Many Endocrinologists believe that a single determination of eucortisolism or a single demonstration of appropriate suppression to dexamethasone excluded Cushing’s syndrome, except in what was previously thought to be the rare patient with episodic or periodic Cushing’s syndrome. We hypothesize that episodic Cushing’s syndrome is relatively common and a single test assessing hypercortisolism may not be sufficient to accurately rule out or diagnose Cushing’s syndrome and retrospectively examined the number of normal and abnormal tests assessing hypercortisolism performed on multiple occasions in 66 patients found to have mild and/or episodic Cushing’s syndrome compared to a similar group of 54 patients evaluated for, but determined not to have Cushing’s syndrome. We found that 65 of the 66 patients with Cushing’s syndrome had at least one normal test of cortisol status and most patients had several normal tests. The probability of having Cushing’s syndrome when one test was negative was 92 % for 23:00 h salivary cortisol, 88 % for 24-h UFC, 86 % for 24-h 17OHS, and 54 % for nighttime plasma cortisol. These results demonstrated that episodic hypercortisolism is highly prevalent in subjects with mild Cushing’s syndrome and no single test was effective in conclusively diagnosing or excluding the condition. Rather, the paradigm for the diagnosis should be a careful history and physical examination and in those patients in whom mild Cushing’s syndrome/disease is strongly suspected, multiple tests assessing hypercortisolism should be performed on subsequent occasions, especially when the patient is experiencing signs and symptoms of short-term hypercortisolism.
Cushing’s syndrome; episodic; periodic; urinary free cortisol; salivary cortisol; cortisol-binding globulin; 17-hydroxycorticosteroids
Congenital adrenal hyperplasia (CAH) is characterized by decreased adrenal hormone production due to enzymatic defects and subsequent rise of adrenocorticotrophic hormone that stimulates the adrenal cortex to become hyperplastic, and sometimes tumorous. As the pathophysiology is basically a defect in the biosynthesis of cortisol, one may not consider CAH in patients with hypercortisolism. We report a case of a 41-yr-old man with a 4 cm-sized left adrenal tumorous lesion mimicking Cushing's syndrome who was diagnosed with CAH. He had central obesity and acanthosis nigricans involving the axillae together with elevated 24-hr urine cortisol level, supporting the diagnosis of Cushing's syndrome. However, the 24-hr urine cortisol was suppressed by 95% with the low dose dexamethasone suppression test. CAH was suspected based on the history of precocious puberty, short stature and a profound suppression of cortisol production by dexamethasone. CAH was confirmed by a remarkably increased level of serum 17-hydroxyprogesterone level. Gene mutation analysis revealed a compound heterozygote mutation of CYP21A2 (I173N and R357W).
Congenital Adrenal Hyperplasia; 21-Hydroxylase Deficiency; Hypercortisolism
The severity of Cushing’s Syndrome (CS) depends on the duration and extent of the exposure to excess glucocorticoids. Current measurements of cortisol in serum, saliva and urine reflect systemic cortisol levels at the time of sample collection, but cannot assess past cortisol levels. Hair cortisol levels may be increased in patients with CS, and, as hair grows about 1 cm/month, measurement of hair cortisol may provide historical information on the development of hypercortisolism. We attempted to measure cortisol in hair in relation to clinical course in six female patients with CS and in 32 healthy volunteers in 1 cm hair sections. Hair cortisol content was measured using a commercially available salivary cortisol immune assay with a protocol modified for use with hair. Hair cortisol levels were higher in patients with CS than in controls, the medians (ranges) were 679 (279–2500) and 116 (26–204) ng/g respectively (P <0.001). Segmental hair analysis provided information for up to 18 months before time of sampling. Hair cortisol concentrations appeared to vary in accordance with the clinical course. Based on these data, we suggest that hair cortisol measurement is a novel method for assessing dynamic systemic cortisol exposure and provides unique historical information on variation in cortisol, and that more research is required to fully understand the utility and limits of this technique.
