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

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.

Download Full-text

Comparison of hydrocortisone and prednisone in the glucocorticoid replacement therapy post-adrenalectomy of Cushing's Syndrome

Oncotarget ◽

10.18632/oncotarget.20597 ◽

2017 ◽

Vol 8 (62) ◽

pp. 106113-106120 ◽

Cited By ~ 2

Author(s):

Kunlong Tang ◽

Liang Wang ◽

Zhongyuan Yang ◽

Yingying Sui ◽

Liming Li ◽

...

Keyword(s):

Replacement Therapy ◽

Cushing’S Syndrome ◽

Cushing's Syndrome ◽

Glucocorticoid Replacement Therapy

Download Full-text

Hair Cortisol Levels in Patients with Adrenal Insufficiency on Glucocorticoid Replacement Therapy.

10.1210/endo-meetings.2010.part2.p14.p2-675 ◽

2010 ◽

pp. P2-675-P2-675

Author(s):

RS Gow ◽

MJ Rieder ◽

G Koren ◽

S Van Uum

Keyword(s):

Adrenal Insufficiency ◽

Replacement Therapy ◽

Hair Cortisol ◽

Glucocorticoid Replacement Therapy ◽

Cortisol Levels

Download Full-text

A New Perioperative Glucocorticosteroid Replacement Therapy for Cushing's Syndrome

10.21203/rs.3.rs-33015/v1 ◽

2020 ◽

Author(s):

Liang Wang ◽

Lin Yang ◽

Yuanxing Yang ◽

Zhe Cui ◽

Liming Li

Keyword(s):

Replacement Therapy ◽

Intravenous Injection ◽

Cushing’S Syndrome ◽

Plasma Cortisol ◽

Clinical Symptoms ◽

Adrenal Adenoma ◽

Cushing's Syndrome ◽

Simple Method ◽

Urine Cortisol ◽

Cortisol Levels

Abstract Background: To evaluate the safety and effects of a new perioperative glucocorticosteroid replacement therapy for Cushing,s syndrome.Methods: A simple method of glucocorticosteroid replacement therapy as follow was adopted for 83 cases of Cushing's syndrome patient which were diagnosed before the operation: No glucocorticosteroid was used before operation, but during adrenal adenoma resection 100 mg hydrocortisone was given by intravenous injection，and another 200 mg hydrocortisone was given on the day of surgery. On day 1 and day 2 postoperative, 100 mg/12h and 100 mg/24h hydrocortisone were given by intravenous injection respectively. Prednisone(10mg/8h) was given from the day 2 postoperative by oral administration, then 5mg was reduced once a week until a maintenance dosage (5mg) was reached. Clinical symptoms were observed, plasma cortisol and 24h urine cortisol levels were intermittently measured post-operation to evaluate the safety and the curative effect of this new glucocorticosteroid replacement therapy.Results: Adrenal insufficiency and steroid withdrawal syndrome did not occur with all patients. Compared with the concentration of urine cortisol preoperation, it was significantly decreased on the day 7 postoperative. Plasma cortisol concentration was significantly decreased on day 6 postoperative compared with preoperative. All the patients were followed up to 6 months, plasma cortisol and 24h urine cortisol levels were all normal.Conclusions: This new glucocorticosteroid replacement therapy was safe, simple, and effective.

Download Full-text

Glucocorticoid Replacement Affects Serum Adiponectin Levels and HDL-C in Patients With Secondary Adrenal Insufficiency

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jc.2019-00420 ◽

2019 ◽

Vol 104 (12) ◽

pp. 5814-5822

Author(s):

Reiko Hayashi ◽

Daisuke Tamada ◽

Masahiko Murata ◽

Tetsuhiro Kitamura ◽

Kosuke Mukai ◽

...

