Acromegaly: Symptoms, Complications, Causes, Diagnosis and Treatments

It is due to excessive growth hormone production (GH), usually by a pituitary growth hormone secretory adenoma.

It is usually due to a pituitary gland tumor, known as a pituitary adenoma.

Pituitary tumors: in more than 95% of cases, the excessive growth hormone is caused by a pituitary tumor, usually a benign microadenoma of the pituitary gland.

Non-pituitary tumor: tumors of the adrenal glands, lungs, and pancreas are involved in some cases. These tumors secrete growth hormone or growth hormone-releasing hormone.

Its prevalence is estimated at 40-130 cases per million inhabitants. If the disorder occurs in childhood, it leads to gigantism instead of acromegaly.

Elevated growth hormone levels stimulate the liver to produce insulin-like growth factor-1 (IGF-1, for its acronym in English). Elevated levels of insulin-like growth factors stimulate the excessive growth of body tissues.

Growth hormone, also known as somatotropin, is a peptide hormone that stimulates growth, cell reproduction, and cell regeneration in humans and other animals. Therefore, it is essential for human development.


It is a type of mitogen specific only for certain types of cells. Growth hormone is a stress hormone that increases glucose concentration and free fatty acids.

A recombinant form of a human growth hormone called somatropin is used as a prescription medication to treat growth disorders in children and growth hormone deficiency in adults.

In the United States, it is only available legally in pharmacies by a doctor’s prescription.

In recent years in the United States, some doctors have begun prescribing growth hormone in elderly patients with growth hormone deficiency (but not in healthy people) to increase vitality.

While it is legal, the efficacy and safety of this use for human growth hormone have not been proven in a clinical trial.

As an anabolic agent, human growth hormone has been used by competitors in sports since at least 1982. It has been banned by the International Olympic Committee and the National Collegiate Athletic Association.

The traditional analysis of urine does not detect doping with human growth hormone, so the ban could not be applied until the early 2000s when blood tests began to distinguish between natural human growth hormone and artificial.

Blood tests conducted by the World Anti-Doping Agency at the 2004 Olympic Games in Athens, Greece, focused mainly on human growth hormone.

In the United States, the only approved growth hormone for livestock is a cow-specific growth hormone called bovine somatotropin to increase milk production in dairy cows.

Retailers can label milk containers produced with or without bovine somatotropin.

Acromegaly affects muscle strength, bone health, and energy levels and can cause unusual physical characteristics and medical complications. It can be years until the changes appear.

Early death is possible, and life expectancy can be reduced by ten years. Three to four people in every million are diagnosed with acromegaly in the United States each year, affecting 60 people in every million simultaneously.

The initial symptom is typically the extension of the hands and feet. There may also be enlargement of the forehead, jaw, and nose. Other symptoms may include joint pain, thicker skin, increased voice, headaches, and vision problems.

Complications of the disease can include type 2 diabetes, sleep apnea, and high blood pressure. Acromegaly is usually caused by the pituitary gland producing too much growth hormone. The condition is not inherited from the parents of a person.

The diagnosis is by measuring growth hormone after a person has drunk glucose or by measuring growth factor I, similar to insulin in the blood. After diagnosis, medical pituitary images are made to look for an adenoma.

If excess growth hormone is produced during childhood, the result is gigantism. Treatment options include surgery to remove the tumor, medications, and radiation therapy. Surgery is usually the most effective treatment when the tumor is smaller.

In those in whom surgery is not practical, drugs of the somatostatin-like or growth hormone receptor type can be used. The effects of radiation therapy are more gradual than surgery or medication.

Without treatment, those affected live on average ten years less; however, the life expectancy is usually average with the treatment. Acromegaly affects approximately 6 per 100,000 people worldwide.

It is diagnosed more frequently in middle age. Men and women are affected with the same frequency.

The first medical description of the disorder occurred in 1772 by Nicolas Saucerotte. The term is from the Greek ἄκρον Akron, meaning “extreme,” and mega μ, queγαmeaning “big.”

Signs and symptoms of acromegaly

Acromegaly is characterized by slowly progressive bodily disfigurement (mainly with the face and extremities) and systemic manifestations.

When a pituitary tumor causes it, as is usually the case, the patient may experience tumor mass effects, such as headaches, visual impairment, and facial pain due to the participation of the fifth cranial nerve.

Characteristics that result from the high level of growth hormone or expanding tumor include:

  • Visibly soft tissue produces increased hands, feet, nose, lips, and ears and a general thickening of the skin.
  • Pronounced protrusion of the eyebrows, often with ocular distension (frontal protuberance).
  • Acrocordón (a benign tumor that forms on the skin).
  • Indications of the carpal tunnel.

