{"id":4423257,"date":"2026-05-27T20:27:08","date_gmt":"2026-05-28T01:27:08","guid":{"rendered":"https:\/\/myendoconsult.com\/learn\/?p=4423257"},"modified":"2026-05-27T21:42:03","modified_gmt":"2026-05-28T02:42:03","slug":"evaluation-of-acromegaly","status":"publish","type":"post","link":"https:\/\/myendoconsult.com\/learn\/evaluation-of-acromegaly\/","title":{"rendered":"Evaluation of Acromegaly"},"content":{"rendered":"\n<h1 class=\"wp-block-heading\">Acromegaly \u2014 High-Yield Notes<\/h1>\n\n\n\n<p class=\"wp-block-paragraph\"><em>Source: MyEndoConsult Team<\/em><\/p>\n\n\n\n<figure class=\"wp-block-image size-full\"><img loading=\"lazy\" decoding=\"async\" width=\"1200\" height=\"600\" src=\"https:\/\/myendoconsult.com\/learn\/wp-content\/uploads\/acromegaly-facts-diagram-300dpi.jpg\" alt=\"\" class=\"wp-image-4423259\" srcset=\"https:\/\/myendoconsult.com\/learn\/wp-content\/uploads\/acromegaly-facts-diagram-300dpi.jpg 1200w, https:\/\/myendoconsult.com\/learn\/wp-content\/uploads\/acromegaly-facts-diagram-300dpi-300x150.jpg 300w, https:\/\/myendoconsult.com\/learn\/wp-content\/uploads\/acromegaly-facts-diagram-300dpi-768x384.jpg 768w, https:\/\/myendoconsult.com\/learn\/wp-content\/uploads\/acromegaly-facts-diagram-300dpi-480x240.jpg 480w\" sizes=\"auto, (max-width: 1200px) 100vw, 1200px\" \/><figcaption class=\"wp-element-caption\">Acromegaly : quick recall numbers. Created with<a href=\"https:\/\/www.biosketch.art\"> Biosketch.art<\/a> medical illustrator<\/figcaption><\/figure>\n\n\n\n<hr class=\"wp-block-separator has-alpha-channel-opacity\"\/>\n\n\n\n<h2 class=\"wp-block-heading\">1. Epidemiology &amp; Etiology<\/h2>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Incidence:<\/strong> 3\u201311 per million\/year; <strong>prevalence ~60 per million<\/strong> (newer data: up to 7.7\/million\/yr in Iceland, 6.9\/100,000 in Italy).<\/li>\n\n\n\n<li><strong>Equal M:F<\/strong>; typical Dx age <strong>40\u201360<\/strong>; younger patients = more aggressive disease.<\/li>\n\n\n\n<li><strong>Diagnostic lag:<\/strong> 5\u201310 years from symptom onset.<\/li>\n\n\n\n<li><strong>>99% cases = benign pituitary somatotroph adenoma.<\/strong> Pituitary carcinoma &lt;1%.<\/li>\n\n\n\n<li><strong>Rare causes:<\/strong> ectopic GHRH (bronchial carcinoid most common peripheral), hypothalamic GHRH (hamartoma, gangliocytoma), ectopic GH (lung, pancreas, adrenal), exogenous GH abuse.<\/li>\n\n\n\n<li><strong>~5% familial<\/strong> \u2014<a href=\"https:\/\/myendoconsult.com\/learn\/topics\/men-1\/\" data-type=\"oen_topic\" data-id=\"4422642\"> MEN1<\/a> most common, also McCune-Albright, FIPA, Carney complex.<\/li>\n<\/ul>\n\n\n\n<hr class=\"wp-block-separator has-alpha-channel-opacity\"\/>\n\n\n\n<h2 class=\"wp-block-heading\">2. GH \/ IGF-1 Physiology \u2014 Testable Points<\/h2>\n\n\n\n<ul class=\"wp-block-list\">\n<li>GH = <strong>191 aa<\/strong>, ~70% circulates as 22 kDa isoform; secreted in <strong>pulses<\/strong> (4\u201311\/24h, mostly nocturnal) \u2192 single random GH is useless.<\/li>\n\n\n\n<li>GH receptor \u2192 <strong>dimerizes<\/strong> \u2192 activates <strong>JAK2 \u2192 STAT5<\/strong> (also MAPK, PI3K\/Akt). Suppressed by SOCS1\u20133, SHP1\/2.<\/li>\n\n\n\n<li>IGF-1: 70 aa, ~48% homology with <a href=\"https:\/\/myendoconsult.com\/learn\/wp-content\/uploads\/insulin-biosynthesis.png\" data-type=\"attachment\" data-id=\"4422757\">proinsulin<\/a>; binds IGF-1R (similar to insulin R, 1\u20135% cross-affinity). IGF-1 mostly <strong>hepatic<\/strong>, but local paracrine\/autocrine IGF-1 drives most growth effects.<\/li>\n\n\n\n<li>IGF-1 binding: <strong>~99% bound<\/strong>; majority in <strong>ternary complex with IGFBP-3 + ALS<\/strong> (150 kDa, half-life <strong>12\u201315 h<\/strong> vs. 10 min for free IGF-1).