Acromegaly

How acromegaly develops

The pituitary gland at the base of the brain releases growth hormone (GH). GH acts mainly through the liver, which makes insulin-like growth factor 1 (IGF-1). IGF-1 drives growth of bone, cartilage, soft tissue and organs.

In acromegaly, a tumor of GH-producing cells (a somatotroph adenoma) releases GH continuously. After puberty, the long bones can no longer lengthen because their growth plates have closed, so bones thicken and soft tissues enlarge instead. If GH excess begins before the growth plates close, in childhood, it causes gigantism, with excessive height.

Acromegaly affects roughly 3 to 14 people per 100,000. It is usually diagnosed between ages 40 and 50, in men and women equally.

Symptoms

Physical changes

• larger hands and feet: rings need resizing, shoe size increases
• coarse facial features: thicker lips, larger nose, prominent brow ridge
• protruding lower jaw (prognathism), gaps appearing between teeth, an altered bite
• enlarged tongue, deeper voice
• thick, oily skin, skin tags, excessive sweating and body odor

Comparing old photographs often reveals changes that family members did not notice.

Other symptoms

• joint pain and early arthritis, especially in the knees, hips and spine
• carpal tunnel syndrome from soft tissue swelling at the wrist
• headaches from the tumor
• loss of peripheral vision if the tumor presses on the optic chiasm
• fatigue and muscle weakness
• loud snoring and sleep apnea
• irregular periods, low libido, erectile dysfunction
• nipple discharge in some women

Complications

Untreated acromegaly shortens life expectancy, mainly through heart and metabolic disease:

• High blood pressure and cardiomyopathy (thickened heart muscle) leading to heart failure
• Type 2 diabetes and insulin resistance, because GH opposes insulin
• Sleep apnea
• Colon polyps, with higher colon cancer risk, so colonoscopy is recommended
• Thyroid nodules and goiter
• Arthritis and vertebral fractures
• Underactive pituitary from tumor pressure

Causes

• Pituitary adenoma: over 95% of cases. Most are macroadenomas (larger than 1 cm) at diagnosis.
• Genetic syndromes: rarely, as part of multiple endocrine neoplasia type 1, Carney complex, McCune-Albright syndrome or familial isolated pituitary adenoma.
• Ectopic GHRH or GH: very rarely, tumors elsewhere (such as pancreatic or lung neuroendocrine tumors) release hormones that stimulate the pituitary.

Diagnosis

1. IGF-1 blood test: the best screening test. A level above the age- and sex-adjusted normal range strongly suggests acromegaly.
2. Oral glucose tolerance test: GH is measured after drinking 75 g of glucose. In healthy people GH falls to very low levels; in acromegaly it does not suppress.
3. Pituitary MRI: shows the size and position of the tumor.
4. Visual field testing if the tumor is near the optic nerves.
5. Tests of other pituitary hormones (cortisol, thyroid, sex hormones, prolactin).
6. Screening for complications: blood pressure, blood sugar, echocardiogram, sleep study and colonoscopy.

Treatment

Surgery

Transsphenoidal surgery, done through the nose or upper lip by an experienced pituitary surgeon, is the first-line treatment for most people. It cures most small tumors and a lower proportion of large or invasive ones. GH levels fall within hours, and soft tissue swelling and sweating improve within days to weeks.

Medicines

Used when surgery does not achieve control, is not possible, or sometimes before surgery:

• Somatostatin receptor ligands (octreotide, lanreotide, pasireotide), given as monthly injections or, for octreotide, as capsules. They reduce GH release and can shrink tumors.
• Pegvisomant, a GH receptor blocker given by injection, which normalizes IGF-1 in most patients but does not shrink the tumor.
• Cabergoline, a dopamine agonist tablet that helps some people with mild disease.

Radiotherapy

Stereotactic radiosurgery or conventional radiotherapy is used for residual tumor that does not respond to other treatment. It works slowly, over years, and can cause underactive pituitary function later.

Monitoring

IGF-1 and GH levels are monitored long-term, along with pituitary hormones, MRI scans, blood pressure, diabetes, heart function and colonoscopy.

Outlook

When GH and IGF-1 levels are brought into the normal range, life expectancy approaches that of the general population. Soft tissue changes, sweating and headaches improve. Bone changes and joint damage do not fully reverse, which is why early diagnosis matters.

Frequently asked questions

What are the early signs of acromegaly?

Early signs include rings or shoes that no longer fit, increased sweating, oily skin, joint aches, headaches, tingling in the hands from carpal tunnel syndrome, snoring and gradual coarsening of facial features. Because changes are slow, comparing old photos is often revealing.

What causes acromegaly?

Over 95% of cases are caused by a benign pituitary tumor that makes too much growth hormone. Rarely, it is part of an inherited syndrome or caused by a tumor elsewhere in the body that stimulates the pituitary. It is not caused by lifestyle factors.

How is acromegaly diagnosed?

Doctors measure IGF-1 in the blood, which is raised in acromegaly. The diagnosis is confirmed if growth hormone fails to fall after drinking a glucose solution. An MRI of the pituitary gland then shows the tumor.

Can acromegaly be cured?

Often, yes. Pituitary surgery cures many people, especially when the tumor is small. When surgery does not fully control it, medicines and radiotherapy can bring hormone levels to normal. Long-term follow-up is still needed to check for recurrence and complications.

What is the difference between acromegaly and gigantism?

Both are caused by excess growth hormone. Gigantism occurs in children before their growth plates close, causing excessive height. Acromegaly occurs in adults, after growth plates have closed, so bones thicken and tissues enlarge rather than the person growing taller.