Medical Care
Prolactinoma
Prolactinoma is the only pituitary adenoma for which long-term medical management is fully satisfactory. Unless the patient presents with an acute threat to vision, hydrocephalus, cerebrospinal fluid leak, or other surgical emergency, medical management with dopamine agonists should be attempted before surgical treatment is considered. Dopamine agonists are potent suppressors of prolactin (PRL) secretion and promptly lower serum PRL levels, abolish galactorrhea, and restore normal gonadal function in most patients with hyperprolactinemia of any cause. Dopamine agonists can also inhibit tumor cell replication in 60-80% of prolactinomas. In small tumors, dopamine agonists cause tumor shrinkage, while the results vary in larger tumors. Successful long-term use of these drugs can obviate the need for pituitary surgery.
Corticotropinoma
The treatment of choice for patients with Cushing disease is transsphenoidal microsurgery. Medical therapy for Cushing disease is adjunctive only. The goal is to inhibit the enzymes responsible for cortisol synthesis with adrenal enzyme inhibitors, such as metyrapone, aminoglutethimide, and ketoconazole. Metyrapone and aminoglutethimide have been the standard therapy, and, when the 2 agents are used in combination, adverse effects may be decreased. Ketoconazole, a broad-spectrum antimycotic drug, inhibits adrenal steroid biosynthesis at several sites, including side chain cleavage and 11B-hydroxylation. Occasionally, patients with ACTH-secreting tumors respond to bromocriptine.
Somatotropinoma
Somatostatin analogs are highly effective therapies for patients with GH excess. Octreotide suppresses circulating GH levels to less than 2.5 µg/L in 65% of patients with acromegaly and normalizes IGF-I levels in 70% of patients. Long-term studies of patients older than 14 years confirm that the effects of octreotide remain well sustained over time. Octreotide also shrinks tumors, but the effect is generally modest.
A continuous subcutaneous infusion of octreotide in a pubertal boy with pituitary gigantism consistently suppressed GH production. New long-acting formulations, including long-acting octreotide and lanreotide, have been reported to consistently suppress GH and IGF-I in patients with acromegaly with once monthly or biweekly intramuscular depot injections. The author has had success in using the sustained-release formulation in a female adolescent with MAS-related GH excess and can provide details upon inquiry.
Dopamine agonists bind to pituitary dopamine type 2 (D2) receptors and suppress GH secretion, although the precise mechanism of action remains unclear. PRL levels are often adequately suppressed; however, GH levels and IGF-I levels are rarely normalized with this treatment modality. Fewer than 20% of patients achieve GH levels less than 5 ng/mL and fewer than 10% achieve normalization of circulating IGF-I levels. Tumor shrinkage occurs in a minority of patients. A dopamine agonist is generally used as adjuvant medical treatment for GH excess. Its effectiveness may be additive to that of octreotide. Long-acting formulations are available, but data on long-term control of GH and IGF-I with these agents are not available.
A novel hepatic GH receptor antagonist has been approved by the US Food and Drug Administration (FDA). Pegvisomant effectively suppresses circulating GH and IGF-I levels in patients with acromegaly due to pituitary tumors, as well as ectopic GHRH hypersecretion. IGF-I levels are normalized in as many as 90% of patients treated daily with this drug for 3 months.
Long-term studies are underway. The ACROSTUDY database provides an opportunity to assess the long-term safety of pegvisomant in the treatment of acromegaly. [13] The main safety focus of this long-term follow up is on the potential risk of increased pituitary tumor size, potential for increased liver enzymes, and effects of pegvisomant at the injection site. There are 33 patients in the cohort younger than 18 years. Overall, it seems a selection bias may exist towards more severely affected patients, most subjects were enrolled in Europe, where pegvisomant is registered for patients in whom every other therapeutic intervention failed to control their acromegaly. In the future, additional data on more patients for longer duration will provide further information about the treatment of this rare condition.
Pediatric experience, although scant, has been published and agrees with the efficacy and adverse event profile reported with adult patients.
Surgical Care
Transsphenoidal surgery is the treatment of choice for Cushing disease in children. Initial remission rates of 70-98% of patients and long-term success rates of 50-98% have been reported. [9]
After surgical treatment of Cushing disease, patients require daily hydrocortisone replacement therapy (8-10 mg/m2/d and education about stress dosing) from the time of surgery until their hypothalamic-pituitary-adrenal functions recover, which usually occurs 6-12 months after surgery.
The preferred primary treatment for the patient with acromegaly is surgery, with a surgical cure rate at 10 years approaching 83% in the largest reported series. [9] Such surgery should be performed at large centers with documented experience, including published outcome and adverse event profiles.
For prolactinomas, surgery has good outcomes with a long-term (10-year) surgical cure rate approaching 82% in the largest reported series with very low morbidity and no mortality.
Irradiation is reserved for the few patients who are intolerant of medication. Irradiation of the pituitary gland in children is not recommended, because it can lead to panhypopituitarism, optic nerve and optic chiasm injury, delayed radiation injury of the brain, increased risk of a second brain tumor, and epilation.
Consultations
Endocrinologists fill a critical role in the diagnosis, preoperative, perioperative, and postoperative management of all pediatric patients with pituitary adenomas.
The experience of the neurosurgeon is critical for the outcome of transsphenoidal adenomectomy. In addition, the referring physician should obtain the published outcome and adverse event profiles for the surgeon and her or his institution. Such information should be discussed with the patient and patient's family prior to referral to another institution.
Long-Term Monitoring
Long term monitoring with both an endocrinologist and a neurosurgeon is recommended. Routine monitoring with laboratory assessment and pituitary imaging will be needed.
Consultation with a genetic counselor could be considered. This would be helpful in guiding genetic testing.
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Pituitary macroadenoma.
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A 16-year-old boy with Cushing disease.
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On the left is an unaffected patient aged 12 years. On the right is the same patient aged 13 years after developing Cushing disease.
