Virilizing Ovarian Leydig Cell Tumor in A Woman with Subclinical Cushing Syndrome

ObjectiveTo report the case of a patient with a virilizing ovarian Leydig cell tumor and subclinical Cushing syndrome attributable to an adrenal adenoma.MethodsDetailed clinical, laboratory, radiologic, and pathologic findings are presented, and the pertinent literature is reviewed.ResultsA 49-year-old woman was referred for evaluation of a left adrenal mass (3.0 by 2.4 cm), which had been diagnosed by computed tomographic scan 4 years previously during a work-up for hirsutism. On examination, she had central obesity, facial hirsutism, and male pattern baldness. Work-up showed elevated total and free testosterone levels of 196 ng/dL (reference range, 20 to 70) and 24 pg/mL (1 to 9), respectively. Other results (and reference ranges) were as follows: dehydroepiandrosterone sulfate, 7.5 μg/dL (10 to 221); corticotropin, 12 pg/mL (5 to 50); morning cortisol, 1.4 μg/dL after a 1-mg overnight dexamethasone suppression test; and urine free cortisol, 48.8 μg/24 h (20 to 100). The testosterone level decreased by 14% after a 2-day low-dose dexamethasone suppression test. Findings on transvaginal ovarian ultrasonography and a computed tomographic scan of the pelvis were normal. A laparoscopic adrenalectomy revealed an adrenal adenoma. On the first day postoperatively, the cortisol level was less than 1.0 μg/dL; however, the testosterone level remained elevated. At 6 months postoperatively, a normal result of a cosyntropin stimulation test indicated recovery of the hypothalamic-pituitaryadrenal axis. Bilateral oophorectomy revealed a 1.3-cm right ovarian Leydig cell tumor. Postoperatively, the testosterone level declined to less than 20 ng/dL.ConclusionTo our knowledge, this is the first case report of a virilizing ovarian Leydig cell tumor in a patient with subclinical Cushing syndrome. (Endocr Pract. 2008;14:358-361)     

Virilizing Adrenal Ganglioneuroma in a Woman with Subclinical Cushing Syndrome

ObjectiveTo describe a patient with a virilizing adrenal ganglioneuroma and subclinical Cushing syndrome.MethodsDetailed clinical, laboratory, radiologic, and pathologic findings are presented, and the pertinent literature is reviewed.ResultsA 56-year-old postmenopausal woman was referred for evaluation of a 3.6- by 3.0-cm right adrenal mass, which had been diagnosed during a work-up for hirsutism. A bilateral oophorectomy done 2 months before the presentation failed to correct the elevated testosterone levels. On examination, she had severe hirsutism on her face, chest, back, and extremities, as well as male pattern baldness and clitoromegaly. Biochemical evaluation showed elevated total and free serum testosterone levels of 319 ng/dL (reference range, 20 to 70) and 78 pg/mL (reference range, 1 to 9), respectively, values in the adult male range. The serum dehydroepiandrosterone sulfate level was 117 μ/dL (reference range, 10 to 152), and the urine free cortisol was 10.4 μg/24 h (reference range, < 45). A laparoscopic adrenalectomy revealed a 5.0-cm adrenal ganglioneuroma containing nests of adrenocortical cells. On the first day postoperatively, the serum cortisol level was < 1.0 μg/dL. At 1 month after adrenalectomy, the total and free testosterone levels had declined to 16 ng/dL and 3.1 pg/mL, respectively. At 2 months postoperatively, normal results of a cosyntropin stimulation test (basal and peak cortisol levels of 13.6 and 20.0 μg/dL, respectively) indicated recovery of the hypothalamic-pituitary-adrenal axis.ConclusionTo our knowledge, this is the first case report of a virilizing adrenal ganglioneuroma with this unique pathologic finding and concomitant subclinical Cushing syndrome. (Endocr Pract. 2008;14:584-587)     

