Preserving bone health is an important goal of care of patients with acromegaly and growth hormone deficiency (GHD). Both disorders are associated with compromised bone health and an increased risk ...of fracture. However, parameters of bone health that are routinely used to predict fractures in other populations, such as aBMD measured by DXA, are unreliable for this in acromegaly and GHD. Additional methodologies need to be employed to assess bone health in these patients. This review summarizes available data on the effects of acromegaly and GHD on parameters of bone health such as aBMD, volumetric bone mineral density (vBMD) and microarchitecture assessed by HRpQCT and other techniques, trabecular bone score (TBS) and fracture assessment. More research is needed to identify reliable predictors of fracture risk and to determine how best to screen for and treat those patients at risk so that bone health is optimized in these patients.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Growth hormone (GH) and insulin-like growth factor 1 (IGF-1) are essential to normal growth, metabolism, and body composition, but in acromegaly, excesses of these hormones strikingly alter them. In ...recent years, the use of modern methodologies to assess body composition in patients with acromegaly has revealed novel aspects of the acromegaly phenotype. In particular, acromegaly presents a unique pattern of body composition changes in the setting of insulin resistance that we propose herein to be considered an acromegaly-specific lipodystrophy. The lipodystrophy, initiated by a distinctive GH-driven adipose tissue dysregulation, features insulin resistance in the setting of reduced visceral adipose tissue (VAT) mass and intra-hepatic lipid (IHL) but with lipid redistribution, resulting in ectopic lipid deposition in muscle. With recovery of the lipodystrophy, adipose tissue mass, especially that of VAT and IHL, rises, but insulin resistance is lessened. Abnormalities of adipose tissue adipokines may play a role in the disordered adipose tissue metabolism and insulin resistance of the lipodystrophy. The orexigenic hormone ghrelin and peptide Agouti-related peptide may also be affected by active acromegaly as well as variably by acromegaly therapies, which may contribute to the lipodystrophy. Understanding the pathophysiology of the lipodystrophy and how acromegaly therapies differentially reverse its features may be important to optimizing the long-term outcome for patients with this disease. This perspective describes evidence in support of this acromegaly lipodystrophy model and its relevance to acromegaly pathophysiology and the treatment of patients with acromegaly.
Bone health is often impaired in patients with hormone-secreting pituitary tumors. Since medical therapy is central to their care, understanding how its use impacts on this is highly ...important.PURPOSEBone health is often impaired in patients with hormone-secreting pituitary tumors. Since medical therapy is central to their care, understanding how its use impacts on this is highly important.This review summarizes a systemmatic review of the literature on the effects of medical therapies for hormone-secreting pituitary tumors on bone.METHODSThis review summarizes a systemmatic review of the literature on the effects of medical therapies for hormone-secreting pituitary tumors on bone.In acromegaly, medical therapy lowers bone turnover marker (BTM) levels, consistent with correction of the high bone turnover of active disease, and overall, areal bone mineral density (aBMD) does not change or increases. Somatostatin-receptor ligand (SRL) and pegvisomant-treated acromegaly patients have persistently reduced volumetric BMD and microarchitectural abnormalities of the peripheral skeleton, deficits that are similar to those in surgically-treated patients. Fracture risk remains elevated in medically-treated acromegaly patients but in conjunction with biochemical control the risk is lessened. Treatment of prolactin-secreting tumors with dopamine agonists is associated with improvements in aBMD, but this does not always fully normalize despite effective medical treatment of the prolactinoma. In one cross-sectional study, prolactinoma patients had lower total volumetric BMD and impaired microarchitecture suggesting that bone microstructure does not fully normalize despite dopamine agonist therapy. Cross-sectional studies show a high rate of VF in patients with prolactin-secreting tumors that is lowered on cabergoline therapy, but still the fracture rate of men and postmenopausal women is higher than that of controls in some studies. Studies on the effects of modern-day medical therapy for Cushing's disease on bone are lacking.RESULTSIn acromegaly, medical therapy lowers bone turnover marker (BTM) levels, consistent with correction of the high bone turnover of active disease, and overall, areal bone mineral density (aBMD) does not change or increases. Somatostatin-receptor ligand (SRL) and pegvisomant-treated acromegaly patients have persistently reduced volumetric BMD and microarchitectural abnormalities of the peripheral skeleton, deficits that are similar to those in surgically-treated patients. Fracture risk remains elevated in medically-treated acromegaly patients but in conjunction with biochemical control the risk is lessened. Treatment of prolactin-secreting tumors with dopamine agonists is associated with improvements in aBMD, but this does not always fully normalize despite effective medical treatment of the prolactinoma. In one cross-sectional study, prolactinoma patients had lower total volumetric BMD and impaired microarchitecture suggesting that bone microstructure does not fully normalize despite dopamine agonist therapy. Cross-sectional studies show a high rate of VF in patients with prolactin-secreting tumors that is lowered on cabergoline therapy, but still the fracture rate of men and postmenopausal women is higher than that of controls in some studies. Studies on the effects of modern-day medical therapy for Cushing's disease on bone are lacking.More research is needed on the effectsof medical therapies for hormone secreting pituitary tumors on bone health.CONCLUSIONMore research is needed on the effectsof medical therapies for hormone secreting pituitary tumors on bone health.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Practice guidelines for the endocrine evaluation and treatment of pituitary incidentalomas are presented, including indications for surgery.
