DOCSLIB.ORG

Jcem2957.Pdf

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Jcem2957.Pdf SPECIAL FEATURE Clinical Review A Critical Analysis of Clinically Available Somatostatin Analog Formulations for Therapy of Acromegaly Robert D. Murray and Shlomo Melmed Department of Endocrinology (R.D.M.), Leeds Teaching Hospitals National Health Service Trust, Leeds LS9 7TF, United Kingdom; and Department of Medicine (S.M.), Cedars Sinai Medical Center, University of California Los Angeles School of Medicine, Los Angeles, Downloaded from https://academic.oup.com/jcem/article/93/8/2957/2598353 by guest on 24 September 2021 California 90048 Context: Short and long-acting somatostatin (SRIF) analogs are approved for clinical use in acro- megaly. Recent analysis of the relative efficacy of octreotide LAR and lanreotide SR on the GH-IGF-I axis in acromegaly favored octreotide LAR in the secondary treatment of patients not preselected by SRIF responsiveness. A novel aqueous formulation of lanreotide, lanreotide Autogel (ATG), has recently been approved and is the predominant (and only in the United States) formulation of lanreotide used clinically. Objective: We performed a critical review of SRIF analog treatment to establish the relative efficacy of three clinically available SRIF analog preparations, octreotide LAR, lanreotide SR, and lanreotide ATG (Somatuline depot in the United States) in control of the GH-IGF-I axis in acromegaly. Data Sources: Data were drawn from MEDLINE and the bibliography of analyses of long-acting SRIF analogs. Data Collection: We reviewed the largest studies of sc octreotide, octreotide LAR, and lanreotide SR, all that included biochemical end-point data for lanreotide ATG, and studies that directly compared the efficacy of octreotide LAR and lanreotide SR. Data Synthesis: Caveats considered included differences in baseline GH and IGF-I values, patient selection, and interassay and intraassay variability, confounding the analysis. Studies comparing patients treated contiguously with lanreotide SR and octreotide LAR are fraught with method- ological problems, however, are suggestive of marginally greater efficacy in control of the GH-IGF-I axis for octreotide LAR. Lanreotide ATG shows noninferiority to lanreotide SR. Five small studies directly comparing octreotide LAR and lanreotide ATG suggest no significant differences between these preparations in control of biochemical end-points. Conclusion: Lanreotide ATG and octreotide LAR are equivalent in the control of symptoms and biochemical markers in patients with acromegaly. (J Clin Endocrinol Metab 93: 2957–2968, 2008) cromegaly is a rare disease resulting from a benign pituitary cular, cerebrovascular, and respiratory disease (2–4). The most A somatotrophinoma in over 95% of cases (1), and is char- robust determinant of excess mortality is the circulating GH level acterized clinically by excessive skeletal growth, soft tissue en- (2, 5), though some studies have suggested that IGF-I levels may largement, disability, and shortened life expectancy. Estimates of contribute to adverse mortality outcomes (6, 7). Successful man- the excess mortality from epidemiological studies suggest an ap- agement requires aggressive reduction of GH levels to less than proximate 2-fold relative risk ascribed primarily to cardiovas- 0021-972X/08/$15.00/0 Abbreviations: ATG, Autogel; SRIF, somatostatin; SSTR, specific receptor subtype. Printed in U.S.A. Copyright © 2008 by The Endocrine Society doi: 10.1210/jc.2008-0027 Received January 4, 2008. Accepted May 2, 2008. First Published Online May 13, 2008 J Clin Endocrinol Metab, August 2008, 93(8):2957–2968 jcem.endojournals.org 2957 2958 Murray and Melmed SRIF Analogs J Clin Endocrinol Metab, August 2008, 93(8):2957–2968 2.5 ␮g/liter (5 mU/liter) to achieve mortality rates equivalent to tively. Collectively, these studies suggested that biochemical con- the normal population (2, 5). trol of acromegaly with clinical improvement could be achieved Therapeutic modalities available to achieve this target include in 50–60% of patients using thrice daily sc octreotide (Table 1). surgery, radiotherapy, and medical therapy. Surgery by a skilled neurosurgeon remains the mainstay of management, especially for small tumors. However, biochemical control is achieved in Long-Acting SRIF Analogs less than 50% of patients with macroadenomas, but greater than 80% of microadenomas (1). Control of GH and IGF-I levels after Octreotide requires sc administration three times per day to radiotherapy occurs over a period of many years and frequently