PubMed Health⌕ Search

Biomedical subjects

S Ezzat

Publications and source records attributed to S Ezzat.

At least 19 recordsLinked to original sources
PubMed1998

Insulin and related factors in premenopausal breast cancer risk.

BACKGROUND: Insulin and insulin-like growth factor I (IGF-I) are important mitogens in vitro and in vivo. It has been hypothesized that these factors may play an important role in the development of breast cancer. METHODS: A case-control study comparing plasma insulin levels in 99 premenopausal women with newly diagnosed node-negative invasive carcinoma of the breast and 99 age-matched controls with incident biopsied non-proliferative breast disease (NP) was conducted. Women with known diabetes were excluded. RESULTS: For the entire study group, mean age was 42.6 +/- 5.1 years and mean weight was 62.9 +/- 10.3 kg. After adjustment for age and weight, elevated insulin levels were significantly associated with breast cancer, Odds Ratio (OR) for women in the highest insulin quintile versus the lowest quintile = 2.83 (95% Confidence Interval [CI] 1.22-6.58). There were no statistically significant differences between cases and controls for IGF-I and IGFBP-1 levels. However, after adjustment for age, the association between plasma levels of insulin-like growth factor binding protein 3 (IGFBP-3) and breast cancer approached statistical significance; OR for highest quintile versus lowest quintile of IGFBP-3 being 2.05 (95% CI, 0.93-4.53). All results were independent of diet and other known risk factors for breast cancer. CONCLUSION: Circulating insulin levels and possibly IGFBP-3 levels are elevated in women with premenopausal breast cancer. This association may reflect an underlying syndrome of insulin resistance that is independent of obesity.

Adult↗
PubMed1998

Psychological features of acromegaly.

Acromegaly is a serious but often undiagnosed condition that is often unrecognized for many years. The delay from onset of symptoms until the time of diagnosis results in a unique constellation of physical and mental problems for patients and health care professionals. The purpose of this chapter is to identify the psychological consequences experienced by individuals affected with pituitary tumors which alter growth hormone release. As little research has been completed on the subject, very little is known, or has been applied, in the treatment of these patients. To identify the presence of psychological features, the research which exists and an in-depth qualitative analysis of the personal experience of one of the author (K.F.), having suffered a pituitary macroadenoma with accompanying acromegaly, is described. Our findings are compared with those from an earlier series and the few published reports.

Acromegaly↗
PubMed1998

Distinct multiple RET/PTC gene rearrangements in multifocal papillary thyroid neoplasia.

Rearrangements involving the RET protooncogene have been implicated in the development of papillary thyroid carcinoma (PC). Transgenic mice, expressing thyroid-targeted RET/PTC-1, develop PC; but the clinical significance of this oncogene remains uncertain. We examined the expression of RET/PTC-1, -2, and -3 in human thyroid microcarcinomas and clinically evident PC to determine its role in early stage vs. developed PC and to examine the diversity of RET/PTC in multifocal disease. RNA was extracted from paraffin-embedded microcarcinomas and clinically evident PCs; the results obtained from paraffin-embedded tissue were confirmed on RNA from corresponding snap-frozen tissue of clinically evident PCs. RT and PCR was performed using primers for RET/PTC-1, -2, and -3; PGK-1 (the housekeeping gene) analysis was used to ensure integrity of the RNA and efficiency of the RT reaction. PCR products were resolved by gel electrophoresis, and Southern hybridization was performed with RET/PTC-1, -2, and -3 probes. A polyclonal antibody to the carboxyterminus of RET was used for immunohistochemistry on paraffin sections. Thirty-nine occult papillary thyroid microcarcinomas from 21 patients were analyzed. Of the 30 tumors (77%) positive for RET/PTC rearrangements, 12 were positive for RET/PTC-1, 3 for RET/ PTC-2, 6 for RET/PTC-3, and 9 for multiple RET/PTC oncogenes. In clinically evident tumors, 47% had RET/PTC rearrangements. Immunohistochemistry demonstrated close correlation with RT-PCR-derived findings. RET/PTC expression is highly prevalent in microcarcinoma and occurs more frequently than in clinically evident PC (P < 0.005). Multifocal disease, identified in 17 of the 21 patients, exhibited identical RET/PTC rearrangements within multiple tumors in only 2 patients; the other 15 patients had diverse rearrangements in individual tumors. Our results indicate that RET/PTC oncogene rearrangements may play a role in early-stage papillary thyroid carcinogenesis, but they seem to be less important in determining progression to clinically-evident disease. In multifocal disease, the diversity of RET/PTC profiles, in the majority of cases, suggests that individual tumors arise independently in a background of genetic or environmental susceptibility.

