Acromegaly is the result of excessive growth hormone production in skeletally mature patients, most commonly from a pituitary adenoma. The same excess of growth hormone in individuals whose epiphyses have not fused will result in gigantism (excessively tall stature).
It is most commonly diagnosed in middle-aged adults and can result in severe disfigurement, serious complicating conditions, and premature death. It has both an insidious onset and slow progression and may be difficult to diagnose in the early stages, only being diagnosed when the external features, especially those of the face, become noticeable.
Clinical presentation is often with a variety of relatively non-specific symptoms or medical problems. These include:
- headache, described more often as "head pain" (due to dural tension)
- muscle pain, often misdiagnosed as fibromyalgia
- joint pain
- vertebral fractures with or without loss of bone mineral density
- carpal tunnel syndrome
- insulin resistance leading to diabetes mellitus
- renal failure
- palmar sweating and seborrhea
In contrast, examination of the patient will often reveal a very characteristic constellation of physical signs:
- enlargement of the hands, feet, nose, tongue, lips and ears
- general thickening of the skin (including cutis verticis gyrata)
- internal organs (especially heart and kidneys)
- vocal cords, resulting in a characteristic thick, deep voice and slowing of speech
- skull, frontal bossing
- mandible: prognathism with gaping teeth
- skin changes
Over 90% of cases are the result of a pituitary adenoma, usually a macroadenoma. The remaining 10% of cases are the result of other tumours of the pancreas, lungs, or adrenal glands that release growth hormone. A very small number of cases result from the excessive use of exogenous growth hormone in athletes.
Typically shows elevated levels of:
- growth hormone
- IGF-1 (insulin growth factor 1)
Evidence of vertebral body fractures, most commonly in the thoracolumbar region lead researchers to recently state that radiographic screening of this region is indicated 4. Vertebral fracture without loss of bone mineral density is related to increased bone turnover markers seen in acromegaly 4. Other features seen in the spine include a DISH-like appearance, posterior vertebral scalloping, increased verterbral height, elongation and widening of the vertebral bodies.
Joints will show the typical patterns of osteoarthritis, and will continue to deteriorate even after biochemical remission is achieved, which is why it is prudent in the clinical setting to monitor the progression of "acromegalic arthropathy" 6,7. There has also been a reported higher incidence of crystal deposition disease.
Terminal phalangeal tufts become hypertrophied and have a "spade appearance", which is called the spade phalanx sign. Joint spaces may be minimally enlarged. Premature osteoarthritis can occur in the advanced stages of acromegaly.
Heel pad thickness may be increased (>25 mm).
Three steps of acromegalic cardiomyopathy have been described 9:
- early phase (reversible): initial cardiac hypertrophy, increased heart rate and systolic output, defined as the hyperkinetic syndrome
- middle phase of untreated or uncontrolled disease: cardiac hypertrophy with signs of diastolic dysfunction
- end-stage of untreated disease (not reversible): dilated cardiomyopathy
Other joints may show ligamentous and cartilaginous hypertrophy, and crystal deposition 7.
Enlarged pituitary with increased gadolinium uptake. The MR diagnosis of a pituitary macroadenoma is relatively straightforward. Dynamic contrast-enhanced MR increases the sensitivity for detecting microadenomas. Microadenomas are hypoenhancing compared to the normal pituitary gland.
Hypertrophy of spinal ligaments and cartilaginous structures and features of osteoarthritis 7.
Treatment and prognosis
The treatment of choice is resection of the secreting adenoma, usually via the transsphenoidal approach. Alternatively, especially in surgically-refractory cases, treatment is with primary somatostatin receptor ligand, with or without concomitant growth hormone receptor antagonist therapy 3. Radiation therapy is also used in medical circumstances where other therapies have not been able to control tumour size, growth and production of excess growth hormone. The most frequently used radiation therapy for acromegaly is gamma knife, with more traditional techniques, including image-guided radiation therapy, associated with increased risk of cerebrovascular mortality.
The severity of symptoms and comorbidities for acromegaly patients is directly related to the level of elevated hormone as well as length of time that the patient was exposed to a high level versus a high-normal, or normal level, making identification and proper diagnosis of great importance 4,6,7. Mortality rates can decrease to those of the general population if appropriate diagnosis and treatment are achieved to normalize serum growth hormone and IGF-1 levels 5.
History and etymology
The word "acromegaly" is derived from the Greek words akros "extremities" and megalos "large".
In 2011 the AIP gene mutation was linked to acromegalic gigantism, found when studying four Irish families who displayed acromegalic and gigantism traits, known as childhood-onset acromegaly (i.e. when a child has gigantism which progresses through adulthood to acromegaly). It is said that there could be hundreds of carriers of this mutant gene, leading researchers to suggest that all childhood-onset acromegaly patients, especially those who have a family history of pituitary adenoma or acromegaly, should be screened and followed 8.
- 1. Fundamentals of diagnostic radiology. editors, William E. Brant, Clyde A. Helms. Philadelphia : Lippincott, Williams & Wilkins, c2007. ISBN:0781765188 (find it at amazon.com)
- 2. Davidson's principles & practice of medicine. Edinburgh; Elsevier/Churchill Livingstone, 2006. ISBN:0443100578 (find it at amazon.com)
- 3. Mangupli R, Rostomyan L, Castermans E et-al. Combined treatment with octreotide LAR and pegvisomant in patients with pituitary gigantism: clinical evaluation and genetic screening. Pituitary. 2016;19 (5): 507-14. doi:10.1007/s11102-016-0732-3 - Pubmed citation
- 4. Anthony JR, Ioachimescu AG. Acromegaly & Bone Disease. Curr Opin Endocrinol Diabetes Obes. 2014 Dec; 21 (6):476-82 doi: 10.1097 Pubmed citation
- 5. Ayuk J, Sheppard MC. Does acromehaly enhance mortality? Rev Endrocr Metab Disord 2008 Mar; 9(1): 33-9. DOI:10.1007/s11154-007-9067-8 Pubmed citation
- 6. Mazzoitti G et.al. Acromegalic osteopathy. Pituitary 2016 Oct 5. DOI:10.1007/s11102-016-0758-6 Pubmed citation
- 7. Colao et. al. The acromegalic arthropathy. J Endrocrinol Invest. 2005; 28 (8 Suppl): 24-31 Pubmed citation
- 8. Chahal HS et. al. AIP mutation in pituitary adenomas in the 18th century and today. N. Engl J Med. 2011 Jan 6; 364 (1): 43-50. DOI:10.1056/NEJMoa1008020 Pubmed citation
- 9. Rosario Pivonello, Renata S. Auriemma, Ludovica F. S. Grasso, Claudia Pivonello, Chiara Simeoli, Roberta Patalano, Mariano Galdiero, Annamaria Colao. Complications of acromegaly: cardiovascular, respiratory and metabolic comorbidities. (2017) Pituitary. 20 (1): 46. doi:10.1007/s11102-017-0797-7 - Pubmed
Metabolic bone disease
- bone mineralisation
- osteosclerosis (differential diagnosis / mnemonic)
- pituitary gland-related
- thyroid gland-related