title: Recombinant human TSH modulates in vivo C-telopeptides of type-1 collagen and bone alkaline phosphatase, but not osteoprotegerin production in postmenopausal women monitored for differentiated thyroid carcinoma.
abstract: In women monitored for thyroid carcinoma, short-term stimulation with rhTSH induced an acute decrease in serum C-telopeptides of type-1 collagen and an increase in serum BALP levels without any effect on OPG production. The inhibitory effect of TSH on bone resorption occurred only in postmenopausal women who showed low BMD and a high bone turnover rate as an effect of L-thyroxine suppressive therapy.
  
  
  BACKGROUND
  It has been recently shown that thyrotropin (TSH) has an inhibitory activity on skeletal remodeling in in vitro conditions. Here, we have aimed at evaluating whether TSH has similar effects in vivo. For this purpose, we have evaluated the sequential profile of serum bone metabolism markers during acute stimulation with recombinant human TSH (rhTSH) in thyroidectomized women monitored for thyroid carcinoma.
  
  
  METHODS
  The study group included 66 thyroidectomized patients, of whom 38 were premenopausal and 28 postmenopausal, who underwent routine rhTSH-assisted whole body radioactive iodine scanning for differentiated thyroid carcinoma. The patients were sequentially evaluated for TSH, free triiodothyronine (FT3), free thyroxine (FT4), bone alkaline phosphatase (BALP), C-telopeptides of type-1 collagen (CrossLaps), and osteoprotegerin (OPG) levels during rhTSH stimulation. The samples were drawn just before and 2 and 7 days after the first administration of rhTSH. BMD was evaluated by ultrasonography at baseline. Seventy-one healthy women (41 premenopausal and 30 postmenopausal) acted as a control group.
  
  
  CONCLUSIONS
  At study entry, all patients had subclinical thyrotoxicosis as effect of L-thyroxine (L-T4) treatment. The patients had higher serum CrossLaps and OPG levels and lower BMD than healthy subjects. Postmenopausal patients showed comparable serum FT4 and FT3 concentrations with those found in premenopausal patients. However, postmenopausal patients showed higher serum CrossLaps (p < 0.001), OPG (p = 0.03), and BALP (p < 0.001) levels and lower BMD (p < 0.001) than those measured in premenopausal patients. Two days after the first administration of rhTSH, all patients had serum TSH values >100 mUI/liter. At this time, serum CrossLaps levels decreased significantly (p < 0.001) and BALP values increased (p = 0.001) with respect to the baseline values in postmenopausal but not in premenopausal patients. rhTSH did not induce any significant change in serum OPG values either in premenopausal or in postmenopausal patients. One week after the first rhTSH administration, serum CrossLaps values decreased again to values comparable with those measured at baseline, whereas serum BALP values remained high. This study shows that subclinical thyrotoxicosis is accompanied by high bone turnover rate with an increase in serum OPG levels compared with euthyroid healthy subjects. Acute increase in serum TSH levels is accompanied by a reversible inhibition of bone resorption. This effect is characterized by a decrease in serum CrossLaps and an increase in BALP levels without any evident effect on OPG production. The activity of TSH occurs specifically in postmenopausal women in whom the negative effects of L-T4 suppressive therapy on bone mass and metabolism are more marked compared with premenopausal women.
authors.affiliation: Department of Clinical and Experimental Medicine, F. Magrassi & A. Lanzara, Second University of Naples, Naples, Italy.
authors.forename: Gherardo
authors.initials: G
authors.lastname: Mazziotti
authors.forename: Francesca
authors.initials: F
authors.lastname: Sorvillo
authors.forename: Marco
authors.initials: M
authors.lastname: Piscopo
authors.forename: Michele
authors.initials: M
authors.lastname: Cioffi
authors.forename: Paola
authors.initials: P
authors.lastname: Pilla
authors.forename: Bernadette
authors.initials: B
authors.lastname: Biondi
authors.forename: Sergio
authors.initials: S
authors.lastname: Iorio
authors.forename: Andrea
authors.initials: A
authors.lastname: Giustina
authors.forename: Giovanni
authors.initials: G
authors.lastname: Amato
authors.forename: Carlo
authors.initials: C
authors.lastname: Carella
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D015415:Biomarkers / Q000097:blood; D001862:Bone Resorption / Q000097:blood*; D002277:Carcinoma / Q000097:blood*; D005260:Female; D006023:Glycoproteins / Q000096:biosynthesis*; D006801:Humans; D008875:Middle Aged; D053244:Osteoprotegerin; D017698:Postmenopause / Q000097:blood; D017697:Premenopause / Q000097:blood; D018160:Receptors, Cytoplasmic and Nuclear / Q000096:biosynthesis*; D018124:Receptors, Tumor Necrosis Factor / Q000096:biosynthesis*; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000097:blood; D013964:Thyroid Neoplasms / Q000097:blood* / Q000628:therapy; D013972:Thyrotropin / Q000008:administration & dosage* / Q000097:blood
chemical_list: D015415:Biomarkers; D006023:Glycoproteins; D053244:Osteoprotegerin; D018160:Receptors, Cytoplasmic and Nuclear; D018124:Receptors, Tumor Necrosis Factor; D011994:Recombinant Proteins; C506030:TNFRSF11B protein, human; D013972:Thyrotropin