The changes caused by acromegaly take time to develop. Changes in physical appearance can be dramatic. They include:

  • A prominent jaw and tongue.
  • Gaps between the teeth.
  • A more prominent front.
  • Swollen hands
  • Big feet.
  • Rough and oily skin.

Other changes include:

  • Tingling and lack of sensitivity in the hands and feet.
  • Intense sweating
  • Headaches.
  • Vision problems.

There may also be an enlargement of the internal organs, including the heart, liver, lungs, and kidneys. It can lead to a condition called gigantism.


The excess growth hormone interrupts carbohydrates’ metabolism, which causes insulin resistance, possibly diabetes, and high cholesterol. Complications can be life-threatening. They include:

Acromegaly leads to pituitary gigantism if it occurs in children before the epiphyseal fusion of the bones. High growth hormone levels can cause pain and arthritis in joints or narrow bone tunnels, such as carpal tunnel syndrome and spinal stenosis.

It feeds the abnormal growth of the head and face, such as prognathism (a protruding jaw), malocclusion of the teeth, and enlargement of the forehead, tongue, ears, fingers, and extremities.

In addition, with acromegaly, the hair may thicken, and the skin may thicken. The respiratory tract also thickens, resulting in sleep apnea and deepening the voice.

Heart disease often occurs because of direct heart detriment or hypertension, high cholesterol, and overwork. Heart disease is the most common cause of death among patients.

In addition to the effect of high growth hormone levels and insulin-like growth factor 1, acromegaly can cause other disorders of another pituitary axis, such as hyperprolactinemia, which can cause amenorrhea galactorrhea, impotence, and loss of libido, hyperthyroidism, and disease of Cushing.

These conditions can cause thyroid, adrenal, or gonadal insufficiency.

Acromegalic patients are more susceptible to neoplasms, possibly due to the increase in insulin-like growth factor-1 in the growth of cancer cells, and 46% have colonic polyps, which can lead to carcinoma.

Additional complications include cholelithiasis (gallstones), hypercalcemia, and hyperphosphatemia.


Adenoma pituitary

Approximately 98% of cases of acromegaly are due to the overproduction of growth hormone by a benign pituitary gland tumor called adenoma.

These tumors produce an excessive growth hormone and compress the surrounding brain tissues as they grow.

In some cases, they can compress the optic nerves. Tumor expansion can cause headaches and visual disturbances.

In addition, the compression of surrounding normal pituitary tissue can alter the production of other hormones, which causes changes in menstruation and discharge in women and impotence in men due to reduced testosterone production.

There is a marked variation in growth hormone production rates and tumor aggressiveness. Some adenomas grow slowly, and the symptoms of excess growth hormone are often not noticed for many years.

Other adenomas proliferate and invade the areas of the surrounding brain or the paranasal sinuses, which are located near the pituitary gland. In general, younger patients tend to have more aggressive tumors.

Most pituitary tumors arise spontaneously and are not genetically inherited. Many pituitary tumors arise from a genetic alteration in a single pituitary cell, leading to more significant cell division and tumor formation.

This genetic change, or mutation, is not present at birth but is acquired during life. The mutation occurs in a gene that regulates the transmission of chemical signals within pituitary cells; permanently activates the signal that tells the cell to divide and secrete growth hormones.

The events within the cell that cause the disordered growth of pituitary cells and the secretion of growth hormone are currently under intense investigation.

Pituitary adenomas and diffuse somatomamotropic hyperplasia may result from the somatic activating mutations GNAS gene, which may be acquired or associated with the McCune-Albright syndrome.

Other tumors

In some patients, acromegaly is not caused by pituitary tumors but by tumors of the pancreas, lungs, and adrenal glands. These tumors also lead to an excess of growth hormone.

Either because they produce the growth hormone themselves or, more often, the hormone-releasing hormone, the hormone that stimulates the pituitary gland to produce growth hormone.

In these patients, the hormone-releasing excess growth hormone can be measured in the blood and states that the cause of acromegaly is not due to a defect of the pituitary gland.

When these non-pituitary tumors are removed surgically, they decrease growth hormone levels and improve the symptoms of acromegaly.

In patients with non-pituitary tumors producing growth hormone-releasing hormone, the pituitary gland may still be enlarged and confused with a tumor.

Therefore, it is essential that doctors carefully analyze all “pituitary tumors” taken from patients with acromegaly to avoid the possibility that a tumor elsewhere in the body is causing the disorder.

Diagnosis of acromegaly

If acromegaly is suspected, medical images and laboratory investigations are usually used together to confirm or rule out the presence of this condition.

Insulin growth factor 1 (IGF-1) provides the most sensitive laboratory test for diagnosing acromegaly.

Moreover, a test of growth hormone suppression after an oral glucose load, a particular laboratory test, will confirm the diagnosis after a positive test result for insulin growth factor 1 (IGF-1, for its acronym in English).