Addison’S Disease in Evolution: An Illustrative Case and Literature Review

ObjectiveTo present a case of symptomatic autoimmune adrenal insufficiency with initially normal serum cortisol and to caution about limitations of the current diagnostic algorithm for adrenal insufficiency, which does not reflect the pathophysiology of early disease.MethodsWe describe the clinical presentation and relevant investigations of a patient ultimately found to have Addison’s disease, which is followed by a focused review of the literature.ResultsA 41-year-old Caucasian woman with autoimmune hypothyroidism, premature ovarian failure, and microscopic colitis presented with nausea, salt craving, increased skin pigmentation, and postural hypotension. Initial bloodwork revealed a normal morning cortisol of level of 19.2 μg/dL (normal, 7.2 to 25 μg/dL) but an adrenocorticotropic hormone (ACTH) level 10 times normal, at 513.6 pg/mL (normal, < 52.5 pg/mL). Her potassium was normal, but her aldosterone level was 4.12 ng/dL (normal, 12.3 to 62.5 ng/dL) and her renin activity was increased (23.0 mg/dL/hour; normal, < 6.0 mg/dL/hour). Six weeks after initial presentation, she was found to have anti-adrenal antibodies. It was not until 10 weeks after her initial symptomatic presentation that her morning cortisol level was found to be subnormal and a formal diagnosis of adrenal insufficiency was made.ConclusionThe present case and literature review reveal that common diagnostic approaches will miss patients with (possibly symptomatic) early adrenal insufficiency. We suggest that serum ACTH level testing or tests of mineralocorticoid function be included in the initial step of investigation for suspected primary adrenal insufficiency. (Endocr Pract. 2014;20:e176-e179)     

Metformin-Responsive Classic Salt-Losing Congenita L Adrenal Hyperplasia Due to 21-Hydroxylase Deficiency: a Case Report

ObjectiveTo study the effect of adding metformin to standard steroid replacement therapy in a patient with classic salt-losing congenital adrenal hyperplasia due to 21- hydroxylase deficiency with suboptimal biochemical and clinical control.MethodsWe present the clinical and laboratory findings before and after the addition of metformin to the therapeutic regimen of the study patient.ResultsA 17-year-old girl had been diagnosed as a neonate with classic salt-losing congenital adrenal hyperplasia caused by 21-hydroxylase deficiency (CYP21A2 deficiency). She was treated with hydrocortisone, 20 mg in the morning and 10 mg at bedtime, and fludrocortisone, 50 mcg daily. While on steroid replacement, she maintained normal serum electrolytes, glucose, blood pressure, and external genitalia, but she continued to express clinical features of obesity, hirsutism, amenorrhea, and acanthosis nigricans. Elevated laboratory measurements included the following: fasting 17-hydroxyprogesterone, 3410 ng/dL; total testosterone, 326 ng/dL; and androstenedione, 390 ng/dL. She was initiated on metformin, 500 mg twice daily after meals. After 3 months, the patient lost 2 kg, amenorrhea resolved, 17-hydroxyprogesterone decreased to 1539 ng/dL, total testosterone decreased to 163 ng/dL, and androstenedione levels remained unchanged.ConclusionsMetformin, an agent known to reduce insulin resistance, further suppressed the 17-hydroxyprogesterone concentration in a patient with classic congenital adrenal hyperplasia on steroid replacement therapy. Metformin may improve clinical and biochemical outcomes in classic congenital adrenal hyperplasia without the risk of iatrogenic Cushing syndrome. (Endocr Pract. 2008;14:889-891)     

Long-Term Management with Octreotide or Cabergoline in Ectopic Corticotropin Hypersecretion: Case Report and Literature Review

ObjectiveTo describe the corticotropin response to long-term octreotide or cabergoline administration in a patient with ectopic corticotropin secretion who underwent adrenalectomy.MethodsWe describe the clinical, radiologic, and biochemical findings of the study patient over the course of 18 years.ResultsA 40-year-old woman was evaluated for Cushing syndrome. On the basis of biochemical indices, Cushing disease was diagnosed and pituitary exploration was performed. No cure was achieved. Computed tomography of the chest revealed a right lung nodule due to a lung carcinoid tumor that was then surgically excised. Because of persistent hypercortisolism, total adrenalectomy was performed. Subsequently, corticotropin levels rose dramatically and hyperpigmentation developed while serum cortisol was in the reference range. The patient was treated with octreotide for 3 years and then with cabergoline for 8 years. While taking octreotide, corticotropin values decreased, accompanied by depigmentation and development of signs of adrenal insufficiency, which led to the reinstitution of supplemental hydrocortisone. Cabergoline induced a similar long-lasting effect on the clinical and biochemical parameters observed. Eight years later, she is still treated with cabergoline, and no lung tumor has been detected.ConclusionsIn this patient with ectopic Cushing syndrome, treatment with either octreotide or cabergoline markedly reduced corticotropin levels and hyperpigmentation. (Endocr Pract. 2010;16:829-834)     

