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Matti Välimäki and Bror-Axel Lamberg

Abstract. Serum thyroglobulin (Tg) was measured in 52 patients 3 months to 15 years (mean 5.3 years) after thyroidectomy with or without subsequent radioablation for differentiated thyroid carcinoma, before and after the interruption of suppressive thyroxine (T4) replacement therapy for 5 weeks. Whole body scintigraphy was carried out at the end of the T4 withdrawal period.

Serum Tg was undetectable (< 3 μg/l) in 38 patients on T4 therapy, in 18 the scintigraphy showed a minimal accumulation in the neck region and in 20 no uptake anywhere after withdrawal of T4. In the former group Tg rose in 10 patients to 4–21 μg/l when off T4 which seemed to correspond to the normal tissue left in situ, in the latter group Tg rose only in 2 patients to 5 and 21 μg/l, respectively. Two patients out of 14 with detectable Tg on T4 had pulmonary metastases as uncovered by whole body scintigraphy (in one of them Tg rose from 12 μg/l on T4 to 1200 μg/l off T4) and 6 patients were suspected for having recidual cancer tissue (2 patients had a negative scintigraphy) because the Tg rose (66– 215 μg/l) over the upper limit of the reference range (< 50 μg/l) after T4 withdrawal.

In conclusion, in the follow-up of patients with differentiated thyroid carcinoma no routine scans are needed as long as serum Tg remains undetectable but further examinations are shortly warranted when detectable Tg is obtained during T4 suppression.

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Hanna Pelttari, Matti J Välimäki, Eliisa Löyttyniemi, and Camilla Schalin-Jäntti

Objective

To study whether post-surgical and/or post-ablative thyroglobulin (Tg) concentrations may serve as independent predictors of disease recurrence in patients treated for TNM stage I or II well-differentiated thyroid carcinoma (WDTC).

Design

An observational retrospective study with a median follow-up of 16 years (range 10–24).

Patients and measurements

Post-operative and post-ablative Tg concentrations, age, tumour size, local infiltration and nodal metastasis at primary surgery as well as disease recurrences and cancer-specific deaths were evaluated in 495 low-risk (TNM stages I and II) patients, the majority of whom had total thyroidectomy and radioactive iodine remnant ablation as initial treatment.

Results

Fifty-one patients (10.3%) experienced disease recurrence during follow-up. In multiple logistic regression analysis, post-ablative Tg concentrations (odds ratio (OR) 3.72, confidence interval (CI) 1.71–8.05, P=0.0009) and local infiltration on primary surgery (OR 2.66, CI 1.03–6.90, P=0.04) were the only independent predictors of recurrence.

Conclusions

Post-ablative Tg concentration is a strong predictor of disease recurrence in WDTC.

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Ajay Gupta, Ville-Valtteri Välimäki, Matti J Välimäki, Eliisa Löyttyniemi, Marilyn Richard, Prasanna L Bukka, David Goltzman, and Andrew C Karaplis

Objective

Mice with osteoblast-specific deletion of parathyroid hormone-related protein (PTHrP) exhibit impaired recruitment and increased apoptosis of osteogenic cells resulting in decreased bone formation and premature osteoporosis. The PTHrP levels within the bone microenvironment are therefore critical in influencing bone mass acquisition. Whether this is applicable in humans has not been established. Here, we studied the association of a variable number of tandem repeats (VNTR) polymorphism in PTHrP with peak bone mass.

Methods

Enrolled in the study were 234 young Finnish males, with median age of 19.6 years (range 18.3–20.6 years). Lifestyle factors, serum bone markers, osteodensitometric measurements (lumbar spine and hip) and calcaneal quantitative ultrasound readings were obtained. The PTHrP VNTR length was determined by the PCR amplification of genomic DNA extracted from peripheral blood and correlated to bone parameters by the multiple regression models.

