Central adrenal insufficiency: who, when, and how? From the evidence to the controversies - an exploratory review

ABSTRACT Central adrenal insufficiency (CAI) is a life-threatening disorder. This occurs when ACTH production is insufficient, leading to low cortisol levels. Since corticosteroids are crucial to many metabolic responses under organic stress and inflammatory conditions, CAI recognition and prompt treatment are vital. However, the diagnosis of CAI is challenging. This is not only because its clinical presentation is usually oligosymptomatic, but also because the CAI laboratory investigation presents many pitfalls. Thus, the clarification of when to use each test could be helpful in many contexts. The CAI challenge is also involved in treatment: Several formulations of synthetic steroids exist, followed by the lack of a biomarker for glucocorticoid replacement. This review aims to access all available literature to synthesize important topics about who should investigate CAI, when it should be suspected, and how CAI must be treated.

Tratamiento sustitutivo en la insuficiencia suprarrenal crónica / Replacement treatment for chronic adrenal failure

La insuficiencia suprarrenal crónica es una enfermedad que se caracteriza por el déficit de las hormonas de la corteza adrenal. Necesita tratamiento sustitutivo de por vida para lograr suplir ese déficit y así poder desarrollar una vida normal y con calidad. Para el éxito del tratamiento sustitutivo es muy importante conocer sus pautas y variantes, lo que resulta un arma en el trabajo diario de los galenos. Conocer las tendencias actuales resulta algo imprescindible, por lo que el propósito del siguiente trabajo es revisar las diferentes variantes del tratamiento que se pueden usar en este grupo de enfermos(AU)

Chronic adrenal failure is a disease characterized by shortage of adrenal cortex hormones. It requires lifelong replacement treatment to overcome this shortage in order to enjoy quality normal life. For the replacement treatment to be successful, it is very important to learn about its guidelines and variants, which is a useful tool in the daily work of physicians. Knowing the present trends is indispensable; therefore, the objective of this paper was to review the different treatment variants that may be used in this group of patients(AU)

Pharmacogenetics of glucocorticoid replacement could optimize the treatment of congenital adrenal hyperplasia due to 21-hydroxylase deficiency

INTRODUCTION: 21-hydroxylase deficiency is an autosomal recessive disorder that causes glucocorticoid deficiency and increased androgen production. Treatment is based on glucocorticoid replacement; however, interindividual variability in the glucocorticoid dose required to achieve adequate hormonal control has been observed. OBJECTIVE: The present study aimed to evaluate the association between polymorphic variants involved inglucocorticoid action and/or metabolism and the mean daily glucocorticoid dose in 21-hydroxylase deficiency patients. METHODS: We evaluated 53 patients with classical forms of 21-hydroxylase deficiency who were receiving cortisone acetate. All patients were between four and six years of age and had normal androgen levels. RESULTS: The P450 oxidoreductase A503V, HSD11B1 rs12086634, and CYP3A7*1C variants were found in 19 percent, 11.3 percent and 3.8 percent of the patients, respectively. The mean ± SD glucocorticoid dose in patients with the CYP3A7*1C and wild-type alleles was 13.9 ± 0.8 and 19.5 ± 3.2 mg/m²/d, respectively. We did not identify an association between the P450 oxidoreductase or HSD11B1 allelic variants and the mean glucocorticoid dose. CONCLUSION: Patients carrying the CYP3A7*1C variant required a significantly lower mean glucocorticoid dose. Indeed, the CYP3A7*1C allele accounted for 20 percent of the variability in the cortisone acetate dose. The analysis of genes involved in glucocorticoid metabolism may be useful in the optimization of treatment of 21-hydroxylase deficiency.

Perioperative management of Cushing's syndrome / 中国实用内科杂志

Surgery is the main treatment for Cushing's syndrome.The disturbed metabolic consequences such as prolonged exposure to excessive glucocorticoid,high glucose and hypertension will add the risks and difficulties to surgery.This paper reviews the perioperative glucocorticoid replacement,correction of the hypercotisolaemia before operation,and prevention of complications after operation.

Determination of Glucocorticoid Replacement Therapy and Adequate Maintenance Dose in Patients with Secondary Adrenal Insufficiency / 대한내분비학회지

BACKGROUND: Determination of the adequate dose of glucocorticoid replacement therapy, in patients with secondary adrenal insufficiency, is of great importance to avoid the consequences of under or over treatment. The aims of this study were: 1) to assess the value of adrenal cortical function tests in determining whether glucocorticoid replacement should be given, and 2) to investigate the adequate maintenance dose of glucocorticoid in patients with secondary adrenal insufficiency. METHODS: Forty patients, with secondary adrenal insufficiency, confirmed by the insulin-induced hypoglycemia test (IHT), were studied. All subjects underwent basal serum cortisol measurement, IHT and 250 g rapid ACTH stimulation tests (AST). The clinical usefulness of these tests, for the determination of glucocorticoid replacement therapy, was evaluated in patients with secondary adrenal insufficiency. 26 of the 40 patients had received prednisolone (Pd) (5 mg per day) replacement due to symptoms from adrenal insufficiency. The dose of Pd was serially changed from 5 to 3.75, and then to 6.25 mg per day, every 3 month. The measured lipid parameters, serum osteocalcin and urinary N-telopeptide were measured and the quality of life evaluated by the administration of an Addisonian questionnaire, both before and after the dose changes. RESULTS: 1) For all tests, cut-offs were selected that would provide adequate specificity and sensitivity. When the cut-offs were set to provide 95% specificity, the corresponding sensitivitycut-off values, obtained with basal serum cortisol, peak serum cortisol in IHT and AST were: 88.4% <5 microgram/dL, 80.7% <11 microgram/dL and 76.9% <16 microgram/dL. 2) The urinary type I collagen N-telopeptide, total cholesterol, HDL- and LDL-cholesterol levels were significantly increased, and the serum osteocalcin levels significantly decreased when the daily dose of Pd was increased to 6.25 from 3.75 or 5 mg. The LDL-cholesterol levels especially, were significantly increased, even though the change in the Pd from 3.75 to 5 mg per day was subtle. CONCLUSION: The basal cortisol levels, HPA axis tests and the symptoms of patients may be helpful to determine whether prednisolone replacement therapy should be given. It is suggest that an adequate dose of glucocorticoid replacement therapy should be not exceed Pd 5mg per day, so as not to have adverse effects on the bone and lipid metabolisms.