Carcinoma, Papillary↗
PubMed1998

Improved diagnostic accuracy of inferior petrosal sinus sampling over imaging for localizing pituitary pathology in patients with Cushing's disease.

The majority of patients with Cushing's disease can be cured by transsphenoidal microsurgery; however, precise localization of the pituitary source of ACTH is not always possible by standard imaging techniques. Bilateral venous sampling from the inferior petrosal sinuses (IPSS) is also useful for diagnosing Cushing's disease, but the interpretation of discordant findings between IPSS and imaging remains problematic. We tested the ability of imaging and IPSS to localize an ACTH-secreting pituitary lesion in comparison to definitive histopathological examination of the pituitary in patients with Cushing's disease (n = 37). Bilateral IPS catheterization was technically feasible in 32 patients and provided evidence of lateralization in 31 patients. Histological examination confirmed a corticotropic adenoma in 28 patients and corticotropic hyperplasia in 2 patients; Crooke's hyaline change was found in 7 patients, among whom 1 subsequently was found to have an ectopic sphenoid corticotropic adenoma, and the remainder had suspected microadenomas that were not identified microscopically. Accurate localization of the pituitary lesion was more frequent when based on IPSS results than on imaging studies (70% vs. 49%, P < 0.06). The 2 tests provided directly discrepant results for 8 patients; among these, IPSS was more likely than imaging to agree with final pathology (63% vs. 13%, P < 0.10). Imaging was entirely normal for another 9 patients, in whom IPSS accurately localized the lesion for the majority (89%; 95% confidence interval: 50-99%). We suggest that IPSS is an effective tool for localizing pituitary pathology and planning surgery for patients with Cushing's disease.

Adrenocorticotropic Hormone↗
PubMed1998

The MEN-1 gene is rarely down-regulated in pituitary adenomas.

The gene for multiple endocrine neoplasia type 1 (MEN-1) has recently been cloned and encodes a putative tumor suppressor protein named menin. We have previously reported inactivating MEN-1 gene mutations associated with loss of heterozygosity (LOH) of the normal allele in tumors of patients with MEN-1 and in some sporadic pituitary tumors. These genetic alterations, however, are noted in no more than 10% of sporadic adenomas. To investigate whether other mechanisms may result in down-regulation of menin gene expression in pituitary adenomas, we examined menin gene expression by semiquantitative RT-PCR in 60 sporadic pituitary adenomas. Ribonucleic acid (RNA) was extracted from surgically resected, morphologically characterized tumors. Primers were designed to amplify a 257-bp fragment spanning exons 4-6 of the MEN-1 gene. A product of the predicted size was amplified from normal pituitary samples as well as from adenomas. Competitive PCR was performed with the housekeeping gene PGK-1 to quantitate menin gene expression. A comparable ratio of menin/PGK-1 messenger RNA was identified in all but three samples; in two tumors with LOH, menin expression was weak, and in one tumor, menin messenger RNA was undetectable, associated with LOH and mutation of the other allele. Reduced expression of menin in some sporadic adenomas is consistent with a putative tumor suppressor role for this gene product. However, lack of menin down-regulation in the majority of these tumors, which exhibit LOH at 11q13 in up to 20% of cases, provides compelling evidence for an additional tumor suppressor gene at this locus, which is more commonly involved in the pathogenesis of pituitary neoplasms.

Adenoma↗
PubMed1997

Insulin-like growth factor binding protein-1 is elevated in patients with polycythemia vera and stimulates erythroid burst formation in vitro.

