging and obesity, in the increase in cardiovascular risk which characterizes these two conditions.

GH deficiency in the adult and bone.

GH acts on various tissues and organs, like liver, kidney, bone and muscle. There are no conclusive data on adult onset GH deficiency (GHD) effects on bone remodeling. In fact reduced, increased or unchanged values of serum markers of bone formation and resorption have been described. However, a direct link between GHD and reduced bone mass in hypopituitarism is supported by reports that GH replacement therapy can improve bone mineral density (BMD) in these patients. Recently, many studies have shown an increased prevalence of osteoporosis in adult-onset GHD patients, and the fracture rate in these subjects seems to be twice that in the non-GH-deficient population. Long-term studies in these years have described a BMD increase in GHD patients during treatment with GH alone or in combination with biphosphonates. To understand if these BMD changes may result in a reduction of fracture risk, it is necessary to carry out a longitudinal follow-up of large cohorts of GHD adults on GH replacement therapy.

Diagnostic and therapeutic consensus on acromegaly.

In February 1999 and May 2000, two workshops were held in Cortina, Italy and Montecarlo, respectively, to develop a consensus defining the diagnosis and treatment of acromegaly. The workshops were sponsored by the Italian Society of Endocrinology, the Pituitary Society and European Neuroendocrine Association. Partecipants from all over the world included endocrinologists, neurosurgeons and radiotherapists skilled in the management of acromegaly. This review paper summarizes the main points of the two consensus statements published following these two workshops.

Ectopic secretion of growth hormone-releasing hormone (GHRH) in neuroendocrine tumors: relevant clinical aspects.

The aim of this article is to briefly review the physiology of growth hormone-releasing hormone (GHRH) and the diagnosis and treatment of GHRH-mediated acromegaly. Moreover, the role of GHRH and its antagonists in the pathogenesis and treatment of cancer will be reviewed. 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. GHRH-producing neurons have been well characterized in the hypothalamus by immunostaining techniques. Hypothalamic tumors, including hamartomas. choristomas, gliomas. and gangliocitomas. may produce excessive GHRH with subsequent GH hypersecretion and resultant acromegaly. 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 and increased GH secretion. The structure of hypothalamic GHRH was infact elucidated from material extracted from pancreatic GHRH-secreting tumors in two patients with acromegaly. Immunoreactive GHRH is present in several tumors, including carcinoid tumors, pancreatic cell tumors, small-cell lung cancers, adrenal adenomas, and pheochromocitomas which have been reported to secrete GHRH. Acromegaly in these patients. however, is uncommon. In a retrospective survey of 177 acromegalic patients only a single patient was identified with elevated plasma GHRH levels. Measuring GHRH plasma levels therefore provides a precise and cost-effective test for the diagnosis of ectopic acromegaly. Peripheral GHRH levels are not elevated in patients with hypothalamic GHRH- secreting tumors, supporting the notion that excess eutopic hypothalamic GHRH secretion into the hypophyseal portal system does not appreciably enter the systemic circulation. Elevated circulating GHRH levels, a normal or small-size pituitary gland, or clinical and biochemical features of other tumors known to be associated with extrapituitary acromegaly, are all indications for extrapituitary imaging. An enlarged pituitary is, however, often found on MRI of patients with peripheral GHRH-secreting tumors, and the radiologic diagnosis of a pituitary adenoma may be difficult to exclude. Surgical resection of the tumor secreting ectopic GHRH should reverse the hypersecretion of GH, and pituitary surgery should not be necessary in these patients. Nonresectable, disseminated or reccurrent carcinoid syndrome with ectopic GHRH secretion can also be managed medically with long-acting somatostatin analogs (octreotide and lanreotide). The presence of GHRH and its receptors in several extrahypothalamic tissues, including ovary, testis and the digestive tract, suggests that GHRH may have a regulatory role in these tissues. As previously mentioned, biologically or immunologically active GHRH and mRNA encoding GHRH have been found in several human malignant tumors. including cancers of the breast, endometrium and ovary and their cell lines. The synthesis and evaluation of analogs with various modifications revealed that certain hydrophobic and helix-stabilizing amino acid substitutions can produce antagonists with increased GH releasing inhibitory potencies and GHRH receptor-binding affinities in vitro. The review of experimental results of these substances are promising altrough no clinical data are yet available. Finally, the advent of these antagonists has allowed significant progress in the understanding of the role of the central and tissue GHRH-GH-IGFs system in the pathogenesis of tumors.