Acromegaly肢端肥大症

∙enlargement of hands, feet, and facial features due to excess growth hormone secretion by pituitary gland or ectopic sourceTypes∙types of pituitary adenomas causing acromegaly include(1)o benign monoclonal growth hormone-secreting pituitary adenoma surrounded by normal pituitary tissue∙found in 90% of patients with acromegaly∙slow growing∙patients usually > 50 years oldo rapidly growing, sparsely granulated adenomas made up of growthhormone-secreting cells∙patients typically younger∙25% of growth hormone adenomas also secrete prolactino primitive acidophil stem cell adenomas∙more common in teenagers∙often causes gigantism∙pathology consistent with mixed single cellular or multicellular plurihormonalimmunoreactivity∙may be called acromegaly with onset after puberty and gigantism with onset before puberty(1) Who is most affected∙no apparent differences in race, gender, or ethnicity among affected individuals(5) mean age at presentation 44 years (Pituitary 1999 Jun;2(1):29)∙incidence about 3-4 per million per year and prevalence 60 per million population reported in reviews(1, 5)∙incidence and prevalence based on registry in Belgium and Luxembourgo based on 418 patients in registryo mean incidence 1.9 cases per million per yearo prevalence 41 cases per million population, ranging from 21 to 61 cases per million in different regions o Reference - Eur J Endocrinol 2007 Oct;157(4):399∙multiple endocrine neoplasia (MEN) type I may include(1)o pituitary adenomao hyperparathyroidismo pancreatic islet cell adenomas or hyperplasias∙hyperprolactinemia -- about 25% of growth hormone-secreting adenomas cosecrete prolactin(1)∙McCune-Albright syndromeo mutation in GNAS gene resulting in triad of cafe au lait skin pigmentation, precocious puberty, and fibrous dysplasia in case report (Intern Med 2007;46(18):1577PDF)∙malignancyo acromegaly associated with increased risk of thyroid cancer and thyroid nodular disease∙based on systematic review of case-control studies∙systematic review of 9 case-control studies evaluating risk of thyroid nodular disease and thyroid cancer in adults with acromegaly∙acromegaly associated with increased▪thyroid cancer (odds ratio [OR] 7.9, 95% CI 2.8-22) in analysis of 5 trials with 757 patients compared to 1,058 controls▪thyroid nodular disease (OR 3.6, 95% CI 1.8-7.4) in analysis of 3 trials with 455 patients compared to 612 controls∙Reference - PLoS One 2014;9(2):e88787EBSCOhost Full Text full-text o acromegaly associated with increased risk of cancer including thyroid, bladder, and kidney, but not colorectal cancer∙based on retrospective cohort study∙333 patients > 15 years old with acromegaly followed for mean 14.6 years∙comparing observed vs. expected cancer rates during total follow-up▪any cancer 48 cases vs. 33.1 cases (standardized incidence ratio [SIR] 1.5, 95% CI1.1-1.9)▪thyroid cancer 6 cases vs. 0.5 cases (all within first 5 years) (SIR 13.4, 95% 4.9-29.3) ▪SIR 28.6 (95% CI 5.89-83.5) in men▪SIR 8.79 (95% CI 1.81-25.9) in women▪colorectal cancer 6 cases vs. 3.2 cases (not significant)∙bladder and kidney cancer risk increased in first 5 years (SIR 7.77, 95% CI 2.12-19.9) but difference not significant over total follow-up∙colorectal cancer risk nonsignificantly increased at 5 years with posttreatment growth hormone level ≥ 2.5 mcg/L (SIR 4.44, 95% CI 0.91-13)∙Reference - Clin Endocrinol (Oxf) 2010 Feb;72(2):278EBSCOhost Full Text∙Carney's syndrome - autosomal dominant mutation in PRPKARIA gene resulting in cutaneous pigmentation, fibromyxoid tumors of the skin, myxomas of the heart, endocrine overactivity in caseCauses∙endogenous sources of excess growth hormone1oo familial syndromes∙multiple endocrine neoplasia (MEN) type I∙McCune-Albright syndrome (premature puberty in girls, cafe au lait spots, fibrous dysplasia of bone)∙Carney's syndrome (cutaneous pigmentation, myxomas, testicular tumors, and pituitary growth hormone-secreting tumor)∙familial acromegalyo pituitary carcinoma rare∙carcinoma defined by presence of extracranial