SAT-158 New Data on High Prevalence and Time of Occurrence of New Onset Hypothyroidism Associated with Mitotane Therapy in a Cohort of Adrenocortical Cancer
Notice bibliographique
Résumé
Abstract Context. Mitotane is a steroidogenesis inhibitor and an adrenocorticolytic drug used to treat adrenocortical cancer (ACC). Central hypothyroidism is recognized in mitotane-treated patients and recent data suggested that mitotane could have an inhibitory effect on TSH-secreting cells in the pituitary gland. Moreover, mitotane may lead to induction of thyroid hormone metabolism. Clinical data on hypothyroidism related to mitotane such as prevalence and time of occurrence was described in a limited number of patients. Objective. To better characterize clinically secondary hypothyroidism in patients with ACC treated with mitotane therapy. Methods. We reviewed retrospectively paper charts and electronic records from patients with histologically confirmed diagnosis of ACC evaluated at our center from 1995-2019. We analysed the pattern of TSH and thyroid function, but also mitotane timing and levels at baseline and during treatment of patients under mitotane therapy. Thyroid hormone assessment including TSH, FT4 and FT3 was performed at least every 3 months during follow-up. Results. Our cohort of 104 patients with ACC includes 84 patients that received mitotane therapy. Among them, thyroid function data was incomplete for 39 cases. Complete data was retrieved from 45 patients. Ten out of 45 (22.2%) patients were already known for primary hypothyroidism and were receiving L-T4 replacement before the initiation of mitotane. Two of 45 (4.4%) patients maintained a normal thyroid function during complete follow up (4.5 years) and 33/45 (73.3%) had new onset hypothyroidism requiring levothyroxine treatment. Of these 33 patients, 22 were females and 11 were males, ranging from 22-74 yo with a median of 46 yo. The number of patients with ENSAT stage I, II, III and IV of disease were 1, 8, 11 and 13 respectively. Thyroid profiles were compatible with central hypothyroidism (low T4 with low or inappropriately normal TSH) in 22/33 patients (66.7%). Interestingly, 6/33 patients (18.2%) developed a TSH elevation with a normal lower-limit or low T4 level. The timeline distribution of the occurrence of hypothyroidism was 21.2% (n:7) at <3 months, 15.2% (n:5) between 3-6 months, 21.2% (n:7) between 6-9 months and 15.2% (n:5) between 9-12 months. 9.1% (n:3) occurred within the second year of treatment (between 12-24 months). However, in 5/33 (15.2%) cases, the exact time of new hypothyroidism onset was undetermined. Conclusion. Mitotane therapy is frequently associated with new onset hypothyroidism with a prevalence of 73% in our cohort of exposed patients and is most likely of central etiology. 72.7% of cases occur in the first year of treatment while 9.1% occur in the second year. This study supports the importance of monitoring thyroid function (including a free T4 level) during the complete course of mitotane therapy.
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Comment cette classification a été obtenuedéplier
Prédiction machine sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Le volet Gemma est une étiquette directe du modèle pour chaque travail de la base, lue sur la notice réduite au titre. Le volet Codex est un classifieur appris des 10 348 étiquettes directes de Codex et calibré sur les taux pondérés de l'échantillon; les champs sans appui suffisant ne portent aucun appel Codex. Le mode candidate est l'union des deux volets; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont pas des étiquettes humaines.
Scores du classifieur distillé par catégorie (deux têtes)
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,000 | 0,003 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,000 |
| Bibliométrie | 0,002 | 0,002 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,001 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,000 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,002 | 0,000 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule source (Gemma direct ou Codex distillé), pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».