SEMINARIOS Trastornos adrenales

Trastornos adrenales

Sandra Milena Acevedo RuedaMD Residente

Medicina Interna UNAB

Introduccion

• Peso: 6 a 11 gramos

• Irrigacion

• Drenaje

• Origen embriologico

Ejes

• Eje hipotalamo hipofisis adrenal

• Eje renina angiotensina aldosterona

Sindrome de Cushing

• ACTH Dependiente– Enfermedad de Cushing (m)– Secrecion ectopica de ACTH tumor no pituitario(h)

• ACTH Independiente– Adenoma adrenocortical– Carcinoma adrenocortical– Hiperplasia adrenal nodular– Causas raras– Iatrogenico

• Enfermedad de Cushing - 90% micro• MEN – 1• ACTH-independent macronodular hyperplasia

(AIMAH) - Multiples Rp• Mutacion PKA - Primary pigmented nodular

adrenal disease (PPNAD) / Carney's complex• Sindrome de McCune-Albright / GNAS-1

(guanine nucleotide binding protein alpha stimulating activity polypeptide 1)

Sindrome de CushingBody Compartment/System Signs and Symptoms

Body fat Weight gain, central obesity, rounded face, fat pad on back of neck ("buffalo hump")

Skin Facial plethora, thin and brittle skin, easy bruising, broad and purple stretch marks, acne, hirsutism

Bone Osteopenia, osteoporosis (vertebral fractures), decreased linear growth in children

Muscle Weakness, proximal myopathy (prominent atrophy of gluteal and upper leg muscles)

Cardiovascular system Hypertension, hypokalemia, edema, atherosclerosis

Metabolism Glucose intolerance/diabetes, dyslipidemia

Reproductive system Decreased libido, in women amenorrhea (due to cortisol-mediated inhibition of gonadotropin release)

Central nervous system Irritability, emotional lability, depression, sometimes cognitive defects, in severe cases, paranoid psychosis

Blood and immune system Increased susceptibility to infections, increased white blood cell count, eosinopenia, hypercoagulation with increased risk of deep vein thrombosis and pulmonary embolism

Tratamiento

QuirurgicoMetiraponaKetoconazol

Exceso de mineralocorticoides

• Sindrome de Conn– Prevalencia no reconocida, hasta 12%

• Hiperaldosteronismo primario– Hiperplasia adrenal micronodular bilateral >>>– Adenoma adrenal unilateral– Carcinoma – Raro (grandes)

Abbreviations: DOC, deoxycorticosterone; ENaC, epithelial sodium channel; GR, glucocorticoid receptor; MR, mineralocorticoid receptor.

Exceso de mineralocorticoides

• Hipertension• Hipokalemia (deb.muscular, paralisis)• Alcalosis metabolica (calambres,tetania)• Remodelacion cardiaca• Dano glomerular• Edemas perifericos

Trends Endocrinol Metab 1994; 5:97

Factors that may affect the ARR and thus lead to false-positive or false-negative results

J Clin Endocrinol Metab. September 2008, 93(9):3266–3281

Factors that may affect the ARR and thus lead to false-positive or false-negative results

J Clin Endocrinol Metab. September 2008, 93(9):3266–3281

Exceso de mineralocorticoides

• Cirugia

• Espironolactona

• Eplerenona

• Amiloride

Incidentaloma

• MEN-1 (MEN1), MEN-2 (RET), Complejo de Carney (PRKAR1A), McCune-Albright (GNAS1)

• Poblacion general 10%

• Hasta un 25% tienen actividad

• Mas frecuente > metastasis tumor solido

Benign Approximate Prevalence (%)Adrenocortical adenoma

Endocrine inactive 60–85 Cortisol-producing 5–10

Aldosterone-producing 2–5Pheochromocytoma 5–10

Adrenal myelolipoma <1Adrenal ganglioneuroma <0.1

Adrenal hemangioma <0.1Adrenal cyst <1

Adrenal hematoma/hemorrhagic infarction <1Indeterminate

Adrenocortical oncocytoma <1Malignant

Adrenocortical carcinoma 2–5Malignant pheochromocytoma <1

Adrenal neuroblastoma <0.1Lymphomas (incl. primary adrenal lymphoma) <1

Metastases (most frequent: breast, lung) 15

Incidentaloma

• DOS PREGUNTAS

– Actividad ?