Is Pseudo-Cushing’s Syndrome in a Critically ILL Patient “Pseudo”? Hypothesis and Supportive Case Report

ObjectiveTo propose a new hypothesis regarding the possible role of glucocorticoid excess in patients with an extended acute illness, based on a patient’s presentation and therapy in a critical care situation.MethodsWe present a detailed case report, review the related literature, and suggest the need for prospective studies to determine the appropriate intervention in critically ill patients with pseudo-Cushing’s syndrome.ResultsA 50-year-old woman with diabetes and obesity who underwent vertical banded gastroplasty had postoperative complications, including refractory gastrostomy leakage, peritoneal and abdominal wall infections, and multiorganism sepsis despite intensive antibiotic therapy and surgical drainage procedures. Her physical appearance, elevated and relatively nonsuppressible plasma cortisol levels, and radiologic study supported a tentative diagnosis of Cushing’s syndrome in a critically ill patient. Intravenously administered itraconazole and rectally administered aminoglutethimide were used to suppress endogenous glucocorticoid synthesis. Glucocorticoids were administered at dosages that provided 1/3 to 1/2 of her expected maximal daily cortisol secretion during her complicated hospital course. Insulin resistance declined with adrenal suppression and infection control, and wound healing improved dramatically. Adrenal suppression was discontinued, and she was reevaluated for hypercortisolism. Results of all studies for Cushing’s syndrome were normal and remained so 1 year later.ConclusionIn our patient, substantially increased glucocorticoid levels were associated with severe insulin resistance, retarded wound healing, and persistent infections. Suppression of endogenous cortisol production and replacement with more physiologic concentrations of glucocorticoid were associated with clinical improvement and appeared to contribute to her recovery. Review of the literature leads us to propose the following hypotheses: (1) that considerably increased stress-induced cortisol concentrations in critically ill patients may contribute to adverse outcomes and (2) that therapeutic suppression of the persistent and substantially elevated glucocorticoid levels in selected cases may be a beneficial therapeutic option. (Endocr Pract. 2007;13:153-158)     

Unusual Cause of Ectopic Secretion of Adrenocorticotropic Hormone: Cushing Syndrome Attributable to Small Cell Prostate Cancer

ObjectiveTo report a rare cause of ectopic adrenocorticotropic hormone (ACTH) secretion leading to severe Cushing syndrome.MethodsWe describe the clinical presentation and management of a case of Cushing syndrome attributable to ectopic ACTH secretion from small cell cancer of the prostate.ResultsIn a 70-year-old man with hypertension and diabetes, congestive heart failure developed. He was found to have severe hypokalemia (serum potassium, 1.7 mEq/L) and a huge pelvic mass on a computed tomographic scan performed because of a complaint of urinary retention. Transurethral biopsy of the prostate showed features of small cell prostate cancer. Hormonal evaluation revealed a high urine free cortisol excretion of 6,214.5 μg/d (reference range, 36 to 137), confirming the diagnosis of Cushing syndrome. A serum ACTH level was elevated at 316 ng/dL (reference range, 10 to 52). An overnight highdose (8 mg orally) dexamethasone suppression test was positive (serum cortisol levels were 43.2 and 41 μg/dL before and after suppression, respectively), and magnetic resonance imaging of the pituitary gland disclosed no abnormalities. A prostate biopsy specimen showed small cell prostate cancer with positive staining for ACTH. The tumor was found to be unresectable, and the poor condition of the patient did not allow for bilateral adrenalectomy. He was treated with ketoconazole and metyrapone, which yielded good temporary control of his Cushing syndrome (24-hour urine free cortisol decreased to 55.2 μg/d). He received 1 cycle of chemotherapy (etoposide and cisplatin), but he died 6 months later as a result of sepsis.ConclusionSmall cell prostate cancer is a rare subtype that can be associated with ectopic secretion of ACTH and severe Cushing syndrome. With this subtype of prostate cancer, Cushing syndrome should be considered and appropriately managed. (Endocr Pract. 2010;16:249-254)     

