Snapshot A 43-year-old man complains of increased hat size and headaches when he wakes up in the morning. Physical exam reveals mild hypertension, prominent jaw with spaces between the teeth, large hands and feet, and generalized muscle weakness. Introduction Clinical definition excessive growth after skeletal epiphyseal closure due to ↑growth hormone (GH) Genetics not hereditary many have a spontaneous mutation leading to persistent ↑ cyclic adenosine monophosphate (cAMP) in somatotroph cells Associated conditions McCune-Albright syndrome multiple endocrine neoplasia neurofibromatosis tuberous sclerosis Epidemiology Rare Middle age presentation due to insidious onset Females and males equally affected ETIOLOGY Pathogenesis most commonly from a benign pituitary adenoma (> 95%) or hyperplasia less commonly from ectopic oversecretion of GH or growth hormone releasing hormone (GHRH), such as hypothalamic, pulmonary, and gastrointestinal ↑ insulinlike growth factor (IGF-1) mediates effects of GH Presentation Symptoms headache sweating clothes and hat fit tightly amenorrhea or impotence deep voice and slow speech Physical exam hypertension diaphoresis mitral valve regurgitation enlarged head with frontal bossing and deepened facial folds enlarged jaw with increased teeth spacing enlarged fingers and feet skin tags doughy-feeling skin neuropathy muscle weakness imaging Magnetic resonance imaging (MRI) of the brain for pituitary adenoma Computed tomography (CT) scan if suspicion for non-pituitary secretion Radiography to evaluate associated skeletal changes Studies Diagnostic testing studies ↑ IGF1 most sensitive good for screening oral glucose load GH levels 2 hours after 75 g or 100 g glucose tolerance very specific good to confirm diagnosis after positive IGF1 screening GH > 1 μg/L is diagnostic pituitary function may indicate co-secretion or disruption secondary to mass effect prolactin thyroid stimulating hormone (TSH) luteinizing hormone (LH) and follicle-stimulating hormone (FSH) adrenocorticotropic hormone (ACTH) chemistry would show hyperglycemia Differential Gigantism distinguishing factor ↑ GH before skeletal epiphyseal closure Pseudoacromegaly possibly medication-related distinguishing factor no increase in GH and IGF-1 Marfan syndrome distinguishing factor collagen disorder Prolactinoma most common secreting pituitary adenoma distinguishing factor prolactin secretion instead of GH no acromegaloid features Treatment Management approach requires a multimodal approach surgical resection is often first line medical therapy or radiation as neoadjuvant or adjuvant or primary if not amenable to surgery requires long term follow up Surgical rapid and effective endonasal transsphenoidal resection first-line treatment for nonfunctioning macroadenomas Medical leads to clinical improvement in 70% somatostatin analog inhibits GH production first-line medical treatment octreotide or lanreotide symptomatic management tumor size reduction prior to surgery also indicated in non-pituitary tumors dopamine agonist second-line medical treatment bromocriptine or cabergoline GH receptor antagonist pegvisomant Radiotherapy usually used as adjunct treatment after resection can also be used as first option of treatment Complications Bitemporal hemianopsia Hypopituitarism Cardiomyopathy and heart failure most common cause of death Diabetes Colon cancer Sleep apnea Carpal tunnel Prognosis High morbidity and mortality if untreated due to associated cardiovascular disease, cerebrovascular disease, and malignancy