maintain GH suppression, and biochemical “escape” was fre- takes more than a decade. Therefore, medical therapy plays a quently observed at the end of the dosing interval impacting on crucial role in a large proportion of patients with acromegaly overall biochemical control. In an effort to increase the dosing who fail to be cured by surgery, or during the interim while the interval and provide more sustained control of GH levels, two Downloaded from https://academic.oup.com/jcem/article/93/8/2957/2598353 by guest on 24 September 2021 effects of radiotherapy are realized. Somatostatin (SRIF) analogs long-acting depot formulations of SRIF analogs, octreotide LAR introduced in the mid-1980s have become the mainstay of med- and lanreotide SR, were developed. Both peptide molecules are ical management (1, 8). SRIF analogs have been used with suc- comprised of eight amino acids with a disulfide bridge, and are cess as primary therapy in which operative intervention is un- formulated as microspheres of biodegradable polymer contain- likely to be curative or is associated with an unacceptable risk of ing the active peptide. Octreotide LAR 10–30 mg is injected im morbidity and mortality (1, 9, 10). every 4 wk and lanreotide SR 30 mg im every 7–14 d. Efficacy of In this review we have confined comparisons of efficacy of both these preparations in the treatment of acromegaly has been long-acting SRIF analogs in patients with acromegaly to the bio- shown in a large number of studies (27–34). Most studies ex- chemical control of disease. Relative tumor shrinkage is an im- amining the efficacy of long-acting SRIF analogs have studied portant determinant of which SRIF analog is used clinically, patients after surgery and/or radiotherapy, however, more re- however, there are currently no data from studies randomizing cently, have included a subset of patients who have been treated patients to different analogs and using tumor shrinkage as a as primary therapy. Current evidence supports a similar rate of primary end-point. Switch studies are of limited value because GH and IGF-I normalization in patients treated as primary or tumor shrinkage is greatest when SRIF analogs are used as pri- secondary therapy (9, 30). Due to difficulties differentiating be- mary therapy and during the first 3-months treatment. tween primary and secondary treatment in most studies, this review will not differentiate between these subgroups. Baldelli et al. (27) and Verhelst et al. (28) studied the efficacy SRIF and Octreotide of lanreotide SR in 118 and 66 patients with acromegaly, re- spectively (Table 1). In both studies patients were switched from SRIF is widely distributed within multiple organ systems, and sc octreotide to lanreotide SR, and the dose of the latter opti- plays an important role in regulating hormone release and other mized on the basis of the biochemistry. Overall, lanreotide SR physiological functions (11). The two most biologically active was found to be more efficacious in controlling GH and IGF-I SRIF isoforms comprise 14 or 28 amino acids. SRIF action is levels than sc octreotide, with 44–77% of patients achieving mediated through five specific receptor subtypes (SSTRs) (1–5) biochemical targets. The largest two studies of octreotide LAR differentially expressed in a tissue-specific pattern, thereby con- enrolled 151 and 110 patients with active acromegaly (29, 30) ferring functional and therapeutic specificity of ligand action (Table 1). In the first of these studies, Lancranjan and Atkinson (12). Somatotrophs preferentially express SSTR2 and SSTR5 (1999) (29) commenced patients on octreotide LAR after 4-wk (13–15), and respond predominantly to SSTR2-binding analogs individualized sc octreotide, whereas in the second study, pa- (16, 17). SSTRs interact with each other (18), indicating complex tients were naive to SRIF analogs (30). Biochemical targets of GH pituitary cell responsiveness to receptor ligands (19). SRIF ana- less than 2.5 ␮g/liter and a normalized IGF-I were achieved in logs also act at the periphery to inhibit GH action (20). Both 63–75% of patients. However, of note is that the overall per- octreotide and lanreotide exhibit similar affinities for SSTR2 and centage of patients controlled by lanreotide SR and octreotide SSTR5 in vitro, and apparent differences in clinical efficacy LAR was not unduly different from that observed in previous discussed in this review, therefore, likely relate to differences studies strictly optimizing the dose of sc octreotide. in pharmacodynamics and pharmacokinetics of the various A direct