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Effect of Active Acromegaly and Its Treatment on Parathyroid Circadian Rhythmicity and Parathyroid Target-Organ Sensitivity

Department of Diabetes and Endocrinology (H.D.W., A.M.A., S.C., A.P., J.P.V.), Royal Liverpool University Hospital, Liverpool L7 8XP, United Kingdom; and Department of Clinical Biochemistry (B.H.D., W.D.F.), Royal Liverpool University Hospital, Liverpool L69 3GA, United Kingdom

Address all correspondence and requests for reprints to: Dr. Helen White, Department of Diabetes and Endocrinology, Link 7C, Royal Liverpool University Hospital, Prescot Street, Liverpool L7 8XP, United Kingdom. E-mail: h.white{at}ukf.net.

Context: Patients with active acromegaly have increased bone turnover and skeletal abnormalities. Biochemical cure of acromegaly may represent a functional GH-deficient state and result in cortical bone loss. Reduced PTH target-organ sensitivity occurs in adult GH deficiency and may underlie the associated development of osteoporosis.

Objective: We examined the effect of active and treated acromegaly on PTH concentration and target-organ sensitivity.

Patients: Ten active acromegalic subjects (GH nadir > 0.3 µg/liter after 75-g oral glucose load and IGF-I above age-related reference range) and 10 matched controls participated in the study.

Design: Half-hourly blood and 3-h urine samples were collected on patients and controls for 24 h. Samples were analyzed for PTH, calcium (Ca), nephrogenous cAMP (NcAMP, a marker of PTH renal activity), ß C-telopeptide (bone resorption marker), and procollagen type-I amino-terminal propeptide (bone formation marker). Serum calcium was adjusted for albumin (ACa). Eight acromegalic subjects who achieved biochemical cure (GH nadir < 0.3 µg/liter after 75-g oral glucose load and IGF-I within reference range) after standard surgical and/or medical treatment reattended and the protocol repeated.

Results: Active acromegalic subjects had higher 24-h mean PTH, NcAMP, ACa, urine Ca, ß C-telopeptide, and procollagen type I amino-terminal propeptide (P < 0.05), compared with controls. Twenty-four-hour mean PTH increased (P < 0.001) in the acromegalic subjects after treatment, whereas NcAMP and ACa decreased (P < 0.05).

Conclusion: Increased bone turnover associated with active acromegaly may result from increased PTH concentration and action. Biochemical cure of acromegaly results in reduced PTH target-organ sensitivity indicated by increased PTH with decreased NcAMP and ACa concentrations. PTH target-organ sensitivity does not appear to return to normal after successful treatment of acromegaly in the short term and may reflect functional GH deficiency.