Keyword(s):

Lipid Profile ◽

Adrenal Insufficiency ◽

Replacement Therapy ◽

Serum Levels ◽

Adrenal Function ◽

Serum Adiponectin ◽

Secondary Adrenal Insufficiency ◽

Glucocorticoid Replacement Therapy ◽

Cortisol Levels ◽

The Relationship

Abstract Context Low serum adiponectin and high-density lipoprotein–cholesterol (HDL-C) levels are risk factors for cardiovascular disease. Patients with primary adrenal insufficiency are at higher risk of cardiovascular complications compared with healthy subjects. However, there is no information on the relationship between adiponectin and glucocorticoid replacement therapy in patients with secondary adrenal insufficiency (SAI). Objective To determine the effects of intrinsic adrenal function and glucocorticoid replacement therapy on serum adiponectin levels and lipid profile in patients with SAI. Design Part 1: a cross-sectional study. Part 2: a randomized, double-blind, crossover study. Setting Osaka University Hospital, Osaka, Japan. Patients Part 1: 58 patients diagnosed with nonfunctioning pituitary adenoma who underwent insulin tolerance test (ITT) for assessment of adrenal function. Part 2: 12 SAI patients randomly received hydrocortisone replacement therapy at a dose of 10, 20, or 30 mg/d for 4 weeks per term for three terms. Outcome Measurements Part 1: we analyzed the relationship between serum cortisol levels during ITT and serum adiponectin levels and the lipid profile. Part 2: serum adiponectin levels and lipid profile were measured every 4 weeks. Results Serum levels of adiponectin and HDL-C correlated significantly with peak cortisol levels after ITT. Serum adiponectin and HDL-C levels were significantly lower in patients with SAI than non-SAI. Serum levels of adiponectin and HDL-C increased in a hydrocortisone dose-dependent manner. Conclusions Glucocorticoid replacement therapy increased serum levels of adiponectin, an adipose-derived anti-atherogenic factor, and HDL-C in patients with SAI.

Download Full-text

Is unilateral adrenalectomy an alternative treatment for ACTH-independent macronodular adrenal hyperplasia?: Long-term follow-up of four cases

Acta Endocrinologica ◽

10.1530/eje.0.1460237 ◽

2002 ◽

pp. 237-240 ◽

Cited By ~ 41

Author(s):

C Lamas ◽

JJ Alfaro ◽

T Lucas ◽

B Lecumberri ◽

B Barcelo ◽

...

Keyword(s):

Adrenal Insufficiency ◽

Replacement Therapy ◽

Cushing’S Syndrome ◽

Alternative Treatment ◽

Cushing's Syndrome ◽

Adrenal Hyperplasia ◽

Unilateral Adrenalectomy ◽

Free Cortisol

OBJECTIVE: ACTH-independent macronodular adrenal hyperplasia is a rare cause of Cushing's syndrome. Bilateral adrenalectomy is considered the treatment of choice, but the patient is obliged to receive lifetime steroid replacement therapy and is susceptible to adrenal insufficiency crisis. New therapeutic alternatives are being proposed as new etiopathological features of the disease are known. Unilateral adrenalectomy of the largest gland can be a safe and effective alternative, but only short-term follow-up is reported in the literature. We present four consecutive patients with ACTH-independent macronodular hyperplasia and long-term remission of Cushing's syndrome after unilateral adrenalectomy. SUBJECTS: Four consecutive patients (two males and two females, mean age 50.3 years) with Cushing's syndrome due to ACTH-independent macronodular adrenal hyperplasia underwent unilateral adrenalectomy of the largest gland. RESULTS: The weight of the resected glands ranged from 26.8 to 210 g. Two patients suffered transient post-surgical adrenal insufficiency and had steroid replacement therapy for 60 and 14 months respectively. After a mean follow-up of 78.8 months (range 30-137 months) all the patients persist without any evidence of Cushing's syndrome. Urinary free cortisol and serum cortisol, after the adrenal insufficiency stage, have always stayed within their normal ranges, but cortisol circadian rhythm and suppressibility after dexamethasone have never normalized. No further enlargement of the contralateral gland has been documented 62 to 126 months after surgery in three of the four patients. CONCLUSIONS: Unilateral adrenalectomy can be an effective and safe alternative treatment for ACTH-independent macronodular adrenal hyperplasia, and can achieve long-term remission of Cushing's syndrome.