Previously, we found that, in the myeloproliferative disorder polycythemia vera (PV), circulating erythroid progenitor cells were hypersensitive to insulin-like growth factor I (IGF-I), an effect shown to occur through the IGF-I receptor. Also, in cells of PV patients, the IGF-I receptor was hyperphosphorylated on tyrosine residues under basal conditions, and its tyrosine phosphorylation in response to exogenous IGF-I was strongly augmented. Thus, because IGF-I appeared to play a role in the pathogenesis of PV, we wished to assess its level in the circulation of these patients. Normally, most of the circulating IGF-I is bound to specific high-affinity IGF binding proteins that can regulate its activity. We determined the circulating levels of IGF-I and two of its key binding proteins, IGFBP-1 and IGFBP-3. In two separate experiments, plasma samples from a total of 23 PV patients age- and sex-matched with 41 normal individuals were compared by radioimmunoassay. The levels of IGFBP-1 in patients with PV (37.80 +/- 4.33 microg/L) were more than fourfold higher than in normals (9.34 +/- 1.34 microg/L) or patients with secondary erythrocytosis (9.47 +/- 1.96 microg/L), whereas the plasma concentrations of IGFBP-3 and IGF-I in these patients were similar to those of normal subjects. Because circulating IGFBP-1 levels may be influenced by insulin, we measured the concentrations of insulin in the same samples. Our data showed that the elevation of circulating IGFBP-1 in PV could not be attributed to low levels of insulin in these patients. The substantial increase in concentration of IGFBP-1 was confirmed on ligand blots performed with (125)I-IGF-I. IGFBP-1 can be either inhibitory or stimulatory to the action of IGF-I under different conditions. We reasoned that if IGFBP-1 were stimulatory for erythropoiesis, an elevated IGFBP-1 level could help to explain the increased sensitivity to IGF-I observed in PV. If IGFBP-1 were inhibitory, it might suggest a compensatory mechanism in which a hyperphosphorylated IGF-I receptor in PV might induce a negative modulator of IGF-I action, in this case IGFBP-1. To distinguish between these two hypotheses, we titrated the effect of IGFBP-1 in the presence of IGF-I with respect to erythroid burst formation and found that IGFBP-1 was strikingly stimulatory. The elevated level of IGFBP-1 coupled with its ability to stimulate erythroid burst formation provide an attractive mechanism to account for the increased sensitivity of erythroid progenitor cells to IGF-I and the consequent overproduction of red blood cells characteristic of PV.

Cells, Cultured↗
PubMed1997

Acromegaly.

Acromegaly can be a serious, chronic, debilitating condition. The disease is often missed for years, resulting in significantly delayed diagnosis. This article reviews recent advances in our understanding of acromegaly and the impact of current approaches on the diagnosis and monitoring of patients with this disorder.

Acromegaly↗
PubMed1997

The c-erbB-2/neu proto-oncogene in human pituitary tumours.

OBJECTIVE: The aetiology of most pituitary tumours remains unknown. We have examined the potential role of neu receptor proto-oncogene in human pituitary tumorigenesis. MATERIALS AND METHODS: Ten non-tumorous pituitary glands and 16 morphologically characterized functional and clinically non-functioning pituitary adenomas were studied. Protein expression was examined by immunohistochemistry, mRNA expression by RT-PCR and competitive PCR, gene amplification by differential PCR, and point mutations by DNA sequencing. RESULTS: Cytoplasmic positivity for neu was identified in a few scattered cells of the non-tumorous adenohypophysis using an antibody to the intracytoplasmic domain of neu, but no membrane staining was found with an antibody to the extracellular domain; the latter is said to reflect gene amplification. mRNA transcript signals of the expected size were identified in the normal adenohypophysis and in all 16 adenomas examined. No increase in the degree of mRNA expression, however, was noted in the different tumour types compared to normal human pituitary tissue as determined by competitive PCR. As neu can be activated to an oncogene by a point mutation in the transmembrane region, nucleotide substitutions in this domain were investigated. Direct sequencing of codon 659 revealed no point mutations in any of the tumours. Furthermore, since amplification of neu has been noted in various human malignancies, DNA from these tumours was examined by differential PCR. No detectable differences were noted between the neu gene and the single-copy reference gene IFN-gamma. CONCLUSION: The neu gene is expressed in adenohypophysial cells and their tumours. In pituitary adenomas, this expression is not associated with gene amplification or activating mutations to suggest a direct role in pituitary tumorigenesis.

