Medical Treatment and Surgical Indications for Functioning Pituitary Adenomas

Abstract

  Functioning pituitary adenomas cause various clinical manifestations due to excess hormones secreted by the tumor. The prevalence is, in order, prolactinoma, acromegaly, and Cushing disease. Surgical treatment is the treatment of choice, except for prolactinoma, while medical therapy is for the patients without endocrinological remission after surgery. Dopamine agonists and somatostatin analogs are the major tumor-target medications, as those receptors are expressed on the majority of the adenoma cells. Also, end-organ-target medications are used as adjuvant therapy for biochemical control.

  Prolactinoma is the most common subtype of functioning pituitary adenomas. Some pitfalls exist in the diagnosis, including non-tumor causes of hyperprolactinemia, macroprolactinemia, hook effect, and possibility of plurihormonal adenoma. Medical treatment with dopamine agonists can achieve tumor shrinkage and hormonal control in a majority of patients. The goal of treatment in prolactinoma is different, depending on the patient's age, sex, and situation. Surgical treatment might be considered positively for macroadenoma in young women in whom strict hormonal control will be required.

  Dopamine agonists, first and second generation of somatostatin analogs, and GH receptors antagonist are used as medical therapy for acromegaly. Through combinations of those medications as well as recent advancements in surgery, the control rate of IGF-1 has been improved. More “certainty” and “safety” will be required for surgical treatment of acromagely.

  Same as acromegaly, surgical treatment is the first choice for Cushing disease. Dopamine agonists and second generation somatostatin analogs as tumor-target medications, and inhibitors of adrenal steroidogenesis or antagonists of glucocorticoid receptors as adjuvant end-organ targets are used as medical treatment. However, the disease control rate is not satisfactory. The presence of MRI-invisible adenoma is an unsolved problem and new imaging modalities are expected.

  Some new medical therapies are in development (undergoing clinical trials), including from molecular-target drugs for tumor control to end-organ targeted selective estrogen receptor modulators as adjuvant therapy. Although those medical treatments will progress, surgery is the ideal modality and mainstay of treatment. The future direction will be to maximally remove the tumor and select an effective adjuvant therapy based on the characteristics of the receptor and gene expression.