ANTINKSČIŲ KRIZĖ: PATOLOGIJOS APŽVALGA IR GYDYMO BEI PREVENCIJOS GALIMYBĖS

Antinksčių krizė − tai ūmi gyvybei pavojinga būklė, le­mianti pacientų, kuriems patvirtintas antinksčių nepa­kankamumas, didesnį mirštamumą. Nepaisant didelės antinksčių nepakankamumo gydymo pažangos, antinks­čių krizė vis dar išlieka viena iš pagrindinių šios grupės pacientų mirties priežasčių, nes jai būdingas sisteminis organizmo pažeidimas, nesant specifinių simptomų, to­dėl sunku diagnozuoti ir neretai pavėluojama gydyti. Šiuo Straipsniuyje plačiau bus aptartasiamas antinksčių krizės aktualumas, ligai būdingąa klinika, gydymo bei prevencijos gairės. Tyrimo tikslas − apžvelgti ir aptarti retos, tačiau gyvy­bei itin pavojingos būklės – antinksčių krizės epidemi­ologijos, diagnostikos bei gydymo naujoves. Atlikta naujausių prevencinių programų bei gydymo gairių, ku­rios leistų sumažinti šios klinikinės būklės atvejų skaičių ateityje, paieška mokslinėje literatūroje. Literatūros šal­tinių paieška vykdyta anglų kalba PubMed, UpToDate, Medscape ir Cohrane medicinos duomenų bazėse. Nau­doti raktiniai žodžiai ir jų deriniai: adrenal crisis, adrenal insufficiency, hydrocortisone, treatment guidelines for adrenal crisis, prevention of adrenal crisis syndrome. Atrinkti 24 viso teksto moksliniai straipsniai, atitikę ty­rimo tikslą ir atlikta jų analizė. Tyrimo rezultatai parodė, kad pagrindinis šią patologiją išprovokuojantis veiksnys yra infekcija, tačiau antinksčių krizės priežastis gali būti operacija, trauma, gliukokortikoidų terapijos plano nesi­laikymas ar itin sunkus fizinis stresas. Pirmoji pagalba, nustačius antinksčių krizę, apima: parenterinį hidrokor­tizono skyrimą, rehidrataciją ir elektrolitų homeostazės atkūrimą. Pagrindinė prevencijos priemonė – pacientų edukacija. Išvados: 1) pirmo pasirinkimo vaistas gydyti antinksčių krizę yra hidrokortizonas; 2) pirmos kartos ir ilgo veikimo gliukokortikoidai prednizolonas ir dek­sametazonas nerekomenduojami, išskyrus atvejus, kai hidrokortizonu nepasiekiama efektyvaus gydymo; 3) laiku pradėtas adekvatus gretutinių ligų, tokių kaip vėžys, autoimuniniai susirgimai, antinksčių nepakankamumas bei infekcijos, gydymas gali sumažinti antinksčių krizės atvejų skaičių; 4) sergantieji Adisono liga, reguliariai naudojantys specialius klausimynus savo būklei įver­tinti, gali reikšmingai sumažinti antinksčių krizės riziką.

Effects of Postnatal Hydrocortisone Treatment on Cytokine Profile in Preterm Infants at Risk of Bronchopulmonary Dysplasia

Systemic hydrocortisone administration has been widely used in preterm infants who are at a risk of bronchopulmonary dysplasia (BPD). However, the effects of hydrocortisone on cytokine profiles have not been examined. We aimed to investigate the effects of postnatal hydrocortisone treatment on serum cytokine levels in extremely preterm infants at risk for BPD. In 29 extremely preterm infants (born at less than 28 weeks of gestational age), we obtained serum from blood samples collected during an early phase (5–20 days) and a late phase (28‒60 days) after birth. We measured the levels of proinflammatory cytokines (tumor necrosis factors α and β, interleukin [IL]-1β, and IL-6), T-helper (Th) 1 cytokines (interferon-γ, IL-2, and IL-12p70), Th2 cytokines (IL-4, IL-5, and IL-10), Th17 cytokine IL-17A, and chemokine IL-8. We found that serum IL-6 and IL-8 levels were significantly higher during the early phase than during the late phase (both P = 0.03). Other cytokines concentrations did not change between the phases. Thirteen infants (45%) received systemic hydrocortisone treatment at a median age of 15 days (IQR 10.0–21.5) after birth due to respiratory deterioration, after which the serum IL-6 levels significantly decreased (P = 0.04). Median duration of treatment was 16.0 (IQR 8.0–34.5) days. Conclusion: Extremely preterm infants show high serum IL-6 and IL-8 levels in the early phase of life. Moreover, postnatal systemic hydrocortisone treatment might suppress IL-6 overproduction.

