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Bone Gla Protein and Sex Hormone-Binding Globulin in Nontoxic Goiter: Parameters for Metabolic Status at the Tissue Level

Department of Endocrinology E, Frederiksberg Hospital Frederiksberg DK-2000
The Department of Endocrinology F. Herlev University Hospital Herlev DK-2730
The Department of Clinical Chemistry, Glostrup Hospital Glostrup DK-2600 Denmark

Address all correspondence and requests for reprints to: Jens Faber, M.D., Department of Endocrinology F, Herlev University Hospital, DK-2730 Herlev, Denmark.

Several patients with nontoxic goiter have reduced serum TSH levels, as measured with new sensitive assays. Whether this is a sign of subclinical hyperthyroidism, thus having the potential of adverse effects on different organs with time, is not known.

We have measured serum levels of 2 markers of thyrometabolic status at the tissue level, bone -carboxyglutamic acidcontaining protein (BGP), reflecting the function of osteoblasts, and sex hormone-binding globulin (SHBG), reflecting the function of hepatocytes, in 44 patients (41 women and 3 men) with nontoxic goiter (11 diffuse and 33 nodular goiters; serum T₄, T₃, free T₄, and free T₃ levels had been normal and stable for at least 0.5 yr). Serum TSH levels ranged from normal to unmeasurably low values (<0.05 mU/L). Serum TSH levels correlated negatively to serum BGP levels (r = –0.60; P < 0.001). Due to the postmenopausal surge in serum BGP levels, premenopausal women (n = 21) were tested separately without changing the significance (r = –0.53; P < 0.02). Expressing serum BGP values as a percentage of the mean value in control subjects of the same age and sex did not change the correlation (r = –0.63; P < 0.001). Six patients had serum BGP levels above the normal range, and patients with reduced serum TSH levels (<0.45 mU/L; n = 12) had significantly enhanced serum BGP levels [median, 1.53 nmol/L (range, 1.02–4.24) vs. 1.23 nmol/L (0.62–3.71); P < 0.05].

Serum TSH also correlated negatively to serum SHBG levels (r = –0.56; P < 0.001; women alone: r = –0.58; P < 0.001). Eight patients had serum SHBG levels above the normal range, and patients with reduced serum TSH levels had significantly enhanced serum SHBG levels, expressed as a percentage of the mean control value for the relevant sex [203% (range, 75–288) vs. 120% (42–317); P < 0.01].

It is concluded that the lower serum TSH levels in patients with nontoxic goiter, the higher are serum BGP and SHBG levels. This suggests a progressively generalized (not only pituitary) tissue overexposure to thyroid hormones, the lower the serum TSH levels. Therefore, the finding of a reduced serum TSH level in patients with nontoxic goiter might reflect supraphysiological levels of T₄ and/or T₃, which could possibly be harmful.

^* Present address: Department of Medicine C, Bispebjerg Hospital, DK-2400.

Received January 1, 1989.

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