Corticotropin-Independent Macronodular Adrenal Hyperplasia Associated With Insulinoma

ObjectiveTo report a case of corticotropin-independent macronodular adrenal hyperplasia (AIMAH) associated with an insulinoma.MethodsWe describe the clinical, radiographic, laboratory, and histopathologic findings of the study patient; review the current protocols for management of AIMAH; and discuss the disease etiology.ResultsA 64-year-old woman with multiple intradermal facial nevi experienced intermittent light-headedness, tremor, and confusion and was found to have a venous plasma glucose concentration of 52 mg/dL. Hypoglycemia and hyperinsulinemia after 18 hours of fasting suggested the presence of an insulinoma. Hepatic venous sampling for insulin after selective arterial calcium injection localized the insulinoma to the pancreatic head. The insulinoma was excised, and there was no recurrence over the 5 years the patient was in our care. During the workup for insulinoma, bilateral adrenal masses were incidentally discovered on computed tomography. Twenty-hour urinary free cortisol excretion was elevated and serum corticotropin was suppressed. Overt signs of Cushing syndrome were not present, and subsequent urinary cortisol measurements were within the reference range for several years. After 4 years, Cushing syndrome developed and bilateral adrenalectomy was performed. AIMAH was diagnosed on the basis of histopathologic findings.ConclusionsThis appears to be the first reported case of AIMAH associated with an insulinoma. In the absence of other stigmata of multiple endocrine neoplasm type 1 and in the presence of multiple nevi, it may represent a novel endocrine syndrome. (Endocr Pract. 2011;17:e43-e47)     

Glucocorticoid- and Androgen-Secreting Black Adrenocortical Adenomas: Unique Cause of Corticotropin-Independent Cushing Syndrome

ObjectiveTo describe the unique association of corticotropin-independent Cushing syndrome caused by cortisoland androgen-secreting black adrenal cortical adenomas with myelolipomatous change.MethodsWe report the clinical, laboratory, radiologic, and pathologic findings from 2 patients who presented with androgen excess and typical signs and symptoms of Cushing syndrome.ResultsEndocrine investigations showed high serum cortisol concentrations that lacked diurnal rhythm, undetectable plasma corticotropin concentrations, and absence of serum cortisol suppression after overnight dexamethasone suppression tests. Serum levels of adrenal androgens were elevated. Computed tomography of the abdomen revealed unilateral adrenal masses (largest lesional diameters 4.0 and 3.1 cm). On the basis of the plurihormonal hypersecretion and the imaging characteristics, adrenocortical carcinoma was considered as a possible diagnosis. However, histopathologic analysis in both patients revealed black adrenal cortical adenomas with myelolipomatous change. After surgery, adrenal androgens normalized, and the signs and symptoms of Cushing syndrome and androgen excess resolved. There was no evidence of recurrent disease at last follow-up.ConclusionsA unique form of corticotropin-independent Cushing syndrome is described: cortisoland androgen-secreting black adrenal cortical adenomas with myelolipomatous change. Although most patients with corticotropin-independent Cushing syndrome associated with androgen excess prove to have adrenocortical carcinoma, the clinician should be aware of the possibility of benign, black adrenal adenomas in this clinical setting. (Endocr Pract. 2011;17:e73-e78)     

Biochemical Diagnosis of Adrenal Insufficiency: the Added Value of Dehydroepiandrosterone Sulfate Measurements

