scholarly journals ENDOCRINOLOGY IN THE TIME OF COVID-19: Management of Cushing’s syndrome

2020 ◽  
Vol 183 (1) ◽  
pp. G1-G7 ◽  
Author(s):  
John Newell-Price ◽  
Lynnette K Nieman ◽  
Martin Reincke ◽  
Antoine Tabarin
Keyword(s):  
Cushing’S Syndrome ◽  
Diagnostic Testing ◽  
Pituitary Surgery ◽  
Cushing's Syndrome ◽  
Local Health ◽  
Protection Measures ◽  
Strict Adherence ◽  
Health Care Structure ◽  
Local Health Care ◽  
Immunosuppressed Patients

Clinical evaluation should guide those needing immediate investigation. Strict adherence to COVID-19 protection measures is necessary. Alternative ways of consultations (telephone, video) should be used. Early discussion with regional/national experts about investigation and management of potential and existing patients is strongly encouraged. Patients with moderate or severe clinical features need urgent investigation and management. Patients with active Cushing’s syndrome, especially when severe, are immunocompromised and vigorous adherence to the principles of social isolation is recommended. In patients with mild features or in whom a diagnosis is less likely, clinical re-evaluation should be repeated at 3 and 6 months or deferred until the prevalence of SARS-CoV-2 has significantly decreased; however, those individuals should be encouraged to maintain social distancing. Diagnostic pathways may need to be very different from usual recommendations in order to reduce possible exposure to SARS-CoV-2. When extensive differential diagnostic testing and/or surgery is not feasible, it should be deferred and medical treatment should be initiated. Transsphenoidal pituitary surgery should be delayed during high SARS-CoV-2 viral prevalence. Medical management rather than surgery will be the used for most patients, since the short- to mid-term prognosis depends in most cases on hypercortisolism rather than its cause; it should be initiated promptly to minimize the risk of infection in these immunosuppressed patients. The risk/benefit ratio of these recommendations will need re-evaluation every 2–3 months from April 2020 in each country (and possibly local areas) and will depend on the local health care structure and phase of pandemic.

scholarly journals Steroid withdrawal syndrome after successful treatment of Cushing’s syndrome: a reminder

2005 ◽  
Vol 153 (2) ◽  
pp. 207-210 ◽  
Author(s):  
A Bhattacharyya ◽  
K Kaushal ◽  
D J Tymms ◽  
J R E Davis
Keyword(s):  
Adrenal Insufficiency ◽  
Replacement Therapy ◽  
Cushing’S Syndrome ◽  
Withdrawal Syndrome ◽  
Pituitary Surgery ◽  
Cushing's Syndrome ◽  
Temporary Increase ◽  
Steroid Withdrawal ◽  
Glucocorticoid Replacement Therapy ◽  
Cortisol Levels

Steroid withdrawal syndrome (SWS) usually refers to relapse of the disease being treated after withdrawal of glucocorticoid therapy, or the symptoms of adrenal insufficiency which occur when glucocorticoids are rapidly reduced or stopped. A less well-recognised form of SWS is that which develops when patients experience a symptom complex similar to that of adrenal insufficiency despite acceptable cortisol levels. We describe three patients who presented with this form of SWS following surgical treatment for endogenous Cushing’s syndrome. All responded well to a short-term increase in the dose of glucocorticoid replacement therapy, with the median duration of the syndrome being 10 months (range 6–10 months). Trough serum cortisol levels above 100 nmol/l, with peaks between 460 and 750 nmol/l were documented in the first two patients at presentation with SWS. It is thought that the syndrome may result from development of tolerance to glucocorticoids, and mediators considered to be important in its development include interleukin-6, corticotrophin-releasing hormone, vasopressin, and central noradrenergic and dopaminergic systems. The exact underlying mechanism for SWS remains unclear. However, with increasing recommendations for use of lower doses of replacement glucocorticoids, its incidence may increase. Physicians need to be aware of this condition, which is self-limiting and easily treated by a temporary increase in the dose of glucocorticoid replacement therapy. It is possible that a slower glucocorticoid tapering regimen than that used in the standard postoperative management of patients undergoing pituitary surgery may reduce the risk of development of SWS.