Adenoma↗
PubMed1997

Altered expression of fibroblast growth factor receptors in human pituitary adenomas.

We have shown that basic fibroblast growth factor (FGF) is heterogeneously expressed by human pituitary adenomas and may be implicated as a growth stimulus for these tumors. There are four mammalian FGF receptor (FGFR) genes encoding a complex family of transmembrane tyrosine kinases. The prototypic receptor is composed of three Ig-like extracellular ligand-binding domains, a transmembrane domain, and a cytoplasmic split tyrosine kinase. Multiple forms of cell-bound or secretable isoforms of FGFR-1, -2, and -3 can be generated by cell- and tissue-specific alternative splicing, resulting in tissue-specific FGF function. Shifts in isoform expression accompany tumor progression in some systems. We examined the normal human adenohypophysis and 40 pituitary adenomas to determine the pattern of FGFR expression by reverse transcription-PCR; all tumors were characterized clinically and morphologically. Ribonucleic acid (RNA) was extracted from frozen tumor tissue and primers were used to distinguish messenger RNA of the secretable first Ig-like domain (I) and those of the transmembrane and kinase domains (K) of each FGFR subtype. The normal pituitary-expressed mRNAs for FGFR-1 I and K, FGFR-2 I and K, FGFR-3 I and K, and FGFR-4 I but not FGFR-4 K; this represents the first report of a truncated isoform of FGFR-4, indicating possible alternative polyadenylation sites in this receptor. Only 3 tumors had the same pattern of expression of the 4 FGFRs as the normal gland. Although all tumors expressed FGFR-1 I, 1 tumor did not express FGFR-1 K, suggesting the production of only a secretable form of FGFR-1 by this tumor. Four tumors were negative for FGFR-2 I and K; 6 expressed the secretable form only, and 17 expressed FGFR-2 K but not I. All tumors expressed FGFR-3 I; 14 had secretable forms only, and no tumors expressed FGFR-3 K alone. As in the normal gland, 13 tumors expressed only the secretable I form of FGFR-4. Unlike the normal pituitary, however, 22 expressed FGFR-4 I and K, indicating a possible tumor-specific transmembrane receptor. Five tumors were negative for FGFR-4 I and K. Expression of FGFR proteins was confirmed by immunohistochemical localization of the C-terminal portion of FGFR-1, -2, -3, and -4; the results correlated with the RNA data in each case. There was no correlation between tumor type, size, or aggressiveness and the expression pattern of FGFRs. Our study suggests that pituitary adenomas have altered FGFR subtype and isoform expression, which may determine their hormonal and proliferative responses to FGFs.

Adenoma↗
PubMed1996

Prevalence of activating ras mutations in morphologically characterized thyroid nodules.

Ras proteins are signal-transducing proteins that share common properties with membrane-anchored G proteins. Mutations at codon 12/13 or codon 61 alter GTP-binding or GTPase activity, respectively. Such activating mutations are present in nearly 30-50% of various malignancies including colon, breast, and lung carcinomas. There are conflicting data regarding the prevalence of ras mutations in the thyroid and their possible pathogenetic role in the different tumor types. To address this question, we examined 45 morphologically characterized thyroid carcinomas, adenomas, and hyperplastic nodules using a highly sensitive single-stranded conformation polymorphism (SSCP) approach combined with DNA-sequencing. DNA from cell lines with known mutations served as controls. A G to A H13 codon substitution replacing an Asp for a Gly residue was detected in 1 papillary carcinoma. Although no H12 or H61 codon substitutions were identified, 2 discrete alterations were identified in codons H17 and 22. No N12/13 codon substitutions were identified. N61 codon substitutions of A to G resulting in a Gly to Arg substitution were detected in 2 papillary carcinomas; the same mutation was also found in one follicular adenoma. Interestingly, K12/13 and K61 ras mutations were not present in any of the tumors examined. These data establish a low prevalence of mutations in all ras gene family members in human thyroid neoplasms. This difference from neoplasms of other organs may explain the relatively indolent biologic behavior of many thyroid tumors and supports an alternate early genetic mutation that is more characteristic of these neoplasms.

Adult↗
PubMed1996

Expression of steroidogenic factor-1 (SF-1) mRNA and protein in the human placenta.

