Central adrenal insufficiency: open issues regarding diagnosis and glucocorticoid treatment

Abstract

Background Central adrenal insufficiency (CAI) is characterized by impaired adrenocorticotropin (ACTH) secretion because of a disease or injury to the hypothalamus or the pituitary, leading to a reduced cortisol production. CAI suspicion arises more frequently in patients with pituitary tumors, cranial irradiation/surgery/injury/infections, as well as after exogenous glucocorticoid withdrawal. Nevertheless, a late diagnosis is not uncommon because CAI may present with nonspecific signs or symptoms, as fatigue or hyponatremia. Content The PubMed database was searched (years 1980–2018), using “central adrenal insufficiency” and “ACTH deficiency” as keywords. Subsequently, reference sections of the retrieved articles were searched. Summary Dynamic tests are needed when morning basal cortisol levels are not sufficient to exclude or to confirm CAI. Short Synacthen Test (SST) is the most used, and Endocrine Society’s guidelines recommend a cortisol peak >500 nmol/L to exclude CAI. Despite thresholds, understanding the pretest probability of ACTH deficiency (the clinical background of the patient) is essential because the diagnostic accuracy of SST in case of a negative result is suboptimal. Glucocorticoid replacement therapy, able to replicate cortisol circadian rhythm, is required in patients with CAI; fludrocortisone treatment is not necessary. Short-acting glucocorticoid drugs (hydrocortisone or cortisone acetate) are the most used; lower doses than previously used are nowadays recommended to reduce cortisol-related comorbidities. Promising results have been obtained with modified-release hydrocortisone, especially regarding glucose metabolism in patients with primary adrenal insufficiency. Outlook An accurate clinical diagnosis and a careful individualized therapy are mandatory in patients with CAI.

What factors have impact on glucocorticoid replacement in adrenal insufficiency: a real-life study

“…The shift to MRHC was generally well tolerated except for three patients that preferred the previous treatment. The observation that patients with pAI were more frequently treated with MRHC than those with sAI both at baseline and at the end of the study is not completely unexpected since MRHC has been extensively studied only in pAI [33] while data in sAI are less conclusive. Mongioì et al have recently reported a less beneficial effect on metabolic profile in sAI patients treated with MRHC [34], although also in these patients was reported a maintained improvement in the clinical condition and subjective well-being.…”

Hypothalamus-pituitary Dysfunction as an Independent Risk Factor for Postoperative Central Nervous System Infections in Patients with Sellar Region Tumors

“…As our multivariate logistic regression analysis indicated, postoperative adrenal insu ciency signi cantly affected the occurrence of PCNSI [20,21]. According to a previous study, much of the excess mortality in patients with adrenal insu ciency is attributable to infectious diseases [22].…”

Clinical presentation and management of acromegaly in elderly patients

“…[24] Central adrenal insufficiency was evaluated with basal serum cortisol or after a short Synacthen test when appropriate. [25] Diagnosis of other hormone deficiencies (central hypothyroidism or hypogonadism) was based on low or inappropriately normal pituitary hormone levels with lower than normal serum fT4 or gonadal steroid hormones.…”