<\/li>\n<\/ul>\n\n\n\n<figure class=\"wp-block-image size-full\"><img loading=\"lazy\" decoding=\"async\" width=\"1200\" height=\"600\" src=\"https:\/\/myendoconsult.com\/learn\/wp-content\/uploads\/igf-gh-signaling.jpg\" alt=\"\" class=\"wp-image-4423276\" srcset=\"https:\/\/myendoconsult.com\/learn\/wp-content\/uploads\/igf-gh-signaling.jpg 1200w, https:\/\/myendoconsult.com\/learn\/wp-content\/uploads\/igf-gh-signaling-300x150.jpg 300w, https:\/\/myendoconsult.com\/learn\/wp-content\/uploads\/igf-gh-signaling-768x384.jpg 768w, https:\/\/myendoconsult.com\/learn\/wp-content\/uploads\/igf-gh-signaling-480x240.jpg 480w\" sizes=\"auto, (max-width: 1200px) 100vw, 1200px\" \/><figcaption class=\"wp-element-caption\">Growth hormone and IGF-1 Physiology. Created with<a href=\"https:\/\/www.biosketch.art\"> Biosketch.art<\/a> medical illustrator<\/figcaption><\/figure>\n\n\n\n<h3 class=\"wp-block-heading\">GH Secretion \u2014 Stimulators vs. Inhibitors<\/h3>\n\n\n\n<figure class=\"wp-block-table\"><table class=\"has-fixed-layout\"><thead><tr><th>\u2191 GH<\/th><th>\u2193 GH<\/th><\/tr><\/thead><tbody><tr><td>Sleep, fasting, exercise, stress<\/td><td>Overeating, obesity, aging<\/td><\/tr><tr><td>Hypoglycemia, \u2193FFA, \u2191amino acids<\/td><td>Hyperglycemia, \u2191FFA, \u2191IGF-1<\/td><\/tr><tr><td>Dopamine, glucagon, sex steroids<\/td><td><strong>Somatostatin<\/strong><\/td><\/tr><tr><td>Ghrelin, klotho, GHRH<\/td><td><\/td><\/tr><tr><td><strong>Pathologic \u2191:<\/strong> acute glucocorticoids, T1DM, renal failure, anorexia, cirrhosis, depression<\/td><td><strong>Pathologic \u2193:<\/strong> chronic glucocorticoids, hyperthyroidism, T2DM<\/td><\/tr><\/tbody><\/table><\/figure>\n\n\n\n<blockquote class=\"wp-block-quote is-layout-flow wp-block-quote-is-layout-flow\">\n<p class=\"wp-block-paragraph\">Pearl: hypothyroidism in children \u2192 \u2193GH\/IGF-1 \u2192 short stature; reversed by T4. GH replacement lowers FT4 \/ raises FT3 via type 2 deiodinase.<\/p>\n<\/blockquote>\n\n\n\n<hr class=\"wp-block-separator has-alpha-channel-opacity\"\/>\n\n\n\n<h2 class=\"wp-block-heading\">3. Pathology \u2014 Adenoma Subtypes (high-yield IHC)<\/h2>\n\n\n\n<figure class=\"wp-block-table\"><table class=\"has-fixed-layout\"><thead><tr><th>Subtype<\/th><th>Frequency \/ Features<\/th><th>Behavior<\/th><\/tr><\/thead><tbody><tr><td><strong>Densely granulated somatotroph<\/strong><\/td><td>30\u201340%; eosinophilic; <strong>GNAS (Gs\u03b1) mutation<\/strong> \u2192 \u2191cAMP<\/td><td>Older pt, slow-growing, <strong>high GH, good SSA response<\/strong><\/td><\/tr><tr><td><strong>Sparsely granulated somatotroph<\/strong><\/td><td>Keratin aggregates (&#8220;fibrous bodies&#8221;); \u2193E-cadherin, \u2193SSTR2<\/td><td>Younger, invasive, <strong>poor SSA response<\/strong><\/td><\/tr><tr><td><strong>Mammosomatotroph<\/strong><\/td><td>Pit-1 lineage, co-stain GH + PRL<\/td><td>Young, early presentation, good SSA response<\/td><\/tr><tr><td><strong>Mixed somatotroph\/lactotroph<\/strong><\/td><td>Bihormonal<\/td><td>Recurrence-prone<\/td><\/tr><tr><td><strong>Mature plurihormonal Pit-1<\/strong><\/td><td>Stains GH\/PRL\/TSH, GATA3+<\/td><td>May present with <a href=\"https:\/\/myendoconsult.com\/learn\/hyperthyroidism-evaluation-algorithm\/\" data-type=\"post\" data-id=\"885338\">thyrotoxicosis<\/a> + non-suppressed TSH<\/td><\/tr><tr><td><strong>Acidophil stem cell<\/strong><\/td><td>GH+PRL precursor, oncocytic<\/td><td><a href=\"https:\/\/myendoconsult.com\/learn\/drugs-causing-hyperprolactinemia-mnemonic\/\" data-type=\"post\" data-id=\"2527025\">Hyperprolactinemia <\/a>disproportionate to size; poor DA response<\/td><\/tr><tr><td><strong>Poorly differentiated Pit-1<\/strong><\/td><td>Spindle cells<\/td><td>Macroadenomas, recurrence-prone<\/td><\/tr><tr><td><strong>Pituitary carcinoma<\/strong><\/td><td>&lt;1%; <strong>Ki67 often &gt;10%<\/strong>; distant mets required for Dx<\/td><td><a href=\"https:\/\/myendoconsult.com\/learn\/mechanism-of-action-of-temozolamide\/\" data-type=\"post\" data-id=\"4404742\">Temozolomide<\/a> + RT<\/td><\/tr><tr><td><strong>Pituitary hyperplasia<\/strong><\/td><td>Uniform enlargement, no focal enhancement<\/td><td><strong>Look for ectopic GHRH or genetic syndrome<\/strong><\/td><\/tr><\/tbody><\/table><\/figure>\n\n\n\n<blockquote class=\"wp-block-quote is-layout-flow wp-block-quote-is-layout-flow\">\n<p class=\"wp-block-paragraph\">Carcinoma is defined by <strong>metastasis<\/strong>, not local invasion.