Steroidogenic factor-1 (SF-1), also known as adrenal-4-binding protein (Ad4BP), is a recently-described transcription factor, which has been shown to be important for the differentiation of steroidogenic tissues. In addition, SF-1 has been implicated in regulating the glycoprotein hormone alpha-subunit gene in a pituitary gonadotroph cell line. Considering that the human placenta produces both steroids and human chorionic gonadotrophin (HCG), we studied the expression of SF-1 in this tissue. Human first trimester and term placentas were collected at the time of therapeutic abortion and birth respectively. Messenger RNA was extracted, reverse transcribed, and used for polymerase chain reaction (PCR) amplification with primers specific for the human SF-1 cDNA sequence. A band of the expected size was obtained from both first and third trimester samples, indicating that SF-1 expression in the human placenta starts early in pregnancy and is maintained until birth. In addition to normal placental samples, JEG3 and JAR choriocarcinoma cells were also analysed and found to express SF-1 mRNA. The identity of the amplified products was confirmed by diagnostic restriction digest and Southern hybridization. SF-1 protein was localized mainly to the nuclei of the cyto- and syncytiotrophoblast and to some mesenchymal villous nuclei by immunocytochemistry using a specific antibody. We conclude that SF-1 is expressed in human first trimester and term placenta, where it could be implicated in the regulation of HCG production, in steroidogenesis, or both.

Base Sequence↗
PubMed1996

Epidermal growth factor and its receptor (EGF-R) in human pituitary adenomas: EGF-R correlates with tumor aggressiveness.

Epidermal growth factor (EGF) has been localized in several human neoplasms and has been shown to have a significant correlation to prognosis. We investigated the potential role of the EGF receptor (EGF-R) system in pituitary tumorigenesis by examining the expression of EGF and EGF-R in the different types of human pituitary adenomas. EGF was identified by immunohistochemistry in all cell types of the nontumorous adenohypophysis and in all types of morphologically characterized functional (n = 9) and nonfunctional (n = 17) adenomas. To confirm local EGF synthesis, ribonucleic acid (RNA) from human pituitary adenomas was reverse transcribed and PCR amplified. Transcript signals of the expected size were identified, with marked variation in 41 of 48 adenomas. To assess possible secretion in vitro, EGF was measured in pituitary tumor culture medium. No measurable quantities of EGF were present in conditioned culture medium from all 35 adenomas examined, consistent with the rapid uptake of EGF by unoccupied functional EGF-R sites. Using a specific monoclonal antibody that recognizes the extracellular ligand-binding domain of the human EGF-R, we found EGF-R in cells in the normal pituitary and in some functional and nonfunctional adenomas with extremely variable intensity. By RT-PCR, EGF-R messenger RNA (mRNA) expression was also identified, with marked variation in all 48 adenomas examined and in the nontumorous pituitary. The highest degrees of EGF-R mRNA expression were present in somatotroph adenomas and the aggressive silent subtype 3 adenomas. Tumors from patients with recurrent acromegaly demonstrated significantly higher levels of EGF-R mRNA than those from patients with nonrecurrent disease. In conclusion, EGF and EGF-R are expressed in a variable manner in all types of human pituitary adenomas. The overexpression of EGF-R in recurrent somatotroph adenomas and aggressive silent subtype 3 adenomas suggests a selective mechanism for the EGF/EGF-R family in the growth of aggressive pituitary tumors.

Adenoma↗
PubMed1996

The transcription activator steroidogenic factor-1 is preferentially expressed in the human pituitary gonadotroph.

