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Acromegaly

Beyond the obvious effects, acromegaly can affect vital bodily systems.

In addition to visible symptoms, acromegaly is responsible for other systemic issues

Symptoms among people with acromegaly can vary and the following physical characteristics may manifest:1,2

  • Prominent forehead
  • Bridge of the nose gets bigger
  • Lips, nose, and tongue become larger
  • Lower jaw juts out
  • Space between teeth increases
  • Hands and feet become larger and swollen
  • Voice becomes deeper
  • Bone changes
  • Skin becomes thick, coarse, and oily
  • Sweating and skin odor increase
  • Skin tags may get larger or darker

Complaints may include:1

  • Joint pain due to hypertrophic arthropathy
  • Wrist pain and numbness from carpal tunnel syndrome
  • Snoring and sleep disorders related to sleep apnea
  • Headaches and visual disturbances (bitemporal hemianopia) 
as a direct result of the pituitary adenoma
  • Erectile dysfunction or low sex drive
  • Abnormal menses in women
  • Sweaty palms and soles (hyperhidrosis)
  • Deepening of the voice

Psychological symptoms can include:3

  • Depression
  • Anxiety
  • Impaired self-esteem

In addition to the physical and psychological characteristics being impacted, people with acromegaly may experience headaches, joint aches, and visual disturbances.1 Some also have an increased risk for colon polyps, which may progress to colon cancer if not addressed.2 Moreover is the concern with systemic conditions associated with acromegaly:1,2

  • Cardiovascular (hypertension and coronary heart disease)
  • Rheumatologic (joint pain, arthritis, and carpal tunnel syndrome)
  • Neurologic (headaches and visual disturbances)
  • Pulmonary (sleep apnea)
  • Neoplastic (added growth of tumors in those with a genetic disposition, benign tumors)
  • Metabolic (type 2 diabetes)
  • Endocrine (endocrinopathies)

The Classical Clinical Signs & Symptoms of Acromegaly

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To minimize associated morbidity and mortality related to the disorder,4,5 it is critical for clinicians to screen, diagnose, and initiate therapy as early as possible.1,6,7 Several clinical studies have reported an increased risk of mortality in people with uncontrolled acromegaly compared to that of the general population: Reports show that there is a three-fold higher incidence of mortality in people with the disorder.8 The deleterious effects associated with acromegaly can be improved by achieving biochemical control, through various modalities including a combination of surgical therapy, medical therapy, and radiotherapy.4,6,8-10

Unfortunately, acromegaly is often diagnosed late, contributing to the high morbidity and mortality rates given the associated cardiovascular, cerebrovascular, and respiratory disorders and malignancies.7,10 Guideline consensus promotes strategies aimed at reducing diagnostic delays in an effort to reduce morbidities and improve quality of life.7

Diagnosis

After obtaining a detailed patient history and physical examination, laboratory tests are typically requested in suspected cases of acromegaly. Biochemical investigations and radiology are the primary methods to ascertain diagnosis.6 IGF-1 and GH are often used as biomarkers for diagnosis of acromegaly; however, 2023 consensus guidelines specify IGF-1 as the primary biomarker for monitoring disease activity and treatment efficacy. This is because GH levels are more directly reflective of the disease state and are crucial for determining the success of therapeutic interventions.7

Diagnostic algorithm for acromegaly7,11

For all biochemical assessments, clinicians should:
  • know which assay is being used
  • which factors influence assay performance
  • how normal ranges are obtained
  • how assay has been calibrated and validated
diagnostic-algorithm

Note: Random GH measured after overnight fasting may be useful for informing prognosis, but not necessary for diagnosis.

IGF=insulin-like growth factor; ULN=upper limit of normal; GH=growth hormone; OGTT=oral glucose tolerance test.

Modified from: Cordero RA, Barkan AL. Diagnosis of acromegaly. Endocr Metab Disord. 2008;9:13–9, and Giustina et al.7,11

14th Acromegaly Consensus Conference Key Findings:7

Biochemical Diagnosis

  • In a patient with typical acromegaly features, a serum level of IGF-1 greater than 1.3 times the upper limit of normal for age confirms the diagnosis.
  • GH measured after overnight fasting may inform prognosis, but is not required for diagnosis.
  • For patients with equivocal results, repeated IGF-1 measurements using the same validated assay can be helpful, and oral glucose tolerance testing might also provide additional information.

