Addison disease

(adrenal insufficiency)

Rare in children. There are many possible causes:

1.         congenital adrenal hyperplasia (see this term), among which the lipoid adrenal hyperplasia (with female sex and hyperpigmentation) as a result of a mutation of the StAR gene (Stereogenic Acute Regulatory protein) that prevents the transfer of cholesterol from the cytoplasm to the mitochondria 

2         congenital adrenal hypoplasia


-   mutation of the NROB1 gene (Xp21.2) coding for the DAX-1 protein [MIM 300 200]; often associated with hypogonatropic hypogonadism, at the time of adolescence: neonatal salt loss syndrome and hypoglycemia, melanoderma; it can also be observed in cases of Xp21 deletion (or complex glycerolkinase deficiency) [MIM 300 679] where it is associated with glycerolkinase deficiency and Duchenne myopathy (see these terms). At   histologic examination of the adrenals, the adult cortical zone is absent and the presence of enlarged cells (so-called cytomegalic) larger than typical fetal cells is observed.


-         autosomal recessive transmission of a mutation or a deletion of the gene coding for SF1 (9q33) [MIM 184 757], a nuclear receptor regulating the transcription of genes involved in steroidogenesis (such as StAR), male sexual differentiation (such as AMH, DAX1, CYP11A1), those that code for steroid hydroxylases, gonadotropins and aromatase; female phenotype


-         in the context of the IMAGe syndrome [MIM 614 732], acronym for Intrauterine  growth retardation, Metaphyseal dysplasia, congenital Adrenal hypoplasia, Genital abnormalities. Autosomal dominant transmission of a pathogenic variant of the CDKN1C gene (11p15.4) (see this term)


-        in case of familial glucocorticoid deficiency (GCCD for GluCoCorticoid Deficiency): low cortisol levels with ACTH resistance, hyperpigmentation, hypoglycemia; 


five different forms can be distinguished: 


1) GCCD 1 [MIM 202 200]: autosomal recessive transmission of a mutation of the MC2R or ACTHR gene (18p11.21):

2) GCCD2 [MIM 607 398]: autosomal recessive transmission of a mutation of the MRAP gene (21q22).

3) GCCD3 [MIM 609 197] associated with a mutation on 8q11.2-q13.2

4) GCCD4 [MIM 614 736]: autosomal recessive transmission of a mutation of the NNT gene (5p12) coding for  a protein in the internal mitochondrial membrane; mineralocorticoid deficiency is sometimes associated

5) GCCD5 [MIM 617 825]: autosomal recessive transmission of a mutation of the TXNRD2 gene (22q11).


3.         intraadrenall traumatic hemorrhage

4.         secondary to maternal hypercorticism

 

During the first 10 to 15 postnatal days, there is vomiting, sometimes diarrhea, dehydration and salt loss syndrome [hypoNa, hyperK, metabolic acidosis, hypoglycemia, with normal or increased natriuresis and  normal or decreased kaliuresis], fainting. Signs of severity are: cardiovascular collapse, respiratory distress, hypotonia, and convulsions (hypoglycemia).

 

1.         adrenoleucodystrophy (see this term)

2         AAA or Allgrove syndrome (see this term)

3         adrenal failure as part of an autoimmune polyendocrinopathy type I (APECED)

4         pituitary malformations: septo-optic dysplasia, holoprosencephaly (see these terms), craniopharyngioma, mutations  of Prop1 or Pit2

5         familial deficiency in glucorticoids (Migeon syndrome): hyperpigmentation, hypoglycemia

6         infectious origin: tuberculosis or CMV, toxoplasmosis infection due to HIV

7         mitochondrial cytopathy: some cases of Kearns-Sayre syndrome (see this term) 

8         Wolman syndrome, Opitz syndrome (see these terms) 

  

Clinical signs: similar to those of the adult. Fatigue, hypotension, skin hyperpigmentation by hypersecretion of MSH (especially at the level of the flexion creases, at the extension side of the joints and at the level of the gums), abdominal pain, anorexia. Hyponatremia and hyperkalemia. Leukopenia with Lymphocytosis.


       iatrogenic causes: after administration of corticosteroids by exogenous route (corticosteroid therapy, asthma [> 500 µg/day of fluticasone], subcutaneous or intraarticular injections), the endogenous production of corticosteroids is disrupted for a few weeks to several months without any predictable duration.

