PMID- 36809657
OWN - NLM
STAT- MEDLINE
DCOM- 20230717
LR  - 20231213
IS  - 1720-8386 (Electronic)
IS  - 0391-4097 (Print)
IS  - 0391-4097 (Linking)
VI  - 46
IP  - 8
DP  - 2023 Aug
TI  - Adrenal insufficiency in thyroid cancer patients treated with tyrosine kinase 
      inhibitors and detected by ACTH stimulation test.
PG  - 1663-1671
LID - 10.1007/s40618-023-02025-3 [doi]
AB  - PURPOSE: Advanced thyroid cancer patients treated with tyrosine kinase inhibitors 
      (TKI) can develop several adverse events (AEs), including adrenal insufficiency 
      (AI). METHODS: We studied 55 patients treated with TKI for radioiodine-refractory 
      or medullary thyroid cancer. The adrenal function was evaluated during follow-up 
      by performing serum basal ACTH, and basal and ACTH-stimulated cortisol. RESULTS: 
      Twenty-nine/55 (52.7%) patients developed subclinical AI during TKI treatment as 
      demonstrated by a blunted cortisol response to ACTH stimulation. All cases showed 
      normal values of serum sodium, potassium and blood pressure. All patients were 
      immediately treated, and none showed an overt AI. Cases with AI were all negative 
      for adrenal antibodies and did not show any adrenal gland alteration. Other 
      causes of AI were excluded. The onset time of the AI, as measured in the subgroup 
      with a first negative ACTH test, was < 12 months in 5/9 (55.6%), between 12 and 
      36 months in 2/9 (22.2%) and > 36 months in 2/9 (22.2%) cases. In our series, the 
      only prognostic factor of AI was the elevated, although moderate, basal level of 
      ACTH when the basal and stimulated cortisol were still normal. The glucocorticoid 
      therapy improved fatigue in most patients. CONCLUSIONS: Subclinical AI can be 
      developed in > 50% of advanced thyroid cancer patients treated with TKI. This AE 
      can develop in a wide period ranging from < 12 to > 36 months. For this reason, 
      AI must be looked for throughout the follow-up to be early recognized and 
      treated. A periodic ACTH stimulation test, every 6-8 months, can be helpful.
CI  - (c) 2023. The Author(s).
FAU - Valerio, L
AU  - Valerio L
AUID- ORCID: 0000-0001-7723-7020
AD  - Department of Clinical and Experimental Medicine, Unit of Endocrinology, 
      University of Pisa, Via Paradisa 2, 56124, Pisa, Italy.
FAU - Giani, C
AU  - Giani C
AD  - Department of Clinical and Experimental Medicine, Unit of Endocrinology, 
      University of Pisa, Via Paradisa 2, 56124, Pisa, Italy.
FAU - Matrone, A
AU  - Matrone A
AD  - Department of Clinical and Experimental Medicine, Unit of Endocrinology, 
      University of Pisa, Via Paradisa 2, 56124, Pisa, Italy.
FAU - Pontillo-Contillo, B
AU  - Pontillo-Contillo B
AD  - Diagnostic and Interventional Radiology Department of Translational Research and 
      New Technologies in Medicine and Surgery, University of Pisa, Via Paradisa 2, 
      56124, Pisa, Italy.
FAU - Minaldi, E
AU  - Minaldi E
AD  - Department of Clinical and Experimental Medicine, Unit of Endocrinology, 
      University of Pisa, Via Paradisa 2, 56124, Pisa, Italy.
FAU - Agate, L
AU  - Agate L
AD  - Department of Clinical and Experimental Medicine, Unit of Endocrinology, 
      University of Pisa, Via Paradisa 2, 56124, Pisa, Italy.
FAU - Molinaro, E
AU  - Molinaro E
AD  - Department of Clinical and Experimental Medicine, Unit of Endocrinology, 
      University of Pisa, Via Paradisa 2, 56124, Pisa, Italy.
FAU - Elisei, R
AU  - Elisei R
AUID- ORCID: 0000-0002-5333-9257
AD  - Department of Clinical and Experimental Medicine, Unit of Endocrinology, 
      University of Pisa, Via Paradisa 2, 56124, Pisa, Italy. 
      rossella.elisei@med.unipi.it.
LA  - eng
GR  - Prot. 2017YTWKWH/PRIN 2017: New insights into the molecular signature of 
      differentiated thyroid cancer: implications for diagnosis, prognosis and therapy/
GR  - IG 2018/Associazione Italiana per la Ricerca sul Cancro/
GR  - Cod 21790/Associazione Italiana per la Ricerca sul Cancro/
PT  - Journal Article
DEP - 20230221
PL  - Italy
TA  - J Endocrinol Invest
JT  - Journal of endocrinological investigation
JID - 7806594
RN  - WI4X0X7BPJ (Hydrocortisone)
RN  - 0 (Tyrosine Kinase Inhibitors)
RN  - 0 (Iodine Radioisotopes)
RN  - 9002-60-2 (Adrenocorticotropic Hormone)
SB  - IM
MH  - Humans
MH  - Hydrocortisone
MH  - Tyrosine Kinase Inhibitors
MH  - Iodine Radioisotopes
MH  - Adrenocorticotropic Hormone
MH  - *Adrenal Insufficiency/chemically induced/diagnosis
MH  - *Thyroid Neoplasms/drug therapy
PMC - PMC10348921
OTO - NOTNLM
OT  - ACTH
OT  - Adrenal insufficiency
OT  - Adverse event
OT  - Cortisol
OT  - Thyroid cancer
OT  - Tyrosine kinase inhibitors
COIS- R.E. is a consultant for EISAI, IPSEN, Loxo and Bayer; the present study was not 
      conditioned by this activity. The other authors have nothing to disclose.
EDAT- 2023/02/23 06:00
MHDA- 2023/07/17 06:42
PMCR- 2023/02/21
CRDT- 2023/02/22 14:00
PHST- 2022/08/09 00:00 [received]
PHST- 2023/01/25 00:00 [accepted]
PHST- 2023/07/17 06:42 [medline]
PHST- 2023/02/23 06:00 [pubmed]
PHST- 2023/02/22 14:00 [entrez]
PHST- 2023/02/21 00:00 [pmc-release]
AID - 10.1007/s40618-023-02025-3 [pii]
AID - 2025 [pii]
AID - 10.1007/s40618-023-02025-3 [doi]
PST - ppublish
SO  - J Endocrinol Invest. 2023 Aug;46(8):1663-1671. doi: 10.1007/s40618-023-02025-3. 
      Epub 2023 Feb 21.