metastases∙case report (noting only 9 previously reported cases) can be found in N Engl J Med 2001 Nov 29;345(22):1645o extrapituitary ectopic secretion of growth hormone by pancreatic islet-cell tumors or lymphoma∙case report of acromegaly caused by growth hormone secretion by non-Hodgkin lymphoma can be found in N Engl J Med 2000 Jun 22;342(25):1871o somatotroph hyperplasia caused by excessive secretion of growth hormone releasing hormone (GHRH) by∙hypothalamic tumors (usually gangliocytomas)∙peripheral neuroendocrine tumors▪pheochromocytoma▪medullary thyroid carcinoma▪adrenal adenoma▪small cell lung cancer▪bronchial carcinoid▪pancreatic islet cell cancer∙mutation in GPR101 gene encoding G-protein-coupled receptor present in 4.4% of 248 patients with acromegaly in genetic analysis (N Engl J Med 2014 Dec 18;371(25):2363)∙exogenous use of human growth hormone to increase mass or for ergogenic effects (Br J Pharmacol 2008 Jun;154(3):542EBSCOhost Full Text)HistoryChief concern (CC)∙o acral enlargement in 86%o maxillofacial changes in 74%o excessive sweating in 48%o arthralgias in 46%o headache in 40%o hypogonadal symptoms in 38%o visual deficit in 26%o fatigue in 26%o weight gain in 18%o galactorrhea in 9%∙o if onset of excessive growth hormone secretion occurs before puberty and closure of bone growth plates, then accelerated growth and gigantismo if onset of excessive growth hormone secretion occurs after puberty and closure of bone growth plates, then accelerated growth of soft tissues with typical picture of∙enlarging hands, feet, and skull (for example, increasing ring, glove, shoe, or hat sizes) ∙jaw prognathism, may lead to bite disorders∙coarse features∙thickening of soft tissue∙skin tags∙hyperhidrosis∙thickened skin∙change in skin texture∙may have gradual enlargement of tongue, thyroid, salivary glands∙symptoms which may result from compressive effect of tumor growth(1)o headaches (suspect pituitary apoplexy with severe acute headache, may occur in 3.5% of patients with acromegaly)o cranial nerve palsy (cranial nerves 3, 4, and 6 affect eye movements)o visual field defects∙symptoms which may result from excess growth hormone(1)o snoring打鼾o narcolepsyo menstrual abnormalitieso galactorrheao decreased libidoo erectile dysfunctiono increased body hair or sexual hairHistory of present illness (HPI)∙diagnosis typically delayed 7-10 years after onset of symptoms(1)∙disease features develop insidiously over decades(1)Medication history∙ask about growth hormone injectionsFamily history (FH)∙ask about familial syndromes(1, 2)o McCune-Albright syndromeo Carney syndromeo familial isolated pituitary adenomaso multiple endocrine neoplasia (MEN) type Io familial acromegalyReview of systems (ROS)∙ask about the following conditions which may be more common in patients with acromegaly(1, 5) o general∙fatigue∙snoringo skin∙hyperhidrosis∙skin tags∙oily textureo cardiovascular system∙shortness of breath∙peripheral edema∙hypertension∙cardiomyopathy∙heart failureo musculoskeletal system∙arthralgias and arthritis∙proximal myopathy∙enlarged hands and feet∙jaw malocclusion∙hypertrophy of frontal bones∙carpal tunnel syndromeo neurologic system∙headache∙visual changes∙paresthesias∙carpal tunnel syndrome∙cranial nerve palsieso gastrointestinal system∙visceromegaly, and enlargement of tongue and salivary glands∙colon polypso genitourinary system∙polyuria∙sexual dysfunctiono endocrine system∙infertility∙menstrual abnormalities, including amenorrhea∙galactorrhea∙sexual dysfunction∙thyromegaly∙hypothyroidism∙diabetes mellitus∙hypertriglyceridemia∙hyperparathyroidism∙multinodular thyroid goiter∙hypercalciuria∙hypopituitarismo respiratory system∙sleep apnea (central sleep apnea and obstructive sleep apnea)∙upper airway obstruction∙ventilatory dysfunction∙macroglossiaPhysical:General physical:∙compare current appearance to review of old photographs★∙general features of acromegaly(1)o hypertensiono coarse featureso thickening of soft tissueo bone enlargementSkin:∙skin tags(1)∙oily