glucocorticoids; pituitary adenoma; cancer; adrenal gland; hormones; cushing hair
Reported cases of cyclical Cushing's syndrome are rare. Of 14 successive patients with Cushing's syndrome nine collected sequential urine samples for the estimation of cortisol:creatinine ratio. Five had cyclical Cushing's syndrome while two had considerable variation in urinary cortisol excretion without a cyclical pattern being established. Two of the five patients with a cyclical syndrome had paradoxical responses to dexamethasone. In only one patient with a cyclical pattern did the cortisol:creatinine ratio fall after treatment with bromocriptine or cyproheptadine, or both. The high incidence of the cyclical form of Cushing's syndrome has important clinical implications. A high index of suspicion of the syndrome is required in patients with symptoms or signs of Cushing's syndrome but with normal cortisol values, in patients with fluctuating cortisol values, and in patients with anomalous responses to dexamethasone. Because of possible variations in steroidogenesis the results of drug studies in Cushing's syndrome must be interpreted cautiously.
Cushing’s syndrome is caused by prolonged exposure to excess glucocorticoids. Diagnosis of Cushing’s syndrome involves a step-wise approach and establishing the cause can be challenging in some cases. Hypertension is present in about 80% of patients with Cushing’s syndrome and can lead to significant morbidity and mortality. Several pathogenic mechanisms have been proposed for glucocorticoid-induced hypertension including a functional mineralocorticoid excess state, up-regulation of the renin angiotensin system and deleterious effects of cortisol on the vasculature. Surgical excision of the cause of excess glucocorticoids remains the optimal treatment for Cushing’s syndrome. Anti-glucocorticoid and antihypertensive agents and steroidogenesis inhibitors can be used as adjunctive treatment modalities in preparation for surgery, and in cases where surgery is contraindicated or has not led to cure.
Cushing’s syndrome; hypertension; glucocorticoids; ectopic ACTH secretion; 11-beta hydroxysteroid dehydrogenase; hypercortisolemia
Endogenous Cushing’s syndrome is a grave disease that requires a multidisciplinary and individualized treatment approach for each patient. Approximately 80% of all patients harbour a corticotroph pituitary adenoma (Cushing’s disease) with excessive secretion of adrenocorticotropin-hormone (ACTH) and, consecutively, cortisol. The goals of treatment include normalization of hormone excess, long-term disease control and the reversal of comorbidities caused by the underlying pathology. The treatment of choice is neurosurgical tumour removal of the pituitary adenoma. Second-line treatments include medical therapy, bilateral adrenalectomy and radiation therapy. Drug treatment modalities target at the hypothalamic/pituitary level, the adrenal gland and at the glucocorticoid receptor level and are commonly used in patients in whom surgery has failed. Bilateral adrenalectomy is the second-line treatment for persistent hypercortisolism that offers immediate control of hypercortisolism. However, this treatment option requires a careful individualized evaluation, since it has the disadvantage of permanent hypoadrenalism which requires lifelong glucocorticoid and mineralocorticoid replacement therapy and bears the risk of developing Nelson’s syndrome. Although there are some very promising medical therapy options it clearly remains a second-line treatment option. However, there are numerous circumstances where medical management of CD is indicated. Medical therapy is frequently used in cases with severe hypercortisolism before surgery in order to control the metabolic effects and help reduce the anestesiological risk. Additionally, it can help to bridge the time gap until radiotherapy takes effect. The aim of this review is to analyze and present current treatment options in Cushing’s disease.
Cushing’s disease; operative treatment; medical therapy; bilateral adrenalectomy; radiotherapy
The purpose of this study was to investigate the clinical and hormonal features of patients with incidentally discovered adrenal adenomas in relation to corticotropin releasing hormone (CRH) testing and the clinical outcome of adrenalectomy.
Materials and Methods
Twenty-three consecutive patients with incidentally detected adrenal adenomas were included in this retrospective study. All the patients underwent abdominal computed tomography scans and hormonal assays, including assessment of circadian rhythms of plasma cortisol and corticotropin (adrenocorticotropic hormone, ACTH), a corticotropin stimulation test, and low-dose and high-dose dexamethasone tests. The patients were reevaluated at regular intervals (6, 12, and 24 months) for a median period of 24 months. Subclinical Cushing's syndrome (SCS) was diagnosed in patients with subtle hypercortisolism who did not present clinical signs of Cushing's syndrome.