Download Full-text

Deep Venous Thrombosis in a Patient With Cushing’s Syndrome

Journal of the Endocrine Society ◽

10.1210/jendso/bvab048.1185 ◽

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.

Download Full-text

Unusual Presentation of Cyclic Cushing’s Syndrome

Journal of the Endocrine Society ◽

10.1210/jendso/bvab048.331 ◽

2021 ◽

Vol 5 (Supplement_1) ◽

pp. A163-A164

Author(s):

Maria del Mar Morales Hernandez ◽

Jessica Castellanos-Diaz ◽

Sreevidya Subbarayan

Keyword(s):

Hip Fracture ◽

Adrenal Insufficiency ◽

Cushing’S Syndrome ◽

Serum Cortisol ◽

Cushing's Syndrome ◽

Ectopic Acth ◽

Free Cortisol ◽

Definitive Therapy ◽

Facial Swelling ◽

Cortisol Levels

Abstract Introduction: About 20–40% of patients with Cushing’s syndrome present with cyclic Cushing’s Syndrome characterized by episodes of cortisol excess interspersed with periods of normal cortisol secretion. A high degree of suspicion is needed to identify patients with cyclical hypercortisolism. Fluctuations in cortisol levels can make this a diagnostic challenge. Rarely, hypocortisolemia and frank adrenal insufficiency can occur. Case Report: A 77-year-old female with history of Cushing’s syndrome and transsphenoidal surgery with no adenoma identified on pathology presented with fatigue and concern for recurrence with ACTH of 358 pg/mL (6–50 pg/mL) and morning serum cortisol of 41.4 mcg/dL. Brain MRI showed a possible 4 mm pituitary adenoma. However, when she was transferred to our hospital, there was no evidence of hypercortisolism with cortisol of 9.5 mcg/dL, ACTH of 33pg/mL, 24 hr urine free cortisol (UFC) of 4.4ug/d (<45ug/d) and she was discharged home after neurosurgery recommended no surgical intervention. A week later, the patient returned to the hospital with nausea and weakness, and found to have cortisol of 4.4mcg/dL, ACTH of 12 pg/mL and UFC of 2.8 ug/d requiring short course of hydrocortisone for adrenal insufficiency. One year later, she presented with hip fracture, worsening weakness, plethora, and facial swelling. UFC was 1,338.3mcg/24 hr(4.0–50.0 mcg/24 hr), AM serum cortisol 58.8mcg/dL and ACTH 304.7 pg/mL. In addition to severe osteoporosis with hip fracture, she had hypertension and impaired fasting glucose. She was treated with Ketoconazole 200mg daily which was titrated until AM cortisol levels decreased from 58.8 mcg/dL to 20 mcg/dL. Patient was discharged on Ketoconazole with plan to complete a Dotatate scan to evaluate for ectopic ACTH production which resulted negative. Shortly thereafter, she returned with hypotension, nausea, and fatigue. Repeat cortisol level was 2.3 mcg/dL with ACTH of 27.6 pg/ml. Ketoconazole was discontinued and patient was started on hydrocortisone for adrenal insufficiency. Hydrocortisone was gradually tapered off. Pituitary MRI and IPSS are planned for further evaluation. Discussion: Cyclic Cushing’s syndrome is diagnosed with three peaks and two troughs of cortisol production. Diagnosis and treatment are challenging since the cycles of hypercortisolism can occur sporadically and rapid fluctuations in cortisol makes it difficult to localize a source. Cortisol fluctuations can affect quality of life and result in complications such as diabetes, hypertension, and osteoporosis. Prompt identification of the source of the Cyclic Cushing’s syndrome is vital to pursue definitive therapy. However, in 9% of cases, there is no identifiable source. In such cases, medical therapy is warranted.

Download Full-text