<\/p>\n<\/blockquote>\n\n\n\n<hr class=\"wp-block-separator has-alpha-channel-opacity\"\/>\n\n\n\n<h2 class=\"wp-block-heading\">4. Clinical Features (organized by system)<\/h2>\n\n\n\n<h3 class=\"wp-block-heading\">Local tumor effects<\/h3>\n\n\n\n<ul class=\"wp-block-list\">\n<li>Headache (often <strong>out of proportion to size<\/strong>), bitemporal hemianopia, cranial nerve palsies.<\/li>\n\n\n\n<li><strong>Hypopituitarism in ~40%<\/strong> (hypogonadism most common).<\/li>\n\n\n\n<li><strong>DI is rare in adenomas<\/strong> \u2192 suggests invasive\/non-adenomatous pathology.<\/li>\n<\/ul>\n\n\n\n<h3 class=\"wp-block-heading\">Soft tissue \/ skeletal<\/h3>\n\n\n\n<ul class=\"wp-block-list\">\n<li>Coarse features, frontal bossing, prognathism, <strong>macroglossia<\/strong>, spade-like hands, \u2191 ring\/shoe size, dental malocclusion.<\/li>\n\n\n\n<li><strong>Hyperhidrosis<\/strong> = one of most sensitive signs.<\/li>\n\n\n\n<li>Skin tags (IGF-1 driven epithelial proliferation), acanthosis, cutis verticis gyrata.<\/li>\n\n\n\n<li><strong>Vertebral fractures up to 60%<\/strong> (active disease); often <em>deformities<\/em> > true fractures. <strong>Volumetric DXA \/ TBS > standard DXA<\/strong> for risk.<\/li>\n\n\n\n<li>Acromegaly arthropathy: <strong>widened joint spaces, cartilage hypertrophy, osteophytes<\/strong> (opposite of OA early on); progresses despite biochemical cure.<\/li>\n<\/ul>\n\n\n\n<h3 class=\"wp-block-heading\">Cardiovascular (60% of mortality)<\/h3>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Anti-natriuretic effect<\/strong> of GH on ENaC in cortical collecting duct \u2192 volume expansion \u2192 HTN (diastolic > systolic).<\/li>\n\n\n\n<li>Three-phase cardiomyopathy: (1) hyperkinetic concentric hypertrophy \u2192 (2) diastolic dysfunction \u2192 (3) systolic failure (3\u20134%, poor prognosis).<\/li>\n\n\n\n<li><strong>Mitral\/aortic regurgitation = irreversible<\/strong> with treatment (cardiomyopathy reversible).<\/li>\n\n\n\n<li><strong>CMR > echo<\/strong> for fibrosis and RV dysfunction.<\/li>\n\n\n\n<li>Arrhythmias 7\u201340%; no clear \u2191 in IHD prevalence in recent data.<\/li>\n<\/ul>\n\n\n\n<h3 class=\"wp-block-heading\">Sleep \/ respiratory<\/h3>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>OSA 40\u201380%<\/strong> (11\u201320\u00d7 general population). Soft-tissue (pharyngeal) > bony changes drive it.<\/li>\n\n\n\n<li>~40% have <strong>persistent OSA<\/strong> after biochemical control.<\/li>\n\n\n\n<li>Central (non-obstructive) apnea also recognized \u2014 direct GH effect on respiratory center.<\/li>\n\n\n\n<li>\u2191 lung volumes, small-airway narrowing, subclinical hypoxemia.<\/li>\n<\/ul>\n\n\n\n<h3 class=\"wp-block-heading\">Metabolic<\/h3>\n\n\n\n<ul class=\"wp-block-list\">\n<li>DM in <strong>~50% at diagnosis<\/strong>; IGT in many more. Insulin resistance \u2193 GLUT1\/GLUT4, \u2191FFA, pro-inflammatory adipose.<\/li>\n\n\n\n<li><strong>\u2191TG, \u2193HDL, \u2191Lp(a), small dense LDL.<\/strong><\/li>\n<\/ul>\n\n\n\n<h3 class=\"wp-block-heading\">Neoplasia (screening matters)<\/h3>\n\n\n\n<ul class=\"wp-block-list\">\n<li>\u2191 <strong>colon polyps &amp; colorectal cancer<\/strong> \u2014 right-sided, larger, multiple, more dysplastic.<\/li>\n\n\n\n<li>\u2191 <strong>thyroid (papillary), breast, kidney, gastric, bladder<\/strong> in cohorts.<\/li>\n\n\n\n<li>Multinodular goiter in 70\u201380%.<\/li>\n<\/ul>\n\n\n\n<h3 class=\"wp-block-heading\">Other<\/h3>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Carpal tunnel ~60%<\/strong> (median nerve swelling itself, not extrinsic compression).<\/li>\n\n\n\n<li>Hypercoagulable (\u2191 fibrinogen, factor VIII).<\/li>\n\n\n\n<li>Renal: \u2191GFR, hypercalciuria, hyperphosphaturia, microalbuminuria, glomerulosclerosis (chronic).