We calculated the responsive index (peak value of ACTH in CRH test/baseline value of ACTH in CRH test). Of 23 patients, 6 had Cushing's syndrome, 8 had SCS, and 9 had a non-functioning tumor. All patients underwent laparoscopic adrenalectomy. Several patients (5 of 6 with Cushing's syndrome and 2 of 8 with SCS) required cortisol replacement therapy after surgery. The remaining patients required no hormonal replacement after surgery. Those who required hormone replacement had a responsive index of less than 1.2. Those who did not need hormone replacement therapy had a responsive index of more than 2.0.
In our limited experience, the responsive index of the CRH test might be a valuable tool for predicting the need for cortisol replacement after surgery in patients with SCS.
Adrenalectomy; Corticotropin-releasing hormone; Cushing syndrome
Cushing’s disease, or pituitary ACTH dependent Cushing’s syndrome, is a rare disease responsible for increased morbidity and mortality. Signs and symptoms of hypercortisolism are usually non specific: obesity, signs of protein wasting, increased blood pressure, variable levels of hirsutism. Diagnosis is frequently difficult, and requires a strict algorithm. First-line treatment is based on transsphenoidal surgery, which cures 80% of ACTH-secreting microadenomas. The rate of remission is lower in macroadenomas. Other therapeutic modalities including anticortisolic drugs, radiation techniques or bilateral adrenalectomy will thus be necessary to avoid long-term risks (metabolic syndrome, osteoporosis, cardiovascular disease) of hypercortisolism. This review summarizes potential pathophysiological mechanisms, diagnostic approaches, and therapies.
The aim of this study was to examine the frequency of Cushing’s syndrome (CS) in obese patients devoid of specific clinical symptoms of Cushing’s syndrome.
A total of 150 obese patients (129 female, 21 male; mean age 44.41 ± 13.34 yr; mean BMI 35.76 ± 7.13) were included in the study. As a first screening step, we measured 24-h urinary free cortisol (UFC). An overnight 1-mg dexamethasone suppression test was also performed on all patients. Urinary free cortisol levels above 100 μg/24 h were considered to be abnormal. Suppression of serum cortisol <1.8 μg/dL after administration of 1 mg dexamethasone was the cut-off point for normal suppression. The suppression of the serum cortisol levels failed in all of the patients.
Measured laboratory values were as follows: ACTH, median level 28 pg/ml, interquartile range (IQR) 14–59 pg/ml; fasting glucose, 100 (91–113) mg/dL; insulin, 15.7 (7.57–24.45) mU/ml; fT4, 1.17 (1.05–1.4) ng/dL; TSH, 1.70 (0.91–2.90) mIU/L; total cholesterol, 209 (170.5–250) mg/dL; LDL-c, 136 (97.7–163) mg/dL; HDL-c, 44 (37.25–50.75) mg/dL; VLDL-c, 24 (17–36) mg/dL; triglycerides, 120.5 (86–165) mg/dL. The median UFC level of the patients was 30 μg/24 h (IQR 16–103). High levels of UFC (>100 μg/24 h) were recorded in 37 patients (24%). Cushing’s syndrome was diagnosed in 14 of the 150 patients (9.33%). Etiologic reasons for Cushing’s syndrome were pituitary microadenoma (9 patients), adrenocortical adenoma (3 patients), and adrenocortical carcinoma (1 patient).
A significant proportion (9.33%) of patients with simple obesity were found to have Cushing’s syndrome. These findings argue that obese patients should be routinely screened for Cushing’s syndrome.
Cushing’s syndrome; Obesity; Screening; Cortisol; Adrenocorticorticotropic hormone
Cushing's syndrome (CS) is a rare but severe clinical condition represented by an excessive endogenous cortisol secretion and hence excess circulating free cortisol, characterized by loss of the normal feedback regulation and circadian rhythm of the hypothalamic-pituitary axis due to inappropriate secretion of ACTH from a pituitary tumor (Cushing's disease, CD) or an ectopic source (ectopic ACTH secretion, EAS). The remaining causes (20%) are ACTH independent. As soon as the diagnosis is established, the therapeutic goal is the removal of the tumor. Whenever surgery is not curative, management of patients with CS requires a major effort to control hypercortisolemia and associated symptoms. A multidisciplinary approach that includes endocrinologists, neurosurgeons, oncologists, and radiotherapists should be adopted. This paper will focus on traditional and novel medical therapy for aggressive ACTH-dependent CS. Several drugs are able to reduce cortisol levels. Their mechanism of action involves blocking adrenal steroidogenesis (ketoconazole, metyrapone, aminoglutethimide, mitotane, etomidate) or inhibiting the peripheral action of cortisol through blocking its receptors (mifepristone “RU-486”). Other drugs include centrally acting agents (dopamine agonists, somatostatin receptor agonists, retinoic acid, peroxisome proliferator-activated receptor γ “PPAR-γ” ligands) and novel chemotherapeutic agents (temozolomide and tyrosine kinase inhibitors) which have a significant activity against aggressive pituitary or ectopic tumors.
