Biomedical subjects

John A H Wass

Publications and source records attributed to John A H Wass.

15 recordsLinked to original sources

PubMed2006

Craniopharyngiomas.

Craniopharyngiomas are rare, mainly sellar/parasellar, epithelial tumors diagnosed during childhood or adult life. Histologically, two primary subtypes have been recognized (adamantinomatous and papillary) with an as yet, unclarified pathogenesis. They may present with a variety of manifestations (neurological, visual, and hypothalamo-pituitary). Despite their benign histological appearance, they often show an unpredictable growth pattern, which, combined with the lack of randomized studies, poses significant difficulties in the establishment of an optimal therapeutic protocol. This should focus on the prevention of recurrence(s), improvement of survival, reduction of the significant disease and treatment-related morbidity (endocrine, visual, hypothalamic, neurobehavioral, and cognitive), and preservation of the quality of life. Currently, surgical excision followed by external beam irradiation, in cases of residual tumor, is the main treatment option. Intracystic irradiation or bleomycin, stereotactic radiosurgery, or radiotherapy and systemic chemotherapy are alternative approaches; their place in the management plan remains to be assessed in adequately powered long-term trials. Apart from the type of treatment, the identification of clinical and imaging parameters that will predict patients with a better prognosis is difficult. The central registration of patients with these challenging tumors may provide correlates between treatments and outcomes and establish prognostic factors at the pathological or molecular level that may further guide us in the future.

Antibiotics, Antineoplastic↗

PubMed2006

GH replacement does not increase the risk of recurrence in patients with craniopharyngioma.

BACKGROUND: A significant number of patients with craniopharyngioma are GH deficient. The safety of GH replacement in these subjects has not been established. OBJECTIVE: To assess the effect of GH replacement upon recurrence in patients with craniopharyngioma. PATIENTS AND METHODS: All the patients with craniopharyngioma followed-up at the Departments of Endocrinology or Paediatrics in Oxford and treated or not with GH were studied retrospectively. These were recruited from the databases of the departments consisting of subjects diagnosed between January 1964 and July 2005. The impact of GH replacement upon recurrence was evaluated after adjusting for possible confounding factors. RESULTS: Forty-one subjects received GH replacement. Nine of them did not have follow-up imaging during GH therapy and were not included in the statistical analyses. The remaining 32 (22 males/10 females) received GH for a mean period of 6.3 +/- 4.6 years (median 5.1, range 0.8-22); 21 started during childhood (13 of them continued after the achievement of final height with an adult dose) and 11 during adult life. The mean duration of their follow-up (from surgery until last assessment) was 10.8 +/- 9.2 years (range 1.9-40). Fifty-three subjects had not received GH therapy (30 men/23 women). The mean duration of their follow-up (from surgery until last assessment) was 8.3 +/- 8.8 years (range 0.5-36). During the observation period, 4 patients treated with GH and 22 non-GH treated ones developed tumour recurrence. After adjusting for sex, age at tumour diagnosis and type of tumour therapy (gross total removal, partial removal, surgery + irradiation), GH treatment was not a significant independent predictor of recurrence (P = 0.06; hazard ratio = 0.309). Similar results were obtained when the impact of GH replacement was assessed according to its duration (P = 0.18; hazard ratio = 0.991/month of treatment). None of the nine patients with insufficient imaging data for inclusion in the statistical analyses [5 men/4 women, 3 treated with GH during childhood/6 during adult life, mean duration of GH therapy 2.9 +/- 2.4 years (median 1.8, range 0.4-7)] showed clinical features suggestive of recurrence during the period of GH replacement. CONCLUSION Based on the data of the craniopharyngiomas database in Oxford, there is no evidence that GH replacement is associated with an increased risk of tumour recurrence.

Adolescent↗

PubMed2006

Guidelines of the Pituitary Society for the diagnosis and management of prolactinomas.

In June 2005, an ad hoc Expert Committee formed by the Pituitary Society convened during the 9th International Pituitary Congress in San Diego, California. Members of this committee consisted of invited international experts in the field, and included endocrinologists and neurosurgeons with recognized expertise in the management of prolactinomas. Discussions were held that included all interested participants to the Congress and resulted in formulation of these guidelines, which represent the current recommendations on the diagnosis and management of prolactinomas based upon comprehensive analysis and synthesis of all available data.

Adenoma↗

PubMed2006

Do the limits of serum prolactin in disconnection hyperprolactinaemia need re-definition? A study of 226 patients with histologically verified non-functioning pituitary macroadenoma.

