Growth hormone nadir during oral glucose load depends on waist circumference, gender and age: normative data in 231 healthy subjects.

Objective  (i) To analyse the predictors of GH suppression after standard glucose load (oGTT) in the healthy population and (ii) to establish the 97th percentile of GH nadir post-oGTT according to these variables. Design  Analytical, retrospective. Measurements  GH nadir after oGTT. Subjects  Two hundred and thirty-one healthy subjects (113 women, 118 men 15-80 years) were studied. Results  The GH nadir after glucose load ranged from 0·01 (<assay detection limit) to 0·65 μg/l was higher in women and was inversely correlated with age, BMI, waist circumference, waist/hip, total cholesterol, triglycerides, basal and maximal glucose and basal insulin levels and directly correlated with basal GH levels, IGF-I SDS and HDL-cholesterol (P values ranging 0·004-<0·0001). On multistep regression analysis, the best predictors of nadir GH levels were waist circumference (t = -9·64, P < 0·0001), gender (t = -3·86, P = 0·0001) and age (t = -3·63, P = 0·0003). The results of comparative analysis among subjects grouped according to these variable showed different results in GH nadir in premenopausal women with waist circumference ≤88 cm (97th percentile 0·65 μg/l), in premenopausal women with waist circumference ≤88 cm and in men of any age with waist circumference ≤102 cm (97th percentile 0·33 μg/l) and in subjects of either gender and any age with waist circumference >88 cm in women and 102 cm in men (97th percentile 0·16 μg/l). Conclusions  The results of this study show that GH nadir after oGTT should be analysed according to gender, menopausal status and waist circumference. The GH cut-off should be limited to the assay used

Cushing, acromegaly, GH deficiency and tendons

Cushing’s syndrome, induced by an endogenous or exogenous cortisol excess, and acromegaly, the clinical syndrome caused by growth hormone (GH) excess in adulthood, as well as the disease induced by GH deficiency (GHD), represent perfect models for the evaluation of the effects induced by chronic exposure in vivo, respectively, to cortisol and GH/IGF-1 excess or deficiency on the complex structure of the tendons as well as on the related post-traumatic repair mechanism. Although the literature is still scant, here in main scientific evidence on this topic is summarized in order to provide suggestions about the management of the above mentioned illnesses, to translate such information in the field of sports medicine and/or traumatology, and to increase and to disseminate knowledge on this misunderstood theme

Effects of initial therapy for five years with somatostatin analogs foracromegaly on growth hormone and insulin-like growth factor-I levels, tumorshrinkage, and cardiovascular disease: a prospective study.

OBJECTIVE: The objective of the study was to evaluate the efficacy of 5 yr of depot somatostatin analogs (SSAs) as first-line therapy in acromegaly. PATIENTS: Patients included 45 de novo patients (18 women and 27 men, aged 20-82 yr); 28 were treated with octreotide-long-acting release and 17 with lanreotide. RESULTS: GH was controlled in 100% and IGF-I levels in 97.8%, tumor shrinkage was 74.9 +/- 22.1 and 78.2+/-14.5%, in the octreotide-long-acting release and lanreotide groups, respectively. There was a significant improvement in the prevalence of hypertension (from 46.7 to 22.2%, P = 0.027), arrhythmias (from 17.8% to zero, P = 0.01), left ventricular hypertrophy (from 82.2 to 42.2%, P < 0.0001), diastolic dysfunction (from 60.0 to 15.6%, P < 0.0001), systolic dysfunction (from 40.0 to 4.4%, P < 0.0001), and hypertriglyceridemia (from 40.0 to 4.4%, P < 0.0001). The prevalence of impaired glucose tolerance (IGT; from 28.9 to 20.0%. P = 0.46) and diabetes mellitus (from 22.4 to 31.1%, P = 0.64) did not change. CONCLUSIONS: In patients with severe comorbidities and those who refuse surgery, 5 yr of exclusive SSA therapy induce successful control of GH and IGF-I; tumor shrinkage (by median 80%), and improvement of hypertension, cardiac performance; and dyslipidemia. No patient was withdrawn from treatment because of side effects, and glucose tolerance was stable. We suggest that first-line SSA treatment may be safely continued in patients with acromegaly, according to an individual patient's indications and preferences

Growth hormone, prolactin, and sexuality.

GH and PRL, although not considered as 'classical' sexual hormones, could play a role in the endocrine control of sexual function both in men and women. Physiologically, PRL seems to be involved in the central control of sexual behavior and activity, by modulating mainly the effects of dopaminergic and serotoninergic systems on sexual function. Indeed, circulating PRL levels increase after orgasm and may potentially play a role in the acute regulation of further sexual arousal following orgasm both in men and women. On the other hand, either short-term or long-term PRL increase can modulate central nervous system areas involved in the control of sexual function and, peripherally, can directly influence mechanisms of penile erection in men, and presently only as an hypothesis, mechanisms related to the sexual response of genitalia in women. Furthermore, chronic hyperprolactinemia is classically associated with hypogonadotropic hypogonadism and sexual dysfunction in both sexes. Successful treatment of chronic hyperprolactinemia generally restores normal sexual function both in men and women although this effect is not only related to relapse of gonadal function. Hypoprolactinemia is recently recognised as a possible risk factor of arteriogenic erectile dysfunction while a possible role on female sexual function is not known. The physiological role of GH on sexual function is not fully elucidated. GH is an important regulator of hypothalamuspituitary- gonadal axis and seems to participate in the regulation of the sexual response of genitalia in men, and potentially also in women. Sexual function in men and women with GH deficiency (GHD) and GH excess, particularly in acromegaly, is scantily studied and GH- or IGF-I-dependent effects are difficult to quantify. Nevertheless, a decrease of desire and arousability both in men and women, together with an impairment of erectile function in men, have been described both in patients with GHD and acromegaly, although it is not clear whether they are dependent directly on the hormone defect or excess or they are consequence of the hypogonadism or the different clinical complications or the physical disfigurement and psychological imbalance, which are associated with the diseases, and are potentially affecting sexual function. Data on beneficial effects of GH replacement therapy and specific surgical or pharmacological approach for acromegaly are far to be fully elucidated although restoring normal GH/IGF-I levels have been associated to improvement of sexual function