Results

The presence of at least one 252 bp allele was associated with increased lumbar spine bone mineral density (BMD; P<0.0034), broadband ultrasound attenuation (BUA; P<0.0012) and speed-of-sound (SOS; P<0.0023) measurements. The correlation with increased lumbar spine BMD (P=0.0008), BUA (P=0.005) and SOS (P=0.001) was further strengthened by the pairing of the 252 bp allele with a 460 bp allele in comparison with those without any 252 bp allele. Electrophoretic mobility shift assays were used to illustrate the potential transcriptional functionality of the VNTR sequence.

Conclusion

The results indicate that the PTHrP VNTR sequence likely modulates local PTHrP expression within the skeletal microenvironment and could serve as a diagnostic predictor of peak bone mass acquisition.

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Tuula Pekkarinen, Ursula Turpeinen, Esa Hämäläinen, Eliisa Löyttyniemi, Henrik Alfthan, and Matti J Välimäki

Objective

Concentrations of 50 and 75 nmol/l are proposed as serum 25-hydroxyvitamin D (25(OH)D) target for older people from the view of bone health. We evaluated vitamin D status of elderly Finnish women in light of these definitions, its relationship to bone mineral density (BMD) and turnover, and improvement by summer sunshine.

Design

Population-based study.

Methods

A total of 1604 ambulatory women aged 62–79 years were studied; 66% used vitamin D supplements. Serum 25(OH)D3 was measured with HPLC before and after summer, and heel BMD in spring. In subgroups, serum parathyroid hormone (PTH) and type I procollagen aminoterminal propeptide (PINP) were analyzed.

Results

In spring, 60.3% of the women had 25(OH)D3 ≤50 nmol/l, and the target of 75 nmol/l was reached by 9.1%. For supplement users, the respective numbers were 52.1 and 11.9%. Serum 25(OH)D3 did not determine BMD or bone turnover measured by serum PINP. Summer sunshine increased serum 25(OH)D3 by 17.4% (P<0.0001), but in autumn 84% of the subjects remained under the target of 75 nmol/l. In supplement users, PTH remained stable but decreased in others during summer (P=0.025).

Conclusions

Vitamin D status of elderly Finnish women is suboptimal if 25(OH)D3 levels of 50 or 75 nmol/l are used as a threshold. It is moderately increased by supplement intake and summer sunshine. However, 25(OH)D3 concentrations did not influence bone density in terms of serum PINP and bone turnover rate.

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Matti J Välimäki, Riitta Tähtelä, James D Jones, James M Peterson, and B Lawrence Riggs

Välimäki MJ, Tähtelä R, Jones JD, Peterson JM, Riggs BL. Bone resorption in healthy and osteoporotic postmenopausal women: comparison markers for serum carboxy-terminal telopeptide of type I collagen and urinary pyridinium cross-links. Eur J Endocrinol 1994;131:258–62. ISSN 0804–4643

We compared two highly specific markers for bone resorption–pyridinium cross-links (pyridinoline (PYR) and deoxypyridinoline (DPR)) in urine and carboxy-terminal telopeptide of type I collagen (ICTP) in serum – in 63 healthy postmenopausal women and 63 women with osteoporosis characterized by more bone resorption than bone formation. The ICTP, PYR and DPR levels were all higher, by 24% (p = 0.001), 16% (p = 0.05) and 25% (p = 0.004), respectively, in the osteoporotic women. For the merged groups, there were significant correlations between serum ICTP concentration and urinary PYR (r = 0.667, p < 0.0001) and DPR (r = 0.452, p < 0.0001) excretion; for the osteoporotic and normal women separately, the r values were 0.73 (p < 0.01) and 0.45 (p < 0.01) for PYR and 0.51 (p < 0.01) and 0.22 (p = 0.08) for DPR versus ICTP respectively. Weak correlations in linear regression between ICTP and various indices of bone formation (osteocalcin, bone-specific alkaline phosphatase and carboxy-terminal propeptide of type I procollagen) disappeared when the correlation between ICTP and pyridinolines was accounted for by calculation of partial correlation coefficients in multiple regression analysis. Serum ICTP concentration appears to discriminate between groups of normal and osteoporotic women as well as urinary pyridinium cross-links, which is thus far the most sensitive method for assessing bone resorption.

