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Horm Metab Res 2007; 39(6): 451-456
DOI: 10.1055/s-2007-980192
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© Georg Thieme Verlag KG Stuttgart · New York

Dynamic Pituitary MRI has High Sensitivity and Specificity for the Diagnosis of Mild Cushing's Syndrome and should be Part of the Initial Workup[*]

T. C. Friedman 1 , E. Zuckerbraun 1 , M. L. Lee 1 , M. S. Kabil 2 , H. Shahinian 2
  • 1Division of Endocrinology, Metabolism, and Molecular Medicine, Charles R. Drew University of Medicine and Science, Los Angeles, CA, USA
  • 2Skull Base Institute, Los Angeles, CA, USA
Further Information

Publication History

received 2.11.2006

accepted 24.1.2007

Publication Date:
18 June 2007 (online)

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Abstract

Aim: The diagnosis of mild or episodic Cushing's syndrome is difficult. The standard tests include 24-hour urinary free cortisol (UFC), night-time blood, or salivary cortisol measurements, and dexamethasone suppression tests. Imaging studies of the pituitary have not been recommended as part of the initial workup (only to help distinguish pituitary Cushing's disease from the ectopic ACTH syndrome) because of poor sensitivity and specificity. With the development of dynamic pituitary MRI which uses multiple coronal dynamic sequences following gadolinium intravenous contrast, we hypothesized that the sensitivity and specificity would be increased and MRI would provide useful information for the initial diagnosis of Cushing's syndrome.

Methods: This was a retrospective chart review examining charts from 87 consecutive patients who were evaluated for Cushing's syndrome in a tertiary Endocrinology clinic over a one-year period. Most patients had mild and/or episodic hypercortisolism. Of these patients, 24 eventually were diagnosed with pituitary Cushing's syndrome by biochemical testing (24-h UFC and urinary 17-hydroxycorticosteroids, 11 PM salivary cortisol measurements, evening plasma cortisol), and 22 had the diagnosis of Cushing's syndrome excluded. Dynamic pituitary MRI (1.5 Tesla) was performed on all patients. The reader of the MRI was blind to the diagnosis.

Results: Twenty-three of 24 patients had a MRI consistent with a pituitary lesion (21 with a microadenoma, two with pituitary asymmetry). In contrast, only 3 of 20 patients (2 patient did not have MRIs) in the Cushing's excluded group had a pituitary lesion on dynamic MRI. Dynamic pituitary MRI had the highest sensitivity and negative predictive value of any testing modalities and its specificity and positive predictive value were similar to that of other tests.

Conclusion: We conclude that almost all patients in this series with Cushing's syndrome have a lesion on dynamic pituitary MRI, a rate much higher than the 50-60% rate reported for non-dynamic MRIs. The false positive rate of 16% in our group of Cushing's excluded patients is similar to the literature value of 10% seen in normal volunteers and is acceptable since MRI is not used solely as a determinant for the diagnosis. While a negative MRI will miss those patients with adrenal or ectopic Cushing's syndrome, those patients can usually be diagnosed by other testing. Thus this preliminary study implies that dynamic pituitary MRI adds valuable information to assist in the diagnosis of Cushing's syndrome and should be ordered as part of the initial workup.

Key words

Cushing's Syndrome - episodic - periodic - MRI - urinary free cortisol - salivary cortisol

1 In honor of George P. Chrousos, M.D., the mentor of TCF at the NIH from 1989 to 1995, who taught him to challenge dogmas and think outside the box.

