🫀 Interná medicína · 78

Kortikoterapia vo vnútornom lekárstve

Definícia

• Kortikoterapia je podávanie glukokortikoidov – vo fyziologických dávkach ako substitúcia pri adrenálnej insuficiencii a v suprafyziologických dávkach ako protizápalová a imunosupresívna liečba mnohých chorôb (napr. reumatologických, pľúcnych, hematologických, gastrointestinálnych).

Etiológia a patogenéza

• Indikácie v pneumológii napr.: akútne exacerbácie CHOCHP, ťažká nekontrolovaná astma, zápalové parenchýmové choroby pľúc (napr. hypersenzitívna pneumonitída).
• Orientačne ekvivalentné dávky (ESE/ES 2024): hydrokortizón 20 mg ≈ prednizón 5 mg; prednizón má asi 4-násobnú glukokortikoidovú potenciu hydrokortizónu.
• Aspoň 1 % populácie užíva dlhodobo glukokortikoidy; riziko adrenálnej insuficiencie závisí od dávky, trvania, potencie, spôsobu podania a individuálnej vnímavosti.
• Os hypotalamus–hypofýza–nadobličky môže potlačiť akýkoľvek spôsob podania vrátane perorálneho, lokálneho, inhalačného, intranazálneho, intravenózneho a intraartikulárneho.

Klinický obraz

• Medzi závažnejšie nežiaduce účinky (najmä pri vysokých dávkach a dlhodobom podávaní) patria napr. osteoporóza, supresia nadobličiek, hyperglykémia, dyslipidémia, kardiovaskulárne choroby, Cushingov syndróm, psychické poruchy a imunosupresia.
• Riziko katarakty aj glaukómu je pri glukokortikoidoch zvýšené a zdá sa, že závisí od dávky.
• Príznaky adrenálnej insuficiencie po glukokortikoidoch bývajú nešpecifické a môžu sa prekrývať s príznakmi základnej choroby.
• Pacient s liečbou glukokortikoidmi (súčasnou alebo predchádzajúcou) a prejavmi exogénneho Cushingovho syndrómu sa má považovať za pacienta s glukokortikoidmi indukovanou adrenálnou insuficienciou.

Diagnostika

• Rutinné testovanie adrenálnej insuficiencie sa neodporúča počas suprafyziologických dávok ani ak pacient glukokortikoidy stále potrebuje pre základnú chorobu.
• Ak sa má potvrdiť obnova osi HPA, prvým testom je ranný sérový kortizol.
• Ranný kortizol > 300 nmol/l (10 μg/dl) orientačne svedčí pre obnovu osi HPA a glukokortikoidy možno bezpečne vysadiť (hodnota sa hodnotí ako kontinuum, nie ako pevná hranica).
• Dospelí začínajúci alebo pokračujúci v liečbe ≥ 2,5 mg/d glukokortikoidu > 3 mesiace: úvodné zhodnotenie rizika zlomenín (anamnéza zlomenín, FRAX od 40 rokov, denzitometria s VFA alebo RTG chrbtice) – ACR 2022.

Liečba

• Krátkodobá liečba < 3 – 4 týždne: glukokortikoidy sa podľa ESE/ES 2024 nemusia postupne znižovať bez ohľadu na dávku a možno ich vysadiť bez testovania.
• Pri dlhodobej liečbe sa o postupné znižovanie možno pokúsiť len vtedy, ak je základná choroba pod kontrolou a glukokortikoidy už nie sú potrebné.
• Stresové krytie u pacientov so súčasným alebo nedávnym užívaním glukokortikoidov bez biochemického vylúčenia adrenálnej insuficiencie: parenterálne glukokortikoidy pri strednom až veľkom strese, výkonoch v celkovej alebo regionálnej anestézii, dlhšej nemožnosti perorálneho príjmu, hemodynamickej nestabilite alebo pretrvávajúcom vracaní či hnačke.
• Prevencia osteoporózy u všetkých pacientov na glukokortikoidoch: primeraný príjem vápnika a vitamínu D, záťažové cvičenie, nefajčenie a obmedzenie alkoholu.

Komplikácie a prognóza

• Adrenálna kríza: pri podozrení parenterálne glukokortikoidy a tekutinová resuscitácia.
• Syndróm z vysadenia glukokortikoidov počas znižovania dávky: pri ťažkom priebehu dočasne zvýšiť dávku na poslednú tolerovanú a predĺžiť znižovanie.
• Glukokortikoidmi indukovaná osteoporóza: dávky ≥ 2,5 mg/d zvyšujú riziko zlomenín chrbtice aj bedra, dávky < 2,5 mg/d riziko zlomenín chrbtice.