ObjectiveTo review biochemical tests used in establishing the challenging diagnosis of adrenal insufficiency.MethodsWe reviewed the relevant literature, including our own data, on various biochemical tests used to determine adrenal function. The advantages and limitations of each approach are discussed.ResultsBaseline measurements of serum cortisol are helpful only when they are very low (≤ 5 μg/dL) or clearly elevated, whereas baseline plasma adrenocorticotropic hormone levels are helpful only when primary adrenal insufficiency is suspected. Measurements of baseline serum dehydroepiandrosterone sulfate (DHEA-S) levels are valuable in patients suspected of having adrenal insufficiency. Although serum DHEA-S levels are low in patients with primary or central adrenal insufficiency, a low level of this steroid is not sufficient by itself for establishing the diagnosis. A normal age- and sex-adjusted serum DHEA-S level, however, practically rules out the diagnosis of adrenal insufficiency. Many patients require dynamic biochemical studies, such as the 1-μg cosyntropin test, to assess adrenal function.ConclusionIn establishing the diagnosis of central adrenal insufficiency, we recommend measurements of baseline serum cortisol and DHEA-S levels. In addition to these, determination of plasma levels of aldosterone, adrenocorticotropic hormone, and renin activity is necessary when primary adrenal insufficiency is suspected. With a random serum cortisol level of ≥ 12 μg/dL in the ambulatory setting or a normal age- and sex-adjusted DHEA-S level (or both), the diagnosis of adrenal insufficiency is extremely unlikely. When serum DHEA-S levels are low or equivocal, however, dynamic testing will be necessary to determine hypothalamic-pituitary-adrenal axis function. (Endocr Pract. 2011;17:261-270)     

Diagnosing Adrenal Insufficiency: Which Test is Best—The 1-μG or the 250-μG Cosyntropin Stimulation Test?

ObjectiveTo review the available literature on the low-dose cosyntropin stimulation test (CST) for the diagnosis of primary and secondary adrenal insufficiency in both nonstressed and acutely ill patients.MethodsWe performed a MEDLINE search of all English-language literature, published between 1965 and 2007, in which the 1-μg and the 250-μg CSTs were compared in patients with primary and secondary adrenal insufficiency.ResultsThe majority of published evidence suggests that the 1-μg CST is more sensitive than the 250-μg CST for the diagnosis of secondary adrenal insufficiency in nonstressed patients. In patients with primary adrenal insufficiency, the low-dose CST is unlikely to add any diagnostic sensitivity to the high-dose CST. In critically ill patients, the 1-μg test is also likely to be more sensitive than the 250-μg test when an appropriate cutoff value is used (25 μg/dL).ConclusionThe 1-μg CST with a cortisol level determined at 30 minutes after stimulation, with use of a cutoff level of 18 to 20 μg/dL in nonstressed patients and less than 25 μg/dL or an increment of less than 9 μg/dL from baseline in critically ill patients, is the best test that is currently available for establishing the diagnosis of secondary adrenal insufficiency. (Endocr Pract. 2008;14: 233-238)     

Cushing’s Disease and Pregnancy: Case Report and Literature Review

ObjectiveTo describe a patient with untreated Cushing’s disease who had 2 spontaneous pregnancies that resulted in healthy babies on both occasions.MethodsWe present a case report with clinical, laboratory, and imaging data and discuss the literature pertaining to pregnancy in patients with Cushing’s syndrome.ResultsA 28-year-old woman came to our endocrinology clinic with a 1-year history of symptoms and signs of Cushing’s syndrome. An elevated 24-hour urinary cortisol excretion and an unsuppressed 1-mg overnight dexamethasone test confirmed the diagnosis. On her next visit, she reported a confirmed pregnancy, which ultimately resulted in the birth of a normal child. Further work-up subsequently showed 2 elevated 24-hour urinary cortisol values, loss of diurnal variation, and an elevated corticotropin level. There was lack of suppression on low-dose and high-dose overnight dexamethasone suppression tests. Magnetic resonance imaging of the pituitary showed normal findings. Inferior petrosal sinus sampling was recommended, but she declined the procedure. The patient returned 3 years later for reevaluation, at which time she reported the birth of another healthy child by cesarean delivery 10 months previously. There were no reported maternal or fetal complications. Examination at this visit revealed buccal pigmentation and proximal myopathy. Investigations showed increased 24-hour urinary cortisol excretion and serum corticotropin levels. Repeated magnetic resonance imaging disclosed a microadenoma on the right side of the pituitary. Unstimulated inferior petrosal sinus sampling showed a gradient to the right; thus, the presence of pituitary-dependent Cushing’s disease was confirmed.ConclusionOur case demonstrates that patients with pituitary-dependent Cushing’s disease are more likely to have spontaneous pregnancies with favorable outcomes than are patients with Cushing’s syndrome due to other causes. Our patient, despite having Cushing’s disease for more than 7 years, had 2 uneventful pregnancies that produced normal healthy children, without exacerbation of her disease during pregnancy. (Endocr Pract. 2007;13: 296-299)     