texture(1)∙hyperhidrosis(1)∙thickened skin - increased skin thickness can be used for evaluating response to therapy(1) HEENT:∙physical features may include(1)o coarse facial featureso frontal bossingo wide nasal bridgeo thickened lipso macroglossiao widely spaced teetho protruding jawo jaw malocclusiono enlarged salivary glands∙examine eyes for(1)o visual field defectso papilledemaNeck:∙thyromegaly(1)∙jugular venous distention in cardiomyopathy(1)Cardiac:∙check for arrhythmia(1)∙findings which may occur with cardiomyopathy(1)o murmuro abnormal heart soundso double apical impulseLungs:∙rales/crackles if heart failure(1)Abdomen:∙visceromegaly may include(1)o hepatomegalyo splenomegalyExtremities:∙enlarged hands and feet may be present(1)∙swollen joints(1)∙carpal tunnel syndrome(1)Neuro:∙check for cranial nerve palsies(1) (cranial nerves 3, 4, and 6 affect eye movements) Rectal:∙enlarged prostate may occur(1)Making the diagnosis∙characteristic clinical features and comorbidities confirmed by biochemical evidence(2)∙evaluation for acromegaly should occur in patients with ≥ 2 comorbidities (AACE Grade A, Level 1)(2) o new-onset diabeteso diffuse arthralgiaso new-onset or difficult-to-control hypertensiono cardiac disease such as biventricular hypertrophy, diastolic, or systolic dysfunctiono fatigueo headacheso carpal tunnel syndromeo sleep apneao diaphoresiso visual losso colon polypso progressive jaw malocclusion∙ biochemical diagnosis can be made with(2)o elevated insulin-like growth factor-1 (IGF-1)o elevated growth hormone (GH) levels without suppression on oral glucose tolerance test (OGTT)∙GH < 1 mcg/L after oral glucose tolerance test is considered normal (AACE Grade C, Level 3) (excludes diagnosis of acromegaly)∙GH < 0.4 mcg/L after oral glucose challenge considered more sensitive (AACE Grade D, Level 4)Differential diagnosis:∙consider unusual causes and associated conditionso pheochromocytomao hyperparathyroidismo hypothyroidismo hyperthyroidismo hypogonadismo adrenocorticotropic hormone (ACTH) deficiencyo hyperprolactinemiao diabetes insipiduso ectopic tumorTesting overview:∙initial testing(1, 2, 5)o insulin-like growth factor-1 (IGF-1) levelo growth hormone (GH) level∙GH after oral glucose tolerance test if acromegaly not excluded(2, 5)o GH < 1 mcg/L is considered normal after oral glucose tolerance test (AACE Grade C, Level 3) (excludes diagnosis of acromegaly)o GH < 0.4 mcg/L after oral glucose challenge considered more sensitive (AACE Grade D, Level 4) ∙testing for source of excess GH if elevated IGF-1 or lack of GH suppressiono magnetic resonance imaging (MRI) of pituitary with and without contrast (AACE Grade B, Level 1)(2)o further testing if no pituitary mass(1, 5)∙computed tomography (CT) chest and abdomen for extra pituitary tumor∙growth hormone releasing hormone (GHRH)∙total body scintigraphyfurther testing if GH-secreting pituitary adenoma(5) ★∙o visual field testingo∙consider testing for associated abnormalities and complications(2)o calcium (screen for hyperparathyroidism)o prolactino glucoseo lipid profileo colonoscopyo electrocardiogram (ECG)o echocardiogramo chest x-rayo visual field testingo sleep studyo thyroid-stimulating hormone (TSH) and thyroid hormone∙if using somatostatin analog (for example, octreotide), consider baseline and periodic ultrasound of gallbladder and bile ductsBlood tests:∙ serum insulin growth factor-1 (IGF-1) levelo use for diagnosis, monitoring, and screening of acromegaly (AACE Grade B, Level 2)(2)o levels remain stable throughout day(5)o correlates with mean growth hormone (GH) levels and clinical features of acromegaly(5)o elevated levels associated with increased morbidity and mortality(5)o levels affected by age and gender (about 14% decrease per decade during adulthood)(5)o greatly elevated IGF-1 level (such as twice the upper limit of normal) reported to suggest acromegaly in patients with clinical features (level 3 [lacking direct]evidence)∙based on diagnostic case-control study of 101 patients who had pituitary surgery for