Latent Adrenal Insufficiency: From Concept to Diagnosis

Abstract

Primary adrenal insufficiency (PAI) is a rare disease and potentially fatal if unrecognized. It is characterized by destruction of the adrenal cortex, most frequently of autoimmune origin, resulting in glucocorticoid, mineralocorticoid, and adrenal androgen deficiencies. Initial signs and symptoms can be nonspecific, contributing to late diagnosis. Loss of zona glomerulosa function may precede zona fasciculata and reticularis deficiencies. Patients present with hallmark manifestations including fatigue, weight loss, abdominal pain, melanoderma, hypotension, salt craving, hyponatremia, hyperkalemia, or acute adrenal crisis. Diagnosis is established by unequivocally low morning serum cortisol/aldosterone and elevated ACTH and renin concentrations. A standard dose (250 µg) Cosyntropin stimulation test may be needed to confirm adrenal insufficiency (AI) in partial deficiencies. Glucocorticoid and mineralocorticoid substitution is the hallmark of treatment, alongside patient education regarding dose adjustments in periods of stress and prevention of acute adrenal crisis. Recent studies identified partial residual adrenocortical function in patients with AI and rare cases have recuperated normal hormonal function. Modulating therapies using rituximab or ACTH injections are in early stages of investigation hoping it could maintain glucocorticoid residual function and delay complete destruction of adrenal cortex.

On Primary Adrenal Insufficiency with Normal Concentrations of Cortisol – Early Manifestation of Addison’s Disease

“…Younes et al quoted that there might be a preclinical stage in the diagnosis of AI where only an abnormal concentration of antibodies against adrenocortical tissue is found 21 . All our cases, however, presented with symptoms and a normal or even paradoxically high-normal or even elevated concentration of cortisol as well.…”

Newly diagnosed autoimmune Addison’s disease in a patient with COVID-19 with autoimmune disseminated encephalomyelitis

“…The risk is likely further increased by the advanced age. Autoimmune adrenalitis, on the other hand, usually occurs at younger ages, with an average of 40 years old (30–50 years) 28 46–48. Therefore, in younger patients with COVID-19 presenting with adrenal insufficiency, it is pertinent to consider autoimmune adrenalitis as an aetiology.…”

Progress in Primary Aldosteronism 7: No better time to meet!

“…The article of Younes et al analyses the role of different selectivity and lateralization indices during adrenal vein sampling on guiding surgical decision towards adrenalectomy in primary aldosteronism 23 . Current clinical guidelines recommend that adrenal vein sampling may not be necessary in patients younger than 35 years who have marked aldosteronism and a solitary adrenal adenoma on imaging.…”