Acromegaly

Background

Acromegaly is a chronic (slowly progressive) condition caused by excess growth hormone in adulthood.

Growth hormone is normally produced by the pituitary gland, a tiny gland located at the base of the brain. The pituitary gland produces a number of different hormones and is controlled by a region of the brain called the hypothalamus. The hypothalamus produces growth hormone-releasing hormone (GHRH) which in turn stimulates the pituitary gland to produce growth hormone. Growth hormone is essential for physical growth in children and adolescents, as it stimulates another hormone, insulin-like growth factor-I (IGF-I). IGF-1 causes the body tissues to gradually enlarge in normal childhood growth but also results in the changes seen in acromegaly.

In more than 98% of patients with acromegaly, the condition is caused by a pituitary adenoma (a non-cancerous tumour of the pituitary gland), which secretes excess growth hormone and/or IGF-1. Rarely acromegaly is caused by a growth hormone- or GHRH-producing tumour located in a distant organ, such as the lung or pancreas.

Acromegaly is a rare condition with around 3–4 new cases per million population per year. It is generally diagnosed in middle-aged people. However, the symptoms are initially quite subtle and may have been present for many years before the diagnosis is made.

Pachydermoperiostosis can mimic acromegaly but is not associated with growth hormone excess.

Clinical features

Excess growth hormone in adulthood does not increase height because the growth plates in adult bones have fused. Children and adolescents are able to grow upwards due to open cartilage growth plates at each end of long bones. After puberty, the growth plates fuse and no further lengthening of the bones is possible. Gigantism is a related condition, where patients are remarkably tall due to excess growth hormone while growth plates are open during childhood.

Initial symptoms of acromegaly can be caused by the physical effects of the tumour on surrounding tissues (eg, headaches, visual disturbances) or by the consequences of overgrowth of bones, cartilage, tissues, and organs.

Skin changes associated with acromegaly include:

• Enlarged swollen feet and hands
• The skin is thickened and may feel doughy
• Thick and hard nails
• Deepening of forehead creases and skin folds on the face
• Noticeably large pores, acne-like comedones (blackheads) and thick swollen eyelids
• Increased body hair (hypertrichosis), excessive sweating (hyperhidrosis), and oily skin (seborrhoea)
• Increased number of skin tags and darkening of the skin (hyperpigmentation)
• Multiple epidermal cysts
• Cutis verticis gyrata
• Acanthosis nigricans
• Hypertrichosis
• Acromegaly has been associated with other dermatologic syndromes including Carney syndrome and McCune-Albright syndrome.

 

 

Skin tags 

Other clinical features of acromegaly include:

• Fatigue and depression
• Joint and back pain, carpal tunnel syndrome, and muscle weakness
• The brow and lower jaw protrude, the nasal bone, lower lip, and the tongue enlarge, and the teeth space out
• The voice may become deeper or hollow sounding.

Complications include:

• A pituitary adenoma may also squash the surrounding normal pituitary tissue and alter production of other pituitary hormones. This can cause menstrual abnormalities and breast discharge in women, and loss of libido and impotence in men. Thyroid hormones and adrenal gland hormones may also be affected.
• Patients with acromegaly are at increased risk of developing diabetes mellitus and dying of cardiovascular disease, respiratory complications, and cancer:
  • Cardiovascular disease includes high blood pressure, enlargement of the heart, abnormal heart rhythms, and heart valve abnormalities.
  • Sleep apnoea, lung overgrowth, and chest wall changes contribute to respiratory dysfunction often resulting in emphysema and bronchiectasis.
  • Increased risk of colon polyps, which may develop into colon cancer if not removed.

Diagnosis

• Blood tests can detect raised levels of growth hormone and IGF-I.
• GHRH levels in the blood can also be measured if clinical features indicate disease outside the pituitary gland.
• A pituitary adenoma can usually be seen on CT scan or MRI.

Treatment

There are three general approaches to the treatment of acromegaly:

• Surgical removal of the pituitary adenoma
• Medication to reduce growth hormone production
• Radiation therapy of the pituitary.

Often a combination of treatment approaches are used, for example surgery can quickly relieve pressure on surrounding structures caused by large pituitary adenomas. However, over the long-term, only around 60% of patients achieve normal levels of growth hormone and IGF-I after surgery. Therefore medication or radiation may also be required for residual disease or relapse.

Long-term follow-up is required to check for relapse and potential cardiovascular, respiratory, and malignant complications.