Subclinical Thyrotoxicosis and the Heart

Burmeister, Lynn A.; Flores, Angel R.

doi:10.1089/105072502760143872

Cited by 23 publications

(15 citation statements)

References 43 publications

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“…TSHR haploinsufficient mice have osteopenia and enhanced osteoclastogenesis in the face of normal thyroid function (5). Patients with subclinical hyperthyroidism or those oversuppressed with thyroxine have osteoporosis (18). Furthermore, serum TSH levels correlate with fracture risk (2), TSHR polymorphisms correlate with bone mass (3), and even a single TSH injection causes a precipitous drop in resorption markers in the absence of changes in thyroid hormone levels (19).…”

Section: Discussionmentioning

confidence: 99%

Intermittent recombinant TSH injections prevent ovariectomy-induced bone loss

Sun

Vukičević²,

Baliram

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

120

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We recently described the direct effects of thyroid-stimulating hormone (TSH) on bone and suggested that the bone loss in hyperthyroidism, hitherto attributed solely to elevated thyroid hormone levels, could at least in part arise from accompanying decrements in serum TSH. Recent studies on both mice and human subjects provide compelling evidence that thyroid hormones and TSH have the opposite effects on the skeleton. Here, we show that TSH, when injected intermittently into rodents, even at intervals of 2 weeks, displays a powerful antiresorptive action in vivo. By virtue of this action, together with the possible anabolic effects shown earlier, TSH both prevents bone loss and restores the lost bone after ovariectomy. Importantly, the osteoclast inhibitory action of TSH persists ex vivo even after therapy is stopped for 4 weeks. This profound and lasting antiresorptive action of TSH is mimicked in cells that genetically overexpress the constitutively active ligand-independent TSH receptor (TSHR). In contrast, loss of function of a mutant TSHR (Pro 3 Leu at 556) in congenital hypothyroid mice activates osteoclast differentiation, confirming once again our premise that TSHRs have a critical role in regulating bone remodeling.osteoclast ͉ osteoporosis ͉ pituitary ͉ osteoblast ͉ bisphosphonate C linical data available since von Recklinghausen's first description of thyrotoxic bone disease, the strong correlation between fracture risk and serum thyroid-stimulating hormone (TSH), recent evidence that TSH receptor (TSHR) polymorphisms are associated with low bone mass, and evidence that bone loss occurs in patients with subclinical hyperthyroidism with normal and low TSH levels all support a role for low TSH in the pathogenesis of hyperthyroid osteoporosis, hitherto attributed solely to high circulating levels of thyroid hormones (1-4).Evidence supporting this premise comes in parallel from genetically manipulated mice lacking receptors for either TSH or thyroid hormones (5, 6). We demonstrated that TSHR deficiency induces a high-turnover osteoporosis, with elevated bone formation and resorption even in TSHR haploinsufficient mice that have normal thyroid function. We found that in ex vivo cell cultures continually exposed to TSH, both osteoblastic bone formation and osteoclastic bone resorption were suppressed. Although these studies point to a primary function for TSH in skeletal homeostasis, data have reestablished a role for the two thyroid hormone receptor (TR) isoforms, TR␣ and TR␤ (6). The deficiency of TR␣ induces osteosclerosis in adult mice, whereas hyperthyroid TR␤-null mice display osteopenia despite high circulating TSH levels (6). Thus, evidence from human and mouse studies underscore the paradigm that both thyroid hormone excess and low TSH levels contribute to hyperthyroid bone loss (7).Hyperthyroidism can arise from adenomatous or inflammatory diseases of the thyroid or from overzealous replacement with thyroid hormones. Hyperthyroidism is Ϸ10-fold more common in women, with an incidence of 1 in 1,000...

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Section: Discussionmentioning

confidence: 99%

Intermittent recombinant TSH injections prevent ovariectomy-induced bone loss

Sun

Vukičević²,

Baliram

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

120

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“…Zielbereich für das TSH ist bei der primären Hypothyreose der untere Normbereich. Eine TSH-Suppression muss wegen möglicher kardialer [20] und osteogener Nebenwirkungen vermieden werden (Ausnahme: Nachsorge bei differenziertem Schilddrüsenkarzinom, hier ist die TSH-Suppression Therapieziel!). Parle et al [21] fanden in einer 10-Jahres-Beobachtungsstudie eine deutlich erhöhte kardiovaskuläre Mortalität bei Untersuchten älter als 60 Jahre,die zu Beginn der Studie ein supprimiertes TSH hatten.Nach Erreichen einer stabilen Euthyreose ist eine Kontrolle des TSH (fT 4 ) alle 6-12 Monate ausreichend.…”

Section: Substitution Von Wachstumshormonunclassified

Substitutionstherapie mit Hormonen

2003

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Die Behandlung von Patienten mit Hormonausfällen und ihre Substitution ist für den endokrinologisch tätigen Arzt eine wesentliche Aufgabe. Dabei kann der Substitutionsbedarf einzelne oder, z. B. bei Erkrankungen der Hypophyse, mehrere Hormone betreffen. Die Frage, ob eine Hormonsubstitution erfolgen sollte, ist von zahlreichen Faktoren wie Alter, Geschlecht und Begleiterkrankungen des Patienten abhängig. Unumstritten ist die Notwendigkeit einer Substitution mit Hydrokortison bei Nachweis einer Nebennierenrindeninsuffizienz oder mit L-Thyroxin bei einer Hypothyreose bei allen Patienten. Die Substitution mit Östrogen-oder Testosteronpräparaten ist im jüngeren Alter für das physische und psychische Wohlbefinden und für den Erhalt der Knochenmasse wesentlich. Bei Patienten mit gesichertem Wachstumshormonmangel sollte die Therapie möglichst im Rahmen von Verlaufsbeobachtungen erfolgen. Der Einsatz der postmenopausalen Hormonersatztherapie mit Östrogenen muss nach aktuellen Untersuchungen kritisch gesehen werden und ist im Wesentlichen auf die Beseitigung der Symptome in den Wechseljahren gerichtet.

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“…and yet it remains controversial particularly as it relates to its treatment [41,42] and to cardiovascular impact [31,39,[44][45][46][47] nevertheless endogenous subclinical hyperthyroidism has been reported to be associated with decreased left ventricular end diastolic volume, increased left ventricular mass, reduced exercise performance [43,48], increased heart rate [48] and induction of arrhythmias [48] including atrial fibrillation [33][34][35]48] and atrial flutter [10,11]. Furthermore it has also been reported, that in patients with subclinical hyperthyroidism, increased factor X activity [41], increased von Willebrand factor [49] and levels of plasma fibrinogen and D-dimer are significantly higher than in the euthyroidic subjects [50].…”

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confidence: 99%