Acromegaly is a disease that is produced by a persistent, inappropriate, excessive secretion of growth hormone. The incidence is 3 to 4 per 1000,000 per year. The male to female ratio is equal. Acromegaly can occur at any age post-puberty but tends to present in the fourth and fifth decades. If the disease develops before puberty it is referred to as gigantism.

In over 99% of cases acromegaly is caused by a pituitary adenoma. The remainder of cases are the result of excess secretion of GHrH by either the hypothalamus or an ectopic source, or even more rarely the ectopic secretion of growth hormone itself.

Growth Hormone

Growth Hormone is a peptide hormone which is secreted by the anterior pituitary gland in response to the release of growth hormone releasing hormone by the hypothalamus. The secretion of growth hormone can be inhibited by somatostatin.

Growth hormone is composed of a single polypeptide chain that contains 191 amino acids. Two disulphide bridges are present.

Some of the functions of growth hormone are induced not by the hormone directly but by the ability of growth hormone to stimulate the production of insulin-like growth factor 1. Much of the production of IGF-1 is undertaken by the liver, but other target organs of growth hormone can also make IGF-1.

The basic essence of growth hormone is to function as an anabolic hormone. This role is most obvious during childhood, from which growth hormone derives its name. Growth hormone stimulates chondrocytes to enlarge and proliferate. The chondrocytes also synthesise greater quantities of the extracellular cartilage matrix. This results in elongation of bones at their epiphyseal growth plates. Growth hormone also promotes the mineralisation of the new cartilage at the growth plates, thus converting it into bone. This mineralisation is assisted by increased absorption of calcium by the intestine.

Growth hormone also stimulates protein synthesis in many other organs and tissues, a function that is concordant with its role of inducing growth. The affected organs and tissues include skeletal muscle, the heart, the skin, connective tissue, the bowel, pancreas, kidney and the parathryoid glands.

Although growth hormone stimulates the growth of the Islets of Langerhans in the pancreas and helps to support them, it also possesses anti-insulin actions, in part by inducing resistance to insulin. Growth hormone stimulates gluconeogenesis by the liver while reducing the uptake of glucose by the liver. The uptake of glucose by skeletal muscle and adipose tissue is also decreased. However, lipolysis is increased, liberating the fatty acids for use by the liver and skeletal muscle that are being instructed not to utilise glucose. Unlike insulin, which stimulates the synthesis of adipose tissue, the anabolic effect of growth hormone is to increase the lean body mass, especially skeletal muscle.

A larger body requires a larger volume of blood and growth hormone does not overlook this requirement: the retention of sodium and water by the kidney is stimulated by growth hormone.

As is the case with the glucocorticoids, the normal level of growth hormone varies during the day and can be highest around one hour after sleep. In addition to its internal regulation by the hypothalamus, the production of growth hormone can be stimulated by fasting, hypoglycaemia, exercise and deep sleep. The release of growth hormone is inhibited by hyperglycaemia and glucocorticoids.

Clinical Features

The changes of acromegaly tend to develop in a slow, insidious fashion that is often not noticed by the patient for many years after the disease has actually begun. Many of the features of acromegaly are due to the anabolic actions of growth hormone and its ability to induce protein synthesis in various target organs. The closure of the epiphyseal growth plates by the time adulthood is reached means that only periosteal bone formation can be stimulated in adults and bones in effect grow sideways (lateral growth) rather than elongating (vertical growth). With bone length and height remanining the same, the elevated protein synthesis in the soft tissues has nowhere to go in terms of increased length and thus bulks out the tissues in a disproportionate fashion to the person's stature.

Acromegaly produces a characteristic facial appearance that may be described as 'heavy' or 'coarse'. The jaw becomes prominent and protruding, yielding a lantern jaw. The increase in the size of the jaw can result in malocclusion of the teeth or arthritis of the temporomandibular joint.

The lips become thick and the nasolabial folds are exaggerated; the nose is often bulbous. The forehead is pronounced due to frontal bossing. The zygomatic arch enlarges, giving prominent cheek bones. The tongue increases in size.

The hands and feet become larger and are sometimes described as being 'spade-like'; performing delicate movements can be difficult. Carpal tunnel syndrome can develop.

The skin is thickened and oily. Excessive sweating can occur. Hirsutism may be found in women.

