Nine patients, from four different families, with autosomal dominant
osteopetrosis were investigated. They all had roentgenological type I disease, characterized by universal, symmetrical
osteosclerosis and enlarged thickness of the cranial vault. All patients appeared clinically euthyroid.
Thyroxine (T4) and tri-iodothyronine (T3) induced oxygen consumption and
glucose uptake were studied in vitro in mononuclear blood cells from patients and control persons. Unstimulated oxygen consumption from patients and controls did not differ, and no difference in unstimulated
glucose uptake was observed. The increase in T4 and T3 stimulated oxygen consumption was significantly lower in cells from patients with
osteopetrosis (T4: 0.007 +/- 0.004 mumol/mg
DNA per h, T3: 0.011 +/- 0.004 mumol/mg
DNA per h) compared with controls (T4: 0.017 +/- 0.003 mumol/mg
DNA per h, T3: 0.023 +/- -0.013 mumol/mg
DNA per h; p less than 0.05, p less than 0.05). Cellular
glucose uptake after T4 and T3 stimulation was significantly lower in patients (T4: 0.032 +/- 0.017 mmol/l per mg
DNA per h, T3: 0.02 +/- 0.017 mmol/l per mg
DNA per h) compared with controls (T4: 0.09 +/- 0.017 mmol/l per mg
DNA per h, T3: 0.08 +/- 0.01 mmol/l per mg
DNA per h; p less than 0.05, p less than 0.01). The reduced oxygen consumption and
glucose uptake indicate
thyroid hormone resistance which may be of pathogenetic importance for the development of autosomal dominant
osteopetrosis type I.