<\/li>\n<\/ul>\n\n\n\n<figure class=\"wp-block-image size-full\"><img loading=\"lazy\" decoding=\"async\" width=\"1200\" height=\"600\" src=\"https:\/\/myendoconsult.com\/learn\/wp-content\/uploads\/acromegaly-facies.jpg\" alt=\"\" class=\"wp-image-4423271\" srcset=\"https:\/\/myendoconsult.com\/learn\/wp-content\/uploads\/acromegaly-facies.jpg 1200w, https:\/\/myendoconsult.com\/learn\/wp-content\/uploads\/acromegaly-facies-300x150.jpg 300w, https:\/\/myendoconsult.com\/learn\/wp-content\/uploads\/acromegaly-facies-768x384.jpg 768w, https:\/\/myendoconsult.com\/learn\/wp-content\/uploads\/acromegaly-facies-480x240.jpg 480w\" sizes=\"auto, (max-width: 1200px) 100vw, 1200px\" \/><figcaption class=\"wp-element-caption\">Acromegalic facies &#8211; Created with<a href=\"https:\/\/www.biosketch.art\"> Biosketch.art<\/a> medical illustrator<\/figcaption><\/figure>\n\n\n\n<hr class=\"wp-block-separator has-alpha-channel-opacity\"\/>\n\n\n\n<h2 class=\"wp-block-heading\">5. Diagnosis<\/h2>\n\n\n\n<h3 class=\"wp-block-heading\">Biochemical (initial)<\/h3>\n\n\n\n<ol class=\"wp-block-list\">\n<li><strong>IGF-1<\/strong> (age- and sex-matched) \u2014 first-line screen. Confounded by liver\/renal disease, malnutrition, DM, pregnancy.<\/li>\n\n\n\n<li><strong><a href=\"https:\/\/myendoconsult.com\/learn\/evaluation-of-acromegaly\/\" data-type=\"post\" data-id=\"4423257\">OGTT with GH suppression<\/a> \u2014 gold standard<\/strong>\n<ul class=\"wp-block-list\">\n<li>75 g glucose \u2192 GH at 0, 30, 60, 90, 120 (\u00b1150) min.<\/li>\n\n\n\n<li><strong>Fail to suppress GH &lt;1.0 ng\/mL (older) or &lt;0.4 ng\/mL (modern ultrasensitive assays)<\/strong> = diagnostic.<\/li>\n\n\n\n<li><strong>~30% show paradoxical rise<\/strong>.<\/li>\n\n\n\n<li>False positives: T1DM, cirrhosis, CKD, adolescence, stress, L-dopa, estrogen, opioids.<\/li>\n<\/ul>\n<\/li>\n\n\n\n<li>GH day curve \u2014 fixed measurable secretion vs. normal undetectable nadirs.<\/li>\n\n\n\n<li><strong>TRH test<\/strong> \u2014 paradoxical GH rise in ~60% of acromegaly (rarely used now).<\/li>\n\n\n\n<li><strong>Co-secretion of PRL in ~1\/3<\/strong> \u2192 measure PRL; exclude macroprolactin if elevated.<\/li>\n\n\n\n<li><strong>Serum GHRH<\/strong> if ectopic source suspected.<\/li>\n<\/ol>\n\n\n\n<figure class=\"wp-block-image size-full\"><img loading=\"lazy\" decoding=\"async\" width=\"1200\" height=\"600\" src=\"https:\/\/myendoconsult.com\/learn\/wp-content\/uploads\/diagram-300dpi-acromegaly-diagnosis-pathway.jpg\" alt=\"\" class=\"wp-image-4423267\" srcset=\"https:\/\/myendoconsult.com\/learn\/wp-content\/uploads\/diagram-300dpi-acromegaly-diagnosis-pathway.jpg 1200w, https:\/\/myendoconsult.com\/learn\/wp-content\/uploads\/diagram-300dpi-acromegaly-diagnosis-pathway-300x150.jpg 300w, https:\/\/myendoconsult.com\/learn\/wp-content\/uploads\/diagram-300dpi-acromegaly-diagnosis-pathway-768x384.jpg 768w, https:\/\/myendoconsult.com\/learn\/wp-content\/uploads\/diagram-300dpi-acromegaly-diagnosis-pathway-480x240.jpg 480w\" sizes=\"auto, (max-width: 1200px) 100vw, 1200px\" \/><figcaption class=\"wp-element-caption\">Acromegaly Testing Pathway. Created with<a href=\"https:\/\/www.biosketch.art\"> Biosketch.art<\/a> medical illustrator<\/figcaption><\/figure>\n\n\n\n<h3 class=\"wp-block-heading\">Imaging<\/h3>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong><a href=\"https:\/\/myendoconsult.com\/learn\/anatomy-of-pituitary\/\" data-type=\"post\" data-id=\"732926\">Pituitary MRI with gadolinium<\/a><\/strong> = standard.<\/li>\n\n\n\n<li><strong>>70% macroadenomas<\/strong> at Dx. Younger patients \u2192 more invasive.<\/li>\n\n\n\n<li><strong>T2 hypointensity \u2192 densely granulated \u2192 good SSA response.<\/strong> T2 hyperintensity \u2192 sparsely granulated \u2192 poor SSA response.<\/li>\n\n\n\n<li><strong>Knosp grade \u22653<\/strong> (crossing lateral tangent of intracavernous\/supracavernous ICA) = invasive, lower surgical cure.<\/li>\n\n\n\n<li><strong>C-11 methionine PET (MET-PET)<\/strong> for residual\/persistent disease post-op.<\/li>\n\n\n\n<li>Gallium-DOTATATE \/ somatostatin receptor scintigraphy for <strong>ectopic GHRH<\/strong> localization.<\/li>\n<\/ul>\n\n\n\n<h3 class=\"wp-block-heading\">Post-treatment monitoring criteria (<strong>memorize<\/strong>)<\/h3>\n\n\n\n<figure class=\"wp-block-table\"><table class=\"has-fixed-layout\"><thead><tr><th>Marker<\/th><th>Cutoff<\/th><th>Interpretation<\/th><\/tr><\/thead><tbody><tr><td>Random GH<\/td><td><strong>&lt;0.4 \u00b5g\/L<\/strong><\/td><td>Remission<\/td><\/tr><tr><td>Random GH<\/td><td><strong>&lt;1.0 \u00b5g\/L<\/strong><\/td><td>&#8220;Safe,&#8221; normalized mortality<\/td><\/tr><tr><td>OGTT GH nadir<\/td><td><strong>&lt;0.4 \u00b5g\/L<\/strong> (Endocrine Society)<\/td><td>Remission<\/td><\/tr><tr><td>OGTT GH nadir<\/td><td><strong>&lt;1.0 \u00b5g\/L<\/strong><\/td><td>Good control<\/td><\/tr><tr><td>IGF-1<\/td><td>Age-\/sex-matched normal<\/td><td>Goal<\/td><\/tr><tr><td>Mean GH on day curve<\/td><td>&lt;2.5 \u00b5g\/L<\/td><td>Disease control (unreliable post-RT)<\/td><\/tr><\/tbody><\/table><\/figure>\n\n\n\n<blockquote class=\"wp-block-quote is-layout-flow wp-block-quote-is-layout-flow\">\n<p class=\"wp-block-paragraph\">Post-op IGF-1 takes <strong>~3 months to normalize<\/strong> \u2192 don&#8217;t interpret too early. Post-op MRI also at 3 months.