Rare plurihormonal Pit-1 adenoma presents as severe isolated clinical hyperthyroidism in 15 year old adolescent

Rachel Palting; Hayley Baines; Kelly Collins

Objective: 15 year old adolescent presented with clinical hyperthyroidism consisting of 6 month weight loss, diarrhea, disrupted sleep, heat intolerance and tremor with objective tachycardia and hypertension. Initial labs demonstrated concomitantly elevated free T4, total T3 and TSH. No concerns for excess growth hormone nor galactorrhea. He was appropriate height for genetic potential and Tanner IV pubertal development. Patient’s presentation led to rare plurihormonal Pit-1 pituitary adenoma despite isolated clinical hyperthyroidism.

Methods: Parents demonstrated normal thyroid function, making presentation suspicious of thyrotropin secreting pituitary adenoma (TSH-oma). Thyroid ultrasound showed a hypervascular goiter without nodules. Patient initiated Atenolol and Methimazole for medical management. Pituitary MRI revealed a 14 mm calcified adenoma. Patient underwent extended endoscopic endonasal resection. Genetic sequencing was pursued.

Results: Diagnostic evaluation revealed elevated TSH, free T4, total T3 and alpha subunit with negative autoimmune studies (Table 1). Prolactin was normal, with appropriate IGF-1, and IGF-BP3 for age and Tanner stage. Alpha subunit/TSH ratio was 0.29, lower than typical TSH-oma ratio of >1. Pre-operatively, Methimazole treatment normalized free T4, while TSH remained elevated. Post resection, TSH decreased to normal and free T4 became low, prompting initiation of Levothyroxine. Alpha subunit became undetectable. Tumor cells were diffusely positive for Pit-1, more than normal pituitary tissue, with many expressing HGH, and few expressing TSH and prolactin.

Table 1 Diagnosis Pre-operative (On methimazole) Day 5 post-operative
TSH (0.40 - 3.98 uIU/mL)	24.23 mU/L	17.88 mU/L	1.24 mU/L
Free T4 (0.6 - 1.2 ng/dL)	>11 ng/dL	0.8 ng/dL	<0.4 ng/dL
Total T3 (87 - 196 ng/dL)	800 ng/dL		34 ng/dL
TSI (<=0.54 IU/L)	<0.10 IU/L
TRAb (<=1.75 IU/L)	<1.00 IU/L
TPO Antibody (0.0-9.0 IU/mL)	<0.4 IU/mL
Tg Antibody (0.0 - 4.0 IU/mL)	>1 IU/mL
Alpha subunit (<0.55)	0.84 ng/mL		<0.15 ng/dL
Prolactin (2.1-17.7 ng/ml)	6.4 ng/dL
IGF-1 (199-537 ng/ml)	253 ng/mL
IGF-BP-3 (2.61-6.31 mg/L)	5.14 mg/L

Conclusion: Initial evaluation was suspicious of TSH-oma, a rare cause of hyperthyroidism and <1% of pituitary adenomas. Furthermore, this case is unique due to isolated clinical and serum hyperthyroidism that contrasts with pathology showing plurihormonal Pit-1 adenoma. This may correlate with the lower alpha subunit/TSH ratio elevation. Genetic sequencing pursued due to reported overlap in TSH-oma with somatic mutation in the THβ gene is pending at time of abstract submission.

IMPE Abstracts

P114