scholarly journals Cyclic Cushing's disease with misleading inferior petrosal sinus sampling results during a trough phase

2015 ◽  
Vol 38 (2) ◽  
pp. E7 ◽  
Author(s):  
Vivien Bonert ◽  
Namrata Bose ◽  
John D. Carmichael
Keyword(s):  
Cushing’S Syndrome ◽  
Cushing’S Disease ◽  
Adrenocorticotropic Hormone ◽  
Diagnostic Testing ◽  
Cushing's Syndrome ◽  
Cushing's Disease ◽  
Inferior Petrosal Sinus ◽  
Inferior Petrosal Sinus Sampling ◽  
Acth Secreting ◽  
Transsphenoidal Resection

Diagnosing Cushing's syndrome is challenging and is further hampered when investigations are performed in a patient with cyclic Cushing's syndrome. A subset of patients with Cushing's syndrome exhibit periods of abnormal cortisol secretion with interspersed normal secretion. Patients can have periods of clinical improvement during these quiescent phases or remain symptomatic. Initial diagnostic testing can be challenging because of the unpredictable durations of the peak and trough phases, and it is especially challenging when the diagnosis of cyclic Cushing's syndrome has not yet been determined. Here, the authors present the case of a patient with Cushing's disease with a pathology-proven adrenocorticotropic hormone (ACTH)–secreting pituitary adenoma and whose initial inferior petrosal sinus sampling (IPSS) results were deemed indeterminate; further studies elucidated the diagnosis of cyclic Cushing's syndrome. Repeat IPSS was diagnostic of a central source for ACTH secretion, and the patient was treated successfully with transsphenoidal resection. Literature concerning the diagnosis and management of cyclic Cushing's syndrome is also reviewed.

scholarly journals Diminished and irregular TSH secretion with delayed acrophase in patients with Cushing's syndrome

2009 ◽  
Vol 161 (5) ◽  
pp. 695-703 ◽  
Author(s):  
Ferdinand Roelfsema ◽  
Alberto M Pereira ◽  
Nienke R Biermasz ◽  
Marijke Frolich ◽  
Daniel M Keenan ◽  
...  
Keyword(s):  
Cushing’S Syndrome ◽  
Approximate Entropy ◽  
Pituitary Surgery ◽  
Pulse Frequency ◽  
Cushing's Syndrome ◽  
Pituitary Thyroid Axis ◽  
Tsh Secretion ◽  
Thyroid Axis ◽  
Serum Tsh ◽  
Active Disease

ContextThe hypothalamus–pituitary–thyroid axis in Cushing's syndrome may be altered. Previous reports have shown diminished serum TSH concentration and decreased response to TRH.ObjectiveWe analyzed serum TSH profiles in relation to cortisol profiles in patients with hypercortisolism of pituitary (n=16) or primary-adrenal origin (n=11) and after remission by pituitary surgery (n=7) in order to delineate aberrations in the hypothalamus–pituitary–thyroid system.InterventionPatients and controls (n=27) underwent a 24-h blood sampling study. Serum TSH and cortisol were measured with precise methods, and data were analyzed with a deconvolution program, approximate entropy (ApEn), and cosinor regression.ResultsPulsatile TSH secretion and mean TSH pulse mass were diminished during hypercortisolism, independently of etiology (P<0.001). TSH secretion was increased in patients in remission only during daytime due to increased basal secretion (P<0.01). Pulse frequency and half life of TSH were similar in patients and controls. TSH ApEn (irregularity) was increased in patients with hypercortisolism (P<0.01), but was normal in cured patients. Cross-ApEn between TSH and cortisol, a measure of pattern synchrony loss, was increased in active disease, indicating (partial) loss of secretory synchrony. The TSH rhythm was phase delayed in hypercortisolemic patients, but normal in cured patients (P<0.01). Free thyroxine levels were decreased only in pituitary-dependent hypercortisolism compared with controls (P=0.003). Total 24-h TSH correlated negatively and linearly with log-transformed cortisol secretion (R=0.43, P=0.001).ConclusionCortisol excess decreases TSH secretion by diminishing pulsatile release, whereas surgically cured patients have elevated nonpulsatile TSH release. Diminished TSH secretory regularity in active disease suggests glucocorticoid-induced dysregulation of TRH or somatostatinergic/annexin-1 control.

