Levine, Alice C.

Abstract Concurrent thyrotropin (TSH) secreting and growth hormone (GH) secreting pituitary adenomas are rare entities. Although tumors of the PIT-1 lineage may coexpress TSH and GH, concurrent biologically active secretion resulting in central hyperthyroidism and acromegaly is uncommon. We report the case of a 42-year-old woman presenting with weight loss, palpitations, amenorrhea, and progressive acromegalic features. Biochemical evaluation revealed central hyperthyroidism with elevated free T4 and inappropriately normal TSH, markedly elevated insulin-like growth factor 1 (IGF-1) and GH, hyperprolactinemia, and elevated α-subunit. Pituitary magnetic resonance imaging demonstrated a 2.7-cm macroadenoma with cavernous sinus extension. She underwent transsphenoidal resection without complications. Pathology confirmed a mature plurihormonal PIT-1 lineage adenoma immunopositive for TSH, GH, and prolactin with a Ki-67 of 3%. Immediately postoperatively, thyrotoxicosis and hyperprolactinemia resolved, IGF-1 levels declined, acromegalic features improved, and menses resumed. Over the ensuing months, thyroid and prolactin tests remained within normal range, but the IGF-1 level remained elevated. This case illustrates the rare presentation of a PIT-1 lineage adenoma secreting biologically active TSH, GH, and prolactin. Comprehensive hormonal evaluation and long-term biochemical and radiologic surveillance are essential, given the risk of incomplete remission despite apparent surgical cure.

Abstract Context Crinecerfont, a first-in-class corticotropin-releasing factor type 1 receptor antagonist, is FDA-approved as an adjunct to the physiologic glucocorticoid (GC) required to treat the underlying adrenal insufficiency in patients (≥4 years old) with classic congenital adrenal hyperplasia (CAH). By reducing elevated adrenocorticotropic hormone, crinecerfont controls excess adrenal androgens, thereby enabling lower GC doses. However, there are no published recommendations for how to reduce supraphysiologic GC doses after initiating crinecerfont. This manuscript aims to provide a framework developed by experienced endocrinologists for reducing supraphysiologic GC doses in patients taking crinecerfont. Evidence Acquisition An experienced panel of 11 endocrinologists discussed strategies and considerations when reducing GC doses and developed an algorithm to guide GC dose reductions after introducing crinecerfont in adults with CAH. Evidence Synthesis Approaches to GC reduction should be individualized based on the patient's therapeutic goals, cortisol needs, lifestyle preferences, and the clinician's experience to set appropriate targets for clinical parameters, androgens, and GC dose regimen. In general, GC doses should be reduced gradually to minimize the risks of developing symptoms of GC withdrawal or adrenal insufficiency. GC doses should be adjusted to the lowest level needed to maintain androgens at goal, without reducing below what is needed for cortisol replacement. Practical considerations during GC dose reduction include switching from longer- to shorter-acting GCs (eg, from dexamethasone to hydrocortisone), optimizing dose distribution to mimic normal circadian cortisol exposure, and consolidating or eliminating doses to improve adherence. Conclusion This framework for reducing supraphysiologic GC doses in adult patients taking crinecerfont may become increasingly relevant as treatment of CAH shifts toward physiologic GC replacement with adjunctive control of adrenal androgens.