JOURNAL OF THE LOUISIANA STATE MEDICAL SOCIETY
REFERENCES
of ACTH dependent Cushing’s syndrome. 5 If a microadenoma (<1cm) or macroadenoma (>1cm) is identified, Inferior Petrosal Sinus Sampling (IPSS) should be performed, which is the gold standard for diagnosis. An IPSS combined with pre- and post-CRH stimulation samples detects Cushing’s disease with 95% sensitivity and 93% specificity. If the pre-CRH central to peripheral ACTH ratio is > 1.7 and a post-CRH central to peripheral ACTH ratio is >3.3, a pituitary source can be confirmed as the site of excess ACTH production, making a final diagnosis of Cushing’s disease. 6 If these ACTH ratio requirements are not met, an ectopic source of ACTH secretion is suspected and must be investigated further, most commonly focusing on lung malignancies. The overall goals of treatment for Cushing’s disease are reversal of clinical signs and symptoms, normalization of endocrine labs, and prevention of recurrence. The definitive treatment for Cushing’s disease is a transsphenoidal adenomectomy. This surgical approach is most successful when the patient has a microadenoma that is well circumscribed and not intertwined in normal pituitary tissue. If the adenoma is not well circumscribed, a subtotal hypophysectomy may be performed; yet, this procedure is associated with greater risk of post-surgical pituitary dysfunction and is not as desirable for patients interested in future fertility. It is also associated with only a 70% remission rate compared to up to 90% with selective adenomectomy. 7 If the adenoma is unable to be resected or if the patient is interested in future fertility, pituitary irradiation may be used as first line treatment for Cushing’s disease (but is often used as second line treatment when surgery fails). If no surgical treatment is possible, Cushing’s disease can bemanaged medically, although this is sub-optimal. Drug classes such as adrenal enzyme inhibitor and adrenolytic agents (ketoconazole, metyrapone, etomidate, mitotane, and mifepristone), pituitary- directed drugs (cabergoline), and somatostatin analogs (pasireotide) are the most commonly used medical therapies. Unfortunately, toxicities due to side effects of these medications often limit their use. 8 A patient is considered to be in remission if the morning cortisol level is <5ug/dL within 7 days after surgery. Remission rates are lower for macroadenomas (~48%) compared to microadenomas (~76%). After surgery, patients require glucocorticoid replacement until theHPAaxis recovers, typicallywithinone year. However, early recovery of the HPA axis may indicate a higher risk for recurrence in the future. Late-night serum or salivary cortisol levels should be monitored, starting at the time of HPA axis recovery, as an elevated value is the earliest detectable sign of recurrence. It is also important that patients with Cushing’s syndrome receive long term follow up for the associated comorbidities, including obesity, hypertension, cardiovascular risk, and osteoporosis, which may never completely resolve. They require follow up for recurrence throughout the remainder of their life. 8
1. Ezzat S, Asa S, Couldwell W, et al. The Prevalence of Pituitary Adenomas, A Systematic Review. Cancer 2004; 101: 613-619. 2. Howlett TA, Rees LH, Besser GM. Cushing's syndrome. Clin Endocrinol Metab 1985; 14:911-945. 3. Woo YS, Isidori AM, Wat WZ, et al. Clinical and biochemical characteristics of adrenocorticotropin-secreting macroadenomas. J Clin Endocrinol Metab 2005; 90:4963-4969. 4. Nieman LK, Biller BM, Findling JW, et al. The diagnosis of Cushing's syndrome: an Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab 2008; 93:1526-1540. 5. Pecori Giraldi F, Pivonello R, Ambrogio AG, et al. The dexamethasone- suppressed corticotropin-releasing hormone stimulation test and the desmopressin test to distinguish Cushing's syndrome from pseudo- Cushing's states. Clin Endocrinol (Oxf ) 2007; 66:251-257. 6. Oldfield EH, Doppman JL, Nieman LK, et al. 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. 7. Biller BM, GrossmanAB, Stewart PM, et al.Treatment of adrenocorticotropin- dependent Cushing's syndrome: a consensus statement. J Clin Endocrinol Metab . 2008; 93:2454-2462. 8. Nieman LK, Biller BM, Findling JW, et al. Treatment of Cushing's Syndrome: An Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2015; 100:2807-2831. Elizabeth Smith, MD, is a Medicine-Pediatrics Resident at Louisiana State University School of Medicine in New Orleans. Catherine Pisano is a medical student at Louisiana State University School of Medicine in New Orleans. Robert Richards, MD, was previously a faculty member of the Endocrine section at LSU School of Medicine in New Orleans. Taniya DeSilva, MD, is the acting section chief and fellowship program director of Endocrinology at LSU School of Medicine in New Orleans. Fred Lopez, MD, is the Richard Vial Professor and Vice Chair of Education in the Department of Medicine at LSUHSC-New Orleans.
J La State Med Soc VOL 170 JANUARY/FEBRUARY 2018 27
Made with FlippingBook Digital Publishing Software