Leczenie farmakologiczne akromegalii

Acromegaly can be treated with several medical modalities. The growth hormone (GH) receptor antagonist pegvisomant, in particular, is able to reduce serum insulin-like growth factor I (IGF-I) concentrations to almost any desired level. Along with this important achievement come other practical issues. The most important is that IGF-I also has metabolic actions, especially the control of serum glucose concentrations. As somatostatin analogues and pegvisomant have their own intrinsic differential effects on serum GH levels and actions as well as on serum IGF-I levels and actions, it should not automatically be assumed that absolute concentrations of these parameters of disease activity reflect the same levels of action. In the ideal situation we should be able to develop treatment of specific target levels for both GH and IGF-I that might even be patient-specific as well. To date we have not moved as far as this, but awareness of treatment-specific differential effects might help us to understand some of the signs and symptoms that we encounter in acromegalic patients. (Pol J Endocrinol 2007; 58 (4): 361-363)W akromegalii możliwe są różne sposoby farmakoterapii. Antagonista receptora hormonu wzrostu (GH, growth hormone) - pegvisomant powoduje obniżenie stężenia insulinopodobnego czynnika wzrostu-I (IGF-I, insulin-like growth factor I) do oczekiwanych wartości. Następstwem tego efektu jest wiele praktycznych konsekwencji. Najważniejsze jest to, że działanie metaboliczne IGF-I odgrywa szczególną rolę w regulacji stężenia glukozy. Podobnie do analogów somatostatyny pegvisomant wykazuje własny wewnętrzny zróżnicowany wpływ na stężenia w surowicy oraz działania GH i IGF-I. Na tej podstawie nie można automatycznie zakładać, że stężenia tych wskaźników aktywności choroby odzwierciedlają taki sam poziom ich działania. W idealnej sytuacji powinna istnieć możliwość rozwoju specyficznej terapii celowanej, ukierunkowanej na poziomy zarówno GH i IGF-I, które mogłoby równocześnie być specyficzne dla pacjenta. Obecnie, nie dysponujemy jeszcze takimi osiągnięciami, ale realizacja typowych dla terapii zróżnicowanych efektów mogłaby pomóc nam zrozumieć niektóre objawy, które stwierdza się u chorych na akromegalię

Pregnancy and acromegaly

INTRODUCTION: Acromegaly is a rare disorder in which, due to the high incidence of secondary hypogonadism, pregnancies are relatively rare. However, some women with acromegaly do get pregnant, which brings along questions about medication, complications and follow-up. This review tries to address these issues and provide the reader with practical information. METHODS: This review summarizes published data. CONCLUSIONS: Acromegaly is a disorder that is characterized by changes in growth hormone (GH), insulin-like growth factor-1 (IGF-1) and insulin concentrations and actions. All these hormones are important in pregnancy as well. In principle, the fetal-placental collaboration between mother and child more-or-less takes over the control over GH and IGF-1, not only in normal physiology but also to a certain extend in acromegaly. When medication for the high GH levels or actions is continued during pregnancy, both dopamine agonists, somatostatin analogs and GH receptor antagonists have been used and the available data suggest that there are no adverse consequences on mother or fetus to date. However, it is strongly advised to stop any medical intervention during pregnancy until more data are available on the safety of these compounds. Also, medical treatment is not needed as tumor size and disease activity are not reported to escape

Pregnancy and acromegaly

Introduction: Acromegaly is a rare disorder in which, due to the high incidence of secondary hypogonadism, pregnancies are relatively rare. However, some women with acromegaly do get pregnant, which brings along questions about medication, complications and follow-up. This review tries to address these issues and provide the reader with practical information. Methods: This review summarizes published data. Conclusions: Acromegaly is a disorder that is characterized by changes in growth hormone (GH), insulin-like growth factor-1 (IGF-1) and insulin concentrations and actions. All these hormones are important in pregnancy as well. In principle, the fetal-placental collaboration between mother and child more-or-less takes over the control over GH and IGF-1, not only in normal physiology but also to a certain extend in acromegaly. When medication for the high GH levels or actions is continued during pregnancy, both dopamine agonists, somatostatin analogs and GH receptor antagonists have been used and the available data suggest that there are no adverse consequences on mother or fetus to date. However, it is strongly advised to stop any medical intervention during pregnancy until more data are available on the safety of these compounds. Also, medical treatment is not needed as tumor size and disease activity are not reported to escape

Extrapancreatic insulin effect of glibenclamide

In eight patients with uncomplicated non insulin dependent diabetes mellitus, serum insulin levels, serum C-peptide levels and blood glucose levels were measured before and after oral administration of glibenclamide 0.1 mg/kg body weight and a test meal, or after a test meal alone. The rise in serum insulin levels persisted longer after glibenclamide. The initial rise in serum insulin was of the same magnitude in both situations, as was the rise in serum C-peptide levels during the entire 5 h study. It is concluded that glibenclamide is able to maintain a more protonged increase in serum insulin levels by inhibiting the degradation of insulin in the vascular endothelial cells of the liver. The inhibition contributes to the blood glucose lowering effect of glibenclamide

Pituitary adenomas, some diagnostic and therapeutical aspects

The treatment of almost all types of pituitary adenomas has changed considerably in recent years. New types of drugs as well as improved application forms of older drug therapies are now becoming more and more available for everyday treatment of patients with these relatively rare diseases. For the most frequently occurring pituitary adenomas the drugs of first choice are described, as well as other available treatments, their indications and efficacies. Also the main side-effects are described

The endocrinology of aging

Most aging individuals die from atherosclerosis, cancer, or dementia; but in the oldest old, loss of muscle strength resulting in frailty is the limiting factor for an individual's chances of living an independent life until death. Three hormonal systems show decreasing circulating hormone concentrations during normal aging: (i) estrogen (in menopause) and testosterone (in andropause), (ii) dehydroepiandrosterone and its sulphate (in adrenopause), and (iii) the growth hormone/insulin-like growth factor I axis (in somatopause). Physical changes during aging have been considered physiologic, but there is evidence that some of these changes are related to this decline in hormonal activity. Hormone replacement strategies have been developed, but many of their aspects remain controversial, and increasing blood hormone levels in aging individuals to those found during mid-adult life has not been uniformly proven to be safe and of benefit.</jats:p

Combined treatment of somatostatin analogues with pegvisomant in acromegaly

Treatment of acromegaly with monotherapy long-acting somatostatin analogues (LA-SSA) as primary treatment or after neurosurgery can only achieve complete normalization of insulin-like growth factor I (IGF-I) in roughly 40 % of patients. Recently, one of the acromegaly consensus groups has recommended switching to combined treatment of LA-SSA and pegvisomant (PEGV) in patients with partial response to LA-SSAs. This combination of LA-SSA and PEGV, a growth hormone receptor antagonist, can normalize IGF-I levels in virtually all patients, requiring that the adequate dose of PEGV is used. The required PEGV dose varies significantly between individual acromegaly patients. One of the advantages of the combination therapy is that tumor size control or even tumor shrinkage can be observed in a vast majority of patients. The main side effects of the combination treatment are gastrointestinal symptoms, lipohypertrophy and transient elevated liver transaminases. In this review we provide an overview of the efficacy and safety of the combined treatment of LA-SSAs with PEGV