comparison of the percentages of patients achieving formulations. GH and IGF-I targets at the end of these four relatively large Recognition that SRIF is the primary physiological negative studies suggests that octreotide LAR exhibits greater efficacy regulator of pituitary GH release led to investigation of a ther- than lanreotide SR. However, in the Lancranjan and Atkinson apeutic role for SRIF in managing acromegaly. Although SRIF (29) study, all patients were selected on the basis of a significant inhibited GH release from somatotrophinomas (21, 22), clinical known prior response to sc octreotide. Therefore, it is likely that usefulness was limited due to a half-life of 2–3 min. This thera- this cohort would have responded well to any clinically available peutic limitation was eased by the development of the SRIF an- long-acting SRIF analog. This interpretation is supported by ex- alog, octreotide, first used in clinical trials in 1984 (23, 24). Two amining the proportion of patients with suppression of GH less of the largest studies using this peptide were published in the than 2.5 ␮g/liter when receiving sc octreotide.
Load more

Recommended publications
  • Drug Code List
    HCPCS/Drug Code List Version 13.2 Revised 6/1/21 List will be updated routinely Disclaimer: For drug codes that require an NDC, coverage depends on the drug NDC status (rebate eligible, Non-DESI, non-termed, etc) on the date of service. Note: Physician/Facility-administered medications are reimbursed using the Centers for Medicare and Medicaid Services (CMS) Part B Drug pricing file found on the CMS website--www.cms.gov. In the absence of a fee, pricing may reflect the methodolgy used for retail pharmacies. Go to data.medicaid.gov for a complete list of drug NDCs participating in the Medicaid drug rebate program. Consult with each Managed Care Organization (MCO) about their coverage guidelines and prior authroization requirements, if applicable. Highlights represent updated material for each specific revision of the Drug Code List. Code Description Brand Name NDC NDC unit Category Service AC CAH P NP MW MH HS PO OPH HI ID DC Special Instructions req. of Limits OP OP TF for measure drug rebate ? 90281 human ig, im Gamastan Yes ML Antisera NONE X X X X Closed 3/31/13. 90283 human ig, iv Gamimune, Yes ML Antisera NONE X X X X Closed 3/31/13. Cost invoice required with claim. Restricted to ICD-9 diagnoses codes 204.10 - 204.12, Flebogamma, 279.02, 279.04, 279.06, 279.12, 287.31, and 446.1, and must be included on claim form, effective 10/1/09. Gammagard 90287 botulinum antitoxin N/A Antisera Not Covered 90288 botulism ig, iv No ML NONE X X X X Requires documentation and medical review 90291 cmv ig, iv Cytogam Yes ML Antisera NONE X X X X Closed 3/31/13.
    [Show full text]
  • Pharmacological Management of Acromegaly: a Current Perspective
    Neurosurg Focus 29 (4):E14, 2010 Pharmacological management of acromegaly: a current perspective SUNIL MANJILA , M.D.,1 Osmo N D C. WU, B.A.,1 FAH D R. KHAN , M.D., M.S.E.,1 ME H ree N M. KHAN , M.D.,2 BAHA M. AR A F AH , M.D.,2 AN D WA rre N R. SE L M AN , M.D.1 1Department of Neurological Surgery, The Neurological Institute, and 2Division of Clinical and Molecular Endocrinology, University Hospitals Case Medical Center, Cleveland, Ohio Acromegaly is a chronic disorder of enhanced growth hormone (GH) secretion and elevated insulin-like growth factor–I (IGF-I) levels, the most frequent cause of which is a pituitary adenoma. Persistently elevated GH and IGF-I levels lead to substantial morbidity and mortality. Treatment goals include complete removal of the tumor causing the disease, symptomatic relief, reduction of multisystem complications, and control of local mass effect. While trans- sphenoidal tumor resection is considered first-line treatment of patients in whom a surgical cure can be expected, pharmacological therapy is playing an increased role in the armamentarium against acromegaly in patients unsuitable for or refusing surgery, after failure of surgical treatment (inadequate resection, cavernous sinus invasion, or transcap- sular intraarachnoid invasion), or in select cases as primary treatment. Three broad drug classes are available for the treatment of acromegaly: somatostatin analogs, dopamine agonists, and GH receptor antagonists. Somatostatin analogs are considered as the first-line pharmacological treatment of acromegaly, although effica- cy varies among the different formulations. Octreotide long-acting release (LAR) appears to be more efficacious than lanreotide sustained release (SR).