Primary hypothalamic lymphoma with clinical findings mimicking pituitary apoplexy: a case report

Background Primary central nervous system lymphoma (PCNSL) is a rare but well-known extra-nodal lymphoma, which usually presents with non-Hodgkin B-cell lymphomas. PCNSL is generally located around the ventricle and is often detected as multiple lesions. It is rarely seen in the area of the hypothalamus. Case presentation We report the case of a 48-year-old Caucasian woman with progressive short-term memory deterioration, headache, mental confusion, diabetes insipidus (DI) and hypopituitarism. Early findings were suggestive of a pituitary apoplexy. The results of tests performed during the initial admission at the tertiary health center revealed hypernatremia, hypopituitarism and DI. Intravenous hydrocortisone treatment was initiated for the secondary adrenal insufficiency, and 75 mcg/day of levothyroxine was started for the secondary hypothyroidism on the fourth day following hydrocortisone treatment. A daily dose of 120 mg desmopressin melt tablet was started twice a day for polyuria/polydipsia after the patient’s volume status was balanced. A brain magnetic resonance imaging scan revealed a mass lesion in the hypothalamic area, which was surrounded by marked edema. Anti-edema treatment was initially started considering the suggestion by our neurosurgery team. The patient’s clinical and laboratory findings improved after the initiation of the anti-edema therapy. Afterwards, a biopsy was performed, which diagnosed a malignant diffuse large B-cell lymphoma. Subsequently, intravenous high-dose methotrexate-based therapy was started; however, after the second cycle of chemotherapy, the patient died due to sepsis. Conclusion In this report, we present a case of hypopituitarism that developed due to the mass effect of hypothalamic lymphoma with clinical findings of pituitary apoplexy. Intracranial masses may cause obvious endocrinological findings related to hypopituitarism, while vague findings may also be observed due to partial failure. Therefore, it is important to perform a comprehensive endocrinological examination at the time of diagnosis in patients with intracranial masses.

RF9 Rescues Cortisol-Induced Repression of Testosterone Levels in Adult Male Macaques

Cortisol inhibits hypothalamic-pituitary-gonadal (HPG) axis whereas RF9, a potent agonist of kisspeptin receptor (GPR54) activates HPG-axis during fasting-induced stress and under normal physiological conditions. However, the effect of RF9 on the cortisol-induced repressed HPG-axis is not studied yet. This study investigated whether exogenous cortisol-induced repression of the HPG-axis can be rescued by RF9. Six intact adult male rhesus monkeys (Macaca mulatta) habituated to chair-restraint were administered hydrocortisone sodium succinate at a rate of 20 mg/kg of body weight (BW) per day for 12 days. Single blood sample was taken by venipuncture from each animal on alternate days for hormones analyses. On experimental day 12, hydrocortisone treated monkeys received a single intravenous bolus of RF9 (n = 3) and vehicle (n = 3). The animals were bled for a period of 4 h at 60 min intervals from an indwelling cannula in the saphenous vein. RF9 was administered intravenously at the dose of 0.1 mg/kg BW immediately after taking 0 min sample. Plasma cortisol and testosterone concentrations were measured by using specific enzyme immunoassays. Hydrocortisone treatment increased plasma cortisol levels (P ≤ 0.0001) and decreased plasma testosterone (P ≤ 0.0127) levels. Interestingly, compared to vehicle, RF9 treatment significantly increased plasma testosterone levels at 120 min (P ≤ 0.0037), 180 min (P ≤ 0.0016), and 240 min (P ≤ 0.0001) intervals in the hydrocortisone treated monkeys. From these results, we concluded that RF9 administration relieves the suppressed HPG-axis in term of plasma testosterone levels in the cortisol treated monkeys.

Corticosteroid Therapy for Brain Tumor Patients with Adrenal Insufficiency

The use of corticosteroids in cases of brain tumors has become common to reduce brain edema. However, the use can cause adrenal insufficiency (AI) if used long-term and in large doses and with rapid withdrawal. In cases of pituitary macroadenoma that has undergone surgery, AI may also occur. AI also affects the treatment of brain tumor patients. Hence, AI is an important problem in brain tumors because almost all patients with brain tumors receive corticosteroids at some point in the course of their disease. The management is similar to another AI with focus of hydrocortisone treatment. The adjustment of hydrocortisone dosage in patients whom undergo brain surgery is similar with another major surgery, whether the adjustment for pituitary adenoma patients whom undergo excision is more complicated and careful due to the high risk and incidence of AI in these patients.

