Only few patients using adjuvant somatostatin analogs are included in mortality series and it is of note that at present no mortality data exist for primary medical treatment including pegvisomant treatment. Most studies have suggested that a lower GH, for example below 2. In some but not all studies normal IGF-I was also associated with improved mortality Ayuk et al ; Biermasz et al a ; Holdaway et al ; Kauppinen et al Discrepancies between studies may be explained by a single GH or IGF-I measurement being used in most studies, which is hardly representative for disease status in the entire follow-up period; by the unavailability of IGF-I in a substantial number of patients; and by GH and IGF-I assay differences.
In addition, individual mortality studies consist of relatively small numbers of patients with large confidence intervals including 1. In acromegaly detailed studies of spontaneous GH secretion have demonstrated increased pulsatility increased pulse frequency , amplified burst mass, and increased basal secretion, associated with decreased regularity Barkan et al ; Ho et al ; van den Berg et al GH assays differ in specificity, sensitivity, and GH standard, and therefore individual clinical endocrine laboratories should establish normal ranges of gender- and age-related GH and IGF-I values and ideally corrected for fat mass or a fat mass-derived parameter Gullu et al ; Bidlingmaier and Strasburger IGF-I concentrations decrease with advancing age.
In addition, gender, sex hormone status, the use of oral estrogens, thyroxin, and body composition can all influence IGF-I concentrations Clemmons The currently available treatment modalities for acromegaly are selective transsphenoidal adenomectomy, radiotherapy, medical treatment, or combinations thereof. This oldest treatment modality was developed a century ago by the Austrian neurosurgeon Schloffer Schloffer It is generally performed via the transnasal, transsphenoidal route and is associated with low morbidity and mortality.
In recent years most neurosurgeons have adopted the endoscope in lieu of the surgical microscope, which has obvious advantages for the patient and also leads to better visualization of the operating field. Other variants of surgical techniques are neuronavigating and real-time intraoperative MRI scanning, aimed at visualization of tiny tumor remnants after resection of the adenoma Fahlbusch et al ; Thomale et al GH secretion pattern is restored when the adenoma is completely removed van den Berg et al Second surgical procedures are generally safe but less successful than primary surgery Long et al The experience of the neurosurgeon is critical for a high cure rate Ahmed et al ; Bates et al Conventional radiotherapy is administered by a linear accelerator 4—8 MeV with a total dose of 40—45 Gy, fractionated in at least 20 sessions.
A rotational field, 2 opposing fields, or a 3-field technique are used. Whether the GH level normalizes post irradiation mainly depends on pre-irradiation serum GH concentration and the time interval between radiotherapy and the measurement of GH and IGF-1 levels. Post-irradiation remission rates are, however, largely affected by the extent of surgical debulking prior to radiotherapy. Barkan and colleagues were the first to question the efficacy of radiotherapy in normalizing serum IGF-I concentrations, with many studies addressing the effects of conventional pituitary irradiation on IGF-I and strict GH criteria being reported thereafter Barkan et al Another radiation technique is radiosurgery, which is the precise, stereotactic delivery of a single high radiation dose to a defined target with a steep dose gradient at the tumor margin Mahmoud Ahmed et al ; Castinetti et al ; Roberts et al This form of radiotherapy is performed using a gamma knife with up to 60 Co sources, a Linac-based system, or proton beams Marcou and Plowman ; Brada et al ; Sheehan et al The perceived advantage of this form of irradiation is that only one session is required.
There is otherwise no convincing evidence as yet that radio-surgery is superior to conventional irradiation in terms of GH control, time needed to reach clinically acceptable GH levels, and incidence of hypopituitarism Landolt et al ; Attanasio et al a ; Biermasz et al Disadvantages of pituitary irradiation other than the development of hypopituitarism include decreased quality of life QoL , the development of secondary tumors, cerebrovascular disease, and increased mortality.
In one cross-sectional study, decreased health-related QoL was described in acromegalic patients in long-term remission Biermasz et al b. These data were confirmed by another QoL analysis of treated acromegalic patients Rowles et al A significant predictor of poor QoL was radiotherapy, but the pathophysiologic mechanism remains unclear. Increased mortality due to cerebrovascular disease was observed in two of the studies Ayuk et al ; Kauppinen et al but not in the other three Bates et al ; Ahmed et al ; Biermasz et al a.
