Stig Valdermarsson

Sestamibi versus thallium subtraction scintigraphy in parathyroid localization : a prospective comparative study in patients with predominantly mild primary hyperparathyroidism

BACKGROUND Technetium 99m sestamibi was recently introduced for the preoperative localization of abnormal parathyroid glands in patients with primary hyperparathyroidism with promising results. However, the sensitivity of sestamibi and thallium to detect abnormal parathyroid glands is partly dependent on the gland size. In this study we compared the sensitivity of sestamibi subtraction scintigraphy with thallium subtraction scintigraphy in patients with predominantly mild increase in serum calcium level. METHODS Thirty-nine patients with primary hyperparathyroidism were included. The mean (+/-SD) serum level of calcium was 2.75 +/- 0.17 mmol/L. In 28 (72%) of the patients the serum level of calcium was less than 2.85 mmol/L. These patients were classified as having mild abnormalities in serum calcium. All patients were investigated before operation with both sestamibi and thallium subtraction scintigraphy. RESULTS In two patients autonomous thyroid adenomas precluded subtraction scintigraphy. Sestamibi subtraction scintigraphy correctly localized 31 (86%) of 36 parathyroid adenomas compared with only 17 (47%) of 36 by thallium subtraction scintigraphy (p < 0.001). There was one false-positive result in the sestamibi group because of a thyroid adenoma, and two of the scans were negative. Both the sestamibi and the thallium subtraction scintigraphy localized one single enlarged gland in all three patients with multiple gland involvement. In no case was multiglandular disease predicted. CONCLUSIONS Sestamibi subtraction scintigraphy is superior to thallium subtraction scintigraphy and has a high sensitivity to localize a solitary parathyroid adenoma in patients with mild increase in serum calcium level. The sensitivity decreases in patients with multiglandular parathyroid disease and concomitant thyroid nodular abnormalities.

Suppression by Calcium of Serum Levels of Intact Parathyroid Hormone in Patients with Primary Hyperparathyroidism

Primary hyperparathyroidism (pHPT) is associated with a right-shifted relation between parathyroid hormone (PTH) secretion and calcium. However, it is also possible that a decreased suppressibility of PTH secretion by calcium is important for maintaining hypercalcemia in pHPT. We therefore compared the suppression of serum levels of intact PTH induced by a 1.5-gram oral calcium load in patients with mild pHPT with that in healthy subjects. The calcemic response to the oral calcium load was the same in the two groups and did not correlate with the degree of PTH suppression or to serum levels of vitamin D metabolites. It was found that serum levels of intact PTH were less suppressed by the oral calcium load in patients than in healthy subjects (p < 0.01), but with a considerable overlap between the two groups. The suppression of serum levels of intact PTH was correlated both to baseline serum total calcium levels (r = -0.55; p < 0.05) and osteocalcin levels (r = -0.69; p < 0.05) in the patients, but no such correlations were seen in the controls. We conclude that patients with pHPT have a decreased suppressibility of PTH secretion by calcium. Although this reduced suppressibility could be important for maintaining hypercalcemia in some patients with pHPT, it does not aid in the differential diagnosis between patients with mild pHPT and healthy subjects.

Immunheterogenität von nebenschilddrüsen-hormonen prä- und postoperativ bei primärem hyperparathyreoidismus