Cyclical Cushing's syndrome first diagnosed after pituitary surgery: a trap for the unwary

1992 ◽  
Vol 36 (3) ◽  
pp. 297-299 ◽  
Author(s):  
A. B. Atkinson ◽  
O. R. McCance ◽  
L. Kennedy ◽  
B. Sheridan
Keyword(s):  
Cushing’S Syndrome ◽  
Pituitary Surgery ◽  
Cushing's Syndrome

scholarly journals SUN-187 A Case of Adrenal Mass with Elevated ACTH and Cortisol in a Woman with No Cushingoid Features

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Tara Rajiyah ◽  
Susan Sam
Keyword(s):  
Cushing’S Syndrome ◽  
Adrenal Mass ◽  
Correct Diagnosis ◽  
Fasting Blood Glucose ◽  
Clinical Signs ◽  
Case Series ◽  
Pituitary Surgery ◽  
Cushing's Syndrome ◽  
T Score ◽  
History Of

Abstract Background Adrenal incidentalomas can present with subclinical Cushing’s Syndrome (SCS), which is defined as elevated cortisol levels without overt clinical signs or symptoms. Inaccuracies in ACTH levels due to issues with the assay and non-classic presentation of Cushing’s Syndrome (CS) can delay appropriate diagnosis and timely intervention. Clinical Case A 50-year-old female with a history of an incidentally discovered 3.4 x 1.8 cm adrenal mass was referred for evaluation of hypercortisolism (midnight salivary cortisol 0.17 μg/dL, normal &lt; 0.09 μg/dL) with lack of suppression of both ACTH (19 pg/mL, normal 6-50 pg/mL) and cortisol (13.1 μg/dL, normal 6.0-18.4 μg/dL) on overnight 1-mg dexamethasone suppression test (DST). Pheochromocytoma work up was negative. Her medical history was remarkable for premature ovarian failure at age 40 and osteoporosis at age 48 (Lumbar spine T-score -3.6, Femoral neck T-score -3.7, Hip T-score -2.7). She denied alcohol abuse and depression screening was negative. She reported high levels of stress and insomnia. She denied muscle weakness, acne, or change to body habitus. Fasting blood glucose was intermittently as high as 212 mg/dl but HbA1c was 5.5%. She did not have a history of hypertension or glucocorticoid use. Her BMI was 20 kg/m2 and she did not appear Cushingoid. A pitutiary MRI showed no evidence of pituitary lesions or enlargement. Discussion and Follow up A non-suppressed ACTH made an adrenal source of cortisol unlikely. The working diagnosis was pseudo-CS secondary to stress, loss of diurnal rhythm due to insomnia, or overlooked depression. She was taking supplements, including biotin, and was asked to discontinue these for two weeks. Repeat 1-mg DST revealed an elevated cortisol of 9.8 μg/dL with a once again non-suppressed ACTH of 20 pg/mL. Her dexamethasone level was 109 ng/dL (normal after 1 mg dexamethasone 180-950 ng/dL), which may suggest slightly faster metabolism. All ACTH levels were run on Immulite assays, which has recently been suggested to be unreliable (1). When repeated using the Roche Assay, ACTH was low at 1.6 pg/mL. Given suppressed ACTH in conjunction with hypercortisolemia and osteoporosis, an adrenal source of CS was confirmed. Diagnosis was further solidified by a DHEA-S level of 11.4 μg/dL (normal 35.4 - 256 ug/dL). She underwent adrenalectomy and pathology revealed adrenal cortical adenomas. Conclusion The correct diagnosis of adrenal CS in this patient was delayed due to erroneously higher ACTH result by the Immulite assay. Similar cases have been reported in the literature with the use of Immulite assays for measurement of ACTH leading to invasive diagnostic procedures and even unnecessary pituitary surgery (1). 1. Greene LW, Geer EB, Page-Wilson G, Findling JW, Raff H. Assay-Specific Spurious ACTH Results Lead to Misdiagnosis, Unnecessary Testing, and Surgical Misadventure-A Case Series. J Endocr Soc. 2019;3(4):763-72.

