Immunotherapy Endocrine toxicity

 

Thyroid disorders

A. Thyrotoxicosis: ddx Grave's ( persistent eye symptoms indicates new onset Grave's), transient thyroiditis( progresses to hypothyroidism)

- if pt very symptomatic, hold IO

-hydrate, atenolol, metoprolol, NSAIDS for neck pain

-check EKG for Afib

-check anti TSH antibodies, anti TPO antibodies, NM thyroid uptake scan

- refer to endocrinology if considering carbimazole

B. Hypothyroidism: may develop de novo or after a phase of hyperthyroidism

-monitor TSH and FT4 every cycle for 6 months, then every other cycles. Monitor TFT for 1 yr after completion of IO. IV contrast can interfere with TFT. 

- G1: TSH elevated persistently > 4.5 times but less than 10 times. Asymptomatic. OK to monitor. Start levothyroxine if symptoms.

-G2: TSH > 10- start levothyroxine.  Start low dose in those with heart disease or elderly. 

-G3/4: severe symptoms, hospitalization. Hold IO. If central hypothyroidism is suspected i.e pituitary dysfunction ( pt will c/o severe fatigue, headache, visual sx, or loss of libido), always give stress dose steroids before starting levothyroxine. Before starting hormone supplementation, check AM cortisol, ACTH (am) , FT4, TSH

-Imaging:pituitary or sellar cut MRI. Specific to evaluate pituitary fossa if hypophysitis is suspected esp if visual sx. Also will rule out pituitary mets as a cause of hypophysitis rather than IO.

Primary Adrenal insufficiency 

•  low ACTH and low am cortisol suggest pituitary dysfunction. High ACTH and low am cortisol suggests Primary adrenal insufficiency.
• Always look at the CT to make sure no adrenal mets as the cause of adrenal insufficiency
• Stress dose steroids, educate patients on importance of stress dose steroids when sicker

Hypopituitarism

Pituitary dysfunction may present as severe fatigue, headache, visual sx, or loss of libido. 

Before starting hormone supplementation, check AM cortisol, ACTH (am) , FT4, TSH. ACTH stim test may be falsely negative 

Always give stress dose steroids before starting levothyroxine if both cortisol and FT4 are low.

-Imaging:pituitary or sellar cut MRI. Specific to evaluate pituitary fossa if hypophysitis is suspected esp if visual sx. Also will rule out pituitary mets as a cause of hypophysitis rather than IO.

Treatment:

• -saline supplementation
• -stress dose steroids: over 2 months reduce daily dose to less than 7.5 mg 
• -antibiotics as indicated
• -thyroid supplementation after steroids are started
• -estrogen or testosterone supplementation only if no hx of endocrine dependent ca such as breast cancer or prostate ca.

Diabetes mellitus

IO associated immune diabetes is similar to type 1 DM and should be managed as type 1 DM. At risk for DKA and needs insulin.

Acute onset of polyuria, polydipsia, weight loss, and lethargy are characteristic presenting features of diabetes that should be evaluated without delay. Urine ketones, acid base status, and electrolytes can be evaluated as screening for DKA and the need for inpatient evaluation. Antibodies, insulin, and C-peptide levels should also be sent to support diagnosis, although the initiation of therapy should not be delayed pending results.

G1: asymptomatic, blood glucose less than 160, no DKA: Continue IO.

G2: Moderate symptoms but no DKA.  Consult endocrinology.  Send urgently: Urine ketones, CMP to look for anion gap and acid base status, and electrolytes ( hyperkalemia in DKA and adrenal insufficiency) as screening for DKA and the need for inpatient evaluation. Antibodies, insulin, and C-peptide levels.

G3: glucose > 250 , G4: glucose > 500: moderate to severe symptoms, DKA or other abnormalities in electrolytes

Diabetes insipidus: rare, but has been reported.