BACKGROUND: The differentiation of a pituitary non-functioning macroadenoma from a macroprolactinoma is important for planning appropriate therapy. Serum PRL levels have been suggested as a useful diagnostic indicator. However, values between 2500 and 8000 mU/l are a grey area and are currently associated with diagnostic uncertainty. OBJECTIVE: We wished therefore, to investigate the serum PRL values in a large series of patients presenting with apparently non-functioning pituitary macroadenomas. PATIENTS AND METHODS: All patients presenting to the Department of Endocrinology in Oxford with clinically non-functioning pituitary macroadenomas (later histologically verified) between 1990 and 2005 were studied. Information documented in the notes on the medications and on the presence of conditions capable of affecting the serum PRL levels at the time of blood sampling was also collected. RESULTS: Two hundred and twenty-six patients were identified (median age at diagnosis 55 years, range 18-88 years; 146 males/80 females; 143 gonadotroph, 46 null cell, 25 plurihormonal and 12 silent ACTH adenomas). All tumours had suprasellar extension. At the time of blood sampling 41 subjects were taking medications capable of increasing serum PRL. Hyperprolactinaemia was found in 38.5% (87/226) of the patients. The median serum PRL values in the total group were 386 mU/l (range 16-3257) (males: median 299 mU/l, range 16-1560; females: median 572 mU/l, range 20-3257) and in those not taking drugs capable of increasing serum PRL 363 mU/l (range 16-2565) (males: median 299 mU/l, range 16-1560; females: median 572 mU/l, range 20-2565). Serum PRL < 2000 mU/l was found in 98.7% (223/226) of the total group and in 99.5% (184/185) of those not taking drugs. Among the three subjects with serum PRL > 2000 mU/l, two were taking oestrogen preparations. CONCLUSIONS: Based on a large series of histologically confirmed cases, serum PRL > 2000 mU/l is almost never encountered in nonfunctioning pituitary macroadenomas. Values above this limit in the presence of a macroadenoma should not be surrounded by diagnostic uncertainty (after acromegaly or Cushing's disease have been excluded); a prolactinoma is the most likely diagnosis and a dopamine agonist should be considered as the treatment of choice.

Adenoma↗

PubMed2005

Association of the TSHR gene with Graves' disease: the first disease specific locus.

The development of autoimmune thyroid disease (AITD) is associated with autoantibodies directed against the thyroid stimulating hormone receptor (TSHR). Previous studies have failed to demonstrate a consistent association between the TSHR and AITD, or any of its sub-phenotypes. In the present study, we analysed the linkage disequilibrium (LD) structure encompassing the TSHR, to identify LD 'blocks' and SNPs, which capture the majority of intra-block haplotype diversity. The haplotype tagging SNPs, plus all common SNPs reported in previous studies were genotyped in 1,059 AITD Caucasian cases and 971 Caucasian controls. A haplotype, across two LD blocks, showed association (P<1 x 10(-6), OR 1.7) with Graves' disease (GD) but not autoimmune hypothyroidism (AIH). We replicated these findings by genotyping the most associated GD SNP, rs2268458, in a separate UK Caucasian cohort of 1,366 AITD cases and 1,061 controls (GD, P=2 x 10(-6), OR 1.3; AIH, P=NS). These results in two independent Caucasian data sets suggest that the TSHR is the first replicated GD-specific locus meriting further fine mapping and functional analysis to identify the aetiological variants.

Case-Control Studies↗

PubMed2005

The value of an acute octreotide suppression test in predicting long-term responses to depot somatostatin analogues in patients with active acromegaly.

