Approach
Acromegaly is an insidious chronic disease. Early physical changes may be unnoticed by patients, family members and other close contacts, and physicians. The diagnosis is often delayed up to 10 years after the appearance of the initial symptoms and signs (by retrospective analysis).[11] By the time the diagnosis is made, the patient's physical appearance has been changed, and the metabolic, cardiovascular, and osteoarticular complications have significantly affected their quality of life. Early symptom recognition is very important for improvement of prognosis and quality of life. Diagnosis is based on biochemical confirmation of growth hormone (GH)/insulin-like growth factor 1 (IGF-1) hypersecretion.
Clinical features
Clinical suspicion of acromegaly should be raised when patients present with the following signs and symptoms.[4][5]
Systemic effects of GH/IGF-1 excess
Morphologic facial changes: frontal bossing, enlarged nose, prognathism and maxillary widening with separation of teeth, macroglossia
Soft-tissue and skin changes: increased sweating, oily skin, skin tags, increased skin thickness and soft-tissue hypertrophy, carpal tunnel syndrome
Respiratory complications: snoring, sleep apnea (central and obstructive), upper airway obstruction
Osteoarticular features: arthropathy, osteoarthritis, vertebral fractures
Cardiovascular features: hypertension, hypertrophic cardiomyopathy, arrhythmias, congestive heart failure
Metabolic complications: impaired glucose tolerance, diabetes mellitus
Organomegaly: for example, thyroid, prostate
Other: hypercalciuria
If GH hypersecretion occurs before closure of the epiphyseal plates, patients will have increased height and gigantism.
[Figure caption and citation for the preceding image starts]: Patient with typical features of acromegalyFrom the collection of Dr Omar Serri; used with patient permission [Citation ends].
Effects of prolactin cosecretion
Decreased libido
Infertility
Amenorrhea, oligomenorrhea
Galactorrhea
Erectile dysfunction
Tumor mass effects
Headaches
Visual field defects
Cranial nerve palsies
Pituitary stalk compression: signs and symptoms of hypopituitarism (vary depending on which hormones are deficient; key diagnostic factors include infertility, amenorrhea/oligomenorrhea, and delayed puberty due to gonadotropin deficiency, and hypoglycemia and hypotension due to adrenal insufficiency); hyperprolactinemia.
Biochemical diagnosis
Biochemical screening for acromegaly involves obtaining plasma measurements of IGF-1 and, if needed, GH (random or fasting) in those displaying suggestive clinical features.[12][13] Acromegaly is excluded in most cases when IGF-1 (sex- and age-matched value) is normal. It is confirmed by an IGF-1 (sex- and age-matched) value above the normal range and absence of GH suppression after an oral glucose load.[4] The cutoff of the GH nadir is <0.4 to 1 micrograms/L (depending on the assay used).[4] Oral glucose tolerance testing (OGTT) is not required if IGF-1 is very elevated and the patient has clear cut features of GH excess; OGTT is indicated in patients with mildly elevated IGF-1 concentrations.[4] The glucose tolerance test should be performed with 75 g oral glucose and measurements of plasma glucose and GH every 30 minutes for 2 hours.
Because GH values vary significantly during the day for normal people, an isolated elevated value does not, in itself, provide evidence for the presence of acromegaly. Malnutrition and systemic diseases with catabolic states, liver failure, hypothyroidism, and exogenous estrogen administration may all lead to falsely elevated, normal, or low IGF-1 levels.[12] In adolescence and pregnancy, IGF-1 levels are physiologically elevated, but most pregnant patients have no increase in tumor size and metabolic complications are uncommon.[14]
With glucose loading, false positive results (failure of GH suppression) can occur in patients with diabetes mellitus, hepatic or renal insufficiency, or anorexia nervosa, and in adolescents. A false negative response to glucose loading may be seen in some patients with acromegaly and only mild degree of GH hypersecretion.[15] However, in all these situations, the associated clinical presentation and the levels of GH and IGF-1 must all be taken into account. When clinical presentation and biochemical results are discordant, repeat testing and follow-up may be necessary.
Evaluation of other pituitary functions
The endocrine assessment of a patient with acromegaly should include baseline testing of corticotroph, lactotroph, thyrotroph, and gonadotroph function by measurements of plasma cortisol, prolactin, thyroid-stimulating hormone and free thyroxine, follicle-stimulating hormone, luteinising hormone, estradiol, or testosterone. Testing of the hypothalamic-pituitary-adrenal (HPA) axis may be needed.[16][17]
Pituitary imaging
Gadolinium-enhanced MRI is the next diagnostic procedure following biochemical confirmation of acromegaly. Rarely, a previously unsuspected pituitary lesion (pituitary incidentaloma) may be discovered during imaging performed for an unrelated reason.[18] Imaging allows for characterization of the pituitary adenoma: definition of its dimensions, determination of extension above the sella turcica, or protrusion into the lateral cavernous sinuses or sphenoid bone. If MRI is not available or if it cannot be performed (e.g., in a patient with a pacemaker), CT scan may be used.
Ectopic GH-releasing hormone/GH secretion
Patients with biochemically confirmed acromegaly and radiographic absence of pituitary adenoma or diffuse pituitary enlargement account for <1% of cases. In these patients, GH-releasing hormone (GHRH) plasma measurement is necessary to investigate the possibility of ectopic GHRH secretion leading to pituitary somatotroph hyperplasia and acromegaly. Chest and abdominal CT scans are used to locate ectopic tumors producing GHRH and/or GH. Total body scintigraphy with radiolabeled somatostatin analog (octreoscan) or Gallium-68 DOTATATE PET scan can be used to locate such tumors and to demonstrate somatostatin receptor expression by the tumor.[12][19]
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