SIGNIFICANT ELEVATION OF GROWTH HORMONE LEVEL IMPACTS SURGICAL OUTCOMES IN ACROMEGALY.

OBJECTIVE: Transsphenoidal adenomectomy (TSA) is first-line treatment for acromegaly. Our aim was to determine the impact of pre-operative biochemical parameters on the outcomes of surgery. METHODS: Retrospective case series of 79 consecutive acromegalics operated between 1994 and 2013. Inclusion criteria were: first TSA, pathology-confirmed growth hormone (GH) adenoma, and follow-up >3 months. Biochemical remission was defined as normal insulin-like growth factor 1 (IGF-1) without adjuvant therapy during follow-up. RESULTS: Median follow-up was 35.4 months (range, 3 to 187 months). Logistic regression analysis showed that the best model to predict long-term remission included the following pre-operative markers: GH, tumor diameter, and cavernous sinus invasion (CSI) (area under the curve, 0.933). A threshold GH of 40 ng/mL was associated with long-term remission (sensitivity, 97%; specificity, 42%). Group A (GH >40 ng/mL) comprised 19 patients (9 men); age, 43 ± 13 years; tumor diameter, 2.7 ± 1.0 cm; 73.7% with CSI; and pre-operative median GH, 77.8 ng/mL (interquartile range [IQR], 66.7 to 107.0 ng/mL). Three patients (15%) in group A achieved remission at 3 months, but 2 patients recurred during follow-up. Group B (GH ≤40 ng/mL) comprised 60 patients (25 men); age, 47 ± 13 years; tumor diameter, 1.6 ± 1.0 cm; 35% with CSI, preoperative median GH, 6.9 ng/mL (IQR, 3.4 to 16.9 ng/mL). Thirty-five patients (58%) in group B achieved remission at 3 months without recurrence during follow-up. Group A had larger tumors and a higher proportion of tumors with CSI (P<.05). CONCLUSION: Both GH and IGF-1 should be measured pre-operatively, as highly elevated GH levels negatively impact long-term surgical remission. This strategy allows early identification of patients who require adjuvant therapy and may decrease time to biochemical control.

Acromegaly and bone disease.

PURPOSE OF REVIEW: To provide an update on current understanding of osteoporosis associated with acromegaly. RECENT FINDINGS: Patients with acromegaly have an increased risk of morphometric vertebral fractures. This seems to correlate with acromegaly activity and its duration, but it persists after biochemical control is achieved. Coexistent hypogonadism, diabetes mellitus and over-replacement with glucocorticoids have additional detrimental effects. Bone mineral density can be normal, increased or decreased, and is usually discordant with occurrence of fractures. However, a decrease in the hip bone mineral density during follow-up has been associated with development of new vertebral fractures. Bone turnover markers are increased and tend to normalize after biochemical control of acromegaly. Hypercalcemia rarely occurs in acromegaly and may be parathyroid hormone-dependent or 1,25 dihydroxy-vitamin D dependent. The latter improves with biochemical control of acromegaly. SUMMARY: Screening with thoracic and lumbar vertebral radiographs is indicated in patients with acromegaly. We recommend biochemical control of acromegaly, treatment of hypogonadism and other risk factors of osteoporosis and avoiding supraphysiologic doses of glucocorticoids. Further studies are needed to understand mechanisms of skeletal fragility in acromegaly and clinical impact of vertebral fractures. Further studies of tailored therapy for patients with acromegaly and osteoporosis are also needed.