Bilateral macronodular adrenocortical disease as a part of McCune Albright Syndrome (MAS) is the most common cause of endogenous Cushing’s syndrome (CS) in infancy. Adrenocortical tumors causing CS in infancy are extremely rare. We report the case of a girl with CS who presented at age 4 months with obesity and growth retardation. Her 8 am paired cortisol and adrenocorticotropic hormone levels were 49.3 μg/dL and <1 pg/mL, respectively with non-suppressed serum cortisol (41 μg/dL) on high-dose dexamethasone suppression test. Abdominal computed tomography scan demonstrated a 5.3x4.8x3.7 cm homogenous left adrenal mass with distinct borders. Laparotomy following pre-operative stabilization with ketoconazole 200 mg/day, revealed a 7.5x5x4 cm lobulated left adrenal mass with intact capsule and weighing 115 grams. Histopathology showed small round adrenal tumor cells with increased nucleo-cytoplasmic ratio and prominent nucleoli. The cells were separated by fibrous septae without any evidence of vascular or capsular invasion– findings consistent with adrenal adenoma. On the 8th post-operative day, after withholding hydrocortisone supplementation, the 8 am cortisol level was <1 μg/dL, suggestive of biochemical remission of CS. The patient improved clinically with a 7.5 kg weight loss over the next 3.5 months. This is perhaps the youngest ever reported infant with CS due to adrenal adenoma. Lack of clinical and biochemical evidence of hyperandrogenism as well as the benign histology in spite of the large tumor size (>7 cm diameter; 115 g) are some of the unique features of our patient.
Conflict of interest:None declared.
Cushing’s syndrome; infancy; adrenal adenoma; ketoconazole
Spontaneous remission is rare in ectopic ACTH syndrome (EAS). We describe four patients with presumed EAS in whom long-term treatment with steroidogenesis inhibitors was followed by prolonged remission of hypercortisolemia. Biochemical testing was consistent with EAS, but imaging failed to identify a tumor. Patients were treated with ketoconazole alone or with mitotane and/or metyrapone to control hypercortisolemia. Dexamethasone was added when a block and replace strategy was used. Treatment with steroidogenesis inhibitors for 3–10 years in these patients was followed by a prolonged period of remission (15–60 months). During remission, the first patient had an elevated ACTH, low cortisol and 24-h urinary free cortisol (UFC), and adrenal atrophy on computerized tomography scan during remission, suggesting a direct toxic effect on the adrenal glands. Cases 2 and 3 had normal to low ACTH levels and low-normal UFC, consistent with an effect at the level of the ectopic tumor. They did not have a history of cyclicity and case 3 has been in remission for ~5 years, making cyclic Cushing’s syndrome less likely. Case 4, with a history of cyclic hypercortisolism, had normal to slightly elevated ACTH levels and low-normal UFC during remission. The most likely etiology of remission is cyclic production of ACTH by the ectopic tumor. Spontaneous and sustained remission of hypercortisolemia is possible in EAS after long-term treatment with steroidogenesis inhibitors; a drug holiday may be warranted during chronic therapy to evaluate this. The pathophysiology remains unclear but may involve several different mechanisms.
Cushing’s syndrome can present with a spectrum of symptoms; however, it is less recognised that psychiatric symptoms can form part of the clinical presenting features. In the investigations for an organic cause for a psychiatric illness, Cushing’s syndrome needs to be considered, especially if there are other features such as hirsutism or hypertension. In this article, the two cases reported demonstrate that a prompt diagnosis is not only important for psychiatric management but also crucial for timely institution of the necessary treatment of life-threatening causes of hypercortisolaemia such as metastatic adrenal carcinoma.
