Acromegaly

ACROMEGALY

Definition and Historical Background

• Definition: Chronic growth hormone (GH) excess from a GH-producing pituitary tumor results in the clinical syndrome of acromegaly.
• Historical Note: Acromegaly was the first pituitary syndrome to be recognized, described by Pierre Marie in 1886.

Epidemiology

• Incidence: The annual incidence is estimated to be about three per 1 million persons in the general population.
• Prevalence of GH-secreting Adenomas: A GH-secreting pituitary adenoma is the second most common hormone-secreting pituitary tumor.

Consequences of Untreated Acromegaly

• Increased Morbidity and Mortality: If untreated, this syndrome is associated with an increased risk of various complications and a higher mortality rate.

CLINICAL FEATURES

Chronic GH Excess Effects

• Acral and Soft Tissue Overgrowth
• Progressive Dental Malocclusion (Underbite) and increased inter-dental distance
• Degenerative Arthritis due to overgrowth of chondral and synovial tissues in joints
• Low-Pitched Sonorous Voice
• Headaches
• Malodorous Hyperhidrosis and Oily Skin
• Perineural Hypertrophy Leading to Nerve Entrapment (e.g., carpal tunnel syndrome)
• Proximal Muscle Weakness
• Carbohydrate Intolerance: May initially present as diabetes mellitus
• Hypertension
• Colonic Neoplasia
• Obstructive Sleep Apnea
• Cardiac Dysfunction

Mass Effects of GH-Producing Pituitary Macroadenomas (> 10 mm)

• Visual Field Defects
• Oculomotor Pareses
• Headaches
• Pituitary Insufficiency

Characteristic Appearance

• Coarsening of Facial Features
• Prognathism (Jaw Protrusion)
• Frontal Bossing
• Spadelike Hands
• Wide Feet
• Progressive Increase in Shoe, Glove, Ring, or Hat Size
• These changes may be subtle and develop slowly, often going unrecognized by the patient, family, or physician.
• Diagnosis Delay: On average, there is an 8.5-year delay from the onset of the first symptoms to the eventual diagnosis.
• Comparison with Earlier Photographs: Useful in confirming clinical suspicion.

DIAGNOSTIC CONSIDERATIONS

GH Levels and Their Limitations

• High Plasma GH Not Always Diagnostic: Basal plasma GH levels can be elevated in:
  • Poorly controlled diabetes mellitus
  • Chronic hepatic or renal failure
  • Conditions with protein-calorie malnutrition (e.g., anorexia nervosa)

Criteria for Acromegaly Diagnosis

1. Lack of GH Suppression
   • GH does not suppress to less than 0.4 ng/dL after an oral glucose load (75–100 g). Learn about the growth hormone suppression test for acromegaly.
2. Elevated Serum IGF-1
   • Increased serum concentration of insulin-like growth factor 1 (IGF-1), adjusted for age and gender.
   • IGF-1 (formerly known as somatomedin C) is a GH-dependent growth factor responsible for many effects of GH.
   • Serum IGF-1 levels are rarely falsely elevated.
   • Exception: During pregnancy, IGF-1 can rise two- to threefold above the upper limit of normal values.

Imaging and Additional Workups

• Magnetic Resonance Imaging (MRI) of the Pituitary
  • Evaluate for adenoma and associated sellar or suprasellar extension.
  • MRI (Coronal View): May show a pituitary macroadenoma eroding the sellar floor, extending into the cavernous sinus, and up to the optic chiasm.
  • MRI (Midline Sagittal View): May show extension of the macroadenoma into the sphenoid sinus and suprasellar region.
• Visual Field Examination
  • Quantitative perimetry to assess for bitemporal hemianopsia or other visual defects.
• If No Adenoma Is Detected on Pituitary Imaging
  • Measure plasma GH-releasing hormone (GHRH) concentration.
  • Perform CT of the chest and abdomen to search for an ectopic GHRH-producing tumor (e.g., pancreatic or small cell lung neoplasm).

TREATMENT

Indications and Goals

• Who Needs Treatment?: All patients with acromegaly.
• Main Goals:
  1. Prevent long-term consequences of GH excess.
  2. Remove the sellar mass.
  3. Preserve normal pituitary tissue and function.

Treatment Options

1. Surgery
   • Transsphenoidal Adenectomy: Performed by an experienced neurosurgeon.
   • Treatment of choice for acromegaly.
2. Targeted Irradiation
   • Gamma Knife Radiotherapy may be used if necessary.
3. Medical Therapy
   • Often used as a supplement or if surgery and/or radiotherapy are contraindicated or incomplete in their control of GH levels. Examples of medical therapy include somatostatin analogs and pegvisomant.

POST-TREATMENT CHANGES

• Regression of Soft Tissue Excess
  • Marked regression after successful surgical treatment.
• Permanent Bone Changes
  • Bone deformities (e.g., enlarged jaw, frontal bossing) do not fully revert.
• Possible Need for Combined Oral and Plastic Surgery
  • Mandibular osteotomies
  • Recession of the supraorbital ridges
  • Rhinoplasties
  • Reduction of tongue size
• Hypertrophic Osteoarthropathy
  • Disabling changes, especially in the hip or other large joints, may require joint replacement.

FOLLOW-UP AND SURVEILLANCE

• Colorectal Screening
  • Patients with acromegaly have an increased risk of colorectal adenomas and cancer.
  • Regular colonoscopic screening is advised.