scholarly journals Crooke's Changes In Cushing's Syndrome Depends on Degree of Hypercortisolism and Individual Susceptibility

2015 ◽  
Vol 100 (8) ◽  
pp. 3165-3171 ◽  
Author(s):  
Edward H. Oldfield ◽  
Mary Lee Vance ◽  
Robert G. Louis ◽  
Carrie L. Pledger ◽  
John A. Jane ◽  
...  
Keyword(s):  
Cushing’S Syndrome ◽  
Medical Center ◽  
Academic Medical Center ◽  
Pituitary Surgery ◽  
Cushing's Syndrome ◽  
Individual Variability ◽  
Histopathological Analysis ◽  
Large Set ◽  
Upper Limit ◽  
Free Cortisol

Context: Although Crooke's changes in the pituitary corticotrophs were initially described in 1935, the prevalence in which the changes occur in patients with Cushing's syndrome (CS) has not been established. Objective: This study aimed to determine the prevalence and assess clinical features associated with the presence or absence of Crooke's changes in a large set of patients with CS. Design: Information from a prospective computer database and retrospective chart review was analyzed. Setting: The setting was an academic medical center. Patients: Consecutive patients (N = 213) who received surgery with a preoperative diagnosis of Cushing's disease are included. Intervention: The patients received pituitary surgery and specimens obtained underwent pathological analysis. Main Outcome Measure: The presence or absence of Crooke's changes was determined by histopathological analysis of the normal pituitary tissue included with the specimen obtained at surgery. Cortisol production was measured by 24-hour urine cortisol production. Results: Crooke's changes occurred in 144 of 177 patients (81%) with a histologically demonstrated ACTH-staining tumor and in 74% of 213 patients diagnosed with CS who had pituitary surgery. The presence of Crooke's changes correlated with the finding of an ACTH-staining tumor removed at surgery and with the degree of hypercortisolism. Among patients with histologically established ACTH-staining tumors the prevalence of Crooke's changes was particularly high in patients with a 24-h urinary free cortisol (UFC) of at least 4-fold the upper limit of normal, in which 91% of patients had Crooke's changes, compared with 74% of patients whose maximum UFC was less than 4-fold the upper limit of normal (P = .008). Conclusions: Crooke's changes occur in 75–80% of patients with CS, and depend on the degree of hypercortisolism and individual variability. Almost all patients with UFC at least 4-fold the upper limit of normal have them, whereas with less severe hypercortisolism the expression of Crooke's changes varies from person to person.

scholarly journals Deep Venous Thrombosis in a Patient With Cushing’s Syndrome

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A581-A581
Author(s):  
Sanah Rana ◽  
Erika Brutsaert
Keyword(s):  
Lower Extremity ◽  
Venous Thrombosis ◽  
Deep Venous Thrombosis ◽  
Cushing’S Syndrome ◽  
Pituitary Tumor ◽  
Pituitary Surgery ◽  
Cushing's Syndrome ◽  
Clotting Factors ◽  
Free Cortisol ◽  
Cortisol Levels