Hypercortisolaemia; Hypercortisolism; Cushing’s syndrome; Psychosis; Depression; Catatonia
We report a case of a 63-year-old man, with a previous history of hypertension and glucose intolerance associated troncular obesity that was emergently admitted to our Institution for evaluation of a severe, constant posterior chest pain which radiated anteriorly and dyspnoea with a suspected diagnosis of acute aortic dissection. A CT scan of thorax and abdomen demonstrated a dissection starting just below left succlavian artery and extending downward to the left renal artery, involving the celiac tripod and superior mesenteric artery. The dissection was classified as Stanford B, De Bakey III. Moreover, CT scan of abdomen revealed incidentally a left adrenal tumor of 25 mm of diameter. An emergent prosthetic graft was placed just below the origin of the left succlavian artery up-to the diaphragmatic hiatus. Furthermore, a diagnostic evaluation of the mass revealed an increase of cortisol production, and a diagnosis of Cushing's syndrome was done and the patient underwent an adrenalectomy via laparotomic approach. We report an association of acute aortic dissection of acute aortic dissection type B associated to Cushing's syndrome.
Cushing's syndrome; Adrenocortical adenoma; Aortic dissection type B
Four cases of Cushing's syndrome are described that were associated with deteriorating morbidity because of the considerable delay from first presentation to a secondary care physician to eventual diagnosis. The clinical diagnosis was delayed in all the four patients, although they had symptoms and signs that were missed by a number of primary and secondary care physicians. Trans-sphenoidal surgery resulted in biochemical cure as well as improvement in the accompanying co-morbidity.
Although still rare, the prevalence of Cushing's syndrome is increasing. Increasing clinical awareness and the use of appropriate screening tests should facilitate earlier diagnosis with reduced morbidity and mortality. Although the syndrome is named after Harvey Cushing, Sir William Osler was probably the first to describe it. Therefore, in deference to Osler's contribution to Cushing's syndrome and the work of Harvey Cushing, it is suggested that to the list of the other eponymous conditions of Osler-Weber-Rendu and Osler's nodes, should be added the delay or misdiagnosis of Cushing's syndrome—"Osler's phenomenon".
Cushing’s disease (CD) is a condition of chronic hypercortisolism caused by an adrenocorticotropic hormone-secreting pituitary adenoma. First-line transsphenoidal surgery is not always curative and disease sometimes recurs. Radiotherapy often requires months or years to be effective, and is also not curative in many cases. Consequently, effective medical therapies for patients with CD are needed. Corticotroph adenomas frequently express both dopamine (D2) and somatostatin receptors (predominantly sstr5). Pasireotide, a somatostatin analog with high sstr5 binding affinity, has shown urinary free cortisol (UFC) reductions in most patients with CD in a large phase 3 trial, with UFC normalization and tumor shrinkage in a subset of patients. Adverse events were similar to other somatostatin analogs, with the exception of the degree and severity of hyperglycemia. Two small trials (one prospective and one retrospective) have suggested that cabergoline, a D2 receptor agonist, could be effective in normalizing UFC, but current long-term data results are conflicting. Combination treatment with pasireotide plus cabergoline and the adrenal steroidogenesis inhibitor ketoconazole has been successful, but further investigation in larger trials is necessary. Retinoic acid also showed interesting results in a recent very small prospective study. Glucocorticoid receptor blockade with mifepristone has recently demonstrated improvement in signs and symptoms of Cushing’s and glycemic control; however, this modality does not address the etiology of the disease and has inherent adverse events related to its mechanism of action. Pituitary-targeted medical therapies will soon play a more prominent role in treating CD, and may potentially become first-line medical therapy when surgery fails or is contraindicated.