    [Show full text]
  • To Download a List of Prescription Drugs Requiring Prior Authorization
    Essential Health Benefits Standard Specialty PA and QL List July 2016 The following products require prior authorization. In addition, there may be quantity limits for these drugs, which is notated below. Therapeutic Category Drug Name Quantity Limit Anti-infectives Antiretrovirals, HIV SELZENTRY (maraviroc) None Cardiology Antilipemic JUXTAPID (lomitapide) 1 tab/day PRALUENT (alirocumab) 2 syringes/28 days REPATHA (evolocumab) 3 syringes/28 days Pulmonary Arterial Hypertension ADCIRCA (tadalafil) 2 tabs/day ADEMPAS (riociguat) 3 tabs/day FLOLAN (epoprostenol) None LETAIRIS (ambrisentan) 1 tab/day OPSUMIT (macitentan) 1 tab/day ORENITRAM (treprostinil diolamine) None REMODULIN (treprostinil) None REVATIO (sildenafil) Soln None REVATIO (sildenafil) Tabs 3 tabs/day TRACLEER (bosentan) 2 tabs/day TYVASO (treprostinil) 1 ampule/day UPTRAVI (selexipag) 2 tabs/day UPTRAVI (selexipag) Pack 2 packs/year VELETRI (epoprostenol) None VENTAVIS (iloprost) 9 ampules/day Central Nervous System Anticonvulsants SABRIL (vigabatrin) pack None Depressant XYREM (sodium oxybate) 3 bottles (540 mL)/30 days Neurotoxins BOTOX (onabotulinumtoxinA) None DYSPORT (abobotulinumtoxinA) None MYOBLOC (rimabotulinumtoxinB) None XEOMIN (incobotulinumtoxinA) None Parkinson's APOKYN (apomorphine) 20 cartridges/30 days Sleep Disorder HETLIOZ (tasimelteon) 1 cap/day Dermatology Alkylating Agents VALCHLOR (mechlorethamine) Gel None Electrolyte & Renal Agents Diuretics KEVEYIS (dichlorphenamide) 4 tabs/day Endocrinology & Metabolism Gonadotropins ELIGARD (leuprolide) 22.5 mg
    [Show full text]
  • Somatostatin Analogues in the Treatment of Neuroendocrine Tumors: Past, Present and Future
    International Journal of Molecular Sciences Review Somatostatin Analogues in the Treatment of Neuroendocrine Tumors: Past, Present and Future Anna Kathrin Stueven 1, Antonin Kayser 1, Christoph Wetz 2, Holger Amthauer 2, Alexander Wree 1, Frank Tacke 1, Bertram Wiedenmann 1, Christoph Roderburg 1,* and Henning Jann 1 1 Charité, Campus Virchow Klinikum and Charité, Campus Mitte, Department of Hepatology and Gastroenterology, Universitätsmedizin Berlin, 10117 Berlin, Germany; [email protected] (A.K.S.); [email protected] (A.K.); [email protected] (A.W.); [email protected] (F.T.); [email protected] (B.W.); [email protected] (H.J.) 2 Charité, Campus Virchow Klinikum and Charité, Campus Mitte, Department of Nuclear Medicine, Universitätsmedizin Berlin, 10117 Berlin, Germany; [email protected] (C.W.); [email protected] (H.A.) * Correspondence: [email protected]; Tel.: +49-30-450-553022 Received: 3 May 2019; Accepted: 19 June 2019; Published: 22 June 2019 Abstract: In recent decades, the incidence of neuroendocrine tumors (NETs) has steadily increased. Due to the slow-growing nature of these tumors and the lack of early symptoms, most cases are diagnosed at advanced stages, when curative treatment options are no longer available. Prognosis and survival of patients with NETs are determined by the location of the primary lesion, biochemical functional status, differentiation, initial staging, and response to treatment. Somatostatin analogue (SSA) therapy has been a mainstay of antisecretory therapy in functioning neuroendocrine tumors, which cause various clinical symptoms depending on hormonal hypersecretion. Beyond symptomatic management, recent research demonstrates that SSAs exert antiproliferative effects and inhibit tumor growth via the somatostatin receptor 2 (SSTR2).