<\/p>\n<\/blockquote>\n\n\n\n<hr class=\"wp-block-separator has-alpha-channel-opacity\"\/>\n\n\n\n<h2 class=\"wp-block-heading\">6. Genetic Syndromes<\/h2>\n\n\n\n<figure class=\"wp-block-table\"><table class=\"has-fixed-layout\"><thead><tr><th>Syndrome<\/th><th>Gene<\/th><th>Clinical clue<\/th><\/tr><\/thead><tbody><tr><td><strong>FIPA<\/strong><\/td><td><strong>AIP<\/strong> (AD)<\/td><td>Young males, high GH, <strong>poor SSA response<\/strong><\/td><\/tr><tr><td><strong>X-LAG<\/strong><\/td><td><strong>GPR101<\/strong> (X-linked)<\/td><td>~80% pre-pubertal acromegaly; mostly female; &lt;5 yo<\/td><\/tr><tr><td><strong>MEN1<\/strong><\/td><td>MEN1 (AD)<\/td><td>Pituitary + parathyroid + pancreas. ~6% of MEN1 get GH adenoma<\/td><\/tr><tr><td><strong>MEN4<\/strong><\/td><td>CDKN1B (AD)<\/td><td>Pit + parathyroid + pheo + thyroid<\/td><\/tr><tr><td><strong>Carney complex<\/strong><\/td><td>PRKAR1A (AD)<\/td><td>Skin lentigines, atrial myxoma, PPNAD-Cushing&#8217;s, somatotroph hyperplasia<\/td><\/tr><tr><td><strong>McCune-Albright<\/strong><\/td><td>GNAS (mosaic)<\/td><td>Caf\u00e9-au-lait, precocious puberty, fibrous dysplasia; acromegaly in 20\u201330%<\/td><\/tr><tr><td><strong>SDH mutations<\/strong><\/td><td>SDHx (AD)<\/td><td>Pheo\/paraganglioma + pituitary<\/td><\/tr><tr><td><strong>NF1<\/strong><\/td><td>NF1 (AD)<\/td><td>Optic glioma, rare adenoma<\/td><\/tr><\/tbody><\/table><\/figure>\n\n\n\n<blockquote class=\"wp-block-quote is-layout-flow wp-block-quote-is-layout-flow\">\n<p class=\"wp-block-paragraph\">Order <strong>AIP<\/strong> testing for any pituitary tumor &lt;30 yo or family history. Order <strong>MEN1<\/strong> if young + hypercalcemia.<\/p>\n<\/blockquote>\n\n\n\n<hr class=\"wp-block-separator has-alpha-channel-opacity\"\/>\n\n\n\n<h2 class=\"wp-block-heading\">7. Complication Screening (at diagnosis, then\u2026)<\/h2>\n\n\n\n<figure class=\"wp-block-table\"><table class=\"has-fixed-layout\"><thead><tr><th>Complication<\/th><th>Test<\/th><th>Frequency<\/th><\/tr><\/thead><tbody><tr><td>HTN<\/td><td>BP \u00b1 ABPM<\/td><td>q6 mo<\/td><\/tr><tr><td><a href=\"https:\/\/myendoconsult.com\/learn\/topics\/type-2-diabetes\/\" data-type=\"oen_topic\" data-id=\"4422489\">DM<\/a><\/td><td>HbA1c, FBG (OGTT in selected)<\/td><td>q6 mo<\/td><\/tr><tr><td>OSA<\/td><td>Epworth \u2192 polysomnography<\/td><td>Annually<\/td><\/tr><tr><td>Cardiomyopathy<\/td><td>ECG, echo<\/td><td>q3\u20135 yr if normal<\/td><\/tr><tr><td>Dyslipidemia<\/td><td>Lipid panel<\/td><td>q6 mo<\/td><\/tr><tr><td><strong>Colon cancer<\/strong><\/td><td>Colonoscopy from <strong>age 40<\/strong>; <strong>rigorous bowel prep<\/strong> (2\u00d7 normal)<\/td><td>q10y if normal; q3\u20135y if polyp + \u2191IGF-1<\/td><\/tr><tr><td>Thyroid nodules<\/td><td>Clinical \u00b1 US<\/td><td>Annually<\/td><\/tr><tr><td>Vertebral disease<\/td><td>Spine X-ray \/ DXA \/ TBS<\/td><td>At Dx, yearly if symptoms<\/td><\/tr><tr><td>QoL<\/td><td>AcroQoL<\/td><td>Annually<\/td><\/tr><\/tbody><\/table><\/figure>\n\n\n\n<hr class=\"wp-block-separator has-alpha-channel-opacity\"\/>\n\n\n\n<h2 class=\"wp-block-heading\">8. Management<\/h2>\n\n\n\n<h3 class=\"wp-block-heading\">Goals<\/h3>\n\n\n\n<ol class=\"wp-block-list\">\n<li>Normalize GH (&lt;1 \u00b5g\/L safe, &lt;0.4 \u00b5g\/L cure) and <strong>age-matched IGF-1<\/strong>.<\/li>\n\n\n\n<li>Resolve mass effects, preserve pituitary function, prevent recurrence, manage comorbidities.<\/li>\n<\/ol>\n\n\n\n<h3 class=\"wp-block-heading\">Surgery \u2014 first line for most<\/h3>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Endoscopic transsphenoidal<\/strong> is now standard.