Clinical Course

The patient underwent transsphenoidal surgery to debulk the tumor, without complications. Pathologic examination of the tumor tissue demonstrated pituitary adenoma with histochemical features indicating production of both GH and prolactin (Figures 5-7).

Tissue section showing the characteristic morphologic features of pituitary adenoma: a monomorphic population of tumor cells with complete effacement of the normal adenohypophyseal acinar architecture (H&E, x200).

Immunostaining for growth hormone showing significantly restricted expression to a small subpopulation of adenoma cells (arrows x200).

Immunohistochemical study revealing strong cytoplasmic positivity for prolactin in the majority of adenoma cells (x200).

Following surgery, the acromegalic features improved dramatically. There were substantial reductions in soft-tissue swelling, joint pain, headache frequency, and blood glucose levels.

The serum GH level normalized rapidly (Figure 8), without the need for further medical treatment. Serum IGF-1 levels normalized as well (Figure 9). Prolactin levels remained markedly elevated (Figure 10), and treatment with cabergoline (a dopamine agonist) was initiated. Initially, the relatively high dose of 1 mg of cabergoline 3 times a week was required to normalize the prolactin level. The dose required to maintain a normal prolactin level declined over many months to 0.5 mg twice a week. Despite the reduction in prolactin levels and surgical debulking of the tumor, hypogonadism persisted, and the patient was treated with transdermal testosterone.

Postsurgical GH levels.

Postsurgical IGF-1 levels.

Postsurgical prolactin levels.

Can this patient be considered cured?

  1. The therapeutic goals in acromegaly are to reduce the morbidity and mortality associated with GH excess to the expected age- and sex-adjusted rates by using safe treatments that remove the tumor mass or control its growth, as well as restore GH secretion and action to normal. The biochemical goals of therapy are to reduce circulating IGF-1 levels to normal age and sex ranges and to reduce serum GH concentrations to less than 1 mcg/L after an oral glucose load.In this patient, following surgery, serum GH levels remained consistently less than 1.0 ng/mL, and IGF-1 levels were within the reference range for his age and sex, indicating cure from acromegaly. The elevated serum prolactin level, as well as the large residual tumor, indicated persistence of a functional prolactinoma. The prolactinoma has been responsive to dopamine agonists, as evidenced by the suppressed serum prolactin levels and stabilization of tumor size in serial MRI examinations.

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How are prolactinomas treated?

  1. There are 2 main reasons to treat prolactinomas: hypogonadism and existing or impending neurologic complications due to the size of the adenoma. Medical management with dopamine agonists (eg, cabergoline, bromocriptine) is considered the first line of treatment, and a decrease in the serum prolactin level is usually achieved within the first few weeks of treatment. Diminution of tumor size may be apparent by MRI as early as 6 weeks following initiation of therapy, and vision may improve within days of treatment.If the patient cannot tolerate dopamine agonist therapy or if the treatment is ineffective, transsphenoidal surgery should be performed. Radiation therapy can be considered for persons with significant residual tumor burden.

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What is the patient's overall prognosis?

  1. The prognosis in a patient with acromegaly is highly dependent on the stage at which the disease is diagnosed. However, no prospective long-term study addressing this issue has been conducted to date. Retrospective studies suggest that the mortality rate associated with acromegaly is at least 2 times that of age-matched individuals in the general population. The most frequent causes of death are cardiovascular and respiratory complications. Patients with acromegaly may be at increased risk for cardiac hypertrophy, hypertension, arthritis, sleep apnea, and development of other neoplastic lesions, particularly in the colon. Epidemiologic studies have confirmed that effective GH-lowering treatment can increase the life expectancy of patients. Treatment is also likely to improve quality of life.

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