Kľúčové pojmy

glukokortikoidy	glucocorticoida
prednizón	prednisonum
hydrokortizón	hydrocortisonum
dexametazón	dexamethasonum
os hypotalamus–hypofýza–nadobličky
adrenálna insuficiencia	insufficientia glandulae suprarenalis
adrenálna kríza
syndróm z vysadenia glukokortikoidov
glukokortikoidmi indukovaná osteoporóza
stresová dávka

📎 Zdroje:

Liu D et al. A practical guide to the monitoring and management of the complications of systemic corticosteroid therapy. Allergy Asthma Clin Immunol 2013, PMC (Introduction)They are used as replacement therapy in adrenal insufficiency (at physiologic doses) as well as in supraphysiologic doses for the management of various dermatologic, ophthalmologic, rheumatologic, pulmonary, hematologic, and gastrointestinal (GI) disorders.
Liu D et al. A practical guide to the monitoring and management of the complications of systemic corticosteroid therapy. Allergy Asthma Clin Immunol 2013, PMC (Introduction)In the field of respirology, systemic corticosteroids are used for the treatment of acute exacerbations of chronic obstructive pulmonary disease (COPD) and severe, uncontrolled asthma, as well as for inflammatory parenchymal lung diseases such as hypersensitivity pneumonitis
ESE/Endocrine Society Joint Clinical Guideline: Diagnosis and Therapy of Glucocorticoid-induced Adrenal Insufficiency (2024), PMC (Table 1)Hydrocortisone 20 mg 1.0 90-120 8-12 Adrenal insufficiency replacement Cortisone acetate 25 mg 0.8 80-120 8-12 Adrenal insufficiency replacement Deflazacort 7.5 mg 1.0 70-120 Not defined Duchenne muscular dystrophy Intermediate-acting glucocorticoids with moderate potency Prednisone 5 mg 4.0
ESE/Endocrine Society Joint Clinical Guideline: Diagnosis and Therapy of Glucocorticoid-induced Adrenal Insufficiency (2024), PMC (Abstract)This results in at least 1% of the population using chronic glucocorticoid therapy, being at risk for glucocorticoid-induced adrenal insufficiency. This risk is dependent on the dose, duration and potency of the glucocorticoid, route of administration, and individual susceptibility.
ESE/Endocrine Society Joint Clinical Guideline: Diagnosis and Therapy of Glucocorticoid-induced Adrenal Insufficiency (2024), PMC (Introduction)Notably, any route of administration has the potential of HPA axis suppression, including oral, topical, inhaled, intra-nasal, intravenous and intra-articular administration.
Liu D et al. A practical guide to the monitoring and management of the complications of systemic corticosteroid therapy. Allergy Asthma Clin Immunol 2013, PMC (Abstract)Osteoporosis, adrenal suppression, hyperglycemia, dyslipidemia, cardiovascular disease, Cushing’s syndrome, psychiatric disturbances and immunosuppression are among the more serious side effects noted with systemic corticosteroid therapy, particularly when used at high doses for prolonged periods.
Liu D et al. A practical guide to the monitoring and management of the complications of systemic corticosteroid therapy. Allergy Asthma Clin Immunol 2013, PMC (Cataracts and glaucoma)The risk of both cataracts and glaucoma is increased in patients using GCs, and this risk appears to be dose-dependent.
ESE/Endocrine Society Joint Clinical Guideline: Diagnosis and Therapy of Glucocorticoid-induced Adrenal Insufficiency (2024), PMC (Clinical features – general remarks)When present, symptoms of adrenal insufficiency are often non-specific and can overlap with those of the disease for which glucocorticoids are prescribed.
ESE/Endocrine Society Joint Clinical Guideline: Diagnosis and Therapy of Glucocorticoid-induced Adrenal Insufficiency (2024), PMC (R 2.10)We suggest that patients with current or previous glucocorticoid treatment presenting with signs and symptoms of exogenous Cushing syndrome are assumed to have glucocorticoid-induced adrenal insufficiency.
ESE/Endocrine Society Joint Clinical Guideline: Diagnosis and Therapy of Glucocorticoid-induced Adrenal Insufficiency (2024), PMC (R 2.4)We recommend against routine testing for adrenal insufficiency in patients on supraphysiologic doses of glucocorticoids, or if they are still in need of glucocorticoid treatment for the underlying disease.
ESE/Endocrine Society Joint Clinical Guideline: Diagnosis and Therapy of Glucocorticoid-induced Adrenal Insufficiency (2024), PMC (R 2.7)If confirmation of recovery of the HPA axis is desired, we recommend morning serum cortisol as the first test.
