Although rarely reported in medical literature, lysosomal acid lipase deficiency (LAL-D) is one of many possible genetic causes of adrenal insufficiency.

LAL-D has a very specific way in which it causes adrenal disease. In a recently published review, Nisticò and colleagues explained: “In LAL-D, adrenal insufficiency is due to calcification of the adrenal gland as a result of the accumulation of esterified lipids; in infantile form, that is Wolman disease, hepatosplenomegaly with hepatic fibrosis and malabsorption lead to death in the first year of life, if not treated with enzyme replacement therapy such as sebelipase alfa.” 

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It is worth noting that adrenal insufficiency is not one of the main presenting signs of LAL-D. “Common presenting symptoms in the late-onset form include dyslipidemia (elevated low-density lipoprotein, low high-density lipoprotein), elevated liver transaminases, hepatomegaly, and splenomegaly,” Wilson and colleagues wrote in another review. These medical issues require far more urgent attention, as they can lead to increased morbidity and mortality. 

In this article, we will be looking at the clinical manifestations of adrenal insufficiency and how it can be treated. 

Features of Adrenal Insufficiency 

In a review published in The Lancet, Husebye and colleagues summed up the characteristic features of adrenal insufficiency as follows: “Hallmark clinical features are unintentional weight loss, anorexia, postural hypotension, profound fatigue, muscle and abdominal pain, and hyponatraemia. Additionally, patients with primary adrenal insufficiency usually develop skin hyperpigmentation and crave salt.” 

In pediatric patients, these hallmark clinical features may not be so prominent. In fact, adrenal insufficiency is notoriously both underdiagnosed and misdiagnosed. Oftentimes, the vague presentation of symptoms prompts physicians to suspect other endocrine causes. 

“Children can be initially misdiagnosed as having sepsis, metabolic disorders, or cardiovascular disease, highlighting the need to consider adrenal dysfunction as a differential diagnosis for an unwell or deteriorating infant,“ Nisticò et al wrote. “With age-related items, clinical features depend on the type of adrenal insufficiency (primary or central) and could manifest in an acute or chronic setting.” 

Read more about LAL-D epidemiology 

The general rule here is that the younger the patient, the more likely it is that adrenal insufficiency is missed. While pediatric patients may present with the symptoms as described above, neonates typically present with failure to thrive and hypoglycemia associated with seizures. The list of differentials for this group of symptoms are rather extensive.

In any case, this condition can be life-threatening. Nisticò and colleagues wrote, “In newborns, cortisol deficiency causes delayed bile acid synthesis and transport maturation, determining prolonged cholestatic jaundice with persistently raised serum liver enzymes.” 

It is safe to say that in a patient diagnosed with LAL-D, symptoms such as failure to thrive and metabolic disorders can easily be mistaken for being complications of the disease and hence receive less medical attention. If physicians can be skilled enough to recognize adrenal insufficiency as a distinct disease that needs to be managed effectively, then a more holistic treatment regime can be developed.

Treating Adrenal Insufficiency

The treatment protocol for adrenal insufficiency is well-documented and has stood the test of time.

“Patients with primary adrenal insufficiency are deficient in glucocorticoids and mineralocorticoids and require replacement of both, together with salt intake as needed. By contrast, individuals with ACTH deficiency due to pituitary or hypothalamic dysfunction after exogenous steroid use usually require only glucocorticoid replacement,” Husebye and colleagues wrote. 

It is possible for patients with adrenal insufficiency to experience adrenal crises, which can be life-threatening. Once suspected, emergency treatment should be administered with haste. “Hydrocortisone should be administered as soon as possible with an intravenous bolus of 4 mg/kg followed by a continuous infusion of 2 mg/kg/day until stabilization. In the alternative, it can be administered as a bolus every four hours intravenously or intramuscularly,” Nisticò et al wrote. 

In addition, patient education plays a central role in helping patients understand how to manage their medical condition under every circumstance. For example, patients should be advised on how to increase their medications when experiencing intercurrent illness or profound stress. Husebye et al wrote, “It is good practice for physicians to provide patients with a steroid card, parenteral hydrocortisone, and training for parenteral hydrocortisone administration, in case of vomiting or severe illness.” This can go a long way in the prevention of adrenal crises. 

Monitoring the efficacy of glucocorticoid therapy, especially in pediatric patients, is especially important. Nisticò and colleagues wrote, “Monitoring glucocorticoid therapy is based on growth, weight gain, and well-being. Cortisol measurements are usually not useful, apart from cases when a discrepancy between daily doses and patient symptoms exists.” Even when dosing is adjusted, some pediatric patients still experience periods of low cortisol concentrations and its corresponding manifestations. 

The main takeaway from this article is that adrenal insufficiency can occur as a direct result of a LAL-D pathology. This knowledge should alert physicians to investigate possible symptoms of adrenal insufficiency and commence treatment accordingly. 

References

Wilson DP, Patni N. Lysosomal acid lipase deficiency. In: Feingold KR, Anawalt B, Boyce A, et al. eds. Endotext [Internet]. MDText.com, Inc.; 2020. Accessed January 21, 2022.

Nisticò D, Bossini B, Benvenuto S, Pellegrin MC, Tornese G. Pediatric adrenal insufficiency: Challenges and solutionsTher Clin Risk Manag. 2022;18:47-60. doi:10.2147/TCRM.S294065

Husebye ES, Pearce SH, Krone NP, Kämpe O. Adrenal insufficiency. Lancet. 2021;397(10274):613-629. doi:10.1016/S0140-6736(21)00136-7