Glucocorticoid Therapy and Cushing Syndrome Differential Diagnoses

  • Author: George P Chrousos, MD, FAAP, MACP, MACE, FRCP(London); Chief Editor: Stephen Kemp, MD, PhD   more...
 
Updated: Mar 5, 2012
 
 

Differential Diagnoses

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Contributor Information and Disclosures
Author

George P Chrousos, MD, FAAP, MACP, MACE, FRCP(London)  Professor and Chair, First Department of Pediatrics, Athens University Medical School, Aghia Sophia Children's Hospital, Greece; UNESCO Chair on Adolescent Health Care, University of Athens, Greece

George P Chrousos, MD, FAAP, MACP, MACE, FRCP(London) is a member of the following medical societies: American Academy of Pediatrics, American College of Endocrinology, American College of Physicians, American Pediatric Society, American Society for Clinical Investigation, Association of American Physicians, Endocrine Society, Pediatric Endocrine Society, and Society for Pediatric Research

Disclosure: Nothing to disclose.

Coauthor(s)

Antony Lafferty, MB ChB, FRACP  Senior Lecturer of Pediatric Endocrinology, Monash University Department of Pediatrics, National Institutes of Health, Bethesda, MD, and Princess Margaret Hospital for Children, Perth, Western Australia

Antony Lafferty, MB ChB, FRACP is a member of the following medical societies: Endocrine Society

Disclosure: Nothing to disclose.

Specialty Editor Board

Thomas A Wilson, MD  Professor of Clinical Pediatrics, Chief and Program Director, Division of Pediatric Endocrinology, Department of Pediatrics, The School of Medicine at Stony Brook University Medical Center

Thomas A Wilson, MD is a member of the following medical societies: Endocrine Society, Pediatric Endocrine Society, and Phi Beta Kappa

Disclosure: Nothing to disclose.

Mary L Windle, PharmD  Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

Lynne Lipton Levitsky, MD  Chief, Pediatric Endocrine Unit, Massachusetts General Hospital; Associate Professor of Pediatrics, Harvard Medical School

Lynne Lipton Levitsky, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Pediatrics, American Diabetes Association, American Pediatric Society, Endocrine Society, Pediatric Endocrine Society, and Society for Pediatric Research

Disclosure: Pfizer Grant/research funds P.I.; Tercica Grant/research funds Other; Eli Lily Grant/research funds PI; NovoNordisk Grant/research funds PI; NovoNordisk Consulting fee Consulting; Onyx Heart Valve Consulting fee Consulting

Merrily P M Poth, MD  Professor, Department of Pediatrics and Neuroscience, Uniformed Services University of the Health Sciences

Merrily P M Poth, MD is a member of the following medical societies: American Academy of Pediatrics, Endocrine Society, and Pediatric Endocrine Society

Disclosure: Nothing to disclose.

Chief Editor

Stephen Kemp, MD, PhD  Professor, Department of Pediatrics, Section of Pediatric Endocrinology, University of Arkansas for Medical Sciences College of Medicine, Arkansas Children's Hospital

Stephen Kemp, MD, PhD is a member of the following medical societies: American Academy of Pediatrics, American Association of Clinical Endocrinologists, American Pediatric Society, Endocrine Society, Phi Beta Kappa, Southern Medical Association, and Southern Society for Pediatric Research

Disclosure: Nothing to disclose.

References

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Diagnosis of Cushing syndrome.
Etiology of Cushing syndrome.
Physical findings in Cushing syndrome.
Table 1. Glucocorticoid Equivalencies[2]
TypeDrugDoseRelative Glucocorticoid PotencyRelative Mineralocorticoid PotencyPlasma Half-Life



(mg)



Biologic Half-Life



(h)



Short-actingCortisol201.02908-12
Hydrocortisone‡250.8280-1188-12
Intermediate-actingPrednisone5416018-36
Prednisolone541115-20018-36
Triamcinolone4503018-36
Methylprednisolone45018018-36
Long-actingDexamethasone0.525-50020036-54
Betamethasone0.625-50030036-54
MineralocorticoidAldosterone0.3030015-208-12
Fludrocortisone21515020018-36
Desoxycorticosterone acetate002070…
Table 2. Effects of Glucocorticoids During Long-Term Therapy
SystemEffects
Endocrine and metabolicSuppression of hypothalamic-pituitary-adrenal (HPA) axis (adrenal suppression)



