Hyperprolactinemia and Hypopituitarism in Acromegaly and Effect of Pituitary Surgery: Long-Term Follow-up on 529 Patients

Abstract

PurposeStudies on hyperprolactinemia and hypopituitarism in acromegaly are limited. We aimed to analyze the preoperative status, postoperative alterations, and correlated factors of hyperprolactinemia and hypopituitarism in acromegaly patients.MethodsThis is a single-center cohort study with long-term follow-up. We prospectively enrolled 529 acromegaly patients. Hyperprolactinemia and hypopituitarism were evaluated by testing hypothalamus-pituitary-end organ (HPEO) axes hormones before and after surgery.ResultsHyperprolactinemia (39.1%) and hypopituitarism (34.8%) were common in acromegaly. The incidences of axis-specific hypopituitarism varied (hypogonadism, 29.7%; hypothyroidism, 5.9%; adrenal insufficiency, 5.1%), and multiple HPEO axes dysfunction was diagnosed in 5.3% of patients. Patients with preoperative hyperprolactinemia [hazard ratio (HR)=1.39 (1.08-1.79); p=0.012], hypogonadism [HR=1.32 (1.01-1.73); p=0.047], and hypothyroidism [HR=3.49 (1.90-6.44); p<0.001] had higher recurrence rates than those without. Age, sex, body mass index, tumor size, invasiveness, prolactin staining, ki-67 index, and GH/IGF-1 levels were significantly correlated with preoperative hypopituitarism and hyperprolactinemia. At median 34-month follow-up after surgery, hyperprolactinemia in 95% and axis-specific hypopituitarism in 54%-71% of patients recovered, whereas new-onset hypopituitarism (hypogonadism, 6.2%; hypothyroidism, 4.0%; adrenal insufficiency, 3.2%) was also diagnosed. A shorter tumor diameter was associated with the normalization of preoperative hyperprolactinemia after surgery. Cavernous sinus non-invasion, a shorter tumor diameter, cure at follow-up, and a lower GH nadir level were associated with the improvement of preoperative hypopituitarism after surgery. A larger tumor diameter was associated with the newly developed hypopituitarism after surgery.ConclusionHyperprolactinemia and hypopituitarism are common among acromegaly patients and predict worse surgical outcomes. After surgery, improvement and worsening of HPEO axes function co-exist. Correlated factors are identified for clinical management.