Cushing’s disease; Pituitary corticotroph adenoma; Somatostatin analog; Cabergoline; Pasireotide; Retinoic acid
Cushing's Disease is caused by oversecretion of ACTH from a pituitary adenoma and results in subsequent elevations of systemic cortisol, ultimately contributing to reduced patient survival. The diagnosis of Cushing's Disease frequently involves a stepwise approach including clinical, laboratory, neuroimaging, and sometimes interventional radiology techniques, often mandating multidisciplinary collaboration from numerous specialty practitioners. Pituitary microadenomas that do not appear on designated pituitary MRI or dynamic contrast protocols may pose a particularly challenging subset of this disease. The treatment of Cushing's Disease typically involves transsphenoidal surgical resection of the pituitary adenoma as a first-line option, yet may require the addition of adjunctive measures such as stereotactic radiosurgery or medical management to achieve normalization of serum cortisol levels. Vigilant long-term serial endocrine monitoring of patients is imperative in order to detect any recurrence that may occur, even years following initial remission. In this paper, a stepwise approach to the diagnosis, and various management strategies and associated outcomes in patients with Cushing's Disease are discussed.
From January 1987 to December 2011, over a total of 25 years, 84 patients with Cushing's syndrome (CS) were identified at a medical center in southern Taiwan. We observed a higher incidence of ACTH-independent CS (75%) than ACTH-dependent CS (25%). A higher incidence of adrenocortical adenoma (58.3%) than Cushing's disease (CD, 21.4%) was also found. The sensitivity of the definitive diagnostic tests for CS, including loss of plasma cortisol circadian rhythm, a baseline 24 h urinary free cortisol (UFC) value >80 μg, and overnight and 2-day low-dose dexamethasone suppression test, was between 94.4% and 100%. For the 2-day high-dose dexamethasone suppression test for the differential diagnosis of CD, the sensitivity of 0800 h plasma cortisol and 24 h UFC was 44.4% and 85.7%, respectively. For the differential diagnosis of adrenal CS, the sensitivities of the 0800 h plasma cortisol and 24 h UFC were 95.5% and 88.9%, respectively. In patients with ACTH-independent CS and ACTH-dependent CS, the baseline plasma ACTH levels were all below 29 pg/mL and above 37 pg/mL, respectively. The postsurgical hospitalization stay following retroperitoneoscopic adrenalectomy was shorter than that observed for transabdominal adrenalectomy (4.3 ± 1.6 versus 8.8 ± 3.7 days, P < 0.001). It was easy to develop retroperitoneal and peritoneal seeding of adrenocortical carcinoma via laparoscopic adrenalectomy.
Women with Cushing’s syndrome (CS) and polycystic ovarian syndrome (PCOS) may present with similar symptoms. Subjects with mild CS lack clinical stigmata of classical CS and often have normal laboratory tests measuring hypercortisolism. Thus, distinguishing mild CS from PCOS may be difficult. We hypothesized that either total testosterone (TT) or bioavailable testosterone (BT) levels or the calculation of the free androgen index (FAI) would be low in patients with mild CS and elevated in patients with PCOS, and could help differentiate the two conditions. TT, BT, and FAI were measured in a group of 20 patients of reproductive age with mild CS and 20 PCOS patients matched for age and BMI. We used receiver operator characteristic (ROC) curves to assess the sensitivity and specificity of these measurements for the diagnosis of CS. TT (p<0.0001), BT (p=0.02), and FAI (p=0.003) were significantly elevated in PCOS patients compared to mild CS patients. Sex hormone-binding globulin was similar in both groups. The optimal cut-point for TT was 1.39 nmol/L, yielding a sensitivity of 95 % and a specificity of 70%. The cut-point for BT was 0.24 nmol/L, resulting in a sensitivity of 75 % and a specificity of 80%. The cut-point for FAI was 5.7, with a sensitivity of 88 % and a specificity of 60 %. We conclude that TT levels may be useful to discriminate between mild CS and PCOS. In patients with signs and symptoms consistent with CS and PCOS, a TT level of <1.39nmol/L warrants a workup for CS.
Cushing’s syndrome; PCOS; episodic; periodic; androgens; testosterone; ROC
Although, there are several tests available, not one of them fulfils the criteria of being an ideal screening test. Continuing the search for an ideal screening test, we explored the use of urine spot cortisol-creatinine ratio as a novel method of evaluating patients with Cushing's syndrome.
A total of 35 subjects were studied and divided into 3 groups - 15 having cushings syndrome, 15 patients with obesity and 5 normal weight subjects. All patients with cushings syndrome were positive for the other screening tests.
