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Single-minded homolog 1 (SIM1) is a transcription factor that plays a role in the development of both the hypothalamus and pituitary. SIM1 gene mutations are known to cause obesity in humans, and chromosomal deletions encompassing SIM1 and other genes necessary for pituitary development can cause a Prader–Willi-like syndrome with obesity and hypopituitarism. There have been no reported cases of hypopituitarism linked to a single SIM1 mutation. A 21-month-old male presented to endocrinology clinic with excessive weight gain and severe obesity. History was also notable for excessive drinking and urination. Endocrine workup revealed central hypothyroidism, partial diabetes insipidus, and central adrenal insufficiency. Genetic evaluation revealed a novel mutation in the SIM1 gene. No other genetic abnormalities to account for his obesity and hypopituitarism were identified. While we cannot definitively state this mutation is pathogenic, it is notable that SIM1 plays a role in the development of all three of the patient’s affected hormone axes. He is now 6 years old and remains on treatment for his pituitary hormone deficiencies and continues to exhibit excessive weight gain despite lifestyle interventions.

ABSTRACT: Objective: Inhaled corticosteroids (ICS) are exogenous glucocorticoids that typically have minimal systemic effects at standard doses. They are metabolized by the cytochrome P450 (CYP450) enzyme pathway in the liver; thus, they can cause unwanted side effects when used in conjunction with medications affecting this system. Here, we present a case of adrenal suppression (AS) secondary to combined usage of ICS and posaconazole, a known CYP450 inhibitor. Methods: Clinical and laboratory data were isolated and are presented. Results: A 9-year-old Caucasian female with history of hyper IgE syndrome. On chronic fluticasone and posaconazole for Aspergillus infection, she presented with fatigue and “facial puffiness” (cushingoid features). Low morning cortisol (0.3 μg/dL) prompted further evaluation. Low-dose (1 μg) adrenocorticotropic hormone (ACTH)-stimulation test with peak cortisol level