Growth failure in children



Hyperinsulinemia/insulin resistance



Abnormal glucose tolerance test result/diabetes mellitus



GIGastric irritation, peptic ulcer



Acute pancreatitis (rare, secondary to insulin resistance and hypertriglyceridemia)



Fatty infiltration of liver (hepatomegaly, rare)



HemopoieticLeukocytosis



Neutrophilia - Increased recruitment from bone marrow, demargination, and decreased migration from blood vessels



Lymphopenia - Migration from blood vessels to lymphoid tissue



Eosinopenia



Monocytopenia



ImmuneSuppression of delayed (type IV) hypersensitivity (important with Mantoux testing for tuberculosis)



Inhibition of leukocyte and tissue macrophage migration



Inhibition of cytokine secretion/action



Suppression of the primary antigen response



MusculoskeletalOsteoporosis, spontaneous fractures



Avascular necrosis of femoral and humoral heads and other bones



Myopathy (particularly of the proximal muscles [eg, unable to comb hair or climb stairs])



OphthalmicPosterior subcapsular cataracts (more common in children)



Elevated intraocular pressure/glaucoma



CNS (neuropsychiatric disorders)Sleep disturbances, insomnia (particularly with long-acting glucocorticoids and nocturnal dosing)



Euphoria, depression, mania, psychosis (more commonly observed in adults)



Obsessive behaviors (children with hypercortisolism are often more studious)



Pseudotumor cerebri (benign increase of intracranial pressure)



Cardiovascular[4] Hypertension[5]



Congestive heart failure in predisposed patients



Other cushingoid featuresMoon facies (broad cheeks with temporal muscle wasting) facial plethora



Generalized and truncal obesity (more marked in adults)



Supraclavicular fat collection



Posterior cervical fat deposition (dorsocervical hump)



Glucocorticoid-induced acne



Thin and fragile skin, violaceous striae (more common in adults)



Impotence, menstrual irregularity



Decreased thyroid-stimulating hormone and triiodothyronine



Hypokalemia (with very high cortisol levels or in the presence of potassium-wasting diuretics), metabolic alkalosis



Table 3. Genetic Causes of Cushing Syndrome
CauseFeaturesGenetics
MEN1Associated with pancreatic tumors producing gastrin, insulin, and/or ACTH that may metastasize to the liver;



multigland hyperparathyroidism, pituitary tumors, lipomas, and angiofibromas



11p13



(MIM 131100)



McCune-Albright syndromeMosaic constitutively activating postzygotic GS alpha mutation that can lead to polyostotic fibrous dysplasia, pigmented skin lesions, gonadotropin-releasing hormone–independent precocious puberty, hyperthyroidism, renal phosphate wasting, and other endocrine and nonendocrine manifestations 20q13.2



(MIM 174800)



Beckwith-Wiedemann syndrome (Risk of adrenal malignancy)Macroglossia; visceromegaly; hyperinsulinemia; omphalocele; and risk of adrenal carcinoma, nephroblastoma, hepatoblastoma, rhabdomyosarcoma, and thoracic neuroblastoma requiring biannual sonograms 11p13



(MIM 130650)



Hemihypertrophy (Risk of adrenal malignancy)Adrenal tumors in association unilateral tissue overgrowth on ipsilateral or contralateral side



Compare upper and lower limbs and look for facial asymmetry



(MIM 235000)[6]
Li-Fraumeni syndrome (Risk of adrenal malignancy)Adrenal neoplasm



Personal or family history of multiple tumors (eg, lung, breast, nasopharynx, CNS, melanoma, pancreas, gonads, prostate)



17p13.1 -TP53 gene



22q12.1



(MIM 191170; 151623)



Carney complexPrimary pigmented nodular adrenal disease (PPNAD); lentigines; myxomas of the heart, skin, and breast; melanotic schwannoma; growth hormone– and prolactin-secreting pituitary adenomas; Sertoli cell tumors of the testis; multiple small hypoechoic thyroid lesions; thyroid carcinoma 2p16 and 17q22-24



(MIM 605244; 160980)



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