BACKGROUND: The long-acting depot somatostatin analogues [octreotide LAR (LAR) and lanreotide (LAN)] are among the most effective available medical therapies for acromegaly. However, published data on a biochemical test suitable for predicting the responsiveness to these depot agents are lacking. AIM: To investigate the value of an acute octreotide suppression test (OST) in predicting the responses to treatment with long-acting somatostatin analogues in patients with active acromegaly. PATIENTS AND METHODS: Thirty patients with active acromegaly [mean GH in GH day curve (GHDC) > 5 mU/l] were subjected to an OST [hourly GH measurements for 6 h following 100 microg subcutaneous (s.c.) octreotide]. Subsequently, 14 patients were treated with LAR, 10 with LAN and 6 received both drugs at different times. The final response to treatment was evaluated when the subjects had achieved 'safe' GH levels (mean GH < 5 mU/l) or after receiving the maximal dose of each drug (maximum duration of treatment 6 months). RESULTS: The nadir GH values during the OST were 2.6 +/- 2.5 mU/l (mean +/- SD, range 0.2-8.7) with a percentage fall of 84.8 +/- 15.7% (mean +/- SD, range 26-99%) from the baseline levels (26.2 +/- 31.5 mU/l, mean +/- SD). All the patients except one showed a decrease of greater than 50%. The mean time to achieve the nadir GH value was 3.8 +/- 1.6 h (mean +/- SD, range 1-6). The nadir GH levels showed a positive correlation with both pre-treatment (i.e. before commencing LAN or LAR) GH values during the GHDC (r = 0.63, P < 0.01) and IGF-I levels (r = 0.56, P < 0.05). The nadir GH values during the OST showed a positive correlation with the achieved mean GH levels in patients treated with LAR (r = 0.66, P < 0.01) but not in the ones treated with LAN. The criterion of GH < 5.25 mU/l during the OST had sensitivity 100%, specificity 80%, positive predictive value (PPV) 94% and negative predictive value (NPV) 100% in predicting achievement of 'safe' GH levels in patients treated with LAR. A less optimal prognostic profile was obtained for subjects treated with LAN with the criterion of GH < 6.05 mU/l during the OST providing sensitivity 92%, specificity 67%, PPV 92% and NPV 67%. The above cut-off GH levels had a PPV of only 77% and 60% in predicting normalization of IGF-I on treatment with LAR or LAN, respectively. CONCLUSIONS: The OST is a reliable tool for the selection of patients with active acromegaly who will achieve 'safe' GH levels on therapy with LAR. Its prognostic profile is less optimal for patients treated with LAN. If GH values during the test fall < 5.25 mU/l (in case of LAR treatment) or < 6.05 mU/l (in case of LAN treatment), there is a 92-94% chance of subsequently achieving 'safe' GH levels after up to 6 months treatment with either of these agents.

Acromegaly↗

PubMed2005

Treatment of pituitary tumors: history.

Over the past century our understanding of the pituitary disease has undergone an amazing evolution, accompanied by impressive advances in the therapeutic approaches to pituitary tumors. This historical review aims to provide insights into the contributions of key medical and scientific pioneers, their occasionally serendipitous discoveries, and the lively global debates, which have ultimately improved the therapeutic targets and the long-term outcome of these patients. The development of the three main modalities is discussed (surgery, irradiation, pharmacotherapy). More recent experimental data, which may provide a path to a stronger therapeutic armamentarium for these undoubtedly challenging tumors, are also briefly reported.

History, 19th Century↗

PubMed2004

Influence of LRP5 polymorphisms on normal variation in BMD.

UNLABELLED: Genetic studies based on cohorts with rare and extreme bone phenotypes have shown that the LRP5 gene is an important genetic modulator of BMD. Using family-based and case-control approaches, this study examines the role of the LRP5 gene in determining normal population variation of BMD and describes significant association and suggestive linkage between LRP5 gene polymorphisms and BMD in >900 individuals with a broad range of BMD. INTRODUCTION: Osteoporosis is a common, highly heritable condition determined by complex interactions of genetic and environmental etiologies. Genetic factors alone can account for 50-80% of the interindividual variation in BMD. Mutations in the LRP5 gene on chromosome 11q12-13 have been associated with rare syndromes characterized by extremely low or high BMD, but little is known about the contribution of this gene to the development of osteoporosis and determination of BMD in a normal population. MATERIALS AND METHODS: To examine the entire spectrum of low to high BMD, 152 osteoporotic probands, their families (597 individuals), and 160 women with elevated BMD (T score > 2.5) were recruited. BMD at the lumbar spine, femoral neck, and hip were measured in each subject using DXA. RESULTS: PAGE sequencing of the LRP5 gene revealed 10 single nucleotide polymorphisms (SNPs), 8 of which had allele frequencies of >5%, in exons 8, 9, 10, 15, and 18 and in introns 6, 7, and 21. Within families, a strong association was observed between an SNP at nucleotide C171346A in intron 21 and total hip BMD (p < 1 x 10(-5) in men only, p = 0.0019 in both men and women). This association was also observed in comparisons of osteoporotic probands and unrelated elevated BMD in women (p = 0.03), along with associations with markers in exons 8 (C135242T, p = 0.007) and 9 (C141759T, p = 0.02). Haplotypes composed of two to three of the SNPs G121513A, C135242T, G138351A, and C141759T were strongly associated with BMD when comparing osteoporotic probands and high BMD cases (p < 0.003). An SNP at nucleotide C165215T in exon 18 was linked to BMD at the lumbar spine, femoral neck, and total hip (parametric LOD scores = 2.8, 2.5, and 2.2 and nonparametric LOD scores = 0.3, 1.1, and 2.2, respectively) but was not genetically associated with BMD variation. CONCLUSION: These results show that common LRP5 polymorphisms contribute to the determination of BMD in the general population.