Objective:
The aim was to formulate practice guidelines ...for endocrine evaluation and treatment of pituitary incidentalomas.
Consensus Process:
Consensus was guided by systematic reviews of evidence and discussions through a series of conference calls and e-mails and one in-person meeting.
Conclusions:
We recommend that patients with a pituitary incidentaloma undergo a complete history and physical examination, laboratory evaluations screening for hormone hypersecretion and for hypopituitarism, and a visual field examination if the lesion abuts the optic nerves or chiasm. We recommend that patients with incidentalomas not meeting criteria for surgical removal be followed with clinical assessments, neuroimaging (magnetic resonance imaging at 6 months for macroincidentalomas, 1 yr for a microincidentaloma, and thereafter progressively less frequently if unchanged in size), visual field examinations for incidentalomas that abut or compress the optic nerve and chiasm (6 months and yearly), and endocrine testing for macroincidentalomas (6 months and yearly) after the initial evaluations. We recommend that patients with a pituitary incidentaloma be referred for surgery if they have a visual field deficit; signs of compression by the tumor leading to other visual abnormalities, such as ophthalmoplegia, or neurological compromise due to compression by the lesion; a lesion abutting the optic nerves or chiasm; pituitary apoplexy with visual disturbance; or if the incidentaloma is a hypersecreting tumor other than a prolactinoma.
Guidelines and consensus statements ensure that physicians managing acromegaly patients have access to current information on evidence-based treatments to optimize outcomes. Given significant novel ...recent advances in understanding acromegaly natural history and individualized therapies, the Pituitary Society invited acromegaly experts to critically review the current literature in the context of Endocrine Society guidelines and Acromegaly Consensus Group statements. This update focuses on how recent key advances affect treatment decision-making and outcomes, and also highlights the likely role of recently FDA-approved therapies as well as novel combination therapies within the treatment armamentarium.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Summary
Monitoring of a patient with acromegaly requires periodic evaluation of levels of GH and IGF‐1, the biochemical markers of this disease. Although the results of these two tests are usually ...concordant, they can be discrepant and how to proceed when they are can be a challenging clinical problem. In some cases, IGF‐1 levels are normal yet GH suppression after oral glucose is abnormal; this pattern may be due to persistent GH dysregulation despite remission. In other cases, IGF‐1 levels are elevated yet GH suppression appears to be normal; this pattern may be observed if the cutoff for GH suppression is inappropriately high for the GH assay being used. Various conditions known to alter GH and IGF‐1 including malnutrition, thyroid disease and oestrogen use as well as the potential for methodological or normative data issues with the GH and IGF‐1 assays should be considered in the interpretation of discrepant results. When a known cause of the discrepancy other than acromegaly is not identified, a clinical decision about the patient’s therapy needs to be made. We adjust treatment in most patients whose results are discrepant based on the IGF‐1 level, continuing current treatment if it is persistently normal or modifying this if it is elevated. The clinical picture of the patient, however, also needs to be incorporated into this decision. All patients should have continued periodic surveillance of both GH and IGF‐1 levels.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Abstract
Background:
Acromegaly is characterized by overproduction of growth hormone (GH) by the pituitary gland. GH stimulates the synthesis of insulin-like growth factor-I (IGF-I), and the somatic ...growth and metabolic dysfunction that characterize acromegaly are a consequence of elevated GH and IGF-I levels. Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are rare, slow-growing neoplasms that have usually metastasized by the time of diagnosis. The majority of GEP-NETs are carcinoid tumors whose syndrome is caused by the hypersecretion of biogenic amines, peptides and polypeptides responsible for the principal symptoms of diarrhea and flushing.
