IMMUNOLOGICAL CROSSFIRE

ENDOCRINOPATHIES IN THE AGE OF IMMUNE CHECKPOINT INHIBITORS

Authors

  • Tharsini Sarvanandan
  • Ying Guat Ooi
  • Jun Kit Khoo
  • Quan Hziung Lim
  • Nicholas Ken Yoong Hee
  • Shireene Vethakkan
  • Lee-Ling Lim
  • Sharmila Paramasivam
  • Jeyakantha Ratnasingam

Keywords:

ENDOCRINOPATHIES, INHIBITORS, IMMUNE

Abstract

INTRODUCTION/BACKGROUND
Pembrolizumab is a PD1 receptor inhibitor which is a type of immune checkpoint inhibitor (ICI) for cancer therapy. Immune-related adverse events (IRAE) are more commonly encountered with increased use.

CASE
A 52-year-old male with recurrent renal cell carcinoma developed endocrinopathies following pembrolizumab. After failure of first-line treatment, he received the first dose of pembrolizumab in November 2022. Six weeks later, he was symptomatic of hyperthyroidism with corresponding biochemistry of TSH <0.01 m IU/L (reference interval 0.55 – 4.8), free T4 of 28.8 pmol/L (reference interval 11.5 – 22.7) and free T3 of 9.7 pmol/L (reference interval 3.5 – 5.5). Following treatment with low dose and tapering carbimazole for eight weeks, he quickly became hypothyroid. Biochemistry showed TSH of 87.3 m IU/L, fT4 of 2.9 pmol/L and fT3 of 1.3 pmol/L. Anti-thyroid peroxidase and anti-thyroglobulin antibodies were negative. Carbimazole was discontinued and levothyroxine 50 mcg daily were commenced. Pembrolizumab was continued. Four months later, he presented with lethargy and postural symptoms. A random serum cortisol level was undetectable at <14 nmol/L (reference interval 145 – 619) and ACTH level was inappropriately normal at 6 pg/ml (reference interval 0 – 46). He denied any polyuria, polydipsia, or symptoms of mass effect. His gonadal function, prolactin and electrolytes were normal. There was marked clinical improvement following hydrocortisone replacement. MRI of the pituitary gland was completely normal. A diagnosis of ICI-induced hypophysitis and thyroiditis was made. He completed the nine cycles of pembrolizumab as initially planned with good cancer response. He remains well on levothyroxine and hydrocortisone replacement.

CONCLUSION
This case illustrates the typical sequelae of ICI-induced endocrinopathy of thyroiditis that occurred earlier and hypophysitis later. All patients in ICI should be monitored at close intervals for hormonal dysfunction and replaced as required.

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Author Biographies

Tharsini Sarvanandan

Endocrine Unit, Department of Medicine, Faculty of Medicine, University Malaya, Kuala Lumpur, Malaysia

Ying Guat Ooi

Endocrine Unit, Department of Medicine, Faculty of Medicine, University Malaya, Kuala Lumpur, Malaysia

Jun Kit Khoo

Endocrine Unit, Department of Medicine, Faculty of Medicine, University Malaya, Kuala Lumpur, Malaysia

Quan Hziung Lim

Endocrine Unit, Department of Medicine, Faculty of Medicine, University Malaya, Kuala Lumpur, Malaysia

Nicholas Ken Yoong Hee

Endocrine Unit, Department of Medicine, Faculty of Medicine, University Malaya, Kuala Lumpur, Malaysia

Shireene Vethakkan

Endocrine Unit, Department of Medicine, Faculty of Medicine,
University Malaya, Kuala Lumpur, Malaysia

Lee-Ling Lim

Endocrine Unit, Department of Medicine, Faculty of Medicine, University Malaya, Kuala Lumpur, Malaysia

Sharmila Paramasivam

Endocrine Unit, Department of Medicine, Faculty of Medicine, University Malaya, Kuala Lumpur, Malaysia

Jeyakantha Ratnasingam

Endocrine Unit, Department of Medicine, Faculty of Medicine, University Malaya, Kuala Lumpur, Malaysia

References

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Published

2024-07-17

How to Cite

Sarvanandan, T., Ooi, Y. G., Khoo, . J. K. ., Lim, Q. H., Hee, N. K. Y. ., Vethakkan, S., … Ratnasingam, J. (2024). IMMUNOLOGICAL CROSSFIRE: ENDOCRINOPATHIES IN THE AGE OF IMMUNE CHECKPOINT INHIBITORS . Journal of the ASEAN Federation of Endocrine Societies, 39(S1), 83–84. Retrieved from https://asean-endocrinejournal.org/index.php/JAFES/article/view/4681

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