Diagnostic Predicament of Secondary Adrenal Insufficiency

ObjectiveTo propose an approach for the diagnosis of secondary adrenal insufficiency(AI) by presentation of 2 clinical cases and review of the literature.MethodsWe describe 2 patients who were considered to have a normal hypothalamic-pituitary-adrenal axis on the basis of an appropriate response to the high-dose (250 μg) cosyntropin stimulation test (HST), with use of a cutoff value of 20 μg/dL. Our first patient had undergone resection of a 4-cm pituitary tumor a few months previously, and the second patient had hyponatremia with empty sella syndrome. Both patients, however, had strong clinical evidence suggestive of secondary AI. On testing by the insulin tolerance test (ITT) in the first patient and the overnight metyrapone test (OMT) in the second patient, secondary AI was diagnosed. We reviewed the literature to compare the utility of the different tests for the diagnosis of secondary AI.ResultsAn 8 am serum cortisol value less than 5 μg/ dL or above 13 μg/dL and a stimulated cortisol level less than 16 μg/dL on both the low-dose cosyntropin stimulation test (LST) and the HST as well as above 22 μg/dL on the LST and above 30 μg/dL on the HST can reliably predict the functional status of the hypothalamic-pituitaryadrenal axis in chronic secondary AI. Values between these utoff points may necessitate further assessment with the OMT or ITT based on clinical suspicion.ConclusionWe recommend a 3-step diagnostic approach, with the first 2 steps performed together—starting with the 8 am basal cortisol determination in conjunction with either the LST (preferably) or the HST. In cases of an indeterminate response coupled with a strong clinical suspicion, the final step should be definitive testing with the OMT or ITT. (Endocr Pract. 2010;16:686-691)     

Adrenocorticotropic Hormone Stimulation Test During High-Dose Glucocorticoid Therapy

ObjectiveTo define the effective time frame of adequate serum cortisol response to the short standard 250-μg adrenocorticotropic hormone stimulation test (ACTH-ST) after initiation of high-dose glucocorticoid therapy in order to assist in the diagnosis of adrenal insufficiency.MethodsWe performed an ACTH-ST at 4 different times in hospitalized patients, who had a documented intact hypothalamic-pituitary-adrenal axis and were receiving high-dose dexamethasone therapy for nonendocrine diseases, to determine the time until the serum cortisol response is compromised. The ACTH-ST was performed at the following time intervals after initiation of dexamethasone therapy—24, 48, 72, and 96 hours. The outcome measures were cortisol levels measured at 0, 30, and 60 minutes after administration of 250 μg of cosyntropin.ResultsOf the overall group of 11 study patients, all those (n = 8) tested within the first 72 hours after initiation of dexamethasone therapy had an adequate response (serum cortisol level at 60 minutes, ≥ 18 μg/dL). Two of the 3 patients tested at 96 hours after initiation of dexamethasone therapy had a suppressed cortisol response at 60 minutes. At 30 minutes, all cortisol levels except 1 were inadequate (< 18 μg/dL).ConclusionThis study suggests indirectly that the ACTH-ST may be used for the diagnosis of suspected adrenal insufficiency within the first 3 days after initiation of empiric glucocorticoid therapy. An inadequate response of serum cortisol at 60 minutes to the ACTH-ST may be indicative of adrenal insufficiency in this setting. Additional studies with more patients in each therapy time point are needed to confirm these initial results. (Endocr Pract. 2009;15:122-127)     

New Diagnostic Cutoffs for Adrenal Insufficiency After Cosyntropin Stimulation Using Abbott Architect Cortisol Immunoassay