– Malignidad ?

>1 cm

Diagnosis Associated FeaturesAutoimmune polyglandular syndrome 1 (APS1) Hypoparathyroidism, chronic mucocutaneous candidiasis, other

autoimmune disorders, rarely lymphomasAutoimmune polyglandular syndrome 2 (APS2) Hypothyroidism, hyperthyroidism, premature ovarian failure, vitiligo,

type 1 diabetes mellitus, pernicious anemiaIsolated autoimmune adrenalitis

Congenital adrenal hyperplasia (CAH) See Table 342-10 (see also Chap. 349)Congenital lipoid adrenal hyperplasia (CLAH) 46,XY DSD, gonadal failure (see also Chap. 349)

Adrenal hypoplasia congenita (AHC) 46,XY DSD, gonadal failure (see also Chap. 349)Adrenoleukodystrophy (ALD), adrenomyeloneuropathy (AMN) Demyelination of central nervous system (ALD) or spinal cord and

peripheral nerves (AMN)Familial glucocorticoid deficiency

- FGD1- FGD2- FGD3

Triple A syndrome

ACTH insensitivity syndromes due to mutations in the ACTH receptor MC2R and its accessory protein MRAP tall statureAlacrima, achalasia, neurologic impairment

Smith-Lemli-Opitz-Syndrome Cholesterol synthesis disorder associated with mental retardation, craniofacial malformations, growth failure

Kearns-Sayre syndrome Progressive external ophthalmoplegia, pigmentary retinal degeneration, cardiac conduction defects, gonadal failure, hypoparathyroidism, type 1 diabetes

IMAGe syndrome Intrauterine growth retardation, metaphyseal dysplasia, genital anomalies

Adrenal infections Tuberculosis, HIV, CMV, cryptococcosis, histoplasmosis, coccidioidomycosis

Adrenal infiltration Metastases, lymphomas, sarcoidosis, amyloidosis, hemochromatosis

Adrenal hemorrhage Meningococcal sepsis (Waterhouse-Friderichsen syndrome), primary antiphospholipid syndrome

Drug-induced Mitotane, aminoglutethimide, arbiraterone, trilostane, etomidate, ketoconazole, suramin, RU486

Bilateral adrenalectomy E.g., in the management of Cushing's or after bilateral nephrectomy

Hiperplasia adrenal congenita

Variant Gene Impact on Steroid Synthesis Diagnostic Marker Steroids in Serum (and Urine)

21-Hydroxylase deficiency (21OHD)

CYP21A2 Glucocorticoid deficiency, mineralocorticoid deficiency, adrenal androgen excess

17-Hydroxyprogesterone, 21-deoxycortisol (pregnanetriol, 17-hydroxypregnanolone, pregnanetriolone)

11-Hydroxylase deficiency (11OHD)

CYP11B1 Glucocorticoid deficiency, mineralocorticoid excess, adrenal androgen excess

11-Deoxycortisol, 11-deoxycorticosterone (tetrahydro-11-deoxycortisol, tetrahydro-11-deoxycorticosterone)

17-Hydroxylase deficiency (17OHD)

CYP17A1 (Glucocorticoid deficiency), mineralocorticoid excess, androgen deficiency

11-Deoxycorticosterone, corticosterone, pregnenolone, progesterone (tetrahydro-11-deoxycorticosterone, tetrahydrocorticosterone, pregnenediol, pregnanediol)

3-Hydroxysteroid dehydrogenase deficiency (3bHSDD)

HSD3B2 Glucocorticoid deficiency, (mineralocorticoid deficiency), adrenal androgen excess

17-Hydroxypregnanolone (pregnanetriol)

P450 oxidoreductase deficiency (ORD)

POR Glucocorticoid deficiency, (mineralocorticoid excess), androgen deficiency, skeletal malformations

Pregnenolone, progesterone, 17-hydroxyprogesterone (pregnanediol, pregnanetriol)

TRATAMIENTO

• Glucocorticoides– Hidrocortisona– Prednisolona

• Mineralocorticoide y sal

Hiperplasia adrenal congenita