 

: unexplained hypotension during anesthesia, collapse under stress conditions


Anesthetic implications: 

substitutive opotherapy to be adapted for the level of stress  (school exam, emotional shock, illness, surgery, fever, stay in hot countries, fight against cold). The basic daily needs are estimated at ± 8 mg/m2 of hydrocortisone as a starting dose. However, higher doses are aften necessary for the children presneting with a congenital hyperplasia of the adrenals (10-15 mg/m2). Monitor the glycemia and the blood ions: risk of hyponatremia and kyperkaliemia. Shorten the preoperative fasting period.


 

N.B.: the principle of doubling the dose of corticosteroids on the eve of surgery is not based on any study and is  recommended neither by The Endocrine Society, nor APAGBI, nor the Royal College of Physicians. It is probably better to administer the usual treatment on the morning of surgery and to administer a dose of hydrocortisone (2 mg/kg) (4 mg/kg for the infant less than 30 days of age) at the induction of anesthesia, then:


major surgery:  continuous infusion of  25 mg/day if < 10 kg

                                                                50 mg/day if 11-20 kg

                                                               100 mg/day if > 20 kg and prepubertal

                                                               150 mg/day if > 20kg and puberty is present
                                             200 mg/day if > 70kg


                                         or 2 mg/kg/6h and 1 mg/kg/6h (max 50 mg) in the postop period

*   minor surgery : a dose of hydrocortisone (2 mg/kg) (4 mg/kg in neonates up to 30 days of age) during induction of anesthesia 2 mg /kg. Double the oral dose on refeeding and for 24 hours.
If the child is on corticosteroid therapy equivalent to > 30mg/m2/day hydrocortisone, there's no need to double the dose: simply administer the usual dose of corticosteroid, but watch out for the appearance of adrenal insufficiency.

 


equivalence dosis (mg)

relative power

hydrocortisone

20

1

cortisone

25

0.8

prednisolone

5

4

methylprednisolone

4

5

dexamethasone

0.5 - 0.75

25

Table of equivalence of steroids

 

References : 

-        Todd GR, Acerini CL, Ross-Russell R, Zahra S, Warner JT, McCance D.
Survey of adrenal crisis associated with inhaled corticosteroids in the United Kingdom.
Arch Dis Child 2002; 87:457-61.

-        Shulman DI, Palmert MR, Kemp SF.
Adrenal insufficiency: still a cause of morbidity and death in childhood.
Pediatrics 2007; 119: e484-94.

-        Finken MJJ, Mul D.
Cushings syndrome and adrenal insufficiency after intradermal triamcinolone acetonide for keloid scars.
Eur J Pediatr 201ą; 169: 1147-9.

-        Speiser PW, Azziz R, Baskin LS, Ghizzoni L et al.
Congenital adrenal hyperplasia due to steroid 21-hydroxylase deficiency : an endocrine society clinical practice guideline.
J Clin Endocrinol Metab 2010; 95: 4133-60.

-        Taylor LK, Auchus RJ, Baskin LS, Miller WL.
Cortisol response to operative stress with anesthesia in healthy children.
J Clin Endocrinol Metab 2013; 98: 3687-93. 

-        Liu MM, Reidy AB, Saatee S, Collard CD.
Perioperatice steroid management: approaches based on current evidence.
Anesthesiology 2017; 127: 166-72.

-        Karamchandani K, Leathem J, Sinz E.
Acute adrenal insufficiency in the perioperative period: a case report.
A&A Practice 2019; 12: 63-5.

-        Woodcock T, Barker P, Daniel S, Fletcher S et al.
Guidelines for the management of glucocorticoids during the peri-operative period for patients with adrenal insufficiency.
Anaesthesia 2020, 75:654-663

-        Heath C, Siafarias A, Sommerfield A, von Ungern-Sternberg BS.
Peri-operative steroid management in the paediatric population.
Acta Anaesth Scand 2021; 65:1187-94. 

-        Mushtaq T, Ali SR, Boulos N , Boyle R,Cheetham T et al,
Developed by the Paediatric Adrenal Insufficiency Group on behalf of the British Society for Paediatric Endocrinology and Diabetes (BSPED). Emergency and perioperative management of adrenal insufficiency in children and young people: British Society for Paediatric Endocrinology and Diabetes consensus guidance.
Arch Dis Child 2023 doi:10.1136/ archdischild-2022-325156


Updated July 2023