Adolescent↗

PubMed2004

Molecular pathology shows p16 methylation in nonadenomatous pituitaries from patients with Cushing's disease.

PURPOSE: The majority of cases of Cushing's disease are due to the presence of a corticotroph microadenoma. Less frequently no adenoma is found and histology shows either corticotroph hyperplasia, or apparently normal pituitary. In this study we have used molecular pathology to determine whether the tissue labeled histologically as "normal" is indeed abnormal. EXPERIMENTAL DESIGN: Tissue from 31 corticotroph adenomas and 16 nonadenomatous pituitaries were subject to methylation-sensitive PCR to determine the methylation status of the p16 gene CpG island. The proportion of methylated versus unmethylated CpG island was determined using combined bisulphite restriction analysis. Methylation status was correlated with immunohistochemical detection of p16. RESULTS: Seventeen of 31 adenomas (54.8%), 4 of 6 cases of corticotroph hyperplasia, and 7 of 10 apparently normal pituitaries showed p16 methylation. Ten of 14 (71%; P = 0.01) adenomas and 2 of 3 cases of corticotroph hyperplasia, which were methylated, failed to express p16 protein. However, only 2 of 7 apparently normal pituitaries that were methylated failed to express p16 protein. Quantitative analysis of methylation using combined bisulphite restriction analysis showed only unmethylated CpG islands in postmortem normal pituitaries; however, in adenomas 80-90% of the cells within a specimen were methylated. The reverse was true for corticotroph hyperplasia and apparently normal pituitaries where only 10-20% of the cells were methylated. Thus, the decreased proportion of cells that were methylated, particularly in those cases of apparently normal pituitary, is the most likely explanation for the lack of association between this change and loss of cognate protein in these cases. CONCLUSIONS: To our knowledge this is the first report that describes an intrinsic molecular change, namely methylation of the p16 gene CpG island, common to all three histological patterns associated with Cushing's disease. Thus, the use of molecular pathology reveals abnormalities undetected by routine pathological investigation. In cases of "apparently" normal pituitaries it is not possible to determine whether the change is associated with adenoma cells "scattered" throughout the gland, albeit few in number, or with the ancestor-clonal origin of these tumor cells.

Adenoma↗

PubMed2004

Systematic dose-extension of octreotide LAR: the importance of individual tailoring of treatment in patients with acromegaly.

OBJECTIVE: The depot long-acting somatostatin analogue octreotide LAR (LAR) provides effective and well-tolerated treatment for acromegaly. Despite a 4-weekly recommended injection frequency, prolonged duration of GH suppression has been observed in some patients following treatment with long-acting somatostatin analogues. The aim of our study was to perform a prospective systematic study to determine whether extending the interval between doses of LAR allows maintenance of 'safe' GH in selected patients with acromegaly. PATIENTS AND METHODS: Twenty-two patients (15 men, seven women), mean age 58.9 years (35-81 years) with active acromegaly (mGH > 5 mU/l), requiring treatment were selected to receive treatment with LAR. Eleven patients had received previous treatment with both transsphenoidal surgery and radiotherapy, while six had received surgery alone. All patients were commenced on treatment with 20 mg LAR intramuscularly (i.m.) every 4 weeks. Mean GH (mGH) was measured after three consecutive injections immediately prior to the fourth injection. The dose frequency was systematically reduced after every four injections if mGH < 5 mU/l. Once mGH > 5 mU/l, the dose frequency was increased and mGH reassessed. RESULTS: The dosing interval was successfully increased to greater than 4 weeks in 20/22 patients (90.9%). Six of 22 (27.3%) were receiving injections every 8 weeks and 3/22 (13.6%) every 12 weeks. GH and IGF-I were lower on treatment compared with baseline (P < 0.01). There was no difference in individual mGH and IGF-I between the values on 4-weekly dosing and those at final dose frequency. There was no relationship between final dose frequency and either mean GH or IGF-I prior to LAR, patient age, or previous treatment. The percentage suppression following 100 micro g octreotide subcutaneously did not predict subsequent dose frequency of LAR. The drug cost if patients had continued at 4-weekly intervals would be UK pound 187 850, compared with UK pound 101 065 for the individually titrated dose frequency (P < 0.01). This represents a final cost of 53.8% of the 4-weekly injection price. CONCLUSION: Individual tailoring of LAR administration maintains control of acromegaly, with reduced injection frequency and improved cost-effectiveness.