Steroidogenic factor-1 (SF-1), also known as adrenal-4-binding protein, is a transcription factor that is important for the differentiation of steroidogenic tissues. We investigated whether SF-1 is expressed in specific hormone-producing cell types in the human pituitary and its adenomas. Pituitary adenomas (n = 35) were collected at the time of surgery, and normal adenohypophyses were obtained from autopsies; 3 corticotroph adenomas were excluded because pit-1 messenger ribonucleic acid (mRNA) expression indicated contamination by nontumorous elements. Expression of SF-1 mRNA was determined by reverse transcription-PCR. SF-1 protein was localized with immunocytochemistry. By reverse transcription-PCR, SF-1 mRNA was found in the nontumorous pituitary and in pituitary adenomas expressing gonadotropins. All 8 gonadotroph adenomas had a strong signal for SF-1. SF-1 mRNA was also detected in 2 of 3 corticotroph adenomas, 2 of 13 somatotroph/mammosomatotroph adenomas, 1 of 6 lactotroph adenomas, and 2 silent subtype 3 adenomas; however, in most of the positive tumors there was also positivity for FSH beta and/or LH beta mRNA, suggesting that contaminating nontumorous gonadotrophs may be the source of SF-1 mRNA signal. SF-1 protein was localized by immunocytochemistry in the nuclei of scattered cells of the nontumorous adenohypophysis that were shown to be gonadotrophs with double immunostaining and in gonadotroph adenomas; nuclear staining was not found in other adenoma types, except in areas shown to contain trapped nontumorous tissue. We conclude that SF-1 expression correlates with the expression of gonadotropins. These findings implicate SF-1 as a cell-specific transcription factor that may regulate gonadotroph differentiation in the pituitary.

Adenoma↗
PubMed1996

ret/PTC-1, -2, and -3 oncogene rearrangements in human thyroid carcinomas: implications for metastatic potential?

The ret/PTC oncogene is unique to papillary thyroid cancer. Three forms of this oncogene, formed by translocation of three different genes to the tyrosine kinase domain of the ret protooncogene, result in constitutive kinase activation. Correlation with clinical outcome is controversial; ret/PTC-1 has been suggested to predict aggressive behavior. There is no morphological description of ret/PTC-positive tumors. We analyzed 60 thyroid carcinomas for ret/PTC expression to determine correlation with clinical history, disease stage, or tumor morphology. Ribonucleic acid extracted from frozen tissue was reverse transcribed; PCR was performed to amplify ret/PTC-1, 2, and -3. The TPC-1 cell line was the positive control for ret/PTC-1. All tumors were characterized morphologically. Clinical data were collected. The 57 papillary and 3 follicular carcinomas were resected from 44 female patients and 15 males. The average age at diagnosis was 46.2 yr (range. 24-83 yr). Three patients had a history of neck irradiation. At diagnosis, 11 patients had extrathyroidal tumor extension, 20 had lymph node metastases, and 1 had lung metastasis. Thirteen patients had tall cell papillary carcinomas; 3 tumors had focal insular or anaplastic dedifferentiation. The average follow-up was 13.4 months, during which 4 patients had recurrent disease. No deaths occurred. One papillary carcinoma (1.7%) was positive for ret/PTC-1, none was positive for ret/PTC-2, and 2(3.4%) were positive for ret/PTC-3. Although all 3 patients who had tumors containing ret/PTC rearrangements were under the age of 45 yr (range, 26-44 yr) and had small tumors (< 1.2 cm), 2 of these 3 patients presented with lymph node metastases, and the third had lymphatic invasion. ret/PTC oncogene expression did not correlate with radiation history. In summary, ret/PTC oncogene rearrangements were found in 3 of 60 (5%) thyroid carcinomas and were not present in tumors with aggressive morphological features. However, we found ret/PTC rearrangements in young patients (< 45 yr of age) with small thyroid carcinomas showing a predisposition for lymphatic involvement, suggesting a possible role in the development of this subgroup of tumors.

Adult↗
PubMed1996

The diagnosis and management of acromegaly: a Canadian consensus report.

OBJECTIVE: To reach a Canadian consensus on the diagnosis and management of acromegaly. OPTIONS DIAGNOSIS: documenting autonomous growth-hormone hypersecretion and imaging of the pituitary. TREATMENT: surgical resection, adjunctive therapy with bromocriptine or octreotide and radiation therapy. OUTCOMES: Reduction of the morbidity and mortality associated with acromegaly. EVIDENCE: Review of international literature. VALUES: Achievement of consensus among a panel of Canadian endocrinologists. BENEFITS, HARMS AND COSTS: Acromegaly is a chronic debilitating condition that is associated with morbidity and mortality. This consensus statement is designed to improve the diagnosis and management of this rare condition in order to minimize the negative outcomes. Costs were not considered. RECOMMENDATIONS: The diagnosis of acromegaly is established by documenting autonomous growth-hormone hypersecretion and by imaging the pituitary. Surgical resection is the cornerstone of treatment; however, adjunctive therapy is often needed. Although growth-hormone reduction is often associated with alleviation of symptoms, an attempt should also be made to normalize levels of growth hormone and its target growth factor, insulin-like growth factor-I (IGF-I). Persistent secretion of excess growth hormone and IGF-I may pose significant long-term health risks. A suggested therapeutic algorithm is provided. The ease of administration of bromocriptine should prompt a trial of therapy with this agent. The subcutaneous use of octreotide is of particular benefit to those patients with persistently high levels of growth hormone and IGF-I that cannot be suppressed by other means. Because acromegaly is relatively rare and complex, its diagnosis and treatment require the concerted efforts of an endocrinologist, an neurosurgeon and a radiation oncologist.