Efficacy of Intravenous Hydrocortisone Treatment in Refractory Neonatal Seizures: A Report on Three Cases

Neonatal seizures are the most common neurological emergency, and neonatal status epilepticus (NSE) remains a controversial entity, with no general consensus about its definition and treatment. Here, we report on three newborns with NSE refractory to first- and second-line antiepileptic drugs successfully treated with intravenous (IV) hydrocortisone. The patients had previously failed therapy with levetiracetam, phenobarbital and midazolam, showing persistent clinical and electrical seizures. Modulation of brain inflammation triggered during prolonged epileptic activity has been thought to potentially explain the beneficial effects of anti-inflammatory treatment.

Paediatric population pharmacokinetic modelling to assess hydrocortisone replacement dosing regimens in young children

Context: Accurate hydrocortisone dosing in children with adrenal insufficiency is important to avoid the risks of over and under treatment including iatrogenic Cushing’s syndrome and adrenal crisis. Objective: To establish a population pharmacokinetic model of hydrocortisone in children and use this to refine hydrocortisone replacement regimens. Design and methods: Pharmacokinetic study of hydrocortisone granules, available in 0.5, 1, 2 and 5 mg dose strengths, in 24 children with adrenal insufficiency aged 2 weeks to 6 years. Cortisol concentrations quantified by LC-MS/MS were used to refine an adult pharmacokinetic model to a paediatric population model which was then used to simulate seven different hydrocortisone treatment regimens. Results: Pre-dose cortisol levels were undetectable in 54% of the 24 children. The developed pharmacokinetic model had good predictive performance. Simulations for the seven treatment regimens using either three- or four-times daily dosing showed treatment regimens delivered an AUC0-24h within the 90% reference range for healthy children except in neonates where two regimens had an AUC below the 5th percentile. Cortisol concentrations at individual time points in the 24 h were outside the 90% reference range for healthy individuals in 50%, 55–65% and 70–75% for children, infants and neonates, respectively, with low cortisol levels being most prevalent. Conclusions: Current paediatric hydrocortisone treatment regimens based on either three- or four-times daily administration replicate cortisol exposure based on AUC0-24h, but the majority of cortisol levels are above or below physiological cortisol levels with low levels very common before the next dose.

Effect of Hydrocortisone on Intradialytic Hypotension: A Preliminary Investigational Study

Introduction. Approximately 15 to 33% of all dialysis treatments are complicated by intradialytic hypotension (IDH). In this study, we tested the hypothesis that the intravenous administration of hydrocortisone prior to HD treatment could prevent IDH or at least decrease the drop in the blood pressure resulting from IDH. Methods. This study was approved by our local ethics committee/IRB (2017/87) and by the Jordan Food and Drug Administration (7/clinical/18). Additionally, it is registered on ClinicalTrials.gov (NCT03465007). In this preliminary investigational study, we screened all chronic hemodialysis patients at our clinic who were 18 years of age or older (n=82) for IDH. There were 14 patients included in the interventional part of this study; patients were given IV hydrocortisone for 3 consecutive HD sessions, followed or preceded by 3 intervention-free sessions where they were given 5 ml of saline as a placebo. Results. The initial total sample size was 82 patients. The frequency of IDH at our clinic was 24.4%. Fourteen out of the 20 patients who were diagnosed with IDH agreed to enroll in the interventional part of our study. The mean age of the patients in the interventional part of our study was 53.5 years (±10.3). These patients included 5 (35.7%) men and 9 (64.3%) women. Upon comparing the number of hypotensive attacks with and without the hydrocortisone administration, we found a significant difference (p=0.003) between the hydrocortisone and placebo treatments in which 12 (85.7%) patients had fewer IDH episodes with the hydrocortisone treatment than with placebo. Conclusion. This preliminary investigational study found that the administration of a stress dose of hydrocortisone prior to hemodialysis could be an effective measure for preventing or minimizing the risk of IDH episodes. Additional prospective studies on this subject are needed. Ruling out adrenal insufficiency in patients diagnosed with IDH is also crucial.