Isolated Adrenocorticotropin Deficiency Concomitant with Graves' Disease: A Case Report and Literature Review

Abstract

A 73-year-old Japanese woman with untreated Graves' hyperthyroidism developed glucocorticoid-induced adrenal insufficiency (AI) after a supraphysiological dose of prednisolone therapy for bronchial asthma. Days later, she had high plasma adrenocorticotropic hormone (ACTH) levels and was expected to recover from glucocorticoid-induced AI. Her plasma ACTH levels remained high over 3 months during a physiological dose of hydrocortisone replacement. However, she suffered a further decrease in her serum cortisol level and was diagnosed with isolated adrenocorticotropin deficiency (IAD), in which bioinactive ACTH likely caused the high ACTH value. IAD should be considered as an unusual disorder associated with Graves' disease, especially in older patients.

Clinical features and autoimmune associations in patients presenting with Idiopathic Isolated ACTH deficiency

“…However, in this series, pituitary MRI was performed in only 27 of 176 patients, and patients with TBI were not excluded, so it is not possible to be certain whether some patients had other causes of ACTH deficiency. Other case reports have described IIAD with a wide range of autoimmune illnesses, including type 1 diabetes, Crohn's disease and Graves’ disease . However, the most commonly associated autoimmune illness in the literature is hypothyroidism, and the data from our case series are in concordance with this, with 9 of the 23 patients diagnosed with primary hypothyroidism.…”

Isolated Adrenocorticotropic Hormone Deficiency and Primary Hypothyroidism in a Patient Undergoing Long-Term Hemodialysis: A Case Report and Literature Review

“…conventional hemodialysis therapy maintains adequate circulating volume and blood electrolyte levels, thereby masking an otherwise obvious electrolyte imbalance attributable to IAD, such as hyponatremia or normal-to-high potassium levels. In addition to these factors, our patient had a normal morning blood cortisol level and a high ACTH level at the time of diagnosis with IAD, which could also be explained by a combination of incomplete corticotroph failure and immunoreactive but biologically inactive ACTH [11,12], which delayed the diagnosis of IAD. Thus, this case highlights the importance of timely dynamic endocrine testing of hypothalamic-pituitary-adrenal function to provide early diagnosis of possible IAD in hemodialysis patients with symptoms suggestive of adrenal insufficiency, such as anorexia, fatigue, and lethargy, even when they do not exhibit electrolyte imbalances or low morning blood cortisol or ACTH levels.…”

“…For example, there have been 2 reported cases of secondary adrenal insufficiency in children with high plasma ACTH levels, due to the expression of immunoreactive but biologically inactive ACTH caused by mutations in the pro-opiomelanocortin gene [11]. An elderly patient with Hashimoto thyroiditis and IAD exhibiting high plasma ACTH levels has also been described, in whom pituitary autoimmunity was likely responsible for disturbed corticotrophs secreting immunoreactive but biologically inactive ACTH [12]. However, all previous reports of hemodialysis patients with IAD were characterized by low plasma ACTH levels, with the exception of our patient (Table 3).…”

“…Dynamic tests assessing the secretion of anterior pituitary hormones showed normal responses of growth hormone, TSH, and prolactin, as well as age-appropriate secretion of luteinizing hormone and follicle-stimulating hormone; although the basal ACTH level was high, no sufficient ACTH or cortisol release was observed after a corticotropinreleasing hormone load (Table 2C). These findings were suggestive of IAD accompanied by immunoreactive but biologically inactive ACTH [11,12].…”