The effect of radiotherapy on mortality is thus as yet to be established. The likelihood of secondary tumor formation after pituitary irradiation is very low Brada et al The three most important drugs used for medical treatment of acromegaly are dopamine agonists, somatostatin analogs, and GH-receptor modulating chemicals.
Bromocriptine, a dopamine agonist, effectively reduces GH secretion in only a minority of GH-secreting adenoma Jaffe and Barkan The efficacy of cabergoline was somewhat better in tumors co-secreting prolactin. Most endocrinologists use long-acting dopamine agonists as adjunct therapy in patients who fail to normalize GH secretion with octreotide monotherapy.
The use of dopaminergic drugs other than cabergoline is probably safer in acromegaly. Somatostatin was isolated in from the hypothalamus and subsequently synthesized Brazeau et al The hormone is processed from a large pre-prohormone into 2 cyclic peptides, consisting of 14 or 28 amino acids. The short form, SS14, is predominantly present in the brain, whereas SS28 is widely distributed in peripheral organs. Somatostatin acts as neuromodulator and neurotransmitter in the brain and as a neurohormone in the regulation of GH and thyroid-stimulating hormone secretion.
Somatostatin acts as neurotransmitter in the extensive myo-enteric plexus, and as hormone in a paracrine and autocrine fashion. Via specific receptors, somatostatin exerts many inhibitory effects on gut and pancreatic hormones, including gastrin, insulin, glucagon, vasoactive intestinal peptide, motilin, and gastric inhibitory polypeptide. Other effects of somatostatin include inhibition of gastric emptying, pancreatic enzymes and bicarbonate secretion, gastrointestinal blood flow and bile flow Brazeau et al ; Reichlin ; Patel Somatostatin acts via a G-protein-coupled receptor, of which 5 subtypes have been cloned and characterized Lamberts et al After binding of somatostatin to its receptor, the activities of adenyl cyclase and of calcium channels are inhibited, whereas phosphotyrosine phosphatase activity and mitogen-activated protein kinases activity are stimulated.
The first two processes are involved in the inhibition of secretory processes, and the latter two may play a role in cell proliferation, eg, activation of the SST3 receptor may induce apoptosis Danilla et al ; Bevan Analogs of somatostatin differ in binding properties to different receptor subtypes Lamberts et al Many benign and malign tumors express one or more somatostatin receptors.
Receptor distribution and density and homogeneity of receptor expression within the tumor determine whether a particular analog can be effectively used therapeutically Krantic et al ; Olias et al The current clinically used analogs, octreotide and lanreotide, inhibit GH secretion via the somatostatin receptor subtypes 2 and 5 Hofland and Lamberts The plasma half-life of these analogs is about 20 times longer than that of native somatostatin, which is less than 3 minutes Lamberts et al Although the most important effect of somatostatin analogs is the inhibition of GH secretion by the adenoma leading to a subsequent decrease in circulating liver-derived IGF-I, part of the peripheral effects of these analogs is caused by the direct inhibition of IGF-I gene transcription after binding to the somatostatin receptor Serri et al ; Murray et al The magnitude of this latter effect in various organs is not exactly known.
Pegvisomant is an engineered GH analog that antagonizes GH at the receptor site, and thus prevents endogenous GH activation of its receptor and subsequent downstream signaling. In a minority of patients 2 out of and 7 out of patients, respectively adenoma size increased during a relatively short treatment period van der Lely et al ; Schreiber et al Careful documentation of tumor size before starting pegvisomant treatment is therefore compulsory and long-term monitoring is advisable. A small number of patients 2 out of cases developed abnormalities in liver function tests, necessitating withdrawal of the drug, although increased liver enzyme levels, ie, more than 3 times the upper level of normal, was observed in 5.
The first pharmaceutical available form of lanreotide BIM was relatively short-acting, requiring multiple dosing, 3 times a day, or subcutaneous infusion. This was nevertheless a major advance in the treatment of many patients who had already undergone unsuccessful surgery and pituitary irradiation and for whom there were no other treatment options Figure 1.
In healthy subjects, maximal serum concentrations of lanreotide were reached after 30 min and the serum half-life was 90 min, 30 times greater than that of native somatostatin Kuhn et al ; Antonijoan et al ; Table 1. Subsequently, a long-acting form of lanreotide was developed by incorporating the drug into polyactide — poly-glycolide microspheres, so that the half-life was considerably prolonged, and the injection interval could be extended to 7—14 days Heron et al The lanreotide release pattern from the long-acting form is biphasic, ie, an early release during 2 days from the drug adsorbed onto the surface of the microspheres, followed by sustained release for about 1 week, starting at day 4, as a result of enzymatic breakdown of the microspheres, followed again by an exponential decrease in drug release.