In primary hyperparathyroidism (pHPT), a preferential release of intact PTH (i-PTH) versus carboxyl-terminal PTH fragments is known to occur. We studied whether the release of amino-terminal PTH fragments (N-PTH) is also changed. Serum levels of i-PTH and N-PTH were determined under basal conditions and following oral intake of calcium in six patients with pHPT before and immediately after surgery and in seven healthy subjects. In the patients, baseline levels of both i-PTH and N-PTH were increased preoperatively. The increase was larger in i-PTH compared to N-PTH. Therefore, the N/i ratio was reduced compared to healthy subjects (P<0.05). On the first postoperative day, serum i-PTH decreased to a larger extent than N-PTH, which increased the N/i ratio above that in healthy subjects (P< 0.05). On the 5th postoperative day, the N/i ratio was normalized. Preoperatively, the suppressibility of i-PTH calcium was impaired in the patients (P<0.05), whereas the suppressibility of N-PTH was normal, resulting in unchanged N/i ratio during the oral calcium load. In contrast, the N/i ratio increased normally during the calcium load at day 5 postoperatively (P<0.05). We therefore conclude that: (1) in pHPT, circulating PTH immunoheterogeneity is altered with a preferential release of intact PTH compared to N-terminal PTH fragments and this alteration is normalized after surgery, (2) the secretion of intact PTH and N-terminal PTH shows different sensitivity to inhibition by calcium.ZusammenfassungBei primärem Hyperparathyreoidismus (pHPT) kann, wie man weiβß, eine Freisetzung eher von intaktem PTH (i-PTH) als von Fragmenten mit end-ständigen Carboxylgruppen erfolgen. Wir untersuchten, ob die Freisetzung von PTH-Fragmenten mit terminalen Aminogruppen (N-PTH) sich ebenfalls ändert. Es wurden die Serumspiegel von i-PTH und N-PTH unter folgenden Bedingungen bestimmt: (1) bei 6 pHPT-Patienten (a) ohne Kalziumgabe, (b) nach oraler Kalziumgabe vor und unmittelbar nach Operation und (2) bei 7 gesunden Personen. Bei ersteren waren präoperativ beide Spiegel — i-PTH und N-PTH — erhöht, die i-PTH-Spiegel etwas stärker. Daher war das Verhältnis N-PTH/i-PTH im Vergleich zu gesunden Personen vermindert (p<0,05). Postoperativ war am 1. Tag das Serum-i-PTH stärker vermindert als das N-PTH, wodurch das N-PTH/i-PTH-Verhältnis gegenüber Gesunden zunahm (p<0,05); am 5. Tag normalisierte sich dieses Verhältnis. Präoperativ verbesserte sich die Supprimierung von i-PTH-Kalzium bei den Patienten, während die Supprimierung von N-PTH-Kalzium normal blieb, was seinen Ausdruck fand in einem unveränderten N-PTH/i-PTH-Verhältnis während der oralen Kalziumeinnahme. Im Gegensatz dazu vergrößerte sich das N-PTH/i-PTH-Verhältnis in normaler Weise während der Kalziumeinnahme am 5. Tag postoperativ (p<0,05). Schlußfolgerungen: (1) Bei pHPT ändert sich die zirkulierende PTH-Immunheterogenität mit einer vorzugsweisen Freisetzung von i-PTH im Vergleich zu N-PTH, und diese Veränderung normalisiert sich nach Operation. (2) Die Sekretion von i-PTH und N-PTH zeigt unterschiedliche Sensitivität gegenüber einer Inhibierung durch Kalzium.Bei primarem Hyperparathyreoidismus (pHPT) kann, wie man weiβs, eine Freisetzung eher von intaktem PTH (i-PTH) als von Fragmenten mit end-standigen Carboxylgruppen erfolgen. Wir untersuchten, ob die Freisetzung von PTH-Fragmenten mit terminalen Aminogruppen (N-PTH) sich ebenfalls andert. Es wurden die Serumspiegel von i-PTH und N-PTH unter folgenden Bedingungen bestimmt: (1) bei 6 pHPT-Patienten (a) ohne Kalziumgabe, (b) nach oraler Kalziumgabe vor und unmittelbar nach Operation und (2) bei 7 gesunden Personen. Bei ersteren waren praoperativ beide Spiegel — i-PTH und N-PTH — erhoht, die i-PTH-Spiegel etwas starker. Daher war das Verhaltnis N-PTH/i-PTH im Vergleich zu gesunden Personen vermindert (p<0,05). Postoperativ war am 1. Tag das Serum-i-PTH starker vermindert als das N-PTH, wodurch das N-PTH/i-PTH-Verhaltnis gegenuber Gesunden zunahm (p<0,05); am 5. Tag normalisierte sich dieses Verhaltnis. Praoperativ verbesserte sich die Supprimierung von i-PTH-Kalzium bei den Patienten, wahrend die Supprimierung von N-PTH-Kalzium normal blieb, was seinen Ausdruck fand in einem unveranderten N-PTH/i-PTH-Verhaltnis wahrend der oralen Kalziumeinnahme. Im Gegensatz dazu vergroserte sich das N-PTH/i-PTH-Verhaltnis in normaler Weise wahrend der Kalziumeinnahme am 5. Tag postoperativ (p<0,05). Schlusfolgerungen: (1) Bei pHPT andert sich die zirkulierende PTH-Immunheterogenitat mit einer vorzugsweisen Freisetzung von i-PTH im Vergleich zu N-PTH, und diese Veranderung normalisiert sich nach Operation. (2) Die Sekretion von i-PTH und N-PTH zeigt unterschiedliche Sensitivitat gegenuber einer Inhibierung durch Kalzium.

Immunoheterogeneity of parathyroid hormone after surgery for primary hyperparathyroidism

Circulating parathyroid hormone (PTH) immunoheterogeneity is altered in primary hyperparathyroidism (pHPT). It is not known, however, whether the relative secretion of various PTH fragments differs between the adenomatous and the non-adenomatous glands in pHPT. We therefore examined the immunoheterogeneity of PTH in patients operated upon because of parathyroid adenoma pre- and 4 days postoperatively during an EDTA-infusion test. Following surgery, baseline levels of amino-terminal PTH (N-PTH) were reduced by a smaller degree than the levels of intact PTH (i-PTH) (P < 0.05) resulting in a higher N/i ratio postoperatively (P < 0.05). Furthermore, the increase in i-PTH and C-PTH fragments during the EDTA infusion test was lower postoperatively than preoperatively (P < 0.05), whereas the increase in N-PTH did not differ. The results therefore suggest that compared with the parathyroid adenoma, the non-adenomatous glands secrete relatively more N-terminal PTH.