PMID- 34663079
OWN - NLM
STAT- MEDLINE
DCOM- 20220322
LR  - 20220322
IS  - 1557-9077 (Electronic)
IS  - 1050-7256 (Print)
IS  - 1050-7256 (Linking)
VI  - 32
IP  - 1
DP  - 2022 Jan
TI  - Cortisol Deficiency in Lenvatinib Treatment of Thyroid Cancer: An Underestimated 
      Common Adverse Event.
PG  - 46-53
LID - 10.1089/thy.2021.0040 [doi]
AB  - Background: Lenvatinib treatment has shown a significant improvement in 
      progression-free survival in patients with metastatic, progressive, 
      radioiodine-refractory differentiated thyroid cancer, although its use is 
      associated with considerable toxicity. Fatigue is one of the most frequent 
      adverse events (AEs). It has been reported that adrenal insufficiency (AI) may be 
      involved in lenvatinib-related fatigue. In our study, we assessed the 
      pituitary/adrenal axis before and during treatment, and the possible involvement 
      of AI in lenvatinib-related fatigue. This was done to clarify the incidence, 
      development, and time course of AI during lenvatinib treatment. Methods: We 
      studied 13 patients who were selected for lenvatinib therapy. Adrenal function 
      was evaluated by measuring cortisol and adrenocorticotropic hormone (ACTH) levels 
      and through the ACTH (250 mug) stimulation test. Results: During treatment, seven 
      patients (54%) developed AI. High levels of ACTH were observed in accordance with 
      the diagnosis of primary AI (PAI). By evaluating the first ACTH test, before 
      starting lenvatinib treatment, we found that patients with <646.6 nmol/L cortisol 
      peak had an increased risk of developing PAI during lenvatinib treatment. Fatigue 
      was observed in 11 patients (84.6%) during lenvatinib treatment. Cortisone 
      acetate treatment induced an improvement in fatigue in six of seven patients 
      (85.7%) in the PAI group, without the need to change the lenvatinib dosage. 
      Conclusions: PAI may be considered one of the most common AEs associated with 
      lenvatinib. Our data strongly suggest that PAI could be involved in 
      lenvatinib-associated fatigue, particularly in patients with extreme fatigue. In 
      this context, early diagnosis of PAI is essential, especially since 
      glucocorticoid replacement therapy can induce a significant improvement in 
      fatigue, without the need to reduce the dosage of lenvatinib. However, further 
      studies are required to confirm these preliminary findings.
FAU - Monti, Salvatore
AU  - Monti S
AD  - Endocrinology and Diabetes Unit, Azienda Ospedaliero-Universitaria Sant'Andrea, 
      "Sapienza" University, Rome, Italy.
FAU - Presciuttini, Federica
AU  - Presciuttini F
AD  - Endocrinology and Diabetes Unit, Azienda Ospedaliero-Universitaria Sant'Andrea, 
      "Sapienza" University, Rome, Italy.
FAU - Deiana, Maria Grazia
AU  - Deiana MG
AD  - Endocrinology and Diabetes Unit, Azienda Ospedaliero-Universitaria Sant'Andrea, 
      "Sapienza" University, Rome, Italy.
FAU - Motta, Cecilia
AU  - Motta C
AD  - Endocrinology and Diabetes Unit, Azienda Ospedaliero-Universitaria Sant'Andrea, 
      "Sapienza" University, Rome, Italy.
FAU - Mori, Fedra
AU  - Mori F
AD  - Endocrinology and Diabetes Unit, Azienda Ospedaliero-Universitaria Sant'Andrea, 
      "Sapienza" University, Rome, Italy.
FAU - Renzelli, Valerio
AU  - Renzelli V
AD  - Endocrinology and Diabetes Unit, Azienda Ospedaliero-Universitaria Sant'Andrea, 
      "Sapienza" University, Rome, Italy.
FAU - Stigliano, Antonio
AU  - Stigliano A
AD  - Endocrinology and Diabetes Unit, Azienda Ospedaliero-Universitaria Sant'Andrea, 
      "Sapienza" University, Rome, Italy.
FAU - Toscano, Vincenzo
AU  - Toscano V
AD  - Endocrinology and Diabetes Unit, Azienda Ospedaliero-Universitaria Sant'Andrea, 
      "Sapienza" University, Rome, Italy.
FAU - Pugliese, Giuseppe
AU  - Pugliese G
AD  - Endocrinology and Diabetes Unit, Azienda Ospedaliero-Universitaria Sant'Andrea, 
      "Sapienza" University, Rome, Italy.
FAU - Poggi, Maurizio
AU  - Poggi M
AD  - Endocrinology and Diabetes Unit, Azienda Ospedaliero-Universitaria Sant'Andrea, 
      "Sapienza" University, Rome, Italy.
LA  - eng
PT  - Journal Article
DEP - 20211231
PL  - United States
TA  - Thyroid
JT  - Thyroid : official journal of the American Thyroid Association
JID - 9104317
RN  - 0 (Phenylurea Compounds)
RN  - 0 (Protein Kinase Inhibitors)
RN  - 0 (Quinolines)
RN  - EE083865G2 (lenvatinib)
RN  - WI4X0X7BPJ (Hydrocortisone)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Drug-Related Side Effects and Adverse Reactions/*complications/diagnosis
MH  - Female
MH  - Humans
MH  - Hydrocortisone/*deficiency/metabolism
MH  - Male
MH  - Middle Aged
MH  - Phenylurea Compounds/*adverse effects/therapeutic use
MH  - Protein Kinase Inhibitors/adverse effects/therapeutic use
MH  - Quinolines/*adverse effects/therapeutic use
MH  - Thyroid Neoplasms/*drug therapy/physiopathology
PMC - PMC8792496
OTO - NOTNLM
OT  - fatigue
OT  - lenvatinib
OT  - primary adrenal insufficiency
OT  - thyroid cancer
COIS- All the authors have nothing to disclose.
EDAT- 2021/10/20 06:00
MHDA- 2022/03/23 06:00
PMCR- 2022/01/17
CRDT- 2021/10/19 05:28
PHST- 2021/10/20 06:00 [pubmed]
PHST- 2022/03/23 06:00 [medline]
PHST- 2021/10/19 05:28 [entrez]
PHST- 2022/01/17 00:00 [pmc-release]
AID - 10.1089/thy.2021.0040 [pii]
AID - 10.1089/thy.2021.0040 [doi]
PST - ppublish
SO  - Thyroid. 2022 Jan;32(1):46-53. doi: 10.1089/thy.2021.0040. Epub 2021 Dec 31.