Acromegaly↗
PubMed1995

Continuous versus intermittent subcutaneous infusion of octreotide in the treatment of acromegaly.

This review evaluates the efficacy, tolerability, and safety of continuous subcutaneous infusion (CSI) relative to intermittent subcutaneous injection (ISI) of the somatostatin analog, octreotide in the treatment of acromegaly. Data was extracted from five clinical series using CSI octreotide in acromegaly, six reports comparing CSI to ISI, and three studies comparing pulsatile subcutaneous infusion (PSI) to ISI. Effects of each drug regimen on the control of growth hormone (GH), insulin-like growth factor (IGF-1), clinical symptomatology, pituitary tumor size, and adverse effects were evaluated. Normalization of serum GH or IGF-1 levels, as well as improvement in clinical symptoms was reported in the majority of the patients studied. Cases in which pituitary adenomas decreased in size were also documented during the study period. When the effects of CSI were compared with ISI, a more pronounced control of GH and IGF-1 was observed. In addition, diurnal GH fluctuation during CSI was significantly reduced relative to ISI in two reports. Moreover, in two patients, CSI achieved similar clinical and biochemical effects at lower doses than when the drug was given by ISI. Finally, adverse effects with CSI may be less severe than with ISI. Continuous subcutaneous infusion of octreotide produced biochemical improvement in 67 of the 88 patients reviewed. When compared with ISI, CSI induced more pronounced biochemical control, often with less fluctuation in GH and IGF-1 levels. Because of a lack of data, definite conclusions regarding the differences between regimens on clinical symptomatology and tolerability could not be discerned. A large prospective, long-term randomized crossover study is recommended to make these determinations.

Acromegaly↗
PubMed1995

A prospective multicenter octreotide dose response study in the treatment of acromegaly.

The somatostatin analog octreotide has proven to be an effective form of treatment for various hypersecretory states including acromegaly. This report describes the effects of escalating doses of octreotide on the growth hormone (GH) profiles, insulin-like growth factor-1 (IGF-1), prolactin (PRL), and adverse effects in 99 patients with acromegaly. Treatment with octreotide was initiated at 50 micrograms sc every 8 h and the dose gradually titrated to a maximum of 1500 micrograms/d if more than 75% of GH determinations in a 12-h day profile were above detection limits. This dose was maintained for the duration of 6 months. Seventy-three percent of patients did not reach the GH reduction criterion at the 300 micrograms dose. Mean GH levels decreased from 33 +/- 4 micrograms/l to 10 +/- 1 microgram/l (p < 0.001) while receiving the 300 micrograms/d dose. The percentage decrease in mean GH levels, however, was dose-independent reaching 50 +/- 5% of baseline with 300 micrograms/d, 55 +/- 5% with 600 micrograms/d, 57 +/- 6% with 900 micrograms/d, and 56 +/- 5% with 1500 micrograms/d. Maximal GH suppression, however, was achieved in 40%, 17%, 7%, and 16% of subjects by the 300 micrograms, 600 mg, 900 micrograms, and 1500 micrograms doses respectively. GH suppression was independent of duration of treatment. While there was a tendency for a greater degree of IGF-1 reduction with the higher doses, the rate of normalization (30-37%) was not influenced by the dose of octreotide administered. Elevated PRL levels also declined with the use of higher doses of octreotide.(ABSTRACT TRUNCATED AT 250 WORDS)

Acromegaly↗