Acromegaly↗

PubMed2003

Angiogenesis in endocrine tumors.

Angiogenesis is the process of new blood vessel development from preexisting vasculature. Although vascular endothelium is usually quiescent in the adult, active angiogenesis has been shown to be an important process for new vessel formation, tumor growth, progression, and spread. The angiogenic phenotype depends on the balance of proangiogenic growth factors such as vascular endothelial growth factor (VEGF) and inhibitors, as well as interactions with the extracellular matrix, allowing for endothelial migration. Endocrine glands are typically vascular organs, and their blood supply is essential for normal function and tight control of hormone feedback loops. In addition to metabolic factors such as hypoxia, the process of angiogenesis is also regulated by hormonal changes such as increased estrogen, IGF-I, and TSH levels. By measuring microvascular density, differences in angiogenesis have been related to differences in tumor behavior, and similar techniques have been applied to both benign and malignant endocrine tumors with the aim of identification of tumors that subsequently behave in an aggressive fashion. In contrast to other tumor types, pituitary tumors are less vascular than normal pituitary tissue, although the mechanism for this observation is not known. A relationship between angiogenesis and tumor size, tumor invasiveness, and aggressiveness has been shown in some pituitary tumor types, but not in others. There are few reports on the role of microvascular density or angiogenic factors in adrenal tumors. The mechanism of the vascular tumors, which include adrenomedullary tumors, found in patients with Von Hippel Lindau disease has been well characterized, and clinical trials of antiangiogenic therapy are currently being performed in patients with Von Hippel Lindau disease. Thyroid tumors are more vascular than normal thyroid tissue, and there is a clear correlation between increased VEGF expression and more aggressive thyroid tumor behavior and metastasis. Although parathyroid tissue induces angiogenesis when autotransplanted and PTH regulates both VEGF and MMP expression, there are few studies of angiogenesis and angiogenic factors in parathyroid tumors. An understanding of the balance of angiogenesis in these vascular tumors and mechanisms of vascular control may assist in therapeutic decisions and allow appropriately targeted treatment.

Adrenal Gland Neoplasms↗

PubMed2003

Site and gender specificity of inheritance of bone mineral density.

UNLABELLED: Differences in genetic control of BMD by skeletal sites and genders were examined by complex segregation analysis in 816 members of 147 families with probands with extreme low BMD. Spine BMD correlated more strongly in male-male comparisons and hip BMD in female-female comparisons, consistent with gender- and site-specificity of BMD heritability. INTRODUCTION: Evidence from studies in animals and humans suggests that the genetic control of bone mineral density (BMD) may differ at different skeletal sites and between genders. This question has important implications for the design and interpretation of genetic studies of osteoporosis. METHODS: We examined the genetic profile of 147 families with 816 individuals recruited through probands with extreme low BMD (T-score < -2.5, Z-score < -2.0). Complex segregation analysis was performed using the Pedigree Analysis Package. BMD was measured by DXA at both lumbar spine (L1-L4) and femoral neck. RESULTS: Complex segregation analysis excluded purely monogenic and environmental models of segregation of lumbar spine and femoral neck BMD in these families. Pure polygenic models were excluded at the lumbar spine when menopausal status was considered as a covariate, but not at the femoral neck. Mendelian models with a residual polygenic component were not excluded. These models were consistent with the presence of a rare Mendelian genotype of prevalence 3-19%, causing high BMD at the hip and spine in these families, with additional polygenic effects. Total heritability range at the lumbar spine was 61-67% and at the femoral neck was 44-67%. Significant differences in correlation of femoral neck and lumbar spine BMD were observed between male and female relative pairs, with male-male comparisons exhibiting stronger lumbar spine BMD correlation than femoral neck, and female-female comparisons having greater femoral neck BMD correlation than lumbar spine. These findings remained true for parent-offspring correlations when menopausal status was taken into account. The recurrence risk ratio for siblings of probands of a Z-score < -2.0 was 5.4 at the lumbar spine and 5.9 at the femoral neck. CONCLUSIONS: These findings support gender- and site-specificity of the inheritance of BMD. These results should be considered in the design and interpretation of genetic studies of osteoporosis.