<\/li>\n\n\n\n<li><strong>Cure rates:<\/strong> microadenoma 70\u201390%; macroadenoma 30\u201350%; invasive macro &lt;50%; giant &lt;20%.<\/li>\n\n\n\n<li>Predictors of cure: smaller size, lower pre-op GH, <strong>no cavernous sinus invasion (Knosp 0\u20132)<\/strong>, older age.<\/li>\n\n\n\n<li>Pre-op SSA can shrink tumor ~50% and improve cardiopulmonary status.<\/li>\n\n\n\n<li>Complications: transient DI (~5% permanent), CSF leak, meningitis, hypopituitarism.<\/li>\n\n\n\n<li>Mortality &lt;0.5% in experienced hands.<\/li>\n<\/ul>\n\n\n\n<h3 class=\"wp-block-heading\">Medical Therapy<\/h3>\n\n\n\n<p class=\"wp-block-paragraph\"><strong><a href=\"https:\/\/myendoconsult.com\/learn\/cabergoline-for-acromegaly\/\" data-type=\"post\" data-id=\"4404708\">Dopamine agonists (cabergoline)<\/a><\/strong><\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li>Oral; dose 1\u20134 mg\/wk (much higher than for prolactinoma).<\/li>\n\n\n\n<li>IGF-1 normalization in <strong>~34%<\/strong> (meta-analysis).<\/li>\n\n\n\n<li><strong>Best use:<\/strong> mild IGF-1 elevation (&lt;2\u00d7 ULN), co-secreting GH+PRL tumors, combo therapy.<\/li>\n<\/ul>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>Somatostatin analogues (1st generation: octreotide LAR, lanreotide ATG)<\/strong><\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li>Bind <strong>SSTR2<\/strong> (and 5).<\/li>\n\n\n\n<li>~50\u201370% achieve safe GH and normal IGF-1.<\/li>\n\n\n\n<li>Doses: octreotide LAR 10\u201330 mg q4wk IM; lanreotide ATG 60\u2013120 mg q4wk deep SC.<\/li>\n\n\n\n<li><strong>AE:<\/strong> GI upset, <strong>cholelithiasis (~50% at 2 yrs)<\/strong>, hypothyroidism, sinus bradycardia, alopecia (rare), variable glycemic effects.<\/li>\n\n\n\n<li><strong>Predictors of response:<\/strong> T2 hypointense, densely granulated, SSTR2a+, anti-Cam5.2+ , low Ki67.<\/li>\n<\/ul>\n\n\n\n<p class=\"wp-block-paragraph\"><strong><a href=\"https:\/\/myendoconsult.com\/learn\/mechanism-of-action-of-pasireotide\/\" data-type=\"post\" data-id=\"4404489\">Pasireotide LAR (2nd generation SSA)<\/a><\/strong><\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li>Binds SSTR1, 2, 3, <strong>5<\/strong> (high affinity).<\/li>\n\n\n\n<li>Slightly better than octreotide in head-to-head; useful in <strong>1st-gen SSA-resistant<\/strong> disease (~20% control).<\/li>\n\n\n\n<li>Useful for headache control.<\/li>\n\n\n\n<li><strong>AE: hyperglycemia is the key issue<\/strong> (much worse than 1st-gen).<\/li>\n<\/ul>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>Oral octreotide<\/strong> \u2014 FDA approved; 40\u201380 mg\/day; ~65% maintain control after switch from injectable.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\"><strong><a href=\"https:\/\/myendoconsult.com\/learn\/pegvisomant-for-acromegaly\/\" data-type=\"post\" data-id=\"4404681\">Pegvisomant \u2014 GH receptor antagonist<\/a><\/strong><\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li>PEGylated modified GH that blocks receptor <strong>dimerization<\/strong>.<\/li>\n\n\n\n<li>Daily SC; 10\u201340 mg\/day.<\/li>\n\n\n\n<li><strong>Normalizes IGF-1 in ~90%.<\/strong><\/li>\n\n\n\n<li><strong>Cannot use GH to monitor<\/strong> \u2014 drug interferes with assay; <strong>monitor IGF-1 only<\/strong>.<\/li>\n\n\n\n<li><strong>AE:<\/strong> LFT abnormalities, injection site reactions, theoretical risk of tumor growth (rarely reported in practice).<\/li>\n\n\n\n<li><strong>Best use:<\/strong> SSA-resistant disease, diabetic patients (favorable glycemic profile).<\/li>\n\n\n\n<li>Combinations: SSA + pegvisomant or cabergoline + pegvisomant \u2192 IGF-1 control >90%.<\/li>\n<\/ul>\n\n\n\n<h3 class=\"wp-block-heading\">Radiotherapy \u2014 adjunct<\/h3>\n\n\n\n<ul class=\"wp-block-list\">\n<li>Used when surgery + medical therapy fail to control disease.<\/li>\n\n\n\n<li><strong>Conventional fractionated:<\/strong> ~4500 cGy in 25 fractions. GH falls ~50% by 2 yrs; IGF-1 normal in ~60% by 10 yrs.<\/li>\n\n\n\n<li><strong>Stereotactic (Gamma Knife \/ SMART):<\/strong> single 15\u201335 Gy; faster GH fall; ~50% biochemical remission at 5 yrs. Avoid if tumor near optic chiasm.