Methods:
The MEDLINE and EMBASE databases were searched for preclinical and clinical studies of octreotide (Sandostatin*),
*Novartis Pharma AG, Basel, Switzerland. a potent synthetic somatostatin analogue, in patients with acromegaly or GEP-NETs.
Objective:
This article reviews the 20 years of clinical experience with octreotide and the impact it has made in patients with acromegaly or GEP-NETs.
Results:
Octreotide has proven to be an essential component in the management strategy of acromegaly and GEP-NETs over the past 20 years. The multiple beneficial effects of octreotide throughout the body, combined with its established safety profile (the most common adverse effects are injection-site pain and gastrointestinal events), have made it an appealing option for clinicians. The advent of the long-acting release (LAR) formulation of octreotide provided additional benefits to patients through monthly administration, while maintaining the efficacy and tolerability profile of the daily subcutaneous formulation.
Conclusions:
Octreotide is a potent synthetic somatostatin analogue that has become the mainstay of medical therapy for tumor control in neuroendocrine disorders such as acromegaly and GEP-NETs. The development of octreotide LAR offered a further advancement; less frequent dosing provided valuable benefits in quality of life to patients, with equivalent efficacy and tolerability. Moreover, recent results from the PROMID study have confirmed the antiproliferative effect of octreotide LAR in patients with well-differentiated metastatic GEP-NETs of the midgut. New therapeutic uses of octreotide are currently under investigation in a variety of clinical settings.
Abstract Measuring the concentration of growth hormone (GH) in blood samples taken during dynamic tests represents the basis for diagnosis of growth hormone related disorders, namely growth hormone ...deficiency and growth hormone excess. Today, a wide spectrum of immunoassays are in use, enabling rapid and sensitive determination of growth hormone concentrations in routine diagnostics. From a clinical point of view several difficulties exist with the use and interpretation of GH assay results in the assessment of GH related disorders: Many physiological factors such as fat mass, age and gender influence the outcome of dynamic tests, overall leading to significant inter-individual differences in GH responses. However, in addition to the physiological variability, considerable variability exists in GH assay results obtained by different immunoassays. Unfortunately, all the new technical advances in the field of GH measurement techniques have not reduced this methodological variability. To a large extent, the actual values reported for the GH concentration in a sample depend on the method used by the respective laboratory. Obviously, such discrepancies limit the applicability of consensus guidelines on diagnosis and treatment in clinical practice. This review summarizes current practices for GH measurement with respect to the methods used, their limitations and the clinical consequences of the existing heterogeneity in GH immunoassay results.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Abstract Context Long-term growth hormone/insulin-like growth factor-1 (GH/IGF-1) excess could increase the risk of cancer in acromegaly, but individual levels of these hormones do not relate to this ...risk. Objective We newly investigated longitudinally-measured IGF-1 levels as a potential predictor of cancer in a large New York City acromegaly cohort. Methods We conducted a prospective, longitudinal study of 598 acromegaly (309 men, 289 women) and 292 clinically nonfunctioning pituitary adenoma (CNFPA) (140 women, 152 men) patients from the same underlying population. GH and IGF-1 levels were measured longitudinally and outcomes were observed during long-term follow-up. Cumulative exposure to IGF-1 excess was tested as a predictor of cancer. We compared cancer prevalence in acromegaly and CNFPA cohorts and incidence in each to that expected from Surveillance, Epidemiology, and End Results (SEER) data. Results Cancer prevalence by last follow-up was 22.6% in acromegaly and 12.7% in CNFPAs (odds ratio OR = 1.99 95% CI, 1.34-2.97) (P = .0005). Overall standardized incidence ratio for cancer was 1.78 (1.51-1.81) in the acromegaly and 1.26 (0.89-1.70) in the CNFPA cohorts. Cumulative exposure to IGF-1 excess, OR = 1.278 (1.060-1.541) (P = .01), years from acromegaly diagnosis to cancer or last follow-up, OR = 1.03 (1.004-1.057) (P = .024), and age at follow up, OR = 1.064 (1.047-1.082) (P < .001), were predictors of cancer. Conclusion Cancer risk is increased in acromegaly, but not in CNFPA patients. Cumulative exposure to IGF-1 excess is a predictor of cancer in acromegaly. Our data suggest that cancer risk in acromegaly relates to the degree and duration of IGF-1 excess and that full appreciation of this risk requires long-term follow up.
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