Matti Välimäki, Third Department of Medicine, Helsinki University Central Hospital, SF-00290 Helsinki, Finland

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Anu Virkkala, Matti Välimäki, Risto Pelkonen, Kauko Huikuri, Arvi Kahri, Leena Kivisaari, Timo Korhonen, Jorma Salmi, and Pentti Seppälä

Abstract.

To determine endocrine activity of adrenal tumours incidentally discovered on CT, we examined 20 consecutive patients. They underwent thorough hormonal assessment and scintigraphic scanning with radioactive cholesterol under dexamethasone suppression (19 patients). Biochemical findings compatible with cortisol hypersecretion were detected in 5 patients. One patient had reduced reserves of cortisol secretion and one had hyporeninemic hypoaldosteronism. The scintigraphy showed no uptake in 10, unilateral uptake in 4, and bilateral uptake in 5 patients. In 3 patients the finding was unilateral on CT, but bilateral on scintigraphy. Signs of autonomous cortisol production were more common among patients who had uptake on scintigraphy. At the operation of 8 patients only benign lesions were found. During the follow-up (9 to 49 months) of the 12 unoperated patients, the tumour disappeared in one and remained unchanged in the others. No changes occurred in the biochemical findings except in one patient whose cortisol response to 1 mg of dexamethasone became abnormal. Since slight hypercortisolism or a bilateral disease often exists behind an incidentally discovered adrenal tumour, we emphasize the importance of careful assessment of cortisol metabolism and a scintigraphic scanning under dexamethasone suppression in the examination of these patients.

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Minna Soinio, Anna-Kaarina Luukkonen, Marko Seppänen, Jukka Kemppainen, Janne Seppänen, Juha-Pekka Pienimäki, Helena Leijon, Tiina Vesterinen, Johanna Arola, Eila Lantto, Semi Helin, Ilkka Tikkanen, Saara Metso, Tuomas Mirtti, Ilkka Heiskanen, Leena Norvio, Mirja Tiikkainen, Tuula Tikkanen, Timo Sane, Matti Välimäki, Celso E Gomez-Sanchez, Ilkka Pörsti, Pirjo Nuutila, Pasi I Nevalainen, and Niina Matikainen

Objective

Endocrine Society guidelines recommend adrenal venous sampling (AVS) in primary aldosteronism (PA) if adrenalectomy is considered. We tested whether functional imaging of adrenal cortex with 11C-metomidate (11C-MTO) could offer a noninvasive alternative to AVS in the subtype classification of PA.

Design

We prospectively recruited 58 patients with confirmed PA who were eligible for adrenal surgery.

Methods

Subjects underwent AVS and 11C-MTO-PET without dexamethasone pretreatment in random order. The lateralization of 11C-MTO-PET and adrenal CT were compared with AVS in all subjects and in a prespecified adrenalectomy subgroup in which the diagnosis was confirmed with immunohistochemical staining for CYP11B2.

Results

In the whole study population, the concordance of AVS and 11C-MTO-PET was 51% and did not differ from that of AVS and adrenal CT (53%). The concordance of AVS and 11C-MTO-PET was 55% in unilateral and 44% in bilateral PA. In receiver operating characteristics analysis, the maximum standardized uptake value ratio of 1.16 in 11C-MTO-PET had an AUC of 0.507 (P = n.s.) to predict allocation to adrenalectomy or medical therapy with sensitivity of 55% and specificity of 44%. In the prespecified adrenalectomy subgroup, AVS and 11C-MTO-PET were concordant in 10 of 19 subjects with CYP11B2-positive adenoma and in 6 of 10 with CYP11B2-positivity without an adenoma.

Conclusions

The concordance of 11C-MTO-PET with AVS was clinically suboptimal, and did not outperform adrenal CT. In a subgroup with CYP11B2-positive adenoma, 11C-MTO-PET identified 53% of cases. 11C-MTO-PET appeared to be inferior to AVS for subtype classification of PA.