<\/li>\n\n\n\n<li><strong>Long-term complications:<\/strong> hypopituitarism (most common \u2014 60% hypogonadal, 50% ACTH-deficient, 40% T4-deficient at 10 yr), secondary brain tumors (~2%), radiation optic neuropathy (~5%), CVA (up to 20% at 20 yr), cognitive impairment.<\/li>\n<\/ul>\n\n\n\n<hr class=\"wp-block-separator has-alpha-channel-opacity\"\/>\n\n\n\n<h2 class=\"wp-block-heading\">9. Pearls &amp; Pitfalls<\/h2>\n\n\n\n<ul class=\"wp-block-list\">\n<li>A <strong>single random GH<\/strong> is diagnostically useless \u2014 always OGTT or IGF-1.<\/li>\n\n\n\n<li><strong>Macroglossia, prognathism, supraglottic edema<\/strong> \u2192 flag the anesthesiologist; <strong>difficult airway<\/strong>.<\/li>\n\n\n\n<li><strong>OGTT can be falsely positive<\/strong> in T1DM, cirrhosis, CKD, adolescence, stress, estrogen\/L-dopa\/opioids.<\/li>\n\n\n\n<li><strong>Valvular disease does not reverse<\/strong> with treatment \u2014 cardiomyopathy mostly does.<\/li>\n\n\n\n<li><strong>Pasireotide \u2192 hyperglycemia.<\/strong> Pegvisomant \u2192 improves glycemia. Octreotide\/lanreotide \u2192 neutral-to-mildly worsening.<\/li>\n\n\n\n<li><strong>Pituitary hyperplasia on histology<\/strong> \u2192 hunt for ectopic GHRH (think bronchial carcinoid).<\/li>\n\n\n\n<li><strong>Pseudoacromegaly differentials:<\/strong> pachydermoperiostosis (HPGD\/SLCO2A1 mutations \u2192 \u2191PGE2), severe insulin resistance syndromes, Marfans, homocystinuria.<\/li>\n\n\n\n<li><strong><a href=\"https:\/\/myendoconsult.com\/learn\/topics\/diabetes-insipidus\/\" data-type=\"oen_topic\" data-id=\"4422292\">DI <\/a>in a &#8220;pituitary adenoma&#8221;<\/strong> \u2192 it&#8217;s probably not an adenoma (think craniopharyngioma, metastasis, hypophysitis).<\/li>\n\n\n\n<li><strong>Colonoscopy preparation needs to be doubled<\/strong> \u2014 slow transit, elongated colon. Right-sided polyps common \u2192 ensure cecum is reached.<\/li>\n\n\n\n<li><strong>Mortality determinants:<\/strong> age and IGF-1 at diagnosis, treatment modality, malignancy, <strong>diagnostic delay<\/strong>.<\/li>\n<\/ul>\n\n\n\n<hr class=\"wp-block-separator has-alpha-channel-opacity\"\/>\n\n\n\n<h2 class=\"wp-block-heading\">10. Quick-Recall Numbers<\/h2>\n\n\n\n<ul class=\"wp-block-list\">\n<li>Prevalence: <strong>~60\/million<\/strong><\/li>\n\n\n\n<li>Diagnostic delay: <strong>5\u201310 years<\/strong><\/li>\n\n\n\n<li>Macroadenomas at Dx: <strong>>70%<\/strong><\/li>\n\n\n\n<li>DM at Dx: <strong>~50%<\/strong><\/li>\n\n\n\n<li>OSA: <strong>40\u201380%<\/strong><\/li>\n\n\n\n<li>Carpal tunnel: <strong>~60%<\/strong><\/li>\n\n\n\n<li>HTN at Dx (ABPM): <strong>~22%<\/strong><\/li>\n\n\n\n<li>Vertebral fractures (active disease): <strong>up to 60%<\/strong><\/li>\n\n\n\n<li>Cholelithiasis on SSA at 2 yr: <strong>~50%<\/strong><\/li>\n\n\n\n<li>Mortality ratio if untreated: <strong>~2\u00d7 normal<\/strong><\/li>\n\n\n\n<li>Surgical cure: micro <strong>70\u201390%<\/strong>, macro <strong>30\u201350%<\/strong>, invasive <strong>&lt;50%<\/strong>, giant <strong>&lt;20%<\/strong><\/li>\n\n\n\n<li>Cure cutoffs: GH <strong>&lt;0.4 \u00b5g\/L<\/strong> (cure) \/ <strong>&lt;1.0 \u00b5g\/L<\/strong> (safe); IGF-1 within age\/sex range.<\/li>\n<\/ul>\n\n\n\n<h3 class=\"wp-block-heading\">Must-Read References on Acromegaly<\/h3>\n\n\n\n<ol class=\"wp-block-list\">\n<li><strong>Katznelson L, Laws ER Jr, Melmed S, et al.<\/strong> Acromegaly: An Endocrine Society Clinical Practice Guideline. <em>J Clin Endocrinol Metab.<\/em> 2014;99(11):3933\u20133951. doi:10.1210\/jc.2014-2700 <em>The foundational US\/European guideline. Diagnostic cutoffs, treatment algorithm, pregnancy management. Still the most-cited reference.<\/em><\/li>\n\n\n\n<li><strong>Fleseriu M, Biller BMK, Freda PU, et al.<\/strong> A Pituitary Society update to acromegaly management guidelines. <em>Pituitary.<\/em> 2021;24(1):1\u201313. doi:10.1007\/s11102-020-01091-7 <em>The modern update that incorporates oral octreotide, novel combinations, and refined treatment goals. Read with Katznelson 2014 as a pair.<\/em><\/li>\n\n\n\n<li><strong>Melmed S, Bronstein MD, Chanson P, et al.<\/strong> A Consensus Statement on acromegaly therapeutic outcomes. <em>Nat Rev Endocrinol.<\/em> 2018;14(9):552\u2013561. doi:10.1038\/s41574-018-0058-5 <em>Defines what &#8220;controlled&#8221; and &#8220;cured&#8221; mean biochemically and clinically \u2014 directly testable cutoffs.