It was subsequently discovered that lanreotide had the unique property of self aggregation under favorable conditions, leading to a stable structure of highly organized nanotubules Valery et al , Maximal serum concentrations are reached after 1—2 days see Table 1 in healthy subjects and the serum half-life amounts to In acromegalic patients maximal values are reached after 3.
The pharmacokinetic differences therefore indicate that octreotide LAR can be better tailored to therapeutic levels, whereas serum levels of lanreotide must be too high for part of the interval between injections in order to be effective in the period before the next administration. The lines represent mean values of 10 simulated profiles. From data of Astruc et al From data of Bronstein et al The first studies with lanreotide were performed using lanreotide Slow Release lanreotide SR.
The drug was first available in vials containing 30 mg, to be injected at 2-weekly intervals. The interval was shortened, however, to 7—10 days when GH was insufficiently suppressed. The drug later also became available in vials containing 60 mg of lanreotide so that the injection interval could be extended to 4 weeks, similar to that of the long established octreotide LAR.
Most patients had undergone pituitary surgery and many were irradiated, either as primary treatment a minority or as adjuvant treatment after noncurative surgery. In addition, in almost all studies patients had been treated with octreotide. Normal mean GH concentration, as defined by the authors generally below 2. Comparative studies of efficacy between octreotide and lanreotide are summarized in Table 4.
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Short-acting octreotide, mostly given 3 times a day, had a similar GH-suppressive effect as lanreotide SR. A limitation of all these studies, with one exception, is that they were not randomized. The overall better efficacy of octreotide LAR compared with lanreotide SR agrees with findings from a recent meta-analysis Freda et al Clinical efficacy studies are summarized in Table 5.
Most of the patients who took part in these studies had undergone pituitary surgery, often with adjuvant irradiation, and almost all patients were on octreotide or lanreotide SR treatment, while a minority also used dopaminergic drugs. The results of these studies should therefore be considered critically, as a selection bias cannot be excluded.
Normal GH, defined as a concentration below 2. Indeed, most of the patients ended receiving the highest dose of mg. These results do not differ from data obtained in patients on lanreotide SR see above. A drawback of these studies is that with the exception of one study none were randomized Andries et al Although the study is rather small it will contribute further data on IGF-I control and tumor reduction.
The studies comparing the efficacy between octreotide LAR and lanreotide are shown in Table 6. Only the small study by Andries was properly designed, and showed equal efficacies of both drugs in terms of normalization of GH. Nevertheless, this study demonstrated a better GH-suppressive effect of octreotide on absolute GH concentrations than lanreotide.
In contrast, the suppressive effect on IGF-I was similar. There was no difference in GH suppressive effect in a small study in 7 patients in whom the 24 h GH secretion was precisely measured with a 10 min blood sampling protocol. Van Thiel et al The most frequent side effects of lanreotide are diarrhea, abdominal pain, and nausea. These symptoms start mostly shortly after an injection, decrease subsequently, and tend to decrease in severity on continuing treatment.
Table 7 lists the side effects mentioned in the clinical studies with the 2 long-acting formulations of lanreotide. The most serious complication of somatostatin analogs is cholelithiasis. The prevalence of somatostatin analog-induced gallstones varies geographically and may be influenced by dietary, environmental, and racial factors. The formation of gallstones involves the inhibition of gallbladder emptying and intestinal motility, inhibition of the secretion of pro-kinetic peptides, including cholecystokinin, and increased intestinal and biliary production of deoxycholic acid, all of which promote the nucleation of cholesterol crystals and their aggregation into stones Dowling et al These figures are smaller than generally cited in literature, but many patients had cholelithiasis caused by previous treatment.
Decrease of tumor size is given only for patients who had no previous radiotherapy or somatostatin analog treatment. Abbreviations: nd, no data available; nc, no significant change of glucose concentrations; nm, not mentioned; LSR, lanreotide slow release; LAUT, lanreotide Autogel. However, local infiltration signs did not decrease the efficacy of the drug.