The mean (standard deviation) of cortisol:creatinine ratio among the 3 groups (cushings, obese and control subjects) was 36.00(24.74), 7.01(2.73) and 3.49(2.68) respectively. Using the cutoff of 12.27 nano mol/ micro mol(based on data of normal subjects) for the urine cortisol creatinine ratio we get a sensitivity of 93.75% and a specificity of 100%. Also the positive and negative predictive value as calculated with this cutoff is 100% and 93.3% respectively.
In this study we found that UCCR is similar in both Obese and Non Obese subjects who did not have cushings syndrome. UCCR is significantly elevated in individuals with Cushing's syndrome as compared to those who do not have cushings syndrome. Also when a cut off of 12.27 nano mol/ micro mol was used this test had a higher sensitivity, however this test had a higher specificity at a cut off of 15.35.
Urine Cortisol creatinine ratio; cushings syndrome; endogenous
Adrenocortical tumors (ACTs) causing Cushing's syndrome are extremely rare in children and adolescents. Bilateral macronodular adrenocortical disease which is a component of the McCune-Albright syndrome is the most common cause of endogenous Cushing's syndrome. We report the case of a boy with Cushing's syndrome who presented with obesity and growth retardation. The child was hypertensive. The biochemical evaluation revealed that his serum cortisol levels were 25.80 μg/dL, with a concomitant plasma ACTH level of 10.0 pg/mL and nonsuppressed serum cortisol on high-dose dexamethasone suppression test (HDDST) to be 20.38 μg/dL. Computed tomography of the abdomen demonstrated a 8 × 6 × 5 cm left adrenal mass with internal calcifications. Following preoperative stabilization, laparotomy was carried out which revealed a lobulated left adrenal mass with intact capsule weighing 120 grams. Histopathological examination revealed a benign cortical neoplastic lesion, suggestive of adrenal adenoma; composed of large polygonal cells with centrally placed nuclei and prominent nucleoli without capsular and vascular invasion. On the seventh postoperative day, cortisol levels were within normal range indicating biochemical remission of Cushing's syndrome. On followup after three months, the patient showed significant clinical improvement and had lost moderate amount of weight and adrenal imaging was found to be normal.
Cushing’s syndrome is characterised by a series of clinical manifestations due to hypersecretion of cortisol. These include: arterial hypertension, diabetes mellitus (DM), asthenia, amenorrhea, osteoporosis and pathological fractures. We describe the case of a 70-year-old woman with Cushing’s syndrome with right adrenal adenoma, vertebral compression fractures (VCFs) and severe secondary osteoporosis. This patient had been diagnosed with Cushing’s syndrome in May 2008, three years after the onset of arterial hypertension and type II DM, treated with insulin; in July 2008, she underwent right adrenalectomy and replacement therapy with cortisone acetate, 37.5 mg/day, in association with a multiple drug regimen for hypertension and DM; she also had an at least 10-year history of dorso-lumbar pain with multiple disc protrusions. As part of a series of investigations for Cushing’s syndrome the patient underwent femoral bone mineral densitometry, recording a T-score <−3, radiographic examination of the dorso-lumbar spine, which revealed collapse of the superior endplate of D7 and a wedge fracture of D8. At the endocrinology centre of reference for Cushing’s syndrome, she began treatment with alendronate 70 mg/day without undergoing blood chemistry tests of bone metabolism and without calcium and vitamin D supplementation. At the end of August 2009, she experienced worsening spinal pain due to a new severe fracture of D9, which was confirmed on MRI as a recent fracture. At the end of December 2009 she received kyphoplasty of D9, antiresorptive therapy and a CAMP-C35 brace.
In January 2010 she was admitted to the specialist rehabilitation unit for functional recovery, in view of her comorbidities, and bone disease investigation, with collection of history relating to osteoporosis risk factors. First- and second-level blood chemistry analyses revealed the presence of iron-deficiency anaemia, mild chronic renal insufficiency, and secondary hyerparathyroidism (PTH 101ng/ml); spinal radiography revealed severe VCFs of D7, D8 and D9, treated with kyphoplasty; the patient was also assessed using the VAS for pain, the FIM to evaluate independence in activities of daily living, and the SF-36 to investigate quality of life. The alendronate treatment was suspended and the patient was given cholecalciferol 300,000 IU, administered as an oral bolus, followed by a maintenance dose of 800 IU/day. When PTH values had returned to normal, she began treatment with teriparatide 20 mcg/day s.c. (therapeutic plan in compliance with Note 79 issued by the AIFA - Italian Drug Agency).
