Acromegaly is a condition in which benign pituitary adenomas lead to an excess secretion of growth hormone (GH) and insulin-like growth factor 1 (IGF-1). In adults, whose epiphyseal plates are closed, the disease causes enlarged hands and feet, coarsened facial features, and pathological growth of internal organs. If the condition occurs in children, before epiphyseal plate closure, it is known as gigantism, which is discussed in a separate article. The first step in diagnosing acromegaly is to measure IGF-1 levels. Further testing includes an oral glucose tolerance test (OGTT) with assessment of GH levels, and evaluation of pituitary tumors via cranial MRI. Management consists of transsphenoidal adenomectomy for operable tumors, or GH-inhibiting medication and radiotherapy if surgery is contraindicated or unsuccessful. Adequate treatment is vital to reduce the risk of complications, such as cardiovascular disease and cerebral aneurysms, as these may considerably increase mortality.
- Prevalence: 1–9/100,000 in the US 
- Age of onset: 3rd decade of life (mean age at diagnosis usually 40–45 years) 
- Sex: ♀ = ♂ 
Epidemiological data refers to the US, unless otherwise specified.
- Benign growth hormone-secreting pituitary adenoma (> 95% of cases) 
- Very rare: neuroendocrine or hypothalamic tumors, paraneoplastic syndromes
- Ectopic secretion of growth hormone by neuroendocrine tumors (e.g., small cell lung carcinoma, pancreatic islet-cell tumor (as found in MEN1)
- ↑ Secretion of growth hormone-releasing hormone (GHRH) from a hypothalamic tumor or in paraneoplastic syndromes (e.g., small cell lung carcinoma, medullary thyroid cancer) 
Physiology of GH and IGF-1
- GH secretion induced by stress, sport, and hypoglycemia; inhibited especially by hyperglycemia or food intake
Hypothalamus secretes →↑ secretion of GH → GH induces IGF-1 synthesis → ↑ serum IGF-1 via liver synthesis which leads to the following effects:
- Binding to IGF-1 and insulin receptors → stimulation of cell growth and proliferation, inhibiting programmed cell death
- ↑ Secretion of from the hypothalamus → ↓ serum GH and IGF-1 (negative feedback)
Effects of a pituitary adenoma
- Overproduction of GH → abnormally high serum IGF-1 levels → overstimulation of cell growth and proliferation → symptoms of acromegaly
- Tumor mass compresses neighboring structures (e.g., optic chiasm) → symptoms of mass effect
- Impaired secretion of other pituitary hormones; , especially gonadotropins → ↓ LH and FSH → ↓ estrogen and testosterone
Excess GH secretion before the conclusion of longitudinal growth (i.e., prior to epiphyseal plate closure) leads to pituitary gigantism with a possible height of ≥ 2 m. After epiphyseal plate closure, GH excess causes acromegaly, but no change in height!
- Tumor mass effects
- Soft tissue effects
- Skeletal effects
Consider acromegaly in patients who report having had to increase hat, shoe, glove, and ring sizes in the past!
Hormone analysis 
- Serum IGF-1 concentration: the best single test
- OGTT with baseline GH and measure GH after 2 hours: the most specific test
- Pituitary MRI 
- Gigantism: excess GH secretion in children, before epiphyseal plate closure
- Marfan syndrome
- Pseudoacromegaly (e.g., medication-induced): insulin resistance, acromegaloid features, normal GH and IGF-1
- Prolactinoma: pituitary tumor; excess of prolactin, not GH
- Familial tall stature
- Sotos syndrome
- McCune-Albright syndrome
The differential diagnoses listed here are not exhaustive.
Transsphenoidal adenomectomy is the method of choice for treating acromegaly. In patients with inoperable tumors or unsuccessful surgery, medication and radiotherapy are indicated to reduce tumor size and limit the effects of GH and IGF-1. 
- Radiotherapy 
- Follow-up 
Complications lead to increased mortality. 
- Cardiovascular complications: the main cause of death
- Impaired glucose tolerance and diabetes mellitus (up to 50% of cases)
- Colorectal polyps and cancer 
- Thyroid enlargement and cancer
- Cerebral aneurysm
- Psychological impairment (↓ quality of life, anxiety, ↓ self-esteem)
We list the most important complications. The selection is not exhaustive.