Other uncommon side effects included sinus bradycardia, asthenia, headache, pruritus, decreased libido, increased serum bilirubin, fatigue, constipation, and hair loss. Some studies have investigated specific aspects of lanreotide action in acromegaly. These include detailed studies on glucose and insulin metabolism, effects on cardiac function, tumor growth, quality of life, and predictors of clinical response. These reports are briefly summarized below. GH is important in regulating glucose tolerance and insulin sensitivity.
GH counteracts the effects of insulin by inhibiting the phosphorylation of the insulin receptor. Moreover, GH also inhibits the phosphorylation of one of the proximate molecules of the insulin signaling cascade, insulin receptor substrate-1 in response to insulin Kuhn et al In acromegaly, several studies have shown that increased GH induces insulin resistance Kasayama et al However, GH also potentiates insulin release which is reflected in the high prevalence of high insulin levels both at rest and after glucose challenge Cerasi and Luft Indeed, many untreated patients exhibit decreased glucose tolerance and more detailed studies have shown reduced insulin-stimulated glucose disposal in muscle and impaired non-oxidative glucose metabolism Sonksen et al ; Wass et al ; Hansen et al ; Foss et al ; Koop et al Effects of somatostatin analogs on glucose homeostasis are the resultant of delayed intestinal absorption of carbohydrates, inhibition of insulin release and increased insulin sensitivity via diminished GH secretion.
Results from studies with lanreotide do not differ essentially from earlier data obtained with octreotide. The acute effects of subcutaneously infused lanreotide were studied in healthy subjects. Oral glucose tolerance worsened during the first day of administration, but was restored on day 7 while drug administration continued Kuhn et al The most precise study used the euglycemic hyperinsulinemic clamp.
Twenty-four patients were studied at baseline and after 6 months treatment with either octreotide LAR or with lanreotide SR. Hemoglobin A1c HbA1c increased significantly. In patients with a normal glucose tolerance at baseline the glucose concentration at min increased, together with decreased and delayed insulin response. Insulin sensitivity increased in all 12 clamped patients. The investigators could not demonstrate differences between octreotide and lanreotide, ie, the effects on GH, IGF-I, and insulin were all similar Baldelli et al The effects of other pharmacologic therapies currently used for the treatment of acromegaly on glucose metabolism and insulin resistance were recently reviewed Pereira et al Acromegaly is associated with increased cardiac morbidity and mortality.
Recognized cardiac manifestations include chronic cardiac failure due to systolic dysfunction cardiomyopathy or isolated diastolic dysfunction Colao et al ; Pereira et al In addition, our group documented the increased prevalence of regurgitant valvular heart disease in acromegaly Pereira et al An important question is whether effective GH-suppressive medication can improve cardiac function. One of the first studies reported on 13 patients treated with lanreotide. In this study there was a parallel decrease in GH and IGF-I and in left ventricular mass index; these data were confirmed in another study Baldelli et al ; Hradec et al Octreotide was used in most studies on cardiac function, because this drug was the earliest available for clinical studies Maison et al These studies indicate that effective GH-suppressive medication improves morphological and functional hemodynamic parameters, although medical therapy does not normalize all parameters.
These observations concur with results of another study, which compared outcome in long-term surgically cured patients with medically controlled patients and which showed better results in the first group van Thiel et al , suggesting that GH-suppressive therapy in its present form is unable to fully correct cardiac dysfunction. The impact of this finding on long-term mortality in acromegaly is unknown.
In the same study, lanreotide inhibited cell proliferation in vitro in 10 out of 13 adenomas Florio et al Lanreotide also stimulates apoptosis as was found in surgically removed GH secreting adenomas to 8.
Other studies in which the decrease in adenoma size could be evaluated are listed in Table 7. In the meta-analysis of 14 clinical studies using somatostatin analogs as primary treatment, Factors not necessarily predictors associated with tumor shrinkage after primary therapy with somatostatin analogs were post-treatment IGF-I, the age of the patient and the percentage GH decrease Colao et al a , and essentially confirming previously reported findings Lucas et al In another meta-analysis of 44 trials, tumor shrinkage was related to the choice of the somatostatin analog.
Preliminary data on biochemical remission of acromegaly after somatostatin analogs withdrawal suggest that some well-responsive patients might be cured, but long-term follow up is clearly needed Ronchi et al QoL remains impaired in acromegaly even after successful pituitary surgery due to persisting joint-related complaints Biermasz et al a. An early open study on the effect of lanreotide SR on QoL suggested a positive effect of treatment Sonino et al However, in another study comprising 52 acromegalic patients no differences could be shown between lanreotide-controlled and noncontrolled patients using the AcroQoL, a questionnaire specifically developed for acromegaly.