IntroductionThe accurate interpretation of the cosyntropin (adrenocorticotropic hormone [ACTH]) stimulation test requires method- and assay-specific cutoffs of the level of cortisol. Compared with a historical cutoff (18 μg/dL) for polyclonal antibody-based immunoassays, lower thresholds were proposed for the Roche Elecsys II assay, which uses a monoclonal antibody. However, cutoffs for other commonly adopted, monoclonal antibody-based cortisol assays were not yet available. Here, we established the thresholds for the level of cortisol specific to the Abbott Architect immunoassay by comparing the measurements of the level of cortisol using 3 immunoassays.MethodsThe ACTH stimulation test was performed in patients with suspected adrenal insufficiency (n = 50). The serum cortisol level was measured using the Abbott Architect, Roche Elecsys II, and Siemens Centaur assays. The results of the Abbott assay were also compared with those of liquid chromatography-tandem mass spectrometry. The receiver operating characteristic analysis was performed to derive new diagnostic thresholds for the Abbott assay using the polyclonal antibody-based Siemens assay as the reference method.ResultsThe concentrations of cortisol measured using the Abbott assay were similar to those measured using liquid chromatography-tandem mass spectrometry and the Roche Elecsys II assay but significantly lower than those measured using the Siemens assay. The optimized threshold for cortisol using the Abbott assay was 14.6 μg/dL at 60 minutes after stimulation (sensitivity, 92%; specificity, 96%) and 13.2 μg/dL at 30 minutes after stimulation (sensitivity, 100%; specificity, 89%).ConclusionWe recommend a threshold of 14.6 μg/dL for the level of cortisol at 60 minutes after ACTH stimulation for the Abbott assay. In comparison with the historical threshold of 18 μg/dL, the application of the new cutoff may significantly decrease false-positive results due to ACTH stimulation testing. The use of assay-specific cutoffs will be essential for reducing misclassification and overtreatment in patients with suspected adrenal insufficiency.     

Corticotropin-Independent Cushing Syndrome in a Child With an Ovarian Tumor Misdiagnosed as Nonclassic Congenital Adrenal Hyperplasia

ObjectiveTo describe a patient with corticotropinindependent Cushing syndrome previously diagnosed and treated as congenital adrenal hyperplasia (CAH).MethodsWe describe the initial manifestations, clinical investigations, and postoperative follow-up of the patient and review similar cases in the literature.ResultsA 5 and 9/12-year-old girl who was initially diagnosed and treated as having CAH and was noncompliant with glucocorticoid therapy presented with weight gain, hypertension, and a mass in the lower abdomen. On physical examination, she was a cushingoid-appearing girl with proximal muscle weakness and notable facial acne. Laboratory findings included elevated serum testosterone, 17-hydroxyprogesterone, dehydroepiandrosterone sulfate, androstenedione, estradiol, and cortisol, as well as elevated urinary cortisol and cortisone. Serum corticotropin was undetectable. She had normal serum electrolytes and plasma renin activity. Computed tomography scan of the abdomen and pelvis showed a cystic mass with a focal enhancing solid component arising from the right ovary, which was subsequently determined to be a steroid cell tumor not otherwise specified.ConclusionAlthough ovarian steroid cell tumors typically secrete gonadal steroids, the rare steroid cell tumors not otherwise specified can secrete both glucocorticoids and gonadal steroids and are an unusual cause of Cushing syndrome. (Endocr Pract. 2008;14:875-879)     