    [Show full text]
  • Regulatory Mechanisms of Somatostatin Expression
    International Journal of Molecular Sciences Review Regulatory Mechanisms of Somatostatin Expression Emmanuel Ampofo * , Lisa Nalbach, Michael D. Menger and Matthias W. Laschke Institute for Clinical & Experimental Surgery, Saarland University, 66421 Homburg/Saar, Germany; [email protected] (L.N.); [email protected] (M.D.M.); [email protected] (M.W.L.) * Correspondence: [email protected]; Tel.: +49-6841-162-6561; Fax: +49-6841-162-6553 Received: 25 May 2020; Accepted: 9 June 2020; Published: 11 June 2020 Abstract: Somatostatin is a peptide hormone, which most commonly is produced by endocrine cells and the central nervous system. In mammals, somatostatin originates from pre-prosomatostatin and is processed to a shorter form, i.e., somatostatin-14, and a longer form, i.e., somatostatin-28. The two peptides repress growth hormone secretion and are involved in the regulation of glucagon and insulin synthesis in the pancreas. In recent years, the processing and secretion of somatostatin have been studied intensively. However, little attention has been paid to the regulatory mechanisms that control its expression. This review provides an up-to-date overview of these mechanisms. In particular, it focuses on the role of enhancers and silencers within the promoter region as well as on the binding of modulatory transcription factors to these elements. Moreover, it addresses extracellular factors, which trigger key signaling pathways, leading to an enhanced somatostatin expression in health and disease. Keywords: somatostatin; pre-prosomatostatin; δ-cells; central nervous system (CNS); gut; hypothalamus; cAMP resonse element (CRE); pancreas/duodenum homeobox protein (PDX)1; paired box protein (PAX)6; growth hormone (GH); brain-derived neurotrophic factor (BDNF); glutamateric system; pancreas 1.
    [Show full text]
  • Hypothalamic-Pituitary Axes
    Hypothalamic-Pituitary Axes Hypothalamic Factors Releasing/Inhibiting Pituitary Anterior Pituitary Hormones Circulating ACTH PRL GH Hormones February 11, 2008 LH FSH TSH Posterior Target Pituitary Gland and Hormones Tissue Effects ADH, oxytocin The GH/IGF-I Axis Growth Hormone Somatostatin GHRH Hypothalamus • Synthesized in the anterior lobe of the pituitary gland in somatotroph cells PITUITARY • ~75% of GH in the pituitary and in circulation is Ghrelin 191 amino acid single chain peptide, 2 intra-molecular disulfide bonds GH Weight; 22kD • Amount of GH secreted: IGF-I Women: 500 µg/m2/day Synthesis IGF- I Men: 350 µg/m2/day LIVER Local IGF-I Synthesis CIRCULATION GH Secretion: Primarily Pulsatile Pattern of GH Secretion Regulation by two hypothalamic in a Healthy Adult hormones 25 Sleep 20 Growth - SMS Hormone 15 Somatostatin Releasing GHRH + GH (µg/L) Hormone Inhibitory of 10 Stimulatory of GH Secretion GH Secretion 05 0 GHRH induces GH Somatostatin: Decreases to allow 0900 2100 0900 synthesis and secretion Clocktime GH secretory in somatotrophs Bursts GH From: “Acromegaly” by Alan G. Harris, M.D. 1 Other Physiological Regulators of GH Secretion Pharmacologic Agents Used to Stimulate GH Secretion Amino Sleep Exercise Stress Acids Fasting Glucose Stimulate hypothalamic GHRH or Inhibit Somatostatin Hypothalamus GHRH SMS Hypoglycemia(Insulin) Pituitary L-dopa Arginine Clonidine GHRH + - SMS Pyridostigmine GH Target Tissues Metabolic & Growth Promoting GH Effects IGF-I Insulin-like growth factor I (IGF-I) Major Determinants of Circulating
    [Show full text]
  • And Signifor LAR (Pasireotide) Prior Authorization with Quantity Limit