References

  • 1 Newell-Price J, Trainer P, Besser M, Grossman A. The diagnosis and differential diagnosis of Cushing's syndrome and pseudo-Cushing's states.  Endocr Rev. 1998;  19 647-672
    CrossrefPubMedGoogle Scholar
  • 2 Arnaldi G, Angeli A, Atkinson AB, Bertagna X, Cavagnini F, Chrousos GP, Fava GA, Findling JW, Gaillard RC, Grossman AB, Kola B, Lacroix A, Mancini T, Mantero F, Newell-Price J, Nieman LK, Sonino N, Vance ML, Giustina A, Boscaro M. Diagnosis and complications of Cushing's syndrome: a consensus statement.  J Clin Endocrinol Metab. 2003;  88 5593-5602
    CrossrefPubMedGoogle Scholar
  • 3 Crapo LM. Cushing's syndrome: a review of diagnostic tests.  Metab. 1979;  28 955-977
    CrossrefPubMedGoogle Scholar
  • 4 Findling JW, Raff H. Diagnosis and differential diagnosis of Cushing's syndrome.  Endocrinol Metab Clin North Am. 2001;  30 729-747
    CrossrefPubMedGoogle Scholar
  • 5 Kaye TB, Crapo L. The Cushing syndrome: An update on diagnostic tests.  Ann Intern Med. 1990;  112 434-444
    PubMedGoogle Scholar
  • 6 Meier CA, Biller BM. Clinical and biochemical evaluation of Cushing's syndrome.  Endocrinol Metab Clin North Am. 1997;  26 741-762
    CrossrefPubMedGoogle Scholar
  • 7 Nieman LK. Cushing's syndrome.  Curr Ther Endocrinol Metab. 1997;  6 161-164
    PubMedGoogle Scholar
  • 8 Orth DN. Cushing's syndrome.  N Engl J Med. 1995;  332 791-803
    CrossrefPubMedGoogle Scholar
  • 9 Ross RJ, Trainer PJ. Endocrine investigation: Cushing's syndrome.  Clin Endocrinol. 1998;  49 153-155
    CrossrefPubMedGoogle Scholar
  • 10 Newell-Price J, Bertagna X, Grossman AB, Nieman LK. Cushing's syndrome.  Lancet. 2006;  367 1605-1617
    CrossrefPubMedGoogle Scholar
  • 11 Oldfield EH, Doppman JL, Nieman LK, Chrousos GP, Miller DL, Katz DA, Cutler Jr GB, Loriaux DL. Petrosal sinus sampling with and without corticotropin-releasing hormone for the differential diagnosis of Cushing's syndrome.  N Engl J Med. 1991;  325 897-905
    Google Scholar
  • 12 Friedman TC. Pseudo-Cushing syndrome. in Margioris AN, Chrousos GP (eds): Contemporary Endocrinology: Adrenal Disorders. Totowa, NJ: Humana Press 2001: 203-218
    Google Scholar
  • 13 Patel SS, Pall ME, Azziz R, Friedman TC. Androgen levels in Women with Cushing's Syndrome and the Polycystic Ovarian Syndrome.  Endocrine Soc (Abstract). 2005;  87 ((P2)) 363
    PubMedGoogle Scholar
  • 14 Foster LB, Dunn RT. Single-antibody technique for radioimmunoassay of cortisol in unextracted serum or plasma.  Clin Chem. 1974;  20 365-368
    PubMedGoogle Scholar
  • 15 Papanicolaou DA, Yanovski JA, Cutler Jr G, Chrousos GP, Nieman LK. A single midnight serum cortisol measurement distinguishes Cushing's syndrome from pseudo-Cushing states.  J Clin Endocrinol Metab. 1998;  83 1163-1167
    CrossrefPubMedGoogle Scholar
  • 16 Burke CW. Biologically active cortisol in plasma of oestrogen-treated and normal subjects.  Br Med J. 1969;  2 798-800
    CrossrefPubMedGoogle Scholar
  • 17 Doe RP, Zinneman HH, Flink HB, Ulstrom RA. Significance of the concentration of non protein bound plasma cortisol in normal subjects, Cushing's syndrome, pregnancy and during estrogen therapy.  J Clin Endocrinol Metab. 1960;  20 1484-1492
    CrossrefPubMedGoogle Scholar
  • 18 Raff H, Homar PJ, Skoner DP. New enzyme immunoassay for salivary cortisol.  Clin Chem. 2003;  49 203-204
    CrossrefPubMedGoogle Scholar
  • 19 Raff H, Raff JL, Findling JW. Late-night salivary cortisol as a screening test for Cushing's syndrome.  J Clin Endocrinol Metab. 1998;  83 2681-2686
    CrossrefPubMedGoogle Scholar
  • 20 Silber RH, Porter CC. The determination of 17,21-dihydroxy-20-ketosteroids in urine and plasma.  J Biol Chem. 1954;  210 923
    PubMedGoogle Scholar
  • 21 Clopper CJ, Pearson E. The use of confidence or fiducial limits illustrated in the case of binomial.  Biometrika. 1934;  26 404-413
    CrossrefPubMedGoogle Scholar
  • 22 McNemar Q. Note on the sampling error of the differences between correlated proportions or percentages.  Psycometrika. 1947;  12 153-157