A single value of growth hormone is not helpful given its pulsatility (levels in the blood vary greatly, even in healthy individuals).

The growth hormone levels taken 2 hours after a glucose tolerance test of 75 or 100 grams is helpful in the diagnosis.

Growth hormone levels are suppressed below 1μg / l in ordinary people, and levels higher than this limit are confirmatory of acromegaly.

Other pituitary hormones should be evaluated to treat the secretory effects of the tumor and the effect of tumor mass on the normal pituitary gland.

They include thyroid-stimulating hormone (HST), gonadotropic hormones (FSH, LH), adrenocorticotropic hormone, and prolactin.

A magnetic resonance imaging of the brain focused on the sella turcica after administering gadolinium allows a clear delineation of the pituitary and hypothalamus and the tumor’s location.

Several other syndromes of overgrowth can cause similar problems.


Pseudoacromegaly is a condition with the usual acromegalic characteristics but without increasing growth hormone and insulin-like growth factor 1 (IGF-1, for its acronym in English).

It is frequently associated with insulin resistance. Cases have been reported due to minoxidil at an unusually high dose.

It can also be caused by a selective defect of post-receptor insulin signaling, which leads to metabolic disruption, but the preservation of mitogenic signaling.


The treatment aims to correct (or prevent) the tumor compression of the surrounding tissues by excising the lesion causing the disease and reducing the levels of growth hormone and insulin growth factor 1 to average values.

The treatment will depend on the tumor’s location, the person’s age, and medical history.

Surgical treatment

The surgery can be carried out to eliminate the pituitary tumor. This would stop the overproduction of growth hormone and relieve pressure on the surrounding tissue.

Transsphenoidal endonasal surgery: a minimally invasive surgery involves the insertion of an endoscope through a small incision in the nasal cavity or upper lip to access the pituitary gland and extract the pituitary adenoma.

The endoscope will pass from the nasal cavity to the sphenoid bone, which is a bone that separates the brain from the rest of the facial structures; it will quickly relieve the symptoms of pressure, as well as the lower levels of high growth hormone.

The recovery time is shorter compared to traditional transsphenoidal surgery.

Transnasal transsphenoidal microscopic surgery: this is a traditional pituitary surgery that uses direct visualization of the tumor with a microscope.

Recent retrospective studies showed a gross total resection with a resolution of the endonasal approach of insulin-like growth factor 1 (IGF-1) comparable to microscopic transsphenoidal transnasal surgery.

Removing the tumor should lead to a drop in growth hormone levels. However, even if the tumor is successfully removed, hormone levels may not return to normal, and additional therapies may be necessary.

When surgery (the usual first-line treatment) does not correct the hypersecretion of growth hormone/insulin growth factor 1, medical treatment with dopamine agonists (particularly cabergoline), somatostatin analogs, and radiotherapy can be used.

Radiation therapy

Radiation therapy can be used alone or as part of a combined approach.

After surgery, radiation therapy can remove the remaining tumor cells. It can also be used together with medications to reduce growth hormone levels.

Conventional radiation therapy is given five days a week for up to 6 weeks, but it can take up to 10 years to return to normal growth hormone levels.

In stereotactic radiosurgery, precision radiotherapy directs intensely focused radiation beams to the tumor, minimizing damage to the surrounding tissue.

This involves fewer sessions than conventional radiation therapy and can reduce growth hormone levels in a shorter time.

It is often administered as an adjunct to surgery to prevent relapse or when surgery can not achieve an acceptable reduction in growth hormone levels. It is associated with the risk of irradiating adjacent brain tissues.

Medication to control growth

As an adjunct to surgery or when surgery is not desirable, acromegaly can be treated with medications only if surgery is considered too risky or impossible due to the tumor’s location.

These aim to stop the rapid growth triggered by preventing the secretion or action of growth hormones. A combination of treatments is probably the best option.

Somatostatin analogs (octreotide, Lanreotide): these act on the somatostatin receptor to cause the inhibition of growth hormone secretion.

It is usually given as intramuscular injections once a month. It can also be used to reduce large pituitary adenomas before surgery.

Dopamine receptor agonists (cabergoline, bromocriptine): these act on D2 receptors and are not as effective as somatostatin analogues. They are often used as attachments.

Growth hormone receptor antagonist (Pegvisomant): this novel drug blocks the growth hormone in the receptors, decreasing the levels of insulin growth factor 1 (IGF-1), while the growth hormone levels are not affected.

It is helpful in patients who are resistant to somatostatin analogs. Thanks to this therapeutic strategy of multiple steps, adequate hormonal control is achieved in most patients, which gives them an average life expectancy.

Comorbidities associated with acromegaly usually improve after treatment, but persistent sequelae can affect the quality of life.