histologically proven somatotroph adenomas who were compared to 149 patients withnon-GH-secreting pituitary macroadenomas or microadenomas and 34 patients withelevated IGF-1 values but negative oral glucose tolerance tests (OGTT)∙median IGF-1 level was elevated > twice the assay-specific upper limit of normal in patients with acromegaly∙Reference - Endocr Pract 2012 Nov-Dec;18(6):817EBSCOhost Full Text∙expert review suggests highly elevated IGF-1 levels (such as > 2 standard deviations) in patients with clinical signs of acromegaly may not need oral glucose tolerance test fordiagnostic confirmation (Expert Opin Med Diagn 2013 Sep;7(5):443)∙ GH(2, 5)o secretion is pulsatileo normal levels usually 0.1-0.2 mcg/Lo values can reach 5-30 mcg/L during secretory pulses, which can overlap values in patients with acromegaly, so random GH levels useful only for excluding acromegaly o do not use serum GH assays interchangeably (not standardized); multiple samples, random GH, and GH after glucose administration have variability and must be used in clinicalcontext (AACE Grade C, Level 3)∙ GH after OGTT(1, 2)o75 g of glucose given orallyo GH measured over period of 2 hours at 30-minute intervalso GH < 1 mcg/L is considered normal after oral glucose tolerance test (AACE Grade C, Level 3) o GH < 0.4 mcg/L after oral glucose challenge considered more sensitive (AACE Grade D, Level 4)o random GH levels generally not useful for diagnosis, but may be necessary for some patients (for example, patients with diabetes mellitus)o GH production may not be suppressed in liver disease, uncontrolled diabetes, malnutrition, anorexia, pregnant women, patients receivingestrogens, or during late adolescence∙ further testing(2)o serum prolactin level (to evaluate for hyperprolactinemia) (AACE Grade A, Level 1)o calcium levels (to assess for hyperparathyroidism and consideration of multiple endocrine neoplasia [MEN1] type 1) (AACE Grade C, Level 3)o test for presence of diabetes (AACE Grade A, Level 3)o assess anterior and posterior pituitary function (for potential hypopituitarism) (AACE Grade A, Level 1) - thyroid-stimulating hormone (TSH) and free thyroxine (FT4) levels also can rule outinappropriate TSH secretion due to thyrotropin-cosecreting tumoro assess cardiovascular risk status including measurement of lipid profile (high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and triglycerides) (AACE Grade C,Level 3)o assess for hypopituitarism and replace hormone axes, especially adrenal and thyroid, as needed (AACE Grade C, Level 4)o insufficient evidence to support testing insulin-like growth factor binding protein-3 or thyrotropin releasing hormone (AACE Grade A, Level 1)Imaging studies:∙magnetic resonance imaging (MRI)o perform dedicated MRI of pituitary (with and without contrast) after biochemical diagnosis of acromegaly (AACE Grade B, Level 1)(2)o MRI of pituitary gland to detect tumor and evaluate(5)∙size (≥ 2 mm can be detected)∙invasiveness∙proximity to optic chiasm∙compression of surrounding structureso MRI during pregnancy (AACE Grade A, Level 1)(2)∙do not routinely perform MRI scans during pregnancy unless evidence of new or worsening visual field compromise∙MRI should be done without contrast agent∙ other imaging(2)o consider computed tomographic (CT) scan of pituitary if MRI contraindicated (such as patient with cardiac pacemaker) (AACE Grade B, Level 1)o consider echocardiography in patients with evidence of left ventricular hypertrophy by electrocardiography or who are symptomatic with shortness of breath (AACE Grade C, Level 3) o colonoscopy recommended due to increased prevalence of colon polyps (AACE Grade C, Level 4) o perform bone densitometry in patients with history of hypogonadism or fracture (AACE Grade C, Level 3)∙American College of Radiology (ACR) Appropriateness Criteria for neuroendocrine imaging in acromegalyo MRI - multiplanar thin sellar imaging∙head MRI without and with contrast usually appropriate (ACR Grade 8)∙head MRI without contrast usually appropriate (ACR