<\/em><\/li>\n\n\n\n<li><strong>Giustina A, Barkan A, Beckers A, et al.<\/strong> A Consensus on the Diagnosis and Treatment of Acromegaly Comorbidities: An Update. <em>J Clin Endocrinol Metab.<\/em> 2020;105(4):e937\u2013e946. doi:10.1210\/clinem\/dgz096 <em>The authoritative reference on cardiovascular, metabolic, bone, sleep, and oncologic complications. Screening recommendations originate here.<\/em><\/li>\n\n\n\n<li><strong>Giustina A, Biermasz NR, Casanueva FF, et al.<\/strong> Consensus on criteria for acromegaly diagnosis and remission. <em>Pituitary.<\/em> 2024;27(1):7\u201322. doi:10.1007\/s11102-023-01360-1 <em>Most recent international consensus on diagnostic and remission criteria \u2014 supersedes older OGTT\/IGF-1 thresholds.<\/em><\/li>\n\n\n\n<li><strong>Colao A, Grasso LFS, Giustina A, et al.<\/strong> Acromegaly. <em>Nat Rev Dis Primers.<\/em> 2019;5(1):20. doi:10.1038\/s41572-019-0071-6 <em>Comprehensive single-source review covering pathogenesis to QoL. Best illustrations and treatment algorithms in the literature.<\/em><\/li>\n\n\n\n<li><strong>Bolfi F, Neves AF, Boguszewski CL, Nunes-Nogueira VS.<\/strong> Mortality in acromegaly decreased in the last decade: a systematic review and meta-analysis. <em>Eur J Endocrinol.<\/em> 2018;179(1):59\u201371. doi:10.1530\/EJE-18-0255 <em>Updated mortality data showing normalization with modern multimodal therapy. Replaces older Holdaway 2008 meta-analysis (which is still worth reading for historical context).<\/em><\/li>\n\n\n\n<li><strong>Melmed S.<\/strong> Acromegaly pathogenesis and treatment. <em>J Clin Invest.<\/em> 2009;119(11):3189\u20133202. doi:10.1172\/JCI39375 <em>Melmed&#8217;s mechanistic review \u2014 still the clearest explanation of GH\/IGF-1 signaling, somatotroph tumorigenesis, and SSTR pharmacology.<\/em><\/li>\n\n\n\n<li><strong>Bogus\u0142awska A, Korbonits M.<\/strong> Genetics of Acromegaly and Gigantism. <em>J Clin Med.<\/em> 2021;10(7):1377. doi:10.3390\/jcm10071377 <em>Comprehensive review of AIP\/FIPA, X-LAG (GPR101), MEN1\/4, Carney complex, McCune-Albright, and 3PAs. Includes genetic testing algorithm.<\/em><\/li>\n\n\n\n<li><strong>Carroll PV, Joshi MN.<\/strong> Acromegaly. In: Feingold KR, et al., eds. <em>Endotext<\/em> [Internet]. South Dartmouth (MA): MDText.com, Inc.; updated September 7, 2022. Available from: <a href=\"https:\/\/www.ncbi.nlm.nih.gov\/books\/NBK279097\/\">https:\/\/www.ncbi.nlm.nih.gov\/books\/NBK279097\/<\/a> <\/li>\n<\/ol>\n\n\n\n\n","protected":false},"excerpt":{"rendered":"<p>Acromegaly \u2014 High-Yield Notes Source: MyEndoConsult Team 1. Epidemiology &amp; Etiology 2. GH \/ IGF-1 Physiology \u2014 Testable Points GH Secretion \u2014 Stimulators vs.&hellip;<\/p>\n","protected":false},"author":1,"featured_media":4423267,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[568],"tags":[],"class_list":["post-4423257","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-board-review"],"_links":{"self":[{"href":"https:\/\/myendoconsult.com\/learn\/wp-json\/wp\/v2\/posts\/4423257","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/myendoconsult.com\/learn\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/myendoconsult.com\/learn\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/myendoconsult.com\/learn\/wp-json\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/myendoconsult.com\/learn\/wp-json\/wp\/v2\/comments?post=4423257"}],"version-history":[{"count":11,"href":"https:\/\/myendoconsult.com\/learn\/wp-json\/wp\/v2\/posts\/4423257\/revisions"}],"predecessor-version":[{"id":4423278,"href":"https:\/\/myendoconsult.com\/learn\/wp-json\/wp\/v2\/posts\/4423257\/revisions\/4423278"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/myendoconsult.com\/learn\/wp-json\/wp\/v2\/media\/4423267"}],"wp:attachment":[{"href":"https:\/\/myendoconsult.com\/learn\/wp-json\/wp\/v2\/media?parent=4423257"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/myendoconsult.com\/learn\/wp-json\/wp\/v2\/categories?post=4423257"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/myendoconsult.com\/learn\/wp-json\/wp\/v2\/tags?post=4423257"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}