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La diagnostica di laboratorio delle malattie del surrene. Raccomandazioni pratiche per l’insufficienza surrenalica primaria

Laboratory diagnostics of adrenal diseases. Practice guidelines for primary adrenal insufficiency

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La Rivista Italiana della Medicina di Laboratorio - Italian Journal of Laboratory Medicine

Riassunto

L’insufficienza surrenalica (IS) è una condizione clinica, potenzialmente pericolosa per la vita, determinata dalla diminuita produzione o azione degli ormoni glucocorticoidi, accompagnata o meno da carenza di mineralcorticoidi o androgeni surrenalici. È dovuta a un’alterazione dell’asse ipotalamo-ipofisi-surrene, per cause surrenaliche [insufficienza surrenalica primaria (ISP) o morbo di Addison], ipofisarie (insufficienza surrenalica secondaria) o ipotalamiche (insufficienza surrenalica terziaria). La prevalenza dell’ISP in Europa è di circa 100 casi per milione, l’incidenza 5 casi per milione/anno, con una frequenza maggiore nella quarta decade di vita e nel sesso femminile. Oggi l’82% dei casi di ISP ha eziologia autoimmune, il 9% infettiva e il 9% da altre cause. L’IS si differenzia in una forma acuta, che costituisce un’emergenza clinica con le manifestazioni proprie dello shock ipovolemico, e una forma cronica, caratterizzata da sintomi e segni che si aggravano progressivamente in base al grado e alla velocità di distruzione del surrene: astenia generalizzata, anoressia, calo ponderale, ipotensione, ipoglicemia, iperpigmentazione cutanea, amenorrea e diminuzione della libido, anemia e depressione. Le presenti raccomandazioni pratiche della Società Italiana di Patologia Clinica e Medicina di Laboratorio riprendono quelle della Endocrine Society del 2016 preparate utilizzando il sistema Grade. Le raccomandazioni principali ribadiscono che: (1) la misura basale di cortisolo sierico totale (CST), l’indice di cortisolo libero (ICL) e il cortisolo salivare del mattino (CSM), associati alla misura della corticotropina (ACTH), rappresentano i test di ingresso per la diagnosi di ISP (test combinato basale); (2) rilevare un valore elevato di renina attiva, associato a un valore basso-normale di aldosterone suggerisce l’esecuzione del test combinato basale; (3) rilevare un valore basso di deidroepiandrosterone solfato (DHEAS) suggerisce l’esecuzione del test combinato basale; (4) rilevare un valore di \(\text{CST}<140\ \mbox{nmol/L}\) (50 μg/L) o di ICL inferiore a 12 o di CSM inferiore a 4,1 nmol/L (1,5 μg/L), associata a un valore di ACTH superiore a 2 volte il limite superiore dell’intervallo di riferimento metodo-dipendente, è fortemente indicativa di ISP; (5) la conferma diagnostica di ISP va effettuata con il test dinamico all’ACTH a dose standard.

Summary

Adrenal insufficiency (AI) is a potentially life-threatening clinical condition caused by decreased production or action of glucocorticoid hormones, with or without deficiency of mineralocorticoid or adrenal androgens. It is due to an alteration of the hypothalamic-pituitary-adrenal axis, for adrenal causes [primary adrenal insufficiency (PAI) or Addison’s disease], pituitary (secondary adrenal insufficiency) or hypothalamic (tertiary adrenal insufficiency). The prevalence of PAI in Europe is about 100 cases per million/year, the incidence is 5 cases per million/year, with a higher frequency in the fourth decade of life and in females. Today 82% of the PAI cases have autoimmune etiology, 9% infectious and 9% other causes. The AI differs in an acute form, which is a medical emergency with hypovolemic shock and a chronic form, characterized by symptoms and signs that gradually worsen depending on the degree and speed of adrenal destruction: generalized weakness, anorexia, weight loss, hypotension, hypoglycemia, skin hyperpigmentation, amenorrhea and decreased libido, anemia and depression. These practical recommendations of the Italian Society of Clinical Pathology and Laboratory Medicine are consistent with those prepared in 2016 by the Endocrine Society using the GRADE system. The main recommendations reaffirm that: (1) the baseline measurement of serum total cortisol (STC) or the free cortisol index (FCI) or morning salivary cortisol (MSC), associated with adrenocorticotropin hormone (ACTH), represent the entrance test for the diagnosis of PAI (baseline combined test); (2) a high value of active renin, associated with a low-normal value of aldosterone should be confirmed by the baseline test combined; (3) a low value of dehydroepiandrosterone sulfate (DHEAS) should be confirmed by the baseline combined test; (4) a value of \(\text{STC}<140\ \mbox{nmol/L}\) (50 μg/L)/FCI lower than 12/MSC lower than 4.1 nmol/L (1.5 μg/L), associated with ACTH value greater than two times the upper limit of method-dependent reference, strongly indicates PAI; 5) the diagnostic confirmation of PAI must be done with ACTH test (standard dose).

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Authors and Affiliations

  1. Laboratorio Unico Interaziendale, Azienda Sanitaria Universitaria Integrata di Udine, Udine, Italia

    Federica D’Aurizio

  2. Laboratorio di Patologia Clinica, Ospedale S. Maria degli Angeli di Pordenone, Azienda Per L’Assistenza Sanitaria 5, Friuli Occidentale, Pordenone, Italia

    Renato Tozzoli

  3. UOC Patologia Clinica, AUSL della Romagna, Pievesestina di Cesena, FC, Italia

    Romolo Marco Dorizzi

  4. UOC Medicina di Laboratorio, Azienda Ospedaliera Pia Fondazione di Culto e Religione Card. G. Panico, Tricase, LE, Italia

    Vincenzo Brescia

  5. UOC Patologia Clinica, Area Vasta 5 Azienda Sanitaria Unica Regionale Marche, Ascoli Piceno, Italia

    Antonio Fortunato

  6. UOC Laboratorio Analisi, IRCCS Ospedale Pediatrico Bambino Gesù, Roma e Dipartimento Medicina Sperimentale, Università di Tor Vergata, Roma, Italia

    Ottavia Porzio

  7. UOC Patologia Clinica, Ospedale San Filippo Neri, Roma, Italia

    Marina Vitillo

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Per il Gruppo di Studio Endocrinologia e Malattie del Metabolismo (GdS-EMM) della SIPMeL.

Altri componenti del GdS-EMM della SIPMeL: B. Caruso, E. Ciotoli, C. Cocco, A. Ferrari, D. Foti, G. Giannone, L. Giovanella, M. Herrmann, G. Ozzola, L. Pecoraro, E. Stenner, E. Toffalori.

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D’Aurizio, F., Tozzoli, R., Dorizzi, R.M. et al. La diagnostica di laboratorio delle malattie del surrene. Raccomandazioni pratiche per l’insufficienza surrenalica primaria. Riv Ital Med Lab 12, 234–242 (2016). https://doi.org/10.1007/s13631-016-0135-5

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