    Signifor (pasireotide) and Signifor LAR (pasireotide) Prior Authorization with Quantity Limit Program Summary Signi for is the only target in this prior authorization program. Signifor LAR is not targeted in this pharmacy prior authorization program. This program applies to Commercial, NetResults A series, SourceRx, and Health Insurance Marketplace formularies. OBJECTIVE The intent of the Signifor (pasireotide) and Signifor LAR Prior Authorization (PA) program is to appropriately select patients for treatment according to product labeling and/or clinical studies and/or clinical practice guidelines. The program will approve for doses within the set limit. Doses above the set limit will be approved if the requested quantity is below the FDA limit and cannot be dose optimized or when the quantity is above the FDA limit and the prescriber has submitted documentation in support of therapy with a higher dose for the intended diagnosis. TARGET DRUGS Signifor (pasireotide) PRIOR AUTHORIZATION CRITERIA FOR APPROVAL Initial Evaluation Signifor will be approved for INITIAL USE when ALL of the following are met: 1. If Signifor, ONE of the following: A. The patient has a diagnosis of Cushing’s disease and ONE of the following: I. The patient has had recurrence or persistence after pituitary surgical resection OR II. The patient is not a candidate for pituitary surgical resection OR B. The patient has another FDA approved diagnosis AND 2. If Signifor LAR, ONE of the following: A. The patient has a diagnosis of acromegaly and ONE of the following: I. The use of requested agent is for adjunctive therapy with irradiation to alleviate acromegaly symptoms OR II.
    [Show full text]
  • A Comparison Between Octreotide-LAR and Lanreotide-SR in the Chronic Treatment of Acromegaly
    European Journal of Endocrinology (1999) 141 267–271 ISSN 0804-4643 CLINICAL STUDY A comparison between octreotide-LAR and lanreotide-SR in the chronic treatment of acromegaly R Cozzi, D Dallabonzana, R Attanasio, M Barausse and G Oppizzi Division of Endocrinology, Niguarda Hospital, Milan, Italy (Correspondence should be addressed to R Cozzi, Division of Endocrinology, Ospedale Niguarda, Piazza Ospedale Maggiore 3, I-20162 Milano, Italy; Email: [email protected]) Abstract Background: At present long-acting somatostatin analogs represent the first-line medical treatment of acromegaly. These drugs produce stable suppression of GH in most sensitive patients and IGF-I normalization in many; they also increase the compliance of acromegalic patients. The recent availability of octreotide (OC)-LAR, a somatostatin analog to be administered at 28-day intervals, has prompted us to compare, in the same group of patients, its effects and those of another somatostatin analog already available, lanreotide-SR (LSR, to be administered at 14-day intervals). Patients: Twelve somatostatin analog-sensitive acromegalic patients with active disease were enrolled in a prospective open sequential study after giving their informed consent. After chronic treatment with LSR (6–24 months), the patients were changed to treatment with OC-LAR, without wash-out. LSR had been administered at individually tailored dosages (30 mg i.m. at 7–21-day intervals, median 10 days – every 7 days in seven patients, 10 days in two patients, 14 days in two patients and 21 days in one patient) according to GH and IGF-I responses. Disease stability was obtained, as shown by maximal GH/IGF-I suppression without any significant hormonal change between the last two control measurements.
