ACROMEGALY
Chronic growth hormone (GH) excess from a GH-producing pituitary tumor results in the clinical syndrome of acromegaly. Acromegaly was the first pituitary syndrome to be recognized, described by Pierre Marie in 1886. If untreated, this syndrome is associated with increased morbidity and mortality. Although the annual incidence is estimated to be only three per 1 million persons in the general population, a GH-secreting pituitary adenoma is the second most common hormone-secreting pituitary tumor. The effects of the chronic GH excess include acral and soft tissue over- growth, progressive dental malocclusion (underbite), degenerative arthritis related to chondral and synovial tissue overgrowth within joints, a low-pitched sonorous voice, headaches, malodorous hyperhidrosis, oily skin, perineural hypertrophy leading to nerve entrapment (e.g., carpal tunnel syndrome), proximal muscle weakness, carbohydrate intolerance (the initial presentation may be diabetes mellitus), hypertension, colonic neoplasia, obstructive sleep apnea, and cardiac dysfunction. The mass effects of GH-producing pituitary macroadenomas (10 mm) are similar to those of other pituitary macroadenomas and include visual field defects, oculomotor pareses, headaches, and pituitary insufficiency.
Patients with acromegaly have a
characteristic appearance with coarsening of the facial features, prognathism,
frontal bossing, spadelike hands, and wide feet. Often there is a history of
progressive increase in shoe, glove, ring, or hat size. These changes may occur
slowly and may go unrecognized by the patient, family, and physician. The
average delay in diagnosis from the onset of the first symptoms to the eventual
diagnosis is 8.5 years. Comparison with earlier photographs
of the patient is helpful in confirming the clinical suspicion of acromegaly.
High plasma GH levels are not
diagnostic of acromegaly. Basal plasma GH levels are increased in patients with
poorly controlled diabetes mellitus, chronic hepatic or renal failure, or
conditions characterized by protein-calorie malnutrition such as anorexia
nervosa. The diagnosis of acromegaly depends on two criteria: a GH level that
is not suppressed to less than 0.4 ng/ dL after an oral glucose load (75–100 g)
and an increased serum concentration (based on normal range adjusted for age
and gender) of insulinlike growth factor 1 (IGF-1, a GH-dependent growth factor
responsible for many of the effects of GH and previously known as somatomedin
C). Serum IGF-1 levels are rarely falsely elevated. IGF-1 levels do rise in
pregnancy two to threefold above the upper limit of gender and age-adjusted
normal values. The laboratory assessment of acromegaly is supplemented with
magnetic resonance imaging of the pituitary and with visual field examination by
quantitative perimetry. If imaging of the pituitary fails to detect an adenoma,
then plasma GH-releasing hormone (GHRH) concentration and CT of the chest and
abdomen are indicated in search of an ectopic GHRH-producing tumor (e.g.,
pancreatic or small cell lung neoplasm).
Treatment is indicated for all
patients with acromegaly. The goals of treatment are to prevent the long- term
consequences of GH excess, remove the sellar mass,
and preserve normal pituitary tissue and function. Treatment options include
surgery, targeted irradiation, and medical therapy. Surgery—transsphenoidal
adenectomy by an experienced neurosurgeon—is the treatment of choice and should
be supplemented, if necessary, with Gamma knife radiotherapy, pharmacotherapy,
or both.
After successful surgical treatment,
there is a marked regression of the soft tissue excess, but the bone changes are permanent. After the soft tissue changes
have stabilized, combined oral and plastic surgery may be indicated (e.g.,
mandibular osteotomies, recession of the supraorbital ridges, rhinoplasties,
and reduction of tongue size). Disabling hypertrophic osteoarthropathy of the
hip or other large joints may require joint replacement. Because of the
increased risk of colorectal adenomas and cancer, patients with acromegaly
should be offered regular colonoscopic screening.