In addition to the patient's appearance changing there is also often an alteration in their voice due to enlargement of the larynx and the paranasal sinuses, which results in a deeper voice.

Rondo Hatton Rondo Hatton

The actor Rondo Hatton suffered from acromegaly. His career spanned the 1930s and the early 1940s. One of his roles was as 'The Creeper' in the film 'The Pearl of Death', which starred Basil Rathbone in his most famous role, that of Sherlock Holmes.

Hypertension is encountered in one third of patients. The mass of the left ventricle increases and the wall becomes thicker. A cardiomyopathy can develop. The cardiovascular abnormalities of acromegaly are the most common cause of death from the disease.

The upper airways become narrowed and obstructive sleep apnoea may develop. The narrowing can be exacerbated by an upper respiratory tract infection.

Central nervous system features can result from the mass effect of the pituitary adenoma. Narrowing of the vertebral foramina can produce compression of the spinal nerve roots. A proximal myopathy may be found.

Joint pain is encountered in around three-quarters of patients and actual arthritis is present in 15-60%, including secondary osteoarthritis. The large joints of the limbs are the most commonly affected joints. Backache can occur because the hypertrophy of the spinal ligaments that happens in the disease makes the ligaments lax.

Hyperprolactinaemia occurs in 40% of patients.

Resistance to insulin and glucose intolerance affect up to 45% of patients while secondary diabetes mellitus occurs in 10 to 20%.

Hypertriglyceridaemia occurs in 20-45%.

Levels of activated vitamin D are increased. Hypercalcuria may develop and increases the risk of renal stones forming. Phosphate absorption is increased and in 50% of patients is sufficient to cause hyperphosphataemia.

Excess secretion of growth hormone during childhood is extremely rare, but if it occurs pituitary gigantism results. The epiphyseal plates of children have not closed and are able to manifest their intended response to growth hormone, that of elongating the bone. In gigantism the excessive levels of growth hormone overdrive this growth. The anabolic effects on the soft tissues allow them to keep pace with the growth of the bones and the result is somebody who is very tall but who does not have the characteristic appearance of acromegaly. However, if the excessive secretion of growth hormone persists once the patient's growth plates have closed then acromegaly can supervene.


The natural variation in the levels of growth hormone throughout the day makes a single measurement of growth hormone unreliable as a means of excluding or confirming the diagnosis of acromegaly. Instead, levels of IGF-1 can be measured. In addition, growth hormone can be subjected to a form of suppression test. The normal response to a glucose load is for the levels of growth hormone to fall. Patients are given 75 to 100g of glucose to consume (usually in the form of a drink). A failure of growth hormone levels to drop below 2 micrograms per litre is a positive test. The oral glucose tolerance test is more commonly employed in the investigation of diabetes mellitus.

Imaging of the pituitary gland should be undertaken. A plain lateral skull X-ray can reveal an enlarged pituitary fossa but CT and MRI are necessary to delineate the pituitary gland properly.

The association of acromegaly with hyperprolactinaemia makes measurement of prolactin levels prudent. It may also be necessary to check other aspects of the function of the pituitary gland and its target endocrine organs.

The usual suspects blood tests (full blood count, urea and electrolytes) are often performed and are supplemented by calcium and liver function tests.


The mainstay of treatment is transphenoidal excision of the pituitary adenoma. The recurrence rate varies from 0 to 13% of patients.

Pharmacological therapy is available in the form of octreotide, which is an artificial somatostatin agonist. Somatostatin is given by subcutaneous injection. Bromocriptine can also suppress the secretion of growth hormone and can be given orally.

Growth Hormone Deficiency

A deficiency of growth hormone may be due to generalised hypopituitarism or a specific lack of growth hormone (or IGF-1).

Growth hormone deficiency that is present at birth may cause hypoglycaemia and jaundice; male babies show micropenis (an unusually small penis). An onset of growth hormone deficiency in childhood will result in a short stature; in extreme cases this can produce an adult height of less than 130cm.

Isolated growth hormone deficiency in adults in extremely rare but is believed to cause imparied concentration and memory, increased body fat and a reduction in muscle mass. Adult onset growth hormone deficiency is more often part of hypopituitarism and its features are therefore likely to be masked by the other hormone deficiencies.