    CrossrefPubMedGoogle Scholar
  • 23 Doppman JL, Frank JA, Dwyer AJ, Oldfield EH, Miller DL, Nieman LK, Chrousos GP, Cutler Jr GB, Loriaux DL. Gadolinium DTPA enhanced MR imaging of ACTH-secreting microadenomas of the pituitary gland.  J Comput Assist Tomogr. 1988;  12 728-735
    PubMedGoogle Scholar
  • 24 Newton DR, Dillon WP, Norman D, Newton TH, Wilson CB. Gd-DTPA-enhanced MR imaging of pituitary adenomas.  AJNR Am J Neuroradiol. 1989;  10 949-954
    PubMedGoogle Scholar
  • 25 Miki Y, Matsuo M, Nishizawa S, Kuroda Y, Keyaki A, Makita Y, Kawamura J. Pituitary adenomas and normal pituitary tissue: enhancement patterns on gadopentetate-enhanced MR imaging.  Radiology. 1990;  177 35-38
    PubMedGoogle Scholar
  • 26 Sakamoto Y, Takahashi M, Korogi Y, Bussaka H, Ushio Y. Normal and abnormal pituitary glands: gadopentetate dimeglumine-enhanced MR imaging.  Radiology. 1991;  178 441-445
    PubMedGoogle Scholar
  • 27 Davis WL, Lee JN, King BD, Harnsberger HR. Dynamic contrast-enhanced MR imaging of the pituitary gland with fast spin-echo technique.  J Magn Reson Imaging. 1994;  4 509-511
    CrossrefPubMedGoogle Scholar
  • 28 Elster AD. High-resolution, dynamic pituitary MR imaging: standard of care or academic pastime?.  AJR Am J Roentgenol. 1994;  163 680-682
    PubMedGoogle Scholar
  • 29 Kucharczyk W, Bishop JE, Plewes DB, Keller MA, George S. Detection of pituitary microadenomas: comparison of dynamic keyhole fast spin-echo, unenhanced, and conventional contrast-enhanced MR imaging.  AJR Am J Roentgenol. 1994;  163 671-679
    PubMedGoogle Scholar
  • 30 Stadnik T, Spruyt D, van Binst A, Luypaert R, d’Haens J, Osteaux M. Pituitary microadenomas: diagnosis with dynamic serial CT, conventional CT and T1-weighted MR imaging before and after injection of gadolinium.  Eur J Radiol. 1994;  18 191-198
    CrossrefPubMedGoogle Scholar
  • 31 Tabarin A, Laurent F, Catargi B, Olivier-Puel F, Lescene R, Berge J, Galli FS, Drouillard J, Roger P, Guerin J. Comparative evaluation of conventional and dynamic magnetic resonance imaging of the pituitary gland for the diagnosis of Cushing's disease.  Clin Endocrinol (Oxf). 1998;  49 293-300
    CrossrefPubMedGoogle Scholar
  • 32 Bishop J, Henkelman RM, Plewes DB. Dynamic spin-echo imaging: theoretical assessment and implementation.  J Magn Reson Imaging. 1994;  4 843-852
    CrossrefPubMedGoogle Scholar
  • 33 Smallridge RC, Czervionke LF, Fellows DW, Bernet VJ. Corticotropin- and thyrotropin-secreting pituitary microadenomas: detection by dynamic magnetic resonance imaging.  Mayo Clin Proc. 2000;  75 521-528
    PubMedGoogle Scholar
  • 34 Hall WA, Luciano MG, Doppman JL, Patronas NJ, Oldfield EH. Pituitary magnetic resonance imaging in normal human volunteers: occult adenomas in the general population.  Ann Intern Med. 1994;  120 817-820
    CrossrefPubMedGoogle Scholar
  • 35 Invitti C, Giraldi FP, de Martin M, Cavagnini F. Diagnosis and management of Cushing's syndrome: results of an Italian multicentre study. Study Group of the Italian Society of Endocrinology on the Pathophysiology of the Hypothalamic-Pituitary-Adrenal Axis.  J Clin Endocrinol Metab. 1999;  84 440-448
    CrossrefPubMedGoogle Scholar
  • 36 Friedman TC. An update on the overnight dexamethasone suppression test for the diagnosis of Cushing's syndrome: limitations in patients with mild and/or episodic hypercortisolism.  Exp Clin Endocrinol Diabetes. 2006;  114 356-360
    Article in Thieme ConnectPubMedGoogle Scholar

1 In honor of George P. Chrousos, M.D., the mentor of TCF at the NIH from 1989 to 1995, who taught him to challenge dogmas and think outside the box.

Correspondence

T. C. FriedmanMD, PhD 

Charles R. Drew University of Medicine & Sciences

Division of Endocrinology

1731 E. 120th St.

Los Angeles

CA 90059

USA

Phone: +1 310 668 51 97

Fax: +1 323 563 93 24

Email: tefriedm@cdrewu.edu

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