    [Show full text]
  • Developing Synthetic Peptide-Based Inhibitors of Human Growth Hormone Receptor
    Developing Synthetic Peptide-Based Inhibitors of Human Growth Hormone Receptor A Thesis Presented to The Honors Tutorial College Ohio University In Partial Fulfillment of the Requirements for Graduation from the Honors Tutorial College with the degree of Bachelor of Science in Chemistry by Maya R. Sattler May 2018 2 Acknowledgements This thesis represents the work a large number of people, to whom I am incredibly grateful. Thank you first and foremost to my adviser, Dr. Justin Holub, whose patience and teaching has been outstanding for the entire three years I have worked with him and been his student, all the way to the final deadline. Thank you to Dr. John Kopchick for allowing me the opportunity to explore a different area of research and a different laboratory environment. Both Dr. Lauren McMills and Dean Cary Frith have offered wonderful support and guidance through my entire HTC career and I will forever be appreciative. There are also many fellow students that have helped me with work and encouragement. Thank you to my fellow students in the Holub laboratory, especially Najah Alqaeisoom who was my first teacher and a delight to work with, and Danushka Arachchige who was always willing to help, no matter the problem. I would also like to thank my colleagues at Edison Biotechnology Institute for their support in all things trivial and otherwise. Dr. Reetobrata Basu in particular made all of the cell work possible through his teaching, assistance, and reassurances. Lastly, I am grateful to a larger community of people in Athens and worldwide that helped me through my four years of undergraduate studies and will continue to support me as I continue to progress.
    [Show full text]
  • V3.23 Durable Medical Equipment, Supplies, Vision and Hearing Hardware Nationwide by HCPCS Code
    TABLE K. — DURABLE MEDICAL EQUIPMENT, SUPPLIES, VISION AND HEARING HARDWARE NATIONWIDE- CHARGES BY HCPCS CODE v3.23 (January - December 2018) PAGE 1 of 95 Status/ Usage HCPCS Code Modifier 1 HCPCS Code Description Charge GAAF Category Indicator 2 A0100 Blank NONEMERGENCY TRANSPORT TAXI Blank $20.81 HCPCS - Non-Drugs A0110 Blank NONEMERGENCY TRANSPORT BUS Blank $61.62 HCPCS - Non-Drugs A0120 Blank NONER TRANSPORT MINI-BUS Blank $183.09 HCPCS - Non-Drugs A0130 Blank NONER TRANSPORT WHEELCH VAN Blank $85.54 HCPCS - Non-Drugs A0140 Blank NONEMERGENCY TRANSPORT AIR Blank $1,211.38 HCPCS - Non-Drugs A0160 Blank NONER TRANSPORT CASE WORKER Blank $2.42 HCPCS - Non-Drugs A0170 Blank TRANSPORT PARKING FEES/TOLLS Blank $303.72 HCPCS - Non-Drugs A0180 Blank NONER TRANSPORT LODGNG RECIP Blank $809.69 HCPCS - Non-Drugs A0190 Blank NONER TRANSPORT MEALS RECIP Blank $181.99 HCPCS - Non-Drugs A0398 Blank ALS ROUTINE DISPOSBLE SUPPLS Blank $132.93 HCPCS - Non-Drugs A0422 Blank AMBULANCE 02 LIFE SUSTAINING Blank $126.28 HCPCS - Non-Drugs A4206 Blank 1 CC STERILE SYRINGE&NEEDLE Blank $0.94 HCPCS - Non-Drugs A4207 Blank 2 CC STERILE SYRINGE&NEEDLE Blank $0.94 HCPCS - Non-Drugs A4208 Blank 3 CC STERILE SYRINGE&NEEDLE Blank $0.94 HCPCS - Non-Drugs A4209 Blank 5+ CC STERILE SYRINGE&NEEDLE Blank $0.94 HCPCS - Non-Drugs A4210 Blank NONNEEDLE INJECTION DEVICE Blank $1,233.33 HCPCS - Non-Drugs A4211 Blank SUPP FOR SELF-ADM INJECTIONS Blank $57.07 HCPCS - Non-Drugs A4212 Blank NON CORING NEEDLE OR STYLET Blank $13.31 HCPCS - Non-Drugs A4213 Blank 20+ CC SYRINGE ONLY
    [Show full text]
  • Acromegaly Caused by a Growth Hormone- Releasing Hormone Secreting Carcinoid Tumour of the Lung: the Effect of Octreotide Treatment