In conclusion, this case underlines the importance of a correct diagnostic and therapeutic approach in patients with severe osteoporosis. Over time, we will evaluate the efficacy of the treatment in preventing new fractures and the whether the use of a bone anabolic agent might be the correct choice also in order to control pain and improve quality of life. There are no reports in the literature of patients with Cushing’s syndrome treated with teriparatide.
A 48-year-old man presented with symptoms consistent with Cushing's syndrome. Subsequent laboratory studies revealed markedly elevated adrenocorticotropic (ACTH) and cortisol levels, as well as a hypoklemic metabolic alkalosis. A pituitary MRI was performed, which revealed a normal pituitary; however, a large mass was seen centered in the ethmoid and paranasal sinuses with a significant amount of extension into surrounding structures. A biopsy was performed and pathology of the specimen was consistent with esthesioneuroblastoma. Immunohistochemical staining further defined the tumor as an ACTH-secreting esthesioneuroblastoma. After total resection of the mass and further treatment with adjuvant radiation therapy, the patient's symtoms completely resolved and the ACTH and cortisol levels were also greatly reduced. This case demonstrates the successful diagnosis and treatment of a rare neoplasm. Ectopic ACTH syndrome due to esthesioneuroblastoma is extremely uncommon with only five other cases being discussed in the literature.
Ectopic ACTH syndrome; Cushing's syndrome; olfactory Neuroblastoma; esthesioneuroblastoma
A 22-year-old G1P0 was admitted at 26 weeks gestation for preeclampsia, hyperglycaemia and cushingoid features. Elevated 24-h urine free cortisol (UFC) and suppressed plasma adrenocorticotrophic hormone (ACTH) suggested ACTH-independent Cushing’s syndrome. Ultrasound showed left adrenal mass. She delivered preterm at 28 weeks due to severe preeclampsia and fetal distress. The infant expired after 4 days. Blood pressure was controlled after delivery and the patient was discharged on ketoconazole. Adrenalectomy was planned postpartum; however, she withdrew consent and was lost to follow-up.
A 33-year-old G1P1 presented with gestational diabetes. Pregnancy was complicated by premature delivery at 31 weeks for fetal distress. The baby improved and survived. Three months postpartum, she was evaluated for osteoporosis after sustaining a fracture from a fall. Cushingoid facies, elevated 24-h UFC, suppressed ACTH and a right adrenal mass on MRI confirmed an ACTH-independent Cushing’s syndrome. She underwent adrenalectomy and improved.
Endogenous Cushing syndrome (CS) is caused by excess adrenal glucocorticoid secretion that is adrenocorticotropin (ACTH)-dependent or independent; ACTH-independent adrenocortical causes of CS account for up to 20% of CS in adults, and 15% in children over age 7 years. In younger children, ACTH-independent CS may account for as many as half of CS cases. In both adults and children, adrenocortical lesions causing CS include the common, isolated and sporadic, solitary cortisol-producing adenoma, the rare adrenocortical cancer, and a spectrum of recently recognized, bilateral hyperplasias (bilateral adrenocortical hyperplasias - BAHs): micronodular adrenal disease (MAD) and its pigmented variant, primary pigmented nodular adrenocortical disease (PPNAD) are mostly genetic processes. Macronodular BAHs, ACTH-independent macronodular hyperplasia (AIMAH) or massive macronodular adrenocortical disease (MMAD) are less frequently genetic and almost never present in children (except in McCune-Albright syndrome); they present often with atypical CS in middle-aged or elderly adults. The majority of benign adrenocortical tumors associated with CS are associated with defects of the cyclic AMP signaling pathway, whereas adrenal cancer is linked to aberrant expression of growth factors and germline or somatic mutations of tumor suppressor genes such as TP53. Adrenalectomy is the preferred mode of treatment for all adrenocortical causes of CS.
adrenal tumors; Cushing syndrome; cyclic AMP signaling; macronodular hyperplasia; primary pigmented nodular adrenocortical disease