Therapeutic Efficacy Target

  • IGF-1 normalized for age

Endocrine Society Clinical Practice Guideline: Diagnosis3

  • Measurement of IGF-1 levels in patients with typical clinical manifestations of acromegaly.
  • Measurement of IGF-1 levels in patients without typical clinical manifestations of acromegaly, but who have several associated conditions.
  • Measurement of IGF-1 in patients with a pituitary mass.
  • Recommend against relying on the use of random GH levels to diagnose.
  • In patients with elevated or unclear IGF-1 levels, the recommendation is to confirm the diagnosis by measuring the lack of suppression of GH to < 1 ɥg/L following documented hyperglycemia during an oral glucose load (OGTT).
  • Recommendation to perform imaging study post-biochemical diagnosis to assess tumor size and presence.
Diagnosis Treatment
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REFERENCES: 1. Adigun OO, Nguyen M, Fox TJ, et al. Acromegaly. [Updated 2023 Feb 2]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan. Available from: https://www.ncbi.nlm.nih.gov/books/NBK431086/. 2. Acromegaly. National Institute of Diabetes and Digestive and Kidney Diseases. Last updated January 2020. Accessed February10, 2024. https://www.niddk.nih.gov/health-information/endocrine-diseases/acromegaly. 3. Katznelson L, Laws ER Jr, Melmed S, et al. Acromegaly: an endocrine society clinical practice guideline. J Clin Endocrinol Metab. 2014 Nov;99(11):3933-51. doi: 10.1210/jc.2014-2700. 4. Dekkers OM, Biermasz NR, Pereira AM, et al. Mortality in acromegaly: a meta-analysis. J Clin Endocrinol Metab. 2008;93: 61–67. doi: 10.1210/jc.2007-1191. 5. Berg C, Petersenn S, Lahner H, et al. Investigative Group of the Heinz Nixdorf Recall Study and the German Pegvisomant Observational Study Board and Investigators. Cardiovascular risk factors in patients with uncontrolled and long-term acromegaly: comparison with matched data from the general population and the effect of disease control. J Clin Endocrinol Metab. 2010 Aug;95(8):3648-56. doi: 10.1210/jc.2009-2570. 6. Ogedegbe OJ, Cheema AY, Khan MA, et al. A Comprehensive Review of Four Clinical Practice Guidelines of Acromegaly. Cureus. 2022;Sep 3;14(9):e28722. doi: 10.7759/cureus.28722. Holdaway IM, Bolland MJ, Gamble GD. A meta-analysis of the effect of lowering serum levels of GH and IGF-I on mortality in acromegaly. Eur J Endocrinol. 2008;159: 89–95. doi: 10.1530/EJE-08-0267. 7. Giustina A, Biermasz N, Casanueva FF, et al. Acromegaly Consensus Group. Consensus on criteria for acromegaly diagnosis and remission. Pituitary. 2024 Feb;27(1):7-22. doi: 10.1007/s11102-023-01360-1. 8. Alhawyan FS. Mortality in Acromegalic Patients: Etiology, Trends, and Risk Factors. Cureus. 2021 Apr 2;13(4):e14265. doi: 10.7759/cureus.14265. 9. Biermasz NR, Dekker FW, Pereira AM, et al. Determinants of survival in treated acromegaly in a single center: predictive value of serial insulin-like growth factor I measurements. J Clin Endocrinol Metab. 2004;89: 2789–2796. doi: 10.1210/jc.2003-032041. 10. Bogazzi F, Colao A, Rossi G, et al. Comparison of the effects of primary somatostatin analogue therapy and pituitary adenomectomy on survival in patients with acromegaly: a retrospective cohort study. Eur J Endocrinol. 2013;169: 367–376. doi: 10.1530/EJE-13-0166. 11. Cordido F, García Arnés JA, Marazuela Aspiroz M, Torres Vela E; grupo de Neuroendocrinología de la Sociedad Española de Endocrinología y Nutrición. Guía práctica de diagnóstico y tratamiento de la acromegalia [Practical guidelines for diagnosis and treatment of acromegaly. Grupo de Neuroendocrinología de la Sociedad Española de Endocrinología y Nutrición]. Endocrinol Nutr. 2013 Oct;60(8):457.e1-457.e15. Spanish. doi: 10.1016/j.endonu.2013.01.012.