Interestingly, in the controlled group, surgically cured patients were much better off than patients controlled with lanreotide Hua et al This observation underscores subtle differences between restoration of normal physiology and effective GH-suppressive medication, as found in intensive GH sampling studies in acromegalic cohorts Biermasz et al c. Finally, in a study of 93 patients with acromegaly control of GH and IGF-I had a positive impact on the subscale appearance, but overall QoL was severely impaired Matta et al A priori conditions for a favorable clinical response to somatostatin analog therapy are the density and distribution of SSTR2a receptors in the adenoma Lamberts et al It is controversial whether a single acute octreotide test can predict the clinical response during long-term treatment.
In this respect 3 studies reported positive results Biermasz et al b ; Gilbert et al ; Karavitaki et al , whereas 3 others concluded that the test was not useful Colao et al ; de Herder et al ; Prokajac et al The absolute height of pretreatment GH levels is obviously another important factor for the efficacy of treatment, and indeed several studies have demonstrated that tumor debulking procedures improved the clinical outcome of medical therapy Colao et al b ; Karavitaki et al Patients with a high chance of curative surgery should be offered this treatment.
However, primary medical treatment should be considered in patients with a high surgical risk, patients with large invasive tumors and obviously in those who refuse surgery. Dose escalation with short-acting octreotide resulted in a better outcome in patients treated with octreotide as primary medication than those who received this drug as adjuvant medication after surgery Newman et al This group and Cozzi and colleagues also found that dose escalating resulted in an even better outcome Cozzi et al ; Colao et al Limitations of these studies are that they are not randomized to primary surgery and that no data are available on long-term effects on survival.
Primary medical treatment may also be aimed at improvement of surgical outcome. Most of the studies addressing this issue had an open label design. Therefore, a conclusive statement cannot be made on this issue. Another, less expensive approach is to combine treatment with dopaminergic agonists Freda ; Cozzi et al More effective is combined treatment with pegvisomant as demonstrated by a single center open labeled study. Long-term efficacy of combined treatment was demonstrated in 32 patients who all normalized IGF-I with pegvisomant in a dose of 40— mg given once weekly 24 patients or twice weekly Neggers et al Preliminary results of the latter study suggest equal efficacy in the two randomized parallel treatment groups towards serum IGF-I normalization, but with a higher incidence of side effects in the combined treatment group Harris et al Considering the number of patients included, these studies will most likely answer questions about the efficacy of combined somatostatin analog and GH-receptor blockage in the treatment of acromegaly.
However, both studies did not exclude previous surgery or radiation therapy, so that any conclusions drawn from these studies may not be applicable to primary medical treatment. Due the favorable receptor binding profile, SOM pasireotide is likely to be a powerful somatostatin analog, which might be used in therapy-resistant cases to the registered somatostatin analogs van der Hoek et al ; Ben-Shlomo and Melmed Clinical Phase II studies in acromegaly are now being carried out in the US with both the short-acting form as well as the slow-release formulation ClinTrial.
Other somatostatin agonists currently developed were recently reviewed Roelfsema et al Potential interesting drugs are chimeric somatostatin analogs. This class of drugs combines dopamine and somatostatin structural elements and retains affinity for specific somatostatin and dopamine receptor subtypes.
These new drugs can not only suppress GH and other pituitary hormones better than currently clinically used drugs, but may also have much stronger antiproliferative actions, at least in vitro Ferone et al ; Zatelli et al The formulation is delivered in prefilled syringes and can be easily injected without medical supervision by the patient or partner after proper training Bevan et al , whereas octreotide LAR requires qualified personnel for administration.
Compared with octreotide LAR the efficacy of lanreotide SR is less, although the differences are not large Freda et al The present formulations of somatostatin analogs can be classified as a second generation of effective GH-suppressive drugs, but these agents are clearly not adequate for all patients, depending on tumor somatostatin receptor status.
New somatostatin analogs include SOM, which is currently being used in several trials in the US, and the potentially very powerful chimeric drugs developed by Ipsen SA. The latter drugs, if successful in phase II—IV studies, will probably take another 5—10 years before becoming available for clinical use by endocrinologists.
