Acromegaly is the result of excessive growth hormone production in skeletally mature patients, most commonly from a pituitary adenoma. The same excess in growth hormone in individuals whose epiphyses have not fused will result in gigantism (excessively tall stature).
It is most commonly diagnosed in adults in middle age 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 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
- internal organs (especially heart and kidneys)
- vocal cords, resulting in a characteristic thick, deep voice and slowing of speech
- skull, prominent frontal brow
- mandible: prognathism with gaping teeth
- skin changes
Over 90% of cases are the result of a pituitary adenoma, usually macroadenomas. 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)
Calvarial thickening, enlarged sinuses and an enlarged sella turcica. Prognathic jaw.
Evidence of vertebral body fractures most commonly in the thoracic and lumbar region lead researchers to recently state that screening with radiographs of these regions is indicated 4. Vertebral fracture without loss of bone mineral density is related to increased bone turnover markers seen in acromegaly 4.
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 spade phalanx sign. Joint spaces may be minimally enlarged. Premature osteoarthritis can set in the advanced stages of acromegaly.
Heel pad thickness may be increased (>25 mm).
Enlarged pituitary with an uptake of gadolinium. The MR diagnosis of a pituitary macroadenoma is relatively straightforward. Dynamic contrast-enhanced MR increases the sensitivity to detect microadenomas. Microadenomas are hypoenhancing as compared to the normal pituitary gland.
Hypertrophy of spinal ligaments and cartilaginous structures and features of osteoarthritis 7.
Other joints may show ligament and cartilaginous hypertrophy, and crystal deposition 7.
Treatment and prognosis
The treatment of choice is resection of the secreting adenoma, usually via transsphenoidal approach. Alternatively, or especially in surgically refractory cases treatment with primary somatostatin receptor ligand with or without concomitant growth hormone receptor antagonist therapy 3. Treatment with radiation therapy is also used in medical circumstances where other therapies have not been able to control tumor size, growth and production of excess growth hormone. The most used radiation therapy in the case of acromegaly is gamma knife, with more traditional techniques including Image guided eadiation therapy. However, treatment with radiation therapies have been associated with increased risk of cerebrovascular mortality.
The severity of symptoms, and comorbidities for patients with acromegaly is directly related to the level of elevated hormone as well as length of time that 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 can reach normal population if appropriate diagnosis and subsequent treatment is achieved to normalize serum GH 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 which was found when studying four Irish families who all displayed acromegalic, and gigantism traits, known as childhood onset acromegaly when a child has gigantism which progresses through adulthood into acromegaly. It is said that there could be hundreds of carriers of this mutant gene leading researchers to suggest all childhood onset acromegaly patients who especially have familial 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
Metabolic bone disease
- bone mineralisation
- osteosclerosis (differential diagnosis | mnemonic)
- pituitary gland-related
- thyroid gland-related