SPOTTERS MEDICINE

ACROMEGALY

Causes, Symptoms, Diagnosis, Treatment, and Prognosis

What Is Acromegaly?

 Acromegaly is a rare, chronic hormonal disorder caused by excessive secretion of growth hormone (GH) in adults after the growth plates (epiphyses) have closed. The excess GH stimulates increased production of insulin-like growth factor-1 (IGF-1), leading to progressive enlargement of the hands, feet, facial bones, and internal organs. The disease develops slowly over many years, and diagnosis is often delayed because the physical changes occur gradually.

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Causes of Acromegaly

The majority of cases are caused by a growth hormone-secreting pituitary adenoma.

Common Causes

·        Pituitary adenoma (GH-secreting) – accounts for more than 95% of cases.

·        Ectopic GH or GHRH secretion (rare)

o   Pancreatic neuroendocrine tumors

o   Lung tumors

·        Genetic syndromes (rare)

o   Multiple Endocrine Neoplasia Type 1 (MEN-1)

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Pathophysiology

Acromegaly develops because of prolonged exposure to excessive growth hormone.

Disease Process:

1.  Excess secretion of GH by the pituitary gland.

2.  GH stimulates the liver to produce increased IGF-1.

3.  IGF-1 promotes:

o   Bone thickening

o   Soft tissue overgrowth

o   Organ enlargement (visceromegaly)

o   Metabolic disturbances including insulin resistance.

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Clinical Features of Acromegaly

The symptoms usually progress slowly over several years.

Skeletal Changes

·        Enlargement of hands and feet

·        Increase in ring size and shoe size

·        Frontal bossing

·        Prominent lower jaw (prognathism)

·        Widened nasal bridge

·        Increased spacing between teeth

·        Enlarged tongue (macroglossia)

Soft Tissue Changes

·        Thickened skin

·        Coarse facial appearance

·        Deep, husky voice due to laryngeal enlargement

·        Excessive sweating

·        Carpal tunnel syndrome

·        Obstructive sleep apnea

Systemic Manifestations

·        Hypertension

·        Diabetes mellitus due to insulin resistance

·        Joint pain and osteoarthritis

·        Chronic back pain

·        Headache

·        Fatigue

·        Enlargement of internal organs

Neurological Features

Large pituitary tumors may compress adjacent structures causing:

·        Persistent headache

·        Visual disturbances

·        Bitemporal hemianopia due to optic chiasm compression

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Diagnosis of Acromegaly

Early diagnosis improves treatment outcomes and reduces complications.

Laboratory Investigations

Serum IGF-1

·        Best screening test

·        Elevated in almost all patients

·        Reflects average GH secretion

Random Growth Hormone

·        Limited diagnostic value

·        GH secretion is pulsatile and varies throughout the day

Oral Glucose Tolerance Test (OGTT)

The confirmatory test for acromegaly.

Positive Test:

·        Growth hormone fails to suppress after oral glucose administration.

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Imaging Studies

·        MRI of the pituitary gland to identify adenoma

·        Visual field examination to detect optic chiasm compression

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Differential Diagnosis

Conditions that may resemble acromegaly include:

·        Gigantism (before epiphyseal closure)

·        Paget's disease of bone

·        Hypothyroidism with coarse facial features

·        Familial coarse facial appearance

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Treatment of Acromegaly

Treatment aims to normalize GH and IGF-1 levels, relieve symptoms, preserve pituitary function, and prevent complications.

Medical Therapy

Somatostatin Analogues

·        Octreotide

·        Lanreotide

These drugs suppress growth hormone secretion and may reduce tumor size.

Growth Hormone Receptor Antagonist

·        Pegvisomant

Blocks the action of GH and lowers IGF-1 levels.

Dopamine Agonists

·        Cabergoline

May be useful in selected patients but is generally less effective than somatostatin analogues.

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Surgical Treatment

Transsphenoidal pituitary surgery is the first-line treatment for most resectable pituitary adenomas.

Benefits include:

·        Rapid reduction in GH levels

·        Relief of pressure symptoms

·        Preservation of normal pituitary tissue when feasible

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Radiotherapy

Radiotherapy may be considered when:

·        Surgery is incomplete

·        Medical therapy is ineffective or not tolerated

·        Residual or recurrent tumor persists

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Complications of Acromegaly

Untreated acromegaly can lead to significant morbidity.

Major complications include:

·        Cardiomyopathy

·        Hypertension

·        Diabetes mellitus

·        Degenerative joint disease

·        Obstructive sleep apnea

·        Colon polyps and increased risk of colorectal malignancy

·        Visual impairment

·        Pituitary apoplexy due to hemorrhage within the adenoma

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Prognosis

The prognosis depends largely on early diagnosis and successful control of growth hormone excess.

·        Early treatment significantly improves symptoms and quality of life.

·        Surgical removal of the tumor can achieve long-term remission in many patients.

·        Persistent elevation of GH and IGF-1 increases the risk of cardiovascular disease, metabolic complications, and premature mortality.

·        With modern surgery and medical therapy, life expectancy approaches that of the general population when hormonal control is achieved.

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Key Points

·        Acromegaly is caused by excessive growth hormone secretion after epiphyseal closure.

·        Pituitary adenoma is the most common cause.

·        Elevated serum IGF-1 is the best screening test.

·        Failure of GH suppression during an oral glucose tolerance test confirms the diagnosis.

·        MRI is the imaging modality of choice for identifying pituitary tumors.

·        Transsphenoidal surgery is the preferred first-line treatment for most patients.

·        Early diagnosis prevents irreversible skeletal changes and reduces cardiovascular and metabolic complications.

DR.C.GANESAN M.D

PROFESSOR OF MEDICINE