ESE/Endocrine Society Joint Clinical Guideline: Diagnosis and Therapy of Glucocorticoid-induced Adrenal Insufficiency (2024), PMC (R 2.7)we suggest that the test indicates recovery of the HPA axis if cortisol is >300 nmol/L or 10 μg/dL and glucocorticoids can be stopped safely
ESE/Endocrine Society Joint Clinical Guideline: Diagnosis and Therapy of Glucocorticoid-induced Adrenal Insufficiency (2024), PMC (R 2.7 – rationale)Although proposing a serum cortisol cut-off of 300 nmol/L (10 μg/dL) as a guide, the panel suggests that the value of serum cortisol is considered as a continuum, rather than an arbitrary cut-off
2022 American College of Rheumatology Guideline for the Prevention and Treatment of Glucocorticoid-Induced Osteoporosis (manuscript, PDF) (Recommendations for fracture risk assessment)For all adults (≥18 years old) initiating or continuing GC therapy ≥2.5 mg/day for >3 months, we strongly recommended initial clinical fracture risk assessment including symptomatic and asymptomatic fracture history, FRAX (age ≥40 only), and BMD with VFA or spine x-rays over no assessment
ESE/Endocrine Society Joint Clinical Guideline: Diagnosis and Therapy of Glucocorticoid-induced Adrenal Insufficiency (2024), PMC (R 2.1)We suggest not to taper glucocorticoids in patients on short-term glucocorticoid therapy of <3-4 weeks, irrespective of the dose. In these cases, glucocorticoids can be stopped without testing due to low concern for HPA axis suppression.
ESE/Endocrine Society Joint Clinical Guideline: Diagnosis and Therapy of Glucocorticoid-induced Adrenal Insufficiency (2024), PMC (R 2.2)Glucocorticoid taper for patients on long-term glucocorticoid therapy should only be attempted if the underlying disease for which glucocorticoids were prescribed is controlled, and glucocorticoids are no longer required.
ESE/Endocrine Society Joint Clinical Guideline: Diagnosis and Therapy of Glucocorticoid-induced Adrenal Insufficiency (2024), PMC (R 3.1)We recommend that patients with current or recent glucocorticoid use who did not undergo biochemical testing to rule out glucocorticoid-induced adrenal insufficiency should receive stress dose coverage when they are exposed to stress.
ESE/Endocrine Society Joint Clinical Guideline: Diagnosis and Therapy of Glucocorticoid-induced Adrenal Insufficiency (2024), PMC (R 3.1B)Parenteral glucocorticoids should be used in case of moderate to major stress, procedures under general or regional anesthesia, procedures requiring prolonged avoidance or inability of oral intake, or when there are signs of hemodynamic instability or prolonged vomiting or diarrhea.
2022 American College of Rheumatology Guideline for the Prevention and Treatment of Glucocorticoid-Induced Osteoporosis (manuscript, PDF) (Summary)Adequate age-appropriate dietary and supplemental intake of calcium and vitamin D, weight-bearing exercise, and avoidance of smoking and excessive alcohol intake is encouraged for all patients receiving GCs.
ESE/Endocrine Society Joint Clinical Guideline: Diagnosis and Therapy of Glucocorticoid-induced Adrenal Insufficiency (2024), PMC (R 3.2)patients with suspected adrenal crisis should be treated with parenteral glucocorticoids and fluid resuscitation.
ESE/Endocrine Society Joint Clinical Guideline: Diagnosis and Therapy of Glucocorticoid-induced Adrenal Insufficiency (2024), PMC (R 2.3)When glucocorticoid withdrawal syndrome is severe, glucocorticoid dose can be temporarily increased to the most recent one that was tolerated, and the duration of glucocorticoid taper could be increased.
2022 American College of Rheumatology Guideline for the Prevention and Treatment of Glucocorticoid-Induced Osteoporosis (manuscript, PDF) (Introduction)GC doses ≥2.5 mg/day increase fracture at both the spine and hip, and GC <2.5 mg/day increase the risk of spinal fractures

Precvičiť tému (6)

Kartičky

Vymenujte závažné nežiaduce účinky systémovej kortikoterapie.

Najprv si odpoveď povedz nahlas alebo v duchu – až potom ju odkry.

Kedy treba myslieť na glukokortikoidmi indukovanú adrenálnu insuficienciu aj pri iných ako perorálnych formách (ESE/ES 2024)?

Najprv si odpoveď povedz nahlas alebo v duchu – až potom ju odkry.

Aké sú zásady prevencie a liečby glukokortikoidmi indukovanej osteoporózy podľa ACR 2022?

Najprv si odpoveď povedz nahlas alebo v duchu – až potom ju odkry.