Effects of treatment of hyperthyroidism on glucose homeostasis, insulin secretion, and markers of bone turnover.
OBJECTIVE
To study glucose and bone metabolism in hyperthyroidism, assess their changes after treatment, and investigate their interrelationships.


METHODS
Thirty patients with hyperthyroidism matched with 32 normal control subjects were studied. After a 10- to 12-hour overnight fast, blood samples were collected for measurement of glucose, insulin, C-peptide, and intact proinsulin levels as well as for measurement of bone markers: serum alkaline phosphatase (ALP), osteocalcin, and procollagen type I C-terminal peptide (PICP) as markers of bone formation and serum C-terminal cross-linked telopeptide of type I collagen (ICTP) as a marker of bone resorption. A 3-hour 75-g oral glucose tolerance test was then performed, with measurement of glucose, insulin, and C-peptide levels every 30 minutes. Patients were studied at baseline and after treatment with an antithyroid drug (carbimazole) for 1 month and 6 months.


RESULTS
Pretreatment fasting glucose, insulin, C-peptide, and intact proinsulin levels were significantly higher in patients with hyperthyroidism than in control subjects. During the 3-hour oral glucose tolerance test, the area under the curve of glucose was significantly elevated in the patients, whereas the 3-hour areas under the curve of insulin and C-peptide were not significantly different between patients and control subjects. Fasting glucose, insulin, C-peptide, and intact proinsulin levels decreased significantly to levels similar to those of the control subjects after 1 month of antithyroid therapy and remained so at 6 months. Pretreatment ALP, osteocalcin, PICP, and ICTP were significantly higher in the patients than in the control subjects. After treatment, all markers of bone turnover decreased significantly to levels similar to those of the control subjects at 1 month (except ALP) and 6 months. Within the study group of patients, baseline PICP, osteocalcin, and ICTP demonstrated positive correlation trends with free triiodothyronine and free thyroxine.


CONCLUSIONS
Abnormal glucose metabolism and increased bone turnover are hallmarks of untreated hyperthyroidism. These factors normalize as early as 4 weeks after initiation of antithyroid therapy. Changes in bone markers, particularly those of resorption, are related to the degree of thyroid hyperactivity.
Al-Shoumer
Kamal A S
KA
Division of Endocrinology & Metabolic Medicine, Mubarak Al-Kabeer Hospital, Jabriya, and the Department of Medicine, Faculty of Medicine, Kuwait University, Safat, Kuwait.
Vasanthy
Bagavathy A
BA
Al-Zaid
Mona M
MM
D000328:Adult; D000469:Alkaline Phosphatase / Q000097:blood; D015415:Biomarkers / Q000097:blood; D001786:Blood Glucose / Q000187:drug effects*; D001862:Bone Resorption / Q000097:blood*; D002096:C-Peptide / Q000097:blood; D002118:Calcium / Q000097:blood; D016022:Case-Control Studies; D024042:Collagen Type I; D005260:Female; D006801:Humans; D006980:Hyperthyroidism / Q000097:blood* / Q000188:drug therapy*; D007328:Insulin / Q000378:metabolism*; D007333:Insulin Resistance; D000078790:Insulin Secretion; D008297:Male; D015675:Osteocalcin / Q000097:blood; D010446:Peptide Fragments / Q000097:blood; D010455:Peptides; D011347:Procollagen / Q000097:blood; D011384:Proinsulin / Q000097:blood; D013971:Thyrotoxicosis / Q000097:blood / Q000188:drug therapy
D015415:Biomarkers; D001786:Blood Glucose; D002096:C-Peptide; D024042:Collagen Type I; D007328:Insulin; D010446:Peptide Fragments; D010455:Peptides; D011347:Procollagen; C052929:collagen type I trimeric cross-linked peptide; C042813:procollagen type I carboxy terminal peptide; D015675:Osteocalcin; D011384:Proinsulin; D000469:Alkaline Phosphatase; D002118:Calcium