Abstract Introduction: Cushing’s syndrome (CS) is associated with a prothrombotic state due to increased activation of several clotting factors. As such, patients are more susceptible to development of post-operative venous thrombosis. We present the case of a patient who underwent pituitary surgery for CS and subsequently developed acute lower extremity deep venous thrombosis (DVT) after stopping anticoagulation upon discharge. Case Report: A 57-year-old female presented with abdominal pain 1 month after gastric bypass surgery. She was found to have intra-abdominal abscesses and started on IV antibiotics. Upon further questioning, she endorsed 2-week history of coarse hair over chin, difficulty climbing stairs, and easy bruising. She had type 2 diabetes and hypertension, both diagnosed 2 years prior. Blood pressure was 169/88 on admission. On exam she had coarse hair on chin, central obesity, scattered ecchymoses, proximal muscle weakness, and no abdominal striae. Labs revealed potassium level of 1.9 mmol/L despite supplementation with 60 meq/day of potassium chloride. Workup showed random cortisol 45 mcg/dl, ACTH 114 pg/ml, elevated urinary free cortisol to 898.6 ug/24 hours, unsuppressed cortisol to 30.6 mcg/dL with low-dose dexamethasone and partial cortisol suppression to 11 mcg/dl with high-dose dexamethasone. MRI brain showed pituitary adenoma measuring 6 x 9 x 2 mm. CRH stimulation test showed rise of ACTH to 302 pg/ml and cortisol to 81.5 mcg/dl consistent with ACTH-dependent hypercortisolism from pituitary tumor. While hospitalized, the patient received thromboprophylaxis with SQ enoxaparin 40 mg daily. Patient was started on ketoconazole and subsequently underwent transsphenoidal resection to remove the pituitary tumor, which effectively reduced her serum cortisol levels. She was started on hydrocortisone replacement. She was discharged to a skilled nursing facility 2 weeks later. However, she did not receive thromboprophylaxis at the facility and was diagnosed with acute lower extremity DVT soon after hospital discharge. Discussion: CS is associated with increased risk of thromboembolic events. Although our patient received DVT prophylaxis in the hospital until discharge 2 weeks after surgery, she developed DVT soon after discharge. This emphasizes the increased susceptibility to development of venous thrombosis even after normalization of cortisol levels following pituitary surgery. A recent retrospective study showed that patients with CS are at higher risk of thromboembolism for approximately 30 to 60 days during the postoperative period. This case highlights that the clotting risk remains elevated in patients with CS for an extended period after successful surgery. In conclusion, patients with CS are at high risk of thromboembolism even after surgery and extended thromboprophylaxis should be considered.

THE CORRELATION BETWEEN ENDOCRINE EXOPHTHALMOS AND EXOPHTHALMOS PRODUCING SUBSTANCE (EPS)

1966 ◽  
Vol 51 (3) ◽  
pp. 359-368 ◽  
Author(s):  
F. Schwarz ◽  
P. J. der Kinderen ◽  
Maria Houtstra-Lanz
Keyword(s):  
Cushing’S Syndrome ◽  
Anterior Pituitary ◽  
Pituitary Surgery ◽  
Normal Subjects ◽  
Serum Levels ◽  
Cushing's Syndrome ◽  
Graves Disease ◽  
Better Than

ABSTRACT The correlation between Endocrine Exophthalmos and serum levels of EPS was investigated in 64 exophthalmic patients; only 2 patients had no demonstrable EPS in their serum. 31 of these patients were suffering from thyrotoxicosis, 11 from Cushing's syndrome and 2 from acromegaly. 20 were euthyroid. The serum of 44 non-exophthalmic subjects was tested: 11 with thyrotoxicosis, 6 with Cushing's syndrome, 4 acromegalics and 23 normal subjects. Only in two of the non-exophthalmic thyrotoxics EPS was found in the serum. Both developed severe ophthalmopathy later in the course of the disease. In all groups of patients a fair correlation was found between the severity of the exophthalmos and EPS levels in the serum. In 8 patients, EPS levels were determined serially during the course of the disease, in some before as well as after pituitary surgery or irradiation. Changes in the EPS levels, corresponded well with the course of the ophthalmopathy. The correlation was better than that reported by some other investigators. In the authors opinion, these divergencies can be explained by differences in the method of EPS determination used. It is concluded that it is very probable that endocrine exophthalmos in Graves' disease as well as in Cushing's syndrome and in acromegaly, is caused by an anterior pituitary factor (EPS).

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