MON-109 - Biochemical Acromegaly (“Micromegaly”) With Suppressed GH And Discordant Pituitary Pathology: A Diagnostic And Therapeutic Challenge

Case: A 48-year-old woman was referred for evaluation of persistently elevated insulin-like growth factor-1 and progressive symptoms including headaches, fatigue, back pain, and swelling of the hands and feet with difficulty fitting prior ring and shoe sizes. She had been diagnosed with bitemporal hemianopsia months earlier. Pituitary MRI showed 2 subtle hypoenhancing lesions measuring 3 mm and 5 mm, equivocal for microadenomas. IGF-1 levels were elevated on 2 occasions (313 and 361 ng/mL). Oral glucose tolerance testing showed appropriate growth hormone suppression (0.987→0.232 ng/mL ,0.304→0.115 ng/mL). Other pituitary hormones were normal. Her history included BRCA1 and SDHA mutations, and prior hysterectomy with bilateral salpingo-oophorectomy. She subsequently underwent transsphenoidal pituitary resection, complicated by transient diabetes insipidus requiring desmopressin. Pathology initially showed a lactotroph adenoma. Postoperative IGF-1 remained elevated after 5 months (261 ng/mL), and MRI showed a 6-mm residual lesion in the left sella. Recurrence was suspected; gamma knife was offered but she refused. Although she experienced transient symptomatic improvement; fatigue, neuropathic symptoms, visual disturbances, and intermittent acral swelling recurred. Repeat testing demonstrated persistently elevated IGF-1 (265, 328 ng/mL) with suppressible GH. Repeat immunohistochemistry revealed strong GH and PIT-1 staining, suggesting a mixed/plurihormonal adenoma. Cabergoline therapy failed to normalize IGF-1. Lanreotide 90 mg every 28 days was initiated, resulting in partial biochemical improvement (IGF-1 223, 219 ng/mL).

Discussion: This case illustrates biochemical acromegaly (micromegaly), characterized by persistently elevated IGF-1 with suppressible GH and subtle/absent classic phenotypic features. Diagnostic complexity was heightened by equivocal MRI findings and discordant initial pathology. Repeat staining demonstrating GH and PIT-1 reactivity supports intermittent or low-level GH secretion sufficient to drive IGF-1 excess. Persistent biochemical activity despite surgery and dopamine agonist therapy highlights the limitations of single-modality treatment in mixed or plurihormonal adenomas. Partial biochemical response to lanreotide underscores the role of somatostatin receptor ligands even when GH suppression is preserved on dynamic testing. A wide variety of cancers have been associated with elevated IGF 1 levels and acromegaly and given her concerning mutations, starting lanreotide could help reduce cancer risk.

Conclusion: Micromegaly represents an underrecognized form of acromegaly with significant diagnostic and therapeutic challenges. Early recognition and sustained treatment are critical to mitigate long-term morbidity associated with persistent IGF-1 excess including increased cancer risk.

*Unless otherwise noted, all abstracts presented at ENDO must not be released to the press or the public until the date and time of presentation. For oral presentations, the abstracts are embargoed until the session begins. The Endocrine Society reserves the right to lift the embargo on specific abstracts that are selected for promotion prior to or during ENDO.*