The snippet could not be located in the article text. This may be because the snippet appears in a figure legend, contains special characters or spans different sections of the article. PMID: All rights reserved. This article has been cited by other articles in PMC. Objective To delineate the role of lanreotide in the treatment of acromegaly. Methods Search of Medline, Embase, and Web of Science databases for clinical studies of lanreotide in acromegaly. Keywords: acromegaly, lanreotide, somatostatin analog, growth hormone, pegvisomant.
Introduction Growth hormone GH , a polypeptide consisting of amino acids and which is secreted by the pituitary gland, has a multitude of effects. Transsphenoidal surgery This oldest treatment modality was developed a century ago by the Austrian neurosurgeon Schloffer Schloffer Radiotherapy Conventional radiotherapy is administered by a linear accelerator 4—8 MeV with a total dose of 40—45 Gy, fractionated in at least 20 sessions.
Medical treatment The three most important drugs used for medical treatment of acromegaly are dopamine agonists, somatostatin analogs, and GH-receptor modulating chemicals. Dopamine agonists Bromocriptine, a dopamine agonist, effectively reduces GH secretion in only a minority of GH-secreting adenoma Jaffe and Barkan Somatostatin analogs Somatostatin was isolated in from the hypothalamus and subsequently synthesized Brazeau et al GH receptor antagonists Pegvisomant is an engineered GH analog that antagonizes GH at the receptor site, and thus prevents endogenous GH activation of its receptor and subsequent downstream signaling.
Pharmokinetics of lanreotide The first pharmaceutical available form of lanreotide BIM was relatively short-acting, requiring multiple dosing, 3 times a day, or subcutaneous infusion. Open in a separate window. Figure 1. Amino acid structure of somatostatin, octreotide. Figure 2. Abbreviation: AUC, area under the curve. Efficacy of lanreotide The first studies with lanreotide were performed using lanreotide Slow Release lanreotide SR. Table 4 Comparison of efficacy of octreotide versus lanreotide SR in acromegaly.
Reference Study design Patient no. Side effects The most frequent side effects of lanreotide are diarrhea, abdominal pain, and nausea. Insulin and glucose homeostasis GH is important in regulating glucose tolerance and insulin sensitivity. Cardiac effects Acromegaly is associated with increased cardiac morbidity and mortality. Quality of life QoL remains impaired in acromegaly even after successful pituitary surgery due to persisting joint-related complaints Biermasz et al a.
Predictors of clinical response A priori conditions for a favorable clinical response to somatostatin analog therapy are the density and distribution of SSTR2a receptors in the adenoma Lamberts et al Primary pharmacologic treatment Patients with a high chance of curative surgery should be offered this treatment. Footnotes Disclosures The authors have no conflict of interest and have received no payment in the preparation of this manuscript.
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Two-year follow-up of acromegalic patients treated with slow release lanreotide 30 mg J Clin Endocrinol Metab. Cardiac effects of slow-release lanreotide, a slow-release somatostatin analog, in acromegalic patients. Pituitary irradiation is ineffective in normalizing plasma insulin-like growth factor I in patients with acromegaly. Preoperative treatment of acromegaly with long-acting somatostatin analog SMS — shrinkage of invasive pituitary macroadenomas and improved surgical remission rate.
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Octreotide Is Effective in Acromegaly But Often Results in Cholelithiasis
Q J Med. Wide variation in surgical outcomes for acromegaly in the UK. Long-term outcome and mortality after transsphenoidal adenomectomy for acromegaly.
Clin Endocrinol Oxf ; 58 — Epidemiology and long-term survival in acromegaly. A study of cases diagnosed between and Acta Med. Endocrinol Metab N Am. Open Athens Shibboleth Log In. Subscribe to Annals of Internal Medicine. Advanced Search. Editorials 1 February William H.
Daughaday, MD. This content is PDF only. Please click on the PDF icon to access. Abstract In this issue, Ho and colleagues 1 summarize their considerable experience in treating acromegaly with the long-acting somatostatin analog, octreotide. Citations Citation. Published: Ann Intern Med. DOI: Related Articles. View More View Less. Related Topics. PubMed Articles. Pasireotide-LAR in acromegaly patients treated with a combination therapy: a real-life study. An artificial intelligent diagnostic system on mobile Android terminals for cholelithiasis by lightweight convolutional neural network.