Bone Density↗

PubMed2002

Oncological complications of excess GH in acromegaly.

Around fifteen percent of the deaths reported in acromegaly are attributable to malignancy (SM Melmed, J Clin Endocrinol Metab 2001;86:2929-2934; A Mestrón, SM Webb, In: Endocrine Society, San Francisco, June 2002 (abstract)), uncontrolled disease is associated with a growth advantage for concurrent neoplasms, which are more likely to be aggressive; however, there is no clear evidence of de novo cancer initiation in acromegaly and no proven causal relationship of acromegaly with malignant disease. Overall and cancer mortality in acromegaly have been shown to correlate with the degree of GH control; if post therapy GH is controlled, both the overall and cancer mortality do not appear to differ from that of the normal population (SM Orme et al., J Clin Endocrinol Metab 1998;83:2730-2734; JD Nabarro, Clin Endocrinol 1987;26:481-512). However, no long-term prospective evaluation of cancer prevalence or its relation to biochemical or clinical disease activity is available. IGF-1 appears to exert a permissive effect on tumorigenesis; there is no clear evidence that tumor initiation is triggered by IGF-1 in acromegaly; nevertheless, since IGF-1 may be higher in neoplasms, aggressive treatment aimed at controlling the disease activity will theoretically be advantageous for acromegalic patients with cancer. The prevalence of colon polyps and colon cancer appear to be incresed in acromegaly as is mortality for colon cancer (Orme et al., 1998), so regular colonoscopy screening and polypectomy would seem advisable, especially in older patients with active acromegaly. Surveillance for prostate cancer in elderly males with high IGF-1, especially if also receiving testosterone replacement therapy, is recommendable, by measurement of serum PSA, rectal examination and/or prostatic ultrasound. In women, mammography should be offered, especially after the age of 50 years, as in the normal population. Neither prostate nor breast cancer have been consistently shown to have an increased prevalence in acromegaly, but larger prospective epidemiological studies are required to study this further.

Acromegaly↗

PubMedDate not supplied

Multiple endocrine neoplasia: spectrum of radiologic appearances and discussion of a multitechnique imaging approach.

Multiple endocrine neoplasia (MEN) is characterized by the occurrence of two or more tumors that may be associated with hyperfunction and malignancy. MEN is caused by genetic defects, and two major types, MEN 1 and MEN 2, are recognized. Each type is characterized by the development of tumors within specific endocrine organs. A multidisciplinary approach involving cooperation between endocrinologists, surgeons, oncologists, and radiologists is pivotal for optimizing patient treatment. Imaging plays a vital role in the diagnosis and management of the disease. To contribute effectively, however, the radiologist must understand the range of anatomic and functional imaging modalities used in the assessment of endocrine disorders. In addition, knowledge of the optimal techniques for evaluating the pituitary, thyroid, parathyroid, pancreatic, adrenal, and foregut carcinoid tumors that occur in these MEN syndromes is essential. Finally, an understanding of the spectrum of disease and of the manifestations of each component is crucial for accurate detection, staging, and surveillance in this diverse patient group.

Diagnostic Imaging↗

PubMedDate not supplied

Pegvisomant: a new treatment modality for acromegaly.

Acromegaly, a multisystemic disease resulting from excessive growth hormone (GH) and insulin-like growth factor-I (IGF-I) levels in adults, is associated with a two-to-threefold increase in mortality. The available treatment options (surgery, radiotherapy and medical treatment with somatostatin analogues or dopamine agonists) fail to achieve the currently accepted goals of therapy in a substantial number of patients. Pegvisomant, a newly developed GH receptor antagonist, represents a novel treatment modality for this disease. It binds with the GH receptor and induces internalization, but blocks receptor signaling events, thereby reducing IGF-I production. The two main published studies suggest that it is the most potent medical therapy with greater specificity, without being dependent on the tumour characteristics. However, apart from its high cost and the dilemmas raised concerning the appropriateness of using serum IGF-I concentrations as a marker of disease activity, it may also occasionally be associated with elevations in liver enzyme levels. Further studies are required to confirm its high success rates as well as to investigate the possibility of inducing an increase in the pituitary tumour size. Currently, pegvisomant is a second line treatment for acromegaly with an adjuvant role and possibly of greater value in cases of resistance to other therapeutic options.

Journal Article↗