Acromegaly and the cardiovascular system

Acromegaly is characterized by an increased cardiovascular morbidity and mortality. In fact, growth hormone and insulin-like growth factor-I excess induces a specific cardiomyopathy. The heart is involved from the very early stages of the disease in which the hyperkinetic syndrome (high heart rate and increased systolic output) takes place. Frequently, if the disease is untreated for many years or unsuccessfully treated, concentric biventricular hypertrophy and diastolic dysfunction can develop and, at least, lead to diastolic congestive heart failure. Rhythm disturbances and valve dysfunction are also frequently described in acromegaly. The coexistence of other complications, such as diabetes and arterial hypertension, can induce the worsening of acromegalic cardiomyopathy. Control of acromegaly by surgery or pharmacotherapy could improve cardiovascular morbidity thanks to decreasing left ventricular mass and reducing cardiac dysfunction. In conclusion, an early diagnosis and a careful evaluation of cardiac function, morphology and activity seem to be mandatory in acromegaly

Medical consequences of acromegaly: what are the effects of biochemical control?

This chapter discusses the effects of biochemical control of acromegaly on cardiovascular diseases, metabolic complications, respiratory abnormalities, malignancies and bone alterations. Acromegaly is associated with increased morbidity and mortality for cardiovascular and respiratory complications, whereas neoplasms seem to be a minor cause of increased risk of death. Other associated diseases are osteoarthritis, carpal tunnel syndrome, fatigue, visual abnormalities and reproductive disorders. Acromegaly results in premature death because of prolonged elevation of GH an IGF-I levels, and a strong biochemical control improves well-being and restores life expectancy to normal. The main goals of medical treatment of acromegaly include normalization of biochemical markers of disease activity, improvement in signs and symptoms of the disease, removal or reduction of tumor mass and preservation of pituitary function

Glucose tolerance and somatostatin analog treatment in acromegaly: a 12-monthstudy.

OBJECTIVE: The objective of the study was to investigate the impact of first-line somatostatin analogs (SSAs) on glucose tolerance (GT) in acromegaly. DESIGN: The design was open and prospective. PATIENTS: One hundred twelve patients [63 with normal GT (56.2%), 24 with impaired GT (21.4%), and 25 with diabetes (22.3%)] were treated with depot SSAs for 12 months: 54 patients (48.2%) achieved mean fasting GH levels less than 2.5 microg/liter in presence of normal IGF-I levels (controlled) during SSA. PRIMARY OUTCOME MEASURES: Fasting glucose and glycosylated hemoglobin levels were measured. RESULTS: At study end, 57 patients had normal GT (50.1% vs. baseline; P = 0.55), 30 had impaired fasting glucose or impaired GT (26.8%, P =0.43) and 25 had diabetes (22.3%; P = 1.0). Twenty-eight patients (25.0%), modified their GT [11 improved (9.8%), 17 worsened (15.2%)]: 90% of the patients with GT improvement achieved control of acromegaly and 89% of those having GT worsening did not (P < 0.0001). The major predictors of GT changing were disease control (t = -4.99; P < 0.0001), baseline GT (t = -2.84; P = 0.0054), and GH levels (t = 2.70; P = 0.008). Fasting glucose levels were predicted by patients' age (t = 2.74; P = 0.0071) and IGF-I levels (t = 2.14; P = 0.035). Glycosylated hemoglobin levels were predicted by disease duration (t = 3.53; P = 0.0006), GH levels (t = 2.70; P = 0.0071), and IGF-I levels (t = 2.11; P = 0.037). CONCLUSIONS: This study showed a similar prevalence of deterioration and improvement of GT 12 months after first-line SSA treatment. Uncontrolled acromegaly during SSA treatment and abnormal GT at baseline were associated with GT worsening

The role of vitamin D in male fertility: A focus on the testis

In the last decade, vitamin D has emerged as a pleiotropic molecule with a multitude of autocrine, paracrine and endocrine functions, mediated by classical genomic as well as non-classical non-genomic actions, on multiple target organs and systems. The expression of vitamin D receptor and vitamin D metabolizing enzymes in male reproductive system, particularly in the testis, suggests the occurrence of vitamin D synthesis and regulation as well as function in the testis. The role of vitamin D in the modulation of testis functions, including hormone production and spermatogenesis, has been investigated in animals and humans. Experimental studies support a beneficial effect of vitamin D on male fertility, by modulating hormone production through genomic and non-genomic actions, and, particularly, by improving semen quality essentially through non-genomic actions. However, clinical studies in humans are controversial. Indeed, vitamin D seems to contribute to the modulation of the bioavailable rather than total testosterone. Moreover, although an increased prevalence or risk for testosterone deficiency was reported in men with vitamin D deficiency in observational studies, the majority of interventional studies demonstrated the lack of effect of vitamin D supplementation on circulating levels of testosterone. The most consistent effect of vitamin D was reported on semen quality. Indeed, vitamin D was shown to be positively associated to sperm motility, and to exert direct actions on spermatozoa, including non-genomic driven modulation of intracellular calcium homeostasis and activation of molecular pathways involved in sperm motility, capacitation and acrosome reaction. The current review provides a summary of current knowledge on the role of vitamin D in male fertility, by reporting clinical and experimental studies in humans and animals addressing the relationship between vitamin D and testis function