Hans Erik Sjöberg and Sigbritt Werner
Elisabet Bucht, Ove Tørring and Hans Erik Sjöberg
Abstract. A radioimmunoassay (RIA) was developed for immunoreactive calcitonin (iCT) in human plasma. Antibodies against synthetic human calcitonin (hCT) coupled to bovine serum albumin (BSA) were raised in rabbits and were directed against the carboxy terminal part of CT. The detection limit of the assay was 8 pg/ml. In 7 males the iCT response to a calcium-clamp was studied. Blood was collected at 0, 30 and 60 min after the start of the calcium infusion. iCT was measured directly in plasma and in extracts obtained after purification of plasma iCT by means of immobilized CT antibodies. There was a good correlation between iCT in plasma samples and extracts, r = 0.993, n = 14 (P < 0.001). Dilution curves of extracts and plasma were parallel with the hCT standard curves. Gel chromatography of the extracts on Sephadex G-50 and G-75 disclosed heterogeneity of iCT in normal plasma during basal conditions as well as during calcium stimulation. Thirty min after the start of the calcium clamp all molecular forms, most likely constituting monomeric and dimeric CT and larger forms, were increased, while after 60 min iCT seemed to constitute predominantly forms larger than monomeric CT. Basal levels of unextracted iCT in healthy males (n = 44, 37 ± 10 years) were 15 ± 9 pg-equivalents/ml (mean ± sd) which was higher than in females (n = 40, 32 ± 9 years) 11 ± 4 pg-equivalents/ml (P < 0.05).
Elisabet Bucht, Margareta Telenius-Berg, Göran Lundell and Hans-Erik Sjöberg
Abstract. The level of immunoreactive calcitonin in the first produced breast milk was in totally thyroidectomized (TX) women 713 ± 307 pg-eq/ml (mean ± sd, N = 7) and in control women 772 ± 329 pg-eq/ml (N = 33), i.e. about 45 times higher than in plasma (see below). On gel chromatography of immunoextracted milk from TX women, immunoreactive calcitonin appeared as high molecular weight forms in the same pattern as in milk from healthy women when the same antiserum (1) was used for immunoextraction and radioimmunoassay (RIA). In another series of experiments, a new antiserum (2) raised in rabbits was used for measurement of immunoreactive calcitonin after immunoextraction with 1. Plasma levels of immunoreactive calcitonin in the TX women during pregnancy were 16 ± 6 pg-eq/ml (N = 6) and during lactation 14 ± 7 pg-eq/ml (N = 5). Immunoreactive calcitonin was undetectable (< 8 pg/ml) in plasma from those TX women in whom lactation had stopped (N = 5). Immunoextraction and gel chromatography of plasma collected during pregnancy and lactation from the TX women showed that the immunoreactive calcitonin present eluted in the region of monomeric calcitonin with both antiserum 1 and 2. In conclusion, high concentrations of high molecular weight forms of immunoreactive calcitonin have been demonstrated in milk from TX patients, most probably devoid of any calcitonin-producing thyroid C-cells. This points to a local production site in the mammary gland. Relatively high levels of immunoreactive calcitonin in plasma during pregnancy and lactation in TX women also indicate extrathyroidal production.
Margareta Blombäck, Per Ola Granberg and Hans Erik Sjöberg
Ricardo E. Feinstein, Elisabet Bucht, Lars Grimelius, Krister Iwarsson, Curt Rönnbäck and Hans-Erik Sjöberg
Abstract. In order to determine whether a short period of general anesthesia influences the levels of serum calcitonin (CTs) and whole blood ionized Ca2+ and pH, 10 rats were sequentially anesthetized at 5-day intervals by halothane, ether, or CO2/O2, respectively, and retroorbital blood samples were collected during anesthesia. We noticed significant differences of serum calcitonin but the role of the anesthetics remains unclear, since other factors also could have accounted for the observed variations. Blood pH was strongly decreased by CO2/O2. Whole blood ionized calcium exhibited marked changes, but no correlation was found between whole blood ionized calcium and serum calcitonin.
Ove Tørring, Bengt Isberg, Hans Erik Sjöberg, Elisabet Bucht and Anna Lena Hulting
Hyperprolactinemia is associated with decreased bone mineral density, which may be caused by the hypogonadism and hypoestrogenicity noticed in patients with hyperprolactinemia. Since calcitonin inhibits the bone resorption, and insulin-like growth factor I (IGF-I) has important anabolic effects on the skeleton, lack of one or both peptides may contribute to the development of osteopenia. We therefore measured the plasma calcitonin and IGF-I levels in nine women with hyperprolactinemia caused by a prolactin-producing pituitary tumor. The calcium-stimulated C-cell reactivity was studied by measuring calcitonin in plasma during a calcium clamp before and after normalization of serum prolactin during treatment with bromocriptine. Basal CT levels were measurable but lower than in healthy controls. Basal IGF-I levels and calcium-stimulated plasma calcitonin were normal in the hyperprolactinemic state and similar to the calcitonin and IGF-I levels during bromocriptine treatment. The serum prolactin levels decreased (p<0·001) and the serum estradiol levels increased (p<0·001). The bone mineral density of the lumbar spine increased significantly during treatment. Thus, basal plasma CT levels are slightly reduced in hyperprolactinemic women. However, the reversible osteopenia in hyperprolactinemic women is less likely to be caused by inhibited IGF-I secretion or by deficient CT levels since the CT response to calcium is normal. In addition, bromocriptine treatment with normalization of prolactin levels is beneficial for the bone mineral content in this condition.
Marie Degerblad, Nabil Elgindy, Kerstin Hall, Hans-Erik Sjöberg and Marja Thorén
Six patients (21–50 years) with growth hormone deficiency and panhypopituitarism were given recombinant growth hormone, somatropin, 0.04–0.1 U·kg·body wt−1·day−1, for 12 months. All patients reported improved well-being with increased working capacity. Bone mineral density, as measured by single photon absorptiometry at two sites on the forearm, showed increased values in 5/6 patients after 12 months when measured at the most distal site (predominantly trabecular bone) and in 4/6 at the more proximal site (predominantly cortical bone). Five patients continued therapy for an additional year and after 18 months a significant increase in bone mineral density was seen at both the distal and proximal sites. The mean annual increase in bone mineral density was 12.0±0.6 (sem)% and 3.8±1.3% at the distal and proximal sites, respectively. In a growth hormone deficient control group without growth hormone therapy, the corresponding values were −2.4±0.6% and −1.9±0.4%, respectively. Lean body mass, estimated anthropometrically, increased significantly after 12 months and total body potassium, measured by whole body counting technique, increased in 4/6 patients. During growth hormone treatment, the IGF-1 values were above the mean values for age and 50% of the values were above the mean + 2 SD. B-glucose, P-insulin, serum IGF-2, procollagen-III peptide and phosphate increased and urea, creatinine and IGF-binding protein-1 decreased during treatment. The beneficial effects of growth hormone substitution, especially on bone mineral density, indicate that growth hormone substitution should be considered in all patients with hypopituitarism and growth hormone deficiency, irrespective of age.