Thyroidectomized patients on LT-4 therapy with advanced medullary thyroid carcinoma treated with selpercatinib show peculiar variations of thyroid function tests

Alessandro Prete; Carla Gambale; Sessa Maria Rita; Cristina Romei; Jaqueline Almeida; Eleonora Molinaro; Rossella Elisei; Antonio Matrone

doi:10.1530/endoabs.101.PS1-05-07

PS1-05-07

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Endocrine Abstracts (2024) 101 PS1-05-07 | DOI: 10.1530/endoabs.101.PS1-05-07

ETA2024 Poster Presentations Clinical thyroid cancer research-1 (10 abstracts)

Thyroidectomized patients on LT-4 therapy with advanced medullary thyroid carcinoma treated with selpercatinib show peculiar variations of thyroid function tests

Alessandro Prete ¹ , Carla Gambale ² , Maria Rita Sessa ³ , Cristina Romei ² , Jaqueline Almeida ² , Eleonora Molinaro ² , Rossella Elisei ² & Antonio Matrone ²

Err

Author affiliations

¹Endocrine Unit, University Hospital of Pisa, Department of Clinical and Experimental Medicine, Pisa, Italy; ²Endocrine Unit, University Hospital of Pisa; ³Chemistry and Endocrinology Laboratory Unit, University Hospital of Pisa

Objectives: In clinical trials assessing efficacy and safety of the highly selective RET inhibitor selpercatinib (Libretto-001 and 531), hypothyroidism was often described. We aimed to evaluate the variation of thyroid function tests (TFTs) in patients with advanced progressive medullary thyroid carcinoma (MTC) treated with selpercatinib at the Unit of Endocrinology of Pisa University Hospital.

Methods: We evaluated clinical and biochemical data of 19 thyroidectomized patients with advanced MTC who started selpercatinib treatment between June 2019 and January 2022. TFTs (fT4, fT3 and TSH) were measured at baseline and at each following evaluation.

Results: Most of the patients were males (68.4%) and, median age at selpercatinib treatment beginning was 54 years. Two patients passed away after 6 and one after 12 months of treatment. During the treatment, all patients showed TFTs alterations. After one month of treatment, in 4/19 (30.8%) patients L-T4 dosage was increased (median 28.5 mg/daily) due to increase in TSH values (>15 mUI/mL), and they were excluded from the following analyses. In the remaining 15 patients, after one month of treatment, TSH significantly increased and fT3 significantly decreased compared with baseline, without significant variation in fT4 levels (Table 1). During a median follow-up of 35 months, TSH levels progressively returned in the referral ranges after a median of 5 months of treatment, but this trend was not observed in fT3 levels (Table 1). Of note, levels of fT4 progressively increased (Table 1).

Table 1 Trends of TFTs during selpercatinib treatment
	Baseline (n = 15)	1 month (n = 15)	12 months (n = 13)	24 months (n = 12)	36 months (n = 8)
TSH mUI/mL (median, IQR)	0.67 (0.27-1.55)	6.68 (3.17-10.5)	2.57 (0.61-9.4)	3.06 (0.44-3.83)	3.05 (0.29-13.79)
p value vs baseline	-	< 0.001	0.063	0.11	0.08
fT3 ng/dL (median, IQR)	3.69 (2.96-4.19)	2.45 (2.1-2.78)	2.33 (2.05-2.76)	2.46 (2.25-2.66)	2.68 (2.40-3.12)
p value vs baseline	-	< 0.001	< 0.001	< 0.001	0.016
fT4 ng/l (median, IQR)	1.38 (1.10-1.63)	1.53 (1.36-1.70)	1.79 (1.65-2.17)	2.05 (1.87-2.51)	1.63 (1.56-2.24)
p value vs baseline	-	0.25	0.0011	< 0.001	0.025
fT3/fT4 ratio (median, IQR)	0.32 (0.31-0.35)	0.19 (0.16-0.25)	0.15 (0.13-0.19)	0.14 (0.13-0.15)	0.18 (0.15-0.21)
p value vs baseline	-	< 0.001	< 0.001	< 0.001	< 0.001
IQR: interquartile range

Conclusions: Selpercatinib treatment induces variations of TFTs in all thyroidectomized patients. The typical landscape is characterized by an early increase of TSH and decrease of fT3 levels. In a follow-up of about 3 years, TSH spontaneously returned in the normal values, while fT3 levels were slightly below and ft4 levels slightly above the normal ranges. Therefore, a careful follow-up should be performed avoiding a hurried increase in L-T4 and/or L-T3 treatment, which should be reserved only for selected cases.