Hypocortisolemia in Graves Hyperthyroidism

ObjectiveTo assess the risk of concomitant adrenal sufficiency in 2 patients with Graves thyrotoxicosis.MethodsWe present the clinical course and laboratory findings of 2 patients with hyperthyroidism associated with low basal serum cortisol and briefly review the literature with regard to possible mechanisms of hypocortisolemia in thyrotoxic states.ResultsTwo women aged 37 and 43 years with longstanding Graves disease presented with hyperthyroidism secondary to nonadherence to prescribed antithyroid medications. Both women also had symptoms suggestive of adrenal insufficiency including nausea, vomiting, and diffuse abdominal pain in Patient 1 and fatigue and hypotension in Patient 2. In both patients, physical examination findings were consistent with hyperthyroidism. Laboratory results of Patient 1 included the following: thyrotropin, < 0.002 mIU/L; free thyroxine, > 6 μg/dL; and total triiodothyronine, 539 ng/dL. Laboratory results of Patient 2 included the following: thyrotropin, < 0.002 mIU/L; free thyroxine, > 6 μg/dL; and total triiodothyronine, 539 ng/dL. Morning basal cortisol levels were 0.9 μg/dL in Patient 1 and 0.6 pg/dL in Patient 2. Because of the low basal serum cortisol levels, the patients underwent a high-dose (250 mcg) cosyntropin-stimulation test; however, both patients had adequate cortisol response. At 60 minutes, serum cortisol concentration was 31.4 μg/dL in Patient 1 and 25.5 pg/dL in Patient 2. After adequately treating the hyperthyroidism, basal cortisol levels in both patients returned to the reference range.ConclusionSymptomatic hypocortisolemia may be present in severe hyperthyroidism, and it resolves with adequate treatment of the hyperthyroidism. (Endocr Pract. 2009;15:220-224)     

Adrenocorticotropic Hormone-Independent Cushing Syndrome Manifesting During Pregnancy

ObjectiveTo report a case of adrenocorticotropic hormone-independent Cushing syndrome(CS) diagnosed and treated surgically during the third trimester of pregnancy and resulting in delivery of a healthy baby boy.MethodsWe present a detailed case report, and we review and evaluate the English-language literature on CS during pregnancy.ResultsDuring pregnancy, the occurrence of CS is a rare event. The diagnosis of CS during pregnancy is difficult to establish because of the normal physiologic hypercortisolemia of pregnancy. In our patient, laboratory testing revealed a random serum cortisol level of 56.5 μg/dL, a suppressed plasma adrenocorticotropic hormone level (< 5 pg/mL), and a substantially elevated 24-hour urinary cortisol (1,708 μg). Noncontrast magnetic resonance imaging of the abdomen disclosed a 3.5-cm left adrenal mass. Laparoscopic left adrenalectomy was successfully performed during the early third trimester, and a healthy baby was born at 36 weeks of gestation by means of a cesarean delivery.ConclusionThe occurrence of CS during pregnancy is rare; however, when it does occur, adrenal tumors are more common than pituitary tumors. Caution should be used during interpretation of laboratory tests to evaluate for CS during pregnancy because of the normal increase in hypothalamic-pituitary-adrenal axis function during pregnancy. The current case demonstrates the safety and utility of noncontrast magnetic resonance imaging for localization of a tumor during pregnancy, as well as the safe use of laparoscopic surgical treatment of CS during the early third trimester. (Endocr Pract. 2010;16:260-263)     

Cushing Syndrome in a Young Woman Due to Primary Pigmented Nodular Adrenal Disease

ObjectiveTo report a case of Cushing syndrome due to apparently sporadic primary pigmented nodular adrenal disease in a young woman.MethodsWe describe the clinical, biochemical, radiologic, and histologic findings of Cushing syndrome due to the rare condition of primary pigmented nodular adrenal disease.ResultsA 30-year-old woman presented with a 2-year history of worsening itch without rash over her shoulders and arms and weight gain, particularly around the abdomen and face. Careful questioning did not elicit any history of exogenous glucocorticoid use (systemic or topical), including hydrocortisone. On examination, the patient had a slightly rounded and plethoric face, a small buffalo hump, central adiposity, and thin skin with a few small striae on her inner thighs. No features of the Carney complex were observed. Investigations showed hypercor- tisolism with suppressed corticotropin and normal adrenal imaging despite documentation of enlarged adrenal glands at removal. High-dose dexamethasone administration was followed by a decrease in urinary free cortisol excretion rather than a paradoxical rise as previously reported in primary pigmented nodular adrenal disease. No mutations were detected in the PRKAR1A gene.ConclusionsPrimary pigmented nodular adrenal disease should be suspected in patients with corticotropinindependent Cushing syndrome who have normal adrenal imaging. The role of genetic testing in apparently sporadic cases is not established, but cumulative experience may be helpful in defining the frequency of PRKAR1A mutations. (Endocr Pract. 2010;16:84-88)