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Hypopituitarism, which refers to insufficiency of one or more hormones of the pituitary, can be due to myriad causes. The clinical and radiological spectrum of the condition is heterogeneous, based on the patient’s age, gender, clinical setting, and/or other past medical history. Hypopituitarism includes central hypocortisolism, hypothyroidism, hypogonadism, and growth hormone deficiency. Both hypo- and hyperprolactinemia can be associated with hypopituitarism, with low prolactin signifying more extensive pituitary damage. Posterior pituitary insufficiency (arginine vasopressin deficiency) occurs either in isolation or with anterior pituitary hormone deficiency. Clinical symptomatology of hypopituitarism is usually nonspecific and insidious in onset and progression. Overall, the most common cause of hypopituitarism is a pituitary adenoma and/or its management (surgery, radiotherapy, pharmacotherapy, or a combination of these). However, it is this subset of patients which is more likely to be identified and managed in a timely manner, possibly alleviating the premature mortality associated with hypopituitarism. What is more challenging is the recognition of hypopituitarism in less common settings, which may be either due to direct involvement of the pituitary (infection, traumatic brain injury, or infiltrative causes) or indirectly as a consequence of the primary process (thalassemia, vasculotoxic snakebite, subarachnoid hemorrhage). These entities are often under-recognized, and increased awareness can help in greater recognition of the burden. Further, pituitary insufficiency in most of these settings is dynamic and may progress, or rarely, show recovery of function. This renders complexity to the problem, but makes it even more imperative to suspect, screen, and appropriately manage patients with less common causes of hypopituitarism.

Context Temozolomide (TMZ) is endorsed as the treatment of choice in aggressive or malignant pituitary adenomas. Objective Herein we describe a case of an aggressive prolactinoma that was resistant to TMZ. We performed a literature review of similar nonresponsive, aggressive prolactinomas. Methods A 40-year-old woman presented with a giant prolactinoma that required cabergoline, transsphenoidal surgery, and radiotherapy to achieve near-normal prolactin and apparently no residual tumor. A year later, she presented with multiple cranial nerve involvement due to a recurrent tumor extending to the infratemporal fossa. She underwent transfrontal surgery, second radiotherapy, and was started on TMZ. Despite 8 cycles of temozolomide (200 mg/m2, 5/28-day cycle), she had progressive disease and ultimately succumbed to the disease. PubMed/MEDLINE, Google Scholar, and prior review articles were searched for manuscripts about patients with aggressive prolactinomas who had been treated with TMZ. Data on demography, duration of therapy, and management outcomes were analyzed in those with progressive disease. Results We identified 94 cases of patients with aggressive/malignant prolactinomas in the literature who had received TMZ. Progressive disease despite TMZ was present in 36 cases (38%). There was a male preponderance (65%) among these and 40% had aggressive prolactinomas, whereas the rest had carcinomas. Patients received a median of 8 cycles (interquartile range, 3.5-11.5) of TMZ. O6-methylguanine-DNA-methyltransferase (MGMT) immunostaining was negative in 35%. Overall mortality at the time of publication was 40%, at a duration varying from 2 to 20 years from diagnosis. Conclusion TMZ resistance in aggressive/malignant prolactinomas is challenging. Progressive disease on optimal TMZ treatment entails the use of newer agents.

Context To diagnose and monitor GH-related disorders, serum IGF-I is a cornerstone, but Indian ethnicity based data, following consensus criteria for establishment of normative data are not available. Objectives To generate normative IGF-I data for chronological age (CA), Tanner stage and bone age (BA) [Greulich & Pyle (GP)] for both genders. Setting and Participants: We conducted a cross-sectional epidemiological study for Indian children (age 5-18 years) that included 2226 apparently normal subjects (1145 males; 1081 females). We used robust clinical exclusion criteria initially and later statistically we removed outliers separately for Age,Tanner Stage & Bone age using software SPSS 26. 0. Outcome Measures:: Serum IGF-I (ng/ml) using the Roche ECLIA & Immunodiagnostic Systems & Immunoassay System (IDS iSYS) were measured and normative data for 2.5th, 5th,10th, 25th, 50th (median), 75th, 90th, 95th and 97.5th centiles were generated. Results Age- and gender-specific serum IGF-I normative data generated from a uniquely large cohort reflected various patterns. With Roche assay, females (n=910) had IGF-I median peak at 13 years (356.85) [BA (n=804) at 14 years (401.5 ng/mL)] and & Tanner (n = 936) stage IV (368) while males (n=959) had median peak at 14 years (329.5) [BA (n=906) at 15 years (351 ng/mL)] & Tanner (n = 986) stage III (311. 0). With IDS iSYS assay, females had IGF-I median peak at Age (n=913) 13 years (397.5), Tanner (n=941) stage IV (418.5) and GP BA (n=843) 14 years (448.5) and males had median peak at Age (n=974) 14 years (376), Tanner (n=1003) stage III (367) and GP BA (n=909) 15-16 years (383). Females had earlier rise & peak and higher IGF-I values with both assays. In Tanner-specific data maximum difference noticed between stage II and III in both genders with both assays. On comparison of both assays, IGF-1 median peak was achieved at similar ages and Tanner stage but all the values are higher with IDS iSYS assay. When reviewed published literature on Caucasians, females had IGF-I median peak at 15 years (300.1) and Tanner stage III (382.8) and males had median peak at 15 years (318.3) and Tanner stage IV (439). The Indian & Caucasian IGF-1 normative data clearly demonstrates that every ethnicity has a unique pattern of growth. Conclusions The normative data on serum IGF-I are ethnicity-specific and it will improve the diagnostic utility of IGF-I in evaluation and management of growth disorders in Indian Children. Using both age- and Tanner stage-specific normative data simultaneously can improve diagnostic work-up. Presentation: Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.