Grade 7)o CT - indicated if MRI not available or contraindicated∙head CT with contrast may be appropriate (ACR Grade 5)∙head CT without and with contrast may be appropriate (ACR Grade 4)∙head CT without contrast may be appropriate (ACR Grade 4)o venous sampling of petrosal sinus indicated in unusual cases in which lateralization indeterminate but otherwise usually not appropriate (ACR Grade 3)o magnetic resonance angiography (MRA) - may be useful if vascular pathology known or suspected∙head MRA without contrast usually not appropriate (ACR Grade 3)∙head MRA without and with contrast usually not appropriate (ACR Grade 3) o head computed tomography angiography (CTA) with contrast indicated for surgical planning or vascular detail if MRI and MRA contraindicated but otherwise usually not appropriate (ACRGrade 2)o tests that are usually inappropriate include x-ray tomography of the head, x-ray sella, and cerebral arteriography (ACR Grade 1)o Reference - ACR Appropriateness Criteria on neuroendocrine imaging (ACR 2012 PDF or National Guideline Clearinghouse 2012 Nov 5:37920)Electrocardiography (ECG):∙consider cardiac evaluation including ECG and echocardiogram, particularly if patient has signs or symptoms suggestive of cardiac involvement (like arrhythmias and shortness of breath) (AACE Grade C, Level 4)(2)Other diagnostic testing:∙perform visual field testing(2)o if reduced peripheral vision or optic chiasmal compression noted on magnetic resonance imaging (AACE Grade A, Level 1)o during pregnancy, at intervals dictated by tumor size and location before pregnancy (AACE Grade C, Level 3)∙consider sleep study for evaluation of sleep apnea (AACE Grade B, Level 3)(2)Treatment overview:∙focus of therapy is for biochemical control of growth hormone (GH) and insulin growth factor-1 (IGF-1) for reduction in mortality risk (AACE Grade C)(2)∙surgery is treatment of choice for patients with microadenomas, noninvasive macroadenomas, or macroadenomas with mass effect (AACE Grade A, Level 1-2)o primary transsphenoidal surgery associated with high cure rate, low recurrence, and few complications (level 2 [mid-level] evidence)o partial surgical tumor removal (debulking) may improve hormone response to somatostatin analogs (SSA) (level 3 [lacking direct] evidence)∙medical therapy if unresponsive to surgery (AACE Grade A, Level 2), if poor surgical candidate, or if macroadenoma without mass effects unlikely to be cured by surgery (AACE Grade B, Level 3)o SSA may be considered first-line medical therapy∙SSA may shrink tumor (level 3 [lacking direct] evidence)∙SSA reported to improve cardiac function and exercise tolerance (level 3 [lacking direct] evidence)∙octreotide (Sandostatin) 50 mg subcutaneously 3 times daily, then adjusted to normalize GH or IGF-1 levels▪may switch to long-acting octreotide 20 mg intramuscularly once every 4 weeks when stable▪octreotide may improve symptoms of acromegaly (level 2 [mid-level] evidence) ∙long-acting lanreotide reported to decrease GH and IGF-1 levels and tumor size, and improve symptoms (level 3 [lacking direct] evidence)∙octreotide long-acting release and lanreotide Autogel reported to be similarly effective (level3 [lacking direct] evidence)o dopamine agonists (cabergoline, bromocriptine)∙consider using dopamine agonists particularly in patients with modestly elevated serum insulin growth factor-1; can use alone or along with SSA (AACE Grade B, Level 3) ∙cabergoline may be more effective and better tolerated than bromocriptine (AACE Grade C, Level 3)∙cabergoline reported to lower IGF-1 levels in a minority of patients when used alone and reported to lower IGF-1 levels in about half of patients when added to SSA in patientsunresponsive to SSA analog alone (level 3 [lacking direct] evidence)o pegvisomant (Somavert) is a GH receptor antagonist∙often used as medical therapy in patients with inadequate response to or tolerability of somatostatin analogs (AACE Grade A, Level 2)∙consider adding pegvisomant in patients with partial response to SSA therapy (AACE Grade C, Level 3)∙may improve symptoms (level 2 [mid-level] evidence), decrease IGF-1 levels and reported to improve cardiac function (level 3 [lacking direct] evidence)∙management during pregnancyo for patients taking SSA discontinue therapy 2-3 months prior to planning pregnancy if appropriate (AACE Grade D, Level 3)o for patients with microadenoma discontinue medical therapy during pregnancy due to unclear risks to the fetus (AACE Grade C)o for patients with macroadenoma without mass effect medical therapy may be withheld for conception with close follow-up with visual field testing (AACE Grade C, Level 3) and reinitiation of therapy for symptoms (AACE Grade C, Level 3)o for patients who have visual field symptoms obtain a magnetic resonance imaging (MRI) and consider surgical and medical therapy (AACE Grade C)∙consider radiation therapy for patients not fully responding to surgery and/or medical therapy (AACE Grade C, Level 4)o stereotactic radiosurgery preferred over conventional radiation therapy unless substantial tumor burden or tumor < 5 mm from optic chiasm (AACE Grade C, Level 4)o radiation therapy reported to lower GH and IGF-1 levels but often associated with hypopituitarism (level 3 [lacking direct] evidence)o gamma knife radiosurgery reported to decrease GH levels and tumor growth (level 3 [lacking direct] evidence)∙provide monitoring of GH and IGF-1 levels as response to therapy and additional testing and monitoring as appropriate for comorbiditiesMedications:Candidates for medical therapy:∙candidates for primary medical therapy (especially with somatostatin analogs (SSAs)) (AACE Grade B, Level 3)(2)o patients with macroadenomas without mass effects unlikely to be cured by surgeryo patients who are poor surgical candidateso patients who prefer medical treatment∙use adjuvant medical therapy if persistent disease after surgery (AACE Grade A, Level 2)(2)∙consider starting medical therapy during pregnancy if evidence of worsening disease (AACE Grade D, Level 3)(2)Somatostatin analogs:Use of somatostatin analogs in acromegaly:∙American Association of Clinical Endocrinologists (AACE) recommendations on SSAs(2) o SSAs may be considered first-line medical therapyo long-acting, depot SSAs available include octreotide long-acting release (LAR) (administered as an intramuscular injection) and lanreotide Autogel (administered as a deep subcutaneous depot injection)o consider using short-acting octreotide subcutaneously, especially for patients with financial constraints or need for rapid onset of action (AACE Grade C, Level 3)o preoperative treatment with somatostatin analogs suggested for patients who are appropriate candidates for surgery∙to reduce surgical risk (AACE Grade B, Level 4)∙to improve biochemical outcomes with surgery (AACE Grade B, Level 2) o effectiveness of SSAs∙SSAs effective in normalizing insulin-like growth factor-1 (IGF-1) and growth hormone (GH) levels in approximately 55% of patients (AACE Grade B, Level 2)∙clinical and biochemical responses to SSAs are inversely related to tumor size and degree of GH hypersecretion (AACE Grade B, Level 2)∙octreotide LAR and lanreotide Autogel have similar efficacy and side effects profiles (AACE Grade B, Level 2)o SSAs reduce pituitary tumor size modestly in approximately 25%-70% of patients, depending on whether they are used as adjuvant or primary therapy; SSAs should not be used fordecompression of local structures if there are mass effects (AACE Grade B, Level 3) o consider adding cabergoline or pegvisomant for further lowering of GH and/or IGF-1 levels in patients with inadequate response to SSAs (AACE Grade B, Level 3)o potential side effects of SSAs include∙gastrointestinal upset∙malabsorption∙constipation∙gallbladder disease∙hair loss∙bradycardia∙worsening glucose controlo radiologic follow-up for gallbladder disease not recommended, but ask patients about potential symptoms during follow-up appointments (AACE Grade B, Level 3)o in patients in whom SSA therapy worsens glucose control, consider (AACE Grade C, Level 3) ∙reducing SSA dose∙adding or substituting with a GH receptor antagonist, or∙diabetes management with glucose-lowering agentso SSA use around pregnancy∙discontinue medical therapy with long-acting SSA 2-3 months before planned pregnancy, depending on patient's clinical status (AACE Grade D, Level 3)∙if patient conceives while receiving SSA therapy, discuss discontinuing SSA, with serial pituitary function follow-up including assessment of adrenal, thyroid, and gonadal function(AACE Grade D, Level 3)∙SSA may shrink tumor (level 3 [lacking direct] evidence)o based on systematic review without clinical outcomeso systematic review of 14 studies of SSAs in 424 patients with acromegaly∙studies included prospective and retrospective cohort studies, case series, and case reports ∙no randomized trials found∙SSA given as primary therapy or prior to surgery or radiation therapy, patients previously treated with surgery or radiation therapy excluded∙SSAs included immediate-release or sustained-release formulationsof octreotide or lanreotide∙stated study outcome included change in pituitary tumor size evaluated by magnetic resonance imaging (MRI) (studies using computed tomography [CT] were excluded) ∙previous treatment with dopamine agonist or SSA allowedo criteria for significant reduction in tumor size ranged from > 10% to > 45% in 12 studies, > 2 mm in 1 study, and "moderate-to-notable +" in 1 studyo proportion of patients having significant reduction in tumor size ranged from 22% to 73% (pooled mean 36.6%)o no significant difference between short-acting octreotide and long-acting preparationso Reference - J Clin Endocrinol Metab 2005 Jul;90(7):4405full-text∙SSAs reported to improve cardiac function and exercise tolerance (level 3 [lacking direct] evidence)o based on systematic review without clinical outcomeso meta-analysis of 18 studies of SSAs in acromegalyo mean weight difference in left-ventricular ejection fraction 3.3%o mean weighted difference in exercise duration 1.6 minuteso Reference - J Clin Endocrinol Metab 2007 May;92(5):1743full-text∙preoperative SSA might increase postoperative biochemical cure rate in patients with acromegaly (level 3 [lacking direct] evidence)o based on systematic review without clinical outcomeso systematic review of 10 studies (3 randomized trials, 2 nonrandomized trials, 5 retrospective cohort studies) evaluating preoperative SSA in 968 patients with acromegaly o primary outcome was biochemical cure (definition varied among studies and included normalization of age-adjusted IGF-1, fasting GH, or GH after oral glucose tolerance test) o follow-up was at 1 to > 24 postoperative weekso preoperative SSA associated with∙increased biochemical cure rate in analysis of 3 randomized trials with 198 patients ▪odds ratio (OR) 3.62 (95% CI 1.88-6.96)▪NNT 1-6 assuming 18% cure rate in controls∙nonsignificant increase in biochemical cure rate in analysis of 10 studies with 968 patients (OR 1.62, 95% CI 0.93-2.82)o Reference - PLoS One 2013;8(4):e61523EBSCOhost Full Text full-textOctreotide:General information:∙analog of somatostatin (GH release-inhibiting factor)∙brand name Sandostatin∙FDA approved for acromegaly to reduce GH and IGF-1 blood levels in patients with inadequate response to or not candidates for surgical resection, pituitary irradiation, and bromocriptine mesylate at maximally tolerated doses∙dosingo start with immediate-release octreotide 50 mcg subcutaneously 3 times daily∙adjust dose based on GH levels measured at 1-4 hour intervals for 8-12 hours after subcutaneous injection or based on single IGF-1 level measured 2 weeks after initiation oftherapy or dose change∙usually maximum effect at 300-600 mcg/day, up to 1,500 mcg/day may be needed o switch to long-acting octreotide 20 mg intramuscularly once every 4 weeks for 3 months ∙may be used after establishing efficacy and tolerance with at least 2 weeks of subcutaneous octreotide; subcutaneous octreotide may be needed for 2-4 weeks after long-actingsuspension given。