    CAsE rEPorT Acromegaly caused by a growth hormone- releasing hormone secreting carcinoid tumour of the lung: the effect of octreotide treatment C.M. de Jager1,*, L.J.M. de Heide1, G. van den Berg4, A. Wolthuis2, W.D. van Schelven3 Departments of 1Internal Medicine, 2Clinical Chemistry and 3Nuclear Medicine, Leeuwarden Medical Centre, the Netherlands, 4Department of Endocrinology, University Medical Centre Groningen, University of Groningen, the Netherlands, *corresponding author (currently: Department of Internal Medicine, University Medical Centre Groningen): +31 (0)50-361 61 61, e-mail: [email protected] AbsTract in acromegaly, the overproduction of growth hormone tumour of the lung, whose pituitary MRI and the presence is usually caused by a pituitary adenoma. We report a of a lesion in the lung led us to the possibility of this 74-year-old woman with acromegaly caused by ectopic rare cause of acromegaly. The response to a long-acting overproduction of growth hormone-releasing hormone somatostatin analogue will be reported as well. (GHrH), a rare diagnosis. The GHrH appeared to be produced by a carcinoid tumour of the lung. Treatment with monthly long-acting octreotide resulted in a reduction CAsE rEPorT in the symptoms and normalisation of the insulin-like growth factor-i, which has been maintained for more than A 74-year-old woman was referred to the hospital with two years now. A review of literature concerning causes anaemia caused by iron deficiency (haemoglobin 3.6 and treatment of ectopic GHrH-producing tumours is mmol/l, normal 7.2-9.0, MCV 59 fl, normal 81-96, ferritin presented.
    [Show full text]
  • How Are Growth Hormone and Insulin-Like Growth Factor-1 Reported As Markers for Drug Effectiveness in Clinical Acromegaly Resear
    Pituitary (2018) 21:310–322 https://doi.org/10.1007/s11102-018-0884-4 How are growth hormone and insulin-like growth factor-1 reported as markers for drug effectiveness in clinical acromegaly research? A comprehensive methodologic review Michiel J. van Esdonk1,2 · Eline J. M. van Zutphen1 · Ferdinand Roelfsema3 · Alberto M. Pereira3 · Piet H. van der Graaf1,4 · Nienke R. Biermasz3 · Jasper Stevens5 · Jacobus Burggraaf1,2 Published online: 31 March 2018 © The Author(s) 2018 Abstract Objective In rare disease research, most randomized prospective clinical trials can only use limited number of patients and are comprised of highly heterogeneous populations. Therefore, it is crucial to report the results in such a manner that it allows for comparison of treatment effectiveness and biochemical control between studies. The aim of this review was to investigate the current methods that are being applied to measure and report growth hormone (GH) and insulin-like growth factor-1 (IGF-1) as markers for drug effectiveness in clinical acromegaly research. Search strategy A systematic search of recent prospective and retrospective studies, published between 2012 and 2017, that studied the effects of somatostatin analogues or dopamine agonists in acromegaly patients was performed. The markers of interest were GH, IGF-1, and the suppression of GH after an oral glucose tolerance test (OGTT). Additionally, the use of pharmacokinetic (PK) measurements in these studies was analyzed. The sampling design, cut-off for biochemical control, reported units, and used summary statistics were summarized. Results A total of 49 articles were selected out of the 263 screened abstracts. IGF-1 concentrations were measured in all 49 studies, GH in 45 studies, and an OGTT was performed in 11 studies.
    [Show full text]